Towards a better understanding of idiopathic epilepsy through metabolic fingerprinting of cerebrospinal fluid in dogs.

Cerebrospinal fluid metabolomics is a promising research technology in the elucidation of nervous system disorders. Therefore, in this work, a cerebrospinal fluid (CSF) metabolomics method using liquid chromatography coupled to mass spectrometry was optimized and validated to cover a wide range of metabolites. An acceptable coefficient of variance regarding instrumental, within-lab and intra-assay precision was found for 95, 70 and 96 of 102 targeted metabolites, together with 1256, 676 and 976 untargeted compounds, respectively. Moreover, approximately 75% of targeted metabolites and 50% of untargeted compounds displayed good linearity across different dilution ranges. Consequently, metabolic alterations in CSF of dogs with idiopathic epilepsy (IE) were studied by comparing CSF of dogs diagnosed with IE (Tier II) to dogs with non-brain related disease. Targeted metabolome analysis revealed higher levels of cortisol, creatinine, glucose, hippuric acid, mannose, pantothenol, and 2-phenylethylamine (P values < 0.05) in CSF of dogs with IE, whereas CSF of dogs with IE showed lower levels of spermidine (P value = 0.02). Untargeted CSF metabolic fingerprints discriminated dogs with IE from dogs with non-brain related disease using Orthogonal Partial Least Squares Discriminant Analysis (R2(Y) = 0.997, Q2(Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.

Generalized myokymia, or neuromyotonia, or both in dogs with or without spinocerebellar ataxia.

BACKGROUND: KCNJ10 and CAPN1 variants cause "spinocerebellar" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear. OBJECTIVE: To investigate the association between KCNJ10 and CAPN1 and myokymia or neuromyotonia, with or without concurrent spinocerebellar ataxia. ANIMALS: Thirty-three client-owned dogs with spinocerebellar ataxia, myokymia neuromytonia, or a combination of these signs. METHODS: Genetic analysis of a cohort of dogs clinically diagnosed with spinocerebellar ataxia, myokymia or neuromyotonia. KCNJ10 c.627C>G and CAPN1 c.344G>A variants and the coding sequence of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1 were sequenced using DNA extracted from blood samples. RESULTS: Twenty-four Jack Russell terriers, 1 Jack Russell terrier cross, 1 Dachshund and 1 mixed breed with spinocerebellar ataxia were biallelic (homozygous) for the KCNJ10 c.627C>G variant. Twenty-one of those dogs had myokymia, neuromyotonia, or both. One Parson Russell terrier with spinocerebellar ataxia alone was biallelic for the CAPN1 c.344G>A variant. Neither variant was found in 1 Jack Russell terrier with ataxia alone, nor in 3 Jack Russell terriers and 1 Yorkshire terrier with myokymia and neuromyotonia alone. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 5 dogs. CONCLUSION: The KCNJ10 c.627C>G variant, or rarely the CAPN1 c.344G>A variant, was confirmed to be the causal variant of spinocerebellar ataxia. We also report the presence of the KCNJ10 c.627C>G variant in the Dachshund breed. In dogs with myokymia and neuromyotonia alone the reported gene variants were not found. Other genetic or immune-mediated causes should be investigated to explain the clinical signs of these cases.

Phenotypic and genetic aspects of hereditary ataxia in dogs.

Hereditary ataxias are a large group of neurodegenerative diseases that have cerebellar or spinocerebellar dysfunction as core feature, occurring as an isolated sign or as part of a syndrome. Based on neuropathology, this group of diseases has so far been classified into cerebellar cortical degenerations, spinocerebellar degenerations, cerebellar ataxias without substantial neurodegeneration, canine multiple system degeneration, and episodic ataxia. Several new hereditary ataxia syndromes are described, but most of these diseases have similar clinical signs and unspecific diagnostic findings, wherefore achieving a definitive diagnosis in these dogs is challenging. Eighteen new genetic variants associated with these diseases have been discovered in the last decade, allowing clinicians to reach a definitive diagnosis for most of these conditions, and allowing breeding schemes to adapt to prevent breeding of affected puppies. This review summarizes the current knowledge about hereditary ataxias in dogs, and proposes to add a "multifocal degenerations with predominant (spino)cerebellar component" category regrouping canine multiple system degeneration, new hereditary ataxia syndromes that do not fit in 1 of the previous categories, as well as specific neuroaxonal dystrophies and lysosomal storage diseases that cause major (spino)cerebellar dysfunction.

