Neuropsychological outcomes after thalamic deep brain stimulation for essential tremor.

INTRODUCTION: Non-motor DBS outcomes have received little attention in ET relative to PD. This study examines neuropsychological outcomes in ET following thalamic VIM DBS. METHODS: Fifty patients completed neuropsychological evaluations preoperatively and approximately seven months postoperatively. Cognition and mood changes were analyzed at the group level and individual level. Additional associations with treatment, disease, and demographic characteristics were assessed. RESULTS: Significant cognitive decline was not observed at the group level. At the individual level, 46% of patients demonstrated at least subtle overall cognitive decline (≥1SD on at least one test within at least two domains). Mild decline (≥1SD) was seen in 10%-29.17% of patients on individual tests across all cognitive domains, with highest rates in verbal memory. Substantial cognitive decline (≥2SD) occurred in less than 9% of the sample across all tests. Factors related to cognitive decline included higher DBS parameter settings, older age of ET onset, intracranial complications, and inability to reduce ET medications postoperatively. Depression and anxiety did not change when accounting for questionnaire items that could be falsely elevated by tremor. CONCLUSION: Substantial cognitive decline after VIM DBS is rare in patients with ET. However, subtle decrements can occur across cognitive domains and particularly in verbal memory. DBS parameter settings may relate to cognitive decline. Further research is needed to better understand possible associations with electrode lateralization and other variables that could also relate to disease progression and test-retest effects. Symptoms of depression and anxiety remain stable.

Unilateral Thalamic Deep Brain Stimulation Versus Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: The predominant neurosurgical approach to medication-refractory essential tremor is thalamic deep brain stimulation (DBS). The emergence of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has reawakened the debate surrounding the use of DBS versus thalamotomy for this indication. Herein, we aimed to provide a contemporary comparison between DBS and MRgFUS. METHODS: Two controlled trials that evaluated DBS and MRgFUS for the unilateral treatment of refractory essential tremor were compared. Clinical outcomes extracted included postural tremor score in the treated upper extremity, quality of life (QoL), and incidence of adverse events (AE). RESULTS: Baseline patient characteristics were comparable in the 2 studies, except that DBS patients were younger and had more severe baseline tremor. Both DBS- and MRgFUS-treated patients had significant tremor improvement that was sustained for 1-year posttreatment, and significant improvement in QoL. The MRgFUS cohort had higher rates of persistent neurologic AE, whereas the DBS group had higher rates of surgery- and hardware-related AEs, including intracranial hemorrhage. CONCLUSIONS: In context of prior literature, both DBS and MRgFUS significantly improve tremor control and QoL. The 2 approaches are predominantly differentiated by their AE-profile. Additional head-to-head comparison on matched clinical populations are required to more accurately compare clinical efficacy and long-term outcomes.

Effects on cognition and quality of life with unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

OBJECTIVE Although neurosurgical procedures are effective treatments for controlling involuntary tremor in patients with essential tremor (ET), they can cause cognitive decline, which can affect quality of life (QOL). The purpose of this study is to assess the changes in the neuropsychological profile and QOL of patients following MR-guided focused ultrasound (MRgFUS) thalamotomy for ET. METHODS The authors prospectively analyzed 20 patients with ET who underwent unilateral MRgFUS thalamotomy at their institute in the period from March 2012 to September 2014. Patients were regularly evaluated with the Clinical Rating Scale for Tremor (CRST), neuroimaging, and cognition and QOL measures. The Seoul Neuropsychological Screening Battery was used to assess cognitive function, and the Quality of Life in Essential Tremor Questionnaire (QUEST) was used to evaluate the postoperative change in QOL. RESULTS The total CRST score improved by 67.3% (from 44.75 ± 9.57 to 14.65 ± 9.19, p < 0.001) at 1 year following MRgFUS thalamotomy. Mean tremor scores improved by 68% in the hand contralateral to the thalamotomy, but there was no significant improvement in the ipsilateral hand. Although minimal cognitive decline was observed without statistical significance, memory function was much improved (p = 0.031). The total QUEST score also showed the same trend of improving (64.16 ± 17.75 vs 27.38 ± 13.96, p < 0.001). CONCLUSIONS The authors report that MRgFUS thalamotomy had beneficial effects in terms of not only tremor control but also safety for cognitive function and QOL. Acceptable postoperative changes in cognition and much-improved QOL positively support the clinical significance of MRgFUS thalamotomy as a new, favorable surgical treatment in patients with ET.

The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.

Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow) or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements). To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA) in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF) with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF), patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.

The therapeutic potential of Berberine chloride hydrate against harmaline-induced motor impairments in a rat model of tremor.

