Successful treatment of stiff man syndrome with intravenous immunoglobulin.

The presence of anti-CV2 antibodies was shown using immunohistochemistry on sections of rat brain and western blots of a soluble fraction of newborn rat brain proteins, as previously reported (figure, B).2 The identity of the antibody was confirmed by immunoprecipitation of the CV2 protein,2 and with an immunohistochemical competition assay in which preincubation of a section of rat brain with the patient's serum blocked the reactivity of a previously characterised biotinylated anti-CV2 antibody (data not shown). Our patient is remarkable because she had several well characterised paraneoplastic antineural antibodies (anti-Hu, anti-Ri, and anti-CV2) in her serum, a finding that until now has not been reported. As anti-Ri antibodies react with neurons of the CNS in a pattern identical to the anti-Hu antibodies, they would have been missed without western blot analysis. This finding supports our view that antigen specificity should always be confirmed by western blot analysis.' Anti-Hu are the best characterised antineuronal antibodies in paraneoplastic syndromes of the CNS.' Detection of these antibodies is almost always associated with small cell lung cancer, although a few other tumours, usually neuroendocrine related, have also been reported.' Low titres of antiHu antibodies (in general, orders of magnitude less than "paraneoplastic titres") are found in 16% of patients with small cell lung cancer without paraneoplastic syndromes.' Although anti-Ri antibodies and Ri antigens have been well characterised,4 many fewer patients have this antibody than other antineuronal antibody associated with paraneoplastic syndromes. Therefore the clinical range of neurological symptoms associated with anti-Ri antibodies is still expanding. As previously reported, the most frequent symptoms associated with anti-Ri antibodies are a predominant gait and truncal ataxia, usually accompanied by opsoclonus.' Other symptoms include myoclonus, axial and limb spasms, encephalomyelitis, and peripheral neuropathy.' Similarly, the range of tumours associated with anti-Ri antibodies is larger than what was previously suggested; it includes breast cancer and, less often, gynaecological cancers,4 small cell lung cancer, and bladder cancer (Dalmau et al, unpublished data). The tumours of all these patients were found to express Ri antigen. The serum of the patient contained another antibody, called anti-CV2, that has been identified in patients with paraneoplastic neurological syndromes (including cerebellar ataxia); the most commonly associated tumour is small cell lung cancer.2 In a series of 11 patients with anti-CV2 associated paraneoplastic neurological syndromes, we identified another patient with small cell lung cancer who harboured both anti-Hu and anti-CV2 antibodies in his serum.2 We do not know which component of the immune response (anti-Hu, anti-Ri, or antiCV2) either in combination or alone, was involved in the neurological dysfunction of our patient. The experience with anti-CV2 antibodies is too limited to draw conclusions about the role of this immune response in neurological symptoms. Patients with antiHu associated encephalomyelitis-sensory neuropathy complex do not usually improve with treatment, whereas symptoms associated with anti-Ri may respond to treatment. ' The fact that our patient had high titres of anti-Hu antibodies, which until now have been invariably associated with encephalomyelitis-sensory neuropathy complex, including predominant cerebellar symptoms, and that the neurological symptoms did not improve with chemotherapy, intravenous immunoglobulin, and steroids, suggest, but do not prove, that the anti-Hu immune response was involved in the patient's symptoms. However, the presence of both anti-Hu and anti-Ri antibodies, the second at titres also similar to those in patients with cerebellar dysfunction associated with anti-Ri, indicates that multiple immune responses against onconeuronal antigens may occur at the same time, and be involved in a specific neurological disorder. JEROME HONNORAT Centre de recherche sur l'ataxie, Hopital Neurologique, Lyon, France JEROME HONNORAT MICHELE AGUERA INSERM U 433, Hopital Neurologique, Lyon, France BENOIT GUILLON ERIC DE FERRON Department ofNeurology, HJpital Laennec, Nantes, France JEAN CHRISTOPHE ANTOINE Service de Neurologie, Hopital de Bellevue, Saint Etienne, France JOSEP DALMAU Department ofNeurology, Memorial Sloan-Kettering Cancer Center, New York, USA