Recurrent CNTN1 antibody-positive nodopathy: a case report and literature review.

Background: Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown. Case presentation: Here, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment's efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L. Conclusion: We present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.

West Nile virus neuroinvasive disease associated with rituximab therapy.

West Nile virus neuroinvasive disease (WNVND) manifests with meningitis, encephalitis, and/or acute flaccid paralysis. It represents less than 1% of the clinical syndromes associated with West Nile virus (WNV) infection in immunocompetent patients. Immunosuppressive therapy is associated with increased risk of WNVND and worse prognosis. We present a patient with WNVND during therapy with rituximab, and a review of the literature for previous similar cases with the goal to describe the clinical spectrum of WNVND in patients treated specifically with rituximab. Our review indicates that the most common initial complaints are fever and altered mental status, brain magnetic resonance imaging often shows bilateral thalamic hyperintensities, and cerebrospinal analysis consistently reveals mild lymphocytic pleocytosis with elevated protein, positive WNV polymerase chain reaction, and negative WNV antibodies. Treatment is usually supportive care, with intravenous immunoglobulins (IVIG) plus corticosteroids and WNV-specific IVIG also used. The disease is usually fatal despite intervention. Our patient's presentation was very similar to prior reports, however demonstrated spontaneous improvement with supportive management only. WNVND is a rare and serious infection with poor prognosis when associated with rituximab therapy. Diagnosis is complicated by absent or delayed development of antibodies. The presence of bilateral thalamic involvement is a diagnostic clue for WNVND. There is insufficient evidence to recommend the use of corticosteroids or IVIG.

Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV).

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of Erns- and E2-specific antibodies and their neutralizing capacity were determined by recently (Erns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND50 ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies.

Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg.

OBJECTIVE: To describe the frequency of antibodies against neurofascin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the associated clinical features. METHODS: Immunocytochemistry was used to identify antibodies to neurofascin 155 (NF155) and 186. Serum reactivity with paranodes and brain tissue was tested with immunohistochemistry of teased-nerve fibers and rat brain. Antibody titers and immunoglobulin (Ig) G isotypes were determined using ELISA. Clinical information was obtained retrospectively. RESULTS: Two of 53 patients, but none of 204 controls, had antibodies to NF155 (p = 0.041). The 2 patients with NF155 antibodies developed severe polyradiculoneuropathy with predominant distal weakness that was refractory to IVIg. Eight additional patients with IVIg-refractory CIDP were then identified from a national database; 2 of them with the same clinical features also had NF155 antibodies. Overall, 3 of the 4 patients with NF155 antibodies had a disabling and characteristic tremor (high amplitude, low frequency, postural, and intention). Patients' antibodies reacted with the paranodes in teased-nerve fibers and with the neuropil of rat cerebellum, brain, and brainstem. Anti-NF155 antibodies were predominantly of the IgG4 isotype in all patients. CONCLUSION: Patients with CIDP positive for IgG4 NF155 antibodies constitute a specific subgroup with a severe phenotype, poor response to IVIg, and disabling tremor. Autoantibodies against paranodal structures associate with distinct clinical features in CIDP and their identification has diagnostic, prognostic, and therapeutic implications. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that autoantibodies to NF155 identify a CIDP subtype characterized by severe neuropathy, poor response to IVIg, and disabling tremor.

IgM-monoclonal gammopathy neuropathy and tremor: a first epidemiologic case control study.

INTRODUCTION: Small case series suggest tremor occurs frequently in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy. Epidemiologic study to confirm this association is lacking. Whether the neuropathy or another remote IgM-effect is causal remains unsettled. MATERIALS AND METHODS: An IgM-MGUS neuropathy case cohort (n = 207) was compared to age, gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy controls (n = 414). Tremor details were extracted from structured neurologic evaluation. All patients underwent nerve conductions. RESULTS: Tremor occurrence was significantly higher in IgM-MGUS case cohort (29%) than in control cohort (9.2%) (p = 0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p = 0.025) and demyelinating nerve conductions (p = 0.020), but 11 of 60 (18%) IgM-MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls, tremor was associated with axonal nerve conductions (p = 0.03) but not with NIS severity (p = 0.57). Tremor occurrence associated with older age in controls, (p = 0.004) but not in IgM-MGUS cases (p = 0.272). Most IgM-MGUS tremor cases (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest-action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the most common type is inherited essential tremor 6/60 (p = 0.04). CONCLUSIONS: This first epidemiologic case-control study validates association between IgM-MGUS neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM-MGUS paraproteinemia may increase tremor expression in persons recognized with common other risk factors for tremor.

Central nervous system involvement in patients with monoclonal gammopathy and polyneuropathy.

