Laryngeal paralysis-polyneuropathy complex in young related Pyrenean mountain dogs

PAPER

Laryngeal paralysis-polyneuropathy complex in young related Pyrenean mountain dogs OBJECTIVES: To characterise clinical, electrophysiological and histopathological findings. To analyse pedigree information in six young related Pyrenean mountain dogs with laryngeal paralysispolyneuropathy complex (LP-PNC). METHODS: A retrospective study of clinical records and pedigrees of six young related Pyrenean mountain dogs with LP-PNC was carried out. RESULTS: All dogs were presented with laryngeal paralysis and concurrent megaoesophagus. Electrodiagnostic testing was performed in three dogs and showed electrophysiological abnormalities in the distal appendicular muscles. Histopathological findings of peripheral nerve samples were dominated by distal axonal degeneration. Clinical, electrophysiological and histopathological findings were supportive of a diagnosis of degenerative, sensorimotor LP-PNC, similar to that reported in young dalmatians and rottweilers. All dogs died or were euthanased by two years of age. An autosomal recessive mode of inheritance was suspected based on pedigree analysis. CLINICAL SIGNIFICANCE: Congenital LP-PNC should be suspected in any young dog presenting with laryngeal dysfunction and other concurrent neurological abnormalities. The prognosis is usually poor. A. GABRIEL, L. PONCELETy, L. VAN HAMz, C. CLERCX, K. G. BRAUND§, S. BHATTIz, J. DETILLEUX* AND D. PEETERS Journal of Small Animal Practice (2006) 47, 144–149 Department of Small Animal Clinical Sciences, and * Department of Genetics, Faculty of Veterinary Medicine, University of Lie`ge, Bd Colonster 20, B44, 4000 Lie`ge, Belgium yVeterinary Anatomy, Faculty of Medicine, Free University of Brussels, Route de Lennik 808, 1070 Brussels, Belgium zDepartment of Small Animal Clinical Studies, Faculty of Veterinary Medicine, University of Ghent, Salisburylaan 133, 9820 Merelbeke, Belgium §Veterinary Neurological Consulting Services, 1476 Lakeview Ridge, Dadeville, AL 36853, USA

144

INTRODUCTION Presumed or confirmed hereditary forms of laryngeal paralysis in young dogs have been reported in Bouviers des Flandres (Venker-van Haagen and others 1978), Siberian huskies and Siberian husky crossbreeds (O’Brien and Hendriks 1986, Polizopoulou and others 2003), white-coated German shepherd dogs (Ridyard and others 2000), dalmatians (Braund and others 1989, 1994), rottweilers (Mahony and others 1998), bull terriers (Cook 1964) and in isolated dogs from different breeds (Harvey and O’Brien 1982). In most cases, clinical signs are noticed at a young age, and include an increasing loss of exercise tolerance, progressive laryngeal Journal of Small Animal Practice

stridor, dysphonia, episodes of dyspnoea and collapse (Cook 1964, Venker-van Haagen and others 1978, Harvey and O’Brien 1982, O’Brien and Hendriks 1986, Braund and others 1989, 1994, Mahony and others 1998, Ridyard and others 2000, Polizopoulou and others 2003). In Bouviers des Flandres, the condition is transmitted in an autosomal dominant way (Venker-van Haagen 1980, Venker-van Haagen and others 1981) and is caused by a loss of motor neurons in the nucleus ambiguus and secondary Wallerian degeneration of the recurrent laryngeal nerves (Venker-van Haagen 1980). In Siberian husky dogs, husky crossbreeds and white-coated German shepherd dogs, the condition is thought to be heritable and might be associated with the white colour of their coat (O’Brien and Hendriks 1986, Ridyard and others 2000, Polizopoulou and others 2003). The origin of the disease in husky dogs and husky crossbreeds has also been attributed to depletion of motor neurons in the nucleus ambiguus (O’Brien and Hendriks 1986, Polizopoulou and others 2003). A laryngeal paralysis-polyneuropathy complex (LP-PNC) due to neurogenic atrophy of intrinsic laryngeal and appendicular skeletal muscles has been described in young dalmatians and rottweilers (Braund and others 1989, 1994, Mahony and others 1998). In these dogs, laryngeal paralysis is found in conjunction with other neurological defects, such as gait abnormalities and megaoesophagus. An autosomal recessive mode of inheritance has been suggested in dalmatians (Braund and others 1994). Recently, an X-linked, recessively inherited polyneuropathy and laryngeal paralysis has been reported in young and adult leonberger dogs (Shelton and others 2003). The disease appears to be a canine variant of human CharcotMarie-Tooth neuropathy. This retrospective study describes the clinical, electrophysiological and histopathological findings, and a pedigree


