Immune-mediated polyneuropathy in cats: Clinical description, electrodiagnostic assessment, and treatment.

BACKGROUND: Suspected immune-mediated polyneuropathy has been increasingly reported in cats, especially in the last decade, but the condition remains poorly understood. OBJECTIVES: Refine the clinical description and review the classification of this condition based on electrodiagnostic investigation and evaluate the benefit of corticosteroid treatment and L-carnitine supplementation. ANIMALS: Fifty-five cats presented with signs of muscular weakness and electrodiagnostic findings consistent with polyneuropathy of unknown origin. METHODS: Retrospective, multicenter study. Data from the medical records were reviewed. The owners were contacted by phone for follow-up at the time of the study. RESULTS: The male-to-female ratio was 2.2. The median age of onset was 10 months, with 91% of affected cats being <3 years of age. Fourteen breeds were represented in the study. The electrodiagnostic findings supported purely motor axonal polyneuropathy. Histological findings from nerve biopsies were consistent with immune-mediated neuropathy in 87% of the tested cats. The overall prognosis for recovery was good to excellent, as all but 1 cat achieved clinical recovery, with 12% having mild sequelae and 28% having multiple episodes during their lifetime. The outcome was similar in cats with no treatment when compared with cats receiving corticosteroids or L-carnitine supplementation. CONCLUSIONS AND CLINICAL IMPORTANCE: Immune-mediated motor axonal polyneuropathy should be considered in young cats with muscle weakness. This condition may be similar to acute motor axonal neuropathy in Guillain-Barré syndrome patients. Based on our results, diagnostic criteria have been proposed.

Acute idiopathic polyradiculoneuritis concurrent with acquired myasthenia gravis in a West Highland white terrier dog.

BACKGROUND: Acute Idiopathic Polyradiculoneuritis, an animal model for the axonal form of the Guillain - Barre Syndrome in humans and the acquired myasthenia gravis are different autoimmune disorders affecting the peripheral nerves and the neuromuscular junction, respectively. Both lead to muscle weakness and possible respiratory failure. The coexistence of these two entities combined in the same patient is rare in humans and, to our knowledge, the present case is the first reported in dogs. CASE PRESENTATION: An 11-year-old West Highland WhiteTerrier female dog was referred to our clinic with a history of symmetrical weakness beginning with the pelvic limbs and evolving cranially, progressing to non-ambulatory flaccid tetraparesis over the preceding week. The history did not reveal signs of a recent other illness, trauma or exposure to a neurotoxin or raccoon bite. The last vaccination was carried out 5 months before presentation. Upon clinical examination, spinal reflexes and postural reactions were decreased in all four limbs and became absent within the following 24 h; perineal reflex was normal, and loss of voice was observed. The patient maintained its ability to urinate and defecate and it had no difficulty to eat or to drink. There were no cerebellar or sensory deficits. The electrophysiological findings revealed positive sharp waves and complex repetitive discharges on the electromyogram, temporal dispersion of compound muscle action potentials associated with polyphasia and a slow motor nerve conduction velocity as signs of demyelination, and an increased latency of F-waves. The cerebrospinal fluid had a normal cellularity with increased protein content. A reduction by 18 % in the amplitudes of the third compound muscle action potential as compared to the first one was observed during a repetitive nerve stimulation, indicating a postsynaptic disturbance. Only the motor electrophysiology was considered in this study. The diagnosis was based on clinical and electrophysiological findings associated with a positive titer for acetylcholine receptor antibodies. CONCLUSION: The diagnosis of MG was based on the typical clinical findings such as dysphonia and dysphagia, decremental response of RNS and positive AChRs antibody titre. Flaccid tetraparesis associated with diminished reflexes, increase of the distal latencies and temporal dispersion which caused lower MNCV, along with the increase of the F wave latencies supported the diagnosis of AIP. A cerebrospinal fluid tap indicated an albuminocytologic dissociation sustaining the radicular implication of AIP. As such, a diagnosis of MG and AIP co-occurrence syndrome was established.

Gene expression profile of Campylobacter jejuni-induced GBS in Bama miniature pigs.

Our aim was to investigate the in vivo gene expression pattern of the Guillain-Barre syndrome (GBS) with DNA microarrays and bioinformatics tools. Oral-infusion model animals mimicking human infection of GBS were analyzed. Tissue samples and body fluids were collected to perform antibody tests and biopsy assays. Gene-expression microarray was conducted with nerve tissues and GBS-related genes were elucidated via bioinformatics tools. Model animals showed typical symptoms of GBS in that mild demyelination was shown by cerebellar white matter and by lumbar enlargement of model animals. Then, 81.25% of the model animals were positive with GM1-IgG antibodies by ELISA. In the microarray analysis, 1,261 genes were identified with statistically different expression (P < 0.05), 21 of which were associated with gene function analysis, gene pathway identification, signal transduction and co-expression network construction. Furthermore, quantitative PCR was used to characterize the gene expression level. We found that genes of HPRT1, PKC and PPARGC-1 were in the core of the network, while the expression of PPARGC-1, SUS2DD and AMPKA2 were significantly inhibited. A total of 21 genes were found to be actively involved in the process of protein transportation, transcriptional regulation, antigen identification and cell cycle regulation during the GBS infection period. The co-expression network indicated an important association between GBS and the 21 genes, especially the down-regulated ones. In conclusion, we demonstrated that GBS-affected hosts had a specific gene expression profile, which may guide the direction of GBS research and therapy.

Immunopathology and Th1/Th2 immune response of Campylobacter jejuni-induced paralysis resembling Guillain-Barré syndrome in chicken.

Immunopathogenesis of Campylobacter jejuni-associated Guillain-Barré syndrome (GBS) is not yet well established probably due to lack of experimental model. Therefore, we studied the Th1/Th2 immune response and pathological changes in C. jejuni-induced chicken model for GBS. C. jejuni (5 × 10(9) CFU/ml) and placebo were fed to 30 chickens each. Stools of all birds were negative for C. jejuni by culture and PCR before experiment. The birds were regularly assessed for disease symptoms up to 30 days. Sciatic nerves from all chickens were examined at 5 days intervals by histopathology and immunohistochemistry, and also for the expression of Th1/Th2 cytokines. Twenty-two chickens (73.3%) developed diarrhea after C. jejuni infection; 18 (60.0%) experimental chickens developed GBS-like paralytic neuropathy. Pathology in the sciatic nerves of these chickens included perinodal and/or patchy demyelination, perivascular focal lymphocytic infiltration, myelin swelling and presence of macrophages within the nerve fibers on 10th-20th post-infection day (PID). Cytokines (IFN-γ, IL-1ß, TNF-α, IL-6 and IL-2) were elevated in early phase (5th-15th PID) and TGF-ß2, IL-10 and IL-4 in the recovery phase (25th-30th PID) of the disease. The study provides evidence that C. jejuni infection in the chicken can provide an experimental animal model of GBS.

Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog.

We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans.

BACKGROUND: Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. METHODS: Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). RESULTS: Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. CONCLUSIONS: The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.