Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease

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Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease

KRACK, Paul, et al.

KRACK, Paul, et al . Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease. The Lancet , 1997, vol. 350, no. 9092, p. 1675

PMID : 9400514

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Research letters

THE LANCET

Stimulation of subthalamic nucleus alleviates tremor in Parkinson’s disease

P Krack, P Pollak, P Limousin, A Benazzouz, A L Benabid

STN in the pathophysiology of parkinsonian tremor. STN stimulation can be considered as an alternative to Vim or pallidal surgery, even in patients severely disabled by parkinsonian rest and postural tremor, since it induces a dramatic effect not only on akinesia and rigidity,¹but also on tremor. In our centre, 49 patients with Vim stimulation for predominant tremor were followed up for longer than 4 years.

In 32 (65%) the most disabling symptoms were motor fluctuations, levodopa-induced dyskinesias, or both, whereas tremor was well controlled. In patients with tremor-dominated PD, STN stimulation should be preferred to Vim stimulation since most of these patients will develop disabling akinesia not improved by Vim stimulation.

1 Limousin P, Pollak P, Benazzouz A, et al. Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet1995;

345:91–95.

2 Benabid AL, Pollak P, Gervason C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.Lancet1991;337:403–06.

3 Lozano AM, Lang AE, Galvez-Jimenez N, et al. Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet1995;

346:1383–87.

4 Bergman H, Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science1990;

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Department of Clinical and Biological Neurosciences, University of Grenoble, Grenoble, France; and Neurology Department, University of Kiel, 24105 Kiel, Germany (P Krack)

Vol 350 • December 6, 1997 1675

Tremor can be a disabling and drug-resistant symptom of Parkinson’s disease (PD). Thalamotomy or thalamic stimulation are known to alleviate this type of tremor, but the benefit of these procedures on rigidity or akinesia is moderate to nil. With improved understanding of the pathophysiology of PD, other surgical therapies have been developed, of which subthalamic nucleus (STN) stimulation is one of the most promising.¹ We studied the efficacy of STN stimulation on tremor in patients with the complete parkinsonian triad.

Of 27 consecutive patients with STN stimulation (26 bilateral) operated on according to a method previously described,¹15 exhibited tremor which rated at least two out of four according to item 20 (rest tremor) of the Unified Parkinson’s Disease Rating Scale (UPDRS) in at least one limb. Patients’ characteristics were the following: nine women and six men, mean age 60 (SD 8) years, duration of the disease 14 (4) years, levodopa dose 1200 (750) mg daily, and 13 patients were treated by dopamine-agonist drugs.

Our study received the approval of the Grenoble University ethical committee and all patients gave written informed consent. The mean preoperative and postoperative UPDRS III (total motor score, maximum 108) and a tremor subscore (five body parts for item 20, two body parts for item 21, maximum score 28) in on-drug and off-drug, and in on-stimulation and off-stimulation (stim) conditions are:

Preoperative Postoperative

Off-drug On-drug Off-drug, Off-drug, On-drug, On-drug off-stim on-stim off-stim on-stim UPDRS III 63 (15) 22 (10) 50 (17) 28 (15) 21 (11) 17 (9) Tremor 11·3 (5·6) 1·2 (2·4) 7·4 (5·2) 2·2 (2·2) 0·6 (1·2) 0·2 (0·4)

The preoperative tremor score in on-drug and off-drug conditions is compared with the postoperative tremor score on-stimulation in the same drug conditions (figure). The improvement was significant (Wilcoxon test) in both on-drug and off-drug conditions (figure).

Stimulation of the ventral intermediate nucleus of the thalamus (Vim) greatly improves tremor in 88% of patients with PD, but rigidity is only moderately improved and akinesia is not improved.² Pallidotomy improves contralateral tremor, but is generally done unilaterally because of high morbidity after bilateral lesions.³So far, the effects of pallidal stimulation on tremor are not well documented. In monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, lesions of the STN have been shown to be effective in alleviating tremor.⁴ Moreover, a rhythmic firing of STN neurons was found synchronous to tremor.⁵Our results favour the importance of the oscillation of a neuronal loop involving

15 Off-medication

On-medication

†

*

Before surger y After surger y on-stimulation 10

Tremor score

5

0

Effect of STN stimulation in tremor in 15 PD patients, 14 with bilateral and one with unilateral stimulation, after a follow-up of 1–12 months

*p<0·01, †p<0·001.