Syringomyelia (SM) and the
Cavalier King Charles Spaniel
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January 2017: UK study identifies characteristics that cause painful Chiari-like malformation and syringomyelia in cavaliers. In a January 2017 article, a team of veteran neurologists and other specialists (Susan P. Knowler [right], Chloe Cross, Sandra Griffiths, Angus K. McFadyen, Jelena Jovanovik, Anna Tauro, Zoha Kibar, Colin J. Driver, Roberto M. La Ragione, Clare Rusbridge) used novel brain-mapping techniques to compare distance and angle measurements from MRI scans of 162 cavalier King Charles spaniels to thereby determine the relationship between the measure of physical characteristics obtainable from MRI scans and resulting risk of pain caused by Chiari-like malformation (CM) and syringomyelia (SM). They found that CM pain appears to be associated with increased brachycephaly (shorteness of muzzle), and that SM can result from different combinations of abnormalities of the forebrain, caudal fossa, and craniocervical junction which make up the neural parenchyma, and impede the flow of cerebrospinal fluid.
The study includes a motion picture which highlights the dynamic changes of the skull conformation and brain parenchyma associated with progressive brachycephaly and airorhynchy [the upward rotation of the front of the palate]. As the video morphs from the control dog to one with CM pain that the nasal bone and hard palate become closer so that the hard palate becomes more horizontal, the nasal cavity and frontal cavity reduce in volume and the rostral forebrain is flattened. As the model progresses into SM case 1 the nasal and rostral forebrain changes become more extreme. In addition to the forebrain changes, the hindbrain is pushed down and the craniocervical junction kinks as a consequence of the cervical vertebral being closer to the skull with flattening of the supraoccipital bone. Consequently there is a “concertina” flexure of the brain with a compensatory increase in height of the cranial fossa. In SM case 2 the concertina flexure is more extreme lower with the cerebellum appear to be folded back under the occipital lobe, and the olfactory bulbs are much in size and displaced.
January 2017: UK study uses MRI scan measurements of hindbrain and craniocervical junction angles and distances to compare Chihuahuas, Affenpinschers and cavaliers with and without syringomyelia. In a January 2017 article, a team of UK researchers (Susan P. Knowler, Anna-Mariam Kiviranta, Angus K. McFadyen, Tarja S. Jokinen, Roberto M. La Ragione, Clare Rusbridge) examined MRI scans of the hindbrains and craniocervical junctions of 99 Chihuahuas, 42 Affenpinschers, and 132 cavalier King Charles spaniels to compare 22 specific features (line distances, angles, and ratios) of dogs with and without syringomyelia (SM), that were originally developed to investigate the genetic basis of Chiari-like malformation (CM) in the Griffon Bruxellois (GB). They concluded:
"The selected morphometries [physical measurements] successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels."
Describing cavaliers specifically, the researchers stated:
"Ten of the fourteen significant variables were found in the CKCS with one, line a-c [see red line a-c in the diagram below], unique to the breed. Line a-c indicates the proximity of the sphenooccipital synchondrosis to the atlas bone. This study confirms the findings of others that the CKCS with SM have a reduced caudal fossa size a presumed consequence of early closure of the spheno-occipital and possibly other cranial sutures. Compared to other breeds including the GB, the CKCS has considerably greater incidence of cerebellar deformation by the supra-occipital bone and vermis herniation. These findings and the coexistence of occipital dysplasia and hypoplasia suggest that the CKCS may have additional predisposing risk factors for SM compared to the other breeds."
Electronic von Frey aesthesiometer (eVF) testing fails to
distinguish pain levels in 70 cavaliers.
November 2016 abstract, UK researchers (H. Williams, S. Sanchis, H.
A. Volk, L. Pelligand, J. Murrell, N. Granger) tested 70 cavalier King
Charles spaniels for skin sensitivity using the Electronic von Frey
aesthesiometer (eVF) (right). The eVF allows application of
increasing pressure onto the skin via a non-invasive plastic tip, until
the dog responds (i.e. demonstrating skin sensitivity threshold). The
eVF screen displays the pressure applied in grams.
The dogs were categorized in three classes: (i) 37 dogs had syringomyelia and clinical signs (syringomyelia-symptomatic – SM-S); (ii) 15 dogs had syringomyelia without clinical signs (syringomyelia-asymptomatic – SM-A); and (iii) 18 dogs had no syringomyelia (syringomyelia-free - SM-F). The researchers found that eVF assessment of skin sensitivity does not differ significantly by syringomyelia status.
November 2016: Cavaliers with ventriculomegaly may also have normal pressure hydrocephalus (NPH). In an October 2016 abstract, German researchers (M. J. Schmidt, A. Hartmann, K. H. von Pückler, L. Hähnsen, N. Ondreka) compared the perfusion of blood in the periventricular white matter of 23 cavalier King Charles spaniels with ventriculomegaly (see white area in photo at right) compared to control dogs consisting of 10 healthy Beagles. They found that cerebral blood flow and volume were significantly lower in the cavaliers. They concluded that the dogs with ventriculomegaly may have a form of normal pressure hydrocephalus (NPH).
September 2016: Acupuncture successfully controls pain symptoms in a CM/SM-affected cavalier. In a September 2016 article, a UK veterinarian (Donal Joseph O'Leary) reports on the successful use of acupuncture to control the signs of pain in a female tricolor cavalier King Charles spaniel suffering from Chiari-like malformation and syringomyelia (CM/SM). The acupuncture was in addition to conventional medical treatment. He noted:
"This patient exhibited signs which suggested it was also suffering from headaches. It often presented with a frowning expression and during these times intensely disliked being touched, rubbed or patted on the head. Acupuncture had a definite positive effect on this patient with reductions in all the signs including the signs of phantom scratching and vocalisation."
August 2016: Southeast Veterinary Neurology offers reduced cost CM/SM screening for cavaliers. Board certified veterinary neurologists Drs. Michael Wong, Nicholas De Pompa, and Simon Kornberg (right) at Southeast Veterinary Neurology (SEVN) have announced they are offering reduced cost screenings ($900.00) of cavalier King Charles spaniels to diagnose Chiari-like malformation and syringomyelia. The package includes a full physical and neurological exam, MRI scan using a high-field 1.5 Tesla MRI unit, anesthesia, a computer disc of the MRI images, and a detailed report reviewing the results in line with the BVA breeding guidelines. All screenings will take place at SEVN's Miami office. Call 305-274-2777 to schedule an appointment. Details are at this Internet link.
August 2016: Cavaliers lead list of CM/SM-affected dogs treated in England primary-care clinics, 2009-2014. In an August 2016 article reviewing the clinical records of 187,326 dogs treated at primary-care veterinary clinics in England, from September 2009 through April 2014, the cavalier King Charles spaniel led the list of dogs diagnosed and treated for Chiari-like malformation and/or syringomyelia (CM/SM). However, the statistics are surprisingly low. Overall, only 93 dogs were diagnosed or treated for CM/SM. Of those, 65 were cavaliers (69.9% of all CM/SM-diagnosed/treated dogs), out of a total of the 4,046 CKCSs which were included in the full study. So, only 1.6% of all cavaliers were diagnosed or treated for CM/SM.
The researchers (Sanchis-Mora S, Pelligand L, Thomas CL, Volk HA, Abeyesinghe SM, Brodbelt DC, Church DB, Thomson PC, McGreevy PD, O'Neill DG) attribute the "underestimation of the true prevalence" of CM/SM to lack of MRI scans. They also noted that a significant proportion of dogs in the study were excluded because a clinical diagnosis was not made despite possible signs of CM/SM being present and because clinical signs could be confused with other diagnosed diseases. They found an increased diagnosis level for insured dogs, suggesting that financial and other constraints on diagnostic procedures may have allowed the true prevalence of CM/SM in the overall population to be underestimated.
Pain was the most common sign reported for CM/SM (67 dogs, 72%). Others were phantom scratching (36 dogs, 38.7%), spontaneous yelping (27 dogs, 29%), neck pain on palpation (16 dogs, 17.2%), and provoked yelping (15 dogs, 16.1%). Treatment records for 89 of the affected dogs showed that 72 dogs received one or more drugs for treatment of CM/SM, and 17 dogs were unmedicated. Gabapentin (48 dogs - 67%), NSAIDs (47 dogs - 65%), and corticosteroids (23 dogs - 32%) were the most commonly prescribed treatments for CM/SM. Two dogs (2.1%) underwent surgery for CM/SM but the outcomes of surgery were not recorded. During the study period, 9 of the 93 dogs were euthanased/died (9.8%) as a result of CM/SM.
June 2016: Ohio State University needs cavaliers for clinical study of Chiari-like malformation and syringomyelia. Dr. Sara Moore of Ohio State University is seeking cavalier King Charles spaniels (CKSC) for a clinical trial to evaluate pain thresholds of cavaliers both with and without Chiari-like malformation and syringomyelia (CM/SM). Both normal and CM/SM-affected dogs are being recruited. The entire test is expected to take only 20 minutes. It will involve a neurlogical examination and then apply steady pressure to the dog's back leg paws, using a von Frey anesthesiometer (VFA) (right) until the dog feels the pressure and pulls its foot away. Anyone conveniently located near Columbus, Ohio may contact the Blue Buffalo Clinical Trials Office by telephone 614-247-8706 or email CVM-ClinicalTrials@osu.edu or check this OSU webpage.
June 2016: In study of 54 cavaliers, craniocervical junction (CCJ) abnormalities fail to predict future SM symptoms. In a June 2016 report, neurologists Sofia Cerda-Gonzalez (right) and Natasha J. Olby conducted a long-term study of 54 cavalier King Charles spaniels (CKCS) to determine if asymptomatic dogs with craniocervical junction (CCJ) abnormalities would predict future development of clinical signs of syringomyelia (SM). Over 80% of the asymptomatic dogs in the study had CCJ abnormalities upon initial examination. Nevertheless, nearly two-thirds of the asymptomatic CKCSs remained asymptomatic throughout the study period. They concluded:
"Craniocervical junction morphology assessed in our study did not appear to predict the development of new and worsened clinical signs or syringomyelia over time in our cohort of CKCS. The relationships between clinical progression and syringomyelia, AOO [overlap of the atlanto-occipital joint], and dorsal bands should be evaluated further in a larger cohort of dogs. Clinical progression in our cohort of medically managed CKCS did not differ substantially from published reports of those treated surgically."
May 2016: UK researchers find evidence that CM in cavaliers may be due to overall brain and skull size. Until now, Chiari-like malformation has been considered a hind brain conformation disorder in cavalier King Charles spaniels. But in an April 2016 abstract presented to the 2016 BSAVA Congress, a team of UK neurological researchers (Chloe Cross, Susan P. Knower, Angus K. McFayden, Jelena Jovanovik, Anna Tauro, Colin J. Driver, Noel Fitzpatrick, Clare Rusbridge) have found evidence that CM may be the result of an overall disorder of the conformation of the CKCS brain and skull.
They examined MRI scans of the skulls of 70 cavaliers, divided into four categories: SM with phantom scratching (15 CKCSs); clinical SM (e.g. pain) but no phantom scratching (17 CKCSs); behavioral signs of pain with CM but no SM (25 CKCSs); and CKCS with no SM and no behavioral signs of pain or scratching (13 dogs -- “CKCS control”). They also had an “other-breed-control” group of 19 dogs (including 5 brachycephalic -- short-muzzled), with normal brain sizes.
They hypothesized that there may be insufficient room within the skull for the forebrain, and that may contribute to backward displacement and overcrowding of the hindbrain. They focused upon the forebrain's olfactory bulb (OB -- also called olfactory lobe), which is at the lower front of the forebrain and directly behind the olfactory receptor cells in the dog’s nose. (See diagram above.) The more brachycephalic (short-muzzled) the dog, the more the OB tends to be lower and the more the frontal lobe tends to be flattened against the front of the skull. (Compare the normal location of the canine forebrain in the diagram at the left below, with the flattened frontal lobe and the lower olfactory lobe of a CM/SM-affected cavalier, at the right below.)
They found that the more severe the CM/SM condition of the cavaliers in the study, the smaller the mean size of the OB, and that there was a significant difference between the cavaliers' OB in the four CM/SM groups and the dogs' OB in the other-breed-control group. They also noticed a trend towards more ventrally (lower) orientated OB with increasing CM/SM severity. They concluded:
“This study suggests that CM should be considered a more global brain and skull conformational disorder with features of extreme brachycephaly including smaller more ventrally orientated OB; however, further work is required and the measurement technique has been refined for future studies. We recommend that future studies into MRI conformation of CM and SM uses rigorous phenotyping based on clinical signs and age.”
EDITOR'S NOTE: This study admittedly is preliminary, as its conclusion suggests. However, it does not begin to explain why the cavalier King Charles spaniel breed has such a high incidence of CM and SM. There must be something unique in the CKCS (and perhaps one or two other breeds), beyond just being brachycephalic, which differentiates them from other short-muzzled breeds which do not have such a high incidence of these two disorders. We suggested as much in our blog entry, “The accordion-muzzled cavalier King Charles spaniel”.
May 2016: UK researchers find that phantom scratching in CM/SM-affected cavaliers is due to the location and size of the syrinx. In an April 2016 abstract presented to the 2016 BSAVA Congress, a team of UK neurological researchers (Zoe R. Nalborczyk, Angus K. McFadyen, Jelena Jovanovik, Anna Tauro, Colin J. Driver, Noel Fitzpatrick, Susan P. Knower, Clare Rusbridge) reported a study of 37 cavalier King Charles spaniels to try to determine why, if affected dogs experience unusual sensations, they nevertheless make little or no skin contact.
They investigated two hypotheses: (1) That the phenomenon of phantom scratching is associated with a large dorsolateral syrinx in the upper cervical spinal cord segments; and (2) Whether there is an association to damage in other areas of the cervical spinal cord and that phantom scratching is not just associated with a dorsolateral syrinx but one that extends to the superficial dorsal horn (SDH).
The study found that phantom scratching is associated with a large dorso-lateral syrinx that extends to the SDH in the C3-C6 spinal segments (C2-C5 vertebrae). The study did not find an association to damage of other areas of cervical spinal cord. They concluded that:
"Phantom scratching in the dog is associated with a large syrinx that extends to the SDH in the C3-C6 spinal segments. We propose that phantom scratching is due to damage to projection neurons in lamina I of the SDH with consequent reduced descending inhibition to the lumbosacral scratching CPG [central pattern generator -- neural circuits controlling a stereotyped sequence of muscle contractions]. ... If a dog has SM extending to the SDH then it is at risk for phantom scratching. If an itchy SM affected dog has no SDH involvement then alternative explanations for scratching (e.g. allergic skin disease) should be investigated."
They added that drugs affecting the SDH may be useful for management of phantom scratching.
May 2016: UK neurological researchers test electronic von Frey aesthesiometer to measure SM-associated neuropathic pain in cavaliers. In an April 2016 abstract presented to the 2016 BSAVA Congress, a team of UK neurological researchers (Heather Williams, Sandra Sanchis, Ludovic Pelligand, Holger Volk, Joanna Murrell, Nicolas Granger) tested the electronic von Frey aesthesiometer (eVF) (at left) on twelve cavalier King Charles spaniels (CKCS) to determine if they could quantify the dogs' cervical skin sensitivity. They decided that the number of dogs was insufficient to reach any conclusions, and they announced plans to study a larger group of CKCSs and divide them by CM/SM status. Their aim is to establish a protocol to quantify neck pain in cavaliers with neuropathic pain.
May 2016: UK study shows SM-affected cavaliers have more blood vessels and stiffer vessel walls adjacent to lateral ventricles. In an April 2016 abstract (titled: "Contents Under Pressure") presented to the 2016 BSAVA Congress, a team of UK neurological researchers (Clare Rusbridge [right], Silvia Guilluna, Daniela Menezes, Duncan Grainger, Anna Tauro, Nicholas Jeffery, Fernando Constantinocasa, Penny Watson, Francisco Salguero) examined brain tissue from 26 deceased cavalier King Charles spaniels -- 18 affected by CM/SM with ventriculomegaly and 8 without SM -- to determine differences in the quantities of blood vessels and the vessels' fibrous tissue between the two groups. They hypothesized that these increased numbers of vessels and fibrous tissues adjacent to syrinx cavities suggested a response to increased intra-cord pressure. They found from their examination of the tissues from the cerebral cortex that SM-affected cavaliers had significant increases in the number of blood vessels, associated with increases in the widths of the vessels' walls due to thicker fibers. They also found abnormal increases in the number of astrocytes (star-shaped glial cells in the central nervous system). They concluded:
"The logical explanation of this histomorphological change is a mechanical response to elevated arterial pressure. This arterial stiffening may further affect the ability to reduce the arterial pulse wave and decrease the CNS compliance."
April 2016: UK neurologist calls for study of whether furosemide can delay syrinx growth in cavaliers. In a brief April 2016 article, UK veterinary neurologist Luca Motta (left) reports studying the effect of furosemide therapy upon the progression of syrinx growth in seven cavalier King Charles spaniels. He states:
"In all seven dogs, syrinx width and length increased at the follow-up MRI and in four cases a new syrinx had developed (Table 1). Furosemide did not prevent further syrinx expansion nor reduce the size of the syrinx but it remains unknown whether the medical treatment may have delayed the inevitable expansion of the syrinx. Studies of a larger population and prospective, randomised, blinded comparisons between different treatments (medical, surgical, medical vs surgical) are needed to ascertain which will produce the best clinical results."
March 2016: Accidental mixed breeding of Griffon Bruxellois (GB) provides an experiment in reducing risk of Chiari-like malformation and syringomyelia. An accidental breeding of a Griffon Bruxellois (GB) -- Brussels Griffon -- and an Australian terrier (right) results in a useful experiment in out-crossing and back-crossing to reduce the incidence of Chiari-like malformation and syringomyelia in that breed. In a March 2016 article, a team of researchers and a Dutch GB breeder (Susan P. Knowler, Henny van den Berg [breeder], Angus McFadyen, Roberto M. La Ragione, Clare Rusbridge) analyzed the offspring and subsequent generation of the cross-breeding over a period of four years.
1. To investigate the effectiveness of a crossbreeding a brachycephalic GB with CM and a mesaticephalic Australian terrier without CM as a means of reducing the incidence of traits associated with CM and risk for SM.
2. To elucidate the inheritance by comparing phenotypic traits related to both CM and SM that have been previously shown to be statistically significant  for the conditions.
