A retrospective case series of clinical signs in 28 Beagles with Lafora disease.

BACKGROUND: Clinical signs and their progression in Beagles with Lafora disease are poorly described. OBJECTIVES: To describe clinical signs in Beagles with Lafora disease. ANIMALS: Twenty-eight Beagles with Lafora disease confirmed by genetic testing or histopathology. METHODS: Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time. RESULTS: Onset of clinical signs was 8.3 years (mean; range, 6.3-13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic-clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic-clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty-one dogs were alive (median age 11.9 years; range, 9.8-18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5-12.6) at time of writing. CONCLUSIONS AND CLINICAL IMPORTANCE: Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic-clonic seizures. Nevertheless, a relatively normal life span can be expected.

A hypomyelinating leukodystrophy in German Shepherd dogs.

BACKGROUND: Shaking puppy syndrome is commonly attributed to abnormal myelination of the central nervous system. HYPOTHESIS/OBJECTIVES: To report the long-term clinical course and the imaging characteristics of hypomyelinating leukodystrophy in German Shepherd dogs. ANIMALS AND METHODS: Three related litters with 11 affected dogs. RESULTS: The 11 affected dogs experienced coarse, side-to-side tremors of the head and trunk, which interfered with normal goal-oriented movements and disappeared at rest. Signs were noticed shortly after birth. Nine dogs were euthanized, 3 dogs underwent pathological examination, and 2 littermates were raised by their breeder. Tremors improved gradually until 6 to 7 months of age. Adult dogs walked with severe residual pelvic limb ataxia. One dog developed epilepsy with tonic-clonic seizures at 15 months of age. Conventional magnetic resonance imaging (MRI) disclosed homogenous hyperintense signal of the entire subcortical white matter in 3 affected 7-week-old dogs and a hypointense signal in a presumably unaffected littermate. Subcortical white matter appeared isointense to gray matter at 15 and 27 weeks of age on repeated MRI. Abnormal white matter signal with failure to display normal gray-white matter contrast persisted into adulthood. Cerebellar arbor vitae was not visible at any time point. Clinical signs, MRI findings, and pathological examinations were indicative of a hypomyelinating leukodystrophy. All parents of the affected litters shared a common ancestor and relatedness of the puppies suggested an autosomal recessive mode of inheritance. CONCLUSION: We describe a novel hypomyelinating leukodystrophy in German Shepherd dogs with a suspected inherited origin.

Assessment of menace response in neurologically and ophthalmologically healthy cats.

OBJECTIVES: Assessment and interpretation of menace response (MeR) in cats can be challenging. The prevalence of abnormal MeR in healthy cats is unknown. The aim of this study was to prospectively evaluate MeR in visually healthy cats. METHODS: Fifty cats without history or clinical evidence of neurological or ophthalmological disease were assessed by two examiners: standing behind the cat (mode A), in front of the cat (mode B), and in front of the cat, covering the contralateral eye (mode C). MeR was scored from 1-5 (absent, weak, moderate, strong, complete). Examination modes were compared concerning presence and score (descriptive statistic, 95% confidence interval, χ2 test). This was compared to a three-level scoring system (negative, reduced, positive). Score reproducibility between the two examiners was assessed (Cohen's kappa [κ] test). Video footage allowed self-re-evaluation and evaluation of the second examiner (κ analysis). Learning/tiring effect (McNemar test), influence of age, body weight (Spearman's rho test), skull type (χ2 test) and being an indoor or outdoor cat (Mann-Whitney U-test) were evaluated. RESULTS: MeR was always elicited with at least one technique. Comparable results were obtained with the five- and three-level scoring systems. Mode A achieved strong/complete (positive) MeR in 84.5%, mode B in 82% and mode C in 60%. Exact score reproducibility between the two examiners was slight to fair (κ = 0.208-0.281). Intrarater agreement for video self-assessment (κ = 0.544-0.639), as well as inter-rater agreement (extrinsic video assessment), was moderate to substantial (κ = 0.584-0.645). No learning/tiring effect ( P = 0.530) or association with body weight ( P = 0.897), age ( P = 0.724), skull type ( P >0.05) and being an indoor/outdoor cat ( P = 0.511) were evident. CONCLUSIONS AND RELEVANCE: The majority of visually healthy cats revealed a strong/complete MeR when the contralateral eye remained uncovered, but 40% failed when the contralateral eye was covered. The most reliable examination mode was achieved standing behind the cat.

Myotonia congenita in a Labrador Retriever with truncated CLCN1.

An eight week old Labrador Retriever puppy presented with stiff-legged robotic gait. Abnormal gait was most evident after rest and improved with prolonged activity. On occasions, initiation of sudden movements would result in collapse with rigidity of the trunk and stiff extended limbs for several seconds. Other clinical signs were excitement-induced upper airway stridor and oropharyngeal dysphagia. Myotonia congenita was diagnosed based on clinical signs, abundant myotonic discharges on electromyography and exclusion of structural myopathies on histology. Whole exome sequencing revealed a case-specific homozygous variant in CLCN1, c.2275A > T resulting in a premature stop codon, p.R759X. The CLCN1 variant was absent from the genomes of 127 Labrador Retriever controls and 474 control dogs from other breeds. This study expands the spectrum of identified canine CLCN1 mutations and the list of affected breeds in myotonia congenita and highlights the potential value of dogs as translational large animal models of human genetic diseases.