Identification of a Novel Idiopathic Epilepsy Risk Locus and a Variant in the CCDC85A Gene in the Dutch Partridge Dog.

(1) Idiopathic epilepsy (IE) is thought to have a genetic cause in several dog breeds. However, only two causal variants have been identified to date, and few risk loci are known. No genetic studies have been conducted on IE in the Dutch partridge dog (DPD), and little has been reported on the epileptic phenotype in this breed. (2) Owner-filled questionnaires and diagnostic investigations were used to characterize IE in the DPD. A genome-wide association study (GWAS) involving 16 cases and 43 controls was performed, followed by sequencing of the coding sequence and splice site regions of a candidate gene within the associated region. Subsequent whole-exome sequencing (WES) of one family (including one IE-affected dog, both parents, and an IE-free sibling) was performed. (3) IE in the DPD has a broad range in terms of age at onset, frequency, and duration of epileptic seizures. Most dogs showed focal epileptic seizures evolving into generalized seizures. A new risk locus on chromosome 12 (BICF2G630119560; praw = 4.4 × 10-7; padj = 0.043) was identified through GWAS. Sequencing of the GRIK2 candidate gene revealed no variants of interest. No WES variants were located within the associated GWAS region. However, a variant in CCDC85A (chromosome 10; XM_038680630.1: c.689C > T) was discovered, and dogs homozygous for the variant (T/T) had an increased risk of developing IE (OR: 6.0; 95% CI: 1.6-22.6). This variant was identified as likely pathogenic according to ACMG guidelines. (4) Further research is necessary before the risk locus or CCDC85A variant can be used for breeding decisions.

CT diagnosis of occipital condyle fracture in a dog presented for severe cervical hyperesthesia.

A 9-month-old male entire Doberman Pinscher presented with acute onset of severe cervical hyperesthesia after a fall. Neurological examination revealed a normal gait with low head carriage and severe cervical hyperesthesia. A CT scan of the cervical vertebral column revealed the presence of a comminuted fracture at the dorsomedial aspect of the right occipital condyle and sclerosis of the underlying bone. Medical management was initiated consisting of an external bandage, strict rest, and pain medication. Due to the lack of clinical improvement, the dog was euthanized 2 months after diagnosis. Histopathology of the lesion was compatible with a healing fracture.

The role of nutrition in canine idiopathic epilepsy management: Fact or fiction?

In the last decade, nutrition has gained interest in the management of canine idiopathic epilepsy (IE) based on growing scientific evidence. Diets can serve their functions through many pathways. One potential pathway includes the microbiota-gut-brain axis, which highlights the relationship between the brain and the intestines. Changing the brain's energy source and a number of dietary sourced anti-inflammatory and neuroprotective factors appears to be the basis for improved outcomes in IE. Selecting a diet with anti-seizure effects and avoiding risks of proconvulsant mediators as well as interference with anti-seizure drugs should all be considered in canine IE. This literature review provides information about preclinical and clinical evidence, including a systematic evaluation of the level of evidence, suggested mechanism of action and interaction with anti-seizure drugs as well as pros and cons of each potential dietary adaptation in canine IE.

Evaluation of the effect of phenobarbital administration on the biochemistry profile, with a focus on serum liver values, in epileptic cats.

