Steven B. Wilkinson

Real-time automated detection and quantitative analysis of seizures and short-term prediction of clinical onset.

Summary: Purpose: We describe an algorithm for rapid realtime detection, quantitation, localization of seizures, and prediction of their clinical onset.

Automated seizure abatement in humans using electrical stimulation

The need for novel, efficacious, antiseizure therapies is widely acknowledged. This study investigates in humans the feasibility, safety, and efficacy of high‐frequency electrical stimulation (HFES; 100–500Hz) triggered by automated seizure detections. Eight patients were enrolled in this study, which consisted of a control and an experimental phase. HFES was delivered directly to the epileptogenic zone (local closed‐loop) in four patients and indirectly, through anterior thalami (remote closed‐loop), to the other four patients for every other automated seizure detection made by a validated algorithm. Interphase (control vs experimental phase) and intraphase (stimulated vs nonstimulated) comparisons of clinical seizure rate and relative severity (clinical and electrographic) were performed, and differences were assessed using effect size. Patients were deemed “responders” if seizure rate was reduced by at least 50%; the remaining patients were deemed “nonresponders.” All patients completed the study; rescue medications were not required. There were 1,491 HFESs (0.2% triggered after‐discharges). Mean change in seizure rate in the local closed‐loop group was −55.5% (−100 to +36.8%); three of four responders had a mean change of −86% (−100 to −58.8%). In the remote closed‐loop, the mean change of seizure rate was −40.8% (−72.9 to +1.4%); two of four responders had a mean change of −74.3% (−75.6 to −72.9%). Mean effect size was zero in the local closed‐loop (responders: beneficial and medium to large in magnitude) and negligible in the remote closed‐loop group (responders: beneficial and medium to large). HFES effects on epileptogenic tissue were immediate and also outlasted the stimulation period. This study demonstrates the feasibility and short‐term safety of automated HFES for seizure blockage, and also raises the possibility that it may be beneficial in pharmaco‐resistant epilepsies. Ann Neurol 2005;57:258–268

Surgical and hardware complications of subthalamic stimulation A series of 160 procedures

Objective: To assess the surgical and hardware complications in a series of 81 consecutive patients undergoing subthalamic (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Methods: The authors prospectively documented surgical and hardware complications occurring at the time of surgery and at subsequent neurologic and surgical evaluations for an average of 17 months, ranging from 1 to 54 months. Results: No patient had a serious surgical complication resulting in death or permanent neurologic deficit. One patient had an intracranial hemorrhage but with no permanent deficit. In follow-up, 2.5% had infections requiring system removal, 3.7% had infections requiring implantable pulse generator (IPG) removal, 12.5% had misplaced leads, and 26.2% had hardware complications including lead migration, lead fracture, extension erosion, extension fracture, and IPG malfunction. Conclusion: Serious complications leading to permanent neurologic deficit are rare after STN DBS for advanced PD. However, long-term follow-up demonstrated that hardware complications are relatively common, having occurred in approximately 26% of these patients.

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor.

Our objective was to investigate the long‐term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty‐nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, seven were explanted prior to 24 months, 11 were lost to long‐term follow‐up, and three died from unrelated causes. Twenty‐five patients were evaluated with follow‐up greater than or equal to 2 years. The last postsurgical follow‐up occurred on average 40.2 ± 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long‐term follow‐up as compared to baseline. There was no change in tremor scores from baseline to long‐term follow‐up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long‐term follow‐up. Three patients had asymptomatic intracerebral hemorrhages and one patient had postoperative seizures. Stimulus‐related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device‐related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long‐term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures.

An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short-term clinical trials, and to multidimensional statistical analysis of therapeutic efficacy.

Summary Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety—in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in-hospital “closed-loop” trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable.

High Frequency Thalamic Stimulation for Inoperable Mesial Temporal Epilepsy

Summary:  Purpose: To assess the safety, tolerability and efficacy of high‐frequency periodic thalamic stimulation in inoperable mesial temporal epilepsy and the usefulness of intracranially evoked responses for assessment of anatomical uniformity of lead placement.

