Australian Research Centre in Sex, Health and Society HIV Futures Seven The Health and Wel being of HIV Positive People in Australia Jeffrey Grierson Monograph SerieS nuMber 88iSbn 9781921915338© La Trobe univerSiTy 2013 Australian Research Centre in Sex, Health and Society HIV Futures Seven The Health and Wel being of HIV Positive People in Australia
On the website doctordansfreedomforum.com full Specifications how to take these tablets. Be sure to check before use.Je l'ai acheté le médicament cialis prix deux ou trois fois, l'effet est des pilules superbes, je ne ne nous a pas déçus même si je suis au dernier étage sur la pilule. Männer werden empfohlen, für mindestens 30 Minuten für den angeblichen Geschlechtsverkehr durchschnittliche Rendite von cialis 20mg zu verwenden.
Vetrec-2011-100449.inddPaperLong-term outcome of Cavalier King Charles spaniel dogs with clinical signs associated with Chiari-like malformation and syringomyelia I. N. Plessas, C. Rusbridge, C. J. Driver, K. E. Chandler, A. Craig, I. M. McGonnell, D. C. Brodbelt, H. A. Volk The disease complex Chiari-like malformation (CM) and syringomyelia (SM) has been
associated with the development of neuropathic pain (NeP), and commonly affects Cavalier
King Charles spaniels (CKCS). This prospective cohort study followed 48 CKCSs with
CM and/or SM and clinical signs suggestive of NeP for a period of 39 (±14.3) months from
diagnosis. At the end of the study, 36 dogs were still alive; five dogs died of an unrelated
or unknown cause, and seven were euthanased due to severe clinical signs suggestive
of NeP. During the follow-up period, the clinical signs of scratching, facial rubbing
behaviour, vocalisation and exercise ability were evaluated. Nine out of 48 dogs stopped
scratching (P<0.001), but there was no statistically significant change in the number of
dogs exhibiting exercise intolerance, vocalisation or facial rubbing behaviour. The overall
severity of clinical signs based on a visual analogue scale (VAS) (0 mm: no clinical signs
100 mm: severe clinical signs) increased (from median 75 mm (interquartile ranges (IQR)
68–84) to 84 mm (IQR 71.5–91), P<0.001). A quarter of the dogs were static or improved. In
general, the majority of the owners felt that the quality of life of their dogs was acceptable.
Medical treatments received were gabapentin or pregabalin and/or intermittently,
carprofen. The owner's perception of their animal's progress, and progress based on VAS,
had strong positive correlation (Spearman's rank correlation (s ) 0.74, P<0.001). Overall,
this study suggests that clinical signs suggestive of NeP progress in three-quarters of CKCSs
with CM and/or SM.
others 2003). SM refers to accumulation of fluid within the paren- Chiari-like malformation (CM) and syringomyelia (SM) is an enfee- chyma of the spinal cord, and is thought to result from CM and result- bling disease complex most prevalent in Cavalier King Charles span- ant changes in the dynamics of cerebrospinal fluid (CSF) flow through iels (CKCS) (Rusbridge and others 2000). CM refers to the apparent the foramen magnum and the cranial part of the cervical spinal cord mismatch in volume between the caudal brain structures and the (Pinna and others 2000, Iskandar and others 2004, March and others caudal skull (Carrera and others 2009, Cross and others 2009, Driver 2005, Cerda-Gonzalez and others 2006, Rusbridge and others 2006, and others 2010), and is associated with herniation of the cerebellum Cerda-Gonzalez and others 2009).
through the foramen magnum (Rusbridge and others 2000, Lu and The estimated prevalence of CM in this breed varies from 92 per cent (Cerda- Gonzalez and others 2009) to 100 per cent (Couturier and others 2008, Carrera and others 2009). SM affects almost half Veterinary Record (2012) doi: 10.1136/vr.100449 of asymptomatic (as perceived by their owners) young CKCS, which I. N. Plessas, DVM, MRCVS,
A. Craig, BVSc; M Vet Clin Studies,
increases up to 70 per cent at the age of six years (Couturier and others C. J. Driver, BSc, BVetMed (Hons),
2008, Parker and others 2011). The prevalence of CKCS with SM that Department of Small Animal Medicine, suffer clinical signs suggestive of NeP is unknown.