Vol 47
March 2006
Ó 2006 British Small Animal Veterinary Association

Laryngeal paralysis-polyneuropathy complex

analysis of six young related Pyrenean mountain dogs with LP-PNC.

MATERIALS AND METHODS This retrospective study looked at the clinical records of six young Pyrenean mountain dogs diagnosed with LP-PNC at the University of Lie`ge, the University of Ghent or the Free University of Brussels. Their familial relationships based on pedigree analysis were also reviewed. Diagnosis of LP-PNC had been made based on the clinical signs present, age of onset of clinical signs, progression of the disease and familial relationship of the dogs. Available work-up, such as neurological examination, haematology and biochemistry, serum total thyroxin (T4), serology for toxoplasmosis and neosporosis, chest radiography, laryngoscopy, electrodiagnostic testing and histopathological examination, was also used in the diagnosis. But the diagnostic work-up for each dog was not always the same due to the retrospective and multicentre aspect of the study.

RESULTS A summary of clinical signs and diagnostic tests performed is given in Table 1. The age of onset of clinical signs ranged from 2
5 to six months. The dogs were presented with different degrees of respira-

tory, gastrointestinal and neurological symptoms of several weeks duration. Clinical signs were generally mild on presentation, with the exception of dog 3 who was presented with severe respiratory and gastrointestinal signs. Respiratory dysfunction was reflected by inspiratory stridor, dypshonia, dyspnoea and exercise intolerance. Gastrointestinal signs were regurgitating and vomiting. Signs of neurological dysfunction included gait abnormalities (hindlimbs being more severely affected than forelimbs), hyporeflexia, weakness, proprioceptive deficits and muscular atrophy. In most dogs, regurgitation occurred more frequently with time, whereas the gait abnormalities and upper respiratory distress worsened only mildly. Neurological examination was not performed in dog 1 and was normal in dog 3 and 4. Moderate proprioceptive deficits and decreased spinal reflexes in all limbs were found on neurological examination in the other dogs, except in dog 6 where spinal reflexes were absent. Bilateral deafness was suspected in dog 2. Routine haematology revealed moderate anaemia (packed cell volume 16 per cent, reference range 37 to –55 per cent) in dogs 1, 2, 4 and 5 and thrombocytopenia (113109/l, reference range 200 to 500109/l) in dog 1. Biochemistry profiles of dogs 2, 4 and 5 were unremarkable and the T4 levels of dogs 4 and 5 were within the normal range. Serological testing against Toxoplasma gondii in dogs 2

and 5 and Neospora caninum in dog 2 were negative. Thoracic radiographs revealed generalised megaoesophagus at presentation in all dogs, although dog 6 was first presented with oesophageal hypomotility, which then progressed to a generalised megaoesophagus over a few weeks. Tracheal hypoplasia was also present in dog 1 and inhalation pneumonia was present in dogs 2, 3 and 5. Pelvic radiographs revealed severe hip dysplasia in dog 5. Bilateral laryngeal paralysis in dogs 1, 2 and 4 and mild left laryngeal paralysis in dogs 5 and 6 were diagnosed during laryngoscopy. Electrodiagnostic testing was performed in three dogs. Brainstem auditory evoked response (BAER) confirmed complete bilateral deafness in dog 2. In this dog, denervation potentials in both cranial tibial muscles, decreased plantar interosseous muscle evoked potentials (2
5 mV with distal tibial nerve stimulation, reference .5
6 mV) and decreased tibial nerve conduction velocity (NCV) (40
3 m/ second, reference .44 m/second) were found. Electrodiagnostic testing in dog 3 revealed spontaneous activity and mildly prolonged insertion potentials in many fore- and hindlimb muscles, especially distally. Proximal nerve stimulation revealed a decrease in amplitude of compound muscle action potentials (CMAPs) (2 mV). The resultant CMAP maintained its amplitude during repetitive stimulation.