3. To clarify the phenotype of CM with an ultimate aim of improving the CM/SM grading system and generate robust EBVs that are appropriate for all breeds.
They rhetorically asked and answered:
"Did the outcross reduce the risk of inherited CM and SM?" --- "An outcross does have the potential to reduce prevalence of inherited CM and SM. ... Although the offspring were too young to confirm SM clear status, the morphometric measurements used in this study provide an indicator of risk for SM."
"Did the study indicate any patterns of inheritance for CM/SM?" --- "This study is too small to make conclusions about inheritance. However, the F2 backcross had CM1 status from CM2 parents despite the high incidence of inherited CM in the other family members. These results, together with the fact CM is known to skip a generation in an earlier familial study of 33 GB, suggests the involvement of recessive traits that are protective against CM and/or gene penetrance is variable involving individual traits that are additive in severity. ... SM2 dog E and SM1 dogs C and K were mated to SM0 dogs. Of their eight offspring two were SM2 and two SM1. SM0 parents A and H when mated together produced both an SM0 and SM2 offspring. All these findings support evidence from two previous studies of inheritance in the BG."
"Is it possible to retain Breed Standard in an outcross?" --- "... The head and body conformation of the F2 backcross abfg is sufficiently similar to the GB breed standard that, in the next generation GB backcross (CM0), a suitable F3 offspring would be accepted in the GB Stud book of the European FCI. Since facial length has a different morphogenesis and embryological origin to that of the basisphenoid and occipital bones it should be possible to select against a reduced hind skull. ... The introduction of new genes in a mixed breed cross means progeny may be phenotypically less predictable. Despite this, the dog skull is particularly variable, and this study has illustrated that with careful selection of external and internal traits in the proposed mate, it might be possible to avoid risk of CM and SM and regain the external conformation which best characterises the breed."
This study has enabled its researchers to refine the definition of Chiari-like malformation, as follows:
"This study supports the hypothesis that CM in the dog is a more global skull disorder rather than a caudal skull abnormality. ... The definition of CM is refined as a more global cranium and craniocervical junction abnormally characterized by insufficiency of the supra and basioccipital bones with compensatory rostral cranium doming, shortening of the skull base and increased proximity of the cervical vertebrae to the occiput resulting in overcrowding of the neural parenchyma in the caudal fossa."
January 2016: Cornell Univ. neurologist Cerda-Gonzalez finds a close association of atlanto-occipital overlapping (AOO) in cavaliers with clinical signs of SM. In a March 2016 report, Cornell University neuroglogist Dr. Sofia Cerda-Gonzalez (right) and her research team (K.F. Bibi, A.T. Gifford, E.L. Mudrak, P.V. Scrivani) examined the MRIs of 271 dogs, measuring the proximity of the atlas to the foramen magnum. They found a close association (higher than previously reported) between atlanto-occipital overlapping (AOO) and small breeds, including cavalier King Charles spaniels, affected with clinical signs of syringomyelia (SM). CKCS were more likely (86%) than non-CKCS (44%) to have AOO.
EDITOR'S NOTE: The atlas is the spinal vertebra (C1) closest to the skull. It sits next to the foramen magnum, which is the hole in the occipital bone. The "atlanto-occipital joint" is the connection between the atlas and the occipital bone, and is stabilized by ligaments. "Atlanto-occipital overlapping" (AOO) is characterized by a decreased distance between the atlas and the occipital bone. In some cases, the dorsal arch of the atlas may actually protrude into the foramen magnum. See the image below (courtesy of: www.wikispaces.com). See also these related articles: May 2009; October 2009; January 2010; April 2013; February 2014; and November 2015.
December 2015: SM syrinx formation computer model discounts likelihood that cerebrospinal fluid abnormalities create syrinxes. In a September 2015 abstract before the ESVN-ECVN, UK researchers (R. Lloyd, S. Cirovic, J. Jovanovik, H. Volk, C. Rusbridge) created a computer model of the spinal cord, subarachnoid space (SAS), dura mater, and the epidural space of a cavalier King Charles spaniel affected with CM/SM. They performed exaggerated movement of the spinal cord during the cardiac cycle, seeking to confirm a theory that abnormities in the circulation of the cerebrospinal fluid (CSF) generate pressures that drive the fluid into the cord. Instead, they found that CSF pressure gradients are unlikely to cause fluid movement into the cord, sufficient to generate syrinxes. They concluded:
"On the other hand, although the shear stress in the cord is low, its location and cyclic nature indicates the possibility that this may be the factor that generates the initial tissue damage, which eventually leads to the formation of syrinxes."
December 2015: Neurologist Jason King sums up Chiari-like malformation. In a December 2015 blog article, US veterinary neurologist Dr. Jason King (right) has written a summary of Chiari-like malformation as he sees it. He clings to what we had thought was some replaced terminology, particularly "Caudal Occipital Malformation Syndrome (COMS)" rather than Chiari-like malformation (CM or CLM) and "syringo-hydromyelia" rather than syringomyelia (SM), but he also provides some newer information about how the spinal cord works and why affected dogs feel phantom sensations. He states:
"The part of the spinal cord that is towards the chest of a person or animal carries information from the brain to the body, instructions on how to move. The part of the spinal cord towards the back of the person or animal carries information from the body to the brain, sensory information if you will. Interestingly enough, SM almost always forms in the sensory part of the spinal cord. So it leads to abnormal sensations rather than weakness or abnormal movments. That means that dogs with SM manifest some very odd and quite varied behaviors secondary to the abnormal sensations that their spinal cord is causing them to feel. Imagine, that every time you got excited your toes began to itch and burn, your ear began to feel hot, or your arm became numb and tingly... The most striking manifestation of this abnormal sensation is called 'phantom scratching'. In this situation, dogs will begin to scratch 'at' their ear, but just a little bit off to the side. Almost as if they were scratching the air!"
December 2015: UK vet schools need cavaliers for neck pain study. Researchers at the UK's University of Bristol vet school and the Royal Veterinary College are conducting a study to find a pain-free method of detecting neck pain of neurological origin in dogs. The study involves owners completing questionnaires and assessments of the dogs' neck skin sensitivity with a pain-free electronic pressure device, a von Frey aesthesiometer (see photo at right), being applied to the skin, while monitoring for the dogs' responses. To take part in the study, email firstname.lastname@example.org. For more details, see this press release.
November 2015: Dr. Loughin summarizes the current view of Chiari-like malformation. In a March 2016 article, veterinary brain surgeon Dr. Catherine Loughlin (right), summarizes the current research on Chiari-like malformation for general practice veterinarians. She writes:
"Chiari-like malformation (CLM) is a condition of the craniocervical junction in which there is a mismatch of the structures of the caudal cranial fossa (CCF), often causing the cerebellum to herniate into the foramen magnum. Affected dogs have a smaller CCF with relatively more brain parenchyma within the fossa compared to unaffected dogs. This smaller CCF leads to cerebellar compression and herniation through the foramen magnum, kinking of the medulla, and disruption of cerebrospinal fluid (CSF) at this junction. This malformation is found most commonly in the Cavalier King Charles spaniel (CKCS), is inherited, and is thought to affect as much as 95% of the population. ... Chiari-like malformation is diagnosed on MRI by identifying cerebellar herniation, cerebellar compression, and attenuation of cerebrospinal fluid, but kinking of the medulla, ventriculomegaly/hydrocephalus, and syringomyelia are also noted in many dogs. Some patients respond favorably to medical management; foramen magnum decompression with a durotomy is the surgical treatment of choice in improving or resolving clinical signs in dogs with Chiari-like malformation."
November 2015: UK researchers need CM/SM-affected cavaliers for pain treatment study. The Royal Veterinary College (RVC) is seeking CM/SM-affected cavalier King Charles spaniels in the UK for a clinical trial to evaluate the effect of pregabalin (Lyrica) on neuropathic pain. Pregabalin, an anticonvulsant, is closely related to gabapentin and was developed by Pfizer, which also developed gabapentin. Pfizer reports that pregabalin is more potent than gabapentin and achieves its effect at lower doses. Referrals to RVC's researchers, Sandra Sanchis-Mora (left), Ludovic Pelligand, Holger A. Volk, and Stobhan M. Abeyesinghe, must be made by veterinarians. The dogs' CM/SM diagnosis must have been made by a recent or pending MRI scan. Suitable dogs should only have received non-steroidal anti-inflammatory drugs as analgesics. Dr. Sanchis-Mora's email address is email@example.com
August 2015: Statistical analysis of MRI-scanned asymptomatic cavaliers show that the presence of a syrinx is a risk factor for later development of clinical signs of CM/SM. In an August 2015 abstract, UK researchers (A. Vanhaesebrouck, L. Doyle, M. Holmes, T. Williams, E. Ives) studied 79 cavalier King Charles spaniels which had been MRI-scanned for pre-breeding screenings between 2006 and 2009. Their age range at the time of the MRI-scans were between 2.2 years and 3.5 years. A syrinx was identified in 32% of the 79 dogs which had been scanned. As of 2013, 16% of the dogs had developed clinical signs compatible with CM/SM, with an age range of 4 years to 7 years. Of those, 36% had a visible syrinx on their earlier MRI-scans, and 7% had no visible syrinx. The researchers concluded that the presence of a syrinx in cavaliers, on an MRI screening, appears to represent a risk factor for later development of clinical signs consistent with CM/SM.
August 2015: UK neurologist seeks CM/SM-affected cavaliers for non-invasive pain assessment study. Dr. Nicolas Granger of the University of Bristol in the UK is seeking referrals of cavalier King Charles spaniels affected with CM/SM for a study of assessing neurological pain with the electronic von Frey aesthesiometer (right), an inexpensive bedside instrument which applies light pressure from its plastic conical tip to the dog's skin to assess pain response. The instrument provides a reading of the applied pressure in grams. The aim of this study is to: (a) validate a practical non-invasive objective method of quantitatively assessing cervical skin hypersensitity in CM/SM-affected dogs; and (b) compare the results with normal CKCSs and dogs affected with other forms of neurological pain. Contact Dr. Granger at firstname.lastname@example.org or +44 (0) 117 331 9113.
August 2015: UK researchers compare anti-convulsants gabapentin and topiramate in a study of 33 cavaliers with CM/SM. In an August 2015 report, a team of UK neurologists (I. N. Plessas, H. A. Volk, C. Rusbridge, A. E. Vanhaesebrouck, N. D. Jeffery) compared the effect of gabapentin versus topiramate, both anti-convulsants, in combination with the NSAID carprofen (Rimadyl) on 33 cavalier King Charles spaniels affected with CM/SM. They found no significant difference upon the quality-of-life of the treated dogs, and that either of the two drugs may be more effective than carprofen alone. They noted that the most common side effect of both gabapentin and topiramate was sedation, and that an additional effect of topiramate was inappetence. Overall, side effects of topiramate were more severe than those of gabapentin.
The brand names of gabapentin are Neurontin and Gabarone, and the brand name of topiramate is Topamax.
August 2015: Belgium researchers find computed tomography (CT) can be used to diagnose syringomyelia in dogs. In an August 2015 report, a team of Belgium researchers (Kaatje Kromhout [left], H. van Bree, B.J.G. Broeckx, S. Bhatti, S. De Decker, I. Polis, I. Gielen) compared computed tomography (CT) and magnetic resonance (MR) scans of 32 dogs, including 12 cavalier King Charles spaniels. They found that low-field MR and multislice CT imaging provided comparable information regarding the presence of SM, and that CT can be used as a diagnostic tool for SM when MRI is not available. They conclude, however, that "CT cannot replace MRI as the standard screening technique for the detection of SM in Cavalier King Charles Spaniel for breeding purposes." See also the November 2014 Research News item by the same team of researchers, reaching the same conclusion.
June 2015: Out-crossing Griffon Bruxellois with Australian terrier reduced Chiari-like malformation and maintained breed standard in second generation. In a June 2015 report at the ACVIM Forum by UK and Dutch researchers (Susan Knowler, Henny van den Berg [right], Eric Noorman, Roberto La Ragione, Clare Rusbridge), they crossed a CM-affected Griffon Bruxellois (GB -- Brussels Griffon) with a normal Australian terrier, and then back-crossed the offspring to a GB. The test group consisted of 12 dogs in the same family, which were used in 8 different mating combinations resulting in 19 progeny. They conclude:
"The quantitative findings in this study revealed these traits to be significant for CM-affectedness. Furthermore the external phenotypes showed that by outcrossing breed types and selecting appropriate conformation characteristics in the F1 generation, it is possible to regain the GB breed standard in the F2 generation and reduce the degree of CM. However this is dependent on careful selection of conformation and screening for CM and SM at 1 year of age. The 4 dogs affected with SM in the study all exhibited reduced caudal skull development compared to their relatives. We showed that traits on MR images were useful to distinguish the phenotype and these exhibited segregation and may be additive towards the severity of CM. It suggests such traits might be useful to quantify the condition and the risk to SM. We propose that grading of CM takes account of quantitative traits that can be used in Estimated Breeding Values (EBV) to assist breeders with their mate selections. Such a system will have to be verified to ensure appropriateness for all breeds at risk."
US researchers find associations between lesions at the atlantoaxial
junction and SM in cavaliers. In a
May 2015 study of 36
mature cavalier King Charles spaniels (5 to 12 years old), US
researchers (S. Cerda-Gonzalez, N. J. Olby, E. H. Griffith) found:
• 34 had Chiari-like malformation (CM);
• 26 had syringomyelia (SM);
• 20 had neuropathic pain.
They also report that 31 of the CKCSs had compressive lesions at the "atlantoaxial junction (AA)" (the joint between the atlas and axis -- the first two cervical vetebrae), and 23 of those dogs with AA also had SM. They concluded that the prevalence of AA bands in older cavaliers appears to be high, and there were significant associations among AA bands, clinical signs, and SM in dogs with CM.
A cavalier King Charles spaniel positioned in an extended/straight position in Figure A, and in a flexion, resembling a standing posture in Figure B. Dorsal atlantoaxial (AA) band-associated compression (long arrow) is more prominent in flexion than in extension. A Chiari-like malformation is also present (short arrow), along with dorsal subarachnoid space dilation cranial to the AA band.
May 2015: NC State vet school needs cavaliers with Chiari-like malformation for pain studies. At the North Carolina State veterinary school, neurologists Natasha Olby and Sofia Cerda-Gonzalez are conducting two studies of cavaliers with Chiari-like malformation.
They expect to use quantitative data from magnetic resonance imaging (MRI) to perform a more appropriate genetic analysis of this important and common disease. The researchers will also investigate sensory thresholds in CM/SM-affected and normal CKCS to improve the ability to document and treat pain in SM patients. The project hopes to define the genetic etiology of the disease with the long-term aim of developing genetic tests for use by breeders, and to quantify the sensory dysfunction experienced by SM-affected dogs to facilitate objective therapeutic trials.
May 2015: Dutch master's student examines MRIs and reports of 848 cavaliers and finds no significant relationship between clinical signs and CM/SM grade. In a May 2015 master's thesis, Netherland's researcher D. L. Schuil reviewed the MRI scans of 848 cavalier King Charles spaniels and answers to questionaires by the dogs' owners. 233 completed surveys were returned. According to the owners 45 dogs had clinical signs (19.3%) and 188 dogs did not (80.7%). From his analysis of the grades of SM and the reported clinical signs, he could not find any significant relationships between the clinical signs and the MRI scans.
April 2015: US neurologists find association between medullary elevation and signs of SM, and that brainstem position relates to SM in CKCSs. In an April 2015 study of 36 cavaliers, US neurologists S. Cerda-Gonzalez, N.J. Olby, and E.H. Griffith reported finding that higher elevation of kinking of the medulla related to neurological clinical signs of CM/SM. They also found that brainstem position measurements at the caudodorsal-most border of the fourth ventricle (called the "obex position") were associated with both the presence and severity of syringomyelia. An obex position measurement of ≤3.5 was sensitive (79%) and highly specific (90%) for the presence of syringomyelia.
(The authors' photo at right shows how the position of the brainstem was evaluated by measuring the distance between the obex (the caudodorsal-most border of the fourth ventricle) and a line drawn parallel to the foramen magnum. This was termed the "obex measurement". )
April 2015: More VetCompass analysis shows low diagnoses of CM and SM in cavaliers. In an April 2015 report by UK and Australian veterinarians (Jennifer F Summers, Dan G O’Neill, David B Church, Peter C Thomson, Paul D McGreevy, David C Brodbelt), the veterinary records of 1,875 cavalier King Charles spaniels treated between 2009 and 2013 and on the database of the VetCompass animal health surveillance project, were dissected. Only 75 of the 1,875 cavaliers had a confirmed KC-registration status. Magnetic Resonance Imaging (MRI) confirmed diagnoses of either syringomyelia (SM), Chiari-like malformation (CM) or both were recorded in approximately 2% of study dogs, with SM ranked 28th among the most frequently recorded specific diagnoses. Regarding this statistic, the authors note:
"Including only those diagnoses of either condition made with reference to MRI results (i.e. excluding those suggested by clinical signs alone) could have underestimated the true level in the population, as not all clinically suspicious cases underwent MRI scanning. The sometimes vague nature of clinical signs may result in failure to offer scanning in some cases, while reluctance (or financial limitations) of owners to pursue MRI diagnosis may be the limiting factor in others. Bias linked to comparative willingness to request high level diagnostic investigation may be of particular relevance in breeding animals, if breeders are more (or less) likely to volunteer breeding animals for MRI through screening programs. The link between signs of SM/CM visible on MRI and appearance of clinical signs can also be inconsistent, as not all dogs with a visible syrinx on MRI display clinical signs at the time of imaging."
April 2015: VetCompass records from 2009-2014 show 37 out of 3,860 CKCSs were diagnosed by MRI to have CM/SM. In an April 2015 report, a team of UK and Australian researchers (Claire Thomas, Sandra Sanchis-Mora, Ludovic Pelligand, Holger Volk, David Church, Paul McGreevy, Peter Thomson, Dave Brodbelt, Dan O’Neill) examined the Veterinary Companion Animal Surveillance System (VetCompass) veterinary clinic records of 187,365 dogs treated from September 2009 to June 2014, to find how many were diagnosed as affected with Chiari-like malformation/syringomyelia (CM/SM) by MRI scans. They found 59 CM/SM cases, of which 37 were cavalier King Charles spaniels (CKCS), out of a CKCS population of 3,860, a CKCS breed prevalence of 0.96%. Practitioners had reported that 84 additional cavaliers were suspected of having CM/SM but were unconfirmed. Other breeds found to be affected were: King Charles Spaniels [a/k/a English toy spaniels] (12 dogs), crossbreed (3 dogs), Yorkshire Terrier (2 dogs), and Affenpinscher, Pug, English Toy Spaniel, Jack Russell Terrier and Chihuahua (1 dog each).
