Cerebrospinal fluid lactate concentrations in dogs with seizure disorders.

BACKGROUND: Cerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown. HYPOTHESIS/OBJECTIVES: Cerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures. ANIMALS: One-hundred eighteen client-owned dogs with seizure disorders. METHODS: Case series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded. RESULTS: Dogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P = .03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P = .12), among dogs with CSF collection at different time points after the last seizure activity (P = .39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P = .42). A significant difference (P = .001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process.

A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels.

The purpose of this study was to report the findings of clinical and genetic evaluation of a 3-month old male Boykin spaniel (the proband) that presented with progressive weakness. The puppy underwent a physical and neurological examination, serum biochemistry and complete blood cell count, electrophysiological testing, muscle biopsy and whole genome sequencing. Clinical evaluation revealed generalized neuromuscular weakness with tetraparesis and difficulty holding the head up and a dropped jaw. There was diffuse spontaneous activity on electromyography, most severe in the cervical musculature. Nerve conduction studies were normal, the findings were interpreted as consistent with a myopathy. Skeletal muscle was grossly abnormal on biopsy and there were necklace fibers and abnormal triad structure localization on histopathology, consistent with myotubular myopathy. Whole genome sequencing revealed a premature stop codon in exon 13 of MTM1 (ChrX: 118,903,496 C > T, c.1467C>T, p.Arg512X). The puppy was humanely euthanized at 5 months of age. The puppy's dam was heterozygous for the variant, and 3 male puppies from a subsequent litter all of which died by 2 weeks of age were hemizygous for the variant. This naturally occurring mutation in Boykin spaniels causes a severe form of X-linked myotubular myopathy, comparable to the human counterpart.

Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease.

BACKGROUND: Presumed autoimmune diseases affecting the central nervous system (CNS) of dogs are common. In people, antibodies against neuronal cell surface antigens that are associated with a wide variety of neurological syndromes have been identified. The presence of cerebrospinal fluid (CSF) autoantibodies that target neuronal cell surface proteins has not been reported in dogs with neurologic disorders. OBJECTIVES: Autoantibodies to neuronal cell surface antigens can be found in the CSF of dogs with inflammatory CNS disease. Our aim was to determine whether 6 neuronal cell surface autoantibodies were present in the CSF of dogs diagnosed with inflammatory and noninflammatory CNS disease. ANIMALS: Client-owned dogs with CNS disease and complete diagnostic evaluation including magnetic resonance imaging and CSF analysis were included. One healthy dog was included as a negative control. METHODS: Cerebrospinal fluid was tested for 6 antigenic targets with a commercially available indirect immunofluorescence assay test kit. RESULTS: There were 32 dogs with neurological disease, 19 diagnosed with inflammatory disease (encephalitis and meningitis), 10 with noninflammatory disease (neoplasia, intervertebral disk disease, degenerative myelopathy, and epilepsy), 2 with no diagnosis, and 1 with neoplasia and meningoencephalitis. Anti-N-methyl-d-aspartate receptor 1 (NMDAR1) antibodies were detected in 3 dogs (3/32; 9.38%). All 3 dogs responded to treatment of meningoencephalomyelitis of unknown etiology (MUE). CONCLUSIONS AND CLINICAL IMPORTANCE: Further evaluation of the prevalence and clinical relevance of CSF and serum antibodies to neuronal cell surface antigens is warranted. Defining antigenic targets associated with encephalitis in dogs might allow diagnostic categorization of MUE antemortem.

Cerebrospinal fluid lactate in dogs with inflammatory central nervous system disorders.

BACKGROUND: Cerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis. HYPOTHESIS: Cerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders. ANIMALS: One hundred two client-owned dogs diagnosed with inflammatory CNS disease. METHODS: Case series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid-responsive meningitis arteritis, meningoencephalitis of unknown etiology). RESULTS: Cerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0-11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P = .48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r = .33, P < .001), absolute large mononuclear cell count (r = .44, P < .001), absolute small mononuclear cell count (r = .39, P < .001), absolute neutrophil cell count (r = .24, P = .01), and protein (r = .44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P = .58). There was no significant association of CSF lactate concentration with survival (P = .27). CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs.

Clinical characteristics, breed differences, and quality of life in North American dogs with acute steroid-responsive meningitis-arteritis.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is a common inflammatory neurologic disorder of dogs for which certain breeds are predisposed. OBJECTIVES: To determine whether breed differences exist in clinical features, treatment response, and relapse in a population of North American dogs with SRMA, and to evaluate the effect of disease on dogs' quality of life (QoL). ANIMALS: Sixty-one client-owned dogs with SRMA: 29 dogs identified through an American Kennel Club-Canine Health Foundation survey and 32 dogs from North Carolina (NC) State Veterinary Hospital. METHODS: Retrospective case series. Caregivers completed an online survey to assess QoL. RESULTS: Breeds represented most often included the Golden Retriever (n = 12), Bernese Mountain Dog (10), Wirehaired Pointing Griffon (9), Boxer (9), and Beagle (6). No breed differences were identified with respect to clinical severity, diagnostic findings, or outcome. Twenty-nine dogs (48%) had ≥1 disease relapse. There was a significant effect of cerebrospinal fluid nucleated cell count on the frequency of disease relapse (P = .003), but no relationship was identified between treatment protocol and relapse. Dogs' QoL was associated with the severity of corticosteroid-related adverse effects (P = .03), which were dose-related (r = .24, P = .02) and more prevalent in Wirehaired Pointing Griffons than in other breeds (P = .04). CONCLUSION AND CLINICAL IMPORTANCE: Golden Retrievers and Wirehaired Pointing Griffons should be considered among the breeds recognized to develop SRMA. Treatment with higher corticosteroid dosages is correlated with more severe adverse effects and worse QoL, but it may not improve clinical outcome.

Comparison of retinal degeneration in the normal goldfish and the megalophthalmic black moor goldfish after optic nerve transection and lens extraction.

A comparison in retinal degeneration was studied in the normal goldfish and the megalophthalmic goldfish after optic nerve transection or lens extraction by the TUNEL (Terminal transferase-mediated dUTP nick end labeling) technique. A significant number of TUNEL positive cells appeared in both cases 7 days after injury, with a more prominent result in the megalophthalmic eye. Lens extraction, had less apoptotic cell death in the experimental retinas.