Susan Heath

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes

Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising new procedure for the treatment of dystonia. The authors present their technical approach for placement of electrodes into the GPi in awake patients with dystonia, including the methodology used for electrophysiological mapping of the GPi in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. Methods. Twenty-three adult and pediatric patients who had various forms of dystonia were included in this study. Baseline neurological status and improvement in motor function resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Implantation of the DBS lead was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. Conclusions. Physiologically guided implantation of DBS electrodes in patients with dystonia is technically feasible in the awake state in most cases, with low morbidity rates. Spontaneous discharge rates of GPi neurons in dystonia are similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than by rates. Active electrode locations associated with robust improvement (> 50% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance of 3.7 mm from the pallidocapsular border. Patients with juvenile-onset primary dystonia and those with the tardive form benefited greatly from this procedure, whereas benefits for most secondary dystonias and the adult-onset craniocervical form of this disorder were more modest.

Pallidal deep brain stimulation in patients with cranial–cervical dystonia (Meige syndrome)

Idiopathic cranial–cervical dystonia (ICCD) is an adult‐onset dystonia syndrome affecting orbicularis oculi, facial, oromandibular, and cervical musculature. ICCD is frequently difficult to treat medically. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective treatment for idiopathic generalized dystonia, however less is known about the effect of GPi DBS on ICCD. In this article, we present the results from a pilot study assessing the effect of GPi DBS in a series of patients with ICCD. Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi. Patients were evaluated with the Burke–Fahn–Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively. At 6 months, patients showed a 72% mean improvement in the BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test). The mean BFMDRS disability score showed a trend toward improvement (P < 0.06). The total TWSTRS score improved 54% (P < 0.043). Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients. Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.

Thalamic Deep Brain Stimulation for Essential Tremor: Relation of Lead Location to Outcome

OBJECTIVE:Thalamic deep brain stimulation (DBS) is commonly used to treat essential tremor, but the optimal lead location within the thalamus has not been systematically evaluated. We examined the relation of lead location to clinical outcome in a series of essential tremor patients treated by thalamic DBS. METHODS:Fifty-seven leads in 37 patients were studied. Lead locations were measured by postoperative magnetic resonance imaging. Contralateral arm tremor was assessed in the DBS-on and DBS-off states using the Fahn-Tolosa-Marin tremor rating scale, with a mean follow-up of 26 months. Lead locations were statistically correlated, using analysis of variance, with percent improvement in tremor resulting from DBS activation. RESULTS:Improvement in tremor score was significantly correlated with lead location in both the anteroposterior and lateral dimensions. In the plane of the commissures, the optimal electrode location was determined statistically to be 6.3 mm anterior to the posterior commissure and 12.3 mm lateral to the midline, or 10.0 mm lateral to the third ventricle. CONCLUSION:Optimal electrode location for thalamic DBS in essential tremor corresponds to the anterior margin of the ventralis intermedius nucleus. Leads located greater than 2 mm (in the plane of the commissures) from the optimal coordinates are more likely to be associated with poor tremor control than leads within 2 mm of the optimal location. The incidence of true physiological tolerance to the antitremor effect of thalamic DBS (defined as poor tremor control in spite of lead location within 2 mm of the optimal site) was found to be 9%.

Subthalamic nucleus deep brain stimulation in primary cervical dystonia

Objectives: The globus pallidus internus (GPi) has been the primary target for deep brain stimulation (DBS) to treat severe medication-refractory dystonia. Some patients with primary cervical or segmental dystonia develop subtle bradykinesia occurring in previously nondystonic body regions during GPi DBS. Subthalamic nucleus (STN) DBS may provide an alternative target choice for treating dystonia, but has only been described in a few short reports, without blinded rating scales, statistical analysis, or detailed neuropsychological studies. Methods: In this prospective pilot study, we analyzed the effect of bilateral STN DBS on safety, efficacy, quality of life, and neuropsychological functioning in 9 patients with medically refractory primary cervical dystonia. Severity of dystonia was scored by a blinded rater (unaware of the patients preoperative or postoperative status) using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and 3, 6, and 12 months postsurgery. Lead location, medications, and adverse events were also measured. Results: STN DBS was well-tolerated with no serious adverse effects. The TWSTRS total score improved (p < 0.001) from a mean (±SEM) of 53.1 (±2.57), to 19.6 (±5.48) at 12 months. Quality of life measures were also improved. STN DBS induced no consistent neuropsychological deficits. Several patients reported depression in the study and 3 had marked weight gain. No patients developed bradykinetic side effects from stimulation, but all patients developed transient dyskinetic movements during stimulation. Conclusions: This prospective study showed that bilateral STN DBS resulted in improvement in dystonia and suggests that STN DBS may be an alternative to GPi DBS for treating primary cervical dystonia. Classification of evidence: This study provides Class III evidence that bilateral subthalamic nucleus deep brain stimulation results in significant improvement in cervical dystonia without bradykinetic side effects.

