Possible therapeutic vaccines for canine myasthenia gravis: implications for the human disease and associated fatigue.

Myasthenia gravis (MG) is caused by T cell-dependent antibodies reactive with acetylcholine receptors. These autoreactive antibodies cause muscle weakness by interfering with neuromuscular transmission via removal of acetylcholine receptors from the neuromuscular junction as well as changing the architecture of the junction itself. Consequently, muscle fatigue is a debilitating aspect of MG often leading to more general feelings of tiredness not directly due to muscle weakness. We have previously described two peptides that are mimetics of antigen receptors on certain autoreactive T and B cells that are involved in MG. When used as vaccines in the rat model of MG, these peptides prevented and ameliorated disease and muscle fatigue by blunting acetylcholine receptor antibody responses. Such disease protection resulted from vaccine-induced anergizing antibodies against acetylcholine receptor-specific T and B cell antigen receptors. The present study prospectively evaluated the efficacy of these two vaccines in spontaneous acquired MG in pet dogs. When compared to historical controls that were prospectively studied, the vaccines increased the proportion of remitted dogs from 17 to 75%. In comparison to retrospectively studied historical controls that spontaneously remitted from MG, the vaccines accelerated the rate of decline in acetylcholine receptor antibody titers which resulted in a 3-fold decrease in the mean time to remission. These results are suggestive of a new type of targeted therapy that can drive autoimmune responses into long-term remission and possibly afford a means of determining whether correction of a physical cause of muscle weakness also corrects the perception of chronic, generalized fatigue.

Neurological disease in wild loggerhead sea turtles Caretta caretta.

Beginning in October 2000, subadult loggerhead sea turtles Caretta caretta showing clinical signs of a neurological disorder were found in waters off south Florida, USA. Histopathology indicated generalized and neurologic spirorchiidiasis. In loggerhead sea turtles (LST) with neurospirorchiidiasis, adult trematodes were found in the meninges of the brain and spinal cord of 7 and 3 affected turtles respectively, and multiple encephalic intravascular or perivascular eggs were associated with granulomatous or mixed leukocytic inflammation, vasculitis, edema, axonal degeneration and occasional necrosis. Adult spirorchiids were dissected from meningeal vessels of 2 of 11 LST brains and 1 of 10 spinal cords and were identified as Neospirorchis sp. Affected LST were evaluated for brevetoxins, ciguatoxins, saxitoxins, domoic acid and palytoxin. While tissues from 7 of 20 LST tested positive for brevetoxins, the levels were not considered to be in a range causing acute toxicosis. No known natural (algal blooms) or anthropogenic (pollutant spills) stressors co-occurred with the turtle mortality. While heavy metal toxicosis and organophosphate toxicosis were also investigated as possible causes, there was no evidence for their involvement. We speculate that the clinical signs and pathologic changes seen in the affected LST resulted from combined heavy spirorchiid parasitism and possible chronic exposure to a novel toxin present in the diet of LST.

Composition of cerebrospinal fluid in clinically normal adult ferrets.

OBJECTIVE: To determine the protein and cellular composition of CSF in healthy adult ferrets. ANIMALS: 42 clinically normal adult ferrets. PROCEDURE: CSF samples were collected from the cerebellomedullary cistern of anesthetized ferrets by use of disposable 25-gauge, 1.6-cm-long hypodermic needles. Samples were processed within 20 minutes after collection. The number of WBCs and RBCs per microliter of CSF was counted by use of a hemacytometer. The total protein concentration was determined by use of an automated chemistry analyzer. RESULTS: Total WBC counts (range, 0 to 8 cells/microL; mean, 1.59 cells/microL) in CSF of ferrets were similar to reference range values obtained for CSF from other species. Twenty-seven CSF samples had <100 RBCs/microL (mean, 20.3 RBCs/microL). A small but significant effect of blood contamination on WBC counts was found between the 27 CSF samples with <100 RBCs/microL and the remaining samples. Protein concentrations in CSF of ferrets (range, 28.0 to 68.0 mg/dL; mean, 31.4 mg/dL) were higher than has been reported for the CSF of dogs and cats. A significant effect of blood contamination on the CSF protein concentration was not found. CONCLUSION AND CLINICAL RELEVANCE: We have established reference range values for WBC counts and protein concentrations in CSF from healthy adult ferrets that may be useful in the clinical investigation of CNS disease. Results of our study indicate that the WBC count is significantly affected by blood contamination of the CSF sample.

Clinical signs, underlying cause, and outcome in cats with seizures: 17 cases (1997-2002).