OBJECTIVES: Phenobarbital (PB) is the most common antiseizure drug (ASD) used for the management of feline epilepsy. In dogs, PB is known to cause serum liver enzyme induction and hepatotoxicity, especially after administration long term or in high concentrations. In cats, insufficient evidence is available to draw similar conclusions. The aim of this study was to evaluate the effect of PB administration on the serum biochemistry profile of epileptic cats. As an additional objective, other adverse effects arising, related to PB treatment, were recorded. METHODS: Medical records of four veterinary centres were retrospectively reviewed for epileptic cats receiving PB treatment. Cats were included if they had a diagnosis of idiopathic epilepsy or structural epilepsy; a normal baseline serum biochemistry profile; at least one follow-up serum biochemistry profile; no concurrent disease or had not received medication that could possibly influence liver function or lead to serum liver enzyme induction. Alkaline phosphatase, alanine aminotransferase (ALT), aspartate transaminase and gamma-glutamyl transferase activities, and total bilirubin, bile acids, glucose, albumin, total protein, urea and creatinine concentrations before and during PB administration were recorded. PB serum concentration was also recorded, when available. RESULTS: Thirty-three cats (24 males, nine females) with a median age of 3 years (range 2 months to 12 years) met the inclusion criteria. Idiopathic or structural epilepsy was diagnosed in 25 (76%) and eight (24%) cats, respectively. The follow-up period ranged from 9 to 62 months. This study found an increase in ALT in three cats, possibly related to a PB serum concentration >30 µg/ml. No statistically significant increase in serum liver enzymes or other evaluated biochemistry parameters was found by comparing pre- and post-treatment parameters. CONCLUSIONS AND RELEVANCE: PB administration did not result in hepatic enzyme induction or other biochemical abnormalities in cats. This strengthens the safety profile of PB as an ASD in cats.

Repetitive transcranial magnetic stimulation in drug-resistant idiopathic epilepsy of dogs: A noninvasive neurostimulation technique.

BACKGROUND: Although repetitive transcranial magnetic stimulation (rTMS) has been assessed in epileptic humans, clinical trials in epileptic dogs can provide additional insight. OBJECTIVES: Evaluate the potential antiepileptic effect of rTMS in dogs. ANIMALS: Twelve client-owned dogs with drug-resistant idiopathic epilepsy (IE). METHODS: Single-blinded randomized sham-controlled clinical trial (dogs allocated to active or sham rTMS) (I) and open-labeled uncontrolled clinical trial (dogs received active rTMS after sham rTMS) (II). Monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), and number of cluster seizures (CS) were evaluated for a 3-month pre-TMS and post-rTMS period and safety was assessed. The lasting effect period of rTMS was assessed in each dog treated by active stimulation using the MSF ratio (proportion of post-TMS to pre-rTMS MSF) and treatment was considered effective if the ratio was <1. RESULTS: No adverse effects were reported. In trial I, MSF and MSDF decreased significantly (P = .04) in the active group (n = 7). In the sham group (n = 5), no significant changes were found (P = .84 and .29, respectively). Cluster seizures did not change significantly in either group. No significant differences were detected between the groups. In trial II, previously sham-treated dogs (n = 5) received active rTMS and significant decreases in MSF and MSDF were noted (P = .03 and .008, respectively). The overall effect of rTMS lasted for 4 months; thereafter, the MSF ratio was >1. CONCLUSIONS AND CLINICAL IMPORTANCE: Repetitive transcranial magnetic stimulation may be a safe adjunctive treatment option for dogs with drug-resistant IE, but large-scale studies are needed to establish firm conclusions.

Comparative pharmacokinetics of imepitoin after oral and rectal administration in healthy dogs.

The purpose of the present study was to investigate if rectal administration of imepitoin in healthy dogs leads to plasma concentrations comparable to those after oral administration. Significantly lower systemic exposure and maximal plasma concentration (Cmax) of imepitoin was achieved after rectal compared to oral administration (P≤0.001). Therefore, this study does not support the rectal administration of imepitoin in dogs.

Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs.

