Dramatic response to zonisamide of post-subarachnoid hemorrhage Holmes’ tremor

Abstract

Holmes’ tremor is an unusual combination of 2–5 Hz resting, postural, and kinetic tremors affecting the unilateral upper extremity, which is usually caused by stroke, trauma, vascular malformations, or tumors involving the midbrain [1]. Abnormal involuntary movements such as tremor affect the quality of life by interfering with simple motor tasks and daily activities. Pharmacotherapy for Holmes’ tremor does not usually achieve satisfactory results and some patients require thalamic surgery to control this tremor [2]. Zonisamide (ZNS), 3-sulfamoylmethyl1,2-benzisoxazole, was originally developed as a broadspectrum antiepileptic drug. Recent clinical studies have suggested several new indications for ZNS, including Parkinson’s disease, essential tremor, and psychiatric diseases [3]. Here we report a patient in whom delayed Holmes’ tremor after subarachnoid hemorrhage responded dramatically to ZNS. A 68-year-old, right-handed woman with a history of hypertension developed headache and drowsiness. Neurological examination revealed dysarthria, right oculomotor nerve paralysis, and left hemiparesis [2/5 by manual muscle testing (MMT)]. On admission, brain computed tomography and magnetic resonance imaging (MRI) showed subarachnoid hemorrhage together with right midbrain hemorrhage (Fig. 1a–c). An aneurysm of the basilar artery/right superior cerebellar artery was detected by MRI and digital subtraction angiography (Fig. 1d, e), and was treated by coil embolization (Fig. 1f, i, j). During follow-up for 15 months, her right oculomotor nerve palsy improved slightly and her left hemiparesis improved to 4/5 on MMT. She was able to look after herself without assistance. However, a slow, strong, and large-amplitude tremor affected her left upper limb. The tremor was worsened by emotional stress and disappeared during sleep. It was exhausting and rendered her left arm useless. T2-weighted and fluid attenuated inversion recovery MRI of the brain showed a low intensity to hyperintense area in the right midbrain, corresponding to the site of hemorrhage, without any evidence of additional vascular pathology in the basal ganglia (Fig. 1g, h). A diagnosis of Holmes’ tremor was made. Her tremor was assessed by employing item 20 (tremor at rest) and item 21 (action or postural tremor) of the Unified Parkinson’s Disease Rating Scale (UPDRS). Initial treatment with levodopa (150 mg/day) and a dopamine agonist (pramipexole at 1.5 mg/day) improved the subscore from 3 to 1 for the resting component of her tremor, but the postural and kinetic components were unchanged (subscore of 4). She refused to take dopaminergic agents because of nausea. Therefore, ZNS was started at a dose of 100 mg twice daily. After a few days, her resting and postural/kinetic tremors were markedly improved from 3 to 1 and from 4 to 1, respectively, and she was able to perform most daily activities by herself, such as cooking, eating meals, changing clothes, and cleaning. ZNS therapy has been well tolerated, and improvement of her tremor persists after 8 months of follow-up. S. Suda (&) M. Yamazaki K. Katsura T. Fukuchi M. Ueda H. Nagayama Y. Katayama Divisions of Neurology, Nephrology, and Rheumatology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan e-mail: suda-sa@nms.ac.jp