Secondary Dystonia in a Novel Mitochondriopathy Responsive to Deep Brain Stimulation Therapy.
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SUBMITTER: Sharma VD
PROVIDER: S-EPMC7781077 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7604663 | biostudies-literature
Project description:Deep brain stimulation (DBS) has been used to treat secondary dystonias caused by inborn errors of metabolism with varying degrees of effectiveness. Here we report for the first time the application of DBS as treatment for secondary dystonia in a 22-year-old male with X-linked adrenoleukodystrophy (X-ALD). The disease manifested at age 6 with ADHD, tics, and dystonic gait, and deteriorated to loss of ambulation by age 11, and speech difficulties, seizures, and characteristic adrenal insufficiency by age 16. DBS in the globus pallidus internus was commenced at age 18. However, after 25 months, no improvement in dystonia was observed (Burke-Fahn-Marsden (BFM) scores of 65.5 and 62 and disability scores of 28 and 26, pre- and post-DBS, respectively) and the DBS device was removed. Treatment with dantrolene reduced skeletal muscle tone and improved movement (Global Dystonia Rating Scores from 5 to 1 and BFM score 42). Therefore, we conclude that DBS was a safe but ineffective intervention in our case with long-standing dystonia, whereas treatment of spasticity with dantrolene did improve the movement disorder in this young man with X-ALD.
| S-EPMC4270865 | biostudies-literature
Project description:Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. Results: Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline. Conclusion: Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.
| S-EPMC7330126 | biostudies-literature
Project description:IntroductionGlobus pallidus internus (GPi) deep brain stimulation (DBS) is widely used in patients with dystonia. However, 10-20% of patients receive insufficient benefits. The objectives of this study are to evaluate the effectiveness of bilateral subthalamic nucleus (STN) DBS along with unilateral posteroventral pallidotomy (PVP) in patients with dystonia who experienced unsatisfactory GPi-DBS and to address the reported rescue procedures after suboptimal DBS or lesion surgery in dystonia patients.MethodsSix patients with isolated dystonia who had previously undergone bilateral GPi-DBS with suboptimal improvement were included. Standardized assessments of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and quality of life using SF-36 were evaluated before surgery and 1, 6 months, and last follow-up (LFU) after surgery. STN bilateral OFF (bi-OFF), unilateral ON (uni-ON), and bilateral ON (bi-ON) states were recorded at LFU. Specific items were used to find publications published before 10 April 2022 regarding rescue procedures after suboptimal DBS or lesion surgery in patients with dystonia for reference. Eleven original studies including case reports/series were identified for discussion.ResultsSubstantial clinical benefits were achieved in all six patients. Significant amelioration was achieved during the 1-month (6.5 ± 7.45; p = 0.0049), 6-month (5.67 ± 6.3; p = 0.0056) follow-ups, and at LFU (4.67 ± 4.72; p = 0.0094) when compared with the baseline (LFU of GPi DBS with on status) (17.33 ± 11.79) assessed by BFMDRS. The percentage of improvement reached 70.6, 74.67, and 77.05%, respectively. At LFU, significant differences were found between the stimulation bi-OFF and uni-ON (11.08 ± 8.38 vs. 9 ± 8.52, p = 0.0191), and between the stimulation bi-OFF and bi-ON (11.08 ± 8.38 vs. 4.67 ± 4.72, p = 0.0164). Trends depicting a better improvement in stimulation bi-ON compared with uni-ON (4.67 ± 4.72 vs. 9 ± 8.52, p = 0.0538) were observed.ConclusionOur results suggest that bilateral STN-DBS plus unilateral PVP may be an effective rescue procedure for patients with isolated dystonia who experienced suboptimal movement improvement following GPi-DBS. However, given the heterogeneity of patients and the small sample size, these findings should be interpreted with caution.
| S-EPMC9434021 | biostudies-literature
Project description:We describe the case of a 42-year-old Japanese woman with childhood-onset myoclonus, dystonia, and psychiatric symptoms, including anxiety, phobia, and exaggerated startle response. The diagnosis was confirmed as myoclonus-dystonia (DYT11) by identifying a mutation in the gene encoding ε -sarcoglycan. Interestingly, while motor-related symptoms in DYT11 generally improve with alcohol ingestion, the patient's symptoms were exacerbated by alcohol intake. Her severe and medically intractable symptoms were alleviated by bilateral deep brain stimulation of the globus pallidus internus, with myoclonus and dystonia scores showing 70% improvement after the surgery compared to presurgical scores. This is the first report of a genetically confirmed case of DYT11 in Japan. This paper together with other recent reports collectively demonstrates that DYT11 patients are distributed worldwide, including Asia. Thus, a diagnosis of DYT11 should be considered when clinicians encounter a patient with childhood-onset myoclonus and/or dystonia with psychiatric symptoms, regardless of ethnic background.