BACKGROUND AND PURPOSE: To evaluate clinical presentation of patients with the clinical triad of monoclonal gammopathy, polyneuropathy and signs of CNS involvement. METHODS: Nineteen patients with monoclonal protein (M-protein, 9 IgM, 10 IgG) were studied. Clinical examination, MRI, cerebrospinal fluid analysis and immune reactivity against myelin-associated glycoprotein and gangliosides in serum were obtained. By immunohistochemistry, different binding patterns of M-proteins to human CNS tissue were investigated. RESULTS: Nine out of 19 patients (four IgM, five IgG) showed one or more clinical signs of CNS involvement. Clinical features associated with signs of CNS pathology were disease duration and greater concentration of IgM paraprotein. The IgM M-protein of two patients strongly stained the cortex/cerebellar neurons in human brain sections. CONCLUSION: Our results complement previous reports that some patients with monoclonal gammopathy and polyneuropathy can develop solitary or disseminated signs of CNS involvement. It indicates that pathological effects of M-proteins are not necessarily restricted to the peripheral nervous system. The specificity and affinity of circulating M-protein to antigens in the CNS might be critical for the development of different clinical phenotypes.

[Glutamate antibodies in the development of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian syndrome in C57B1/6 mice].

The experiments on mice C57B1/6 with MPTP-induced Parkinsonian syndrome have shown that preliminary and simultaneous intranasal injection of glutamate antibodies inhibit development of the syndrome. Administration of glutamate antibodies decreased tremor, rigidity and increased horizontal locomotion, movement velocity in the open field.

CD44 overexpression by oligodendrocytes: a novel mouse model of inflammation-independent demyelination and dysmyelination.

The CD44 transmembrane glycoprotein family has been implicated in cell-cell adhesion and cell signaling in response to components of the extracellular matrix but its role in the nervous system is not understood. CD44 proteins are elevated in Schwann cells and oligodendrocytes following nervous system insults, in inflammatory demyelinating lesions, and in tumors. Here, we tested the hypothesis that elevated CD44 expression influences Schwann cell and oligodendrocyte functions by generating transgenic mice that express CD44 under the control of the 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) promoter. These mice failed to develop peripheral nerve or CNS tumors. However, they did develop severe tremors that were associated with CNS dysmyelination and progressive demyelination. Loss of CNS myelin was not due to alterations in early oligodendrocyte precursor differentiation, proliferation, or survival. Myelination in the PNS appeared normal. In no instance was there any evidence of an inflammatory response that could account for the loss of CNS myelin. These findings suggest that CNPase-CD44 mice are a novel model for noninflammatory progressive demyelinating disease and support a potential role for CD44 proteins expressed by glial cells in promoting demyelination.

VIM thalamic stimulation for tremor in a patient with IgM paraproteinaemic demyelinating neuropathy.

We demonstrate the effect of deep brain stimulation of the ventral intermediate thalamic nucleus on intractable action tremor, in a 72-year-old man suffering from neuropathy associated with monoclonal gammopathy.

Dermatitis herpetiformis and neurological dysfunction.

Dermatitis herpetiformis and coeliac disease are gluten sensitive diseases, which have common immunopathological and genetic mechanisms. Neuropsychiatric complications have been reported in up to 26% of patients with coeliac disease. This is probably an overestimate, because of the chance associations with some common neurological conditions such as epilepsy. The pathogenesis is speculative but it has been postulated that gluten is neurotoxic possibly via immune mechanisms. The frequency of neurological dysfunction in patients with dermatitis herpetiformis has not been characterised. Patients with dermatitis herpetiformis might be expected to be particularly susceptible to neuronal damage as some continue to consume gluten when their dermatological symptoms are controlled by dapsone. Thirty five patients were recruited with dermatitis herpetiformis from dermatology clinics at St Mary's Hospital, London and Queen's Medical Centre, Nottingham and investigated for evidence of neurological abnormality. All patients underwent a full neurological examination and were asked about their neurological and general medical history by means of a structured questionnaire. Serum samples were taken and screened for the presence of anti-neuronal antibodies (anti-Hu and Yo) as well as anti-gliadin (IgA and G) anti-endomysial (IgA), and anti-tissue transglutaminase (IgA) antibodies. Neurophysiological tests were carried out where appropriate. Only two patients were identified with unexplained neurological abnormalities (one essential tremor, and one chorea). Two other patients had a history of migraine. The patient with chorea also had borderline/equivocally positive anti-Hu antibodies by immunofluorescence assay. All other samples were negative for anti-neuronal antibodies. Fifteen patients were positive for anti-gliadin antibodies (IgA and/or IgG), four for anti-endomysial antibodies (monkey oesophagus or umbilical cord), and six for anti-tissue transglutaminase antibodies. The presence of these antibodies did not correlate with the presence of neurological abnormalities. No cases of "gluten ataxia" were identified. In conclusion, there was no convincing evidence for immune mediated neurological damage in this pilot study of dermatitis herpetiformis.

[Possibility of using the indirect fluorescent antibody technic to analyze immunoglobulins in certain neurogenetic diseases]. / O vozmozhnosti ispol'zovaniia metoda nepriamoi immunofliuorestsentsii dlia analiza immunoglobulinov pri nekotorykh neirogeneticheskikh zabolevaniiakh.

Results of examining the sera of 11 normal donors and 37 patients with various neutogenetic diseases using, the Coons indirect immunofluorescence technique are presented. The patients' immunoglobulins could be better fixed on nervous tissue components than those of the control donors. This seems likely to be due to both a rise in the content of serum immunoglobulins and accumulation of specific anticerebral antibodies in the patients' blood. It is suggested that in all cases of using indirect immunofluorescence the quantitative determination of immunoglobulins and serum titration should be carried out.