CACNA1H antibodies associated with headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL).

BACKGROUND: Patients with the syndrome of headache with neurological deficits and lymphocytosis (HaNDL) typically present with recurrent and temporary attacks of neurological symptoms and cerebrospinal fluid lymphocytosis. AIM AND METHODS: To identify potential HaNDL-associated antibodies directed against neuronal surface and/or synapse antigens, sera of four HaNDL patients and controls were screened with indirect immunohistochemistry, immunofluorescence, cell-based assay, radioimmunoassay, protein macroarray and enzyme-linked immunosorbent assay (ELISA). RESULTS: Although HaNDL sera did not yield antibodies to any of the well-characterized neuronal surface or synapse antigens, protein macroarray and ELISA studies showed high-titer antibodies to a subunit of the T-type voltage-gated calcium channel (VGCC), CACNA1H, in sera of two HaNDL patients. CONCLUSION: Our results support the notion that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis and occurrence of neurological symptoms.

Progressive encephalomyelitis with rigidity and myoclonus: a syndrome with diverse clinical features and antibody responses.

BACKGROUND/AIMS: To better characterize progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome and identify novel PERM phenotypes. METHODS: The clinical features and antibody status of PERM patients were investigated using immunoblots, cell-based assays, RIA, protein macroarray and ELISA. RESULTS: Two patients with supratentorial involvement showed abnormal PET or EEG findings. One patient was discovered to have renal cell carcinoma, and protein macroarray revealed Ma3-antibodies. Another patient with leucine-rich, glioma-inactivated 1 (LGI1) and glutamic acid decarboxylase (GAD) antibodies showed a good response to immunotherapy. CONCLUSION: The heterogeneity of the immunological features suggests that PERM is caused by diverse pathogenic mechanisms. Seropositivity to well-characterized neuronal cell surface antigens might indicate a good treatment response.

Effect of short-term interferon-ß treatment on cytokines in multiple sclerosis: significant modulation of IL-17 and IL-23.

Therapeutic effect of interferon-ß (IFN-ß) treatment has been associated with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg) cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple sclerosis (MS) has not been studied. To investigate the short-term effects of IFN-ß treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL-10, IL-4, IFN-γ, IL-9 and TGF-ß in relapsing remitting MS patients before and 2 months after IFN-ß treatment by ELISA. MS patients showed increased IL-17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy controls. IFN-ß treatment only reduced IL-17 and IL-23 levels, whereas the levels of other cytokines remained unchanged. IFN-ß treatment appears to exert its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS pathogenesis needs to be further studied.

Aquaporin-4 antibodies are not present in patients with idiopathic intracranial hypertension.

OBJECTIVES: We aimed to investigate anti-aquaporin-4 (AQP-4) water channel antibodies, affecting cerebrospinal fluid (CSF) secretion and absorption, in idiopathic intracranial hypertension (IIH) patients. METHODS: Patients fulfilling the modified Dandy's diagnostic criteria for IIH were included and their clinical features and CSF findings were reviewed. Their serum samples and control groups were investigated by immunofluorescence and a cell-based assay for anti-AQP-4 antibodies and by immunohistochemistry for IgG binding patterns. RESULTS: Twenty-nine patients diagnosed with IIH were investigated. We could not detect any anti-AQP-4 antibodies in our series. However, we identified different serum IgG binding patterns in 11 IIH patients. CONCLUSION: There is only one report investigating the anti-AQP4 antibodies in IIH. Our study with a larger sample confirmed the results of this report and indicated that AQP4 antibodies did not have a primary role in IIH pathogenesis, but provided some support for the contribution of inflammatory mechanisms in IIH.

Long extensive transverse myelitis associated with aquaporin-4 antibody and breast cancer: favorable response to cancer treatment.