Other statistics in the study: (a) the median (interquartile range) age at diagnosis was 4.33 years; (b) the most common clinical signs associated with CM/SM were expression of pain (14 dogs), characteristic CM/SM-associated motor signs (scratching or facial rubbing without underlying skin disease) (11 dogs) and ataxia or weakness (7 dogs). Analgesics (alone or in combination) were prescribed to 49 cases, the most common analgesic treatments being gabapentin (32 dogs), NSAIDs (18 dogs), glucocorticoids (30 dogs) and tramadol (13 dogs). Practitioners reported 31 dogs (63.26%) showed apparent clinical improvement following treatment.
EDITOR'S NOTE: The significance of these statistics regarding the percentage of CM/SM in the cavalier needs to be taken with a giant grain of salt. First of all, they contradict nearly all findings of the percentages of CM/SM within the CKCS in other studies. This study may be a "consider the source" situation, and several questions come to mind. Like, do most general practice vets even know enough about SM to recognize the need for MRIs? And, what role did insurance play in the vets' decisions about having MRI scans performed? We suspect this report properly will be marked down as a gross anomaly.
April 2015: UK research finds no correlation between barometric pressure changes and comfort levels of cavaliers with CM/SM. In an April 2015 report, UK researchers William Warman, Edward Ives, and Clare Rusbridge compared daily barometric pressure changes with the comfort levels (reported by dogs' owners) of 22 cavalier King Charles spaniels (CKCS) affected by Chiari malformation and syringomyelia (CM/SM) for 3 months. They found no evidence supporting an association between barometric pressure and the degree of discomfort experienced by CKCS with CM/SM.
March 2015: Mississippi State University surgeons report long-term success of Chiari-like malformation surgeries. In a March 2015 report, the neuro-surgery team at Mississippi State University (N. Ortinau, S. Vitale, E. Y. Akin, M. Beasley, Andy Shores, right) surveyed 17 patients following foramen magnum decompression surgeries over three years. They found that none of the dogs has required additional surgery to date, and that all but one had some improvement in quality of life after surgery, and none were judged to deteriorate to less than the pre-surgical status. They concluded that the surgical procedure, combined with medical therapy, resulted in favorable long-term outcomes.
March 2015: Flanders, Belgium requires CM/SM and MVD testing of cavalier breeding stock. The government of the Flemish region of Belgium announced on March 3, 2015, new breeding rules for cavalier King Charles spaniels, requiring that all breeding stock be tested for mitral valve disease (and Chiari-like malformation and syringomyelia) in order for litters to be registered by the Flemish government. Twenty other breeds also will now have additional testing requirements.
Joke Schauvliege (left), Flemish Minister for Environment, Nature and Agriculture, signed the ministerial decision, which will come into force, along with details of the testing procedures, 10 days after official publication in the government's journal, which is expected to occur in April. The new regulation is the result of a study ordered by Minister Schauvliege two years ago, involving the calculation of the genetic diversity and most common health problems in the 21 breeds, which also includes the Schipperke, Papillon, Bichon Frise, Groenendael, Petit Brabancon, Ardennes cattle dog, Laekenois, Bloodhound, Golden Retriever, Irish setter and border collie.
November 2014: UK researchers find asymptomatic cavaliers with a syrinx appear more likely to display clinical signs later in life than those without. In a November 2014 study of 79 cavalier King Charles spaniels without any symptoms related to Chiari-like malformation or syringomyelia, a team of researchers (Edward J. Ives [left], L. Doyle, M. Holmes, T.L. Williams, A.E. Vanhaesebrouck) at the Queen's Veterinary School Hospital, University of Cambridge in the UK investigated an association of magnetic resonance imaging findings in asymptomatic dogs and clinical signs in later life. They found that a significantly greater proportion of CKCSs with a syrinx visible on MRI screening showed clinical signs in later life (9/25, 36%) than dogs without a visible syrinx (4/54, 7%). However, they concluded that whether their findings can be used to indicate the likelihood of an asymptomatic CKCS developing clinical signs consistent with SM in later life warrants further study with a larger group of dogs.
November 2014: Belgian researchers find no significant difference between CT scans and MRI scans detecting Chiari-like malformation in cavaliers. In a November 2014 study of 15 cavalier King Charles spaniels by a team of Belgian researchers, they compared computed tomography (CT) scans with MRI scans and analyzing them statistically, they found "no significant difference between the different observers and techniques for the detection of CH [cerebellar herniation] and measurement of CHL [cerebellar herniation length]." However, they found, "Overall, the CHL was longer on the CT images." They concluded:
"Both techniques are useful for detecting CH and measuring CHL. Because CHL does not have a known direct impact on the clinical presentation of CM, CT can be used as a diagnostic tool in a routine clinical practice for CM in CKCS when MRI is not available. We emphasize that MRI is the standard screening technique in CKCS for breeding purposes to detect the presence of CM and SM and, at the current time, CT cannot replace MRI."
The two images above are (A) an MRI midsagittal T2WSE image and (B) a postcontrast CT image (soft tissue window) of the brain of the same CKCS. The supraoccipital bone (red asterisk), basioccipital bone (green asterisk) and occipitoatlantoaxial joint is visible (white asterisk). The foramen magnum limit is set (black line) from the rostrodorsal aspect of the supraoccipital bone to the most caudal aspect of the basioccipital bone. The cerebellar herniation length (mm, white line) is measured caudal from the foramen magnum. See also, this March 2014 item below.
November 2014: Colin Driver joins the UK's Canine Chiari and Syringomyelia Research Group. Colin John Driver (right), BSc BVetMed(Hons) MVetMed PhD DipECVN MRCVS, and European Specialist in Veterinary Neurology and Neurosurgery, has left private practice in Hampshire to join the Canine Chiari and Syringomyelia Research Group at Fitzpatrick Referrals and the University of Surrey in the UK. He will continue work on his Ph.D. thesis entitled “The pathogenesis of syringomyelia secondary to Chiari-like malformation in dogs” at the University of Ghent in Belgium.
October 2014: Syringomyelia in South African cavaliers is 41%. South African veterinary neurologist A. J. Carter reported in a paper before the World Small Animal Veterinary Assosciation Congress (WSAVA) in September 2014 that SM "is highly prevalent within the South African Cavalier King Charles Spaniels." He found that the prevalence is 41%.
October 2014: Three definitions of Chiari-like malformation are compared in asymptomatic non-CKCS dogs. In an October 2014 study by a team of UK researchers (T.R. Harcourt-Brown (right), J. Campbell, C. Warren-Smith, N.D. Jeffery, N.P. Granger), they examined MRI scans of 199 dogs -- 14 cavaliers and 185 dogs of other breeds -- to establish the prevalence of Chiari-like malformation (CM) in non-CKCS dogs which met three different defintions of CM. The three definitions are:
1. Indentation: "Indentation of the caudal aspect of the cerebellum -- defined as a concave, rather than flattened or convex, caudal border of the cerebellum."
2. Impaction: "Impaction of the cerebellar vermis into the foramen magnum -- defined as deformation of the shape of caudo-ventral vermis into a point such that the angle between lines drawn along the caudal and ventral borders of the cerebellum meet at an acute, rather than an obtuse, angle. This definition was considered analogous to descent into the foramen magnum that has been used previously."
3. Herniation: "Herniation of the cerebellar vermis through the foramen magnum -- defined as extension of the cerebellar vermis caudal to a line drawn between the ventral aspect of the supraoccipital bone (opisthion) and the caudal border of the basioccipital bone (basion)."
They found that, among the 185 non-CKCS dogs, indentation was identified in 44% and impaction in 22%. No non-CKCS dogs showed herniation; 29% of CKCSs showed herniation (11–55%). They concluded:
"We conclude there is a high prevalence of cerebellar indentation and impaction in the normal canine population, suggesting they are unreliable as defining factors for CM. Our data supported the hypothesis that some measures of brachycephaly are associated with indentation or impaction, but the overlap in these measurements among breeds showed that construction of control groups based on subjective assessment of skull type could be inappropriate. Instead, it may be better for future studies investigating the relationship between abnormalities of the caudal cranial fossa and clinical signs or syringomyelia to define control groups based on the absence of specific anatomical features considered important (eg, cerebellar herniation, obstruction to CSF flow at the foramen magnum)."
EDITOR'S NOTE: It appears that the authors of this study divided one definition of CM into three -- indentation, impaction, and herniation. But herniation always has been part of the definition of CM, so to find other breeds with indentation and impaction but no herniation -- as this study found no herniation among the non-CKCSs -- does not mean these other breeds had CM. It just means the other dogs did not have CM.
October 2014: SM study of all cavaliers registered in Denmark in 2001 shows 15.4% have SM symptoms after age 6 years. In a 6+ year study of all 240 cavalier King Charles spaniels registered in Denmark in 2001, the researchers found that 15.4% had SM symptoms after age 6 years, and that 93% of asymptomatic SM dogs remained asymptomatic at age 6 years. Thirteen symptomatic and 9 asymptomatic siblings participated in a litter study. 21 of 22 littermates had syrinxes (95%). Syrinx diameter and mean syrinx : spinal cord ratio were significantly correlated with clinical signs (P < .01). Estimated heritability of symptomatic SM was 0.81. They concluded that the prevalence of symptomatic SM is high and that genetics have a high impact on clinical disease expression.
August 2014: Study of 84 American Brussels Griffons finds syringomyelia and Chiari-like malformation to be prevalent. In an August 2014 study of 84 "American" Brussels Griffon dogs, researchers A.C. Freeman, S.R. Platt, M. Kent, E. Huguet, C. Rusbridge, and S. Holmes found that SM and CM are "prevalent" and that "Syrinx size is associated with neurologic deficits, CM, larger ventricles, a smaller craniocervical junction height, neurologic deficits, and cerebellar herniation."
The stats: 65% had CM. 52% had SM. 28% had neurologic deficits and 20% had neck pain. 52% of the SM dogs were clinically normal.
July 2014: UK researchers find two aspects of cavalier skull conformation are associated with the development of SM. A team of UK veterinary neurology researchers, Thomas J. Mitchell, Susan P. Knowler, and Clare Rusbridge, and consultants in the Netherlands and Canada, Henny van den Berg and Jane Sykes, examined the skulls of 133 cavaliers to determine if skull measurements could predict the presence or development of syringomyelia (SM), They found that as the dog's cranium is shortened and broadened, the risk of developing SM increases. They stated in their July 2014 article:
"The study found two aspects of conformation to be associated with the development of SM in the CKCS: the cephalic index and the distribution of cranium across the length of the head. It was found that a higher cephalic index and, separately, a lower percentage of the cranium distributed caudally [towards the back of the head] were significantly associated with disease development."
"The cephalic index is the ratio of the width of the cranium of an organism (taken behind the cheekbones in this study) divided by its length (i.e., in the horizontal plane, or front to back). It is usually expressed as a %. It differs from craniofacial index in that it does not relate to the length of the muzzle."
"The conformational indicator of caudal cranium distribution was found to significantly, correctly classify cases as SM clear or affected at the level of three years of age, five years of age, and when comparing a sample of SM clear dogs over five years to those affected and younger than three. Cephalic index was able to significantly, correctly classify cases at the latter level. Results suggest that these indicators are irrelevant of age (after 18 months of age), gender and parity. These, therefore, represent invaluable tools in determining breeding plans in that they are not only protective against developing the condition in the first three years of life but they are protective against developing the condition at all, maintaining SM clear status beyond the age of five years."
See also a YouTube video explaining this article.
July 2014: UK's Royal Veterinary College seeks CKCSs for neuropathic pain assessment study. The Royal Veterinary College is conducting a study of clinical signs and behaviors which predict presence or severity of neuropathic pain in cavalier King Charles spaniels with Chiari-like malformation and syringomyelia. In this study, RVC proposes to identify if thermal and pressure sensory testing improves clinical assessments of neuropathic pain in dogs. RVC is recruiting healthy UK CKCSs and cavaliers affected by CM/SM and their owners to participate in the development of an owner questionnaire and the validation of a sensory testing protocol to be used to evaluate severity of NeP and response to treatment. This is a non-invasive and interactive study for both pets and their owners. For further information, please contact:Sandra Sandlis at email@example.com or 01707 666605.
May 2014: US neurologists find that high compression lesions due to thickened dural bands may relate to more severe pain and more severe syringomyelia in cavaliers. In a May 2014 abstract prepared for the June 2014 ACVIM Forum, USA Drs. S. Cerda-Gonzalez, N.J. Olby, E.H. Griffith assessed 36 cavalier King Charles spaniels for neurologic pain and dysfunction. They found that 20 of the dogs demonstrated neuropathic pain; that dural bands (compressive lesions caused by abnormally thickened dura matter at the craniocervical junction) were present in 31 of the dogs; that 34 of the dogs had Chiari-like malformation; that 23 of the dogs had syringomyelia (and 21 of those 23 dogs had dural bands). They also found that dural bands were associated with both the presence and severity of clinical signs and the presence of SM, and that higher compression indices were associated with more severe SM. They concluded that:
"Dural bands appear to play a significant clinical role. Compression indices provide a better assessment of dural band severity compared to grading."
May 2014: German researchers compare CKCSs with other breeds and find body weight can affect brain volumes, but no brain volume difference between CKCSs with and without SM. In a May 2014 study, a team of German neurologists and other specialists (Martin J Schmidt, Kerstin H Amort, Klaus Failing, Melanie Klingler, Martin Kramer and Nele Ondreka, all of Justus-Liebig-University in Giessen, Germany) compared 20 cavaliers with SM and 20 cavaliers without SM and 35 brachycephalic dogs of other breeds and 35 non-brachycephalic dogs of other breeds, to determine if their brain volumes were affected by their body weights. They report that they could not find a difference in absolute or relative brain volumes between CKCSs with and without SM after relating these values to body weight; and that relative volume of the hindbrain parenchyma (caudal fossa parenchyma percentage) was larger in brachycephalic dogs than in CKCSs, without causing herniation or SM. They concluded that:
"An influence of body weight exist in dogs, which can be sufficiently large to render conclusions on the difference in volumes of the brain and skull unsafe unless some account of the body weight is taken in the analysis. The results of this study challenge the role of overcrowding for the development of SM in dogs."
April 2014: UK's Dogs Trust funds the search for genes for syringomyelia and painful Chiari-malformation in cavaliers. The UK's Dog Trust has awarded the University of Surrey a major grant to fund "Identification of gene(s) predisposing to syringomyelia associated with Chiari-like malformation in the Cavalier King Charles". Dr. Clare Rusbridge will lead the research in collaboration with Dr. Zoha Kibar, of the Montreal University CHUM Research Centre. The team plans to use an approach called "Qualitative Trait Locus" (QTL) analysis which involved linking two types of information -– phenotypic data (trait measure-ments) and genotypic data (usually molecular markers) -- in an attempt to explain the genetic basis of variation and to find a genetic cause for both painful Chiari-malformation and syringomeylia in the breed and lead to improved diagnosis and treatment options.
April 2014: Researchers identify two genomic regions associated with Chiari-like malformation (CM) in the Brussels Griffon. In an April 2014 report, a team of geneticists and neurologists led by Dr. Zoha Kibar (others: Philippe Lemay, Susan P. Knowler [right], Samir Bouasker, Yohann Nédélec, Simon Platt, Courtenay Freeman, Georgina Child, Luis B. Barreiro, Guy A. Rouleau, and Clare Rusbridge) has identified two DNA regions strongly associated with Chiari-like malformation in the Griffon Bruxellois dog. Using a quantitative trait locus (QTL) approach linking DNA molecular markers with MRI information, they were able to identify the two novel genomic regions involved in development of the skull and which also have been associated with a disease linked to Chiari malformation in humans. However, this is just another step towards a hopeful solution to CM and SM in this breed. As they state at the end of their report:
"While QTL analysis represents a strong tool used to identify associations between multiple traits and diseases, our limited cohort size did not suffice to obtain a strong genetic portrait of this complex disease. While the genetic complexity of this disease has probably been reduced by the high homogeneity of a purebred dog, it remained largely oligogenic and no single major locus could be found. However, our study has successfully identified new QTL associated to CM and provides novel insights into the complex genetics of this disease. Clearly additional genetic studies in larger cohorts and/or novel genomic approaches (for example whole genome or targeted exome sequencing) are needed to further investigate these regions and better define their contribution to CM in the dog."
March 2014: German doctorate dissertation concurs that the causes of Chiari-like malformation and syringomyelia are related to a growth disturbance of the cranial base .A German doctoral student, Annabell Johanna Grübmeyer, reports in her January 2014 dissertation that all 107 cavaliers examined by computed tomography and MRI had Chiari-like malformation and that 63 of the CKCSs had syringomyelia. The purposes of the study were to determine if a shortening of the cranial base give rise to pathological changes in CM and the development of SM, and if there is a difference in the cranial base length with or without syringomyelia. She found that the incidence of SM correlated with age and indices of skull base, presphenoid, and basisphenoid, with reduced lengths of the cranial base, presphenoid, and the basioccipital bones and an increase in breadth in dogs with syringomyelia. She concluded that the results support the assumption that the cause of the Chiari-like malformation and syringomyelia is up to a growth disturbance of the cranial base.
March 2014: Belgium researchers find computed tomography (CT) can be used to diagnose Chiari-like malformation in CKCSs. In a 2013 study of nine cavaliers with neurological disorders, a team of Ghent University (Belgium) veterinary radiologists compared the dogs' MRIs and computed tomographs (CTs) and concluded:
"The statistical analysis suggested that both techniques are useful for detecting CH [cerebellar herniation]. However because the bias was significantly different from zero, one of the methods consistently led to the determination of longer or shorter HL [cerebellar herniation length] than the other method. For most comparisons, the HL was on average longer on CT. MRI provides greater soft tissue detail with no beam-hardening artifacts, which may improve the delineation of the cerebellum. Because HL does affect a diagnosis of CM, so CT can be used as a primary diagnostic tool for diagnosing CM in CKSs when MRI is not available."