Long-term follow-up of pallidal deep brain stimulation in two cases of Huntington's disease

Background Deep brain stimulator (DBS) implantation has been shown to be effective in the treatment of various movement disorders including Parkinsons disease, essential tremor and dystonia. However, there is limited information regarding the potential use of DBS in Huntingtons disease (HD). In this study, the authors present their findings on the long-term motor and neurocognitive results of two HD patients (patient 1: 57 years, 42 cytosine-adenine guanine (CAG) repeats; patient 2: 50 years, 41 CAG repeats) who underwent staged bilateral globus pallidus interna DBS surgery. Methods The patients were evaluated at baseline and at five timepoints throughout a 2-year postoperative during which motoric ratings ((Unified Huntingtons Disease Rating Scale), Activities of Daily Living scores (HD-ADL) and neurocognitive testing) were obtained. Results Both patients had a sustained decline in chorea 2 years after initial DBS surgery. Despite this improvement in chorea, one patient has had continuing deterioration in gait, bradykinesia and dystonia scores, which has caused his ability to perform activities of daily living to return to his baseline level of functioning prior to DBS surgery. Both patients have experienced further gradual decline in neurocognitive functioning, which appears to be independent of DBS and most likely related to disease progression. Conclusion DBS implantation may be a potential treatment option for a subset of HD patients who have significant functional deficits due to chorea. However, appropriate selection of the best candidates for DBS appears to be challenging, given the difficulty in predicting disease course in HD due to its variable nature.

Multiple target deep brain stimulation for multiple sclerosis related and poststroke Holmes' tremor.

Background: The results from thalamic deep brain stimulation (DBS) for atypical tremor syndromes including tremor from multiple sclerosis (MS) and stroke are often disappointing. Three recent case reports have suggested that simultaneous stimulation of multiple thalamic targets can result in sustained improvement in such cases. Methods: We analyzed the effectiveness of multiple target DBS in one patient with MS-related tremor and another with poststroke Holmes’ tremor. Results: In the patient with MS tremor, we implanted bilateral ventralis intermedius (V.im.) and ventralis oralis anterior (V.o.a.) thalamic electrodes; this patient had significant tremor improvement with stimulation of either V.im. or V.o.a. targets; however, we did not observe additive effects with simultaneous stimulation. In our patient with a poststroke Holmes’ tremor, we implanted DBS electrodes in unilateral V.im., V.o.a., and the globus pallidus internus (Gpi); this patient had moderate tremor reduction with Gpi stimulation alone; neither V.im. nor V.o.a. stimulation provided additional benefit. Conclusion: In one patient with MS tremor, simultaneous V.im. and V.o.a. stimulation was not superior to V.im. or V.o.a. stimulation alone. In one case of Holmes’ tremor, Gpi stimulation was a useful alternative to thalamic stimulation.

Fluoroscopic, EMG-guided injection of botulinum toxin into the longus colli for the treatment of anterocollis

BACKGROUND Anterocollis is a form of cervical dystonia characterized by forward neck flexion. While botulinum toxin is the treatment of choice for cervical dystonia, patients with anterocollis, who receive injections into the sternocleidomastoid and anterior scalene muscles, represent a disproportionate number of treatment failures. Deep cervical muscles such as the longus colli likely play an important role in neck flexion but are not routinely injected. OBJECTIVE To describe a technique for longus colli injection in cases of anterocollis and to report the clinical outcomes of 10 such injections of botulinum toxin. METHODS Three patients were referred for evaluation and treatment of anterocollis. All had previous treatment failures with sternocleidomastoid/anterior scalene injections or no activity noted on needle EMG investigation of these muscles. All patients received injections of botulinum toxin into the longus colli under fluoroscopic and EMG guidance. RESULTS All patients experienced symptomatic improvement (eight of 10 injections). Two patients reported mild dysphagia without serious complications after dose increases in botulinum toxin. CONCLUSIONS Incomplete muscle selection may be one cause of treatment failures in anterocollis. Deep cervical flexors such as the longus colli represent an under-recognized potential target for symptomatic treatment of anterocollis.

