Successful Radiofrequency Lesioning of the Pallidothalamic Tract in Paretic Form Focal Hand Dystonia With Paradoxical Unexpected Response to Intraoperative Test Electrical Stimulation: A Case Report.

We report a case with paretic focal hand dystonia, which at first glance was diagnosed as writer's cramp, with poor performance only when playing the guitar and writing but with increased muscle tension around the elbow rather than in the fingers and hands. The muscle tension was around the elbow and the pallidothalamic tract (PTT) was selected as the proximal muscle target with less permanent complications. During the operation, the PTT test electrical stimulation was impaired only for guitar playing, but not for other hand movements. Therefore, test lesioning at a lower temperature and for a shorter time improved the symptoms, so we were convinced that this was the target site and coagulated this site, i.e., the PPT, at the usual temperature and time. With only one target lesioning, the patient's symptoms disappeared for six months. Careful history taking and physical examination to identify the site of muscle tension is important in determining the target of paretic form dystonia. In addition, test lesioning at a lower temperature and for a shorter time is useful if the test electrical stimulation produces a paradoxically unexpected response.

Impact of Audio-Visual Complexity on Symptomatology of Laryngeal Dystonia: A Virtual Reality Study.

BACKGROUND: Laryngeal dystonia (LD) is an isolated focal dystonia characterized by involuntary spasms in laryngeal muscles selectively impairing speech production. Anecdotal observations reported the worsening of LD symptoms in stressful or vocally demanding situations. OBJECTIVES: To examine the impact of surrounding audio-visual complexity on LD symptomatology for a better understanding of disorder phenomenology. METHODS: We developed well-controlled virtual reality (VR) environments of real-life interpersonal communications to investigate how different levels of audio-visual complexity may impact LD symptoms. The VR experiments were conducted over five consecutive days, during which each patient experienced 10 h of 4100 experimental trials in VR with gradually increasing audio-visual complexity. Daily reports were collected about patients' voice changes, as well as their comfort, engagement, concentration, and drowsiness from using VR technology. RESULTS: After a weekly VR exposure, 82% of patients reported changes in their voice symptoms related to changes in background audio-visual complexity. Significant differences in voice symptoms were found between the first two levels of the audio-visual challenge complexity independent of study sessions or VR environments. CONCLUSION: This study demonstrated that LD symptoms are impacted by audio-visual background across various virtual realistic settings. These findings should be taken into consideration when planning behavioral experiments or evaluating the outcomes of clinical trials in these patients. Moreover, these data show that VR presents a reliable and useful technology for providing real-life assessments of the impact of various experimental settings, such as during the testing of novel therapeutic interventions in these patients. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Antipsychotics and chronic dystonia at a Botulinum Toxin clinic.

Background: Chronic dystonia, characterised by sustained muscle contractions and abnormal postures, poses clinical challenges, especially when associated with antipsychotic medication use. Aim: To delineate the demographic and clinical profiles of adults with dystonia and examine the association with antipsychotic medication. Setting: Botulinum Toxin Clinic at Tygerberg Hospital, Cape Town, South Africa. Methods: We conducted a retrospective cohort study of adult patients seen at the Botulinum Toxin Clinic between January 2018 and June 2022. Results: Of the 119 patients studied, those assessed with antipsychotic-induced dystonia (32.69%) presented at a younger age (p < 0.001), were more likely female (p = 0.04), received higher average dose of Botulinum toxin (p < 0.001), and incurred a higher estimated Botulinum toxin treatment cost (p = 0.01) compared to those with primary dystonia. Logistic regression identified age and Botulinum toxin dose as factors associated with psychotropic-related dystonia (p = 0.005 and p = 0.012, respectively). Conclusion: Clinical and demographic factors are associated with dystonia in adults taking antipsychotic medication. These patients generally manifested symptoms at an earlier age, had a higher male prevalence, and required prolonged treatment with Botulinum toxin, leading to increased costs. In those assessed with antipsychotic-induced dystonia, a comorbid diagnosis of a mood disorder was more common than that of a psychotic disorder. Contribution: By identifying the demographic and clinical profile of individuals with dystonia because of antipsychotic medication, this study provides a basis for preventative strategies and enhanced patient care.

Interdisciplinary Consensus in Evaluating the Severity Subscale of the Original and Revised Toronto Western Spasmodic Torticollis Rating Scale Through Video-Based Assessment: An Inter-Rater Reliability Study.

