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  • Autoantibodies to neuronal surface antigens in thyroid antibody-positive and -negative limbic encephalitis.

    24 October 2018

    BACKGROUND: Thyroid antibodies (Thy-Abs) are frequently detected in various autoimmune disorders in coexistence with other systemic autoantibodies. In association with an encephalopathy, they are often taken as evidence of Hashimoto's encephalitis (HE). However, the presence of Thy-Abs in a cohort of limbic encephalitis (LE) patients and their association with anti-neuronal autoimmunity has not been explored. PATIENTS AND METHODS: We investigated thyroid and anti-neuronal antibodies in the sera of 24 LE patients without identified tumors by cell-based assay and radioimmunoassay and evaluated their clinical features. RESULTS: There was a female predominance in Thy-Ab-positive LE patients. Five of the eight Thy-Ab-positive patients and six of the 16 Thy-Ab-negative patients had antibodies to voltage-gated potassium channel (VGKC), N-methyl-D-aspartate receptor (NMDAR) or undefined surface antigens on cultured hippocampal neurons. There were trends towards fewer VGKC antibodies (1/8 vs. 5/16, P = 0.159) and more NMDAR antibodies (2/8 vs. 1/16, P = 0.095) among the Thy-Ab-positive LE patients; antibodies to undefined surface antigens were only identified in Thy-Ab-positive patients (2/8 vs. 0/16, P = 0.018). There were no distinguishing clinical features between Thy-Ab-positive patients with and without neuronal antibodies. However, patients with anti-neuronal antibodies showed a better treatment response. CONCLUSION: Thy-Abs can be found in a high proportion of patients with non-paraneoplastic LE, often in association with antibodies to specific or as yet undefined neuronal surface antigens. These results suggest that acute idiopathic encephalitis patients with Thy-Abs should be closely monitored for ion-channel antibodies and it should not be assumed that they have HE.

  • Prospective study into the incidence of Lambert Eaton myasthenic syndrome in small cell lung cancer.

    24 October 2018

    INTRODUCTION: The Lambert Eaton myasthenic syndrome (LEMS) is a paraneoplastic disorder associated with raised serum voltage-gated calcium channel (VGCC) antibodies in patients with small cell lung cancer (SCLC). VGCC can also be found in patients with SCLC and cerebellar ataxia. This was a prospective study to assess the incidence of clinical and subclinical LEMS or other neurologic disease in patients with SCLC. PATIENTS AND METHODS: Sixty-three unselected patients with cytologically or histologically confirmed SCLC consented to participate. Pretreatment assessment included a neurologic symptom questionnaire, examination for physical signs of LEMS or ataxia, measurement of serum titers of antibodies to P/Q-type VGCCs by radioimmunoassay in all patients and electrophysiological examination where appropriate. RESULTS: Neurologic symptoms unrelated to LEMS occurred in 26% of patients. Five patients (8%) had raised serum VGCC antibodies (range, 69-1553 pM/l) diagnostic of LEMS, two (3%) of whom had LEMS on clinical and electrophysiological grounds. Both also had mild cerebellar ataxia. There was no association between serum VGCC antibody titer and survival. CONCLUSION: Routine measurement of VGCC antibodies in patients without clinical LEMS is unlikely to assist either in management of SCLC or in assessment of prognosis.

  • Paraneoplastic neurological autoimmunity and survival in small-cell lung cancer.

    24 October 2018

    The autoimmune disorder of Lambert-Eaton myasthenic syndrome (LEMS) associates with small cell lung carcinoma (SCLC) in 50-60% of cases. It has been postulated that patients who harbour paraneoplastic neurological syndromes such as LEMS have an improved tumour prognosis compared to other patients with the tumour but without neurological deficit. In this intermediate report of an ongoing prospective study, 100 consecutive patients with biopsy-proven SCLC underwent full neurological examination and serum was taken for autoantibody analysis. Antibodies to voltage-gated calcium channels were detected in 10 patients, however only 4 had clinical and electrophysiological features of LEMS, 1 had limbic encephalitis, whilst the remaining 5 had no neurological signs. A further 6 patients had onconeural antibodies; only one had a paraneoplastic syndrome, sensory neuropathy. The median survival of the four antibody positive LEMS patients (19.6 months) was considerably greater than that for the antibody negative (8.9 months) or antibody positive patients as a whole (10.5 months). Although preliminary, these results suggest that functionally effective antibodies present in the sera of patients with LEMS may confer a survival advantage.

  • Autoantibodies in childhood opsoclonus-myoclonus syndrome.

    24 October 2018

    Opsoclonus-myoclonus syndrome or Dancing Eye Syndrome (OMS/DES) is a rare neurological disorder of children, which associates with neuroblastoma (NB) in approximately 50% of cases. We examined sera from five patients with (OMS-NB(+)) and five without NB (OMS-NB(-)) for autoantibodies. OMS-NB(-) IgG bound to the surface of a NB cell line, whereas IgG from OMS-NB(+) and from NB patients without OMS/DES bound only to permeabilised cells. Both OMS-NB(+) and OMS-NB(-) reduced proliferation of NB cells. We also present a case report of a child with OMS/DES without NB who made a complete recovery without treatment. Serum antibodies at presentation bound to the surface and decreased NB cell proliferation but had decreased 9 weeks later when the child was asymptomatic. These results demonstrate that sera from some OMS/DES patients contain IgG antibodies that are potentially pathogenic.

  • Cerebellar ataxia in non-paraneoplastic Lambert-Eaton myasthenic syndrome.

    24 October 2018

    Lambert-Eaton myasthenic syndrome (LEMS) is an immune-mediated disorder of the neuromuscular junction that rarely is associated with cerebellar ataxia (CA). We describe two patients with non-paraneoplastic LEMS associated with CA who showed high levels of anti-P/Q-type voltage-gated calcium channels antibodies in the serum and cerebrospinal fluid, and reduced CMAP with increment after brief maximum voluntary contraction in electrophysiological studies. We suggest that LEMS should be considered in the differential diagnosis of patients with CA.