Table 1. Summary of clinical signs and diagnostic tests performed in six Pyrenean mountain dogs with laryngeal paralysispolyneuropathy complex

Age at onset of clinical signs (months) Age at presentation (months) Age at death/euthanasia (months) Inspiratory stridor Regurgitation/vomiting Abnormal gait/weakness Dysphonia Muscular atrophy Abnormal tendino-muscular reflexes Deafness (assessed by electrodiagnostic testing) Laryngeal paralysis Megaoesophagus Inhalation pneumonia Blood tests Electrodiagnostic testing Histopathology

Dog 1

Dog 2

Dog 3

Dog 4

Dog 5

Dog 6

3 4 4 1 1 1 1 ND ND ND

2 5 16 1 1 1 1 ND 1 1

,6 8 8 1 1 1 1 1 2 ND

3 5 8 1 1 1 1 ND 2 ND

5 7 19 1 1 1 1 1 1 ND

2 6 19 1 1 1 1 1 1 ND

1 1 2 CBC ND 1

1 1 1 CBC, BC, toxo, neo 1 ND

1 1 1 ND 1 1

1 1 1 CBC, BC, T4 ND ND

1 1 1 CBC, BC, toxo, T4 ND 1

1 1 2 ND 1 ND

1 Positive, ND Not done, 2 Negative, CBC Complete blood count, BC Biochemistry, toxo toxoplasma serology, neo neospora serology, T4 Serum total thyroxine

Journal of Small Animal Practice


Vol 47
March 2006
Ó 2006 British Small Animal Veterinary Association

145

A. Gabriel and others

The NCV could not be determined as there was no CMAP produced on distal nerve stimulation. In dog 6, slightly decreased CMAP amplitude (3 to 4 mV) and decreased NCV (41
2 m/second) of the left tibial nerve were found. Positive sharp waves occurred in the dorsal cricoarytenoid muscle during expiration and motor unit potentials were synchronous with inspiration. Inhalation pneumonia was treated with 20 mg/kg amoxicillin/clavulanate (Synulox; GlaxoSmithKline) every 12 hours for four weeks and supportive treatment of several small meals a day given from a height was conducted for oesophageal dysfunction. Dogs 2, 3 and 4 died of suspected fulminant inhalation pneumonia. The others were euthanased at the owners’ request because of the poor prognosis in dog 1, inhalation pneumonia in dog 5 and worsening clinical signs, mainly gastrointestinal and respiratory, in dog 6. Postmortem examination of dogs 1 and 3 showed no gross abnormality other than the megaoesophagus. Both recurrent laryngeal nerves and the brainstem of dog 1 were sent for histopathological studies. No abnormality was found at the

brainstem level and moderately severe changes, dominated by axonal degeneration, were apparent in the recurrent laryngeal nerves. In dog 3, samples were taken from the vagus, sciatic, accessory, hypoglossal, recurrent laryngeal, radial, glossopharyngeal and trigeminal nerves. In teased nerve fibre studies, lesions were observed in most of the nerves, and were more pronounced in recurrent laryngeal, accessory and vagus nerves. Changes included varying stages of axonal degeneration, such as the presence of myelin ovoids and balls (Fig 1). Glossopharyngeal and trigeminal nerves showed no axonal degeneration, although excessive segmentation was seen in many fibres. In semi-thin sections, scattered ovoids were found in accessory, vagus and radial nerves. Focal ovoids were noted in recurrent laryngeal, sciatic and hypoglossal nerves. This study showed no changes in glossopharyngeal and trigeminal nerves. Ultrastructural examination was carried out in vagus, sciatic, accessory, hypoglossal and recurrent laryngeal nerves. Lesions were most prominent in recurrent laryngeal nerves. Changes included scattered evidence of axonal degeneration (Fig 2), myelino-axonal necrosis (Fig 3) especially

