Quantitative assessment of hsp70, IL-1ß and TNF-α in the spinal cord of dogs with E40K SOD1-associated degenerative myelopathy.

Inflammation is involved in the pathogenesis of many neurodegenerative diseases. Canine degenerative myelopathy (DM) is a progressive adult-onset neurodegenerative disease commonly associated with an E40K missense mutation in the SOD1 gene. DM has many similarities to some familial forms of human amyotrophic lateral sclerosis (ALS) and may serve as an important disease model for therapy development. Pro-inflammatory mediators such as interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and heat shock protein (hsp) 70 play a role in the pathogenesis of ALS. The focus of the current work was to determine whether an inflammatory phenotype is present in canine DM as defined by IL-1ß, TNF-α, and hsp70 responses in cerebrospinal fluid (CSF) and spinal cord tissue. Concentrations of hsp70, IL-1ß and TNF-α were below the limits of detection by ELISA in the CSF of both normal and DM-affected dogs. Immunohistochemical staining for hsp70 was significantly increased in ependymal cells lining the spinal cord central canal of DM-affected dogs (P = 0.003). This was not associated with increased IL-1ß or TNF-α staining, but was associated with increased CD18 staining in the gray matter of DM-affected dogs. These results suggest that hsp70 in spinal cord tissue is a potential inflammatory signature in canine DM.

Epilepsy in horses: aetiological classification and predictive factors.

REASONS FOR PERFORMING THE STUDY: In contrast with reports in man and small animals, a systematic classification of seizures in horses is lacking. OBJECTIVES: The purpose of this study was to classify seizures based on their aetiology and to characterise epilepsy in 104 horses presented for seizures at the Ohio State University Veterinary Medical Center between 1988 and 2009. METHODS: In a retrospective observational study, seizures were classified by aetiology based on history, clinical observations, diagnostic investigations (e.g. electroencephalograms, cerebrospinal fluid and computed tomography imaging of the head) and post mortem examinations, when available. Univariate and multivariate logistic regression analyses were performed. RESULTS: Epilepsy (i.e. 2 or more recurrent seizures) was identified in 70% of cases, and further classified as symptomatic (i.e. structural brain pathology, 35.6% of cases), cryptogenic (i.e. unknown, 54.8% of cases) and idiopathic (i.e. suspected genetic predisposition, 2.7% of cases). Normal neurological examination on admission, the presence of seizures unprovoked by any identified factors and paroxysmal epileptiform activity on electroencephalogram recordings were all strongly (P<0.05) correlated with epilepsy on univariate analysis. For a horse with generalised seizures, the odds of having epilepsy was 7 times lower compared with a similar horse with partial seizures (P<0.05) in multivariate modelling. CONCLUSIONS: Seizure aetiology was symptomatic or cryptogenic in most horses, whereas reactive seizures and idiopathic epilepsy were less common. POTENTIAL RELEVANCE: This study is the first attempt to classify seizures and to characterise epilepsy in a referral-based equine population. Predictive factors of epilepsy in horses were similar to those reported in other species and may assist the clinician with the early diagnosis of epilepsy.

Fibrocartilaginous embolic myelopathy in miniature schnauzers.

In large- and giant-breed dogs, fibrocartilaginous embolic myelopathy (FCEM) is a well-recognized syndrome of acute spinal cord infarction caused by embolization of fibrocartilage. The miniature schnauzer is reportedly the most frequently affected small breed, although clinical data from only six miniature schnauzers with FCEM is available in the literature. The purposes of this study were to determine the relative frequency of FCEM compared to other causes of myelopathy in miniature schnauzers, to characterize the clinicopathological features of FCEM in 38 miniature schnauzers, and to directly compare FCEM and intervertebral disk herniation in miniature schnauzers with respect to age at diagnosis; gender; neuroanatomical localization; and progression, asymmetry, and severity of neurological deficits. Fibrocartilaginous embolic myelopathy was the most common cause of myelopathy in miniature schnauzers. Age at diagnosis, asymmetry and severity of neurological deficits, and lack of progression of clinical signs after 24 hours assisted in distinguishing FCEM from intervertebral disk herniation. Fibrocartilaginous embolic myelopathy-related mortality in miniature schnauzers was significantly lower than mortality rates reported for affected large and giant breeds. Only 22% of miniature schnauzers were euthanized because of their disease, although the vast majority of survivors failed to achieve complete neurological recovery.

Generalized tremors in dogs: 24 cases (1984-1995).