BACKGROUND: Paroxysmal dyskinesias (PDs) are a group of central nervous system diseases characterized by episodes of abnormal involuntary hyperkinetic movement without altered consciousness that increasingly have been recognized in dogs. OBJECTIVES: To present the phenotypical characterization, treatment, and outcome of a PD observed in Maltese dogs. ANIMALS: Client-owned Maltese dogs (n = 19) with presumed diagnosis of PD. METHODS: Data were collected retrospectively from medical records (2014-2019), and supporting information was added prospectively by using a questionnaire directed to the owners of the affected dogs. RESULTS: The episodes were characterized mainly by sudden dystonia of ≥1 limbs and generalized body tremors with preserved consciousness. The mean age of clinical onset was 5.4 years. Episode frequency varied widely both among and within individuals. Median episode duration was 4.5 minutes. Most episodes were stress- or exercise-induced. Acetazolamide was administered to 6 dogs, and 4 dogs experienced a decrease in episode frequency. In 7 dogs that received a gluten-free diet, 6 dogs became episode-free. In 4 dogs, the episodes stopped spontaneously and in 2 dogs no medication or specific diet was given and the episodes continued at the same frequency. CONCLUSIONS AND CLINICAL IMPORTANCE: Given the breed predisposition and regional distribution of the disease, additional research should focus on elucidating the underlying genetic cause doing so might advance both our understanding of the pathophysiology and treatment of this disease, not only in dogs, but also in humans. Regardless of the treatment protocol selected, prognosis appears fair to good.

Accuracy of transcranial magnetic stimulation and a Bayesian latent class model for diagnosis of spinal cord dysfunction in horses.

BACKGROUND: Spinal cord dysfunction/compression and ataxia are common in horses. Presumptive diagnosis is most commonly based on neurological examination and cervical radiography, but the interest into the diagnostic value of transcranial magnetic stimulation (TMS) with recording of magnetic motor evoked potentials has increased. The problem for the evaluation of diagnostic tests for spinal cord dysfunction is the absence of a gold standard in the living animal. OBJECTIVES: To compare diagnostic accuracy of TMS, cervical radiography, and neurological examination. ANIMALS: One hundred seventy-four horses admitted at the clinic for neurological examination. METHODS: Retrospective comparison of neurological examination, cervical radiography, and different TMS criteria, using Bayesian latent class modeling to account for the absence of a gold standard. RESULTS: The Bayesian estimate of the prevalence (95% CI) of spinal cord dysfunction was 58.1 (48.3%-68.3%). Sensitivity and specificity of neurological examination were 97.6 (91.4%-99.9%) and 74.7 (61.0%-96.3%), for radiography they were 43.0 (32.3%-54.6%) and 77.3 (67.1%-86.1%), respectively. Transcranial magnetic stimulation reached a sensitivity and specificity of 87.5 (68.2%-99.2%) and 97.4 (90.4%-99.9%). For TMS, the highest accuracy was obtained using the minimum latency time for the pelvic limbs (Youden's index = 0.85). In all evaluated models, cervical radiography performed poorest. CLINICAL RELEVANCE: Transcranial magnetic stimulation-magnetic motor evoked potential (TMS-MMEP) was the best test to diagnose spinal cord disease, the neurological examination was the second best, but the accuracy of cervical radiography was low. Selecting animals based on neurological examination (highest sensitivity) and confirming disease by TMS-MMEP (highest specificity) would currently be the optimal diagnostic strategy.

Canine Nonstructural Megaesophagus as a Clinical Sign of Potential Neurological Disease: 99 Cases.

Knowledge regarding the etiology and prognosis for canine megaesophagus (ME) is currently limited to small case series that may now be out of date in light of recent advances in the understanding of neurological syndromes and the availability of advanced diagnostic testing. Ninety-nine dogs diagnosed with nonstructural ME were included. Congenital idiopathic ME was present in 10 cases, with complete resolution of clinical signs in a single case. Eighty-nine cases were considered acquired, with most cases being either idiopathic (42.7%) or associated with myasthenia gravis (38.2%). Idiopathic cases represented a smaller percentage of acquired ME than previously reported. Death or euthanasia directly related to ME occurred in almost 50% of acquired cases, whereas clinical signs persisted in ∼20% of cases and resolved in 30% of cases. A diagnosis of an underlying etiology, in particular myasthenia gravis, was associated with a better outcome in acquired ME. ME continues to be a challenging condition to manage, with a guarded-to-poor prognosis, particularly when an underlying etiology is not identified. Thorough diagnostic testing for an underlying neurological disorder is important in cases with ME as this may allow institution of appropriate treatment and the potential for a better prognosis.

Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study.