OBJECTIVE: To determine clinical signs, results of diagnostic testing, underlying cause, and outcome in cats with seizures. DESIGN: Retrospective study. ANIMALS: 17 cats with seizures. PROCEDURE: Only those cats in which an underlying metabolic abnormality causing the seizures had been identified, diagnostic imaging of the brain and CSF analysis had been done, or a necropsy had been performed were included. Seizures were classified as being a result of metabolic disease, symptomatic epilepsy (ie, epilepsy resulting from a structural lesion of the brain), or probably symptomatic epilepsy (ie, epilepsy without any extracranial or identifiable intracranial disease that is not suspected to be genetic in origin). RESULTS: 3 cats had seizures associated with an underlying metabolic disease (hepatic encephalopathy), 7 had symptomatic epilepsy (3 with neoplasia and 4 with meningoencephalitis), and 7 had probably symptomatic epilepsy. Six of the 7 cats with symptomatic epilepsy died or were euthanatized within 3 months after the diagnosis was made, whereas 6 of the 7 cats with probably symptomatic epilepsy survived for at least 12 months after the diagnosis was made. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats with probably symptomatic epilepsy may have a good long-term prognosis.

Clinical evaluation of rabies virus meningoencephalomyelitis in a dog.

A 6-month-old, female, mixed-breed dog presented for acute, progressive, flaccid paraplegia and bilateral pelvic-limb hyperesthesia. A lymphocytic pleocytosis with 366 mg/dL protein was found on cerebral spinal fluid (CSF) evaluation. Electromyography (EMG) demonstrated positive sharp waves and fibrillations in the left pelvic limb; the M wave of the left sciatic nerve was not obtainable by nerve stimulation. Seizures and dementia began during recovery from anesthesia. Six days after onset of paralysis, the dog was euthanized. Direct fluorescent antibody testing of the brain was positive for raccoon rabies virus. This case demonstrates clinical evaluation, CSF analysis, and EMG in an animal with rabies meningoencephalomyelitis.

Cerebral phaeohyphomycosis caused by Cladosporium spp. in two domestic shorthair cats.

Two domestic shorthair cats presented for clinical signs related to multifocal central nervous system dysfunction. Both cats had signs of vestibular system involvement and anisocoria, and one had generalized seizure activity. Cerebrospinal fluid analysis revealed a neutrophilic pleocytosis with protein elevation in one cat and pyogranulomatous inflammation in the second. Electroencephalography and brain-stem auditory-evoked potentials in the first cat confirmed cerebral cortical and brain-stem involvement. Euthanasia was performed in both cats, and postmortem diagnoses of phaeohyphomycosis secondary to Cladosporium spp. were made based on histopathology and fungal culture in both cats.

Comparison of fine-needle aspiration and surgical-tissue biopsy in the diagnosis of canine brain tumors.

OBJECTIVE: To compare the diagnoses obtained using fine-needle aspiration (FNA) and surgical-tissue biopsy of focal cerebral masses with the histologic diagnoses obtained via necropsy. STUDY DESIGN: A prospective case series. SAMPLE POPULATION: Ten client-owned adult dogs of various breeds. All dogs had clinical signs of cerebral disease and had a focal brain mass identified using magnetic resonance imaging; all were eventually euthanatized. METHODS: Immediately after euthanasia, the brains were removed en bloc from the cranial cavity. FNAs were obtained from each mass using a 22-gauge hypodermic needle and a 12-mL syringe. Cytologic preparations were made from each aspirate. A 14-gauge Tru-cut biopsy needle was used to obtain a core tissue sample from each mass. The biopsy specimens were fixed in 10% buffered formalin and submitted for histologic evaluation. The brains were similarly fixed and stained. Six-micrometer-thick transverse sections of the brain were examined microscopically. RESULTS: Neoplasia was confirmed in all dogs histologically in the 6-microm transverse sections. Four meningiomas, 2 astrocytomas, 2 oligodendrogliomas, 1 pituitary adenocarcinoma, and 1 neurofibrosarcoma were identified. FNA correctly identified all of the masses as neoplastic. Cytologic diagnoses correlated with the histologic interpretation in 5 of the masses (50%). Tru-cut biopsy specimens identified all 10 masses as neoplastic; in 9 of the 10 (90%), the diagnosis correlated with the histologic diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: FNA is a sensitive method that can be used to determine the presence of neoplasia in the brain, but is not as definitive as the Tru-cut biopsy in determining the specific type of cerebral neoplasm.