A 6-month-old, male, intact mixed breed dog was presented for a 3-month history of progressive generalized weakness. Neurologic examination revealed non-ambulatory tetraparesis, weakness of the head and neck, and decreased withdrawal reflexes in all limbs consistent with a generalized neuromuscular disorder. Electromyography and motor nerve conduction velocity were normal. Repetitive nerve stimulation showed a decremental response of the compound muscle action potential with improvement upon intravenous administration of edrophonium chloride. The serum acetylcholine receptor (AChR) antibody titer was within reference range. Cerebrospinal fluid analysis was unremarkable. A presumptive diagnosis of post-synaptic congenital myasthenic syndrome (CMS) was made. Treatment with pyridostigmine bromide was initiated with titrated increases in dosage resulting in an incomplete improvement in clinical signs. The dog was euthanized 2 months after initiation of treatment due to poor quality of life. Immunostaining for localization of antibodies against end-plate proteins in muscle biopsies was negative. Immunofluorescence staining for AChRs in external intercostal muscle biopsies showed absence of AChRs and biochemical quantitation showed a markedly decreased concentration of AChRs with no detectable AChR-bound autoantibody which confirmed the diagnosis of a CMS. Evaluation for the CHRNE mutation previously identified as the causative mutation of CMS in Jack Russell Terriers was performed and was negative. This is the first reported confirmed case of CMS in a mixed breed dog and provides a review of typical clinical and diagnostic findings as well as treatment considerations.Keywords: congenital myasthenic syndrome, myasthenia gravis, dog, pyridostigmine bromide, mixed breed, CHRNE Case pReseNtatIoNA 6-month-old, male, intact mixed breed dog [6.54 kg (14.4 lb)] was referred with a 3-month history of progressive generalized weakness. The dog was adopted at approximately 3 months of age after having been found as a stray. At the time of adoption, the dog was perceived to be normal. About 1 week later, it was noted that the dog developed an abnormal, stiff gait after playing and would sometimes fall over. The dog was also having difficulty posturing to defecate. Despite empirical treatment with clindamycin (12.3 mg/kg, PO, BID) and steroids (unknown type or dose), the dog displayed progressive episodes of weakness and falling following activity that eventually progressed to non-ambulatory tetraparesis over the next several months. On presentation, physical examination revealed grade 3/6 left and right apical systolic murmurs. Echocardiogram revealed mitral valve dysplasia causing systolic anterior motion of the mitral valve with severe dynamic left ventricular outflow tract obstruction and mild mitral regurgitation. In addition, there was a mild dynamic right ventricular outflow tract obstruction. Atenolol (1 mg/kg, PO, BID) was initiated. On neurologic examination, the dog was non-ambulatory tetraparetic (lower motor neuron qu...

Familial narcolepsy secondary to breed‐specific mutations in the hypocretin receptor 2 gene and sporadic narcolepsy associated with hypocretin ligand deficiencies occur in dogs. In this report, a pituitary mass is described as a unique cause of narcolepsy‐cataplexy in a dog. A 6‐year‐old male neutered Dachshund had presented for acute onset of feeding‐induced cataplexy and was found to have a pituitary macrotumor on magnetic resonance imaging (MRI). Cerebral spinal fluid hypocretin‐1 levels were normal, indicating that tumor effect on the ventral lateral nucleus of the hypothalamus was not the cause of the dog's narcolepsy‐cataplexy. The dog was also negative for the hypocretin receptor 2 gene mutation associated with narcolepsy in Dachshunds, ruling out familial narcolepsy. The Dachshund underwent stereotactic radiotherapy (SRT), which resulted in reduction in the mass and coincident resolution of the cataplectic attacks. Nine months after SRT, the dog developed clinical hyperadrenocorticism, which was successfully managed with trilostane. These findings suggest that disruptions in downstream signaling of hypocretin secondary to an intracranial mass effect might result in narcolepsy‐cataplexy in dogs and that brain MRI should be strongly considered in sporadic cases of narcolepsy‐cataplexy.

OBJECTIVE To evaluate the pharmacokinetics of zonisamide following rectal administration of 20 or 30 mg/kg suspended in sterile water or polyethylene glycol (PEG) to healthy dogs and determine whether either dose resulted in plasma zonisamide concentrations within the recommended therapeutic target range (10 to 40 μg/mL). ANIMALS 8 healthy mixed-breed dogs. PROCEDURES Each dog received each of 2 doses (20 or 30 mg/kg) of zonisamide suspended in each of 2 delivery substrates (sterile water or PEG) in a randomized crossover study with a 7-day washout period between phases. A blood sample was collected from each dog immediately before and at predetermined times for 48 hours after zonisamide administration. Plasma zonisamide concentrations were determined by high-performance liquid chromatography, and data were analyzed with a noncompartmental model. RESULTS Mean maximum plasma concentration, time to maximum plasma concentration, mean residence time, and elimination half-life did not differ significantly among the 4 treatments. The mean maximum plasma concentration for all 4 treatments was less than the therapeutic target range. The mean ± SD area under the concentration-time curve for the 30 mg/kg-in-water treatment (391.94 ± 237.00 h•μg/mL) was significantly greater than that for the 20 mg/kg-in-water (146.19 ± 66.27 h•μg/mL) and 20 mg/kg-in-PEG (87.09 ± 96.87 h•μg/mL) treatments. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that rectal administration of zonisamide at doses of 20 and 30 mg/kg failed to achieve plasma zonisamide concentrations within the recommended therapeutic target range. Therefore, rectal administration of zonisamide cannot be recommended as a suitable alternative to oral administration.