Loss-of-function mutations in SGCE found in Japanese patients with myoclonus-dystonia.

SGCE myoclonus-dystonia is a monogenic form of dystonia with an autosomal dominant mode of inheritance that co-occurs with a myoclonic jerk. In this study, we present 12 Japanese patients from nine families with this disease. Targeted next-generation sequencing covering major causative genes for monogenic dystonias identified nine distinct SGCE mutations from each of the families: three nonsense, two frameshift, two missense, one in-frame 15 bp deletion, and one splice donor site mutations, of which four were previously unreported. One missense mutation (c.662G>T, p.Gly221Val) was located at the 3' end of exon 5 (NM_001099400), which was predicted to cause aberrant splicing according to in silico predictions. Minigene assays performed together with the c.825+1G>C mutation demonstrated complete skipping of exon 5 and 6, respectively, in their transcripts. The other missense (c.1345A>G, p.Met449Val) and 15 bp deletion (c.168_182del, p.Phe58_Leu62del) mutations showed a significant reduction in cell membrane expression via HiBiT bioluminescence assay. Therefore, we concluded that all the detected mutations were disease-causing. Unlike the other detected mutations, p.Met449Val affects only isoform 3 (NP_001092870 encoded by NM_001099400) among the variously known isoforms of SGCE. This isoform is brain-specific and is mostly expressed in the cerebellum, which supports recent studies showing that cerebellar dysfunction is a key element in the pathophysiology of SGCE myoclonus-dystonia.

Bilateral Radiofrequency Ventral Intermediate Thalamotomy for Essential Tremor.

INTRODUCTION: With the advent of MR-guided focused ultrasound, the importance of the efficacy and safety of bilateral ventral intermediate (Vim) thalamotomy for essential tremor (ET) has increased. However, reports on bilateral Vim thalamotomy for ET remain scarce. METHODS: To review the results and complications of bilateral Vim thalamotomy for the treatment of ET in the upper extremities, we retrospectively analyzed the patients with ET who underwent bilateral Vim thalamotomy with radiofrequency (RF) thermal coagulation. As bilateral simultaneous thalamotomy can cause surgical complications, thalamotomy was performed in stages. The interval between the first and second thalamotomies was 21.3 ± 14.7 months. We evaluated the efficacy using the Clinical Rating Scale for Tremor (CRST) before and after the first and second treatments, respectively. We also evaluated the complications before and after the first and second treatments, respectively. Moreover, we assessed the adverse events. RESULTS: Seventeen patients were included in the study. The mean follow-up period following the second thalamotomy was 29.3 ± 15.0 months. The CRST part A + B scores were 34.9 ± 9.7, 20.8 ± 7.0, and 7.4 ± 6.8 before, following the first (40.4% improvement, p < 0.0001) and second thalamotomies (78.6% improvement, p < 0.0001), respectively. Nine patients presented with prolonged adverse events, including dysarthria, dysgeusia, dysphagia, tongue numbness, unsteady gait, and postural instability at the last available evaluation. All adverse events were mild and did not interfere with the patient's daily activities. DISCUSSION/CONCLUSIONS: Bilateral Vim thalamotomy with RF thermal coagulation was an effective treatment for ET in both upper extremities. Despite most possible complications being mild, additional studies with a larger sample size are required to ensure patient safety.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Focal Hand Dystonia: A Pilot Study.

BACKGROUND: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for the treatment of focal hand dystonia (FHD) is not well known. OBJECTIVE: We aimed to prospectively investigate the efficacy of MRgFUS thalamotomy for the treatment of FHD. METHODS: We performed MRgFUS thalamotomy of the ventro-oral (Vo) nucleus in 10 patients with FHD. We evaluated the scores of the Writer's Cramp Rating Scale (WCRS, 0-30; higher scores indicating greater severity), Tubiana Musician's Dystonia Scale (TMDS, 0-5; lower scores indicating greater severity), and Arm Dystonia Disability Scale (ADDS, 0%-100%; lower scores indicating greater disability) at baseline and 3 and 12 months post-treatment. RESULTS: WCRS, TMDS, and ADDS scores significantly improved from 6.3 ± 2.7, 1.4 ± 0.5, and 58.7% ± 14.3% at baseline to 1.6 ± 3.1 (P = 0.011), 5.0 ± 0 (P = 0.0001), and 81.6% ± 22.9% (P = 0.0229) at 12 months, respectively. There was one prolonged case of dysarthria at 12 months. CONCLUSION: We show that MRgFUS Vo-thalamotomy significantly improved FHD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Long-Term Successful Outcome of Dystonic Head Tremor after Bilateral Deep Brain Stimulation of the Ventral Intermediate and Ventro-Oral Internus Nuclei: A Case Report and Literature Review of Dystonic Head Tremor.