K. E. Chandler, BVetMed, PhD,
Faculty of Veterinary Science, University Clinical signs typically associated with CM and/ or SM include DipECVN, FHEA, MRCVS, of Sydney, Australia cervical scoliosis, thoracic and pelvic limb ataxia, thoracic limb paresis D. C. Brodbelt, MA VetMB PhD DVA
I. M. McGonnell, PhD,
and signs suggestive of neuropathic pain (NeP) (Rusbridge and others Department of Veterinary Basic 2006). NeP most often manifests as allodynia (pain arising from a H. A. Volk, DVM, PhD, DipECVN,
Sciences, Royal Veterinary College, non-noxious stimulus, i.e. gentle palpation) or dysaesthesia (sponta- neous or evoked unpleasant sensation which manifests as phantom Department of Veterinary Clinical scratching, facial/ear rubbing) (Rusbridge and Jeffery 2008). One fre- Sciences, Royal Veterinary College, E-mail for correspondence: quent sign of SM attributed to dysaesthesia and/or allodynia is phan- tom scratching. Phantom scratching is characterised by a pelvic limb C. Rusbridge, BVMS, PhD, DipECVN,
scratching action to the shoulder and neck area, often without making Provenance: not commissioned; skin contact, and typically on one side only. Unlike scratching associat- externally peer reviewed Goddard Veterinary Group, Stone Lion ed with skin disease, dogs will often scratch whilst walking (Rusbridge Veterinary Hospital, London, UK Accepted September 21, 2012 and Jeffery 2008). It is not yet fully understood how CM/SM causes 10.1136/vr.100449 Veterinary Record 1 of 5
NeP. However, histopathological studies of SM in CKCS have found the spinal cord parenchyma with a transverse diameter of greater than that dogs which had expressed signs of NeP suffered an asymmetrical or equal to 2 mm (Driver and others 2010).
syrinx with profound alteration of the structure of the dorsal horn laminae, and had reduced expression of the pain-related neuropeptides Assessment of clinical signs
substance P, and calcitonin gene-related peptide (Hu and others 2012a). A questionnaire was used to assess the following factors in a face-to- Glial and fibrous proliferation were also associated with expression face interview at the initial visit, and then by telephone for the follow of clinical signs (Hu and others 2012b). Chiari-I malformation/SM up: name of the animal and owner, sex of the animal and neutering causes clinical signs of NeP in up to 80 per cent of human beings with status, date of birth and death, if applicable, whether it was euthana- this disorder, and up to 35 per cent of affected dogs (Todor and oth- sia or natural death, cause of death, general health status, history of ers 2000, Rusbridge and others 2007). NeP has an important impact brain or spinal cord diseases other than CM/SM, if the dog had evi- on the affected person's quality of life (QOL) and neurobehaviour dence of inflammation in the external ear canal, history and clinical (Gustorff and others 2008), and a recent study in dogs (Rutherford and signs of skin disease, seizures, exercise intolerance, whether there was others 2010) confirmed an association between the degree of NeP and another MR scan performed following their initial visit, if the animal fear/anxiety-related behavioural changes.
underwent craniocervical decompression, if the animal had been diag- Medical and surgical treatment options exist for dogs with CM/SM. nosed with a heart murmur, and what grade it was. The owners were Medical management includes the use of NSAIDs, drugs that reduce CSF also asked to confirm the presence of the following signs: phantom production (omeprazole, cimetidine), corticosteroids and antiepileptic scratching of shoulder and/or neck, facial and ear rubbing, vocalisa- drugs that have analgesic properties (gabapentin, pregabalin). However, tion and spinal pain. At the initial consult, all dogs were examined by there is no scientific evidence to prove the efficacy of these drugs in the a board-certified neurologist, and had unremarkable complete blood management of NeP associated with CM/SM in dogs (Rusbridge and cell count and serum biochemistry profile. A VAS was used by the others 2006, Rusbridge and Jeffery 2008, Wolfe and Poma 2010). Surgical authors to assess the frequency and intensity of clinical signs sugges- management (craniocervical decompression) is frequently performed in tive of NeP. A 100 mm line ranging from 0 mm (asymptomatic dogs people with Chiari-I malformation, with and without SM, to alleviate exhibiting normal exercise ability, no scratching, no facial rubbing and clinical signs (Tubbs and others 2003). Following surgery, 80 per cent of no vocalisation) to 100 mm (dogs with severely compromised exercise dogs improved, but there was no resolution of the syringes, and nearly al activity, scratching more than five times a day and vocalising more dogs continued to exhibit clinical signs suggestive of NeP postoperatively than five times a week) was used for the VAS assessment by intersect- (Vermeersch and others 2004, Dewey and others 2005, 2007, Rusbridge ing the line with a second perpendicular line drawn by the observer, 2007). Additionally, 25–47 per cent of the operated dogs showed recur- based on the subjective severity of the signs reported. To ensure con- rence or deterioration of the clinical signs within 0.2–3 years after sur- sistency as much as possible between scorers, two of the authors,i ii gery (Dewey and others 2005, 2007, Rusbridge 2007).
responsible for the initial scoring underwent training, which involved To the authors' knowledge there are currently no data regarding independent scoring of clinical signs until their score varied less than the long-term outcome of non-surgically managed dogs with clini- three per cent. The follow-up information gathered by calling the cal signs suggestive of NeP secondary to CM/SM. This prospective owners was cross-referenced to the history from the referring veteri- cohort study follows 48 CKCS dogs with clinical signs suggestive of narian. The owners were asked what medication the animal received, NeP due to CM and/ or SM for a period of 39 (±14.3) months.
