Pregabalin Add-On vs. Dose Increase in Levetiracetam Add-On Treatment: A Real-Life Trial in Dogs With Drug-Resistant Epilepsy.

Epilepsy is a common neurological disorder affecting 0.6-0.75% of dogs in veterinary practice. Treatment is frequently complicated by the occurrence of drug-resistant epilepsy and cluster seizures in dogs with idiopathic epilepsy. Only few studies are available to guide treatment choices beyond licensed veterinary drugs. The aim of the study was to compare antiseizure efficacy and tolerability of two add-on treatment strategies in dogs with drug-resistant idiopathic epilepsy. The study design was a prospective, open-label, non-blinded, comparative treatment trial. Treatment success was defined as a 3-fold extension of the longest baseline interseizure interval and to a minimum of 3 months. To avoid prolonged adherence to a presumably ineffective treatment strategy, dog owners could leave the study after the third day with generalized seizures if the interseizure interval failed to show a relevant increase. Twenty-six dogs (mean age 5.5 years, mean seizure frequency 4/month) with drug-resistant idiopathic epilepsy and a history of cluster seizures were included. Dogs received either add-on treatment with pregabalin (PGB) 4 mg/kg twice daily (14 dogs) or a dose increase in levetiracetam (LEV) add-on treatment (12 dogs). Thirteen dogs in the PGB group had drug levels within the therapeutic range for humans. Two dogs in the PGB group (14.3%; 2/14) and one dog in the LEV group (8.3%; 1/12) achieved treatment success with long seizure-free intervals from 122 to 219 days but then relapsed to their early seizure frequency 10 months after the study inclusion. The overall low success rates with both treatment strategies likely reflect a real-life situation in canine drug-resistant idiopathic epilepsy in everyday veterinary practice. These results delineate the need for research on better pharmacologic and non-pharmacologic treatment strategies in dogs with drug-resistant epilepsy.

Clinical Course and Diagnostic Findings of Biopsy Controlled Presumed Immune-Mediated Polyneuropathy in 70 European Cats.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011-2019). Median age at onset was 10 months (range: 4-120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

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.

Seizure frequency discrepancy between subjective and objective ictal electroencephalography data in dogs.

BACKGROUND: Many studies of epilepsy in veterinary medicine use subjective data (eg, caregiver-derived histories) to determine seizure frequency. Conversely, in people, objective data from electroencephalography (EEG) are mainly used to diagnose epilepsy, measure seizure frequency and evaluate efficacy of antiseizure drugs. These EEG data minimize the possibility of the underreporting of seizures, a known phenomenon in human epileptology. OBJECTIVE: To evaluate the correlation between reported seizure frequency and EEG frequency of ictal paroxysmal discharges (PDs) and to determine whether seizure underreporting phenomenon exists in veterinary epileptology. ANIMALS: Thirty-three ambulatory video-EEG recordings in dogs showing ≥1 ictal PD, excluding dogs with status epilepticus. METHODS: Retrospective observational study. Ictal PDs were counted manually over the entire recording to obtain the frequency of EEG seizures. Caregiver-reported seizure frequency from the medical record was categorized into weekly, daily, hourly, and per minute seizure groupings. The Spearman rank test was used for correlation analysis. RESULTS: The coefficient value (rs ) comparing reported seizure to EEG-confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048-0.64, P = .03). Other rs values comparing history against various seizure types were: 0.36 for motor seizures and 0.37 for nonmotor (absence) seizures. CONCLUSIONS AND CLINICAL IMPORTANCE: A weak correlation was found between the frequency of reported seizures from caregivers (subjective data) and ictal PDs on EEG (objective data). Subjective data may not be reliable enough to determine true seizure frequency given the discrepancy with EEG-confirmed seizure frequency. Confirmation of the seizure underreporting phenomenon in dogs by prospective study should be carried out.

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.

Imepitoin for treatment of idiopathic head tremor syndrome in dogs: A randomized, blinded, placebo-controlled study.

BACKGROUND: Idiopathic head tremor syndrome is a paroxysmal movement disorder of unknown etiology. Spontaneous remission may occur, but owners may request treatment in severely affected dogs with continued episodes. Controlled studies of the disease are not available. HYPOTHESIS/OBJECTIVES: A drug with gamma amino butyric acid-ergic and anxiolytic effects will decrease head tremor episodes. ANIMALS: Twenty-four dogs with severe nonremitting head tremor and presumptive clinical diagnosis of idiopathic head tremor syndrome. METHODS: Prospective, blinded, placebo-controlled clinical trial to compare imepitoin with placebo in dogs with frequent episodes of idiopathic head tremor. Evaluation of efficacy used the quotient T2/T1 that represented prolongation of the head tremor-free period compared to a 3-month baseline. A dog was considered a responder if tremors subsided or if the head tremor-free period was 3× longer than the longest period during baseline (T2/T1 ≥ 3). Sample size calculations considered a large effect of imepitoin on T2/T1 (Cohen's d = 0.8). RESULTS: There were no responders in the placebo group (0/12). In the imepitoin group, the responder rate was 17% (2/12; P = .18) with T2/T1 3.8 and 4.0. Mean T2/T1 was 1.0 ± 1.4 in the imepitoin and 0.4 ± 0.4 in the placebo group (P = .37). CONCLUSION AND CLINICAL IMPORTANCE: Imepitoin did not result in a significant overall benefit. Future studies should focus on treatment of subgroups with a common pathophysiology and similar comorbidities.