Subthalamic nucleus deep brain stimulation in isolated dystonia: A 3-year follow-up study

Objective: To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Twenty patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia were studied (14 were followed for 36 months). The primary endpoints were change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 36 months compared to preoperative baseline. Multiple secondary outcomes were also assessed (ClinicalTrials.gov NCT00773604). Results: Eighteen of 20 patients showed improvement 12 months after STN DBS with sustained benefit persisting for 3 years (n = 14). At 36 months, BFMDRS motor scores improved 70.4% from a mean 17.9 ± 8.5 to 5.3 ± 5.6 (p = 0.0002) and total TWSTRS scores improved 66.6% from a mean 41.0 ± 18.9 to 13.7 ± 17.9 (p = 0.0002). Improvement at 36 months was equivalent to that seen at 6 months. Disability and quality of life measures were also improved. Three hardware-related and 24 stimulation-related nonserious adverse events occurred between years 1 and 3 (including 4 patients with dyskinesia). Conclusions: This study offers support for long-term tolerability and sustained effectiveness of STN DBS in the treatment of severe forms of isolated dystonia. Classification of evidence: This study provides Class IV evidence that STN DBS decreases long-term dystonia severity in patients with medically refractory isolated dystonia.

THALAMIC DEEP BRAIN STIMULATION FOR ESSENTIAL TREMOR

OBJECTIVE Thalamic deep brain stimulation (DBS) is commonly used to treat essential tremor, but the optimal lead location within the thalamus has not been systematically evaluated. We examined the relation of lead location to clinical outcome in a series of essential tremor patients treated by thalamic DBS. METHODS Fifty-seven leads in 37 patients were studied. Lead locations were measured by postoperative magnetic resonance imaging. Contralateral arm tremor was assessed in the DBS-on and DBS-off states using the Fahn-Tolosa-Marin tremor rating scale, with a mean follow-up of 26 months. Lead locations were statistically correlated, using analysis of variance, with percent improvement in tremor resulting from DBS activation. RESULTS Improvement in tremor score was significantly correlated with lead location in both the anteroposterior and lateral dimensions. In the plane of the commissures, the optimal electrode location was determined statistically to be 6.3 mm anterior to the posterior commissure and 12.3 mm lateral to the midline, or 10.0 mm lateral to the third ventricle. CONCLUSION Optimal electrode location for thalamic DBS in essential tremor corresponds to the anterior margin of the ventralis intermedius nucleus. Leads located greater than 2 mm (in the plane of the commissures) from the optimal coordinates are more likely to be associated with poor tremor control than leads within 2 mm of the optimal location. The incidence of true physiological tolerance to the antitremor effect of thalamic DBS (defined as poor tremor control in spite of lead location within 2 mm of the optimal site) was found to be 9%.

Thalamotomy-Like Effects From Partial Removal of a Ventral Intermediate Nucleus Deep Brain Stimulator Lead in a Patient With Essential Tremor: Case Report.

BACKGROUND AND IMPORTANCE The ventral intermediate nucleus of the thalamus is a primary target of deep brain stimulation (DBS) in patients with essential tremor. Despite reliable control of contralateral tremor, there is sometimes a need for lead revision in cases of infection, hardware malfunction, or failure to relieve symptoms. Here, we present the case of a patient undergoing revision after ventral intermediate nucleus (Vim) DBS failed to control his tremor. During the electrode removal, the distal portion of the lead was found to be tightly adherent to tissue within the deep brain. Partial removal of the electrode in turn caused weakness, paresthesias, and tremor control similar to the effects produced by thalamotomy or thalamic injury. CLINICAL PRESENTATION A 48-year-old man with essential tremor had bilateral Vim DBS leads implanted 10 years earlier but had poor control of his tremor and ultimately opted for surgical revision with lead placement in the zona incerta. During attempted removal of his right lead, the patient became somnolent with contralateral weakness and paresthesias. The procedure was aborted, and postoperative neuroimaging was immediately obtained, showing no signs of stroke or hemorrhage. The patient had almost complete control of his left arm tremor postoperatively, and his weakness soon resolved. CONCLUSION To the best of our knowledge, this is the first reported case of cerebral injury after DBS revision and offers insights into the mechanism of high-frequency electric stimulation compared with lesions. That is, although high-frequency stimulation failed to control this patients tremor, thalamotomy-like injury was completely effective.