and what was their perception of the progress of their animal's condi- tion (worse, unchanged, better) and QOL. The follow-up information Materials and methods
was subsequently given a second score (VAS) by one of the authors.ii Study design
The author who assessed the VAS at the follow up was blinded to the A prospective cohort study was performed following 48 CKCS dogs initial score. In addition, the volume of the caudal cranial fossa, the with CM and/ or SM disease complex for a mean period of 39 (±14.3) parenchyma within the caudal cranial fossa, and the sizes of the ven- months from treatment termination.
tricles and syringes were measured at the time of diagnosis using previ- ously described methodology (Driver and others 2010) and compared with the progression of the assessed clinical signs.
CKCSs between the ages of one and 13 years (median 46 months), and bodyweight of 4–13 kg (median 9.5 kg), were recruited from the general population in the UK by advertising through the veterinary Statistical analysis was performed with a commercial software pack- press and national CKCS health societies, into a two-week trial of age (Prism 5 for Mac, Graphpad Software 2007). Paired nominal a novel neuropathic pain medication, which was performed under categorical data were compared using the McNemar's χ2 test. All the Animals (Scientific Procedures) Act 1986, and was approved by quantitative data were assessed for normality of distribution with the institution's ethics committee. After the end of the drug trial, the D'Agostino and Pearson omnibus normality test and graphically. dogs were followed prospectively for a mean period of 39 (±14.3 SD, Means and SDs were calculated for normally distributed continuous 4–107) months for this study.
data (means (±SD)), and medians and interquartile ranges (IQR) were Dogs with other medical or neurological conditions that could determined for non-parametric data (median (IQR)). A Wilcoxon's have influenced the preceding pharmacological study were excluded, signed rank test was used for statistical evaluation of paired, non-para- such as brain or spinal cord diseases, other than CM/SM; CKCS metric data. The unpaired t test (parametric data) or Mann-Whitney U which had undergone craniocervical decompression; those with evi- test (non-parametric data) were used for comparing the morphometric dence of inflammation in the external ear canal (erythema, discharge, values between dogs with and without deterioration of clinical signs lichenification); with a history and clinical signs of skin disease; sei- assessed by VAS as appropriate. The association between owner's per- zures at the time of diagnosis; or with a systolic heart murmur of ception of their animal's progress (worse, unchanged, better) and pro- greater than grade II/VI. Thus, owners were questioned about gen- gress based on VAS, was evaluated with Spearman's rank correlation. eral health status, exercise intolerance and clinical signs suggestive A P value of 0.05 or below was considered significant.
of pruritus and pain. Recruitment and inclusion criteria were: CKCS with clinical signs suggestive of NeP (such as spinal hyperaesthesia on palpation, facial rubbing, vocalisation and/or phantom scratching) Sixty-one CKCS were initially considered for this study. Of these, (Rusbridge and others 2006, Rusbridge and Jeffery 2008) which scored eight were excluded due to the absence of clinical signs attribut- 50 or more on the visual analogue scale (VAS), underwent MRI of the able to CM/SM (n=3), craniocervical decompression (n=1), grade brain and spinal cord (Driver and others 2010, Loderstedt and others III/VI systolic heart murmur (n=2), generalised pyoderma (n=1), and 2011), and were subsequently diagnosed with CM and/or SM by a board-certified neurologist. CM was defined as evidence of cerebellar herniation or indentation by the supraoccipital bone (Lu and others 2003), and a syrinx was defined as a fluid-containing cavity within 2 of 5 Veterinary Record 10.1136/vr.100449
otitis externa (n=1). Fifty-three dogs underwent MRI of the brain and the whole spinal cord. Of these, three were excluded because To the authors' knowledge, this is the first report of clinical signs MRI studies were incomplete and two were excluded because of suggestive of NeP associated with CM/SM being progressive in the evidence of disc extrusion at C2–C3. Therefore, 48 dogs with MRI majority of dogs when treated non-surgically. In this study, morpho- confirmed CM and clinical signs suggestive of NeP were included metric values did not seem to play a significant role in the progres- and followed up for a period of 39 (±14.3) (mean (±SD)) months sion or improvement of the clinical signs. Three-quarters of the dogs from diagnosis, prospectively. There were 25 male dogs (17 neu- displayed progression of clinical signs, whereas, one-quarter remained tered) and 23 female (16 neutered). Thirty-nine dogs (81 per cent, static or improved. Despite the deterioration of the clinical signs in the 95 per cent CI 69.9 per cent to 92.1 per cent) had SM at the time majority of these dogs, 75 per cent were still alive 39 (±14.3) months of diagnosis.