BACKGROUND: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. OBJECTIVES: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. ANIMALS: Client-owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. METHODS: Randomized parallel group clinical trial. Patients were randomly allocated to the IN-MDZ (n = 21) or IV-MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05. RESULTS: IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN-MDZ (100 seconds) was superior (P = .04) to IV-MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN-MDZ and IV-MDZ, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.

Determination of magnetic motor evoked potential latency time cutoff values for detection of spinal cord dysfunction in horses.

BACKGROUND: Transcranial magnetic stimulation (TMS) and recording of magnetic motor evoked potentials (MMEP) can detect neurological dysfunction in horses but cutoff values based on confirmed spinal cord dysfunction are lacking. OBJECTIVES: To determine latency time cutoff for neurological dysfunction. ANIMALS: Five control horses and 17 horses with proprioceptive ataxia. METHODS: Case-control study with receiver operating characteristic curve analysis, based on diagnostic imaging, TMS, and histopathological findings. Horses were included if all 3 examinations were performed. RESULTS: Diagnostic imaging and histopathology did not show abnormalities in the control group but confirmed spinal cord compression in 14 of 17 ataxic horses. In the remaining 3 horses, histopathological lesions were mild to severe, but diagnostic imaging did not confirm spinal cord compression. In control horses, latency time values of thoracic and pelvic limbs were significantly lower than in ataxic horses (20 ± 1 vs 34 ± 16 milliseconds, P = .05; and 39 ± 1 vs 78 ± 26 milliseconds, P = .004). Optimal cutoff values to detect spinal cord dysfunction were 22 milliseconds (sensitivity [95% CI interval], 88% [73%-100%]; specificity, 100% [100%-100%]) in thoracic and 40 milliseconds (sensitivity, 94% [83%-100%]; specificity, 100% [100%-100%]) in pelvic limbs. To detect spinal cord dysfunction caused by compression, the optimal cutoff for thoracic limbs remained 22 milliseconds, while it increased to 43 milliseconds in pelvic limbs (sensitivity, 100% [100%-100%]; specificity, 100% [100%-100%] for thoracic and pelvic limbs). CONCLUSIONS AND CLINICAL IMPORTANCE: Magnetic motor evoked potential analysis using these cutoff values is a promising diagnostic tool for spinal cord dysfunction diagnosis in horses.

Truncating SLC12A6 variants cause different clinical phenotypes in humans and dogs.

Clinical, pathological, and genetic findings of a primary hereditary ataxia found in a Malinois dog family are described and compared with its human counterpart. Based on the family history and the phenotype/genotype relationships already described in humans and dogs, a causal variant was expected to be found in KCNJ10. Rather surprisingly, whole-exome sequencing identified the SLC12A6 NC_006612.3(XM_014109414.2): c.178_181delinsCATCTCACTCAT (p.(Met60Hisfs*14)) truncating variant. This loss-of-function variant perfectly segregated within the affected Malinois family in an autosomal recessive way and was not found in 562 additional reference dogs from 18 different breeds, including Malinois. In humans, SLC12A6 variants cause "agenesis of the corpus callosum with peripheral neuropathy" (ACCPN, alias Andermann syndrome), owing to a dysfunction of this K+-Cl- cotransporter. However, depending on the variant (including truncating variants), different clinical features are observed within ACCPN. The variant in dogs encodes the shortest isoform described so far and its resultant phenotype is quite different from humans, as no signs of peripheral neuropathy, agenesis of the corpus callosum nor obvious mental retardation have been observed in dogs. On the other hand, progressive spinocerebellar ataxia, which is the most important feature of the canine phenotype, hindlimb paresis, and myokymia-like muscle contractions have not been described in humans with ACCPN so far. As this is the first report of a naturally occurring disease-causing SLC12A6 variant in a non-human species, the canine model will be highly valuable to better understand the complex molecular pathophysiology of SLC12A6-related neurological disorders and to evaluate novel treatment strategies.

Magnetic motor evoked potentials of cervical muscles in horses.

