Paraneoplastic opsoclonus-myoclonus

Clinical features
Opsoclonus is defined by the presence of spontaneous, arrhythmic, large amplitude conjugate saccades occurring in all directions of gaze without a saccadic interval. The pathogenesis of the opsoclonus-myoclonus syndrome is unclear. Neuropathologic studies have demonstrated mild perivascular inflammatory infiltrates in the brainstem and minimal loss of Purkinje cells in the cerebellum. Opsoclonus may occur in viral, toxic and metabolic encephalopathies. In oncologic patients, opsoclonus can result from brain tumors or as part of a paraneoplastic disorder. Paraneoplastic opsoclonus is observed in three clinical settings, 1) pediatric patients with neuroblastoma, 2) adult female patients with anti Ri antibodies, whose underlying tumor is usually breast cancer, and 3) adult patients without onconeural antibodies whose tumor is almost always small cell lung cancer (SCLC). There are individual case reports associated with other tumors including carcinoma of the uterus, Fallopian tube, breast, bladder, thyroid, thymus, chondrosarcoma, and Hodgkin's disease.

Opsoclonus is usually associated with myoclonus of the limbs and trunk, and sometimes encephalopathy; these symptoms cannot be clinically differentiated from those caused by non-paraneoplastic etiologies. Ataxia predominates in the trunk and may cause severe gait difficulty and frequent falls. Unlike PCD, limb ataxia is usually mild. Other symptoms suggesting a more diffuse involvement of the brainstem include nausea, dizziness, dysarthria, dysphagia, diplopia, and decreased hearing. CSF may show mild inflammatory changes and oligoclonal bands. Cranial MRI and CT scans are usually normal. EEG may be normal or demonstrate generalized slow activity, without epileptic discharges. The disease has a subacute onset with frequent fluctuations of symptoms; in some patients symptoms may resolve spontaneously.

Associated antibodies
Anti-Ri antibodies identify those patients with opsoclonus whose underlying tumor is usually breast cancer. Not all patients with anti-Ri antibodies present opsoclonus but the majority develop symptoms of brainstem involvement characterized by supranuclear gaze palsies, parkinsonism, rigidity, dizziness, dysarthria, and dysphagia.
A few patients with opsoclonus and SCLC or neuroblastoma may harbour anti-Hu antibodies.

Treatment
The opsoclonus-myoclonus syndrome seems to improve with immunotherapy. The absence of controlled studies and the spontaneous recovery in some patients, particularly the non-paraneoplastic cases, prevent to make a definite statement. As in other paraneoplastic neurological syndromes, treatment of the tumor is crucial to achieve a good response of the syndrome.

Selected references

1. Anderson NE, Budde-Steffen C, Rosenblum MK, et al. Opsoclonus, myoclonus, ataxia and encephalopathy in adults with cancer: A distinct paraneoplastic syndrome. Medicine 1988; 67: 100-9.
2. Bataller, L.; Graus, F.; Saiz, F. et al. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus- myoclonus. Brain 2001;124: 437- 43.

3. Luque FA, Furneaux HM, Ferziger R, et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991; 29: 241-51.
4. Pranzatelli MR. The neurobiology of the opsoclonus-myoclonus syndrome. Clin Neuropharmacol 1992; 15: 186-228.
5. Sutton IJ, Barnett MH, Watson JDG, et al. Paraneoplastic brainstem encephalitis and anti-Ri antibodies. J Neurol 2002;249:1597-8.

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