involving medium and larger-caliber fibres, occasional Bu¨ngner’s bands, focal macrophages containing myelin debris, endoneural fibroblasts and the variable presence of unmyelinated fibres devoid of axons (Fig 4). Many unmyelinated fibres appeared swollen with a watery appearance to axons and a loss of organelles. Antemortem nerve biopsies of dog 5 were taken from superficial peroneal and saphenous nerves. Teased nerve fibre studies revealed moderately severe axonal degeneration in the superficial peroneal nerve. Semi-thin sections of the same nerve showed focal evidence of axonal degenerating ovoids, and apparent loss of myelinated fibres in some areas. No significant changes were observed in the saphenous nerve. Ultrastructural studies of both nerves revealed increased endoneural fibrosis and a loss of myelinated fibres, occasional ovoids and the multifocal presence of denervated Schwann cells involving both myelinated and unmyelinated fibres. Familial relationships Dogs 1, 2 and 3 were siblings, and the others came from three different litters, but were all related to the first one

FIG 1. Teased nerve fibre preparations showing stages of axonal degeneration. (A) Segmentation into large ovoids (MO). (B) Mixture of myelin ovoids and balls (MB). (C) Clusters of small myelin balls (CMB) occurring at widely separated intervals. (D) Normal myelinated fibre with a node of Ranvier (NR)

146

Journal of Small Animal Practice


Vol 47
March 2006
Ó 2006 British Small Animal Veterinary Association

Laryngeal paralysis-polyneuropathy complex

DISCUSSION

FIG 2. Axonal degeneration with pleomorphic vesicular structures. Uranyl acetate/lead citrate 15,700.

(Fig 5). Three littermates of the affected dogs were presented with clinical symptoms compatible with LP-PNC and had died after developing signs of pneumonia. Inhalation pneumonia was the most likely diagnosis, but was not confirmed by thoracic radiography. In total, the nine affected dogs (out of 33) came from five different related litters. The sire was common to seven of those dogs and was the grand-sire of the two other dogs. The dams and sire showed common ancestry. Unfortunately, it was not possible to get information about the disease status of all the dogs, which made it impossible to get correct percentages of the prevalence of the disease. However, based on the

information available the estimated prevalence of the disease was 27 per cent, which was compatible with an autosomal recessive mode of inheritance. The Singles method developed by Li and Mantel (1968) was used to test the null hypothesis that the disease has an autosomal recessive inheritance. This method calculates the segregation ratio for field data in which families with at least one affected offspring are identified and corrects for the bias due to the truncate ascertainment. The segregation ratio was estimated at 22
58 per cent and was not statistically different (P.0
05) from 0
25, which suggests LP-PNC is transmitted as an autosomal recessive disease.

FIG 3. Myelinated fibre transformed into an ovoid (myelinoaxonal necrosis). Uranyl acetate/lead citrate 15,700. Journal of Small Animal Practice