later, with an acceptable QOL for the owners. All the owners of these At the end of the study, 36 dogs (75 per cent, 95 per cent CI 62.75 dogs indicated that if their dogs' QOL was severely compromised, per cent to 87.25 per cent) were still alive, four dogs died naturally at then they would opt for euthanasia. This study shows that non- home with signs of suspected congestive heart failure (a postmortem surgical management of this condition can be an acceptable option examination was not performed), one dog was euthanased due to an considering that there is no evidence for better management in dogs.
aggressive ovarian tumour that had metastasised to other organs, and The clinical course of the clinical signs seen in our study is similar seven were euthanased due to severe signs of NeP. The mean age at to what has been reported in human beings with unoperated SM asso- diagnosis was 53.2 (±33.1) months, and the mean age at the end of the ciated with type I Chiari malformation, and/or underdevelopment of study, or death, 92.3 (±30.5) months.
posterior fossa (Bogdanov and Mendelevich 2002). It has been suggest- Overall, 39 dogs were treated medically with gabapentin ed that the natural history of symptomatic SM associated with type (Neurontin, 10 mg /kg every 8–12 hours), pregabalin (Lyrica, I Chiari malformation, and/or signs of posterior fossa underdevelop- 2–4 mg /kg every 8 hours) and/or intermittently carprofen ment, is characterised by an initial relatively rapid clinical progression (Rimadyl, 2 mg/kg every 24 hours) and nine dogs were not on accompanied with distended cavities. If surgery is not performed, then any medication for the management of NeP. Nine out of 48 dogs a state of syrinx equilibrium may be reached, that is, no further expan- stopped scratching (P < 0.001), but there was no statistically signifi- sion of the syrinx, although this may be associated with irreversible cant change in the number of dogs exhibiting compromised exercise spinal cord damage. Eventually, in some cases, there may be MRI signs ability, vocalisation or facial rubbing behaviour. The median VAS of cavity collapse (Vaquero and others 2011). A possible explanation is of the clinical signs increased in the study population significantly that there was destruction of spinothalamic and lemniscal tracts by the (P < 0.001) from the initial median VAS of 75 mm (IQR 68–84 mm) syringes, so that pain could no longer be perceived (Hatem and others to follow up VAS 84 mm (IQR 71.5–91 mm) (Fig 1). The severity 2010). A further possibility is that the caudal cranial fossa and brain of clinical signs based on VAS deteriorated in 36 (75 per cent, 95 per parenchyma adjust to compensate for the overcrowding of the caudal cent CI 62.75 per cent to 87.25 per cent) dogs. From these dogs, 31 cranial fossa (Hamilton and others 2011).
(86 per cent, 95 per cent CI 76.18 per cent to 95.82 per cent) were Rusbridge (2007) followed up 15 CKCSs that underwent crani- treated with gabapentin or pregabalin, and carprofen. The remain- ocervical decompression for 0.2–2.3 years after surgery, and despite ing five dogs did not receive any treatment. A quarter of the dogs an initial clinical improvement in 80 per cent of the dogs, 47 per cent (95 per cent CI 12.75 to 37.25) were static (n=7, 14.5 per cent) or deteriorated in a mean time of 1.3 years. Ten out of these 15 dogs improved (n=5, 10.5 per cent).
had severe signs of NeP, and medical treatment was not successful. The owner's perception of their animal's progress, and progress Despite the initial improvement though, all dogs continued to exhib- based on VAS, was strongly positively correlated (Spearman's rank it signs of NeP, and surgery did not change the size of the cervical correlation (s )=0.74, P<0.001). All the owners of the dogs that were syringes. Similar findings were described by Vermeersch and others alive at the end of the study reported that their dog's QOL was not (2004) and Dewey and others (2005, 2007). One cause of deteriora- severely compromised, and had that been the case, they would have tion was attributed to scar tissue adhering to exposed neural tissue and opted for euthanasia. There was no significant association between preventing adequate CSF flow. Further studies that follow up cases morphometric values (volume of the caudal cranial fossa, the paren- for a longer period of time are needed to be able to compare the long- chyma within the caudal cranial fossa, and the sizes of the ventricles term outcome of conservative and surgical treatment, but it seems that and syringes) at the time of diagnosis between dogs with and without craniocervical decompression may not have more favourable long- deteriorating clinical signs.
term outcomes in the management of neuropathic pain.
In three out of eight female entire bitches, the owners reported Nine of the 48 dogs had CM only. Traditionally, clinical signs sug- periodical aggravation of the CM/SM-related clinical signs during oes- gestive of NeP in CKCS have been associated with CM and SM, but trus. Six dogs developed seizures during the study.
from our study, we found that CM only may contribute to these signs, too. The pathophysiology of these clinical signs in dogs with CM is not well understood, but the overcrowding of the foramen mag- num might be applying pressure onto brainstem nuclei causing signs suggestive of NeP (Rusbridge and Jeffery 2008). Unfortunately, there is no evidence for this theory, but in the human literature, there are several reports associating Chiari malformation with trigeminal neu- ralgia that resolves after craniooccipital decompression or placement of vetriculoperitoneal shunt (Gnanalingham and others 2005, Vince and others 2010).
