Polyneuropathy of Finnish horses characterised by inflammatory demyelination and intracisternal Schwann cell inclusions.

REASON FOR PERFORMING STUDY: A neurological disorder characterised by pelvic limb metatarsophalangeal joint extensor paresis has been observed in numerous horses in Scandinavia for the last decade. Very little has been formally reported and there have been no detailed assessments of the neurological signs or neuropathological lesions. OBJECTIVES: To describe the epidemiological and pathological features of an outbreak of 'Scandinavian knuckling syndrome' in a riding stable in southern Finland. METHODS: Clinical neurological examination of 4 cases and neuropathological assessment of tissues of one case were performed. RESULTS: Eleven out of 17 horses fed on ryegrass from a common source showed progressive clinical signs of metatarsophalangeal extensor paresis necessitating euthanasia of 7 horses. Nervous system lesions in one horse consisted of a novel demyelinating, mildly inflammatory peripheral neuropathy, with BiP/GRP positive rough endoplasmatic reticulum Schwann cell inclusions. CONCLUSIONS: The clinical signs and lesions documented differ from any previously described equine polyneuropathy and suggest a primary Schwann cell lesion. POTENTIAL RELEVANCE: The classification of this disease as a novel demyelinating polyneuropathy may assist focused epidemiological investigations.

Benign familial juvenile epilepsy in Lagotto Romagnolo dogs.

BACKGROUND: Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. ANIMALS: Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. METHODS: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. RESULTS: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs.

This case report documents two pathological variations of potentially inherited, cerebellar cortical abiotrophy in two unrelated Lagotto Romagnolo breed dogs. The first dog had an atypical lesion in the cerebellar cortex with depletion of cerebellar granular cell layer and sparing of the Purkinje cell layer. The second case had degenerative changes in both Purkinje and granular cell layers. The clinical picture was similar in both cases presented, although the severity of the signs of cerebellar dysfunction varied.

Diagnostic Utility of Wireless Video-Electroencephalography in Unsedated Dogs.

BACKGROUND: Poor agreement between observers on whether an unusual event is a seizure drives the need for a specific diagnostic tool provided by video-electroencephalography (video-EEG) in human pediatric epileptology. OBJECTIVE: That successful classification of events would be positively associated with increasing EEG recording length and higher event frequency reported before video-EEG evaluation; that a novel wireless video-EEG technique would clarify whether unusual behavioral events were seizures in unsedated dogs. ANIMALS: Eighty-one client-owned dogs of various breeds undergoing investigation of unusual behavioral events at 4 institutions. METHODS: Retrospective case series: evaluation of wireless video-EEG recordings in unsedated dogs performed at 4 institutions. RESULTS: Electroencephalography achieved/excluded diagnosis of epilepsy in 58 dogs (72%); 25 dogs confirmed with epileptic seizures based on ictal/interictal epileptiform discharges, and 33 dogs with no EEG abnormalities associated with their target events. As reported frequency of the target events decreased (annually, monthly, weekly, daily, hourly, minutes, seconds), EEG was less likely to achieve diagnosis (P < 0.001). Every increase in event frequency increased the odds of achieving diagnosis by 2.315 (95% confidence interval: 1.36-4.34). EEG recording length (mean = 3.69 hours, range: 0.17-22.5) was not associated (P = 0.2) with the likelihood of achieving a diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Wireless video-EEG in unsedated dogs had a high success for diagnosis of unusual behavioral events. This technique offered a reliable clinical tool to investigate the epileptic origin of behavioral events in dogs.

Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas.

