Restoring Balance: Paraneoplastic Cerebellar Degeneration

A 63-year-old woman was evaluated for 3 months of gradually worsening tremors in her legs. The tremors were worse in the right leg, increased in amplitude on standing or walking, and were absent at rest. She also had a milder tremor of her head. She had no headache, confusion, weakness, numbness, or dyscoordination. Her medical history was unremarkable other than 60 pack-years of tobacco use. Physical examination was reported as normal except for a postural tremor affecting all extremities, more so on the right side. She was diagnosed with essential tremor and prescribed primidone.

There was no significant improvement in her tremors after 1 month of treatment with primidone, and in addition to the postural tremors a new vocal tremor was noted. The presumptive diagnosis remained essential tremor, and she was sequentially prescribed propranolol, alprazolam, and gabapentin, none of which helped reduce her tremors.

Brain magnetic resonance imaging, nerve conduction studies and electromyography, and routine laboratory studies did not suggest an alternative diagnosis. She was seen for follow-up on 2 subsequent occasions, 5 and 7 months after symptom onset. Three months later, she was referred to our neurology clinic for first evaluation.

She presented to our clinic with worsening tremor and dysarthria, and new vertical diplopia with rightward gaze and periodic jumping or oscillating of objects in her vision. She was afebrile with a blood pressure of 114/74 mm Hg and heart rate of 62 beats/min. Her respiratory rate was 20 breaths/min with 98% oxygen saturation. There was no adenopathy. She had normal heart sounds, normal rate and rhythm, and no murmurs. Her lungs were clear. Her abdomen was soft, nontender, and without masses. There were no skin lesions or edema of the extremities.

She was alert and attentive. A low-frequency course postural tremor was noted throughout the right greater than left hemi-body and head that increased in amplitude with movement. She had dysmetric saccadic movements in all directions of gaze, difficulty maintaining ocular fixation, nystagmus that worsened in upgaze, dysarthric and dysrhythmic speech, and ataxic extremity movements that were worse on the right. There was no weakness, numbness, headache, nausea, or recent weight loss.

Brain magnetic resonance imaging with contrast showed nonspecific white matter changes within the cerebral hemispheres and no other lesion or abnormal parenchymal or meningeal enhancement. The serum leukocyte count was 7430/mm3 with 42% granulocytes, 49% lymphocytes, 5% monocytes, 3% eosinophils, and 1% basophils. Hemoglobin level was 14.9 g/dL, hematocrit was 43.2%, and platelet count was 184,000/mm3. Serum electrolytes, creatinine, liver, and thyroid function test results were normal. Erythrocyte sedimentation rate was 12 mm/h, C-reactive protein was 0.2 mg/L, and heavy metal toxicity screening was negative.

Lumbar puncture was performed with opening pressure of 12 cm of water. Cerebrospinal fluid was clear and colorless with 2 leukocytes per cubic millimeter, 91 erythrocytes per cubic millimeter, glucose level of 70 mg/dL, and protein level of 23 mg/dL. There were no oligoclonal bands, and cultures were sterile.

This previously healthy woman presented with new asymmetric tremor affecting her extremities and head. Initially, there was no ataxia or dysmetria and no worsening of the tremor as a target was approached. The tremor was exacerbated by movement and was therefore thought to be a postural, or action, tremor. Essential tremor is one of the prototypical postural tremors and usually has an asymmetric onset and frequency in the 10 Hz range, and slow progression over years. Although the response rate to medications for essential tremor is highly variable, the patient’s progressive course, development of new symptoms, and nonimprovement with medications raised concern for alternative diagnoses.