BACKGROUND: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is widely employed for cervical dystonia (CD) evaluation. OBJECTIVE: To assess the inter-rater reliability of the severity subscale of the original and revised TWSTRS using video recordings. METHODS: Three raters, a PhD student with a nursing degree, a physiotherapist specialized in CD, and a neurologist-in-training independently rated all videos. The inter-rater reliability was assessed with the intra-class correlation coefficient (ICC). RESULTS: The total severity score of both tools demonstrated a good inter-rater reliability (ICC = 0.87 to 0.88). The inter-rater reliability of individual sub-items varied from poor (ICC = 0.29) to excellent (ICC = 0.9). CONCLUSIONS: The total severity score of both TWSTRS showed good inter-rater reliability in a multidisciplinary team, indicating their applicability for online patients' assessment. We recommend using the total subscale for outcome comparison. Furthermore, there is a need for more accurate definitions of duration factor and shoulder elevation.

Movement disorders in dengue encephalitis: a case report and literature review.

Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV). The clinical manifestations of DENV infection range from mild febrile illness to severe dengue shock syndrome and dengue hemorrhagic fever. Recently, its neurological manifestations have been reported. The mechanisms of neurological complications in DENV infection are often attributed to neurotropism or may be immune-mediated. A double-doughnut sign is a radiological pattern of signal changes in the bilateral thalami, resembling a doughnut. Although this sign has been reported with dengue encephalitis, Japanese encephalitis, and other neurotropic infections, its co-occurrence with mixed movement disorders is rare. We report a case of dengue encephalitis involving a spectrum of movement disorders in the form of jaw opening dystonia, stereotypies, parkinsonism, and tremors during recovery. Magnetic resonance imaging showed bilateral thalami involvement with a double-doughnut sign. The patient was managed with pulse steroid therapy and benzodiazepines and showed gradual improvement in symptoms. Movement disorders with DENV infection are rare and self-limiting.

Atrophy of cerebellar lobule VI and primary motor cortex in cervical dystonia - a region of interest-based study.

BACKGROUND: Recently, a network model of cervical dystonia (CD) has been adopted that implicates nodes and pathways involving cerebellar, basal-ganglia and cortico-cortical connections. Although functional changes in the cerebello-thalamo-cortical network in dystonia have been reported in several studies, structural information of this network remain sparse. OBJECTIVE: To characterize the structural properties of the cerebellar motor network in isolated CD patients. This includes cerebellar lobules involved in motor processing, the dentate nucleus (DN), the thalamus, and the primary motor cortex (M1). METHODS: Magnetic resonance imaging data of 18 CD patients and 18 healthy control subjects were acquired. In CD patients, the motor part of the Toronto Western Spasmodic Torticollis Rating Scale was assessed to evaluate motor symptom severity. The volume of cerebellar lobules I-VI and VIII, the DN and thalamus, and the cortical thickness (CT) of M1 were determined for a region of interest (ROI)-based quantitative analysis. Volumes/CT of these ROIs were compared between groups and associated with motor symptom severity in patients. RESULTS: The volume of lobule VI and the CT of M1 were reduced in CD patients. The volumes of the other ROIs were not different between groups. No association was identified between the structural properties of lobule VI or M1 and the severity of CD motor symptoms. CONCLUSION: Atrophy within the cerebellum and M1 contributes to CD's complex motor network pathology. Further investigations are needed to ascertain the mechanisms underlying the local volume loss.

Movement disorders in Megalencephalic Leukoencephalopathy with subcortical cysts - A case series.

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) has been described in the literature mostly as early-onset leukodystrophy with cerebellar ataxia being the main clinical phenotype. However, other associated movement disorders have also been reported discretely. CASES: Here, we present seven cases of MLC. Cerebellar ataxia was common in them, while dystonia was present in six, parkinsonism in one and stereotypy in two. Six of them, belonging to the Agarwal community, had the common c.135dup variant. CONCLUSION: Our observation highlights the presence of movement disorders in MLC beyond cerebellar ataxia and phenotypic variability of the c.135dup variant, prevalent in the Agarwal community.

Dystonic Tremor as Main Clinical Manifestation of SCA21.