Vol 47
March 2006
Ó 2006 British Small Animal Veterinary Association

Congenital LP-PNC is a disease where laryngeal paralysis is associated with concurrent distal polyneuropathy in young dogs (Braund and others 1994). To the authors’ knowledge, this is the first report of LP-PNC in young Pyrenean mountain dogs. The condition has previously been reported in Dalmatians, rottweilers and leonberger dogs (Braund and others 1989, 1994, Mahony and others 1998, Shelton and others 2003). The age of onset of clinical signs in the dogs of the present report (from 2
5 to six months) was similar to that described in Dalmatians and rottweilers with LPPNC (Braund and others 1994, Mahony and others 1998), whereas, in leonberger dogs it ranged from one to nine years of age (Shelton and others 2003). Clinical signs varied in severity among the affected dogs of the present study, which is similar to the results found in leonberger dogs (Shelton and others 2003). In this breed, dogs affected at a younger age were presented with more severe clinical signs than dogs affected at an older age (Shelton and others 2003). In the Pyrenean mountain dogs, regurgitations became more frequent with time, whereas gait abnormalities and respiratory distress worsened only mildly. The six Pyrenean mountain dogs in the current study died either of inhalation pneumonia or were euthanased. Most Dalmatians and leonberger dogs with LP-PNC were also euthanased because of inhalation pneumonia (Braund and others 1994, Shelton and others 2003). In rottweilers, the reason for euthanasia was the dyspnoea and gait abnormalities (Mahony and others 1998). All dogs in the current study were presented with laryngeal paralysis and oesophageal dysfunction as part of the neurological deficits. Concurrent megaoesophagus was also present in most Dalmatians (Braund and others 1989, 1994) and one of five rottweilers with LP-PNC (Mahony and others 1998), but not in leonberger dogs (Shelton and others 2003). Tracheal hypoplasia in dog 1 was determined using the ‘‘tracheal lumen diameter at the thoracic inlet diameter’’ ratio 147

A. Gabriel and others

FIG 4. Denervated Schwann cell subunits from non-myelinating Schwann cells (arrow) and normal unmyelinated fibres (arrowheads) with axons (a). Uranyl acetate/lead citrate 19,500.

method (TD/TI) (Harvey and Fink 1982). Concurrent congenital megaoesophagus and tracheal hypoplasia have been described in dogs with no other abnormalities (Coyne and Finland 1992). In these cases, abnormal embryogenesis was considered as a possible cause of concurrent megaoesophagus and hypoplasia of the trachea, due to the same primordial tissue origin (Coyne and Finland 1992). In the cases in the present report, tracheal hypoplasia was considered unrelated to the megaoesophagus that was caused by polyneuropathy. Dog 2 had complete bilateral deafness confirmed by BAER. This was also reported in one of the rottweiler puppies affected with LP-PNC (Mahony and others 1998). In view of the young age of the affected dog and the fact that no external cause of deafness could be identified, congenital deafness was suspected. Congenital deafness has already been reported in the Pyrenean mountain dog breed (Strain 1996, 1999, Coppens and others 2000). The inner ear morphology of a six-week-old male Pyrenean mountain puppy revealed bilateral cochleo-saccular degeneration (Coppens and others 2000). The same histological pattern occurs in

Dalmatians affected by congenital sensorineural deafness (Strain 1996, 1999). In Dalmatians, the inheritance of deafness is associated with pigmentation genes (extreme piebald gene), but the exact transmission is very complex and has not yet been elucidated (Strain 1996, 1999). The Pyrenean mountain dog, among other canine breeds, is also a carrier of the piebald gene, but genetic transmission has not yet been clarified (Strain 1996). Whether congenital deafness was associated with LP-PNC or was just an incidental finding needs further investigation. Unfortunately, BAER were not evaluated in the five other dogs. Electrodiagnostic testing was performed in three dogs only and revealed denervation potentials and a decrease in motor NCV in appendicular muscles. The major findings were CMAP amplitude loss in dogs 2, 3 and 6 and motor NCV decrease in dogs 2 and 6. The distal distribution of the electrophysiological abnormalities was indicative of distal polyneuropathy. The same electrophysiological abnormalities were reported in Dalmatians (Braund and others 1994), rottweilers (Mahony and others 1998) and leonberger dogs (Shelton and others 2003).

? ? ?

?

?

?

?

?

?

?