BACKGROUND: When surgical treatment of cervical vertebral malformation is considered, precise localization of compression sites is essential, but remains challenging. Magnetic motor evoked potentials (mMEP) from paravertebral muscles are useful in localizing spinal cord lesions, but no information about cervical muscle mMEP in horses is available yet. Therefore, the aim of this study was to determine the possibility, normal values, inter- and intra-observer agreement and factors that have an effect on cervical mMEP in healthy horses. METHODS: Transcranial magnetic stimulation was performed on 50 normal horses and 4 (2 left, 2 right) muscle responses were recorded at the middle of each cervical vertebra (C1-C7) and additionally just caudal to C7 to evaluate cervical nerves (Cn) Cn1 to Cn8. Latency time and amplitude of the recorded mMEP were defined by both an experienced and an unexperienced operator. RESULTS: Latency increased gradually from 14.2 ± 1.38 ms for Cn3 to 17.7 ± 1.36 ms for Cn8, was significantly influenced by cervical nerve (P < 0.01), gender (P = 0.02) and height (P = 0.03) and had a good intra-observer agreement. The smallest mean amplitude (4.35 ± 2.37 mV) was found at Cn2, the largest (5.99 ± 2.53 mV) at Cn3. Amplitude was only significantly influenced by cervical nerve (P < 0.01) and had a low intra-observer agreement. No significant effect of observer on latency (P = 0.88) or amplitude (P = 0.99) measurements was found. CONCLUSION: mMEP of cervical muscles in normal horses are easy to collect and to evaluate with limited intra- and inter-observer variation concerning amplitude and should be investigated in future studies in ataxic horses to evaluate its clinical value.

Magnetic Motor Evoked Potential Recording in Horses Using Intramuscular Needle Electrodes and Surface Electrodes.

To date, motor evoked potential (MEP) recording in animals is often performed using intramuscular monopolar needle electrodes. Their placement and use has several disadvantages. Adhesive surface electrodes appear to be attractive because they are painless and easy to place. Because these are not used in horses, a scouting study is performed to (1) explore the applicability of surface electrodes in horses (2) determine the repeatability of motor latency times (MLTs) and amplitude measurements, and (3) to investigate if MLTs and amplitude values of surface electrode recordings were similar to intramuscular needle electrode recordings. Transcranial MEP recordings were performed by both coated needle and surface electrodes on ten sedated warmblood horses. Mean MLTs for the thoracic limbs were 20.8 ± 1.5 ms for needle and 21.2 ± 1.4 ms for surface electrode recording and 39.4 ± 3.8 ms and 39.2 ± 3.8 ms for the pelvic limbs, respectively. Mean amplitude values were 8.3 ± 4.1 and 7.2 ± 4.7 mV for the thoracic limbs and 4.2 ± 3.1 and 3.8 ± 2.4 mV for the pelvic limbs, respectively. A good agreement and repeatability for MLTs but insufficient agreement and repeatability for amplitude between both recording types were determined by Bland-Altman plots and Passing-Bablok regression and coefficients of variation calculation. In conclusion, this preliminary study shows that surface electrode recording of MEP is possible and well tolerated in horses. Surface recordings were repeatable and look similar to the intramuscular recordings when regarding MLTs, but overshadowing effects of large test-to-test variations precluded a conclusion concerning amplitude.

The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs.

SeSAME/EAST syndrome is a multisystemic disorder in humans, characterised by seizures, sensorineural deafness, ataxia, developmental delay and electrolyte imbalance. It is exclusively caused by homozygous or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar syndrome in two families belonging to the Malinois dog breed, based on clinical, neurological, electrodiagnostic and histopathological examination. Genetic analysis detected a novel pathogenic KCNJ10 c.986T>C (p.(Leu329Pro)) variant that is inherited in an autosomal recessive way. This variant has an allele frequency of 2.9% in the Belgian Malinois population, but is not found in closely related dog breeds or in dog breeds where similar symptoms have been already described. The canine phenotype is remarkably similar to humans, including ataxia and seizures. In addition, in half of the dogs clinical and electrophysiological signs of neuromyotonia were observed. Because there is currently no cure and treatment is nonspecific and unsatisfactory, this canine translational model could be used for further elucidating the genotype/phenotype correlation of this monogenic multisystem disorder and as an excellent intermediate step for drug safety testing and efficacy evaluations before initiating human studies.