Stereotactic Radiosurgery for Movement Disorders

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Stereotactic Radiosurgery for Movement Disorders

Joel Bauman and John Y. K. Lee

The field of movement disorder functional neurosurgery has undergone a renaissance over the past 15 years. In large part, this is due to the rise of deep brain stimulation (DBS) in the treatment of medically refractory movement disorders. Within this setting, permanently destructive neuroablative procedures have become less popular. However, Gamma Knife (Elekta Instruments AB, Stockholm, Sweden) and occasionally linear accelerator (linac)–based radiosurgical units to perform thalamotomies and pallidotomies may still have some role in the neurosurgeon’s ability to treat movement disorders. Neuroablation with high-dose radiation is the least invasive method, eliminating complications such as hemorrhage, infection, and hardware breakage. It can thus be performed on patients with significantly higher surgical risk factors for open procedures, such as medical comorbidities and intolerance of an awake procedure. Here we review the evidence for radiosurgical lesioning in the treatment of patients with medically refractory movement disorders. For comparison and context, we also briefly review the evidence for radiofrequency ablation as well as DBS.

Surgical Thalamotomy and Thalamic Deep Brain Stimulation

Until Benabid introduced DBS in 1987, radiofrequency (RF) lesioning of the ventral intermediate nucleus (Vim) of the thalamus was the primary method for treatment of medically intractable tremor-predominant Parkinson disease and essential tremor.1–3 Before considering the merits of radiosurgical thalamotomy, it is worthwhile to review the role of conventional RF thalamotomy in the treatment of tremor, particularly as it compares with DBS. In patients with essential tremor, Schuurman et al compared DBS to RF lesioning and found results slightly favoring DBS.⁴ Tremor suppression was achieved in 79% of patients who had had a thalamotomy, compared with 90% of patients who underwent DBS. More patients who underwent DBS achieved functional improvement. In addition, Tasker compared data from patients who had undergone RF thalamotomy and thalamic stimulation and found clearly superior results with DBS.⁵ He found tremor recurrence in 15% of patients who had had a thalamotomy, as opposed to 5% of patients who underwent DBS. Of the patients who had a thalamotomy, 23% required repeat procedures for tremor control. Only half of the thalamotomy cohort obtained 50% improvement in dexterity, writing, and drinking, whereas all of the DBS subgroup achieved improvement. Furthermore, thalamotomy resulted in a decline in writing performance in 23% of patients, as opposed to no patient in the DBS group, whereas all of the patients who underwent DBS achieved better than 50% improvement in dexterity, writing, and drinking ability.

Complications of thalamotomy can be significant, especially when performed bilaterally. Common complications of bilateral thalamotomy include dysarthria and ataxia,^5–7 which have resulted in a desire to avoid bilateral ablation procedures. Schuurman et al found that patients who had RF thalamotomy were more likely to develop somnolence, cognitive deterioration, dysarthria, and ataxia compared with a randomized prospective cohort of patients who underwent DBS, although both groups had excellent symptomatic control of tremor.⁸ When these complications occur in patients who undergo DBS, an adjustment of the stimulation parameters can usually correct these problems.⁵ These studies highlight the factors behind the shift away from ablative procedures: efficacy, safety, and reversibility of adverse effects. Unlike thalamotomy, the therapeutic index of DBS (e.g., the difference between beneficial effect and adverse effect) can be navigated through careful programming.⁹ It is in this context that the use of radiosurgical thalamotomy must be considered.

Radiosurgical Thalamotomy

Gamma Knife thalamotomy differs from RF thalamotomy in several key aspects. Gamma Knife thalamotomy is minimally invasive: there is no incision, bur hole, or physical penetration of any brain parenchyma. Thus, the risk of hemorrhagic or infectious complications is potentially lower than RF thalamotomy. In contrast, targeting for a Gamma Knife thalamotomy relies solely on imaging-defined anatomy. Physiologic macrostimulation and microelectrode recording are not available to assist the operator. Additionally, lesion generation is delayed and can be variable in size, as suggested by some recent publications.10 Thus, Gamma Knife thalamotomy has both advantages and disadvantages that may shape its role in the treatment of movement disorders.

The current technique for targeting the Vim thalamus is similar to conventional stereotactic procedures. The Leksell model G stereotactic frame (Elekta) is attached to the patient’s head, and high-resolution magnetic resonance (MR) images are obtained with a 1.5 tesla scanner. Contrast-enhanced images are acquired, including through the basal ganglia, midbrain, third ventricle, and anterior and posterior commissures (AC, PC). Axial fast inversion recovery sequences are performed for optimal gray-white differentiation and identification of the internal capsule. The Vim contralateral to the predominant tremor extremity is targeted as follows: anterior-posterior is one quarter the AC distance plus 1 mm anterior to PC; laterality is one half the third ventricle width plus 11 mm; superior-inferior is 2.5 mm superior to the AC-PC line. The 20% isodose line of the 4 mm collimator shot is placed medial to the internal capsule. A gamma angle of 110 degrees sometimes allows for better conformity to Vim in anterior-posterior and superior-inferior planes. On the model U Gamma Knife, beam blocking is not necessary, and a gamma angle of 60 to 70 degrees is used. The maximum dose of 130 to 140 Gy is delivered with one 4 mm isocenter.

