Subthalamic Area Deep Brain Stimulation Research Articles

Spinocerebellar ataxia 21 and phenotypic variability within a single family (P9-11.004)

<h3>Objective:</h3> We describe four patients within a family who presented to our movement disorders centers for evaluation of unsteady gait, tremor, and cognitive impairment found to have the same pathogenic variant in TMEM240. We describe their clinical courses and response to treatments to include posterior subthalamic area deep brain stimulation (PSA DBS) and provide accompanying video. <h3>Background:</h3> Spinocerebellar ataxia 21 (SCA21) is a rare cause of autosomal dominant ataxia with few patients (~50) published. It is an early-onset, slowly progressive cerebellar ataxia and may also have tremor, parkinsonism, oculomotor abnormalities, cognitive impairment, and psychiatric conditions. Given its rarity, the neurodevelopmental phenotype has not been well defined and phenotypic variability within the same variant has not yet described. <h3>Design/Methods:</h3> The index case, 12 year-old girl, presented with mild intellectual disability, severe action tremor since infancy, oculomotor abnormalities, anxiety, and depression. The full brother was noted to have mild action tremor since early childhood, speech delay and growth delay. The paternal half-brother presented with progressively worsening action tremor since early childhood which became impairing in adolescence as well as similar oculomotor abnormalities, learning disabilities, ADHD, and OCD. The father of the patients had onset of mild non-progressive action tremor of the hands since age 8, progressive ataxia, mild parkinsonism, mild intellectual disability and new onset progressive memory impairment. All patients were found to have the same pathogenic variant in TMEM240 (c.196G&gt;A p.G66R)). <h3>Results:</h3> The index patient tried numerous oral medications as well as botulinum neurotoxin (BoNT) injections without improvement. She underwent PSA DBS with marked improvement in tremor. Tremor in the paternal half-brother responded well to BoNT injections. The father underwent treatment for parkinsonism with carbidopa-levodopa and was started on rivastigmine without improvement. <h3>Conclusions:</h3> SCA21 is a slowly progressive autosomal dominant spinocerebellar ataxia with variable neurodevelopmental phenotypes including multiple movement disorders within the same variant. <b>Disclosure:</b> Dr. Hull has received publishing royalties from a publication relating to health care. Dr. Parnes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. Dr. Parnes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. The institution of Dr. Parnes has received research support from NIH. The institution of Dr. Parnes has received research support from Alexion. Dr. Jankovic has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Jankovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Revance, Allergan. The institution of Dr. Jankovic has received research support from Baylor College of Medicine. Dr. Jankovic has received research support from Abbvie. The institution of Dr. Jankovic has received research support from Abbvie.

Posterior subthalamic area deep brain stimulation for recurrent tremor after ventral intermediate nucleus thalamotomy: a case report

Neurosurgical treatments, including both lesioning procedures and deep brain stimulation (DBS), are considered effective treatments for patients with intractable essential tremor (ET). However, it can be challenging to arrive at the decision to perform a second surgical attempt for recurrent ET after the initial neurosurgical treatment because of the uncertainty of successful results. We encountered a 49-year-old man who complained of recurrent tremor after ventral intermediate nucleus thalamotomy. The patient underwent DBS in the posterior subthalamic area (PSA), resulting in significantly reduced tremor and improved daily function. Although there are various surgical options for recurrent ET, DBS targeting the PSA induces favorable tremor control and can be successfully used as a salvage therapy after thalamotomy.

Bilateral Posterior Subthalamic Area Deep Brain Stimulation for Essential Tremor: A Case Series.

BackgroundDeep brain stimulation (DBS) of the posterior subthalamic area (PSA) provides a potentially effective treatment for medication-refractory essential tremor (ET).ObjectiveTo study the clinical benefits and adverse-event profile of bilateral PSA-DBS for refractory ET.MethodsSeven patients with refractory ET underwent bilateral PSA-DBS surgery under general anesthesia between September 2017 and May 2018. Clinical outcome assessments, using the Essential Tremor Rating Scale, were performed at 1-, 6-, and 12-month follow-up, except for the last assessment of one patient who was followed up to 9 months. Analysis was focused on changes in patients’ motor symptoms and quality of life following surgery as well as documenting the adverse-event profile associated with the surgical PSA-DBS treatment.ResultsAfter surgery, patients’ motor symptoms, including upper limb tremor and head tremor, were improved by 84.2% and their quality of life by 81.25% at 1-month follow-up. The clinical benefits to patients were maintained at 6-month and last follow-up. Adverse side effects included dysarthria (n = 4), balance disorder (n = 2), and paresthesia of the right limb (n = 1). No habituation effects were observed throughout the follow-up.ConclusionBilateral PSA-DBS seems to offer an effective and safe alternative treatment for medically intractable ET, warranting further research into its clinical utility, adverse-event profile, and comparative effectiveness.

Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Refractory Holmes Tremor

Three right-handed patients diagnosed with Holmes tremor (HT), who suffered from pharmacotherapy-refractory tremor, were eligible for unilateral posterior subthalamic area deep brain stimulation (PSA-DBS). All patients were evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Clinical Global Impression scale (CGI) before DBS, 6, and 12 months after the PSA-DBS as well as at the last follow-up. In all patients, we observed a significant improvement of tremor control as demonstrated by changes in the FTMTRS and the CGI scales. Mean improvement of tremor in all patients was 56% for the FTMRTS with a corresponding change in the CGI scale. Our study demonstrates that PSA-DBS is efficacious in the treatment of HT. Indeed, PSA is a promising target for DBS for intractable proximal and distal tremor, even in cases of previous, suboptimal functional neurosurgery. The beneficial effect lasts over a long-term follow-up. PSA-DBS may be considered as an alternative target of DBS in tremor treatment.

Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography

ObjectiveTo compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT). Patients and MethodsDouble-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery. ResultsPSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients. ConclusionDTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes' tremor

Holmes' tremor (HT) is generally considered to be a symptomatic tremor associated with lesions of the cerebellum, midbrain, or thalamus. Deep brain stimulation (DBS) therapy for essential tremor and parkinsonian tremor has proved quite successful. In contrast, surgical treatment outcomes for HT have often been disappointing. The use of 2 ipsilateral DBS electrodes implanted in parallel within the thalamus for severe essential tremor has been reported. Since dual-lead stimulation within a single target can cover a wider area than single-lead stimulation, it produces greater effects. On the other hand, DBS of the subthalamic area (SA) was recently reported to be effective for refractory tremor. The authors implanted 2 DBS electrodes (one at the nucleus ventralis oralis/nucleus ventralis intermedius and the other at the SA) in 4 patients with HT. For more than 2 years after implantation, each patient's tremor was evaluated using a tremor rating scale under the following 4 conditions of stimulation: "on" for both thalamus and SA DBS; "off" for both thalamus and SA DBS; "on" for thalamus and "off" for SA DBS; and "on" for SA and "off" for thalamus DBS. The tremor in all patients was improved for more than 2 years (mean 25.8 ± 3.5 months). Stimulation with 2 electrodes exerted greater effect on the tremor than did 1-electrode stimulation. Interestingly, in all patients progressive effects were observed, and in one patient treated with DBS for 1 year, tremor did not appear even while stimulation was temporarily switched off, suggesting irreversible improvement effects. The presence of both resting and intentional/action tremor implies combined destruction of the pallidothalamic and cerebellothalamic pathways in HT. A larger stimulation area may thus be required for HT patients. Multitarget, dual-lead stimulation permits coverage of the wide area needed to suppress the tremor without adverse effects of stimulation. Some reorganization of the neural network may be involved in the development of HT because the tremor appears several months after the primary insult. The mechanism underlying the absence of tremor while stimulation was temporarily off remains unclear, but the DBS may have normalized the abnormal neural network. The authors successfully treated patients with severe HT by using dual-electrode DBS over a long period. Such DBS may offer an effective and safe treatment modality for intractable HT.

Post subthalamic area deep brain stimulation for tremors: a mini-review

Deep brain stimulation (DBS) in the thalamic ventrointermediate nucleus (VIM) is the traditional target for the surgical treatment of pharmacologically refractory essential tremor or parkinsonian tremor. Studies in recent years on DBS in posterior subthalamic area (PSA), including the zona incerta and the prelemniscal radiation, have shown promising results in tremor suppression, particularly for those tremors difficult to be well controlled by VIM DBS, such as the proximal postural tremor, distal intention tremor and some cerebellar outflow tremor in various diseases including essential tremor and multiple sclerosis. The adverse effect profile of the PSA DBS is mild and transient, without lasting or striking dysarthria, disequilibrium or tolerance, in contrast to VIM DBS, particularly bilateral DBS. However, the studies on PSA DBS so far are still limited, with a handful of studies on bilateral PSA, and a short follow up duration compared to VIM. More studies are needed for direct comparison of these targets in the future. A review here would help to gain more insight into the benefits and limits of the PSA DBS compared to that in VIM in the clinical management of various tremors, particularly for those difficult to be well controlled by traditional VIM DBS.