Head tremor in patients with dystonia is referred to as dystonic tremor. During surgical treatment, numerous targets may be selected, including the internal segment of the globus pallidus and the ventral intermediate (Vim) nucleus; however, there is no consensus concerning the most effective treatment target. We report herein a case of dystonic head tremor in which improvement persisted for 5 years after deep brain stimulation (DBS) of the bilateral thalamic Vim and ventro-oral internus (Voi) nuclei. The patient, a 67-year-old woman, has a horizontal head tremor associated with cervical dystonia that had been resistant to drug treatment over 3 years. Immediately following surgery, dystonia and tremor symptoms had completely improved. Voice volume declined and dysarthria occurred but improved upon adjusting the stimulation conditions. Over 5 years, both head tremor and cervical dystonia have been completely controlled, and no other obvious complications have been observed. As the Voi nucleus receives pallidothalamic projections involved in dystonia and the Vim nucleus receives cerebellothalamic projections involved in tremors, stimulating these 2 nuclei with the same electrode appears reasonable in the treatment of dystonic tremor. This case suggests that Vim-Voi DBS may be effective for treating dystonic head tremor.

[Radiofrequency Lesioning Surgery for Movement Disorders].

Radiofrequency lesioning surgery is primarily performed to treat Parkinson's disease, dystonia, and tremor. Its effects are similar to those of deep brain stimulation (DBS). However, Radiofrequency lesioning surgery has not been popularized, possibly due to the over-evaluation of its risks. The current most available targets for the treatment of movement disorders include ventral intermediate (Vim) nucleus, ventral oral (Vo) nucleus, and globus pallidus internus (GPi). Vim thalamotomy is available for Parkinsonian tremor, essential tremor, dystonic tremor, and other various kinds of tremor, and it is highly effective. Bilateral vim thalamotomy is feasible when properly performed on tiny lesions on the bilateral vim nucleus. Vo thalamotomy is mainly available for focal hand dystonia. The safety profile of bilateral Vo thalamotomy has not yet been established, but it is thought that it may lead to irreversible hypophonia and dysarthria. Pallidotomy is selected for treatment of dystonia and Parkinson's disease. Although unilateral pallidotomy is a safe procedure, it can cause medically refractory parkinsonism including postural reflex disturbance and gait disorder. Delayed infarction on the posterior limb of internal capsule is another major concern associated with pallidotomy and can lead to hemiparesis. Correct understanding is absolutely essential to ensure the safety of radiofrequency lesioning surgery.

Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report.

BACKGROUND: We report the first case of transcranial magnetic resonance-guided focused ultrasound (MRgFUS) for mesial temporal lobe epilepsy (MTLE). CASE PRESENTATION: The target was located 20 mm lateral from the midline and 15 mm above the skull base (left hippocampus). Despite the application of maximal energy, the ablation temperature did not exceed 50 °C, probably because of the low number of effective transducer elements with incident angles below 25 degrees. The skull density ratio was 0.56. Post-operative magnetic resonance imaging did not reveal any lesion and the patient remained almost seizure-free for up to 12 months. CONCLUSIONS: This preliminary case report suggests that MRgFUS may be effective for treating cases of MTLE. Therefore, the safety and feasibility of MRgFUS should be evaluated in future studies with larger numbers of participants and longer follow-up duration.

[Bilateral Pallidal Deep Brain Stimulation for Dystonic Camptocormia Induced by Repetitive Abdominal Muscle Exercise:A Case Report].