Essential tremor (ET) is a progressive neurological disorder with motor and non-motor symptoms. It has conclusively been shown that modulation of glutamate receptors could ameliorate ET. Recent studies have suggested that Berberine (BBR) has an inhibitory effect on glutamate receptors. Therefore, BBR may have therapeutic effects on ET. In this study, male Wistar rats (n=10 in each group) weighing 40-60 g were divided into control, harmaline (30 mg/kg, i.p.) and berberine (10, 20 or 50mg/kg, i.p, 15 min before harmaline injection) groups. Open field, rotarod, wire grip and foot print tests were used to evaluate motor performance. The results indicated that the administration of BBR (10 and 20mg/kg) attenuated harmaline-induced tremor in rats, but the beneficial effects of BBR could not be identified at dose 50mg/kg. In addition, BBR ameliorated gait disturbance in doses of 10 and 20mg/kg. The high dose of BBR not only failed to recover step width but also showed an adverse effect on left and right step length. The results indicate that BBR only in dose of 20mg/kg recovers mobility duration. The current study found a dose-dependent manner for the therapeutic effects of BBR in ET. Our study provides the initial evidence for the effects of BBR on motor function. Since BBR exerts its effects mainly through regulation of neurotransmitter release or blocke of NMDA receptors, thus, it is predicted that BBR ameliorate harmaline effect through blockade of NMDA receptors or glutamate release. This is an important issue for future research to evaluate the possible mechanisms involved.

Functional assessment and quality of life in essential tremor with bilateral or unilateral DBS and focused ultrasound thalamotomy.

BACKGROUND: Thalamic deep brain stimulation (DBS) has largely replaced radiofrequency thalamotomy as the treatment of choice for disabling, medication-refractory essential tremor. Recently, the development of transcranial, high-intensity focused ultrasound has renewed interest in thalamic lesioning. The purpose of this study is to compare functional outcomes and quality of life in essential tremor patients treated with either bilateral Vim DBS or unilateral procedures (focused ultrasound or DBS). We hypothesized that all three would effectively treat the dominant hand and positively impact functional outcomes and quality of life as measured with the Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire. METHODS: This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n = 57), unilateral Vim DBS (n = 13), or unilateral focused ultrasound Vim thalamotomy (n = 15). Tremor was rated for all patients before and after treatment, using the Clinical Rating Scale for Tremor and Quality of Life in Essential Tremor Questionnaire. RESULTS: Patients undergoing bilateral DBS treatment had more baseline tremor and worse quality of life scores. Patients had significant improvements in tremor symptoms and quality of life with all three treatments. Both DBS procedures improved axial tremor. No difference was seen in the degree of improvement in upper extremity tremor score, disability, or overall quality of life between bilateral and either unilateral procedure. CONCLUSIONS: Bilateral thalamic DBS improves overall tremor more than unilateral DBS or focused ultrasound treatment; however, unilateral treatments are equally effective in treating contralateral hand tremor. Despite the greater overall tremor reduction with bilateral DBS, there is no difference in disability or quality of life comparing bilateral versus unilateral treatments.

Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality.

BACKGROUND: Ventral intermediate thalamic nucleus (VIM) deep brain stimulation (DBS) is an effective treatment for tremor, but there is limited data on long-term efficacy and mortality after VIM-DBS. Here we report the analysis of patient satisfaction and mortality in all patients treated in our center 1996-2010 with VIM-DBS for essential tremor (ET). METHODS: Forty-six consecutive patients were included in this study. Medical records were reviewed, and a follow-up questionnaire was sent to all surviving patients. RESULTS: Seventy percent of all possible participants (26 patients) answered the questionnaire. Follow-up time for the responding patients was median 6.0 years (2-16). Median self-reported score on visual analogue scale of the initial postoperative effect on tremor was 8.5 (0.1-10), with a significant reduction to 7.4 (0-10) at follow-up (p = 0.001). Patients reported a median score of 10 (0-10) for overall patient satisfaction with VIM-DBS treatment. Eight patients (17%) died after median 8.9 years (0.6-15) after surgery, at median age 77.4 years (70-89). One patient (2%) committed suicide seven months after the operation. Calculated standard mortality ratio among ET patients was 1.3 (CI 0.6-2.6), similar to the general population. CONCLUSION: We found no significant increase in mortality in this cohort of VIM-DBS operated ET patients compared to the general population in Norway. The patients reported high long-term satisfaction and continuing effect of VIM-DBS on tremor even after many years. VIM-DBS therefore seems to be an effective symptomatic long-term treatment of ET. However, one patient committed suicide. Only one other suicide has previously been reported after VIM-DBS. It is therefore still unclear whether VIM-DBS increases suicide risk.

Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor.