BACKGROUND: Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed dogs, such as Chihuahuas. OBJECTIVES: To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neurologic deficits and to investigate the association of CM/SM-related clinical signs with signalment, SM, or CCJ abnormalities. ANIMALS: Fifty-three client-owned Chihuahuas. METHODS: Prospective study. Questionnaire analyses and physical and neurologic examinations were obtained before magnetic resonance and computed tomography imaging. Images were evaluated for the presence of SM, CM, and atlantooccipital overlapping. Additionally, medullary kinking, dorsal spinal cord compression, and their sum indices were calculated. RESULTS: Scratching was the most common CM/SM-related clinical sign and decreased postural reaction the most common neurologic deficit in 73 and 87% of dogs, respectively. Chiari-like malformation and SM were present in 100 and 38% of dogs, respectively. Syringomyelia was associated with the presence of CM/SM-related clinical signs (P = 0.034), and medullary kinking and sum indices were higher in dogs with clinical signs (P = 0.016 and P = 0.007, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Syringomyelia and CCJ abnormalities are prevalent in Chihuahuas. Syringomyelia was an important factor for the presence of CM/SM-related clinical signs, but many dogs suffered from similar clinical signs without being affected by SM, highlighting the clinical importance of CCJ abnormalities in Chihuahuas.

Paroxysmal Dyskinesia in Border Terriers: Clinical, Epidemiological, and Genetic Investigations.

BACKGROUND: In the last decade, a disorder characterized by episodes of involuntary movements and dystonia has been recognized in Border Terriers. OBJECTIVES: To define clinical features of paroxysmal dyskinesia (PD) in a large number of Border Terriers and to study the genetics of the disease. ANIMALS: 110 affected and 128 unaffected client-owned Border Terriers. METHODS: A questionnaire regarding clinical characteristics of PD was designed at Utrecht University and the University of Helsinki. Thirty-five affected Border Terriers underwent physical examination and blood testing (hematology and clinical biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs and electroencephalograms (EEG) between episodes were obtained in 10 affected dogs. A genomewide association study (GWAS) was performed with DNA of 110 affected and 128 unaffected dogs. RESULTS: One hundred forty-seven questionnaires were included in the study. The most characteristic signs during episodes were dystonia, muscle fasciculations, and falling over. The majority of owners believed that their dogs remained conscious during the episodes. A beneficial effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners changed their dogs' diet to a hypoallergenic, gluten-free diet, and all reported reasonable to good improvement of signs. Clinical examinations and diagnostic test results were unremarkable. The GWAS did not identify significantly associated chromosome regions. CONCLUSIONS AND CLINICAL IMPORTANCE: The survey results and EEG studies provided further evidence that the observed syndrome is a PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates that inheritance of PD in Border Terriers probably is complex.

Magnetic resonance imaging findings in Finnish Spitz dogs with focal epilepsy.

Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were evaluated. General clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast enhancement after gadolinium injection was identified in this dog's right parietal cortex. However, no such changes were observed in repeated magnetic resonance images. Special emphasis was given to seizure history to determine any correlations between seizure intervals and MRI findings. Our results indicate that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity in detecting epileptogenic areas in our patients with focal seizures. Reversible MRI changes in 1 dog could have been caused by seizures.

LGI Proteins and Epilepsy in Human and Animals.

Leucine-rich glioma-inactivated (LGI) protein was first thought to have a suppressor effect in the formation of some cancers. Developments in physiology and medicine made it possible to characterize the function of the LGI protein family and its crucial role in different conditions more precisely. These proteins play an important role in synaptic transmission, and dysfunction may cause hyperexcitability. Genetic mutation of LGI1 was confirmed to be the cause of autosomal dominant lateral temporal lobe epilepsy in humans. The LGI2 mutation was identified in benign familial juvenile epilepsy in Lagotto Romagnolo (LR) dogs. Cats with familial spontaneous temporal lobe epilepsy have been reported, and the etiology might be associated with LGI protein family dysfunction. In addition, an autoimmune reaction against LGI1 was detected in humans and cats with limbic encephalitis. These advances prompted a review of LGI protein function and its role in different seizure disorders.

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long-Term Follow-Up Study.

BACKGROUND: Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long-term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult-onset epilepsies. HYPOTHESIS/OBJECTIVES: The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood. ANIMALS: A total of 25 LR with a history of BFJE and 91 control dogs of the same breed. METHODS: Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog's activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case-control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy. RESULTS: Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood. CONCLUSIONS AND CLINICAL IMPORTANCE: Although the long-term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.