DBS for ET

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Background

Essential tremor (ET) is the most common movement disorder (1). In patients who remain refractory to medical therapy, one surgical option is the placement of a deep brain stimulator (DBS) in the ventral intermediate (Vim) nucleus of the thalamus. DBS replaces the physiologic effect of a thalamotomy (by radiofrequency or radiosurgical technique), with the advantages of being adjustable and reversible. There are now numerous studies on the safety and efficacy of DBS for essential tremor (2-5,29).

Pathophysiology

ET is characterized by bilateral action tremor of the hands and forearms, head, and less commonly voice, in the absence of other neurologic signs (7). The vast majority of patients with ET suffer from mild tremor which can be treated with various medications; however, a smaller subset of patients suffer significant disability. Approximately 10% of patients presenting to a movement disorder clinic suffer from severe motor disabilities, which can be practically defined as any tremor which feeding, drinking, writing, or, in the case of vocal tremor, with communication (8). Although the natural history of ET has not been systematically studied, it is widely accepted that ET is a slowly progressive disease in which major spontaneous improvements are never seen. As ET advances, the frequency of the tremor decreases and the amplitude increases. For these patients, the first line medical treatments include propanolol and primidone (9). For those who fail medical therapy, surgery is an effective option.

Theory behind DBS

The theoretical basis for targeting the Vim nucleus of the thalamus for the relief of tremor is not well understood. Vim receives its major afferent projections from deep cerebellar nuclei which then project to the motor cortex (10). Microelectrode recording of the Vim in patients with essential tremor identifies cells discharging in bursts that are time-locked to the patient's tremor, suggesting that tremor is associated with abnormal discharge in the cerebellothalamic pathway (11). Interruption of this pathway via lesioning or stimulation provides some theoretical basis for the empirical observation of tremor improvement, but a more precise understanding is still unknown. Although the Vim nucleus of the thalamus is the target for both thalamotomy and DBS, the results and side-effect profiles differ between the two therapies. Stereotactic thalamotomy for ET has been performed and patients have been studied for the past fifty years. It is effective in 73 to 93 percent of patients with incapacitating tremor (12-14). However, this destructive lesioning procedure is associated with permanent complications. (12, 13, 15, 16). In addition, bilateral thalamotomy carries an even higher risk of dysarthria as well as debilitating cognitive complications and is thus no longer recommended (17, 18). Given the high rate of complications with bilateral thalamotomy and because of the destructive nature of the procedure, Benabid et al. introduced high-frequency deep brain stimulation using permanently implanted brain electrodes as an effective alternative in 1987 (19). Since that initial publication, DBS has gained in popularity because of its reversibility, adjustability, and lower side effect profile. High frequency stimulation of the Vim nucleus of the thalamus has been shown to be highly effective in the suppression of tremor (4, 19-23). The stimulation provides tremor relief on the contralateral side to the stimulator, completely eliminating tremor in as many as 50% of patients. In the North American multi-center trial, unilateral DBS of the Vim thalamus in 29 patients provided moderate to marked improvement of tremor at one year (2). In a European multi-center study, 89% of 37 patients with ET demonstrated significant tremor relief at one year (4). Recent follow-up studies for both the North American and European multi-center studies have demonstrated maintenance of benefit at two years and six years respectively (5, 21). The results of our study corroborate the improved patient outcome that can be seen with placement of indwelling brain stimulators.

Benefits

In addition to suppression of the primary symptom of tremor, DBS has been shown to improve quality of life as measured by standardized scales (24). Patients report a dramatic improvement in their handwriting, ability to drink liquids from a cup, and to conduct pursuits they had previously abandoned such as golf and social activities. Schuurman et al. randomized patients with ET to thalamotomy (n=6) or thalamic stimulation (n=7) and demonstrated improved functional status in the thalamic stimulation group as compared to the thalamotomy group as measured with the Frenchay Activities Index (24). Tremor suppression was achieved in both groups at similar rates.

Side Effects

The side effects of thalamic stimulation include dysarthria (in 3 to 18 percent of patients), paresthesias (in 6 to 36 percent), dystonia (in 2 to 9 percent), balance disturbance (in 3 to 8 percent), ataxia (in 6 percent), and limb weakness (in 4 to 8 percent) (2, 23, 25). These side effects are mostly reversible and tolerable as patients prefer to keep the stimulator on despite these side effects. (26) In addition, the neurologic and cognitive complications from DBS appear to be reduced when compared to the complications associated with thalamotomy. In their randomized trial between thalamotomy and thalamic stimulation, Schuurman et al. demonstrated more complications in the patients randomized to thalamotomy (24). In addition, Troster et al. used extensive and sophisticated neuropsychological methods to demonstrate that patients with Vim thalamic stimulation have preserved cognitive functioning (27). Hence, the neurologic and cognitive complications of DBS appear to be lower than that of lesioning methods.

Surgical Technique

At the University of Pittsburgh, we perform DBS surgery under local anesthesia using the Leksell stereotactic system (Elekta Instruments, Atlanta, GA) (29). The anterior (AC) and posterior (PC) commissures were noted. Fast inversion recovery sequences in the axial and coronal plane are used to identify the location of the internal capsule, and to help select a safe trajectory from the pre-coronal frontal lobe cortical surface down into the thalamus. The standard thalamic target is: ¼ of the AC-PC distance plus 1-2mm, anterior to PC; ½ the third ventricle width plus 11mm, lateral into the thalamus; depth is at the AC-PC line. The lateral target is adjusted to avoid the medial edge of the internal capsule. We use a 14mm burr hole and the Stim-Lock fixation device to secure the lead. The DBS electrode lead is inserted into the thalamus for stimulation testing. Different electrode contacts are used for stimulation, with testing that used 170 to 185 Hertz, a 90 microsecond pulse width, and 0 to 3 volts. If stimulation led to tremor cessation without side effects, the electrode is kept in place. Although some centers use microelectrode recording, we typically do not except in rare cases. For example, if the patient would have described a weak arm or leg, or increased muscle tone, the lead was to be moved medially by 1.5 mm. If numbness or tingling was persistent, the lead was to be moved 2mm anterior. If little or no tremor response was found upon initial lead placement, the lead was to be moved 1-2 mm posterior.

Assessing outcomes

Neurologic improvement in tremor is tested by selecting items from the Fahn-Tolosa clinical tremor rating scale. Surgical complications can include lead breakage, temporary erythema of the pulse generator incision requiring oral antibiotics, pocket site infection, electrode migration (rare with current fixation devices) requiring surgery to pull back the lead, neck or chest injury (rare), and mild hand tingling during stimulation. These types of complications must continue to be carefully documented and carefully considered in the decision to place a deep brain stimulator.


References

Reference List

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