An optic neuropathy is probably the most specific associated syndrome with the CRMP-5 antibody, as described by Cross and colleagues. There is subacute visual loss, disc swelling, and a cellular reaction in the vitreous. Most patients have features of another paraneoplastic syndrome. Several authors have remarked on the occurrence of chorea as a presenting symptom along with basal ganglionic changes on MRI. It is difficult for us to make sense of the clinical features aside from the optic neuropathy (really an optic neuritis), but they seem comparable to the perivenous inflammatory encephalitis and neuritis of the anti-Hu syndromes. Presumably this antibody accounts for some of the odd subacutely progressive syndromes previously thought to be antibody-negative; testing for this antibody might be included when an unusual paraneoplastic syndrome is suspected. The heterogeneity of antibody response to these expressed proteins may account for different clinical manifestations of the immune process but there is no certain evidence yet of their pathogenetic role.
In recent years, there have been reports of retinopathy as a paraneoplastic syndrome that is distinct from the above-described optic neuropathy. Small cell carcinoma of the lung has been the most common underlying malignancy. In about half of the reported cases, retinal symptoms preceded the discovery of the tumor by several months. The lesion is in the photoreceptor cells, and antiretinal antibodies (directed against a calcium-binding protein, recoverin) have been identified in the serum. Photosensitivity, ring scotomas, and attenuation of the retinal arterioles are the main clinical features; Jacobson and coworkers suggested that they constitute a diagnostic triad.
Paraneoplastic Stiff Person Syndrome and Related Neuromuscular Disorders (See Chap. 46)
Occasionally stiff person syndrome occurs as a paraneoplastic disease. Lesser degrees of unexplained mild rigidity are seen from time to time, perhaps as a consequence of loss of spinal cord interneurons. Folli and associates described 3 female patients with breast cancer who developed a state of generalized motor hyperexcitability and rigidity. These patients generally have no antibodies to glutamic acid decarboxylase (GAD), as in the sporadic cases of stiff person syndrome; probably there are antibodies to other synaptic proteins.
The “chorée fibrillaire” of Morvan is an extraordinary disorder of continuous muscle fiber activity, insomnia, and hallucinosis that may be caused by a paraneoplastic antibody to voltage-gated potassium channels, as discussed in Chap. 46. This same antibody, as well as acetylcholine receptor antibodies, has been associated with paraneoplastic neuromyotonia (Isaac syndrome), seen in cases of lung cancer, lymphoma, and thymoma. The subtleties that distinguish these syndromes of continuous muscle fiber activity are discussed in Chap. 46.
The Lambert-Eaton syndrome is perhaps the most common paraneoplastic neurologic syndrome; it is associated with antibodies directed against calcium channels, as mentioned earlier. This disorder, which may occur concurrently with other paraneoplastic syndromes such as cerebellar ataxia, is discussed in Chap. 46. Basal ganglia syndromes, chorea in particular, are associated with the anti-Hu and CRMP-5 antibodies as already noted. A myoclonus syndrome without ataxia or opsoclonus is reported from time to time in the literature and probably is a derivative of one of the better-characterized antibody diseases.