CONTEXT: Long extensive transverse myelitis (LETM) seldom develops in patients with breast cancer who are aquaporin-4 antibody (Aqp-4 Ab)-positive. Whether this association is coincidental is not well understood. FINDINGS: A 62-year-old woman presented with treatment-resistant LETM and Aqp-4 Ab. Two months later, a stage 3 invasive ductal carcinoma was detected in her right breast. Following tumor resection and chemotherapy, her neurologic symptoms and magnetic resonance imaging findings significantly improved and serum Aqp-4 Ab disappeared. The breast tumor samples of this patient and neurologically normal patients showed inflammatory infiltrates and Aqp-4 expressing cells. CONCLUSION/CLINICAL RELEVANCE: The temporal association between tumor treatment, amelioration of clinical findings, and seroreversion suggest that coexistence of cancer and LETM is not coincidental. Cancer screening should be considered at least in treatment-resistant LETM cases.

Steroid-responsive recurrent limbic encephalitis associated with small cell lung cancer and neuropil antibodies.

Paraneoplastic limbic encephalitis (PLE) associated with small cell lung cancer (SCLC) often presents with antibodies to intracellular antigens and a poor outcome even after tumor resection and immunotherapy. We report a PLE patient presenting with generalized seizures, shortterm memory impairment and medial temporal lobe hyperintensity in MRI. Initial screening revealed significantly elevated thyroid antibody levels suggesting Hashimoto's encephalopathy. Following methylprednisolone treatment, her seizures ceased, MRI findings disappeared and memory impairment showed a partial resolution in 5 months. Two months later, she developed further generalized seizures. Chest X-ray showed a mass lesion, which was demonstrated by needle biopsy to be a small cell lung carcinoma (SCLC). The panel of onconeural antibodies including cell-membrane antigens was negative. However, the patient's serum and cerebrospinal fluid IgG, obtained during both exacerbations, immunolabeled cytoplasm and dendrites of Purkinje cells, cerebellar and hippocampal molecular layers, basal ganglia, thalamus, and the surface of cultured hippocampal neurons, in a manner distinct from previously identified neuropil antibodies associated with SCLC. These neuropil antibodies appear to be associated with a favorable response to treatment. Further studies are required for determination of the target antigen.

Antineuronal antibodies in migraine patients with white matter lesions.

Magnetic resonance imaging (MRI) studies occasionally display focal hyperintense lesions within the white matter of migraine patients. No immunological factors associated with these lesions have been defined so far. To investigate the relationship between MRI lesions and antineuronal antibody response, 17 migraine patients with white matter lesions (WML), 19 migraine patients without WML, 20 multiple sclerosis patients with WML and with no headache history, and 20 healthy individuals were enrolled, and their sera were examined by indirect immunohistochemistry for the presence of immunoglobulin G (IgG) reacting with the rat brain tissue. Migraine patients with and without WML essentially showed identical demographic and clinical features and frequencies of systemic autoantibodies. However, migraine patients with WML displayed a significantly higher frequency of antineuronal antibodies than those without WML (12/17 vs. 2/19, p = .0004). Serum IgG of migraine patients predominantly reacted with the cytoplasm of neurons and the molecular layer of cerebellum. None of the multiple sclerosis patients and healthy controls displayed antineuronal antibodies. Our results imply the involvement of inflammation in migraine pathogenesis.

Enhanced complement consumption in neuromyelitis optica and Behçet's disease patients.

The complement system is essential in the pathogenesis of inflammatory central nervous system disorders. To investigate the involvement of complement pathways in neuromyelitis optica (NMO), levels of breakdown products for classical (C4d), alternative (FBb) and common (sC5b-9) pathways were measured in the sera of 28 NMO and control patients (30 Behçet's disease (BD), 29 multiple sclerosis (MS)) and 31 healthy controls by ELISA. Classical and/or alternative pathway consumption was enhanced in NMO and BD patients as compared to MS patients and healthy controls. Our results suggest that NBD and NMO differ from MS by the predominance of complement system involvement.