Interestingly, there was a significant improvement in scratching (nine dogs stopped scratching), whereas, the VAS got significantly worse. New research findings in the area of pruritus may give an explanation for this. Pruritus, traditionally, has been associated with a submodality or subquality of pain (Sun and others 2009). Advances in this area have elucidated differences between pruritus and pain, but have also obscured the distinction between them. Pruritus and pain appear to be independent sensations because nociceptive and pruri- ceptive stimuli each elicit unique behavioural responses (Davidson FIG 1: Scatter plots showing the distribution of Visual Analogue Scale (mm) in Cavalier King Charles spaniel dogs with clinical signs and others 2010). Sun and Chen (2007) reported that they have iden- at the beginning of the study (initial) and 39±14.3 months later tified the first gene in the spinal cord of mice, linked with pruritus, (follow up) (bar represents median; Wilcoxon's signed rank test, and that it is responsible for the expression of gastrin-releasing pep- *represents P < 0.001) tide receptors (GRPR). These GRP receptors were found in a group 10.1136/vr.100449 Veterinary Record 3 of 5
of spinal cord cells called lamina-I neurones that relay both itch and shared ethical dilemma with human sufferers of CM/SM complex. pain sensation to the brain. However, Sun and others (2009) believe For each owner, this will be an individual decision, and based on the that there is a specific subpopulation of GRPR neurones, located in bond they have with their pets, and also the potential economic deci- the superficial dorsal horn within the lamina-I, that are specific only sions. Finally, it is important to mention that this study is document- for the pruritic sensation (labelled-line hypothesis). Destruction of the ing the progression of a specific set of clinical signs in a group of dogs described neurones in mice and stimulation afterwards with various with CM and/or SM, and not the progression of the disease itself. pruritic agents showed up to an 85 per cent reduction of pruritus com- Radiological progression of the disease has not yet been reported. pared with the controlled group, but nociception and motor function Fifteen per cent (95 per cent CI 4.9 to 25.1) of the study population appeared to be unaffected (Sun and others 2009). Many attempts to was euthanased at the request of the owner due to the severity of the localise the pathway of these GRPR neurones all the way up to the clinical signs. However, in the remaining surviving dogs, despite the thalamus (where they finally project) failed, but it is still believed progression of the clinical signs, the majority of the owners felt that that the pruriceptive pathway is different to the nociceptive path- QOL of their dogs was acceptable.
way in the spinothalamic tract neurones that project to the posterior and ventral posterior region of the thalamus (Sun and others 2009). Further research is needed to elucidate the difference between these The authors would like to acknowledge the owners of the patients two pathways.
who participated in this study, and the veterinarians who referred Another interesting finding of this study is that despite the fact them to us. The authors would like to thank the various CKCS health that history of seizures at the time of diagnosis was an exclusion cri- clubs for their continuous support for the investigation of these con- terion, six dogs (12.2 per cent) developed seizures in the investigated ditions. Finally, the authors also would like to thank the Clinical period of time. It was suggested that seizures may be related to ven- Investigation Centre of the Royal Veterinary College and its research triculomegaly secondary to overcrowding of the caudal cranial fossa office for assessing the manuscript according to the Royal Veterinary (Rusbridge and others 2006), however, a recent study could not show College's code of good research practice (authorisation number: a relationship between ventroculomegaly and seizures (Driver and others 2012). This finding is more likely related to idiopathic epilepsy which is common in this breed (Rusbridge and Knowler 2004) or other unknown pathologies. In human beings, epilepsy, in conjunc- BOGDANOV, E. I. & MENDELEVICH, E. G. (2002) Syrinx size and duration of symp- tion with type I Chiari malformation, is occasionally reported. Two toms predict the pace of progressive myelopathy: retrospective analysis of 103 unop- subtypes are described: the first as an incidental finding in the diag- erated cases with craniocervical junction malformations and syringomyelia. Clinical nostic work-up of patients with idiopathic epilepsies, and the second Neurology and Neurosurgery 104, 90–7
where both type I Chiari malformation and epilepsy occur as part of BOND, A., SHINE, P. & BRUCE, M. (1995) Validation of visual analogue scales in anxiety. International Journal of Methods in Psychiatric Research 5, 1–9
a more widespread developmental disorder (Granata and Valentini BOONSTRA, A. M., RENEMAN, M. F., POSTHUMUS, J. B., STEWART, R. E. & SCHIPHORST PREUPER, H. R. (2008) Reliability and validity of the visual analogue In three out of eight female entire bitches, the owners reported scale for disability in patients with chronic musculoskeletal pain. International Journal of periodical aggravation of the CM/SM-related clinical signs during oes- Rehabilitation Research 31(2), 165–169
CARRERA, I., DENNIS, R., MELLOR, D. J., PENDERIS, J. & SULLIVAN, M. (2009) trus. Hubscher and others (2010) reported that oestrogen (17b-estradi- Use of magnetic resonance imaging for morphometric analysis of the caudal cranial ol) administration reduces experimentally induced allodynia in rats, fossa in Cavalier King Charles spaniels. American Journal of Veterinary Research 70, 340–345
but there is no literature to support that oestrogens can deteriorate the CERDA-GONZALEZ, S., OLBY, N. J., BROADSTONE, R., MCCULLOUGH, S. & signs of NeP. To the authors' knowledge, there is no involvement of OSBORNE, J. A. (2009) Characteristics of cerebrospinal fluid flow in Cavalier King oestrogens in the pathophysiology of NeP, and this may be an inter- Charles Spaniels analyzed using phase velocity cine magnetic resonance imaging. Veterinary Radiology and Ultrasound 50, 467–76
esting finding that requires further investigation. Perhaps the stress CERDA-GONZALEZ, S., OLBY, N. J., PEASE, T. P., MCCULLOUGH, S., MASSOUD, associated with the oestrus can aggravate the perception of NeP, in a N. & BROADSTONE, R. (2006) Morphology of the caudal fossa in cavalier King similar way that mood affects the pain perception in human beings Charles spaniels. Journal of Veterinary Internal Medicine 20, 736
(Gustorff and others 2008).