FIG 5. Laryngeal paralysis-polyneuropathy complex (LP-PNC) in a pedigree Pyrenean mountain dog. Squares indicate males. Circles indicate females. Filled symbols indicate LP-PNC-affected pups examined at the universities of Lie`ge, Ghent and Brussels. Half-filled symbols indicate dogs strongly suspected to be affected by LP-PNC by questioning their owners or breeders but not examined by the authors of the present paper. All littermates of affected pups are shown arranged on a horizontal line connecting vertical lines descending from the symbols for their parents. Littermates of the affected pups for which no information could be obtained regarding their health status are indicated by a question mark within the symbol

148

Journal of Small Animal Practice


Vol 47
March 2006
Ó 2006 British Small Animal Veterinary Association

Laryngeal paralysis-polyneuropathy complex

Teased nerve fibres, semi-thin sections and ultrastructural studies of peripheral nerve samples revealed lesions dominated by distal axonal degeneration. The lesions included increased endoneural fibrosis and myelinated fibre loss, occasional ovoids, presence of denervated Schwann cells involving both myelinated and unmyelinated fibres, and focal macrophages containing myelin debris. There was no evidence of demyelination or infiltrating inflammatory cells. These findings are characteristic of LP-PNC and similar to those observed in Dalmatians (Braund and others 1989, 1994) and rottweilers (Mahony and others 1998). Morphometric analysis was not performed because of the paucity of nerve samples and different fixative solutions employed which would have interfered with measurements. In further studies, morphometric studies would be interesting to compare the distribution of lesions from proximal and distal portions of nerves from the same animal. The LP-PNC described in the present report appeared sensorimotor in nature, as seen by the clinical signs due to the peripheral polyneuropathy and involvement of mixed function nerves, but further investigations are needed to determine whether exclusively sensory nerves are involved. The predominant abnormality in leonberger dogs was chronic myelinated nerve fibre loss with a shift of the axonal size frequency distribution towards smaller fibres within the common peroneal nerve (Shelton and others 2003). Evidence of demyelination and remyelination was found in less severely affected nerve biopsy specimens (Shelton and others 2003). In all dogs, clinical signs developed when they were less than six months old, indicating that the condition is congenital and possibly hereditary. Both male and female dogs were affected by the disease. Although detailed breeding data were not available, the fact that approximately 25 per cent of the related litters were affected indicates an autosomal recessive mode of inheritance. With the Singles method, the estimated segregation ratio was also compatible with that hypothesis. However, more data are necessary to con-

Journal of Small Animal Practice

firm this hypothesis. The inbreeding in this pedigree provides an ideal environment for the amplification of deleterious alleles. In rottweilers (Mahony and others 1998), Dalmatians (Braund and others 1994) and leonbergers (Shelton and others 2003) the exact mode of transmission has not yet been determined. An autosomal recessive mode of inheritance is suspected in the Dalmatians (Braund and others 1994), whereas an X-linked recessive transmission of the disease is suggested in leonberger dogs (Shelton and others 2003). The prognosis for Pyrenean mountain dogs with LP-PNC seems poor, even with palliative treatment. The Pyrenean mountain dogs in the present report died or were euthanased because of inhalation pneumonia or regurgitations before they were 19 months old (median age 12 months). In the study of Dalmatian dogs, most died or were euthanased within a month or two of diagnosis (Braund and others 1994). The affected rottweilers were euthanased before six months of age (Mahony and others 1998). The onset of clinical signs in the leonberger dogs was much later; time of death or euthanasia was not indicated (Shelton and others 2003). Conclusions LP-PNC was described in six young related Pyrenean mountain dogs in Belgium. Clinical and pathological findings were similar to those reported in Dalmatians and rottweilers, but differed from those reported for the leonberger breed. Prognosis was poor, as most dogs were euthanased within a few months of presentation. The condition is possibly inherited as an autosomal recessive trait. LP-PNC should be suspected in any young dog presenting with laryngeal dysfunction with concomitant regurgitation or gait abnormalities. Acknowledgements The authors would like to thank Mr and Ms Sittinger for their help in providing breeding data and contact addresses of the owners of some dogs. Owners and referring veterinarians are also thanked for their kind cooperation.