Editor's Note: Since this study was limited to detecting Chiari-like malformation, there remains a question of the comparative value of CT-scanning for diagnosing syrinxes.
March 2014: Syringomyelia in Hong Kong Pet Population: 2003-2013. In a review of MRIs of 182 dogs in Hong Kong, in a September 2013 abstract before the 26th Symposium of the ESVN-ECVN (published in March 2014), researchers found only four cavalier King Charles spaniels had SM. The most common breed was the Pomeranian (62 cases), followed by the Chihuahua (36 cases), and the Yorkshire terrier (20 cases).
March 2014: Danish study finds 15.4% CKCSs with symptomatic SM and progression from asymptomatic to symptomatic as late as after 6 years. In a multi-year study by a team of researchers at the University of Copenhagen -- M.S. Thofner, A.A. Madry, C.S. Stougaard, C.S. Knudsen, H. Berg, C.S.E. Jensen, R.M.L. Handby, and M. Berendt -- of all 240 cavaliers born and registered in Denmark in 2001, they report in a September 2013 abstract before the 26th Symposium of the ESVN-ECVN (published in March 2014):
"This study found a high prevalence (15.4%) of symptomatic SM in the Danish CKCS population and revealed that despite positive SM findings on MRI, affected dogs may be clinically silent. Asymptomatic dogs may develop clinical signs rather late in life (in this study after the age of six). Despite the high number of affected dogs, euthanasia motivated by SM is relatively moderate. From a clinical point of view our results necessitate further examination of the progression of the disease and assessment of the threshold of outbreak of clinical symptoms."
February 2014: UK researchers find skulls of Brussels Griffons with Chiari-like malformation have skull-shape differences. In a February 2014 article, UK researchers Susan P. Knowler, Angus K. McFadyen, Courtenay Freeman, Marc Kent, Simon R. Platt, Zoha Kibar, and Clare Rusbridge, compared 155 Brussels Griffons with Chiari-like malformation (CM) to normal Griffons. They found that Griffons with CM had taller foreheads and that the CM had caused the shape of the brain to change, with severely affected animals having their cerebellum pushed underneath the main part of the brain. They have included a YouTube video showing a normal Griffon's skull and brain morphing into one with Chiari-like malformation.
In an accompanying press release, Dr. Rusbridge stated:
"Our latest discoveries will be significant in driving this research forward and hopefully allow us to identify which genes may be associated with the condition. Our next steps will be to apply our technique to other breeds with Chiari malformation and investigate more sophisticated ways of screening, so that risk of disease can be detected more easily, at an earlier age and with a single MRI scan.
"We want to engage breeders and give them practical advice about the condition, but it is also important that the public recognises that breeding dogs in a certain way to influence how they look might not be in the animal’s best interest. There are responsible breeders out there, who have invested in screening and who are breeding for health as well as producing attractive puppies, and it is vital that people only look to buy from them."
In their report, the authors conclude:
"This study supports the view that CM is a multifactorial condition that includes the shortening of the entire basicranium, loss of convexity of the supraoccipital bone, invagination of the cerebellum under the occipital lobes and possibly by increased proximity of the atlas to the occiput. As a compensatory change, there is increased height of the rostral cranial cavity and lengthening of the dorsal cranial vault. Overcrowding in the caudal cranial fossa and the craniocervical junction is a defining feature. The study provides the basis of a quantitative assessment of CM which might identify risk of syringomyelia and suggests that CM should be redefined so that account is taken of the overcrowding of the entire cranial fossa and craniocervical junction with reorganization of the brain.
January 2014: Dr. Penny Watson looks for ties between fibrosis in MVD, SM, and chronic pancreatitis in CKCSs. Dr. Penny Watson (right) of UK's Cambridge University's veterinary school is spearheading a new study into whether several of the CKCS breed's hereditary health problems are the result of the same genetic defect. Specifically, she intends to explore the possibility that disparate cavalier diseases, including mitral valve disease (MVD), syringomyelia (SM), and chronic pancreatitis are connected at the cellular level by unusual patterns of fibrotic changes. "Pronounced perivescular fibrosis", a feature in dogs with chronic pancreatitis, also has been tied to a condition of the central nervous system in cavaliers with SM. Dr. Watson has suggested that deterioration of cavaliers' mitral valves also may be a result of a process connected to the causes of fibrosis.
The CKCS breed's documented overabundance of serotonin, a neurotransmitter protein, has been identified as a plausible mechanism which may trigger the development of fibrotic changes in the heart's valves. Her study entails establishing primary stellate cell (SC) cultures from CKCS and define 5HT receptor subtype expression. Stellate cell (SC) activation is a key event in the development of hepatic and pancreatic fibrosis. Serotonin has been shown to activate SCs via 5HT receptors. The study is measuring the response of these cells to serotonin and other stimulators of fibrosis. She then intends to attempt to block SC activation in vitro using 5HTreceptor antagonists. Increased understanding of the factors driving fibrosis will be of benefit to the CKCS and may allow a drug trial in the breed.
November 2013: Univ. of Glasgow thesis reports MRI noise causes hearing loss and reduced cochlear function in dogs. In a 2013 Master of Science (Research) thesis at the University of Glasgow, Rebecca Elisabeth Venn reports that all of 36 dogs (including four cavalier King Charles spaniels) which underwent MRI scans, experienced reduced cochlear function and more than half of the 36 dogs had hearing loss using Distortion Product Otoacoustic Emissions (DPOAE) testing. Ms. Venn noted that the post-MRI testing was not repeated weeks after the MRIs, so it is not known if the hearing loss was temporary or permanent. She also noted that evidence from human MRI noise exposure suggests that the hearing loss is temporary. She recommends that "all dogs having MRI studies performed should have ear protection as a standard precautionary measure."
November 2013: Finnish Kennel Club sets official SM scanning guidelines; to publish results. The Finnish Kennel Club has established a set of official scanning guidelines for syringomyelia. It also will begin publishing the results for SM-scanned dogs in January 2014. See details (in Finnish only) here.
October 2013: Dr. Rusbridge summarizes the current status of CM/SM research. In a wide-ranging article published in the Autumn 2013 EJCAP Online issue for the Federation of European Companion Animal Veterinary Associations (FECAVA), Dr. Clare Rusbridge thoroughly summarizes the current status of research in canine Chiari-like malformation and syringomyelia. She concludes:
"Chiari-like malformation and syringomyelia is an inherited disorder with a high morbidity in many brachycephalic toy breeds. It is characterised by overcrowding of the craniocervical junction, obstruction of CSF flow through the foramen magnum and development of fluid filled cavities in the central spinal cord. Although some cases are asymptomatic, dogs with Chiari-like malformation and syringomyelia can present with neurological signs of which the most important is pain. Surgical and medical treatment options are available but these have limited success and from a welfare point of view it would be better to implement a breeding program limiting the occurrence of this disabling disease."
October 2013: UK's Dr. Peter Smith asks why SM surgeries are failures. In a December 2013 editorial in the Veterinary Journal ("Pathogenesis and pain in Chiari-like malformation"), UK neurologist Dr. Peter M. Smith (right) makes his maiden appearance among CM/SM veterinary journal articles by seeming to criticize others' studies for focusing on the cerebellum protruding through the foramen magnum (i.e., the Chiari-like malformation), indicating that perhaps CM and SM may be coincidental rather than SM due to CM. He suggests the need to understand why the syrinx forms, in order to improve surgical treatments and strategies aimed at preventing development of the syrinx. He then asks, seemingly out of the blue:
"Why, then, does the syrinx not collapse in dogs that undergo decompressive surgery? Perhaps surgery fails to address the key problem in affected dogs."
He does not mention any findings that decompression surgeries have not been successful. While they may not cause the syrinx to collapse, it does not mean that most of those surgeries have been unsuccessful in easing or eliminating the pain and stopping the progression. He goes on:
"Although veterinary studies document exploration of the sub-arachnoid space during surgery, it is possible that this is insufficient to fully restore normal CSF flow at the foramen magnum. ... It seems it is now time to divert our attention from simple morphological observations of the CKCS skull to developing a better understanding of the pain suffered by affected dogs. With greater insight into how the syrinx develops, ably documented by Driver et al. (2013), we should not only aim to understand why some dogs that undergo surgery fail to resolve their syrinx, but perhaps also try to pre-empt the development of the syrinx in the first place."
Dr. Smith does not offer any new strategies aimed at preventing development of syrinxes or achieving better understanding of the pain suffered by affected dogs.
September 2013: New study of the causes of pain and discomfort suffered by cavalier King Charles spaniels with CM and/or SM. Dr. Clare Rusbridge of Fitzpatrick Referrals in the UK and others are conducting a study to understand the causes of pain and discomfort in cavalier King Charles spaniels, seeking to improve the ability to predict painful episodes, and to anticipate and better manage break-through pain, in order to improve the quality of life of cavaliers suffering from CM. Owners of CKCSs with CM and/or SM are asked to complete a questionnaire and then follow the protocol issued by the researchers. Details are here.
August 2013: German dissertation reports that cavaliers' cranial base growth plates close very early at 5th month. In a 2013 doctorate dissertation, German Dr. Melanie Klinger studied the cranial base growth plates of 58 cavaliers and 24 other brachycephalic dogs and 67 mesocephalic dogs for the their first 18 months. She found that:
"In the CKCS the growth plate closure occurred about the 5th month of life. The second group which was composed of the brachycephalic participants of the study followed next. Finally the synchondrosis sphenooccipitalis ossificated in representatives of mesocephalic breeds around the 13.5th month."
"The results confirm the assumption that the premature ossification of the sphenooccipital synchondrosis is the cause of the reduced skull length for brachycephalic breeds. ... With regard to the pathogenesis of the CM the present results support the exceptional position which the CKCS possesses among the brachycephalic breeds."
See also, this June 2013 item.
August 2013: UK researchers suggest CM causes reduced craniospinal compliance, resulting in pressure changes causing SM. UK neurologists C.J. Driver, H.A. Volk, C. Rusbridge, and L.M. Van Ham, in an August 2013 review of the relationship between Chiari-like malformation and syringomyelia, propose that the extent of cerebellar pulsation seen in cavaliers with CM and SM may be a reflection of "craniospinal compliance". They define craniospinal compliance as "the sum of the ability of both the cranial and spinal compartments to accommodate changes in parenchymal, blood or CSF volumes, which all exist in a state of dynamic equilibrium." They propose that CM is the cause of that reduced craniospinal compliance, resulting in a larger pressure difference between the blood and cerebral spinal fluid (CSF) in the cranial and spinal systems. They conclude, "... however, it remains unclear whether this is a cause or effect of this change."
June 2013: Royal Veterinary College still needs 3 more cavaliers to compare neuropathic pain medications for SM. The Royal Veterinary College is seeking three more UK cavaliers diagnosed with symptomatic CM and/or SM to participate in a study comparing two neuropathic pain medications. Eligible dogs must show clinical signs of neck/ back pain, air scratching, facial rubbing, screaming/ yelping episodes or wobbliness. Dogs with kidney or gastro-intestinal disease cannot be included. For more information, contact Johnny Plessas at the RVC at firstname.lastname@example.org or 01707 666366 or click here.
June 2013: UK researchers find cavaliers affected with CM/SM have greater cerebellar pulsation during the cardiac cycle. In a June 2013 study in the Veterinary Journal, UK researchers C.J. Driver, V. Watts, A.C. Bunck, L.M. Van Ham, and H.A. Volk found that cavalier King Charles spaniels affected with syringomyelia (SM) have significantly greater cerebellar pulsation of cerebrospinal fluid (CSF) during the contraction in the cardiac cycle than non-CKCS control dogs and cavaliers with Chiari-like malformation (CM) only. They concluded that their finding suggests that cerebellar pulsation plays a role in the pathophysiology of SM secondary to CM in dogs.
The panelists discussed the two current theories -- the piston theory and the intramedullary pulse pressure theory -- which share the belief that herniation of the cerebellum creates a high-pressure pulse of CSF during cardiac contraction ("systole"). As this wave establishes a difference in pressure between the subarachnoid space and the spinal cord, it is subjected to a distending centrifugal force distal to the blockage, favoring the formation of a syrinx. The primary objective of the study was to use cardiac-gated cine MRI to compare the degree of cerebellar pulsation during the cardiac cycle between three groups: small breed dogs without CM, CKCS with CM alone, and CKCS with CM and SM. A secondary objective was to assess the correlation between cerebellar pulsation and the width of the syrinx, when present.
June 2013: UK & German researchers find earlier closure of cavaliers' cranial joints than in other breeds. In a June 2013 study by UK and German researchers Martin J. Schmidt, Holger Volk, Melanie Klingler, Klaus Failing, Martin Kramer, and Nele Ondreka, they examined MRIs of 174 dogs under 18 months of age, to compare the open or closed status of cranial joints ("synchondroses") between mesaticephalic (e.g., Labrador retriever), brachycephalic (e.g., pug), and cavalier King Charles spaniel dogs. They found statistically significant differences in the closure time of the joint between the skull's sphenoid bone and occipital bone between all three categories of the dogs. They have concluded that earlier closure of the spheno-occipital joint in the CKCS could explain the breed's "caudal occipital malformation syndrome (COMS)".
EDITOR'S NOTE: This group's use of "COMS" probably is due to Drs. Schmidt's, Kramer's, and Ondreka's belief that "Chiari-like malformation" does not appropriately describe the disorder. See their September 2012 comments.
June 2013: UK & German neurologists find connection between venous drainage and parenchyma overcrowding in CKCSs with CM/SM. In a June 2013 report, UK and German neurology researchers Joe Fenn, Martin J. Schmidt, Harriet Simpson, Colin J. Driver, and Holger A. Volk, having compared 22 cavaliers with SM and 12 without SM, found that in CKCSs with SM the percentage of space taken by venous sinuses in the brain is significantly lower than the volume occupied by the brain's parenchyma. Venous sinuses are a network of channels in the brain, which receive blood from the brains veins and also receive cerebrospinal fluid (CSF) and empty blood into the jugular vein.
The report concludes that: "These results support a role for reduced venous drainage and parenchymal ‘overcrowding’ of the CCF [caudal cranial fossa] in the pathophysiology of SM."
May 2013: CM/SM Trust website is up. The website of the CM/SM Trust's canine chiari and syringomyelia research is up and running. Click here. It provides information about CM/SM in both humans and dogs and is worth a good long look. There is extensive information about research projects, upcoming events, biographies of leading researchers and supporters, where and how to contribute, and even a gift shop.
May 2013: UK Kennel Club announces syringomyelia as a "candidate" for EBVs. The UK Kennel Club, in its 2012 Dog Health Group Annual Report, announced that syringomyelia (along with mitral valve disease) "are candidates for the development of EBVs [estimated breeding values] but require appropriate data collection procedures to be in place." The report goes on:
"A BVA/KC scheme for syringomyelia was launched in 2012 and once enough data has accumulated through the scheme then EBVs for the condition will become a possibility."
For more information about EBVs, see our webpage on the topic.
April 2013: German researchers find relationship between pain and asymmetrical syrinxes and dorsal horn involvement in cavaliers with SM. In a 2013 study of 26 cavaliers (11 dogs without clinical signs of pain; 6 dogs with pain and symmetrical syrinxes; 9 dogs with pain and asymmetrical syrinxes), German researchers found "an association" between pain and SM asymmetry, and they found "a strong association" between pain and dorsal horn involvement of SM. CKCSs with clinical signs of pain showed either asymmetrical syrinxes or involvement of the dorsal horn gray matter. They also found that cavaliers with clinical signs of pain showed a presence of interleukin-6 (a key component of the nervous system’s response to injury) and substance P (a neurokinin that regulates the immune functions of spinal glial cells) in their cerebrospinal fluid (CSF). The researchers conclude that the release of interleukin-6 and substance P is a factor in the development of persistent pain in cavaliers with SM. They suggest that this information could offer new diagnostic and treatment options for CKCSs with SM. (In the study's photo above, the top three syrinxes are asymmetrical; the bottom three are symmetrical.)
February 2013: UK neurologists report cavaliers' CM/SM may either result from independent development of the occipital bone and cerebellum or dysregulation of a growth mechanism signal. In a February 2013 report, UK researchers T. A. Shaw, I. M. McGonnell, C. J. Driver, C. Rusbridge, and H. A. Volk compared MRI scans of 45 CKCSs, 38 dogs of other small breeds, and 26 Labrador retrievers, and concluded:
"The data support the hypothesis that CM/SM in CKCS is a multifactorial disease process governed by the effects of increased hindbrain volume and impaired occipital bone development. The present authors recently reported that CM/SM is linked to increased cerebellar volume (Shaw and others 2012). In view of this, the aetiopathogenesis of CM/SM may equivocally be mediated by conditions independently affecting the developing occipital bones and cerebellum, or by dysregulation of a signalling mechanism coordinating the growth of the developing hindbrain and occipital skull."
January 2013: UK's Bristol University seeks CKCS head size data worldwide for The Conformational Indicators Study. Thomas Mitchell, Bristol University researcher, has announced that The Conformational Indicators Study (of whether there is a relationship between head size and shape and CM or SM) now can accept shape and size data from cavaliers worldwide via a new website.
Mr. Mitchell states:
"We are now at the point where we can progress the research further and collect some data internationally for analysis and discussion. We have compiled an instruction manual of measurements that everyone can follow, and we have a fancy webpage where everyone can input the information. By doing this, we will be able to get some definitive answers for the questions that have been brought up here and validate some of our theories! I have already been hard at work taking measurements in the UK to contribute and likewise Henny in the Netherlands, and we will continue to do so; however, this part of the study will allow for people to contribute measurements of all their MRId dogs worldwide! Of course - I will be able to measure the UK dogs, so anybody who wishes to get involved in the UK can contact me directly to organise a visit by email at email@example.com The best thing about this study is that it is going to give all breeders an evidence base to work from in choosing what conformation they want to strive for - hopefully one that will enable better results upon health testing - long in advance of matings, etc."
The instructional guide for compiling the data is at www.cmsmtrust.org/resources/Catalogue-of-Measurements.pdf The data may be input on an on-line measurement collection form here: www.cmsmtrust.org/page31/page47/Mes/index.php
January 2013: US neurologists need previously MRI'd cavaliers for brain/skull size study. Dr. Sofia Cerda-Gonzalez of Cornell University in New York and Dr. Natasha J. Olby of North Carolina State University are performing a study looking into the relationship between brain structure/skull size and clinical changes (development, worsening, or absence of clinical signs) in cavalier King Charles spaniels. This study will help to better understand which, if any, MRI findings are predictive of a cavalier developing new or more pronounced clinical signs in the future. Such information is crucial to understanding the clinical significance of imaging findings and being able to make more informed treatment decisions for Cavaliers.