OBJECTIVE: To characterize clinical features, diagnostic evaluation, and treatment outcome for dogs with generalized tremors. DESIGN: Retrospective case series. ANIMALS: 12 white purebred and 12 nonwhite mixed-breed and purebred dogs. PROCEDURE: Medical records of dogs examined for tremors between January 1984 and July 1995 were reviewed. History, signalment, abnormalities on physical and neurologic examinations, results of diagnostic testing, and diagnosis were recorded for each dog. Results were divided into the following 3 categories on the basis of the cause of the tremors: inflammatory, noninflammatory, and idiopathic. Cause was determined by results of CSF analyses or a history of toxin exposure. RESULTS: The only noninflammatory cause of generalized tremors identified in these dogs was mycotoxin ingestion. Steroid-responsive tremor syndrome had developed in 22 of 24 dogs, half of which had abnormal results of CSF analyses. Most dogs were young adults between 1 and 5 years old. More than half of the dogs were nonwhite mixed-breeds and all weighed < 15 kg (33 lb). Eighty percent of the dogs responded to immunosuppressive treatment within 3 days. CLINICAL IMPLICATIONS: Inflammatory and noninflammatory causes for generalized tremors in dogs result in similar clinical signs, so a logical diagnostic and treatment approach is needed. Steroid-responsive tremor syndrome should be considered in small- to medium-breed, young adult dogs, regardless of coat color. A rapid and complete response to immunosuppressive treatment is expected.

Methylmalonic and malonic aciduria in a dog with progressive encephalomyelopathy.

A 12 week old female Labrador retriever dog with signs of progressive diffuse degeneration of the brain and spinal cord was found to have methylmalonic and malonic aciduria. Over a 5 month period, the dog developed neurologic signs compatible with disease of the central nervous system with predominant diffuse cerebral and right lateralizing brainstem deficits. Gross pathological examination of the brain showed that the lateral, third, and fourth ventricles of the brain were markedly enlarged and associated with white and grey matter atrophy. Syringomyelia and hydromyelia of the central canal into the dorsal funiculus of the spinal cord beginning at the level of the cervical intumescence and extending to the lumbar intumescence was also present. Significant biochemical abnormalities include methylmalonic and malonic aciduria, mild lactic and pyruvic aciduria. There was also accumulation of citric acid cycle intermediates including succinic, aconitic, and fumaric acids. Disordered fatty acid oxidation was suggested by increased excretion of adipic, ethylmalonic, suberic and sebacic acids. Neither ketoacidosis nor hyperammonemia were present, and serum cobalamin levels were normal. Overall, this dog demonstrates an inborn error of metabolism resulting in abnormal organic acid accumulation associated with a neurodegenerative disease.

A retrospective study of cavernous sinus syndrome in 4 dogs and 8 cats.

Cavernous sinus syndrome (CSS) is characterized by deficits in more than one of the cranial nerves (CN) that traverse the cavernous sinus at the base of the cranial vault: CN III (oculomotor), IV (trochlear), VI (abducens), and the first two branches of CN V (trigeminal). Records from 4 dogs and 8 cats with CSS diagnosed over a 14-year period were reviewed. The most common clinical signs were ophthalmoparesis or ophthalmoplegia, mydriasis with no direct or consensual pupillary light reflexes, ptosis, decreased corneal sensation, and decreased retractor oculi reflex. All cats had initial signs referable to a left CSS lesion (one had bilateral CSS), whereas in all dogs the lesions were localized to the right cavernous sinus. Median ages at diagnosis were 9 and 10 years of age for dogs and cats, respectively. Cerebel lomedullary cisternae cerebrospinal fluid analysis in 6 animals was useful as a sensitivebut nonspecific diagnostic test of an intracranial inflammatory or neoplastic lesion. Magnetic resonance imaging scans provided a more definitive diagnostic test in all dogs, revealing a contrast-enhancing mass on T1 weighted scans in the region of the cavernous sinus. A definitive pathological diagnosis was obtained in 2 dogs: a primary intracranial neoplasm and a metastatic intracranial neoplasm. A definitive diagnosis was obtained in 6 cats: metastatic neoplasm (n = 1), primary intracranial neoplasm (n = 1), primary intracranial infectious disease (n = 2), and associated systemic infectious disease (n = 2). The prognosis associated with CSS in dogs and cats was considered guarded to poor.

Seizure classification in dogs from a nonreferral-based population.

