Paraneoplastic neurological syndromes

This review discusses recent advances and current controversies in the aetiology, investigation and management of paraneoplastic neurological syndromes.

Antibody studies continue to define potential target autoantigens in paraneoplastic neurological syndromes and although pathogenic activity has been demonstrated for anti-glutamate receptor antibodies identified in a subset of patients with cerebellar ataxia, a role for paraneoplastic antibodies in the development of neuronal dysfunction has not been established in the majority of cases. As a result, attention has turned towards clarifying the role of adaptive cellular immunity in the pathogenesis of paraneoplastic neurological syndromes and several studies have defined expanded populations of cytotoxic T lymphocytes specific for epitopes derived from neuronal antigens in patients with paraneoplastic neurological syndromes. In vitro studies demonstrate the potential for antigen-specific cytotoxic T lymphocytes to restrict tumour growth and metastasis, but further investigation is needed to identify the mechanisms by which cytotoxic T lymphocytes could induce neuronal death. Clinical studies have demonstrated that effective tumour treatment can in some instances lead to improvement or stabilization of neurological symptoms. This is an encouraging observation since increased numbers of diagnostic paraneoplastic antibodies can now be reliably tested for and the use of [18F] fluoro-2-deoxyglucose positron emission tomography can facilitate earlier tumour diagnosis in patients presenting with paraneoplastic neurological syndromes.

Advances in the clinical management of patients with paraneoplastic neurological syndromes have occurred despite the fact that in most cases the immune effector mechanisms that lead to the development of neurological dysfunction remain to be characterized.