Treatment of Paraneoplastic Neurological Syndromes

(PNS) are rare complications of cancer that often herald the tumour diagnosis. Whereas some syndromes affect only certain parts of the nervous system, other syndromes involve both central and peripheral neurons, resulting in complex clinical manifestations. The syndromes are believed to be immune-mediated, caused by T cell, B cell and macrophage responses to antigens present on tumour cells and on neurons and glia cells (Figure 1). Activation of B cells results in the production of onconeural antibodies that are highly useful diagnostic markers for a paraneoplastic aetiology. According to diagnostic criteria, the presence of a well-characterized onconeural antibody in a patient with neurological symptoms defines the disease as paraneoplastic even in the absence of detectable malignancy. Onconeural antibodies are detected in about 60% of patients with PNS. PNS and onconeural antibodies have been discussed in a previous review in this journal. The symptoms as well as the severity of the PNS are heterogenous, depending on which parts of the peripheral and central nervous system are affected. Some syndromes have a high mortality rate, such as paraneoplastic encephalomyelitis and brain stem encephalitis, whereas other syndromes are less lethal but leave the patients with disabling neurological deficits, such as paraneoplastic cerebellar degeneration and peripheral neuropathy. The rapidly progressive and often dramatic nature of the PNS symptoms requires urgent therapeutic considerations. Nevertheless, the rarity of PNS limits the number of published therapy studies, in particular studies with a prospective design. Thus, there is no class I or II evidence for PNS therapy except for the syndromes that affect the neuromuscular junction (paraneoplastic myasthenia gravis, Lambert-Eaton myasthenic syndrome, and neuromyotonia). Many patients receive concomitant anti-neoplastic therapy and immunotherapy, but so far there is no standard care for any of the PNS. This review focuses on the therapeutic options of PNS, but does not include the autoimmune neuromuscular diseases.