Comparison of thalamotomy to deep brain stimulation of the thalamus in essential tremor

To compare outcome in Essential Tremor (ET) patients who have undergone either thalamotomy or Deep Brain Stimulation (DBS) of the thalamus.

Efficacy of unilateral deep brain stimulation of the vim nucleus of the thalamus for essential head tremor

Essential tremor is a common movement disorder. Deep brain stimulation of the VIM nucleus of the thalamus has been reported to be efficacious for reducing essential hand tremor. The effect of deep brain stimulation of the thalamus on essential head tremor has not been well studied. Therefore, we evaluated the effect of DBS of the thalamus in 38 patients with essential head tremor. Head tremor scores prior to surgery were compared with scores at 3, 6, and 12 months postimplant with stimulation “on” and “off.” The 3‐month evaluations were blinded for 24 patients and all others were open‐label. There was a significant improvement in head tremor at all postimplant evaluations compared with baseline. Essential head tremor can be reduced with deep brain stimulation of the VIM nucleus of the thalamus and, pending the results of other controlled trials, should be considered as a treatment option for patients with disabling essential head tremor unresponsive to medication.

Synovial cysts of the lumbar spine: Diagnosis, surgical management, and pathogenesis: Report of eight cases

BACKGROUND Synovial cysts are uncommon extradural degenerative lesions associated with symptoms of lower back pain and radiculopathy. Most of these lesions occur in the lumbar spine at the L4-5 level and to a lesser extent at the L5-S1 and L3-4 levels. METHODS A retrospective study involving eight patients seen by the neurosurgery service from January 1, 1989, to May 30, 1994, was analyzed. The type, duration, and distribution of symptoms were evaluated, along with the patients age and sex. All patients had lumbosacral spine x rays and magnetic resonance imaging. Four had a computed tomography-myelogram of the lumbar spine. All patients underwent a laminectomy or hemilaminectomy and cyst excision, and all were followed for a minimum of 1 year. The presence of a synovial cyst was confirmed by histopathology. RESULTS Of the eight patients, seven had dramatic pain relief with five having complete resolution of pain. The single care of persistent pain was found to be due to scar tissue at the operative site. All five cases of preoperative lower extremity weakness showed complete resolution. Dysesthesia was either unchanged or decreased. CONCLUSIONS Surgery is a safe, effective treatment for patients with lumbar synovial cysts and is the treatment of choice for these lesions.

Preoperative Clinical Predictors of Response to Bilateral Subthalamic Stimulation in Patients with Parkinson’s Disease

Background: Younger age and a response to a supra-threshold levodopa challenge have been reported to predict a favorable response to bilateral subthalamic nucleus (STN) stimulation. Objective: To identify and evaluate clinical factors which predict a positive outcome after bilateral STN stimulation in patients with Parkinson’s disease, using each patient’s typical doses of antiparkinsonian medication rather than a supra-threshold levodopa challenge. Methods: Forty-five Parkinson’s disease patients who underwent bilateral STN implantation were included in the study. There were 33 men and 12 women. Mean age and disease duration were 59.4 and 12.7 years, respectively. All patients underwent Unified Parkinson Disease Rating Scale (UPDRS) evaluations in the medication off and on states at baseline and postsurgically with stimulation on at 3, 6 and 12 months. The percentage improvement in UPDRS motor scores at baseline (medication off vs. on) was compared with the percentage improvement after stimulation optimization (baseline medication off vs. follow-up medication off/stimulation on). Results: The preoperative percentage improvement in UPDRS motor scores with antiparkinsonian medications was predictive of the postoperative percentage improvement in the UPDRS motor scores in the medication off/stimulation on state (r = 0.53, p < 0.001). However, preoperative UPDRS motor scores in the medication on state were more strongly correlated with the postsurgical effect of stimulation (r = 0.64, p < 0.001). The postoperative improvement in UPDRS motor scores with stimulation did not correlate with age, disease duration or time to programming optimization. Conclusions: The preoperative percentage improvement in UPDRS motor scores with antiparkinsonian medications and UPDRS motor score in the medication on state at baseline are the strongest clinical predictors of responsiveness to bilateral STN stimulation.