On initial evaluation for onset of seizure disorders at nonreferral veterinary practices, 50 previously healthy dogs were enrolled in a study to determine the probability of identifying a specific cause for the seizures. Treatment was not administered prior to entry of dogs in the study. On the basis of antemortem and postmortem test results, 22 dogs (44%) were classified as having primary epileptic seizures (PES; idiopathic or without identifiable cause), 23 (46%) had secondary epileptic seizures (SES; identifiable intracranial cause), and 5 (10%) had reactive epileptic seizures (RES; metabolic or transient noxious cause). Forty-one dogs (82%) had 2 or more seizures before evaluation, with 37 (90%) of these dogs classified as having epilepsy on the basis of an underlying chronic brain disorder. For these 41 dogs, 17 (41%) had PES, 20 (49%) had SES, and 4 (10%) had RES. Among the 9 dogs (18%) with nonrecurring seizures, 5 had PES, 3 had SES, and 1 had RES. Generalized seizures were the most common first-observed seizure type associated with all etiologic classifications in all dogs with recurring and nonrecurring seizures. Diagnosis of SES was statistically more probable when the dog was less than 1 or more than 7 years old at the first seizure, when the first seizure was a partial seizure, or when the first seizure occurred between midnight and 8 AM. A diagnosis of RES was statistically more probable only when the interval between the first and second seizure was brief (< or = 4 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)

Bromide therapy in refractory canine idiopathic epilepsy.

On a retrospective basis, the response to adding chronic oral bromide (BR) to phenobarbital (PB) administration in 23 refractory canine idiopathic epileptics between 1986 and 1991 was studied. The mean age for an observed first seizure was 24 months (range 7 to 72) for all dogs. Thirteen (57%) dogs were males with no breed predisposition observed. All dogs were diagnosed as having idiopathic epilepsy based on normal metabolic and neurologic diagnostic evaluations. Dogs were evaluated before BR therapy for a mean time of 22 months (range 5 to 75 months). Seventeen dogs (74%) received multiple antiepileptic drugs (AEDs) before BR therapy. All animals were maintained on PB at least 4 months before the onset of BR therapy, with a mean trough serum concentration of 37.8 mcg/mL and no improvement in seizure severity or recurrence. Twelve dogs presented with generalized isolated seizures and 11 with generalized cluster seizures (two or more seizures within 24 hours) as their first seizure. The effects of BR therapy were evaluated for a mean time of 15 months (range 4 to 33), with 17 dogs (74%) followed for 12 or more months. The mean BR serum concentration for the 0 to 4 months time period was 117 mg/dL compared with 161 mg/dL for the greater than 4 months period. Overall, response to BR therapy was associated with a reduction in the total number of seizures in 83% of the dogs when compared with their respective pre-BR period. For those followed for 1 year after BR, there was a 53% reduction in the number of seizures compared with the previous 12 months. Furthermore, owners reported a decrease in seizure intensity (65% of dogs) and change to a less severe seizure type (22% of dogs) in those dogs that continued to have seizures. Seizure-free status was obtained in 26% of the dogs with protection continuing up to 31 months in one dog. No correlations could be determined between response to BR and either age of onset of the first seizure or interval from the first AED therapy to BR therapy. Adverse effects of concomitant BR and PB therapy were polydipsia (56% of dogs), polyphagia (30% of dogs), excessive sedation (30% of dogs), and generalized ataxia (17% of dogs). As a result of BR treatment, the PB dosage was reduced in eight dogs (35%). In conclusion, concomitant BR and PB was well tolerated in dogs of this study and was effective in treating refractory canine idiopathic epilepsy, regardless of prior interval of seizure activity or previous treatment.

Mechanisms of seizure disorders.

Epilepsy, one of the most common neurologic disorders treated by veterinarians, is also one of the least understood. A dysregulation of neural excitability appears to underlie most seizures; yet, it is still not clear whether the disorder is one of excess excitation, failure of inhibition, or a combination of both. This paper presents normal neural physiology followed by current theories regarding the pathophysiology of epilepsy so that the reader may better understand the rationale explained in later chapters regarding the choice of anticonvulsant therapies.

Epilepsy resistant to anticonvulsant therapy.

The objective when treating a patient with refractory epilepsy is to control the seizures without drug toxicity. This is accomplished in a stepwise fashion: 1) use a drug known to be effective in the species being treated, 2) verify that the owner is complying with the prescribed dosage regimen, 3) monitor serum drug levels with samples taken at trough blood concentrations, 4) observe for adverse drug reactions/interactions, and 5) test for metabolic or structural brain injuries that would explain the poor drug response. By following these steps and individualizing the treatment for each patient, you should be able to obtain seizure control in the majority of patients.

Neuroradiographic diagnosis and surgical repair of tethered cord syndrome in an English bulldog with spina bifida and myeloschisis.

A 3-month-old English Bulldog had excretory incontinence and sensory deficits in the distribution of pudendal nerves. Noncontrast radiography, myelography, and computed tomography revealed spina bifida beginning at L7, an expanded subarachnoid space caudal to L7, and a taut, thick filum terminale. Microsurgical exploration of the lumbosacral spine confirmed the presence of a tethered cord, and the filum terminale was transected. The spinal cord immediately migrated cranially about 1 cm. Although some sensory improvement was evident during a 2-week postoperative period, the dog was euthanatized. Postmortem examination confirmed spina bifida and atrophy of sacral nerve roots and perineal muscles, thoracic hemivertebrae, and hydrocephalus.