As such, they are inviting owners of CKCSs that have had an MRI of their brain and/or neck performed four or more years ago to participate in this effort. Through the study, they will provide a no-cost MRI of the brain and neck to a limited number of cavaliers. Owners of participating dogs will be asked to fill out a simple questionnaire, and will be provided with the results MRI imaging at the time of participation. If you are interested in participating, contact Dr. Cerda-Gonzalez at firstname.lastname@example.org or at 607-253-3060.
November 2012: UK clinic studies thermal imaging to detect CM/SM. Stephanie Godfrey of Veterinary Thermal Imaging Limited in Churt, Surrey, UK is studying thermal imaging of dogs to detect Chiari-like malformation and syringomyelia. She states:
"A study came to my attention from an American Veterinarian, Dr. Dominic Marino. A preliminarily study was carried out to establish if a thermographic imaging protocol would be feasible for dogs suspected of having Chiari- Like Malformation (CLM). The preliminarily results have shown that dogs with abnormal MRI findings revealed a 'cooler thermographic pattern' compared to those with normal MRI results. This suggested that thermal imaging may be a useful imaging modality for the screening of CLM detection in dogs. As a veterinary thermographer, I decided that I would like to trial a study over here in the UK to see if this 'cooler reading' would show a correlation to the MRI findings."
The procedure used to explore the use of thermal imaging for the screening of CLM is non-invasive. Thermal images are taken of the dog's head and neck. The images can be taken without the need for sedation, and in the dog's home. The thermographer then examines these images, along with MRI results, to see if a correlation can be seen between skull and neck structures in the affected animals.
Veterinary Thermal Imaging Limited is located on Hale House Lane, Churt, Surrey, GU10 2JG. For more information, contact Stephanie Godfrey at Stephanie.email@example.com, telephone 0844 544 3314, website www.veterinary-thermal-imaging.com
November 2012: German researchers assess effect of gabapentin on post-operative pain after intervertebral disc surgery. In a November 2012 report in Veterinary Anaesthesia and Analgesia, involving 63 dogs, German neurologists compared the pain-relief value of gabapentin when added to opioid analgesia. They concluded that gabapentin administered orally twice a day "did not result in a detectable reduction in pain behaviour compared to background opioid analgesia alone." However, they recommend further studies to determine if the results were related to effective background analgesia or an ineffective dose of gabapentin.
October 2012: UK researchers conclude that neuropathic pain progresses in 75% of CKCSs with CM and/or SM. In an October 2012 study by leading UK CM/SM researchers, they studied the clinical signs of neuropathic pain in 48 cavalier King Charles spaniels for a mean average of over a three year period. Nine of the 48 dogs had only CM. None had been treated surgically. They found that the clinical signs suggest that neuropathic pain progressed in 75% of the dogs with either CM/SM or just CM. They noted that it is not fully understood how CM/SM causes neuropathic pain, and that their study does not make any such finding.
October 2012: UK's Penderis views CKCS's high prevalence of CM and limited genetic diversity as "major difficulties". In an editorial in the Veterinary Journal, UK researcher Dr. Jacques Penderis comments upon recently reported research into Chiari-like malformation and syringomyelia in the cavalier King Charles spaniel. He concludes:
"The high prevalence of Chiari-like malformation in the breed and the confirmation that brain morphology is directly influenced by head phenotype (Hussein et al., 2012), suggests that Chiari-like malformation in the CKCS is likely to be the inadvertent consequence of misguided breeder selection to emphasise certain cranial features deemed to be desirable. The high breed prevalence of Chiari-like malformation (estimated at 95%) points to limited genetic diversity within the CKCS, resulting in major difficulties if breeding away from conformations associated with Chiari-like malformation is attempted in the future."
October 2012: UK's Bristol Univ. plans study of cavaliers' head shapes for CM/SM characteristics. Thomas Mitchell, a researcher at the University of Bristol, in Bristol, UK, seeks to answer the common question, "Can you tell if a dog has CM or SM by looking at it?" He heads "The Conformational Indicators Study" and is investigating the extent to which conformational characteristics -- the external appearance of dogs, such as head shape -- indicate the presence of Chiari-like malformation (CM) and/or syringomyelia (SM). The study seeks to determine if aspects of the conformation are risk factors for CM/SM. This may identify an additional method of indicating disease by measuring the head and body of the dogs, and thereby enable cavalier breeders (and Griffon Bruxellois breeders) to identify which prospective breeding stock to scan and perhaps allow breeders to decide on future matings based upon the overall conformation of the dog and not only on the results of MRI scans.
Breeders of cavaliers with current MRI certificates are being sought to aid this study. All information obtained in the study will be kept confidential, and privacy will be maintained throughout the study. First, the participating breeders are asked to submit their dogs' MRI certificates to a confidential email address, fax number, or postal box. A trained researcher would visit the breeders' premises (or dog show or other breed event) and take a series of non-invasive measurements. A unique ID number will be assigned to each dog, so that the researcher will not know in advance the MRI status of the dog. The ID number also will provide owner confidentiality.
If you are a cavalier breeder and are willing to participate or have questions, contact Thomas Mitchell at CMSMresearch@gmail.com or join the group's Facebook page. See also Dr. Clare Rusbridge's blog article for more information.
September 2012: UK researchers find that CKCSs with SM have narrower jugular foramen than unaffected CKCSs. In a September 2012 report, a team of UK researchers compared 20 cavaliers with SM and 20 without SM and found that the jugular foramen (a space between the temporal bone and the occipital bone, containing the jugular vein), was narrower in the SM-affected cavaliers. They concluded that the narrower gap of the jugular foramen in SM-affected CKCSs may affect the pressure waves of cerebrospinal fluid (CSF) and serve as an additional factor (other than cerebellar herniation) causing SM.
July 2012: Australian vet surgeons find cavalier with life-threatening dysphagia caused by Chiari-like malformation. A team of Australian veterinary surgeons report of foramen magnum decompression surgery resolving a cavalier King Charles spaniel suffering from life-threatening dysphagia (difficulty in swallowing food caused by disease or impairment of the nervous system). They conclude that CM can be a cause of dysphagia in dogs.
July 2012: UK researchers find no connection between Chiari-like malformation and epilepsy in cavaliers. In a 2012 report in the Veterinary Journal, UK neurology researchers C.J. Driver, K. Chandler, G. Walmsley, N. Shihab, and H.A. Volk examined the MRIs of 85 cavalier King Charles spaniels, looking for a relationship between Chiari-like malformation (CM), ventriculomegaly, and seizures in the dogs. The 85 CKCSs all had CM; 27 of them also had had seizures. They found no association between CM, ventriculomegaly, and the seizures. The seizures were classified as having partial onset -- meaning that they occur in in one area of the brain, unlike generalized seizures which typically affect nerve cells throughout the brain -- in 61% of the dogs. They also stated that "Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported."
July 2012: International neuropathic pain study is completed; results are awaited. A multi-school clinical study evaluating the efficacy of a novel treatment for the control of pain associated with syringomyelia in cavalier King Charles spaniels has been completed, We first reported this study in November 2007. The study was part of a collaborative effort between a pharmaceutical company, and the vet schools at the UK's Royal Veterinary College, the University of Pennsylvania, and the University of Minnesota. The study recruited patients from November 2007 to October 2008 and after screening 119 dogs, a total of fifty two patients participated in the trial. Following statistical analysis, the report is that the results are promising, and that there is potential for further development of this new medication to help alleviate the pain associated with syringomyelia.
July 2012: UK Kennel Club adds a CM/SM recommendation for cavaliers to its Assured Breeder Scheme. Effective July 1, 2012, the UK Kennel Club's Assured Breeder Scheme recommends that all CKCSs being bred first comply with the BVA/KC Chiari Malformation/Syringomyelia Scheme breeding guidelines. This is not a mandatory requirement for participants of the Assured Breeder Scheme.
June 2012: UK researchers report results of questionnaires on neuropathic pain in CM/SM- affected cavaliers. In a 2012 study, UK researchers (Lynda Rutherford, Annette Wessmann, Clare Rusbridge, Imelda M. McGonnell, Siobhan Abeyesinghe, Charlotte Burn, and Holger A. Volk). of cavaliers with neuropathic pain report on the results of extensive questionnaires completed by the owners of 122 CM/SM-affected CKCSs. They found that owners who noticed evidence of neuropathic pain in their dogs also found the dogs to have increased fear-related behaviors (such as acting more fearfully when approached by strangers, or when in unfamiliar situations, or when sudden loud noises occurred, such as thunderstorms). These dogs also were more clingy to their owners and appeared to be more fearful when left alone. They also showed decreased willingness to exercise, and problems in settling, including sleep disturbances. Not surprisingly, the study also showed that owners found that their affected dogs had reduced quality of life.
June 2012: German researchers dispute that cavaliers have Chiari-like malformation. In a June 2012 report in Veterinary Radiology & Ultrasound, German neurologists and radiologists Martin J. Schmidt, Martin Kramer, and Nele Ondreka compared the volumes of occipital bones of cavaliers with and without syringomyelia and of French bulldogs. They did not find a reduced volume of the occipital bone of CKCSs, compared to the bulldogs. They concluded:
"These results do not support occipital hypoplasia as a cause for syringomyelia development, challenging the paraxial mesoderm insufficiency theory. This also suggests that the term Chiari-like malformation, a term derived from human studies, is not appropriate in the Cavalier King Charles spaniel."
EDITOR'S NOTE: The authors of this article seemed mired in the pre-2010 definition of Chiari-like malformation. They state:
"... [T]he Chiari-like malformation in the Cavalier King Charles spaniel is characterized by indentation of the occipital (bone) with cerebellar herniation and is more correctly termed caudal occipital malformation syndrome."
They also appear to be unduly dismissive of the studies beginning in 2009 which found that the cavalier's cerebellum is relatively larger than that in other breeds. The authors of this June 2012 article did not include cerebellum size in their study, and their comment about the 2009-2012 reports simply is:
"Results of studies proposing a mismatch between cerebellar and caudal cranial fossa volume in this breed and in comparison to other breeds were controversial. In some studies, there was a mismatch between caudal fossa parenchyma and caudal fossa volume in dogs with syringomyelia and overcrowding was proposed as a cause of syringomyelia development. In most studies, however, no difference was found between caudal fossa volume in Cavalier King Charles spaniels with and without syringomyelia, although this was not universal." (Emphasis added.)
April 2012: RVC to compare chicken and mouse cerebellar development with that of CKCSs. Royal Veterinary College researchers Dr. Imelda McGonnell and Dr. Holger Volk plan to investigate cerebellar development in various chicken, dogs and mouse models, in hopes that this research will lead to a better understanding of the Chiari-like malformation disease process and provide therapeutic targets. This project is being jointly undertaken in the laboratories of Drs. McGonnell and Volk at the RVC and Dr. Albert Basson at the Dept Craniofacial Development, Kings College London, and is being funded by the Wellcome Trust. Read more here.
April 2012: UK researchers find an association between syringomyelia and the cavalier's oversized cerebellum. In an April 2012 report, UK researchers Thomas A. Shaw, Imelda M. McGonnell, Colin J. Driver, Clare Rusbridge, and Holger A. Volk, confirmed previous studies that cavalier King Charles spaniels have proportionately larger cerebellums than other small breeds and Labradors. They also found an association between the CKCS's oversized brains and SM. 75 cavalier MRI scans were reviewed. They concluded:
"These findings support the hypothesis that it is a multifactorial disease process governed by increased cerebellar volume and failure of the CCF to reach a commensurate size."
April 2012: RVC needs cavaliers to compare neuropathic pain medications for SM. The Royal Veterinary College is seeking UK and US cavaliers diagnosed with symptomatic CM and/or SM to participate in a study comparing two neuropathic pain medications. Eligible dogs must show clinical signs of neck/ back pain, air scratching, facial rubbing, screaming/ yelping episodes or wobbliness. Dogs with kidney or gastro-intestinal disease cannot be included.
The RVC and the Queen Mother Hospital Royal Veterinary College and Queens Veterinary School Hospital and Stone Lion Veterinary Group, all in the UK, as well as the College of Veterinary Medicine, Iowa State University, in Ames, Iowa USA, are participating. For more information, email firstname.lastname@example.org or click here.
April 2012: Geoff Skerritt and Dr. Luca Motta find shunt surgery successful for relieving SM pain. UK neurosurgeons Geoffrey Skerritt and Dr. Luca Motta report in an April 2012 study that:
"[Syringosubarachnoid shunt] S-S shunting is a safe and relatively effective surgical technique that may improve the neurological signs and the quality of life of dogs affected by CM and associated SHM/SM. Postoperative complications or lack of clinical improvement may occur in a small number of cases and a secondary surgery may be needed. This study also suggests that the S-S shunt may lead to a satisfactory outcome in dogs where the FMD [foramen magnum decompression] technique has failed. Comparisons between different surgical techniques are needed to create objective criteria that may suggest which procedure will produce the best surgical results."
The researchers performed surgeries on nine cavaliers and two Yorkshire terriers. Ten of the dogs survived the study. They also devised a Pain Score Scheme (see table above under Symptoms) to evaluate the levels of pain the dogs experienced both before and following the surgeries.
March 2012: UK's BVA and KC issue CM/SM breeding guidelines. The British Veterinary Association (BVA) and the UK's Kennel Club (KC) issued in March 2012 a set of Chiari-like malformation and syringomyelia (CM/SM) breeding guidelines, with the aim of removing from breeding programs, cavalier King Charles spaniels with early-onset SM, and thereby reducing or even eliminating the incidence of CM/SM in future generations of cavaliers. This SM breeding protocol is limited to cavaliers (and other breeds) registered with the UK's Kennel Club. The two USA national cavalier clubs have refused to acknowledge the existence of any SM breeding guidelines, and the US clubs place no restrictions on breeding cavaliers with CM/SM.
December 2011: The Cavalier Foetal Tissue Research Project's website is online. Sheena Stevens has created a website about the Cavalier Foetal Tissue Research Project: http://www.ftrproject.com Check it out to learn more about this research program and how to contribute funds to it. Also, read more about the project here.
December 2011: UK researchers confirm that cavaliers with only CM suffer pain and that CM/SM is progressive. In a December 2011 study at the Royal Veterinary College, researchers studied 49 clinically affected CKSCs. They found: (a) 25% did not have SM; (b) the severity of SM was positively correlated with patient age; and (c) there is a very high potential for CKCS with clinical signs of CM/SM to develop SM in more than one spinal cord region.
October 2011: Univ. of Penna. cardiologists study torsemide as alternative to furosemide. University of Pennsylvania veterinary cardiologists report that they have tested the loop diuretic torsemide as alternative to furosemide in dogs with advanced heart failure, including a 12 year old cavalier. They have found torsemide "has several characteristics that make it suitable for treatment of advanced heart failure including longer half-life, increased potency of diuretic action, and anti-aldosterone effects."
October 2011: SM Breeding Protocol Statistics. In an October 2011 report of the statistical results of following the SM protocol, the researchers, Dr. Rusbridge, Penny Knowler, and A. K. McFadyen stated that:
"This study investigated the early outcome of existing SM breeding guidelines. Six hundred and forty-three dogs, 550 Cavalier King Charles spaniels (CKCS) and 93 Griffon Bruxellois (GB), were identified as having either one (454 dogs) or both parents (189 dogs) with MRI-determined SM status.
• Offspring without SM were more common when the parents were both clear of SM (SM-free; CKCS 70 per cent, GB 73 per cent).
• Conversely, offspring with SM were more likely when both parents had SM (SM-affected; CKCS 92 per cent, GB 100 per cent).
• A mating of one SM-free parent with an SM-affected parent was risky for SM affectedness with 77 per cent of CKCS and 46 per cent of GB offspring being SM-affected.
It is recommended that all breeding dogs from breeds susceptible to SM be MRI screened; that the SM status at five years old is established; and all results submitted to a central database that can be used by dog breeders to better enable mate selection based on estimated breeding values."
September 2011: UK researchers examine distribution of pain-related neuropeptides in cavaliers with SM. They observe that CKCSs with clinical signs of SM also show disruption in the structure of their spinal cord's dorsal horn. See report summary. The researchers conclude:
"This current study provides evidence to suggest that the disruption of the dorsal horn structure is a significant event in the production of clinical signs in CKCS. The spinal cord dorsal horn in symptomatic CKCS is significantly more asymmetric than that of control animals, whereas the asymptomatic CKCS have changes that are midway between control and symptomatic CKCS. This suggests the possibility that progression from mild to severe asymmetry in CKCS is associated with development of clinical signs; however such a conclusion cannot be definitively supported by this study because of the cross sectional nature of the data collected."
September 2011: Researchers find that SM is associated with degenerative changes in the spinal cord. In a study published in the Journal of Comparative Pathology, researchers H.Z. Hu, Clare Rusbridge, F. Constantino-Casas, and Nick Jeffery report that:
"SM is associated with degenerative changes in the spinal cord and may develop through primary disruption of ependymal integrity followed by vascular hypertrophy and proliferation. Glial and fibrous proliferation appears to be associated with expression of clinical signs."
The ependyma is the epithelial membrane which lines the spinal cord. Vascular hypertrophy means the increase in the volume of blood vessels. Glial are cells that provide protection for the brain's neurons (right), among other things.
Commenting on the findings by one of the article's authors, Dr. Clare Rusbridge, she writes on her blog:
"The pathology suggested that the primary development of syringomyelia is associated with central canal dilatation and damage which is accompanied by blood vessel changes. This is an important finding because there is so much debate on how syringomyelia develops in all species."
August 2011: Head position affects extent of cerebellar herniation in MRI scans. UK researchers examining 14 CKCS MRI scans (7 with CM/SM and 7 with just CM) comparing scans in both extended and flexed head positions. In their report, they have found the degree of cerebellar herniation was significantly worse in dogs with a flexed compared to an extended head position. When cerebrospinal fluid (CSF) space between the cerebellum and brainstem was compared in CKCS with and without SM, there was a significant increase in CSF space in CKCS with CM alone compared to those with CM/SM when head position was flexed. Based upon their findings, they state that it may be appropriate to position patients in a more flexed head position for optimal imaging in order to identify morphologic changes more accurately. They stated that this is important to consider for imaging CKCS with CM especially when studying the pathogenesis of CM/SM.