Camptocormia is a rare and disabling movement disorder resulting in forward bending of the trunk. Camptocormia has many etiologies, although it is frequently observed patients with in Parkinson's disease and dystonia. Deep brain stimulation(DBS)of the globus pallidus internus(GPi)and subthalamic nucleus effectively treats camptocormia in Parkinson's disease and dystonia patients. Herein, we report a case of dystonic camptocormia induced by repetitive abdominal muscle exercise in which treatment was administered using bilateral GPi-DBS. A 54-year-old woman developed dystonic camptocormia at 53 years of age. Prior to the onset of symptoms, she regularly performed 200 abdominal muscle exercises per day. Oral medications, and botulinum toxin and lidocaine injections, were ineffective. Truncal anterior bending occurred while standing and walking. The patient underwent bilateral GPi-DBS, which instantly and dramatically improved her symptoms. The Burke-Fahn-Marsden dystonia rating scale subscore for the trunk before and after bilateral pallidotomy was 6 and 0, respectively. No perioperative adverse events were observed. Symptomatic relief persisted for 2 years. This case suggest that camptocormia can result from repeated abdominal muscle exercise, and that bilateral GPi-DBS may be a feasible and long-term efficacious procedure for dystonic camptocormia.

[Bilateral Pallidotomy for Tardive Dystonia:A Case Report].

Tardive dystonia is a movement disorder related to the use of dopamine-receptor-blocking drugs. Several reports have shown that deep brain stimulation of the globus pallidus internus(GPi-DBS)is effective in treating tardive dystonia. However, a few reports demonstrated the efficacy of ablation of the GPi(pallidotomy). We herein report a case of tardive dystonia successfully treated with bilateral pallidotomy. A 32-year-old man developed severe tardive dystonia 10 years after the chronic use of antipsychotic drugs. Withdrawal of the drugs and botulinum toxin injections were ineffective. The patient underwent bilateral pallidotomy for tardive dystonia because of rejection of the implanted DBS devices. Significant improvement was observed, with a 95% decrease in the Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS)movement score, and no severe adverse events occurred. Symptomatic relief persisted for nine months. Pallidotomy is a feasible and efficacious procedure for tardive dystonia treatment without the use of hardware implantations.

Pallidotomy for Writer's Cramp after Failed Thalamotomy.

BACKGROUND/AIMS: Although many reports have confirmed the effects of stereotactic thalamotomy for writer's cramp, pallidotomy for writer's cramp is yet to be investigated. METHODS: After a 22-year-old woman with writer's cramp had undergone stereotactic thalamotomy twice, symptomatic relief was only temporary. Because her dystonic symptoms spread around the proximal part of the upper limb, she underwent unilateral pallidotomy 21 months after the second thalamotomy. RESULTS: Unilateral pallidotomy improved her dystonic symptoms without any adverse effects immediately after the surgery. During a follow-up observation of 1 year, no recurrent writer's cramp was observed. CONCLUSION: For writer's cramp, when symptoms cannot be improved by thalamotomy, pallidotomy may achieve an effective outcome.

Stereotactic Thalamotomy for Hairdresser's Dystonia: A Case Series.

BACKGROUND: Hairdresser's dystonia is a rarely reported form of focal hand dystonia, and the clinical course and treatment remains poorly understood. OBJECTIVES: The aim of this report was to clarify the impact of thalamotomy on hairdresser's dystonia. METHODS: Four consecutive patients with hairdresser's task-specific dystonia evaluated at Tokyo Women's Medical University Hospital between 2008 and 2013 were treated with stereotactic thalamotomy, and were recruited for this case series. RESULTS: The mean age at the onset of symptoms was 37.25 ± 10.64 years, the median duration of symptoms was 4.25 ± 1.3 years, and the mean follow-up period was 17 ± 12.37 months. Two of the 4 patients returned to work with significant improvement following the stereotactic thalamotomy and the beneficial effects persisted for the duration of their clinical follow-up. The other 2 patients experienced transient improvements for up to 3 months. Surgical complications included only dysarthria in 2 patients, and did not interfere with their daily activities. No patients experienced a deterioration of dystonic symptoms after thalamotomy. CONCLUSION: Although the benefits of thalamotomy remain vulnerable to incorrect or insufficient coagulation, stereotactic thalamotomy may be a feasible and effective procedure for patients with hairdresser's dystonia.

Long-term improvement of musician's dystonia after stereotactic ventro-oral thalamotomy.