COUTURIER, J., RAULT, D. & CAUZINILLE, L. (2008) Chiari-like malformation and syringomyelia in normal Cavalier King Charles spaniels: a multiple diagnostic imaging There are limitations to this study, considering the selection cri- approach. Journal of Small Animal Practice 49, 438–443
teria. Only dogs with VAS of 50 or more underwent MRI, and were COX, J. & DAVISON, A. (2005) The visual analogue scale as a tool for self-reporting of included in the study. However, we do not feel that selecting for dogs subjective phenomena in the medical radiation sciences. Radiographer 52(5), 22
with prominent clinical signs is a significant limitation of the study CROSS, H. R., CAPPELLO, R. & RUSBRIDGE, C. (2009) Comparison of cerebral cra- nium volumes between Cavalier King Charles spaniels with Chiari-like malformation, as they reflect the general population of dogs that are presented to a small breed dogs and Labradors. Journal of Small Animal Practice 50, 399–405
neurologist for investigation of this condition. There is possible bias DAVIDSON, S. & GIESLER, G. (2010) The multiple pathways for itch and their interac- from the owners and the veterinary surgeons when assessing the tions with pain. Trends in Neurosciences 33, 550–558
clinical signs. Also, one of the most important problems is that pain DEWEY, C., BERG, J., BARONE, G., MARINO, D. J. & STEFANACCI, J. D. (2005) Foramen magnum decompression for treatment of caudal occipital malformation syn- is a subjective variable and may have been inappropriately assessed drome in dogs. Journal of the American Veterinary Medical Association 227, 1270–1275
considering that the dogs cannot verbally communicate their level of DEWEY, C. W., MARINO, D. J., BAILEY, K. S., LOUGHIN, C. A., BARONE, discomfort. Moreover, we can only assume that CM/SM is the cause G., BOLOGNESE, P., MILHORAT, T. H., & POPPE, D. J. (2007) Foramen magnum of the described clinical signs and that these signs are suggestive of decompression with cranioplasty for treatment of caudal occipital malformation syn- neuropathic pain. A follow-up MRI was not performed, so we cannot drome in dogs. Veterinary Surgery 36, 406–415
DRIVER, C. J., CHANDLER, K., WALMSLEY, G., SHIHAB, N. & VOLK, H. A. (2012) exclude the possibility of development of other spinal diseases in the The association between Chiari-like malformation, ventriculomegaly and seizures in study period that may affect the progression of the clinical signs. The cavalier King Charles spaniels. The Veterinary Journal (In press) http://dx.doi.org/10.1016/j.