The researchers also found:
"When CSF space between the cerebellum and brainstem was compared in CKCS with and without SM, there was a significant increase in CSF space in CKCS with CM alone compared to those with CM/SM when head position was flexed. In their cine MR imaging study of CSF flow dynamics in CKCS with CM or CM/SM, Cerda-Gonzalez and others (2009a) found that turbulent CSF flow and jets are associated with SM presence and severity and CSF flow velocity at C2/3 is inversely related to the presence of SM. The reduced CSF space in CM/SM dogs reported in this study could explain this jet like CSF flow in dogs with CM/SM compared to those with CM alone."
This could mean that the severity of CM/SM, or even the presence or future presence of SM, could be predicted based upon the measure of cerebrospinal fluid space between the cerebellum and the brainstem. If so, this could go a long way to distinguishing whether a CM-only cavalier is either likely or unlikely to develop SM in the future. This distinction could be a way to fine-tune a breeding protocol, considering that we now know that over half of cavaliers with SM develop it after their 3rd birthday. If we could reliably count on this measurement of CSF space to tell us if a young dog will, or will not, develop SM in the future, then we could more reliably select SM-free breeding stock at a younger age than the present 2.5 years and the 3+ years the researchers may recommend in the future.
June 2011: Montreal team of researchers identify chromosome 2 region associated with Chiari-like malformation in the Brussels Griffon breed. See summary here. Researchers include Lemay P, Trinh QH, Dubé MP, Rusbridge C, Rouleau GA, and Kibar Z.
June 2011: UK researchers find that CM is progressive in CKCSs; that foramen magnum size and cerebellar herniation increase significantly. UK researchers, including Drs. Rusbridge, Driver, and McGonnell, reported to the ACVIM in a June 2011 study that twelve CM-affected cavaliers' foramen magnums and the length of cerebellar herniation "increased significantly" between MRI scans which averaged 9.5 months apart. they concluded:
"This work could suggest that overcrowding of the caudal cranial fossa in conjunction with the movements of cerebrospinal fluid and cerebellar tissue secondary to pulse pressures created during the cardiac cycle causes pressures on the occipital bone. This leads to a resorption of the bone and therefore an increase in caudal cranial fossa and foramen magnum size allowing cerebellar herniation length to increase."
June 2011: UK researchers report CKCS has relatively larger cerebellum than both small breeds and Labradors. In a June 2011 report to the ACVIM, UK researchers, including Drs. McGonnell, Driver, and Rusbridge, compared cerebellar size of cavaliers with other small breed dogs and with Labrador retrievers. They conclude: "Our findings show that the CKCS has a relatively larger cerebellum than small breed dogs and Labradors and there is an association between increased cerebellar volume and SM in CKCS."
June 2011: Long Island Veterinary Specialists report 97.3% accuracy in thermography diagnosing Chiari-like malformation in CKCSs. Drs. Catherine Loughin and Dominic Marino released a June 2011 study of 105 cavaliers, comparing the results of medical infrared imaging (MII), also called thermography, with MRIs to detect the presence of CM. The results: "The top of head and front of head ROI [regions of interest] were 89.2% and 97.3% successful in identifying dogs with CLM. Based on these preliminary findings, MII may be a viable screening tool to detect CLM in dogs." Thermography does not require sedation.
June 2011: Omeprazole profoundly increases dogs' serum gastrin concentration in two weeks. US researchers studying the effect of two weeks of omeprazole doses on healthy dogs reported "a profound and sustained increase in serum gastrin concentration in dogs. This effect is rapidly reversible after cessation of the treatment. No effect on calcium metabolism was observed."
June 2011: Alastair Cockburn to study pain due to SM. The Universities Federation for Animal Welfare (UFAW) has awarded a Research Training Scholarship to Alastair Cockburn of the University of Bristol. He will investigate methods for assessing pain, underlying emotional state and quality of life in dogs with chronic pain conditions of syringomyelia and osteoarthritis. The aim of the research project is to deliver a useful clinical tool to measure chronic pain in dogs, a problem area due to the often very subtle changes in behavioral indicators of pain and the difficulty of assessing underlying emotional state and cumulative experience of pain – factors of critical importance in assessing quality of life.
June 2011: UK study of 555 cavaliers shows percentage with SM up to 70% in older dogs with no symptoms. A UK study of 555 (reportedly) asymptomatic CKCSs found 25% of 12 month olds with syringomyelia, increasing to 70% in cavaliers 6 years and older. The researchers concluded:
"The evidence for a lower prevalence in younger animals is more reliable (because of the higher numbers included in the present study and the lower likelihood of false inclusion) and this effect lasts until dogs are at least three years of age. This finding has important implications for the design of a screening test procedure and may conflict with the current recommendations that the optimum age for screening should be 30 months. These data would imply that it is probable that dogs aged up to three years may yet have reduced odds for the diagnosis of syringomyelia. However, there is a need for the dogs to be creened when they are reasonably young so that breeders can decide at an early stage whether their animals are suitable for breeding; many breeders would consider 36 months unduly old. ... The high lifetime prevalence of syringomyelia raises concerns for the welfare of the CKCS breed and also suggests that eliminating the genetic risk factors for the disease by selective breeding may be difficult, because the heritability has previously been shown to be complex, and the prevalence of the determinant genes within the population is therefore likely to be high. The true prevalence of syringomyelia in the general CKCS population is expected to be higher than that found in this sample population because symptomatic dogs were specifically excluded."
May 2011: Somatosensory-evoked potentials' (SEP) amplitude is more sensitive measure of spinal cord function in CKCSs with SM. UK researchers report that SEP amplitude at the C1 vertebra was a more sensitive measure of spinal cord function in CKCSs with syringomyelia, compared with results of EMG or TMMEP assessment. Measurement of SEP amplitude may have use as an objective assessment of the evolution and treatment of this disease. Read the details here.
March 2011: UK researchers find that the development of syringomyelia is accompanied by alterations in cerebrospinal fluid composition. Read their summary here.
February 2011: Rupert’s Fund Report for 2010. Rupert's Fund reports that in 2010, its fund raising paid for 29 dogs (all over 6 years except for one over 5 year years old male). The average age was 7.7 years and the oldest dog scanned was 12 years. Results: 18 CKCS were graded A (11 females and 7 males); 11 CKCS were graded D (6 female and 5 males). All had CM, two with only mild CM. Dr. Clare Rusbridge and Penny Knowler report:
"Older dogs scanned have highlighted that SM can be late onset and/or progressive. Several dogs were selected because they already had previously scanned clear but had subsequently developed SM even after the age of 4 years. Such valuable additional information allows the researchers to investigate factors which might influence why some syrinxes progress rapidly and others don’t. Analysis of litters produced using the interim breeding guidelines revealed that higher numbers of dogs which were SM-clear over five years were produced if a parent was also clear of SM over 5 years.
"Donations from RF continue to fund MRIs. Priority is given to male dogs over 6 years, particularly if they have already had a SM-clear scan, but we are also interested in stud dogs of 5 years of age and bitches that have had a scan over 4 years of age or unknown MRI status over 8 years of age and asymptomatic. However, all requests made for Rupert's Fund are considered on an individual basis, and no one should be deterred in applying if they can justify how it helps the breed."
January 2011: Chiari-like malformation has been re-defined. On the website of syringomyelia researcher Dr. Clare Rusbridge, CM now is defined as "a condition characterized by a mismatch in size between the brain (too big) and the skull (too small). There is not enough room for the brain and the back part (cerebellum and medulla) is pushed out the foramen magnum." The foramen magnum is a hole in the back of the skull -- in the occipital bone -- leading to the spinal cord. Dr. Rusbridge goes on to explain that the cavalier appears to have a brain more appropriate for a bigger dog. Go here for more discussion.
January 2011: UK researchers find distribution of SM along entire spinal cord of cavaliers; syrinx size positively correlated with age. In MRI studies of 49 cavaliers, reported in 2011 in the Veterinary Journal, Dr. Clare Rusbridge and others found that "Syrinx formation was present in the C1–C4 region and in other parts of the spinal cord. The maximal dorsoventral syrinx size can occur in any region of the spinal cord." Seventy-six per cent of CKCS with a cranial cervical syrinx also had a syrinx in more caudal spinal cord regions.
They concluded that, "MRI restricted to the cervical region may underestimate the extent of SM and the severity of the disease process in the majority of dogs." Therefore, so-called "mini-MRI-scans" of only the cervical region, such as those scans for breeding protocol purposes, may not necessarily locate all syrinx which an SM-affected cavalier may have. They also found that total syrinx size positively correlated with the age of the dog.
October 2010: Long Island Veterinary Specialists has started "The Canine Chiari Institute", with the mission "To improve the lives of dogs afflicted with Chiari-like Malformation and related disorders through research and continuing education." Its website is under construction, but parts of it are operative.
October 2010: Current results of following the SM Breeding Protocol. In an interim report of the statistical results of 393 cavalier offspring of MRI-scanned breeding stock, Dr. Clare Rusbridge stated that:
• Matings of Code A CKCS to Code A CKCS have
produced 75.9% offspring with no SM.
• Matings of Code A CKCS to either Code D, E, or F CKCS have produced 41.9% offspring with no SM.
• Matings of Code A CKCS to unscanned CKCS have produced 50.0% offspring with no SM.
• Matings of Code D CKCS to Code D, E, or F CKCS have produced no offspring free of SM
June 2010: Canadian researchers find TMMEP, SSEP, SEP and BAER testing for SM do not work. In a 2010 report, a group of Canadian neurologists tested fifty cavaliers to evaluate the validity of BAER as well as transcranial magnetic motor evoked potentials (TMMEP), somatosensory evoked potentials (SSEP), and spinal evoked potentials (SEP), compared to MRIs. The researchers found: "TMMEP, SSEP, SEP and BAER do not appear to be valuable tests in detecting functional abnormalities of the motor and sensory pathways throughout the central nervous system of CKCS dogs with and without neurological signs secondary to SM diagnosed by MRI."
They also found a significant linear correlation between the severity of neurologic dysfunction and size of the syrinx, with a larger syrinx being associated with more severe neurologic signs.
June 2010: UK researchers report severe SM relates to greater hindbrain - caudal fossa volume mis-matches. In an abstract (A Comparison of Ventricular and Caudal Fossa Volumes in Cavalier King Charles Spaniels > 5 years of age that have not developed Syringomyelia vs those Affected when < 2 years) presented to the BSAVA by Colin Driver, Dr. Rusbridge, et al., they found that severe SM in cavaliers under 2 years old is associated with greater mis-match between hindbrain and caudal fossa volume than found in older CKCSs with CM but no SM. MRIs of 21 cavalier King Charles spaniels under 2 years affected with CM/SM, and 14 CKCSs over 5 years with only CM were analyzed.
June 2010: A UK study of 59 cavalier King Charles spaniels (71% having syringomyelia) confirms earlier findings that the variations in the dimensions of the cavaliers' posterior cranial fossa* is not associated with syringomyelia. Instead, this study, led by Colin Driver, BSc, BVetMed (Hons), MRCVS, points to two other possible connections. First, they found that a cavalier with a higher volume of parenchyma (brain matter) within the cranial fossa is more likely to have SM, and the greater the volume of parenchyma, the larger the syrinx. They state:
"There was a significant difference in [percentage of parenchyma within the caudal cranial fossa] CCFP between those without or with SM. ... More marked brain and skull volume mismatches result in SM because a higher parenchyma percentage (CCFP) is associated with the presence of a cervical syrinx. This could explain the high incidence of SM secondary to CM in CKCS reported by Rusbridge and Knowler (2003). Although statistically significant, the difference in means for CCFP between the two groups appears small. It is therefore hypothesised that only a small difference in parenchymal volume is necessary to influence the development of a cervical syrinx. Furthermore, as the total volume of parenchyma and ventricular CSF within the CCF correlates with cervical syrinx dimensions, it can be hypothesised that more marked overcrowding of the caudal fossa results in greater compression of the subarachnoid space and subsequent syrinx dilatation."
Second, they also found a direct relationship between between the dimensions of the ventricles** and the size of the syrinx. They state:
"Furthermore, there is an association between ventricle and syrinx dimensions which supports the theory that SM development is the result of altered CSF dynamics."
* The posterior (or caudal -- for "rear") cranial fossa is part of the cavity within the skull. It contains the brainstem and cerebellum, and towards its rear, it is enclosed by the occipital bone, which also frames the opening called the foramen magnum.
** Brain ventricle: One of a system of four communicating cavities within the brain that are continuous with the central canal of the spinal cord. The four ventricles consist of the two lateral ventricles, the third ventricle and the fourth ventricle.
The researchers also discuss some What-Could-Be theories (a few admittedly are laden with technical verbiage: (1) "CM might be the result of paraxial mesoderm insufficiency during embryogenesis"; (2) "There is failure of communication between the paraxial mesoderm and the cranial somites with the closing neural tube, resulting in loss of coordination between skull and brain growth (paraxial mesoderm forms the supraoccipital bone, somitic mesoderm forms the exoccipital and basioccipital bones)"; (3) "Overgrowth of the cerebellum causes the mis-match because CKCS have proportionately more hindbrain parenchyma than other small breed dogs"; and (4) "Early growth plate closure may result in CM because despite the dynamic nature of osseous tissue, it would be unable to accommodate the developing brain."
They concluded that:
"The mild but significant difference of CCFP in CKCS with or without SM reflects the clinical difficulty in identifying those dogs that will develop SM. This study does not correlate the presence of SM with clinical signs or disease progression, which would be important for guiding the choice of therapeutic intervention. It therefore remains appropriate to continue to make clinical decisions on the basis of severity of clinical signs. Further studies evaluating these measurements as prognostic indicators are therefore warranted."
May 2010: Dr. Rusbridge reports genetic researchers may have found the site for SM on the cavalier's genome. In a May 20, 2010 update on her website, Dr. Rusbridge publishes an interim report in highly technical wording, which states that they have located a haplotype which contains mutations in SM-affected dogs and does not contain such mutations in unaffected cavaliers. Gene sequencing and additional mapping of the locus is under way.
May 2010: Dr. Clare Rusbridge says microchips can interfere with MRI scans. Dr. Rusbridge stated that if a microchip is located near the upper spinal column being scanned, it could block the view of a syrinx. She said that a microchip will warp the image, resulting in a hole in the scan. She recommended that microchips be placed as low as possible over the thoracic vertebrae. Dr. Rusbridge spoke on May 2, 2010 at a syringomyelia symposium sponsored by the Griffon Bruxellois Club of the UK.
May 2010: Dr. Sarah Blott issues her first report on using estimation of breeding values (EBVs). She writes in her May 2010 article:
"EBVs will allow breeders to distinguish between potential parents of high and low risk, after removing the influence of life history events. Analysis of current population structure, including numbers of dogs used for breeding, average kinship and average inbreeding provides a basis from which to compare breeding strategies. Predictions can then be made about the number of generations it will take to eradicate disease, the number of affected individuals that will be born during the course of selective breeding and the benefits that can be obtained by using optimisation to constrain inbreeding to a pre-defined sustainable rate."
April 2010: Dr. Thomas Schubert uses LactoSorb SE mesh instead of titanium in CM cranio-plasty surgeries. LactoSorb SE is a biodegradable polymer designed to resorb in the human body by hydrolysis within a year. It is being used instead of titanium mesh in cranioplasty surgeries performed on cavaliers by Dr. Thomas Schubert at the University of Florida. This product reportedly is equal in strength to titanium at initial placement, retains 70% of its initial strength for the first eight weeks, and then gradually is eliminated from the body. It is manufactured by Biomet Microfixation, LLC of Jacksonville, Florida.
March 2010: UK researchers ask owners to describe how their SM-affected cavaliers behave. Drs. Lynda Rutherford and Holger Volk of The Royal Veterinary College's neurology service offer an on-line questionnaire for owners to complete, about the impact of SM on the owner's dog and the owner's life. They state, "It is also important to consider the general 'happiness' in a breed as this might have an impact on how an animal can live with a certain condition. We hope this information will help other owners caring for dogs with SM as well as veterinary surgeons in communicating issues associated with the disease."
This is available to cavalier owners worldwide. Go to http://www.surveymonkey.com/s/3XT8BPV and enter the password CKCS3 to start the questionnaire. If you wish, all information you give will be anonymous and untraceable.
March 2010: Contribute to RUPERT’S FUND. RUPERT’S FUND is a project to help fund MRI scans of Cavaliers aged 6 years and older. These scans are a critical part of the Syringomyelia Genome Research Project, which is nearing completion. Please help these senior dogs help the breed’s future! As little as £10.00 makes a difference.
Rupert's Fund lets every single one of us do something positive for the breed we love. All that is asked is that donations be made in UK pounds sterling, and that the minimum amount be 10 UK pounds. If you use PayPal, it’s really easy to make donations. You can select the currency (which means the researchers get the most out of your donation if you pick "pounds sterling"). If you are in the UK, and can write sterling cheques, you can make donations this way as well. Go to http://rupertsfund.com and follow the instructions.
February 2010: MRI scans of Australian CKCS breeding stock shows 50% with SM. Dr. Georgina Child, board certified veterinary neurologist at the Small Animal Specialist Hospital in North Ryde, NSW, Australia, spoke to the CKCS Club of NSW about syringomyelia this month and reported that of 60 cavaliers which have been MRI scanned under the SM breeding protocol, 50% have been found to have syrinxes on their MRIs. None of these scanned dogs had any symptoms of SM, and all were potential breeding stock. Their syrinxes ranged from 2 mm to over 5 mm in size.
October 2009: Auburn University researchers use swine tissue and body fat to prevent scar tissue after CM surgeries. Veterinary surgeons, including Dr. Andy Shores, board certified neurologist at Auburn, and Dr. Jill Narak, now at the University of Tennessee, and Dr. Michelle Carnes, now at Veterinary Specialists of South Florida, have performed foramen magnum decompression (FMD) surgeries on 14 dogs, including 11 CKCSs. Instead of inserting titanium mesh when closing the incision, they performed a duroplasty using swine intestinal submucosa and covering it with fat tissue graft (FAATG) from the dog's gluteal region.
