Pallidal deep brain stimulation is effective, and improves quality of life in primary segmental and generalized dystonia

Background –  Dystonia is one of the most prevalent movement disorders, and may lead to abnormal postures, pain, significant disability and social isolation if not well treated. In widespread segmental or generalized dystonia efficient treatment options were lacking until the recent introduction of deep brain stimulation of the internal globus pallidus (pallidal DBS).
Methods –  The first case series and single-blinded controlled study showed promising results regarding the effect of pallidal DBS on dystonic movements, pain and disability, but the impact of this treatment on health-related quality of life (HRQoL) remained uncertain. Then, as part of the first randomized, and sham stimulation-controlled trial performed by the DBS for Dystonia Study Group, HRQoL was evaluated using the Short Form-36 Health Survey (SF-36) at baseline, after the 3 months sham-controlled phase, and after 6 months of continuous pallidal DBS, in 40 patients with severe primary segmental or generalized dystonia.
Results –  The 3-month sham-stimulation controlled phase resulted in significant improvement of dystonic movements, pain and disability in the active stimulation group, and four of the eight SF-36 domain scores also improved significantly compared with the sham-stimulated group. After 6 months of active stimulation in all patients, significant improvement in all eight SF-36 domains was observed, with comparable improvement in the segmental and generalized dystonia groups.
Conclusion –  Convincing evidence has been obtained that pallidal DBS effectively reduces dystonia-related symptoms, and markedly improves HRQoL in patients suffering from otherwise intractable, primary segmental or generalized dystonia, thus providing new opportunities for this patient group.     

Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: a clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia.

The results of deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in six patients with generalized, focal, and segmental dystonia are presented. Pre- and postoperative assessments are given for one patient with generalized inherited dystonia and for five patients with idiopathic segmental or cervical dystonia. Clinical symptoms were evaluated before and 3-12 months after surgery using the Burke-Fahn-Marsden (BFM) dystonia rating scale for primary torsion dystonia and the Tsui scale for cervical dystonia. The Short-Form Health Survey (SF-36) was completed by each patient to document preoperative and postoperative health status. Also, neurological status was documented by video before and during chronic stimulation. Magnetic resonance imaging studies were performed to show the anatomical localization of the electrode leads. Five patients showed a progressive improvement within 7 days. One patient with cervical dystonia and Meige's syndrome showed no improvement for 3 months, but beneficial effects were observed after 12 months. On average, the BFM movement scale scores decreased by 72.5% and Tsui scale scores by 63%. SF-36 showed an improvement in health status by an average of 36% according to eight different health categories. We conclude that chronic high-frequency Gpi stimulation in different types of dystonia is a very effective and safe treatment.     

A family with a hereditary form of torsion dystonia from Northern Sweden treated with bilateral pallidal deep brain stimulation

To evaluate pallidal DBS in a non‐DYT1 form of hereditary dystonia. We present the results of pallidal DBS in a family with non‐DYT1 dystonia where DYT5 to 17 was excluded. The dystonia is following an autosomal dominant pattern. Ten members had definite dystonia and five had dystonia with minor symptoms. Four patients received bilateral pallidal DBS. Mean age was 47 years. The patients were evaluated before surgery, and “on” stimulation after a mean of 2.5 years (range 1–3) using the Burke‐Fahn‐Marsden scale (BFM). Mean BFM score decreased by 79 % on stimulation, from 42.5 ± 24 to 9 ± 6.5 at the last evaluation. Cervical involvement improved by 89%. The 2 patients with oromandibular dystonia and blepharospasm demonstrated a reduction of 95% regarding these symptoms. The present study confirms the effectiveness of pallidal DBS in a new family with hereditary primary segmental and generalized dystonia. © 2009 Movement Disorder Society     

Bilateral pallidal stimulation for sargoglycan epsilon negative myoclonus

We report on the clinical efficacy of bilateral globus pallidus internus deep brain stimulation in two patients with myoclonus dystonia/essential myoclonus who lack mutations in the epsilon sarcoglycan gene.The primary outcome measures were the Burke–Fahn–Marsden Dystonia Scale motor severity and the Unified Myoclonus Rating Scale scores, and the secondary outcome measure was the 36-item Short Form Health Survey score at the last postoperative follow up. Neuronal firing rates were also calculated from microelectrode recordings.At the last postoperative follow-up (16 weeks for Patient 1 and 18 weeks for Patient 2), there was 57.1% (Patient 1) improvement in the Burke–Fahn–Marsden Dystonia Scale motor severity score and 31.3% (Patient 1) and 69% (Patient 2) in the Unified Myoclonus Rating Scale score while individual SF-36 scores showed improvement in most subdomains.Bilateral globus pallidus internus deep brain stimulation can be effective in ameliorating epsilon sarcoglycan negative myoclonus with or without concurrent dystonia. Whether an epsilon sarcoglycan negative status represents a less favorable prognostic factor for pallidal deep brain stimulation remains to be elucidated.     

