Neuro-ophthalmological signs and symptoms are usually present in
paraneoplastic syndromes of the central nervous system. Unlike
opsoclonus, less characteristic eye movement abnormalities are difficult to recognize as presenting symptoms of
paraneoplastic syndromes. In this setting, the detection of several
antibodies, including anti-Hu, Yo, Ma2, Ri, Tr, CV2/CRMP5 or voltage-gated
calcium channel antibodies may help to establish that the neuro-ophthalmological disorder is paraneoplastic. Among the recently characterized
antibodies, those against the Ma
proteins often associate with brainstem
encephalitis and vertical gaze
paralysis. A small subset of patients with
opsoclonus and
ataxia harbor
anti-Ri antibodies. In other patients, there is preliminary evidence that the
autoantigens of
opsoclonus reside in the postsynaptic density, but no dominant antibody marker has been identified.
Uveitis and
optic neuritis are rare accompaniments of
paraneoplastic encephalomyelitis; some of these patients harbor anti-CV2/CRMP5 in association with other
antibodies. Studies on paraneoplastic retinopathy indicate that immunity to
retinal proteins other than
recoverin can result in a similar syndrome to that associated with
recoverin antibodies, and that
melanoma-associated retinopathy may associate with several
retinal antibodies.
SUMMARY: There is increasing recognition of an extensive variety of neuro-ophthalmological abnormalities as manifestations of
paraneoplastic syndromes and of several antineuronal
antibodies as
clinical markers of these disorders. Basic immunological studies support the pathogenic role of some of these
antibodies, and are elucidating the pathogenic mechanisms that underlie these and other antibody-associated
paraneoplastic syndromes.