Vol 47
March 2006
Ó 2006 British Small Animal Veterinary Association

References BRAUND, K. G., SHORES, A., COCHRANE, S., FORRESTER, D., KWIECIEN, J. M. & STEISS, J. E. (1994) Laryngeal paralysis-polyneuropathy complex in young Dalmatians. American Journal of Veterinary Research 55, 534-542 BRAUND, K. G., STEINBERG, H. S., SHORES, A., STEISS, J. E., METHA, J. R., TOIVIO-KINNUCAN, M. & AMLING, K. A. (1989) Laryngeal paralysis in immature and mature dogs as one sign of a more diffuse polyneuropathy. Journal of the American Veterinary Medical Association 194, 1735-1740 COOK, W. R. (1964) Observations on the upper respiratory tract of the dog and cat. Journal of Small Animal Practice 5, 309-329 COPPENS, A. G., RE´SIBOIS, A. & PONCELET, L. (2000) Bilateral deafness in a Maltese terrier and a Great pyrenean puppy: inner ear morphology. Journal of Comparative Pathology 122, 223-228 COYNE, B. E. & FINLAND, R. B. (1992) Hypoplasia of the trachea in dogs: 103 cases (1974-1990). Journal of the American Veterinary Medical Association 201, 768-772 HARVEY, C. E. & FINK, E. A. (1982) Tracheal diameter: analysis of radiographic measurements in brachycephalic and nonbrachycephalic dogs. Journal of the American Animal Hospital Association 18, 570-576 HARVEY, C. E. & O’BRIEN, J. A. (1982) Treatment of laryngeal paralysis in dogs by partial laryngectomy. Journal of the American Animal Hospital Association 18, 551-556 LI, C. C. & MANTEL, N. (1968) A simple method of estimating the segregation ratio under complete ascertainment. American Journal of Human Genetics 20, 61 MAHONY, O. M., KNOWLES, K. E., BRAUND, K. G., AVERILL, D. R. & FRIMBERGER, A. E. (1998) Laryngeal paralysis-polyneuropathy complex in young Rottweilers. Journal of Veterinary Internal Medicine 12, 330-337 O’BRIEN, J. A. & HENDRIKS, J. (1986) Inherited laryngeal paralysis. Analysis in the husky cross. Veterinary Quarterly 8, 301-302 POLIZOPOULOU, Z. S., KOUTINAS, A. F., PAPADOPOULOS, G. C. & SARIDOMICHELAKIS, M. N. (2003) Juvenile laryngeal paralysis in three Siberian Husky x Alaskan malamute puppies. Veterinary Record 153, 624-627 RIDYARD, A. E., CORCORAN, B. M., TASKER, S., WILLIS, R., WELSH, E. M., DEMETRIOU, J. L. & GRIFFITHS, L. G. (2000) Spontaneous laryngeal paralysis in four white-coated German shepherd dogs. Journal of Small Animal Practice 41, 558-561 SHELTON, D. G., PODELL, M., PONCELET, L., SCHATZBERG, S., PATTERSON, E., POWELL, H. C. & MIZISIN, A. P. (2003) Inherited polyneuropathy in Leonberger dogs: a mixed or intermediate form of Charcot-MarieTooth disease? Muscle & Nerve 27, 471-477 STRAIN, G. M. (1996) Aetiology, prevalence and diagnosis of deafness in dogs and cats. British Veterinary Journal 152, 17-36 STRAIN, G. M. (1999) Congenital deafness and its recognition. Veterinary Clinics of North America: Small Animal Practice 29, 895-907 VENKER-VAN HAAGEN, A. J. (1980) Investigations of the pathogenesis of hereditary laryngeal paralysis in the Bouvier. University of Utrecht, The Netherlands. Thesis VENKER-VAN HAAGEN, A. J., BOUW, J. & HARTMAN, W. (1981) Hereditary transmission of laryngeal paralysis in Bouviers. Journal of the American Animal Hospital Association 17, 75-76 VENKER-VAN HAAGEN, A. J., HARTMAN, W. & GOEDEGEBUURE, S. A. (1978) Spontaneous laryngeal paralysis in young Bouviers. Journal of the American Animal Hospital Association 14, 714-720

149