BACKGROUND: Spinocerebellar ataxia type 21 (SCA21) is a rare inherited neurological disorder characterized by motor, cognitive, and behavioral disturbances, caused by autosomal dominant TMEM240 variants. OBJECTIVES: To identify the genetic cause of a dystonic tremor with autosomal dominant inheritance. METHODS: Six subjects of a multi-generational French family affected by tremor and dystonia were studied. Each patient underwent a comprehensive clinical assessment and a whole-exome sequencing analysis. RESULTS: All six subjects presented with early-onset prominent hand dystonic tremor and multifocal/generalized dystonia, secondarily developing mild cerebellar ataxia. The younger generation showed more pronounced cognitive and behavioral impairment. The known pathogenic TMEM240 c.509C>T (p.P170L) variant was found in heterozygosis in all subjects. CONCLUSIONS: Dystonic tremor can represent the core clinical feature of SCA21, even in absence of overt cerebellar ataxia. Therefore, TMEM240 pathogenic variants should be considered disease-causing in subjects displaying dystonic tremor, variably associated with ataxia, parkinsonism, neurodevelopmental disorders, and cognitive impairment.

Woodhouse-sakati syndrome with no reportable MRI findings: a case report.

BACKGROUND: Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive condition caused by biallelic pathogenic variants in the DCAF17 gene, with fewer than 200 cases reported in the literature. Symptoms first emerge in middle-late adolescence with a spectrum of hypogonadal and progressive neurological features. CASE PRESENTATION: We present a case of WSS with no reportable T2-weighted, apparent diffusion coefficient mapping and susceptibility weighted MRI findings. This differs from cases reported in the current literature. Our patient developed abnormal movements in both legs, clumsiness of the hands, dysarthria, and swallowing difficulties. Moreover, she presented with alopecia manifesting as frontal and temporal balding, severe dystonia with painful dystonic spasms primarily in the left upper limb, as well as primary amenorrhea. She was not independently ambulatory on presentation, requiring wheelchair assistance. Genetic testing, the crucial test for a definitive diagnosis, was undertaken in Qatar and confirmed WSS. Treatment provided includes botulinum toxin injections and deep brain stimulation, providing better dystonia control, with progress in walking and strength exercises, and overall remarkable improvement. Intensive neurorehabilitation regimes were also deployed from admission, including physiotherapy, occupational therapy and speech and language therapy. CONCLUSION: This case adds to the current literature on WSS manifestations, with all previously reported cases having positive MRI findings, unlike our case.

Prolonged Lower Limb Dystonia and Dysphonia Following General Anesthesia in a Patient on Hydroxyzine.

We present a case of prolonged lower limb movement disorder following general anesthesia in a female patient in her early forties. She presented with vigorous, regular synchronous, rhythmic, and jerky movements during the immediate postoperative period lasting around forty minutes. Her past anesthetic history suggests varying degrees of postoperative movement disorders. Our patient was on long-term hydroxyzine for her skin condition. She had uneventful anesthetics before the prescription of hydroxyzine for her skin condition. All post-anesthetic dystonic events were reported while she was on hydroxyzine. Dystonic reactions during the perioperative period are rare and mostly occur during induction and emergence, which usually be transient. Our patient had prolonged lower limb dystonia resulting in severe muscular pain and lethargy for a few days. Further, she once developed transient aphasia and prolonged dysphonia following total intravenous anesthesia. This clinical finding could be a part of spasmodic laryngeal dystonia, which has not been reported previously. We correlate this rare postoperative dystonic reaction with propofol and possibly with the concurrent use of hydroxyzine. As differential diagnosis can widely vary, the correlation of clinical findings with movement disorders is important for the diagnosis. Alterations of anesthetic techniques avoiding propofol and holding hydroxyzine are advisable in such rare clinical situations. Early diagnosis of perioperative movement disorders will prompt specific treatments, such as anticholinergic medications, for dystonia.

Unilateral Stereotactic Radiofrequency Lesioning as a Surgical Treatment Option for Meige Syndrome.

