Chapter 13: Paraneoplastic Neurologic Syndromes

INTRODUCTION

General Considerations

Immune-mediated paraneoplastic neurologic syndromes (PNSs) are a rare group of disorders in patients with cancer. They develop remotely and cause damage to neural structures, rather than as a direct effect of cancer or metastases. In general, patients present with neurologic symptoms, with cancer neither evident at onset nor previously diagnosed. Even when cancer is identified, it is often indolent and not widely metastatic although lymph node involvement is not unusual. PNSs can affect any part of the nervous system and mimic virtually any neurologic disorder; as a result, they are often diagnosed late, when permanent damage has already occurred.

The reported incidence of 0.9–6% of patients is likely an underestimate because the lack of pathognomonic findings makes the diagnosis of PNSs challenging. Some patients also develop neurologic symptoms that are likely paraneoplastic in origin but without an identifiable antibody. For example, Lambert-Eaton myasthenic syndrome (LEMS) occurs in 3% of patients with small cell lung cancer (SCLC), but almost 50% of patients with SCLC develop muscle weakness that may be paraneoplastic.

Pathogenesis

The PNSs are generally thought to occur because of abnormal autoimmunity, although the details remain unclear. The hypothesis is that the primary tumor expresses an onconeural antigen that is normally exclusive to the nervous system, or testes in anti-Ma–related syndromes (Table 13–1), provoking an autoimmune response that leads to neurologic symptoms. This hypothesis is supported by the presence of serum and cerebrospinal fluid (CSF) autoantibodies and T cells that react against the nervous system and the associated cancer. The exact mechanism of damage to the nervous system by the autoimmune response is not known for most PNSs, except LEMS and myasthenia gravis, which are primarily B-cell mediated with a T-cell component.