BRAIN INJURY, 1 9 9 1 , VOL. 5, NO. 2,213-218

Case study

Treatment of post-traumatic midbrain resting-kinetic tremor with combined levodopa/carbidopa and carbamazepine

ROBERT L. HARMON, DAVID F. LONG andJEANNINE SHIRTZ Bryn Mawr Rehabilitation Hospital, Malvern, PA 19355, USA

(Received 30 April 1990; accepted 27 May 2990)

A patient with a post-traumatic midbrain haemorrhagic lesion documented by magnetic resonance imagmg (MRI) presented with a combined resting-kinetic contralateral upper extremity tremor. The resting tremor component responded to levodopa/carbidopa, while the kinetic component improved with the addition of carbamazepine.

Introduction

Various post-traumatic movement disorders have been described, including tremors related to lesions in the midbrain [l]. These tremors are ofien refractory to management, although improvement has been noted with stereotactic thalamotpmy [2,3] and medications such as propranolol and clonazepam [1,4]. Additionally, levodopa has been found to suppress a post-traumatic postural and kinetic tremor [5] and a ‘rubral’ tremor associated with an arteriovenous malformation (AVM) and a subarachnoid haemorrhage [6]. A case is now presented of a combined resting-kinetic tremor following traumatic brain injury with an associated midbrain lesion. The response of the tremor to pharmacological management is presented and discussed.

Case report

A 36-year-old, left-handed, diabetic female sustained traumatic brain injury in a motor vehicle accident. Following brief loss of consciousness, neurological deficits included left hemiparesis and diplopia. Compute tomography (CT) of the head revealed an area of increased density in the right thalamic and midbrain region. Cerebral arteriography was without evidence of vascular malformation or aneurysm. Neurological deficits cleared rapidly and the patient was discharged from the acute-case hospital 9 days post-injury. About 2 months later, the patient developed a combined resting-kinetic tremor of the left

Address correspondence to: Robert L. Harmon, MD, Department of Rehabilitation Medicine, University of Wisconsin-Madison Medical School, E3/348 Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.

0269-9052/91 $3.00 0 1991 Taylor & Francis Ltd.

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Figure 1 . (a,b) ,MRI images of thr hmirr .Awir!p ,7 /rsioir i r r the right red ~ U C ~ K U S and adjacent tgmenta l area.

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Post-traumatic midbrain resting-kinetic tremor with levodopa/carbidopa and curbamazepine 2 15

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Figure 2 (a). Surface E M G recordings ofselected /I$ upper extremity muscles (top to bottom: deltoid, biceps brachii, triceps, extensor carpi radialis longus) showing (a) E M G activity with continuous tremor resting compo- nent oJmedications and (b) E M G activity during intermittent tremor resting component on optimal levadopa/ carbidopa and carbamarepine dosages (vertical scale- 1 m Vldivision; horizontal scare-200 ms/division).

upper extremity. Magnetic resonance imaging (MRI) of the brain 1 month post-injury revealed an area of signal alteration in the right red nucleus and adjacent tegmental area (Figure 1). Over the next 6 months, the tremor progressively worsened to where the patient was unable to use the left upper extremity for any s u e d task including writing or drinlung from a cup.

The tremor was virtually continuous at about 3 Hz at rest, with tremor amplitude increasing with activity such as attempted rapid finger movement or writing. Tremor amplitude was maximal for wrist flexion/extension and pronation/supination with proximal spread prominant with activity. Finger-to-nose testing of the left upper extremity showed the tremor movements to remain in the plane of wrist flexion/extension rather than exhibiting side-to-side displacement. The lefi upper extremity tended to assume a flexor synergy posture with the patient sitting at rest or during ambulation. Mild left hemiparesis, mild word-finding dif€iculties and concentration deficits were also noted on examination. No palatal myoclonus was observed. There was no significant rigidity or akinesia appreciated.

A series of therapeutic trials were undertaken. The tremor remained disabling, despite

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trunk stabilization and application of 0.5 kg and 1 kg weights to the lefi upper extremity. Approximately 50% improvement in the tremor was noted with propranolol 70 mg/day orally in divided doses, but this was discontinued due to diabetic concerns. Primidone (100 mg/day in divided doses) and amantadme (200 mg/day in divided doses) provided no objective benefit. However, with levodopa, significant improvement was noted in the tremor resting component to the degree that it had become only intermittent. The dosage was gradually titrated to 25 mg/250 mg (carbidopa/levodopa) six times/day orally for maximal response. Improvement in the tremor kinetic component was observed when carbamazepine was added at 200 mg orally three timedday to achieve serum levels of 6-8 pg/ml; carbamazepine alone, however, &d not objectively improve the tremor. The tremor returned to the original intensity of the resting and kinetic components when the levopoda/carbidopa and carbamazepine were weaned off and again improved to the optimal response when the above regiment was reinstated.

