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PARANEOPLASTIC LIMBIC ENCEPHALITIS AND LAMBERT EATON MYASTHENIA–AN IMMUNOLOGICAL PROFILE OF A NEW SYNDROME?
  1. Seema Kalra,
  2. Paul Gozzard,
  3. Andre Leonard,
  4. Paul Maddison,
  5. Saiju Jacob
  1. University Hospitals of North Staffordshire; Queens Medical Centre, Nottingham; Queen Elizabeth Neuroscience Centre, University Hospitals of Birmingham

    Abstract

    We report a case of paraneoplastic limbic encephalitis (LE) and Lambert Eaton myasthenic Syndrome (LEMS) with a novel immunological onco–neural profile: Voltage Gated Calcium Channel (VGCC) antibodies, high titre Voltage Gated Potassium Channel (VGKC) complex antibodies of non–LGI1 non–Caspr2 type and Sry–like high mobility box (SOX2) antibodies) with probable small cell lung carcinoma (SCLC).

    A 76–year–old heavy smoker presented with a 6–month history of dry mouth, dry cough, anorexia, weight loss, dysarthria and dysphagia, dizziness, limb weakness, and reduced mobility. Examination showed profound postural hypotension and features of Lambert–Eaton myasthenic syndrome (LEMS) ie proximal limb wasting and weakness, diminished deep tendon reflexes with post–exercise potentiation along with bilateral facial weakness and bulbar palsy. Electromyography confirmed LEMS and ruled out Neuromyotonia. Over 6 weeks he developed confusion, behavioural change, hypersomnolence, and complex partial seizures suggestive of limbic encephalitis (LE). Autonomic dysfunction worsened. Electroencephalography showed generalised cerebral slowing with epileptiform discharges from temporal lobes. Computerised Tomography revealed sub–mental, sub–clavicular, hilar, para–aortic and portocaval lymphadenopathy with increased uptake on Positron Emission Tomography (PET) scanning. Attempts at needle aspiration and open biopsy were non–diagnostic and tissue diagnosis could not be made. Postural hypotension, LEMS and LE failed to respond to multiple pharmacological interventions including steroids and intravenous immunoglobulin. He declined lumbar puncture and further investigations, deteriorated further, and later died of sepsis. Post–mortem was not performed.

    VGKC antibodies were detected at high titres of 2337 pM (normal<100 pM) on dendrotoxin radioimmunoprecipitation assays.1 VGCC antibodies were detected at 97pM (normal<50pM).2 LGI1 and Caspr2 antibodies were both negative at 1:20 dilution on cell based assays. The cerebellar section staining pattern (1:100 dilution) was similar to that described in anti–glial nuclear antibodies. Subsequent testing confirmed the presence of SOX 2 antibodies.3 Other limbic encephalitis associated antibodies (Hu, Ri, Yo, Ma2, CV2/CRMP5, amphiphysin, GAD, alpha3–acetylcholine receptor, NMDAR, GABAbR and AMPAR) were all negative.

    LEMS is associated with VGCC antibodies and coexistent tumours in almost 60% of patients, most commonly small–cell lung cancer. Antibodies to SOX1/2 are highly suggestive of an underlying SCLC.3 Coexistence of LEMS with other paraneoplastic disorders is unusual and typically includes cerebellar ataxia, albeit rarely.2 The most common additional onconeural antibody found in SCLC–LEMS is anti–Hu, in approximately 30% of cases.2 There are only very rare case reports of co–existence of LEMS with anti–Hu–antibody–associated LE.4 We elaborate on this previously described rare clinical syndrome of LE and LEMS and demonstrate a novel immunological association with concurrence of non–LGI1, non–CASPR2 high–titre–VGKC antibodies, with VGCC and SOX antibodies indicating a highly probable SCLC.

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