"In dogs that require FMD in the treatment of COMS, this modified technique using a FAATG should be considered. Current clinical outcomes of patients that were treated for COMS using this technique showed excellent results similar to current published literature without intraoperative complications and clinical improvement with a decrease in clinical signs postoperatively. The use of the titanium mesh, placement of the screws, and the exothermic reaction of the overlying methyl methacrylate may contribute to tissue trauma. The authors conclude that with the results of this study, this procedure is clinically effective and the use of a titanium mesh, additional hardware and methyl methacrylate offers no advantage in canine COMS patients."
August 2009: UK researchers find no significant difference in spinal canal widths of 59 SM and 19 non-SM cavaliers.
August 2009: UK researchers find that cavaliers do not have a proportionately smaller caudal fossa compared to other small breeds, but that the CKCS's brain is comparatively large. They wrote:
"When compared with Labradors, CKCS had proportionately the same volume of parenchyma in their caudal fossa, hence there is a mismatch of volumes with too much parenchyma in a too small caudal fossa causing overcrowding. ... Other small breeds of dogs had a proportionately smaller volume of parenchyma in their caudal fossa which can explain why, despite having a similar sized caudal fossa to CKCS, they do not experience overcrowding. It is hypothesised that through the miniaturisation process of other small dogs, both the cranium and brain are proportionately smaller but in CKCS only the cranium has reduced in volume, hence why there is a higher incidence of CM in CKCS than other small breeds.
"Cavalier King Charles spaniels also had a greater percentage of their cranial fossa filled with parenchyma (cranial fossa parenchyma percentage) compared with small breeds and Labradors which had a similar percentage. Overcrowding in CKCS might therefore occur due to a mismatch in volumes in both the caudal fossa and cranial fossa of the skull, suggesting the cranial fossa is also involved in the pathophysiology of CM."
A possible cause of CM? In the same 2009 report comparing the cerebral cranium volumes of the CKCS with those of other small breeds and the Labrador retriever, Hannah Cross and Drs. Claire Rusbridge and Rodolfo Cappello conclude:
"The results support mesoderm* insufficiency or craniosynostosis* as the pathogenesis of Chiari-like malformation (CM) in CKCS. It presents evidence for overcrowding of the caudal fossa due to a mismatch of brain parenchyma and fossa volumes as to why CKCS and not other small dogs are affected."
* The mesoderm is the middle of the three primary germ cell layers -- the others being ectoderm and endoderm -- in the early stage of an embryo. The mesoderm is responsible for developing various tissues and structures, such as bone, muscle, connective tissue, and the middle layer of the skin. Mesoderm insufficiency during embryology may cause insufficient scope for the mesoderm and ectoderm layers to develop. Craniosynostosis is the premature closure of the skull's growth plate.
May 2009: Cavalier fetal and neonatal specimens show signs of CM. Dr. Imelda McGonnell of the Department of Veterinary Basic Sciences, The Royal Veterinary College, has been leading a study looking at anomalies in different stages from the cavalier's early growth in the uterus to its maturity. The study has been examining aborted fetuses and deceased young puppies that have died for any reason. In an interim report, Dr. McGonnell advises that abnormal cell division in the immature occipital bone may cause growth of the skull to not keep up with the growth of the cerebellum. She writes:
"Anatomical investigations have shown that the occipital bone overlying the cerebellum has an abnormal bulge in the centre. These investigations also show that the cerebellum is compressed in CKCS foetuses at birth. However this compression is not yet sufficient to cause descent of the brain into the foramen magnum. The region of the compression in the brain corresponds to the region where we see the bulge in the bone. It suggests that the abnormal skull is compressing the brain. When we looked at the occipital bone in more detail, using sectioning, we saw that there was a region where there were more cells than normal – this was the region of the bulge. These cells were also immature – they had not formed proper bone. We looked at the part of the spinal cord nearest the brain but did not see SM. We will continue to examine the remainder of the spinal cord.
"When we looked at the cerebellum, we also found that there were more cells in parts of the cerebellum. When we counted the numbers of cells that were dividing, they were statistically significantly increased. Usually if there are too many cells being produced, we see lots of cells dying. However we found there were fewer cells dying. Both the increased cell division and reduced cell death make the cerebellum bigger. We also saw that some cells in the cerebellum that control co-ordination of movement were also not properly formed. This all tells us that both the brain and the bone are growing too much and that as a result, some of the cells are more immature at birth than they should be.
"This all points to this condition being caused by abnormal cell division. Importantly, it tells us that the brain and bone are not able to communicate with each other. In the normal situation, if the brain was growing too much, the bone should keep up with it. In the CKCS this relationship is lost.
"We will follow up these findings by investigating what is controlling the cell division in the brain and bone. We will also investigate why these two tissues are unable to communicate with each other."
Owners willing to participate should contact Sheena Stevens in Devon, UK, telephone 01884 821080, email Kilnshena@hotmail.com The nervous system degenerates rapidly after death and must be handled appropriately, so please contact Ms. Stevens as soon as or ideally before the dog has been euthanatized.
April 2009: Dr. Clare Rusbridge has introduced her website, veterinary-neurologist.co.uk, which discusses SM extensively, as well as other neurological disorders which she has researched. Her doctoral thesis, a 200+ page book, Chiari-like Malformation and Syringomyelia in the Cavalier King Charles Spaniel, also is available online.
April 2009: German study of the volumes of cranial cavities in Cavaliers with Chiari-like malformation and other brachycephalic dogs concludes "that descent of the cerebellum into the foramen magnum and the presence of syringohydromyelia in CKCSs are not necessarily associated with a volume reduction in the CF of the skull." The study included 40 Cavaliers and 25 dogs of other brachycephalic breeds.
March 2009: Study finds that Cavaliers have shallower caudal cranial fossa and abnormal occipital bones than control breeds. In a 2009 Scottish study led by Dr. Jacques Penderis, of 70 Cavaliers and 80 dogs of other breeds, the researchers found that "all [of the] CKCSs had abnormalities in occipital bone shape. ... CKCSs had a shallower caudal cranial fossa and abnormalities of the occipital bone, compared with those of mesaticephalic dogs. These changes were more severe in CKCSs with syringomyelia."
January 2009: Drs. Cerda-Gonzalez and Olby find occipital hypoplasia to be the most important factor associated with neurologic signs of SM. Drs. Cerda-Gonzalez and Olby and others report in Veterinary Radiology & Ultrasound that:
"Factors associated with the presence of neurologic signs [of SM] included syringohydromyelia and the ratio of caudal fossa/total cranial cavity volume; dogs with signs had significantly larger syringo-hydromyelia than asymptomatic dogs. Caudal fossa size was not associated with syringohydromyelia. A positive association was identified between foramen magnum size and length of cerebellar herniation. The prevalence of craniocervical junction abnormalities is high in Cavalier King Charles Spaniels. While several factors are associated with neurologic signs, occipital hypoplasia appears to be the most important factor."
November 2008: Rusbridge's & Knowler's "Summary of genetic studies of Chiari-like Malformation with Syringomyelia (CM/SM) in the Cavalier King Charles Spaniels (CKCS)". Dr. Clare Rusbridge and Penny Knowler have published an updated summary of the genetic studies of CM and SM in the Cavalier. Read it here. They also are seeking MRI scans of dogs 5 years old or older and which do not have SM, along with MRIs of those dogs' family members. Here is there introduction to their Summary:
"If we find the gene/s it is possible to prevent CM/SM rather than treat it and the fact that Clare was able to obtain collaboration with such an eminent geneticist as Dr Guy Rouleau has made this a possibility. We still have a way to go with this complex disorder. Unlike Chiari-like malformation, Syringomyelia is an acquired condition and a syrinx may develop at different rates over a period of time. Some dogs may never develop symptoms so you wouldn't know it was there. However these dogs when bred together can produce puppies with large painful syrinxes. This is our focus. Dogs that have pain and suffer. To help find all the factors that contribute to the formation of a syrinx we need to find 'normal' cavaliers. We are looking for dogs that been MRI'd over 5/6 years or older who DO NOT have Syringomyelia and their relatives if possible. Please help. I have written to Lesley Jupp and asked for our request to be passed to Regional Clubs but it is the ordinary members that make up a club and you can make a difference by having your older dogs scanned or encouraging information to be shared if you know of any."
The MRI report and pedigree should be sent to Clare (email email@example.com) or Penny (email firstname.lastname@example.org).
November 2008: Fetal and neonatal specimens of Cavaliers. Dr. Imelda McGonnell of the Department of Veterinary Basic Sciences, The Royal Veterinary College, has been leading a study looking at anomalies in different stages from the Cavalier's early growth in the uterus to its maturity. The study has been examining aborted fetuses and deceased young puppies that have died for any reason. In an interim report, Dr. McGonnell advised that little or no cerebellar herniation has been observed at birth. The researchers have not seen a single case of proper cerebellar herniation in any of the stillborn pups submitted. Owners willing to participate should contact Sheena Stevens in Devon, UK, telephone 01884 821080, email Kilnshena@hotmail.com The nervous system degenerates rapidly after death and must be handled appropriately, so please contact Ms. Stevens as soon as or ideally before the dog has been euthanatized.
October 2008: Dr. Rusbridge Revises CM/SM Treatment Options Chart. Dr. Clare Rusbridge has updated her diagram of how to treat Cavaliers and other dogs showing clinical signs of pain and discomfort with MRI diagnosis of CM/SM. See her 2008 CM/SM Treatment Algorithim.
October 2008:UK Kennel Club Plans Standardization of MRI Scanning for Syringomyelia. In July 2008, the UK Kennel Club held a conference which included veterinary neurologists, geneticists, CKCS club representatives, and the Animal Health Trust (AHT), at which they agreed to develop a protocol to standardize MRI scans for syringomyelia, which would include setting a minimum age for scans. On October 24, the panel of veterinary neurologists involved presently in MRI scanning met in London, and agreed upon a proposed "British Veterinary Association (BVA) / Kennel Club (KC) Syringomyelia MRI screening scheme" for scanning and evaluation. The panel will present their proposal to the BVA and KC at a meeting set for November 25. The panel requests that all CKCS clubs encourage their members to send copies of their Cavaliers' MRI scan results to AHT. Contact Dr. Blott at the Genetics Department, Animal Health Trust, Lanwades Park Kentford, Newmarket, Suffolk CB8 7UU, telephone +44 1638 751000, fax +44 1638 555606, website: www.aht.org.uk
October 2008: Estimates of SM heritability. Dr. Sarah Blott, of UK's Animal Health Trust, reported to the UK neurologists at their October 24 meeting that:
"Early estimates of the heritability of SM suggest it is around 0.7-0.8 or that 70-80% of the variation between individuals is genetic in origin and about 20-30% is environmental. The heritability is sufficiently high that genetic selection against the disease should be very successful. Heritabilities for CM, cerebellar herniation and ‘medullary kinking’ are also very high. Genetic correlations between these traits and SM are positive and less than one. This suggests that different genes may be controlling the expression of SM and CM and that it will be possible to select against SM even if dogs have CM.
"The computer model can also take account of other inherited disease, such as mitral valve dysplasia, and generates an Estimated Breeding Values (EBV) for each dog. An EBV is the best measure available for complex traits of the genetic potential of individuals. EBVs can be calculated for most CKCS even if they have not been MRI scanned, as long as they are related to dogs that have been scanned. The predicted EBV of an individual is half the EBV of its sire plus half the EBV of its dam. All dogs will have an EBV at birth but the EBV may be modified by the dog’s subsequent clinical record or MRI scan and by information coming from other relatives. The EBV becomes more accurate as information on offspring becomes available, because we start to gain insight into which half of the sire and dam genes were actually inherited when we see transmission of the genes to offspring. The accuracy of the EBV increases with numbers of offspring and this may take some time to achieve."
May 2008: Companion Animal Welfare Council (CAWC) Workshop Report on SM in the CKCS. A workshop of the CAWC has issued a report on syringomyelia in the cavalier King Charles spaniel. It states:
"Recent efforts, as yet unpublished, to learn more about the genetics of the disease have indicated that it has a high heritability. One implication of this is that intense efforts to eliminate it through selective breeding might be effective over a rather few generations (eg 4 or 5). However, syringomyelia is not the only genetic problem in CKCS, mitral valve disease also has a high prevalence and the need for simultaneous tackling of these diseases (and avoiding further inbreeding) complicates the approach.
"Efforts at the Animal Health Trust are being directed to the development of optimum breeding strategies and the establishment of a web-based interface for use by breeders to help them identify potential mates for their dogs that present the least risk of perpetuating genetic diseases. A third element of the programme will involve educational initiatives for breeders on these matters.
"CAWC is keen to assist in driving forward initiatives for tackling welfare problems that have arisen through selective breeding of companion animals. At this workshop various actions were proposed or emerged, including: That there seems to be a need for further debate about the relative merits of the three approaches to tackling these kinds of welfare problems (breeding to reduce prevalence or eliminate within the breed, outbreeding to reduce prevalence or eliminate, or ceasing to breed at all from potential carriers). That breed clubs and the Kennel Club might work more closely together further to find ways to make more health and welfare information available. That scientists studying the epidemiology and genetics of the disease should get together with breed club representatives, facilitated by the Kennel Club, to devise a scheme for collection of data on the epidemiology of the disease (including systems for assessing MRI results), for use in pursuit of its control or elimination.
"CAWC will explore ways to facilitate the first of these and looks forward to hearing of timescales for and progress with the second two initiatives and also of progress with other initiatives outlined at the workshop, including: development of genetic tests, development of web-based mate-selection advice, and initiatives for education and provision of better information on health and welfare for prospective owners."
The CAWC provides "independent advice and to inform public debate on matters relating to the welfare of companion animals. It pursues its objectives through undertaking independent and objective studies of companion animal welfare issues, identifying where further action is required, and preparing and publishing reports thereon. The Council is open to requests for objective views, advice and the carrying out of independent studies on issues concerned with the welfare of companion animals. CAWC is funded by the Welfare Fund for Companion Animals." CAWC may be contacted at CAWC Secretariat, The Dene, Old North Road, Bourn, Cambridge CB23 7TZ, website: www.cawc.org.uk, email: email@example.com
May 2008: Role of Estimated Breeding Values (EBV) for SM to grade genetic potential of Cavalier breeding stock. Dr. Sarah Blott, PhD (Quantitative Genetics), MSc (Animal Breeding), of the Genetics Department of the Animal Health Trust, in the UK, has published her notes from a May 18, 2008 presentation, "Genetics of Syringomyelia and Breeding Strategies to Reduce Occurrence" at the Cavalier King Charles Spaniel Clubs Liaison Meeting in the UK. Read it here. Dr. Blott may be contacted at Genetics Department, Animal Health Trust, , Lanwades Park Kentford, Newmarket, Suffolk CB8 7UU, telephone +44 1638 751000, fax +44 1638 555606, website: www.aht.org.uk
April 2008: CM/SM Status Report From Geoffrey Skerritt. Mr. Geoffrey Skerritt, BVSc, MIBiol ,CBiol, DipECVN, FRCVS, reported in April 2008 that SM is a "clinical disaster" facing Cavalier King Charles spaniels. He wrote:
"At ChesterGates Referral Hospital, and before that Cranmore Veterinary Centre, we have seen approximately 600 Cavalier King Charles Spaniels since we were aware of this condition, and our experience is that about 85% of these are showing clinical signs and/or MRI features of CM. Work by geneticists has established that this is an inherited disease although there is some dispute about the precise factors that are genetically transmitted. The inheritance not only results in visibly affected dogs but, as carrier status almost certainly exists, an appreciable proportion of the 15% are capable of transmitting the condition. So, it is likely that there is only a handful of Cavaliers that do not possess genetic factors for CM, and maybe none in the UK. Admittedly CM is not a fatal disease on its own but it can be severely disabling and it seems that some individuals suffer considerable discomfort and actual pain; human Chiari patients can give a clear description of the sensations that result from the disruption of nervous tissue in the development of syringomyelia.
"To ignore CM and continue breeding of Cavaliers with no effort to exclude affected dogs is frankly irresponsible. The situation is almost irretrievable because of the high incidence, and success in saving the breed will take hard decisions and 100% cooperation by breeders. The Kennel Club could be highly influential in the rescue effort; awards in the show ring should not be given to affected dogs. All Cavaliers should be screened with MRI and provided with a certificate that clearly states the MRI findings. I should add that MRI is a highly accurate and advanced technique which can clearly differentiate between dogs that have CM and those that do not. However, it does not identify carriers that have no evidence of the condition. Incidentally I feel that there should be no need for sponsorship of an MRI screening scheme except for pet owners of poor means. Breeders should be prepared to pay something for the service – we, the operators of MRI have already made a huge reduction in the cost of scanning on the screening scheme."
Mr. Skerritt may be contacted at ChesterGates Animal Referral Hospital, Telford Court, ChesterGates, Chester, UK, CH1 6LT, telephone 01244 853823, email GCSkerritt@aol.com. (April 2008).
March 2008: Identification of Genes Causing Chiari I Malformation with Syringomelia in the CKCS. Dr. Zoha Kibar, at the University of Montreal, is planning a study to identify and characterize the gene(s) defective in Chiari-like malformation (CM) and SM. She states that, "Identification of the CM/SM gene(s) will allow the development of a DNA test that will allow breeders to identify carriers and devise breeding strategies with the aim of reducing or eliminating this devastating condition in the dog. These studies will also help us better understand the pathogenic mechanisms involved in CM/SM for better treatment strategies."
Dr. Kibar is a molecular geneticist in charge of fine mapping and identification of the gene(s) at the Centre for the Study of Brain Diseases, CHUM – Montreal. For more information about Dr. Kibar, click here. The aim of the project is to identify markers and genes for SM, so that dogs can be conclusively tested at birth. Financial sponsors thus far include AKC Canine Health Foundation, American Cavalier King Charles Spaniel Club Charitable Trust, and Cavalier King Charles Spaniel, USA Health Foundation.