Background Meige syndrome is a segmental dystonia affecting the head and neck, with bilateral blepharospasm as the primary symptom. First-line treatment typically involves Botox injections. For cases resistant to this treatment, bilateral deep brain stimulation of the globus pallidus internus (GPi) is considered. This study explores the efficacy of unilateral radiofrequency (RF) lesioning as an alternative surgical treatment for Meige syndrome. Methods We investigated six cases of medically refractory Meige syndrome treated with unilateral RF lesioning between October 2022 and August 2023. The procedures utilized the Leksell Stereotactic System (Elekta, Stockholm, Sweden) and the StealthStation S8 system (Medtronic, Dublin, Ireland). Target coordinates were initially set at 8-9 mm lateral and 1-2 mm inferior to the mid-commissure point (MCP) for the pallidothalamic tract (PTT), and 20 mm lateral, 2 mm anterior, and 3.0-4.5 mm inferior to the MCP for GPi, with fine adjustments based on MRI findings. Results The mean age of patients was 53. 3 ±16.5 years. Five patients underwent PTT RF lesioning, while one received GPi RF lesioning (pallidotomy). No surgical complications were reported. The Burke-Fahn-Marsden Dystonia Rating Scale scores were 32.9 ± 19.4 preoperatively and 17.7 ± 13.9 three months postoperatively, reflecting an average improvement of 42.7%. The Jankovic Rating Scale scores were 7.17 ± 0.76 preoperatively, 2.33 ± 2.34 the day after surgery (average improvement of 67%), and 3.50 ± 1.64 three months postoperatively (average improvement of 51%). Bilateral facial symptoms improved in four patients (67%). Conclusion Unilateral RF lesioning for Meige syndrome demonstrated the potential to improve bilateral symptoms and may be considered a viable treatment option for patients with refractory cases.

Beyond Pallidal or Subthalamic Deep Brain Stimulation to Treat Dystonia.

Deep brain stimulation of the subthalamic nucleus and globus pallidus internus is approved by the Food and Drug Administration for treating dystonia. Both targets have shown effectiveness in improving symptoms, but post-operative outcomes can vary significantly among patients. This variability has led researchers to explore alternative neuromodulation targets that might offer more consistent results. Emerging research has highlighted several promising new targets for DBS in dystonia. This review examines pre-clinical and clinical data on novel DBS targets for dystonia and explores non-invasive neuromodulation studies that shed light on the disease's underlying pathological circuitry.

Directional Stimulus-Evoked Pallidal Electrophysiology in Primary Dystonia.

Background: Deep brain stimulation for dystonia improves motor symptoms but variable and delayed responses challenge patient selection, targeting, and device programming. Case Report: Here we studied intracranial electrophysiology in a patient with primary dystonia and observed evoked resonant neural activity (ERNA) in the globus pallidus interna. These local stimulus-evoked potentials displayed refractory periods and paired-pulse facilitation at clinically relevant interstimulus intervals. Sensing from directional DBS contacts localized ERNA to an effective stimulation site in the ventral posterolateral portion of the pallidum. Discussion: To the best of our knowledge, this is the first observation of ERNA in the globus pallidus interna in a patient with primary dystonia. Stimulus-evoked activity could eventually guide both directional and adaptive stimulation for dystonia and other complex neuropsychiatric disorders.

Genetic Risk Factors in Isolated Dystonia Escape Genome-Wide Association Studies.

BACKGROUND: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia. OBJECTIVE: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia. METHODS: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation. RESULTS: This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small. CONCLUSIONS: Moderate single-nucleotide polymorphism-based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Management of tardive dyskinesia and tardive dystonia with clozapine: A retrospective study.

AIM: This retrospective study aimed to evaluate the long-term effectiveness of switching to clozapine in the management of tardive syndromes (TS). METHODOLOGY: The treatment records of patients who had TS at the time of starting clozapine, were reviewed and demographic and clinical data was extracted on a predesigned performa. RESULTS: About three-fourth (74.2 %) of the study subjects had tardive dystonias and two-third (69.7 %) had tardive dyskinesia at the time of starting clozapine. About half (48.5 %) of the patients had both tardive dystonia and dyskinesia. A small proportion (13.6 %) also had tardive akathisia at the time of starting clozapine. About three-fourth (72.2 %) of the patients had >50 % reduction, and about two-third (66.6 %) of the patients had >75 % reduction and nearly half (54.5 %) of the patients had complete resolution of dyskinesia at the last follow-up. Similar trends were seen in reduction in dystonia, i.e., >50 % reduction in 74.3 %, >75 % reduction in 62.2 % and complete resolution was seen in 56.1 %. CONCLUSIONS: The present study suggest that clozapine is useful in the management of drug induced tardive dyskinesia and tardive dystonia.