The spinal fluid usually contains elevated protein and a few lymphocytes. As with paraneoplastic encephalomyelitis, most of the cases associated with small cell lung cancer demonstrate the anti-Hu antibody. A small but uncertain proportion of this same syndrome is due to anti-CRMP5 antibody, usually associated with small cell lung cancer. As mentioned, neuropathy and encephalomyelitis often occur together. The sensory neuronopathy–ganglionopathy that is related to Sjögren disease and an idiopathic variety do not have this antibody, making its presence a reliable marker for lung cancer in patients with sensory neuronopathy. The polyneuropathy and sensory neuronopathy is refractory to almost all forms of treatment, or there is a transient benefit, and most patients die within months of onset, but there have been reports of brief remissions with plasma exchange and intravenous gamma globulin applied early in the illness. Resection of a tumor can halt progression of the neurologic illness.
For many years, this disorder was considered to be quite uncommon, but it is perhaps the most characteristic of the paraneoplastic syndromes. In reviewing this subject in an earlier edition of this textbook 1970, Adams and Victor were able to find only 41 pathologically verified cases; in a subsequent review (Henson and Urich), only a few more cases were added. The actual incidence is much higher than these figures would indicate. At the Cleveland Metropolitan General Hospital, in a series of 1,700 consecutive autopsies in adults, there were 5 instances of cerebellar degeneration associated with neoplasm. In the experience of Henson and Urich, about half of all patients with nonfamilial, late-onset cerebellar degeneration proved sooner or later to be harboring a neoplasm. Large series of cases have been reported from the Mayo Clinic and the Memorial Sloan-Kettering Cancer Center (Hammack et al and N.E. Anderson et al, respectively). We see several such cases yearly, but have also encountered numerous instances of an identical syndrome with no cancer evident and no antibodies that are probably a result of diverse causes summarized in Chap. 5 and Table 5-1.
In approximately one-third of the cases, the underlying neoplasm has been in the lung (most often a small cell carcinoma)—a figure reflecting the high incidence of this tumor. However, the association of ovarian carcinoma and lymphoma, particularly Hodgkin disease, accounting for approximately 25 and 15 percent, respectively, is considerably higher than would be expected on the basis of the frequency of these malignancies. Carcinomas of the breast, bowel, uterus, and other viscera have accounted for most of the remaining cases (Posner, 1995).
The cerebellar symptoms have a subacute onset and steady progression over a period of weeks to months; in more than half the cases, the cerebellar signs are recognized before those of the associated neoplasm.