OBJECTIVE: Musician's dystonia is a task-specific movement disorder that causes twisting or repetitive abnormal finger postures and movements, which tend to occur only while playing musical instruments. Such a movement disorder will probably lead to termination of the careers of affected professional musicians. Most of the currently available treatments have yet to provide consistent and satisfactory results. We present the long-term follow-up results of ventro-oral thalamotomy for 15 patients with musician's dystonia. METHODS: Between October 2003 and September 2010, 15 patients with medically intractable task-specific focal hand dystonia that occurred only while playing musical instruments underwent ventro-oral thalamotomy. We used Tubiana's musician's dystonia scale to evaluate the patients' pre- and postoperative neurological conditions. RESULTS: All patients except 1 (93%) experienced dramatic improvement of dystonic symptoms immediately after ventro-oral thalamotomy. The mean follow-up period was 30.8 months (range=4-108 months). None of the patients experienced recurrence or deterioration of symptoms during the follow-up periods. INTERPRETATION: Ventro-oral thalamotomy remarkably improved musician's dystonia, and the effect persisted for a long duration.

Efficacy and safety of zolpidem for musician's dystonia.

Background: The efficacy and safety of zolpidem in treating musician's dystonia are not well understood. Objective: We aimed to retrospectively investigate the efficacy and safety of zolpidem for musician's dystonia. Methods: We retrospectively reviewed medical records between January 2021 and December 2023 to identify patients with musician's dystonia who had been prescribed zolpidem. The Tubiana's musician's dystonia rating scale (range, 1-5; lower scores indicating greater severity) was used to evaluate musician's dystonia. Results: Fifteen patients were included in this study. The mean effective dose of zolpidem was 5.3±2.0 mg. The mean effective duration of zolpidem was 4.3±1.2 h. With zolpidem administration, the Tubiana's musician's dystonia rating scale score significantly improved from 2.2±1.0 to 4.3±0.8 (48.9% improvement, p<0.001). Two patients (13.3%) discontinued the drug owing to unsatisfactory results or sleepiness. Conclusion: This study suggests that zolpidem may be an alternative treatment option for musician's dystonia.

Long-term follow-up of task-specific tremor after thalamotomy: a retrospective observational study.

OBJECTIVE: This study aimed to report the long-term results of thalamotomy in 23 patients with task-specific tremor. METHODS: Data of 23 patients with task-specific tremor who underwent ventralis intermedius nucleus and posterior part of ventro-oral nucleus thalamotomy at the Tokyo Women's Medical University Hospital between 2010 and 2022 were retrospectively analyzed. To evaluate neurological conditions, the severity of task-specific tremor was divided into 0 (no tremor), 1 (slightly tremulous), 2 (moderately tremulous), 3 (accomplishing tasks with great difficulty), and 4 (unable to complete tasks). We also used the subscores "handwriting" (0-4) and "spiral drawing" (0-4) of the Clinical Rating Scales for Tremor. Evaluation scales were presented as medians and interquartile ranges. RESULTS: The severities of task-specific tremor were 3.0 (3.0-4.0) preoperatively and 0.0 (0.0-0.0, p < 0.0001) at the last available evaluation. The writing and spiral drawing of the Clinical Rating Scales for Tremor significantly improved from 3.0 (3.0-4.0) and 3.0 (2.0-3.0) preoperatively, respectively, to 0.0 (0.0-0.0, p < 0.0001) and 0.0 (0.0-0.0, p < 0.0001) at the last available evaluation, respectively. The mean clinical follow-up period was 62.7 ± 26.0 months. Seven (30.4%) patients had focal hand dystonia, which newly developed on the ipsilateral side of the tremor at 2-45 months after the surgery. No serious complications were observed. INTERPRETATION: Thalamotomy significantly improves task-specific tremor with high long-term efficacy, and long-term follow-up is important because focal hand dystonia can develop postoperatively.

Spinal cord stimulation and intrathecal baclofen therapy: combined neuromodulation for treatment of advanced complex regional pain syndrome.