There are several case series of Gamma Knife thalamotomy patients in the literature, documenting the success of this technique for the treatment of tremor. Friehs et al first examined thalamic radiosurgical lesioning in patients who had a contralateral RF lesion or a previously mapped lesion.¹¹ To date, Ohye et al have reported radiosurgical thalamotomy in 70 patients with Parkinson disease.¹⁰ Tremor was suppressed by at least two thirds in over 80% of patients, with continued effect even after 10 years in some patients.^10,12 However, a significant subset of these patients had undergone a prior contralateral stereotactic procedure or ipsilateral procedure and were thus receiving a radiosurgical “boost.” In this respect, the anatomical targeting was assisted. Duma et al reported a series of 38 radiosurgical thalamotomies over a 5-year period. In this series of patients, 24% had complete relief of tremor, 55% had “excellent or good” improvement in their tremor, and 21% of patients had only “mild” or no relief of tremor. Median follow-up was 28 months.^13,14 Importantly, only four of these patients underwent bilateral procedures.

Young et al published the largest series of patients undergoing Gamma Knife thalamotomy. The authors retrospectively reviewed records of 158 patients who had undergone radiosurgical thalamotomy for tremor, including 102 patients with Parkinson disease and 52 with essential tremor (ET).¹⁵ Four-year follow-up data were available for 48% of the patients, including 74 patients with Parkinson disease and 16 with ET. Fifty-nine of the patients with Parkinson disease (79.7%) and 14 of the patients with ET (87.5%) were still tremor free or nearly tremor free at this interval. Two patients experienced permanent neurologic deficits, including hemiparesis and mild facial paresthesias. One patient sustained a transient deficit. No cognitive changes were reported. Young et al’s finding of 88% of patients tremor free or nearly tremor free at 4 years following Gamma Knife thalamotomy is remarkable; however, the results for ET should be interpreted with caution, as follow-up involved less than one third of the treatment group. Similarly, Niranjan et al found that Fahn-Tolosa-Marin grades of tremor, handwriting, and drawing showed marked improvement after radiosurgical thalamotomy, including complete tremor arrest in 75% of patients with ET.¹⁶ In an update of the Pittsburgh series, Kondziolka et al demonstrated significant improvement in action tremor in 88% of patients with Gamma Knife thalamotomy.¹⁷ Typically, the response time was 1 to 4 months; however, three patients improved significantly within 2 days. Tremor and handwriting scores were both improved in 69% of patients. Three patients (12%) had no change in their tremor and writing scores. One patient experienced a mild right hemiparesis and speech impairment following radiosurgery. Another patient had a transient mild right hemiparesis and dysphagia. No other complications were noted. The overall complication rate was 7.7% (2/26). Both patients eventually maintained only mild neurologic deficits.

One difference between Gamma Knife radiosurgical thalamotomy and RF thalamotomy is the time for radiosurgical lesioning to take effect. Benefits and complications from radiosurgery occur between 1 and 12 months after the procedure.^10,13,16 This delay is due to the time needed for radiation to functionally damage or destroy the targeted tissue. The lesion effect can be accelerated with increased doses;¹⁸ however, the optimal dose for Gamma Knife radiosurgical lesioning has not been established. Peak central doses can range from 120 to 200 Gy. Duma et al reported an improved clinical outcome with higher doses, suggesting a dose-response curve.¹⁴ However, Okun et al reported a high percentage of complications in a series of eight patients, seven of whom were treated with a maximum dose of 200 Gy.¹⁹ To date, a systematic study of dose-response-complication rate has not been performed. Nonetheless, most neurosurgeons perform radiosurgical lesioning for functional disorders at lower doses (e.g., 140 Gy).¹⁶

Because of the delay in effect after Gamma Knife thalamotomy, an accurate documentation of complications requires vigilant follow-up. In Young et al’s series, 3 of 74 patients developed a complication.¹⁵ Other reports consist of single events without mention of the total number of procedures or patients undergoing treatment. Siderowf et al reported one case of a complex, involuntary movement after Gamma Knife radiosurgical thalamotomy.²⁰ Unfortunately, particular dose parameters were not specified in that case report. Okun et al reported a series of eight patients who developed multiple complications, including hemiplegia, homonymous visual field deficit, hand weakness, dysarthria, hypophonia, aphasia, arm and face numbness, and pseudobulbar laughter.¹⁹

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