The levodopa/carbidopa and carbamazepine regimen improved the lefi upper extremity tremor to where the patient could again use this arm for functional tasks such as opening doon and carrying objects, although writing was still impaired. Timed buttoning of four shirt buttons improved from 51.8 s off the medications to 20.7 s on the optimum regmen; tymg of the lefi shoelace from 46.7 s to 27.2 s, and Purdue Pegboard? testing t Business Programs Division, Science Research Associates Inc., 155 North Wacker Drive, Chicago, Illinois 60606. USA.

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Post-traumatic midbrain resting-kinetic tremor with levodopa/carbidopa and carbamazepine 2 17

from not being able to manipulate the test components with the left hand to completing two to five tasks with the left hand on repeated testing.

Surface electromyographic (EMG) recordings of selected left upper extremity muscles involved by the tremor resting component were performed with the patient both on and off the optimum levodopa/carbidopa and carbamazepine regimen. The tremor resting component EMG activity was notably diminished in multiple muscles with the medications but the frequency was not significantly changed (Figure 2).

Discussion

Kremer and associates [7] identified three patients with coarse ‘Parkinsonian-like’ tremor following traumatic midbrain injury. Subsequent studies have continued to support the importance of midbrain structures in the development of post-traumatic tremors, although radiographic confirmation has not always been available [l]. In the case presented, a lesion in the red nucleus and adjacent tegmental region contralateral to the involved extremity was documented on MRI. The associated tremor had two components that could be differentiated pharmacologically, with levadopa/carbidopa improving the resting component and the further addition of carbamazepine improving the kinetic component.

While two previous cases of midbrain tremor responding to levadopa have been reported [5,6], specific response of the tremor resting component appears unique to the present case. Carbamazepine has been effective for cerebellar outflow tremors in patients with multiple sclerosis and strokes [S]. The cerebellothalomo cortical relay has been considered important to the generation of these cerebellar tremors, with the thalamic ventralis intermedius nucleus a possible site for carbamazepine action [8]. Ohye and associates [9] have reported that in monkeys a lesion of the nigrostriatal pathway is needed, in addition to involvement of the cerebellothalamic tracts crossing the red nucleus region and the parvocellular division of the red nucleus, in order to produce spontaneous tremor. If these findings hold true for man, they suggest an explanation for the improvement of the tremor in the present case on combined levadopa/carbidopa and carbamazepine. Further investigations of the response of specific components of post-traumatic midbrain tremors to specific pharmacological agents appear warranted.

Acknowledgement

The authors wish to thank Pamela Harmon, RN, for her technical assistance.

References

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2. ANDREW, J., FOWLER, C. J. and HARRISON, M. J. G.: Tremor after head injury and its treatment by stereotaxic surgery. Journal of Neurology, Neurosurgery and Psychiatry, 45: 815-819, 1982.

3. BULLARD, D. E. and NASHOLD, B. S.: Post-traumatic movement disorders. In: L.D. Lunsford (Ed.) Modern Stereotactic Neurosurgery. (Martinus Nijhoff Publishing, Boston), pp. 341-352, 1988.

4. BIARY, N., CLEEVES, L., FINDLEY, L. and KOLLER, W.: Post-traumatic tremor. Neurology, 39:

5. SAMIE, M. R., SELHORST, J. B., KOLLER, W. C.: Post-traumatic midbrain tremors. Neurology,

6. FINDLEY, L. J., GRESTY, M. A,: Suppression of ‘rubral’ tremor with levadopa. British Medical

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8. SECHI, G. P., ZUDDAS, M., PIREDDA, M., et a!.: Treatmcnt of cerebellar tremors with carbamazcpinc: a controlled trial with long-tcrm follow-up. Neurology, 39: 1 1 1 3-1 11 5, 1989.

9. OHYE, C., SHIBAZAKI, T., WADA, H., e f al.: A spccial role of the parvocellular red nucleus in lesion-induced spontaneous tremor in monkcys. Behaviour Brain Research, 28: 241-243, 1988.

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