The effects of frequency in pallidal deep brain stimulation for primary dystonia

Abstract. The effect of stimulation frequency for pallidal deep brain stimulation in five patients with either generalized or segmental dystonia was evaluated three to twelve months postoperatively via a randomized, double-blind paradigm. The quality of life and the severity of dystonic symptoms improved by approximately 60% and 43% respectively using a frequency of 130 Hz. Compared with 130 Hz a significant further clinical improvement was observed at frequencies of 180 and 250 Hz, which contrasted with a significant deterioration at lower frequencies (5, 50 Hz) compared to 130 Hz.     

Anxiety and depression in primary and secondary dystonia: A burden on health related quality of life

Dystonia is a reason of visible chronic motor and/or psychological disability that may influence the quality of life. Our aim was to investigate depression and anxiety in patients with primary and secondary dystonia, and to evaluate their effects on the quality of life. Patients with primary and secondary dystonia, and age-matched healthy volunteers were enrolled in the study. Anxiety and depression was evaluated with Hospital Anxiety Depression (HAD) scale. Short Form-36 was used to assess the quality of life in both study groups. Both mean anxiety and depression subscales scores were found to be increased in the patients with dystonia, when compared with the control group (p < 0.05). There were no statistically significant differences in the HAD scores patients with primary and secondary dystonia (p > 0.05). When compared with controls, all domains of SF-36 were found to be decreased in patients with dystonia contributing to a deterioration in the HR-QoL (p < 0.05). Among dystonia patients, a statistically significant decrease was found in all domains of SF-36, except vitality and mental health in secondary dystonia (p < 0.05). Multiple regression analysis revealed that secondary dystonia, long term disease, depression and anxiety have a great impact on quality of life of patients with dystonia. Dystonia can be considered as an important risk factor for anxiety and depression which leads to a deterioration in the quality of life of patients.     

Neuromodulation in Dystonia: Current Aspects of Deep Brain Stimulation

Among the surgical treatment options for patients with medically refractory dystonia chronic deep brain stimulation (DBS) of different targets in the basal ganglia circuitry has become one of the most important tools. The globus pallidus internus nowadays is the target of choice, while there is only limited experience with other targets. At this time, patients with primary (genetic or sporadic) generalized and segmental dystonia, and patients with (complex) cervical dystonia are thought to be the best candidates for pallidal DBS. Advantages of DBS are its reversibility, its adjustability, and the continuous access to modify the target in the basal ganglia. The present review gives an account on the development of surgical neuromodulation therapy for dystonia, surgical approaches, hardware‐related problems, DBS programming and patient management, and clinical outcome. Studies conducted according to the practices of evidence‐based medicine confirm the results of early pilot studies. The wide majority of patients achieve beneficial lasting outcome at a relatively low rate of manageable side‐effects. Along with improvement of the movement disorder, studies report on amelioration of quality‐of‐life surrogates. We also provide an overview on DBS surgery in less common dystonic syndromes, such as craniofacial dystonia, status dystonicus, task‐specific dystonia, paroxysmal dystonia, camptocormia, and secondary dystonias, including choreoathetosis, hemidystonia, tardive dystonia, and pantothenate kinase‐associated neurodegeneration. Furthermore, we discuss the implications of intra‐operative microelectrode recordings and pallidal field potentials for the pathophysiology of dystonia and the particular possible mechanisms of DBS in dystonia. Finally, future perspectives are outlined.     

Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections

The purpose of this study was to analyze the health-related quality of life (HRQL) of patients with cervical dystonia (CD) and the impact of botulinum toxin A (BTX-A) therapy in these patients. The authors recruited 101 patients with CD, all previously treated with BTX-A. Both before and 4 weeks after injection of BTX-A the patients were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), a Visual Analogue Scale for pain (VAS: 0-100%), the Short Form 36 health survey questionnaire (SF-36), and the Montgomery-Asberg Depression Rating Scale (MADRS). A control group of 84 healthy volunteers was also evaluated. The patients? baseline SF-36 scores were worse in all the domains when compared with those of the controls. Depression was found in 47.5% of the patients. Improvements were noticed 4 weeks after the single BTX-A injections in all the SF-36 domains, and in the VAS, TWSTRS and MADRS scores. The TWSTRS results did not correlate with any of the SF-36 subscores. Stepwise backward regression analysis revealed depression as the main predictor of poor HRQL, as well as female sex, poor financial situation, and living alone. On contrary, longer treatment with BTX-A was associated with better scores. Cervical dystonia has a marked impact on HRQL and treatment with BTX-A injections has a beneficial effect, seen both in objective and in subjective measures. Depression in CD patients is a main predictor of worse HRQL.     

The impact of blepharospasm and cervical dystonia on health-related quality of life and depression

The aim of the study was to evaluate and compare health-related quality of life (HR-QoL) and depression in essential blepharospasm (BSP) and idiopathic cervical dystonia (CD), to identify the clinical and demographic factors associated with poor HR-QoL in both disorders and to analyse the effect of Botulinum Toxin A (BtxA) therapy. Two hundred-twenty consecutive patients with BSP (N = 89, 62 % women, mean age 64 years, mean disease duration 7 years) and CD (N = 131, 64 % women, mean age 53 years, mean disease duration 8 years) recruited from routine referrals to eight Austrian dystonia clinics were included. HR-QoL was measured by the Short Form 36 (SF-36) and depression by the Beck Depression Inventory (BDI). At baseline, patients with CD and BSP scored significantly worse in all eight SF-36 domains compared with an age-matched community sample. In addition, 47 % of patients with CD and 37 % of those with BSP were depressed. Women with BSP scored significantly lower in all SF-36 domains and were more depressed than male patients. In contrast, there was no significant effect of gender on HR-QoL and depression in CD. Neck pain had a significant impact on all SF-36 domains and represented the main determinant of depression in CD. Although BtxA therapy resulted in a significant improvement of clinical symptoms in BSP and CD, HR-QoL did not improve in BSP and only two of the eight SF-36 domains improved significantly in patients with CD. The present study for the first time demonstrated that BSP has a substantial impact on health status emphasizing the need for psychological support with interventions aimed at treating depression in these patients. Our results provide further evidence for the profound impact of CD on HR-QoL and indicate the importance of an adequate management of neck pain in addition to reducing the severity of dystonia in CD. The mismatch between objective BtxA derived improvement of dystonia and lack of change of HR-QoL as determined by the SF-36 illustrates the need for optimized disease specific quality of life rating scales in patients with craniocervical dystonia.     

High rates of fatigue and sleep disturbances in dystonia

Background: Nonmotor symptoms in dystonia are increasingly recognized to impair the quality of life. The primary objective of this study was to determine the prevalence of fatigue and sleep disturbances in dystonia and to ascertain their impact on quality of life using standardized questionnaires. Methods: Dystonia patients presenting to a Botulinum toxin clinic were prospectively administered Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory (MFI), Epworth Sleepiness Scale (ESS) and Parkinson's Disease Sleep Scale (PDSS) for assessment of fatigue and sleep disturbances. Health-related Quality of life (HRQOL) was determined using MOS SF-36 scale and depressive symptoms were assessed using the Beck Depression Inventory II. Results: Ninety-one patients with dystonia participated (66 women, 25 men, mean age 60 ± 17 years). Nine subjects had generalized dystonia, 18 segmental dystonia and 64 had focal dystonia. Moderate to severe fatigue was present in 43% of the cohort (FSS), excessive daytime somnolence in 27% (ESS) and other sleep disturbances in 26% (PDSS). FSS and MFI scores correlated significantly with HRQOL even when controlled for depression and sleep disturbances. Excessive daytime somnolence and nocturnal sleep disturbances correlated significantly with the HRQOL; however, these effects were not seen for daytime somnolence when controlled for depression. Psychometric testing found adequate reliabilities and convergent validities for both fatigue and sleep scales. Conclusion: Fatigue and sleep disturbances revealed high prevalence rates in this large, first of its dystonia study. They negatively impacted the quality of life even when controlled for comorbid depression.     

Deep brain stimulation for dystonia: outcome at long-term follow-up

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.     

Bilateral pallidal stimulation for idiopathic segmental axial dystonia advanced from Meige syndrome refractory to bilateral thalamotomy.