March 2008: Transcranial Magnetic MEP to assess motor and sensory pathways in Cavaliers' spinal cords. Drs. Roberto Poma and K. C. Wolfe of the Ontario Veterinary College, University of Guelph, in Ontario, report they are conducting a study to assess the functional integrity of the descending (motor) and ascending (sensory) pathways in CKCS dogs with magnetic resonance imaging of cervical spinal cord and brain suggestive of SM and Chiari-associated SM. They state:
"Stimuli applied to the scalp can excite the motor pathways, inducing muscle action potentials from fore- and hind limbs. A motor evoked potential (MEP) can be elicited by transcranial magnetic stimulation. Transcranial Magnetic MEP (Transcranial Magnetic Motor Evoked Potential) is not painful and can be performed with or without sedation. ... In veterinary medicine especially, TMMEP has been used to assess the correlation between severity of clinical signs and motor evoked potentials (MEP) in large-breed dogs with cervical spinal cord diseases, in Doberman Pinscher with cervical vertebral instability and in chondrodystrophic breeds with intervertebral disc disease. ... In CKCS dogs with clinical signs of SM, intermittent neck pain is the most common neurological sign observed. The pain is likely to be multifactorial and related to obstruction of CSF flow and spinal cord damage. Damage to the dorsal horn of the spinal cord is a key feature in the chronic pain of SM The dorsal horn of the spinal cord is the most important relay center for transmission of sensory information to the brain. Somatosensory evoked potentials of the cervical spinal cord were performed in human patients affected by SM. Abnormal SEP latencies were detected in patients with neck pain supporting a sensory etiology affecting the cervical spinal cord of dogs affected with SM."
Drs. Poma and Wolfe may be reached at telephone 519-824-4120, ext. 54129, email firstname.lastname@example.org
January 2008: "Radiographic morphology of the cranial portion of the cervical vertebral column in Cavalier King Charles Spaniels and its relationship to syringomyelia". Researchers at the Department of Veterinary Medicine, University of Cambridge, England (Stalin CE, Rusbridge C, Granger N, Jeffery ND) published in January 2008 a report of their study to compare radiographic morphology of the atlantoaxial region between Cavaliers and other breeds and determine whether there was an association between radiographic morphology of the atlantoaxial region and syringomyelia in CKCSs. Sixty-five Cavaliers and 72 other dogs were examined. The result was that "the amount of overlap of the atlas and axis and the relative size of the spinous process of the axis were significantly smaller in CKCSs than in dogs of other breeds. However, the amount of widening of the atlantoaxial joint that occurred when the neck was moved from a neutral to a flexed position was not significantly different between groups, and no association was detected between syringomyelia and excessive atlantoaxial joint space widening or between syringomyelia and an excessively small axial spinous process." They concluded "that these differences do not account for why some CKCSs develop syringomyelia and others do not."
November 2007: Study of the treatment of neuropathic pain associated with syringomyelia in Cavalier King Charles Spaniels. The Royal Veterinary College of the University of London is conducting a clinic trial, beginning in November 2007, to assess the therapeutic value of a novel pharmacological agent in CKCSs with syringomyelia. Dogs enrolled onto the study will be treated with this novel agent, given orally, for 14 days. The researchers anticipate that the novel agent will ease clinical signs and offer a therapeutic advantage over current analgesic remedies. Eligibility Requirements: CKCS with SM confirmed by a MRI within 8 months prior to enrollment; clinical signs of: scratching, pain, sensitivity to touch; dogs must weigh 4Kg-12Kg; dogs must be aged 1yr – 10yrs; dogs currently on other pain medications are still eligible but a changeover program will be implemented.
Participating dogs will receive free MRIs, CSFs, pre-anaesthetic blood profiles, and neurological evaluations if not been performed in the last 8 months. As a post study incentive, a veterinary care voucher will be given and may be used towards treatment of the condition. Contact: Clinical Investigation Centre, Veterinary Clinical Sciences, Royal Veterinary College, Tel: (01707) 666605, email: email@example.com
October 2007: "The search for the gene(s) predisposing to Chiari 1 malformation with syringomyelia." At the International Symposium on Syringomyelia held in October 2007 in Rugby UK, Dr. Guy A. Rouleau, (M.D., Ph.D., Director, Centre for the Study of Brain Diseases, Montreal, Canada) reported: "Pedigree analysis in a large database of over 5,500 CKCS has suggested that Cm/SM is inherited where all clinically affected dogs share a small number of common ancestors. To date, no genetic factor predisosing to CMI has been identified in either humans or dogs. He further stated:
"The CKCS is the only known naturally-occurring animal with a high frequency of CMI. We constructed a genealogy of more than 10,600 related CKCS dogs spanning 24 generations across 3 continents (North America, Australia, and Europe) from over 600 MRI confirmed dogs. A molecular genetic study of 173 CKCS dogs identified six chromosomal regions with potentionally significant results: chromosomes 3, 5, 9, 11, and 15. We are currently performing additional studies in additional dogs. Confirmed chromosomal regions will be further studied, with the aim of identifying the causative mutation(s) and gene(s). Identification of the CM/SM gene(s) will allow the development of a genetic test for the identification of carriers for breeding purposes with the ultimate aim of reducing or eliminating this devastating condition in the CKCS breed."
October 2007: Alternatives to MRI Scans: Dr. Curtis W. Dewey, board certified veterinary neurologist and board certified veterinary surgeon, Cornell University in Ithaca, New York, and Dr. Dominic J. Marino, board certified veterinary neuro-surgeon and chief of staff at Long Island Veterinary Specialists (LIVS) in Plainview, New York, Dr. Georgina Barone (board certified veterinary neurologist), and other specialists at LIVS also have been researching the possible use of the brain stem auditory evoked response (BAER) test, infrared thermography (IRT), and helical (spiral) computed tomography (CT), as screening tools for identifying adult CKCSs with CM. BAER is a clinical electro-diagnostic tool used to evaluate hearing ability as well as the functional integrity of the brain stem.
In an October 2007 update, Dr. Marino reported that 38 Cavaliers had been evaluated thus far. Of those, one dog had a normal MRI, BAER, and thermographic evaluation; 23 dogs without clinical signs of SM had abnormal MRI findings, with 16 of those 23 dogs (69.6%) also having abnormalities with BAER testing; and 14 dogs with clinical signs of SM had abnormal MRI findings, and 13 of those 14 dogs (92.8%) also had abnormal BAER tests. He concluded that “BAER testing may play a more useful role in screening ‘clinical’ dogs rather than dogs without clinical signs.”
Dr. Marino also reported that each dog was imaged with thermography, both awake and under general anesthesia. He stated that the complete analysis of thermal patterns is on-going, but that preliminary results revealed “cooler” thermographic patterns in dogs with abnormal MRI findings compared with the one dog with a normal MRI. Magnetic resonance imaging findings were classified as mild, moderate, and severe correlated with thermographic findings, 100%, 50%, and 0% of the time respectively. Based on these very preliminary findings, Dr. Marino concluded in his October 2007 report that "thermography may be a viable imaging modality to use as a screening tool to detect CLM in dogs." Dr. Marino may be contacted at telephone 516-501-1700, email Bongorno@aol.com LIVS's website is www.LIVS.org
September 2007: Dr. Rusbridge's Syringomyelia News Autumn 2007 Research Update
June 2007: Association between frontal-sinus size and SM. Dr. Deweyand others (Drs. Peter V. Scrivani, Margret S. Thompson, Kevin R. Winegardner, and Janet M. Scarlett) report in a June 2007 article of a study of 62 dogs (four of them were CKCSs) that there may be an association between frontal-sinus size and SM in Cavaliers and other small-breed dogs. They state:
"Our data do suggest, however, that the pathogenesis of syringohydromyelia in small-breed dogs may involve the supratentorial portion of the cranial cavity. We postulate that syringohydromyelia develops in many small-breed dogs and certain breeds in particular as a result of global malformation of the entire cranial cavity or supratentorial portion of the cavity and is not limited to the infratentorial portion of the cranial cavity. If this is true and results can be generalized to the target population, our understanding of the pathogenesis of syringohydromyelia in small-breed dogs and several aspects of clinical management (e.g., screening and diagnostic testing, breeding recommendations for dogs with dome-shaped heads, and treatments) will require further investigation."
May 2007: Study of possible correlation between head shape and CM/SM in Cavaliers and other toy breeds. Dr. Rusbridge and Ms. Knowler report in their April/May 2007 Research Newsletter the the preliminary results of pilot study looking at the possible correlation between head shape and CM/SM in different toy breeds. They report:
"In response to some observations made by breeders on head shape, a simple pilot study was devised. Dogs were selected on the basis of head length/breadth ratio, degree of doming, and presence or absence of a ski-slope shape to the back of the head. CM/SM status was confirmed by MRI. Early results of this pilot study found no correlation, however the investigation is still ongoing. This study has been a tremendously valuable exercise in other ways. On the basis of head shape, some dogs had been presumed to be affected, and owners had originally elected against MRI screening. However some of these dogs were actually found to be free of the condition. This suggests that it is not yet possible to predict CM/SM by a visual assessment of head shape. It also provided the opportunity to obtain blood DNA samples for the Genome study in Montreal. In particular, we would like to thank Lee Pieterse for co-ordinating the project in Australia. She and her husband Frank also contributed $4000 towards the research. Sandy Smith in Canada, generously donated $8000 from the ‘For the Love of Ollie’ Fund. An additional sum of $4000 came from the ‘Syringomyelia DNA Research’ Fund. Total $16,000." Donate to For the love of Ollie or directly to SM DNA Research!
January 2007: Dr. Rusbridge's Syringomyelia News 2007 Research Update
January 2007: Geneticist to Research SM Breeding Protocol. Dr. Rusbridge and Ms. Knowler report in their Syringomyelia News 2007 Research Update that Dr. Sarah Blott MSc PhD of the Genetics Department at the Animal Health Trust has joined the CM/SM research team. Dr. Blott is a geneticist with a particular interest in developing breeding schemes for companion animals. She combines state-of-the-art knowledge in quantitative genetics with molecular genetic markers.
June 2006: Development of Clinical Signs and CSF Flow. Dr. Natasha J. Olby, board certified veterinary neurologist, and Dr. Sofia Cerda-Gonzalez, both at North Carolina State University's College of Veterinary Medicine's Department of Clinical Sciences, reported in June 2006 that they and team members at IAMS Pet Imaging Center, Raleigh, NC. are in the process of conducting a three year study to determine whether abnormalities of the caudal fossa and cervical spine predict future development of clinical signs of SM.
The NC State/IAMS Pet Imaging Center team also has been studying the dynamics of cerebrospinal fluid flow in Cavalier King Charles Spaniels, and the extent to which head positions of the dogs affect the flow patterns. They reported in June 2006 finding that turbulent flow occurs in dogs with SM and can be found within syrinxes, and that CSF flow velocity may be higher within the dorsal subarachnoid space of affected dogs. They stated that additional studies are needed to determine whether their findings are significant. For more information, go to http://www.cvm.ncsu.edu/docs/neuro_studies.html or contact Dr. Cerda-Gonzalez at firstname.lastname@example.org.
June 2006: Progression of SM as Puppies Grow. Dr. Curtis W. Dewey, board certified veterinary neurologist and board certified veterinary surgeon, Cornell University in Ithaca, New York, is planning to begin a project of repeated MRI scanning of litters of Cavalier King Charles spaniel puppies to identify the prevalence of Chiari-like malformation in the breed, and its progression as the puppies grow. For more information, contact Dr. Dewey at email@example.com
April 2006: Full Genome Scan & Genetic Mapping. Dr. Rusbridge and Ms. Knowler reported in August 2005 that their study of Cavalier King Charles spaniels diagnosed with syringomyelia has shown that the disease is a common condition in Cavaliers and appears to be more severe and have an earlier onset with increased inbreeding, especially when breeding from affected dogs. They have been leading a successful effort to collect DNA from thousands of Cavaliers from throughout the world, to conduct a survey to identify DNA markers. In an April 2006 research update, Dr. Rusbridge reports that "a full genome scan looking for the causal gene/s of syringomyelia and mitral valve disease is underway!" (A Dr. Clare Rusbridge video DVD "Syringomyelia Seminar" is available by contacting firstname.lastname@example.org ). The Cavalier Health Foundation (associated with the Cavalier King Charles Spaniel Club, USA) has contributed a grant to help underwrite this project. Donate to the Cavalier Health Foundation and For the love of Ollie or directly to SM DNA Research!
Also participating are Marie Pierre Dube, a genetics epidemiologist at the Montreal Heart Institute, and Dr. Zoha Kibar, the molecular geneticist in charge of fine mapping and identification of the gene(s) defective in SM in CKCSs, at the Centre for the Study of Brain Diseases, CHUM – Montreal. The study is searching for recessive genes which may be the cause of the disease. The researchers suspect that the disorder is not due to a simple recessive gene, but rather a complex trait. Their future plans include genotyping, linkage disequilibrium analysis gene mapping, and positional candidate gene cloning. Dr. Kibar commented about her current gene study, as follows:
"Breeders should understand that our study will not be the magic solution that will help them identify dogs that will not develop SM for breeding purposes (at least not in the short term). But identifying a gene will open the door to understanding pathways involved in the development of this disease and hopefully in the long run, a cure for these suffering dogs. Of course we are also interested in the biology. Irrespective of the complexity we are dealing with, we have to try to understand the disease with the tools we have and hence the genetic approach. And irrespective of this complexity, and if we don’t want to think about the multifactorial etiology, the breeding protocol scheme Dr. Rusbridge came up with is the best solution for now. Then later we can deal with the causes."
In the April 2006 update, Dr. Kibar reports:
"Both Syringomyelia and Mitral valve disease are particularly common in the Cavaliers. Such high incidence in a particular breed as compared to other breeds suggests the involvement of genetic factors. The mode of inheritance including the number, identity and relative contribution of the causative genes is not determined yet. The etiology of both conditions could be further complicated by variable penetrance of the various genotypes and the involvement of environmental factors.
"The first step which is genetic mapping is currently underway. Due to the complex inbreeding in the CKCS, a preliminary genetic analysis was necessary to evaluate the informativeness of the genetic markers and hence the feasibility of a whole genome scan in such breed. Consequently, 10 dogs were selected for genotyping with 122 markers distributed among the 38 autosomes and X chromosome. The markers were found to be sufficiently polymorphic and informative. Next, 200 dogs were selected for a whole genome scan, primarily for Chiari malformation. However with additional phenotypic information on mitral valve disease, it is possible to use the same data to map the gene(s) defective in this disease. The whole genome scan was conducted at the Mammalian genotyping Center [Center for Medical Genetics] at the Marshfield Clinic in Wisconsin, USA. The genotyping data will now be analyzed using both linkage-based and association studies. In the latter, we will be taking advantage of the founder effect demonstrated for both these disorders in the CKCS breed.
"This strategy involves: 1) genetic mapping of the underlying gene(s), 2) identification of these defective gene(s) using the positional candidate gene approach and characterization of the mutation(s) and 3) initial functional characterization of the protein(s) encoded by the gene(s). This will help better understand the underlying pathogenic mechanisms for better diagnosis, prognosis and clinical management of these devastating conditions. These studies will also help unravel some of the complexity involved in this malformation in humans and in the embryonic development of the affected structures."
Canadian physicians and researchers Dr. Guy A. Rouleau, at McGill University, and Dr. Berge Minassian, at the University of Toronto also are participating in this research. Drs. Rouleau's and Minassian's experience includes having isolated the canine gene deemed responsible for Lafora's disease, a form of epilepsy. Dr. Clare Rusbridge and Penny Knowler may be reached at Stone Lion Veterinary Centre, 41 High Street, Wimbledon, London, SW19 5AU, telephone 0208 946 4228, email Dr. Rusbridge email@example.com email Ms. Knowler firstname.lastname@example.org
April 2006: Positioning for MRIs: In April 2006, the Cavalier King Charles Spaniel Club, UK announced that it will be funding research into whether the positioning of the dog's head in the MRI's receiving coil influences the accuracy of the resulting MRI scan of the dog's brain and spinal canal. Dr. Rusbridge and Dr. Nick Jeffery, BVSc PhD CertSAO DSAS (soft tissue) DECVN DECVS FRCVS, at the University of Cambridge's Department of Veterinary Medicine, in Cambridge, England will be conducting this project. This research is expected to lead to greater accuracy and uniformity in MRI scans of dogs with CM and SM. For more information, contact Dr. Rusbridge at Stone Lion Veterinary Centre, 41 High Street, Wimbledon, SW19 5AU, telephone: 00 44 208 9464228, email email@example.com or Dr. Jeffery at telephone 01223 337621, email firstname.lastname@example.org (April 2006)
March 2006: Repeated MRIs Study: In March 2006, the Cavalier King Charles Spaniel Club of Canada (CKCSCC) announced plans for a syringomyelia research project to be conducted by Dr. Roberto Poma, DMV, DVSc, ACVIM Neurology, Assistant Professor, Department of Clinical Studies, Ontario Veterinary College. Participating Cavalier King Charles Spaniels first will undergo a preliminary examination, including blood work, by Dr. Poma to determine eligibility for the project. Once accepted, the dogs will have MRIs at a cost of about $600.00 (Canadian). The preferred age of participating Cavaliers is as young as 5 1/2 months. A second evaluation will be conducted 3.5 years. However, depending on the findings of the first MRI, the dog may be examined again at 1.5 years and then again at 3.5 years. As group of older dogs, over age 3.5 years, also may be included, with their data collected as a subset grouping. Anyone interested in having their Cavaliers participate in this program should contact Pat Barrington of the CKCSCC's Health & Education Committee to receive a questionnaire or for more information. Her email address is email@example.com
2005: Ultrasound As SM Detector. Drs. Dominik Faissler and John McDonnell, board certified veterinary neurologists at the Cummings School of Veterinary Medicine at Tufts University in Massachusetts, are researching the use of ultrasonography to diagnose syringohydromyelia in dogs. In a 2005 interim report, the researchers stated, "This preliminary study indicates that cervical spinal cord ultrasound can be useful as a diagnostic aid for CM. It cannot rule out a diagnosis of CM, however no false positives were found. To investigate the sensitivity and specificity of this imaging modality blinded U/S examination of large numbers of dogs after MRI evaluation is planned."
2004: Post-mortem studies of Cavaliers: Owners of deceased Cavalier King Charles spaniels, which had been diagnosed with syringomyelia or Chiari-like malformation are urged to donate their dogs' bodies to researchers for post-mortem studies to enable the designing of a protocol for dealing with pathological material. Any owners interested in contributing their late Cavaliers to SM research should contact any of these researchers: Dr. Nick Jeffery, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 OES, telephone 01223 337621, email firstname.lastname@example.org; Dr. Jim Anderson, Glasgow University, email Gvsa07@udcf.gla.ac.uk; Dr. Rodolfo Cappello, The Royal Veterinary College, University of London, email RCappello@RVC.AC.UK; or Dr. Curtis Dewey, Cornell University, email email@example.com The nervous system degenerates rapidly after death and must be handled appropriately, so please contact these researchers as soon as or ideally before the dog has been euthanatized.