OBJECTIVE: Spinal cord stimulation (SCS) is one of the widely used procedures for the treatment of complex regional pain syndrome (CRPS). However, complete pain relief is rarely achieved, and the SCS effect diminishes over time. Recently intrathecal baclofen (ITB) therapy is reported to be a modality for treating fixed dystonia related to CRPS. Other reports have suggested that ITB therapy can enhance the effect of SCS in patients with neuropathic pain. We report the effectiveness of combined SCS and ITB therapy, focusing on the role of ITB therapy as an adjunctive therapy for controlling symptoms of advanced CRPS. METHODS: Five affected extremities of 4 patients with CRPS (2 male; mean age, 32.5 years) refractory to conservative treatment were evaluated retrospectively. Three patients underwent SCS implantation first, with ITB pumps being implanted a few years later. Bolus ITB injection was administered under temporary percutaneous SCS in 1 patient. Pain intensity was evaluated using the visual analogue scale (VAS) before and after ITB administration. RESULTS: Pain relief of more than 50% was observed in the upper extremity of 1 patient and one of more than 30% was observed in 2 patients. The mean pain reduction rate in all 4 patients was 28.9% before and 43.8% after treatment. All patients, including those without any improvements in VAS score, showed decreased postural abnormalities after combined SCS and ITB therapy. Improvement in postural abnormalities, such as fixed dystonia or paroxysmal tremor-like movements, resulted in overall pain relief by reducing pain fluctuations. CONCLUSIONS: Combined SCS and ITB neuromodulation decreases pain intensity in refractory CRPS cases or improves associated abnormal dystonic posture and movement disorders and reduces pain fluctuations.

Myotomy and Selective Peripheral Denervation Based on 18F-FDG PET/CT in Intractable Cervical Dystonia: A Case Report.

Cervical dystonia, characterized by the involuntary contraction of cervical muscles, is the most common form of adult dystonia. In a patient with intractable cervical dystonia, we carried out a myotomy of the left obliquus capitis inferior and selective peripheral denervation (SPD) of the posterior branches of the C3-C6 spinal nerves based on preoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). The patient was a 65-year-old, right-handed man with an unremarkable medical history. His head rotated involuntarily to the left. Medication and botulinum toxin injections were ineffective, and surgical treatment was considered. 18F-FDG PET/CT imaging revealed FDG uptake in the left obliquus capitis inferior, right sternocleidomastoideus, and left splenius capitis. Myotomy of the left obliquus capitis inferior and SPD of the posterior branches of the C3-C6 spinal nerves was performed under general anesthesia. During the 6-month follow-up, the patient's Toronto Western Spasmodic Torticollis Rating Scale score improved from 35 to 9. This case shows that preoperative 18F-FDG PET/CT is effective in identifying dystonic muscles and determining the surgical strategy for cervical dystonia.

Complex regional pain syndrome after mRNA-based COVID-19 vaccination.

We describe the case of a 17-year-old woman diagnosed with complex regional pain syndrome (CRPS) at a pain clinic after the second dose of the COVID-19 vaccine. She was referred to our department for surgical treatment of movement disorder seven months after the second inoculation. Baclofen (50 µg), administered intrathecally, improved the involuntary movements of her right hand. After administration of zolpidem (5 mg), involuntary movements of the right index finger almost disappeared. However, neither zolpidem nor intrathecal baclofen improved the limited range of motion of the first joint of the left-hand finger. Despite various reports on CRPS development after vaccination, only one case post COVID-19 vaccination has been reported. Therefore, healthcare providers should keep in mind that CRPS can appear after the COVID-19 vaccination.

Radiofrequency ablation of the pallidothalamic tract and ventral intermediate nucleus for dystonic tremor through the parietal approach.

Background: The thalamic ventral intermediate nucleus (Vim) and globus pallidus internus are far apart and cannot be captured using a single electrode. Case Description: We describe our experience with a patient with dystonic tremors of the head and upper and lower extremities who showed symptomatic improvement after radiofrequency (RF) ablation using a parietal lobe approach with a single trajectory to capture the pallidothalamic tract and Vim. A 46-year-old man developed head tremors at 41 and a right-sided neck tilt three years later. Five years after the onset of the head tremors, tightness of the larynx during speech and tremors in both the upper and lower limbs also appeared. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was 24, and the Fahn-Tolosa-Marin Tremor Rating Scale (FTM) score was 48. We captured the pallidothalamic tract and Vim along a single trajectory by locating the entry point in the inferior parietal lobule. One week after treatment, the TWSTRS and FTM scale scores were 9 (62.5%) and 30 (37.5%), respectively. No adverse events were observed. Conclusion: This case suggests that in dystonic tremors involving abnormalities of the basal ganglia-thalamo-cortical and cerebello-thalamo-cortical circuits, a single electrode can be used to approach both circuits through the parietal lobe approach.