Meige syndrome is an adult-onset dystonic movement disorder that predominantly involves facial muscles, while some patients with this syndrome develop spasmodic dysphonia and dystonia of the neck, trunk, arms, and legs. We report that all dystonic symptoms that had been refractory to both pharmacotherapy and bilateral thalamotomy were markedly alleviated by bilateral pallidal stimulation in a patient with segmental axial dystonia advanced from Meige syndrome.     

高频与低频重复经颅磁刺激对脑外伤患者认知功能的影响

目的 探讨脑外伤患者行高频与低频重复经颅磁刺激对其认知功能的影响.方法 选取2017年7月～2019年5月之间我院收治的90例脑外伤患者,随机分为三组,各30例.A组采用常规康复治疗,B、C组在此基础上均给予重复经颅磁刺激治疗,B组为低频(1Hz)刺激、C组为高频(5Hz)刺激.比较三个组患者治疗前后MoCA、ADL、...     

Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystonia

The aim of this study was to assess health-related quality of life (HRQoL), using the Short Form Health Survey-36 (SF-36), in 70 cervical dystonia (CD) patients after long-term botulinum toxin (BTX) treatment (median 5.5 years), and to identify factors determining reduced HRQoL. We used combined patient-and physician-based measures to assess both CD severity [Toronto Western Spasmodic Torticollis Rating Scale, (TWSTRS)] and effect of long-term BTX treatment, and the Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire-30 to assess psychological distress. Mean SF-36 domain scores of the CD patients were reduced by <1 SD compared with age- and gender-matched population samples. High TWSTRS total scores and high HAD-depression (HAD-D) scores were the main factors associated with reduced scores in the physical and mental SF-36 domains, respectively. Patients evaluated to have a 'good effect' of long-term BTX treatment ( n  = 47), had significantly lower median TWSTRS total score, and a 3× lower frequency of high HAD-D scores, than those evaluated to an 'unsatisfactory effect' ( n  = 23). In conclusion, most CD patients enjoy a good HRQoL after long-term BTX therapy. Reduced HRQoL was associated with more severe disease and/or depressive symptoms.     

Health related quality of life is improved by botulinum neurotoxin type A in long term treated patients with focal dystonia

OBJECTIVES: The advent of botulinum neurotoxin type A (BoNT/A) gave rise to substantial progress in the treatment of focal dystonias. In the light of the high costs of the toxin and the necessity to establish valid outcome indices for this treatment apart from sheer reduction of dystonic muscle tone and posture, the impact of focal dystonia and its treatment with BoNT/A on patients' health related quality of life (HRQL) was determined. METHODS: Fifty patients with cranial and cervical dystonia treated long term with BoNT/A were enrolled in a prospective, open labelled cohort study. The HRQL was assessed using the EuroQol (EQ-5D) and the short form 36 health survey questionnaire (SF-36) at baseline before BoNT/A injections and at two follow up visits after 6 and 12 weeks covering one BoNT/A treatment period with maximum effect size at the first follow up. RESULTS: Compared with a general population sample, a considerable negative impact of focal dystonia on HRQL was found in patients under investigation. In both disease types, BoNT/A treatment led to a significant improvement in several HRQL dimensions, in particular providing moderate to marked effect sizes in the fields of mental health and pain. The impairment of HRQL due to pain as well as the BoNT/A induced improvement within this SF-36 subscore were significantly higher in patients with cervical dystonia. Under BoNT/A therapy, no correlation was found between changes of clinical outcome scores and HRQL measures. CONCLUSIONS: The data confirm that BoNT/A is able to induce a significant, but temporary amelioration of several aspects of HRQL in both types of focal dystonia. This may substantially contribute to the patients' subjective benefit from the therapy. Moreover, the data provide further arguments to accept high costs of the BoNT/A treatment in these severely handicapped patients, as a consequence of its considerable benefit on quality of life.     

Relationships between disability, quality of life and prevalence of nonmotor symptoms in Parkinson's disease