OBJECT: The goal of this study was to evaluate short- and long-term benefits in quality of life (QOL) after unilateral deep brain stimulation (DBS) for essential tremor (ET). METHODS: Patients who received unilateral DBS of the ventral intermediate nucleus of the thalamus between 1997 and 2010 and who had at least 1 follow-up evaluation at least 1 year after surgery were included. Their QOL was assessed with the Parkinson Disease Questionnaire-39 (PDQ-39), and ET was measured with the Fahn-Tolosa-Marin tremor rating scale (TRS) prior to surgery and then postoperatively with the stimulation in the on mode. RESULTS: Ninety-one patients (78 at 1 year; 42 at 2-7 years [mean 4 years]; and 22 at >7-12 years [mean 9 years]) were included in the analysis. The TRS total, targeted tremor, and activities of daily living (ADL) scores were significantly improved compared with presurgical scores up to 12 years. The PDQ-39 ADL, emotional well-being, stigma, and total scores were significantly improved up to 7 years after surgery compared with presurgical scores. At the longest follow-up, only the PDQ-39 stigma score was significantly improved, and the PDQ-39 mobility score was significantly worsened. CONCLUSIONS: Unilateral thalamic stimulation significantly reduces ET and improves ADL scores for up to 12 years after surgery, as measured by the TRS. The PDQ-39 total score and the domains of ADL, emotional well-being, and stigma were significantly improved up to 7 years. Although scores were improved compared with presurgery, other than stigma, these benefits did not remain significant at the longest (up to 12 years) follow-up, probably related in part to changes due to aging and comorbidities.

Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life.

OBJECTIVES: To report long-term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health-related quality of life (HRQoL) in patients with essential tremor (ET). MATERIALS AND METHODS: Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview. RESULTS: There was a decrease of DBS efficacy on tremor between 1 and 7 years post-operatively. The marked improvement in ADL at 1 year was no longer sustained at long-term, except for the ability to eat. Social life remained improved. CONCLUSION: Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co-morbidities may impact on the well-being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.

The effect of deep brain stimulation on quality of life in movement disorders.

Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.

Biobehavioral intervention for older adults coping with essential tremor.

Four questions were addressed: (a) does biobehavioral intervention result in within-session reduction of tremor severity; (b) do relaxation and electromyographic (EMG) biofeedback training produce differential effects; (c) do within-session treatment effects generalize to daily performance; and (d) are reductions in tremor severity maintained at follow-up assessment? Three adults, ages 51, 77, and 83, each with a diagnosis of essential tremor (ET), and a long standing history of tremor of the hands uncontrolled by medication, took part. A repeated pre-post-training single-case experimental design embedded within a sequential A--B--C--D design was used; in addition, 1 participant received a return to the B phase. Outcome measures included within-session clinical and self-ratings of tremor severity, surface electromyography (sEMG) of forearm muscles, and daily self-ratings of tremor at home. Tremor was measured while participants engaged in eating or drinking tasks. The Behavioral Relaxation Scale (BRS) served as a process measure to assess relaxation proficiency. Clinical ratings of tremor and the BRS had high interobserver agreement. Visual inspection and statistical tests of single-case data were used to evaluate outcomes. Each participant showed significant within-session improvements on various measures of tremor and improvement during intervention as compared to baseline phases. There were no clear-cut differences between relaxation and biofeedback phases. Improvements declined somewhat at a 12-week follow-up. Relationships among measures of tremor are discussed. Biobehavioral interventions hold promise for older adults coping with ET. Further research is needed using an array of biobehavioral measures to assess intervention outcome.

A novel quality of life instrument for deep brain stimulation in movement disorders.

OBJECTIVE: To develop a short instrument to examine quality of life (QoL) which specifically addresses patients with movement disorders treated by deep brain stimulation (DBS). DESIGN: The instrument was developed within an existing concept of a modular questionnaire (questions on life satisfaction: "general life satisfaction" QLS(M)-A, and "satisfaction with health" QLS(M)-G), in which each item is weighted according to its relative importance to the individual. METHODS: Items were generated by interviews with 20 DBS patients, followed by item reduction and scale generation, factor analysis to determine relevant and final questionnaire items, estimation of reliability, and validation based on the medical outcome study 36 item short form health survey (SF-36) and the EuroQol (EQ-5D) (data from 152 patients with Parkinson's disease, essential tremor, or idiopathic torsion dystonia, including 75 patients with DBS). RESULTS: Initial questionnaires were reduced to 12 items for a "movement disorder module" (QLS(M)-MD), and five items for a "deep brain stimulation module" (QLS(M)-DBS). Psychometric analysis revealed Cronbach's alpha values of of 0.87 and 0.73, and satisfactory correlation coefficients for convergent validity with SF-36 and EQ-5D. CONCLUSIONS: QLS(M)-MD and QLS(M)-DBS can evaluate quality of life aspects of DBS in movement disorders. Psychometric evaluation showed the questionnaires to be reliable, valid, and well accepted by the patients.