The mechanisms by which tumors produce their remote effects are incompletely understood. Perhaps the most plausible theory, as intimated above, is that they have an autoimmune basis. According to this theory, antigenic molecules are shared by certain tumors and central or peripheral neurons. The immune response is then directed to the shared antigen in both the tumor and the nervous system. The evidence for such an autoimmune mechanism is most clearly exemplified by the Lambert-Eaton syndrome, in which an antibody derived from a tumor binds to voltage-gated calcium channels at neuromuscular junctions (see Chap. 46).
Furthermore, in some types of paraneoplastic disorders, there is provocative evidence that the inciting tumor has antigen on its surface and self-binding of the antibody may inhibit tumor growth. This may account for the difficulty in detecting diminutive small cell lung cancers that underlie some of the paraneoplastic syndromes. It should be noted, however, that there is no evidence that suppressing or removing the antibody leads to growth of the tumor.
The occurrence of regional and bilateral encephalomyelitic changes in association with carcinoma has been described by several authors (Corsellis et al; Henson and Urich; Posner, 1995). In most of the reported cases, the encephalitic process has been associated with carcinoma of the bronchus, usually of the small cell type, but all types of neoplasms, including Hodgkin disease, have been implicated. Histologically, this group of paraneoplastic disorders is characterized by extensive loss of neurons, accompanied by microglial proliferation, small patches of necrosis, and marked perivascular cuffing by lymphocytes and monocytes. Foci of lymphocytic infiltration have been observed in the adjacent leptomeninges as well. These pathologic changes may involve the brain and spinal cord diffusely, but more often they predominate in a particular part of the nervous system, notably in the medial temporal lobes and adjacent nuclei (“limbic encephalitis,” Fig. 30-24), the brainstem, the cerebellum (see earlier), or the gray matter of the spinal cord. The symptoms will, of course, depend on the location and severity of the inflammatory changes and may overlap. Most cases are subacute, meaning specifically a progression over a few weeks or months, but often the main symptoms in mild form become apparent in a matter of days. Rare instances of remission have been reported.
The most distinctive features of paraneoplastic limbic encephalitis consists of a confusional–agitated state, memory defect (Korsakoff syndrome), seizures, hallucinations, and dementia—singly or in various combinations and evolving subacutely (Gultekin et al); an amnestic component is almost universal and the central feature in most cases.
Vertigo, nystagmus, ataxia, nausea and vomiting, and a variety of ocular and gaze palsies reflect a different process of paraneoplastic brainstem encephalitis. As indicated above, these symptoms may be joined with cerebellar ataxia, and another group has an additional sensory neuropathy. We have seen instances of this condition involving only the midbrain and others involving only the medulla, the latter with unusual breathing patterns including gasping, inspiratory breath holding, and vocal–respiratory incoordination, and yet others with chorea and additional basal ganglionic features. Pathologic studies have partially clarified this form of paraneoplastic disorder. In some cases, few changes were demonstrable in the brain, even though there had been a prominent dementia during life. Contrariwise, widespread inflammatory changes may be found without clinical abnormalities having been recorded during life.