Patients with Parkinson's disease suffer from a variety of motor and nonmotor symptoms (NMS), report reduced quality of life and increased disability. Aims of this study are to assess the impact of Parkinson's disease on disability and quality of life, to evaluate the relationships between them and NMS prevalence. In this cross-sectional study, adult patients were consecutively enrolled and administered the World Health Organization Disability Assessment Schedule (WHO-DAS II), the 36-Item Short-Form Health Survey (SF-36) and the Non Motor Symptoms Questionnaire (NMSQuest). One-sample t-test was used to compare WHO-DAS II and SF-36 scores with normative value. Pearson's correlation was performed between NMSQuest, WHO-DAS II and SF-36 summary scales. Independent-sample t-test was used to compare NMSQuest, WHO-DAS II and SF-36 scores in patients with Hoehn & Yahr stage <3 and ≥ 3. In total, 96 patients were enrolled. SF-36 and WHO-DAS II scores were significantly worse than the normative values. Correlation coefficients between NMSQuest, WHO-DAS II and SF-36's mental score were moderate, and were high between WHO-DAS II and and SF-36's physical score. Patients with Hoehn & Yahr stage ≥ 3 reported reduced quality of life, higher disability and more NMS. Parkinson's disease severity is strongly associated with reduced quality of life, increased disability and NMS prevalence. Disability and quality of life assessment tools measure psychosocial facets that are similar specifically with regard to physical health component of health-related quality of life, are sensitive enough to capture differences related to disease's progression and increased prevalence of NMS.     

Acute deep-brain stimulation of the internal and external globus pallidus in primary dystonia: functional mapping of the pallidum

BACKGROUND: Dystonia is a syndrome characterized by prolonged muscle contractions that cause sustained twisting movements and abnormal posturing of body parts. Patients with the severe and generalized forms can benefit from bilateral high-frequency pallidal stimulation. OBJECTIVE: To investigate the functional map of the globus pallidus (GP) in patients with primary generalized dystonia. DESIGN: Prospective multicenter, double-blind, video-controlled study in patients treated at a university hospital. SETTING: University secondary care centers. PATIENTS: Twenty-two patients with primary generalized dystonia. INTERVENTIONS: Acute internal and external pallidal deep-brain stimulation or pallidal deep-brain stimulation. MAIN OUTCOME MEASURES: The clinical effects of acute bilateral high-frequency ventral vs acute dorsal pallidal stimulation were assessed with the Movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale. Intrapallidal localization of the contacts of the quadripolar electrodes was performed using a 3-dimensional atlas-magnetic resonance imaging coregistration method by investigators blinded to the clinical outcome. RESULTS: Bilateral acute ventral stimulation of the GP significantly improved the Burke-Fahn-Marsden Dystonia Rating Scale score by 42% and resulted in stimulation of contacts located in the internal GP or medullary lamina in 18 of 21 patients. Bilateral acute dorsal pallidal stimulation, primarily localized within the external GP, had variable effects across patients, with half demonstrating slight or no improvement or even aggravation of dystonia compared with baseline. CONCLUSIONS: Ventral pallidal stimulation, primarily of the internal GP or medullary lamina or both, is the optimal method for the treatment of dystonia. The varying effects across patients of bilateral acute dorsal pallidal stimulation, primarily of the external GP, suggest that unknown factors associated with dystonia could have a role in and contribute to the effects of the electrical stimulation.     

Surgery for other movement disorders: dystonia, tics

PURPOSE OF REVIEW: Various movement disorders are now treated with stereotactic procedures, particularly deep brain stimulation. We review the neurosurgical treatment of dystonias and tics, focusing mainly on the surgical aspects and outcome of deep brain stimulation. RECENT FINDINGS: Pallidal stimulation is nowadays the mainstay surgical treatment for patients with dystonia, particularly generalized dystonia. Various well designed recent clinical trials support the efficacy of the procedure. Improvements of 40-80% have been reported in primary generalized, segmental and cervical dystonia. For secondary dystonia, a similar outcome has been described in patients with tardive dystonia and pantothenate kinase-associated neurodegeneration. In patients with Tourette's syndrome, the results of the first trials with thalamic and pallidal deep brain stimulation have been very promising. Improvements of 70-90% in the frequency of tics have been reported with surgery in both targets. SUMMARY: Deep brain stimulation has become an established therapy for dystonia and is currently being used to treat Tourette's syndrome. With accumulation of experience, clinical features that are more responsive to surgery and the best surgical candidates will be revealed. This will likely improve even further the outcome of surgery for the treatment of these disorders.     

Pallidal deep brain stimulation improves quality of life in segmental and generalized dystonia: Results from a prospective,randomized sham‐controlled trial

As part of the first randomized, sham‐timulation controlled trial on deep brain stimulation (DBS) in primary segmental or generalized dystonia, health‐related quality of life (HRQoL) was assessed by SF‐36. After the 3‐month sham‐controlled phase, significant HRQoL improvement occurred only in the active‐stimulation group. The open‐label extension phase resulted in a significant improvement in all SF‐36 domains following 6 months of neurostimulation. These results demonstrate a favorable impact of DBS on HRQoL in primary dystonia. © 2007 Movement Disorder Society