Limbic encephalomyelitis

General characteristics

One stereotyped paraneoplastic syndrome is characterized clinically by subacute loss of memory leading to anxiety, confusion, behavioural changes, and alteration in mood; there is a high frequency of partial complex or generalized seizures (Bakheit et al. 1990; Dalmau et al. 1992).

The encephalitis may extend outside the limbic system, causing motor deficits, cranial nerve palsies, and central respiratory involvement when the brainstem is involved. Not infrequently, the clinical phenotype merges into other forms of paraneoplastic disease.

Morphology

All these features arise from neuronal loss and gliosis, together with diffuse perivenous inflammatory cell infiltration seen in the other paraneoplastic disorders, maximally in CA1 layers of the hippocampus, although this may extend to other parts of the limbic system and associated cortex. The cerebrospinal fluid also shows a mild reactive lymphocytic pleocytosis, raised immunoglobulin, and oligoclonal bands. Anti-Hu is the serological marker of this paraneoplastic disorder.

Aetiology

The syndrome usually occurs in patients with small cell carcinoma of the lung, but has been reported in association with germinal tumours (Burton et al. 1988) and malignant thymoma (McArdle and Milligen 1988). More recently, Voltz et al. (1999) have implicated testicular tumours and antigens in 10 cases of paraneoplastic limbic and brainstem encephalitis, all sharing the presence of anti-Ta auto-antibody directed against the Ma2 antigen. As expected, in this series, neurological presentation usually preceded detection of the tumour, often by several months.

It has been suggested that these cases respond to removal of the primary tumour, and that others arrest spontaneously, but this may reflect the small numbers that have been studied in detail by comparison with more frequent cases of progressive cerebellar degeneration.

A retrospective review of 51 cases, of whom the majority had small cell lung cancer, indicated that successful tumour therapy is associated with improved outcome of the paraneoplastic syndrome; immunotherapy did not adversely affect tumour outcome, but neither did it favourably influence the features of encephalomyelitis (Keime-Guibert et al. 1999). In one anti-Ta associated case, the illness was characterized by spontaneous remissions and with a response to radical treatment of the primary tumour Voltz et al. (1999).