VAS itself, as with other scoring systems, is subject to bias, and its reproducibility can be questioned; however, the scorers in this study DRIVER, C. J., RUSBRIDGE, C., CROSS, H. R., MCGONNELL, I. & VOLK, H. A. (2010) Relationship of brain parenchyma within the caudal cranial fossa and were trained to be as consistent as possible in their observations. The ventricle size to syringomyelia in Cavalier King Charles spaniels. Journal of Small Animal VAS is a recognised tool for measuring subjective phenomena, such Practice 51, 382–386
as anxiety, pain, QOL (Bond and others 1995, Grunberg and others GNANALINGHAM, K., JOSHI, S. M., LOPEZ, B., ELLAMUSHI, H. & HAMLYN, 1996, Cox and others 2005), and it has been used extensively in peo- P. (2005) Trigeminal neuralgia secondary to Chiari's malformation–treatment with ventriculoperitoneal shunt. Surgical Neurology 63, 586–8
ple, and increasingly in veterinary literature. It seems to be reliable GRANATA, T. & VALENTINI, L. G. (2011) Epilepsy in type 1 Chiari malformation. (Boonstra and other 2008, Hielm- Bjorkman and others 2011), more Neurological Sciences 32, 306
responsive (Scrimshaw and others 2001), and easy to use, compared GRUNBERG, S., GROSHEN, S., STEINGASS, S., ZARETSKY, S. & MEYEROWITZ, with other pain-scoring systems. When reviewing the length of this B. (1996) Comparison of conditional quality of life terminology and visual analogue scale measurements. Quality of Life Research 5, 65–72
cohort study, euthanasia was a factor. The ability for human own- GUSTORFF, B., DORNER, T., LIKAR, R., GRISOLD, W., LAWRENCE, ers to eliminate their animals' suffering through euthanasia is not a K., SCHWARZ, F. & RIEDER, A. (2008) Prevalence of self-reported neuropathic pain 4 of 5 Veterinary Record 10.1136/vr.100449
and impact on quality of life: a prospective representative survey. Acta Anaesthesiologica RUSBRIDGE, C. (2007) Chiari-Like Malformation with Syringomyelia in the Cavalier Scandinavica 52, 132–136
King Charles Spaniel: long-term outcome after surgical management. Veterinary Surgery HAMILTON, S., DE RISIO, L., RUSBRIDGE, C., DRIVER, C., DENNIS, R., MCGONNELL, I. & VOLK, H. (2011) Changes over time in caudal cranial fossa RUSBRIDGE, C., CARRUTHERS, H., DUBÉ, M. P., HOLMES, M. & JEFFERY, N. D. volumes and of cerebellar herniation in Cavalier King Charles Spaniels with Chiari- (2007) Syringomyelia in cavalier King Charles spaniels: the relationship between syrinx like malformation. Research Abstract Program of the 2011 ACVIM Forum Denver, dimensions and pain. Journal Small Animal Practice 48, 432–436
Colorado, June 15–18, 2011. Journal of Veterinary Internal Medicine 25, 728–728
RUSBRIDGE, C., GREITZ, D. & ISKANDER, B. J. (2006) Syringomyelia: current con- cepts in pathogenesis, diagnosis, and treatment. Journal of Veterinary Internal Medicine 20,
HATEM, S.M., ATTAL, N., DUCREUX, D., GAUTRON, M., PARKER, F., PLAGHKI, L. & BOUHASSIRA, D. (2010) Clinical, functional and structural determinants of RUSBRIDGE, C. & JEFFERY, N. D. (2008) Pathophysiology and treatment of neuro- central pain in syringomyelia. Brain 133, 3409–22
pathic pain associated with syringomyelia. The Veterinary Journal 175, 164–72
HIELM-BJOKMAN, A. K, KAPATKIN, A. S.,RITA, H. J. (2011) Reliability and valid- RUSBRIDGE, C. & KNOWLER, S. P. (2004) Inheritance of occipital bone hypoplasia ity of a visual analogue scale used by owners to measure chronic pain attributable to (Chiari type I malformation) in Cavalier King Charles spaniels. Journal of Veterinary osteoarthritis in their dogs. American Journal of Veterinary Research 72, 601–607
Internal Medicine 18, 673–678
HU, H. Z., RUSBRIDGE, C., CONSTANTINO-CASAS, F. & JEFFERY, N. (2012a) RUSBRIDGE, C., MACSWEENY, J. E., DAVIES, J. V., CHANDLER, K., Histopathological Investigation of Syringomyelia in the Cavalier King Charles Spaniel. FITZMAURICE, S. N., DENNIS, R., CAPPELLO, R. & WHEELER, S. J. (2000) Journal of Comparative Pathology 146,192–201
Syringomyelia in cavalier King Charles spaniels. Journal of the American Animal Hospital HU, H. Z., RUSBRIDGE, C., CONSTANTINO-CASAS, F. & JEFFERY, N. (2012b) Association 36, 34–41
Distribution of substance P and calcitonin gene-related peptide in the spinal cord of RUTHERFORD, L., WESSMANN, A., RUSBRIDGE, C., MCGONNELL, I., Cavalier King Charles Spaniels affected by symptomatic syringomyelia. Research in ABEYESINGHE, S., BURN, C. & VOLK, H. A. (2010) A questionnaire based behav- iour analysis of Cavalier King Charles Spaniels with neuropathic pain due to Chiari- Veterinary Science 93, 318–320