Recurrent polyp formation with Candida tropicalis infection and otitis in a dog.

To describe a case of a recurrent Candida tropicalis otitis externa, media and interna in a dog with an ear polyp. A 9-year-old Irish Setter was presented with 2 episodes of otitis sinistra, left-sided vestibular syndrome and Horner syndrome 7 months apart. At the first episode a benign ear polyp was extracted and Candida tropicalis cultured from the left middle ear. The neurological signs disappeared within 7 days, the Candida infection was more difficult to treat. Seven months later, a polyp was found in the ear again and cytology was consistent with Candida tropicalis. A unilateral left total ear canal ablation with lateral bulla osteotomy was performed and a middle ear culture confirmed Candida tropicalis. Treatment led to resolution of clinical signs. Candida tropicalis, an emerging pathogen, should be considered in cases of recurrent yeast otitis and may be difficult to treat.

[Canine meningoencephalitis and meningitis: retrospective analysis of a veterinary hospital population]. / Meningoenzephalitis und Meningitis beim Hund: retrospektive Analyse einer Klinikpopulation.

OBJECTIVE: Characterization of the etiology of meningoencephalitis and meningitis in dogs through an analysis of a veterinary hospital population. MATERIAL AND METHODS: Retrospective study (2011-2016) with evaluation of clinical and diagnostic data of dogs with cerebrospinal fluid (CSF) pleocytosis (> 5/µl). Only dogs with cytological evaluation of CSF or pathological examination of CNS were included. Results of CSF cytology and examination for infectious diseases were reviewed. RESULTS: A total of 62 dogs met the inclusion criteria. 14.5 % (n = 9) were classified as reactive CSF pleocytosis due to other structural CNS disease, such as neoplasia or infarct. Meningoencephalitis or meningitis of unknown origin was diagnosed in 56.5 % (n = 35). In 29.0 % (n = 18), investigations for infectious diseases or presence of bacteria in CSF cytology (n = 5) indicated an infectious etiology. This infectious etiology appeared reliable in 6 dogs (9.7 %) based on the examination findings, in 9 dogs (14.5 %), there was only a suspicion of infectious meningoencephalitis or meningitis and in 3 dogs (4.8 %), the findings were of uncertain significance. CONCLUSION: The most common cause of CSF pleocytosis was meningoencephalitis or meningitis of unknown origin. Nevertheless, there was evidence of a possible infectious etiology in 29 % of the dogs. For a reliable diagnosis, it is important to assess the CSF cytology and to conduct investigations for infectious diseases. CLINICAL RELEVANCE: Meningoencephalitis or meningitis of unknown origin requires immunosuppressive therapy. Therefore, CSF cytology and investigations for infectious diseases are important for an exclusion of infectious meningoencephalitis or meningitis.

Effect of prior general anesthesia or sedation and antiseizure drugs on the diagnostic utility of wireless video electroencephalography in dogs.

BACKGROUND: Ambulatory wireless video electroencephalography (AEEG) is the method of choice to discriminate epileptic seizures from other nonepileptic episodes. However, the influence of prior general anesthesia (GA), sedation, or antiseizure drug (ASD) on the diagnostic ability of AEEG is unknown. HYPOTHESIS/OBJECTIVES: The use of sedation/GA or ASD treatment before AEEG recording may affect the diagnostic ability of AEEG and the time to first abnormality on AEEG. ANIMALS: A total of 108 client-owned dogs undergoing ambulatory AEEG for paroxysmal episodes. METHODS: Retrospective cohort study. Proportions of diagnostic AEEG and time to first abnormality were compared between dogs that received sedation/GA or neither for instrumentation as well as dogs receiving at least 1 ASD and untreated dogs. RESULTS: Ambulatory EEG was diagnostic in 60.2% of all dogs including 49% of the sedation/GA dogs and 68% of dogs that received neither (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.02-5.00; P = .05). The AEEG was diagnostic in 51% of dogs receiving at least 1 ASD and 66% of untreated dogs (OR, 1.95; 95% CI, 0.9-4.3; P = .11). No difference was found in time to first abnormality between sedation/GA or neither or ASD-treated or untreated dogs (P = .1 and P = .3 respectively). Ninety-five percent of dogs had at least 1 abnormality within 277 minutes. CONCLUSION AND CLINICAL IMPORTANCE: Sedation/GA and concurrent ASD administration were not identified as confounding factors for decreasing AEEG diagnostic capability nor did they delay the time to first abnormality. A 4-hour minimal recording period is recommended.

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1.

The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization.