Cerebellar Paraneoplastic Syndromes

October 6, 2016

Ovarian tumors are most often associated with paraneoplastic syndromes, but other tumors can produce antibodies that target CNS structures.

Paraneoplastic syndromes, a group of distinctive neurological syndromes, are a relatively uncommon and unusual consequence of cancer. They are identified by neurological signs and symptoms that are caused by antibodies that are produced by tumors, most notably gynecologic tumors.

Paraneoplastic cerebellar syndromes are among the most well described subtypes of these syndromes. Cerebellar paraneoplastic syndromes are associated with the rapid onset of dramatic cerebellar signs and symptoms, and a notable absence of potentially accountable cerebellar lesions on brain imaging studies.

Symptoms of Cerebellar Paraneoplastic Syndromes 

Cerebellar paraneoplastic symptoms are distressing for patients, often sudden in onset, and notably characterized by obvious and intense cerebellar signs and symptoms. Cerebellar ataxia is characterized by a major deficit in balance, impaired limb coordination, and diminished fine motor movement that may be symmetric or asymmetric. Marked nystagmus is apparent when the eyes are resting and may become exaggerated with eye movement. Typically, the sensory visual effects of the eye movement abnormalities add to the symptoms of profound dizziness, nausea, and physical imbalance. Nystagmus may be symmetric or asymmetric. Other encephalopathic or myasthenic signs and symptoms have also been described along with the cerebellar symptoms or in the absence of cerebellar symptoms. 

The Workup and Management of Cerebellar Paraneoplastic Syndromes 

The clinical workup of cerebellar paraneoplastic syndromes begins by ruling out a vascular lesion, a brain mass, an infection, inflammation, or demyelination that could explain the neurological symptoms and physical findings. Once a central nervous system etiology has been ruled out, the characteristic symptoms of cerebellar ataxia, nystagmus, and coordination deficit may raise the suspicion of a paraneoplastic etiology. Thus, antineuronal nuclear antibodies are usually the next line in the workup. ANNA 1, anti-Ri, and anti-Yo are among the antibodies ordered in a paraneoplastic workup. Some laboratory facilities run a paraneoplastic panel or a group of antineuronal antibody tests. These antibodies may be present in the blood or CSF of individuals who have paraneoplastic syndrome.

The workup of paraneoplastic neurological syndromes is tricky. The cerebellar variants are the most clinically striking. However, it is most typically described that patients present with neurological signs before they have a cancer diagnosis and even before the tumor is large enough to reveal a mass on imaging studies of the ovaries, breast, thyroid, lymphatic system, or lungs. Ovarian tumors are the most often associated with paraneoplastic syndromes, but other tumors can produce antibodies that target the cerebellum or other central nervous system structures.

When a paraneoplastic syndrome is clinically suspected and antibodies are detected, suspected tumors can be surgically removed. Significant improvement or complete resolution of neurological symptoms can result after surgical removal of the gynecologic tumor. While visible masses are not characteristic, biopsy specimens are likely to be abnormal. If symptoms do not resolve after surgical excision, anti inflammatory treatment or immunosuppression to diminish the activity of autoantibodies has been reported to be effective.

Typically, surgical excision of a suspected tumor in the setting of paraneoplastic syndrome requires the skill of a highly trained and well-experienced surgeon.

Have you ever diagnosed paraneoplastic syndrome? Was it difficult to convince your surgical/gynecology colleagues of the diagnosis?

Reference: Höftberger R, et al. Update on neurological paraneoplastic syndromes. Curr Opin Oncol. 2015 Nov;27(6):489-495.