Arterial thromboembolic disease in a dog with blastomycosis localized in a hilar lymph node.

An 8-year-old mixed-breed dog was evaluated for caudal paresis. Transient lameness of the left hind and left forelimbs had developed during the preceding week. Clinical findings included conscious proprioceptive deficits, hyporeflexive tendon reflexes and decreased pain perception, coolness in the hind limbs and left forelimb, and absence of femoral pulses. A fluid-dense mass was radiographically identified adjacent to the left atrium. Echocardiography revealed a mass in the left atrium and spontaneous contrast in the left ventricular lumen and aortic root. The dog was euthanatized because of its deteriorating condition. A large mass was adhered to the dorsal left atrial wall and had eroded into the atrial lumen. A sterile blood clot was attached to this site, and sterile thrombi were in the terminal portion of the aorta. Histologically, the mass was found to be hilar lymph node with chronic pyogranulomatous inflammation containing organisms characteristic of Blastomyces dermatitidis.

Neurology of the geriatric patient.

Owing to improvements in health care, more animals are living to advanced ages. Many abnormal neurologic conditions can affect these patients, but those most commonly associated with advancing years include degenerative, neoplastic, and idiopathic processes. An understanding of the "normal" age-related changes seen on a neurologic examination must be kept in mind when evaluating geriatric patients. Special care and consideration of the patient and client are often required in managing these cases, especially because treatment protocols are often unsuccessful or do not exist, resulting in a prognosis that is often poor at best.

Production of immunoglobulin G and increased antiviral antibody in cerebrospinal fluid of dogs with delayed-onset canine distemper viral encephalitis.

Sera and cerebrospinal fluid (CSF) from four dogs with delayed-onset canine distemper viral (CDV) encephalitis (old dog encephalitis) were compared with samples from dogs with acute CDV and from recently vaccinated controls. Dogs with old dog encephalitis (ODE) had elevated CSF IgG concentrations (122 micrograms/ml) compared to controls (13 micrograms/ml) without elevated CSF albumin; their CSF IgG index was significantly greater. CSF proteins banding in the alkaline region of isoelectric focusing gels were immunochemically identified as IgG. Detectable viral neutralizing antibody was present in ODE CSF, and formed a larger proportion of IgG in CSF than in serum. Serum samples containing 2 mg IgG bound to all viral polypeptides of both R252 and Onderstepoort CDV isolates by immunoblot analysis. CSF samples of ODE patients bound viral antigens when diluted to contain as little as 5-40 micrograms IgG, while patient serum could be diluted to 40-200 micrograms IgG content compared to serum IgG of 100 micrograms/ml in vaccinated controls. Serial CSF dilutions consistently bound to H and NP polypeptides at the highest dilutions, similar to the binding of serums from recently vaccinated dogs. Thus, dogs with delayed-onset CDV encephalitis have elevated concentrations of CSF IgG, much of which is virus-specific, with an antigen binding pattern similar to that of sera of recently immunized dogs.

Equine herpes myeloencephalopathy.

The neurologic form of EHV-1 infection appears to be the result of central nervous system infarction caused by vasculitis, which is initiated in endothelial cells of small blood vessels. The etiologic agent is equine herpesvirus-1, subtype 1. There is some evidence to suggest that the neurologic form of the disease actually results from reactivation of a previous infection. Whether the vasculitis that causes the central nervous system injury is the direct result of the infection or an immune response to the infection has not been determined. The clinical signs are rapid in onset, nonprogressive, and many horses may improve. The diagnosis must often remain tentative, particularly in horses that recover, because there is no single reliable confirmatory test. The prognosis is generally good, although recovery may be slow and incomplete. Supportive therapy is essential, and administration of corticosteroids may be useful. There is no specific therapy for the virus or for the vasculitis. Currently no vaccine can be claimed to protect against the central nervous system form of the disease. Vaccination is recommended, however, to reduce the incidence of respiratory disease, abortion, and neonatal death on the farm. Repeated vaccination is necessary to maintain presumably protective antibody concentrations. Vaccination every 3 to 4 months may decrease the incidence of EHV-1 infection on the farm and therefore may indirectly prevent the occurrence of the neurologic form of the disease.

Indication and use of electrodiagnostic aids in neurologic disease.

Electrodiagnostic aids, electromyography, auditory brainstem response testing, and electroencephalography are extensions of the neurologic examination and provide valuable information about the nervous system. This article discusses the use and interpretation of electrodiagnostic aids in equine neurology as well as the equipment that is employed. It is hoped that with a better understanding of the available electrodiagnostic aids, they will come into greater use.