NMDA-receptor antibody and anti-Hu antibody positive paraneoplastic syndrome associated with a primary mediastinal seminoma

Abstract

Paraneoplastic neurological syndromes (PNS) are mostly immune-mediated, tumor-associated disorders that can develop years before detection of any malignancy. Their prevalence varies among different tumor types. Diagnostic criteria for PNS include the presence of a classical or nonclassical clinical syndrome in association with antineuronal antibodies and the presence of any malignancy [1]. We report the case of a 32-year-old male, who presented with a 2-year history of progressing neurological deficits starting with headaches, muscle pain and weight loss. Nine months later, the patient had developed two generalized epileptic seizures, optic and acoustic hallucinations, oculomotor disturbances, gait ataxia and signs of polyneuropathy. Over time, investigations in external hospitals had led to the assumption of an autoimmune encephalitis according to the following findings: a T2-sequence hyperintense alteration of the right hippocampus in the magnetic resonance imaging (MRI), positive oligoclonal bands but normal cell count in the cerebrospinal fluid, and positive serum tests for Anti-Huand N-Methyl-D-aspartic acid-receptor (NMDA-R) antibodies. Serum antibodies against acetycholine receptors and repeated tumor search remained negative. Treatments with prednisolone, intravenous immunglobuline and plasmapheresis were not effective. On clinical examination we saw a 32-year-old, cachectic and wheelchair bound patient with complex oculomotor disturbances including an anisocoric, converged right pupil with disturbed abduction and a dysfunction of horizontal movements of both eyes. There were signs of dysphagia and dysphonia. Severe generalized muscle atrophy and muscle pain were accompanied by pareses focused on the muscles of the neck causing a dropped head, but pareses were also found in the muscles of the proximal upper limb region and the distal lower limbs. Severe gait and limb ataxia and signs of polyneuropathy predominantly of the lower limbs including pallhypaesthesia and arreflexia made it impossible for the patient to stand or walk. Considering the fast progression of symptoms several diagnostics were repeated: cerebral MRI (1.5 T) showed an unchanged T2-hyperintense, non-contrast enhancing signal alteration of the right hippocampal area (Fig. 1). The patient’s serum was again tested positive (Indirect immunofluorescence test [2], Euroimmun Medical Laboratory Diagnostics, Luebeck, Germany) for anti-Hu-antibodies (titre 1:1,000, reference \1:10) and NMDA-R antibodies (titre 1:320, reference\1:10). The patient denied repetition of lumbar puncture at this point. Electroneurography demonstrated a mostly demyelinating sensorimotor I. Pohley M. Wittstock R. Benecke A. Wolters Department of Neurology, University of Rostock, Rostock, Germany