| S-EPMC3970395 | biostudies-literature
Project description:While deep brain stimulation (DBS) treatment is relatively rare in children, it may have a role in dystonia to reduce motor symptoms and disability. Pediatric DBS studies are sparse and limited by small sample size, and thus, outcomes are poorly understood. Thus, we performed a systematic review of the literature including studies of DBS for pediatric (age < 21) dystonia. Patient demographics, disease causes and characteristics, motor scores, and disability scores were recorded at baseline and at last post-operative follow-up. We identified 19 studies reporting DBS outcomes in 76 children with dystonia. Age at surgery was 13.8 ± 3.9 (mean ± SD) years, and 58% of individuals were male. Post-operative follow-up duration was 2.8 ± 2.8 years. Sixty-eight percent of patients had primary dystonia (PD), of whom 56% had a pathological mutation in DYT1 (DYT1+). Across all patients, regardless of dystonia type, 43.8 ± 36% improvement was seen in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (-M) scores after DBS, while 43.7 ± 31% improvement was observed in BFMDRS disability (-D) scores. Patients with PD were more likely to experience ≥ 50% improvement (56%) in BFMDRS-M scores compared to patients with secondary causes of dystonia (21%, p = 0.004). DYT1+ patients were more likely to achieve ≥ 50% improvement (65%) in BFMDRS-D than DTY1- individuals (29%, p = 0.02), although there was no difference in BFMDRS-M ≥ 50% improvement rates between DYT1+ (66%) or DYT1- (43%) children (p = 0.11). While DBS is less common in pediatric patients, individuals with severe dystonia may receive worthwhile benefit with neuromodulation treatment.
| S-EPMC6500764 | biostudies-literature
Project description:Generalized dystonia, both primary and secondary forms, and axial dystonias such as tardive dystonia, and idiopathic cervical dystonia are responsive to globus pallidus interna (GPi) DBS. There is a paucity of investigations probing the impact of DBS on adult-onset axial dystonia. We assessed the efficacy of GPi DBS in four patients with rare adult-onset axial dystonia.Primary outcome measure was improvement in the motor component of the Burke-Fahn-Marsden (BFM) rating scale. Secondary outcome measures were quality of life as determined by the SF-36 questionnaire, time to achieve best possible benefit and DBS parameters that accounted for the best response. In patients with prominent concomitant cervical dystonia we also used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS).GPi DBS improved BFM scores by 87.63 ± 11.46%. Improvement in total severity scale of TWSTRS was 71.5 ± 12.7%. Quality of life also remarkably improved as evidenced by 109.38 ± 82.97 and 7.05 ± 21.48% percent change in psychometrically-based physical component summary (PCS), and a mental component summary (MCS) score respectively.GPi DBS is a very effective treatment for adult-onset axial dystonia. Considering its refractoriness to medical therapy and significant impact on quality of life DBS should be considered for this disorder.
| S-EPMC4879957 | biostudies-literature
Project description:BackgroundDystonia is a movement disorder substantially affecting the quality of life and the ability to work. A proportion of patients does not respond to first line pharmacotherapy. Deep brain stimulation (DBS) is established as a primary operative treatment option for severe drug resistant dystonia. We studied dystonia patients treated with DBS in Finland between the years 2007-2016 to evaluate the use and outcomes of DBS treatment.MethodsWe analysed the hospital records of dystonia patients, who underwent DBS operation during 2007-2016 in Finland. The clinical and technical parameters were recorded as well as preoperative assessments and treatments. The response to DBS was evaluated retrospectively using the Global Dystonia Rating Scale (GDS).ResultsOut of 585 dB implantations during the study period, 37 were done for dystonia. The clinical response improved significantly with time in the isolated focal dystonia group, and at 12 months, 22 of 32 patients had over 50% alleviation of the GDS score. There was only one subclinical intracerebral haemorrhage, and four infections leading to revision. Speech impairment and limb coordination problems were common stimulation- related adverse events and were mostly resolved or relieved with the adjustment of stimulation parameters.ConclusionsDBS seems to be beneficial in dystonia. Although DBS is indicated for dystonia in Finland, the number of operations did not increase at the same rate as DBS operations in general. DBS appears to be a safe and effective treatment for focal as well as generalized dystonia.
| S-EPMC6589889 | biostudies-literature
Project description:The pattern of reoccurrence of symptoms after discontinuation of deep brain stimulation (DBS) has not been systematically studied in dystonia. Eight patients (mean age (SD) 53.8 (14.4) years) with segmental dystonia at a mean follow-up of 11.3 (4.2) months were studied after implantation of bilateral DBS electrodes in the internal globus pallidus using a standard video protocol and clinical rating scales, immediately and at 2 and 4 h after switching off DBS. Dystonic signs returned sequentially, with a rapid worsening of phasic and a slower worsening of tonic dystonic components. In all patients, phasic dystonic features appeared within a few minutes, whereas the tonic elements of dystonia reoccurred with a more variable delay. Differential clinical effects when withdrawing DBS might reflect its influence on different pathophysiological mechanisms in dystonia.
| S-EPMC2117641 | biostudies-literature
Project description:BACKGROUND:Subthalamic nucleus deep brain stimulation (STN DBS) surgery is clinically effective for treatment of cervical dystonia; however, the underlying physiology has not been examined. We used transcranial magnetic stimulation (TMS) to examine the effects of STN DBS on sensorimotor integration, sensorimotor plasticity and motor cortex excitability, which are identified as the key pathophysiological features underlying dystonia. METHODS:TMS paradigms of short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) were used to examine the sensorimotor integration. Sensorimotor plasticity was measured with paired associative stimulation paradigm, and motor cortex excitability was examined with short interval intracortical inhibition and intracortical facilitation. DBS was turned off and on to record these measures. RESULTS:STN DBS modulated SAI and LAI, which correlated well with the acute clinical improvement. While there were no changes seen in the motor cortex excitability, DBS was found to normalise the sensorimotor plasticity; however, there was no clinical correlation. CONCLUSION:Modulation of sensorimotor integration is a key contributor to clinical improvement with acute stimulation of STN. Since the motor cortex excitability did not change and the change in sensorimotor plasticity did not correlate with clinical improvement, STN DBS demonstrates restricted effects on the underlying physiology. CLINICAL TRIAL REGISTRATION:NCT01671527.
| S-EPMC7498178 | biostudies-literature