like malformation and syringomyelia. Proceedings of 23rd Annual ESVN/ ECVN HUBSCHER, C. H., FELL, J. D. & GUPTA, D. S. (2010) Sex and hormonal variations Symposium: Neuro-surgery and Neuro-Imaging, Cambridge, 16–18 September 2010: 99 in the development of at-level allodynia in a rat chronic spinal cord injury model. SCRIMSHAW, S. V. & MAHER, C. (2001) Responsiveness of visual analogue and Neuroscience Letters 477, 153–156
McGill pain scale measures. Journal of Manipulative and Physiological Therapeutics ISKANDAR, B. J., QUIGLEY, M. & HAUGHTON, V. M. (2004) Foramen magnum cerebrospinal fluid flow characteristics in children with Chiari 1 malformation SUN, Y. G. & CHEN, Z. F. (2007) A gastrin- releasing peptide receptor mediates the itch before and after craniocervical decompression. Journal of Neurosurgery (Paediatrics 2) sensation in the spinal cord. Nature 448, 700–703
SUN, Y. G., ZHAO, Z. Q., MENG, X. L., YIN, J., LIU, X. Y. & CHEN, Z. F. (2009) The LODERSTEDT, S., BENIGNI, L., CHANDLER, K., CARDWELL, J. M., RUSBRIDGE, cellular base of itch sensation. Science 18, 1531–1534
C., LAMB, C. R. & VOLK, H. A. (2011) Distribution of syringomyelia along the TODOR, D. R., HARRISON, T. M. & MILHORAT, T. H. (2000) Pain and syringomy- entire spinal cord in clinically affected Cavalier King Charles Spaniels. The Veterinary elia: a review. Neurosurgical Focus 8, 1–6
Journal 190, 359–63
TUBBS, R. S., MCGIRT, M. J. & OAKES, W. J. (2003) Surgical experience in 130 pedi- atric patients with Chiari malformations. Journal of Neurosurgery 99, 291–296
LU, D., LAMB, C. R., PFEIFFER, D. U. & TARGETT, M. P. (2003) Neurological signs VAQUERO, J., FERREIRA, E. & PARAJÓN, A. (2011) Spontaneous resolution of syr- and results of magnetic resonance imaging in 40 cavalier King Charles Spaniels with inx: report of two cases in adults with Chiari malformation. Neurological Sciences 33,
Chiari type 1 like malformations. Veterinary Record 153, 260–263
MARCH, P. A., ABRAMSON, C. J., SMITH, M. & MURAKAMI, J. (2005) CSF flow VERMEERSCH, K., VAN HAM, L., CAEMAERT, J., TSHAMALA, M., TOEYMANS, abnormalities in caudal occipital malformation syndrome. Scientific Proceedings from O., BHATTI, S. & POLIS, I. (2004) Suboccipital craniectomy, dorsal laminectomy of 23rd ACVIM Forum. Lakewood, Colorado: Baltimore, American College of Veterinary C1, durotomy and dural graft placement as a treatment for syringohydromyelia with Internal Medicine, 2005:854–855 cerebellar tonsil herniation in cavalier King Charles spaniels. Veterinary Surgery 33,
PARKER, J. E., KNOWLER, S. P., RUSBRIDGE, C. & JEFFERY, N. (2011) Prevalence of asymptomatic syringomyelia in cavalier King Charles spaniels. Veterinary Record VINCE, G. H., BENDSZUS, M., WESTERMAIER, T., SOLYMOSI, L., ERNESTUS, R. I. & MATTHIES, C. (2010) Bilateral trigeminal neuralgia associated with Chiari's PINNA, G., ALESSANDRINI, F., ALFIERI, A., ROSSI, M. & BRICOLO, A. (2000) type I malformation. British Journal of Neurosurgery 24, 474–476
Cerebrospinal fluid flow dynamics study in Chiari I malformation: implications for WOLFE, K. C. & POMA, R. (2010) Syringomyelia in the Cavalier King Charles spaniel dog. Canadian Veterinary Journal 51, 95–102
syrinx formation. Neurosurgical Focus 8(3), E3
10.1136/vr.100449 Veterinary Record 5 of 5
Long-term outcome of Cavalier King Charles
spaniel dogs with clinical signs associated
with Chiari-like malformation and
I. N. Plessas, C. Rusbridge, C. J. Driver, et al.
published online October 25, 2012 Veterinary Recorddoi: 10.1136/vr.100449 Updated information and services can be found at: These include: This article cites 42 articles, 4 of which can be accessed free at: Published online October 25, 2012 in advance of the print journal.
Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Advance online articles have been peer reviewed, accepted for publication, edited andtypeset, but have not not yet appeared in the paper journal. Advance online articles are citable and establish publication priority; they are indexed by PubMed from initialpublication. Citations to Advance online articles must include the digital object identifier (DOIs) and date of initial publication. To request permissions go to: To order reprints go to: To subscribe to BMJ go to:
Medical Form PART A To be completed by Applicant and reviewed by DoctorPART B To be completed by Doctor 1 Please complete this form immediately. 3 Post or fax the other copy to the London office 2 Make a copy of your completed form. immediately or give it to your interviewer to forward. Keep one copy (original or photocopy) to take with you to the