Objective-To evaluate the effect of intravenous high dose human immunoglobulin (IVIg) therapy on the clinical course and autoantibody titres of patients with neurological paraneoplastic syndromes. Methods-Twenty two patients with paraneoplastic encephalomyelitis and sensory neuronopathy syndrome associated with anti-Hu antibodies (18) Neurosurg Psychiatry 1996;60:388-392)

We retrospectively evaluated the effect of plasmapheresis (PE) in seven patients with paraneoplastic encephalomyelitis (PEM), small-cell lung carcinoma, and anti-Hu antibodies, and four patients with paraneoplastic cerebellar degeneration (PCD), ovarian or breast cancer, and anti-Yo antibodies. In addition to PE, patients received prednisone (nine), cyclophosphamide (eight), or treatment of the tumor (five). All but one patient were severely disabled by the time PE began. The clinical outcome was compared with that of five patients (PEM, four; PCD, one) who only had treatment of the tumor. Only one of these five patients had a severe neurologic deficit at the onset of the antineoplastic treatment. No patient improved. Two patients treated with PE and antineoplastic therapy and three who only received treatment of the tumor remained stable for at least 6 months. Four of the five patients with a stable course started the treatment when the neurologic deficit was not severe. We conclude that the efficacy of PE with other immunosuppressive therapies in the stabilization of the neurologic deficit is uncertain.

No abstract

Recurrent deletions of chromosome fragments observed in neoplasms are thought to participate in tumor development through the inactivation of tumor-suppressor genes. In gliomas, the most frequent deletions involve chromosome arms 9p, 10q, 17p, 19q and 22q. We have analysed deletions of chromosome 22 in gliomas by studying loss of heterozygosity (LOH) at 8 microsatellite loci. LOH for this chromosome fragment was observed in 17/70 (24%) cases, most of them encompassing the region which encodes the gene altered in neurofibromatosis 2 (NF2), an inherited disease which predisposes to tumors of the nervous system. To investigate the possible involvement of the NF2 tumor-suppressor gene in the tumorigenesis of gliomas, we searched for alterations in its genomic structure and in its mature transcript. Northern-blot and reverse transcriptase-PCR experiments showed that the NF2 transcript is expressed and does not demonstrate obvious structural alterations. Moreover, analysis, at the genomic level, of the 16 coding exons of the NF2 gene by denaturing gradient gel electrophoresis failed to detect any somatically acquired point mutations. Altogether, these data strongly suggest that, although gliomas demonstrate recurrent chromosome 22 deletions most frequently encompassing the NF2 region, the NF2 gene is not altered in these tumors.

We studied the intrathecal synthesis of the anti-Hu antibody (also called type 1 antineuronal nuclear autoantibody) in 14 patients with isolated paraneoplastic subacute sensory neuronopathy (SSN) and 16 with paraneoplastic encephalomyelitis (PEM). Patients with PEM had higher anti-Hu titers in the CSF (p = 0.003) but not in the serum than those with SSN. Only one patient (7%) with SSN had a positive intrathecal anti-Hu antibody synthesis whereas this was present in 14 (88%) of the 16 patients with PEM (p < 0.0001). The correlation between the intrathecal production of anti-Hu antibodies and PEM supports the role of autoimmune mechanisms in the pathogenesis of PEM. The absent intrathecal synthesis of anti-Hu antibodies in patients with SSN suggests easier accessibility of the systemic immune reaction to the sensory neurons probably due to the partial absence of blood-nerve barrier in the dorsal root ganglia.