Severity of Antipsychotic-Induced Cervical Dystonia Assessed by the Algorithm-Based Rating System.

Background: The severity of antipsychotic-induced cervical dystonia has traditionally been evaluated visually. However, recent advances in information technology made quantification possible in this field through the introduction of engineering methodologies like machine learning.Methods: This study was conducted from June 2021 to March 2023. Psychiatrists rated the severity of cervical dystonia into 4 levels (0: none, 1: minimal, 2: mild, and 3: moderate) for 101 videoclips, recorded from 87 psychiatric patients receiving antipsychotics. The Face Mesh function of the open-source framework MediaPipe was employed to calculate the tilt angles of anterocollis or retrocollis, laterocollis, and torticollis. These were calculated to examine the range of tilt angles for the 4 levels of severity of the different types of cervical dystonia.Results: The tilt angles calculated using Face Mesh for each level of dystonia were 0° ≤ θ < 6° for none, 6° ≤ θ < 11° for minimal, 11° ≤ θ < 25° for mild, and 25° ≤ θ for moderate laterocollis; 0° ≤ θ < 11° for none, 11° ≤ θ < 18° for minimal, 18° ≤ θ <25° for mild, and 25° ≤ θ for moderate anterocollis or retrocollis; and 0° ≤ θ < 9° for none, 9° ≤ θ < 17° for minimal, 17° ≤ θ < 32° for mild, and 32° ≤ θ for moderate torticollis.Conclusion: While further validation with new cases is needed, the range of tilt angles in this study could provide a standard for future artificial intelligence devices for cervical dystonia.

Efficacy and Safety of DaxibotulinumtoxinA for Injection in Cervical Dystonia: ASPEN-1 Phase 3 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: ASPEN-1 was a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, duration of response, and safety of 2 doses of DaxibotulinumtoxinA for Injection (DAXI), a novel botulinum toxin type A formulation in participants with cervical dystonia (CD). METHODS: Adults (aged 18-80 years) with moderate-to-severe CD (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] total score ≥20) were enrolled at 60 sites across 9 countries in Europe and North America. Participants were randomized (3:3:1) to single-dose intramuscular DAXI 125U, 250U, or placebo and followed for up to 36 weeks after injection. The primary end point was change from baseline in TWSTRS total score averaged across weeks 4 and 6. Key secondary end points included duration of effect, Clinical and Patient Global Impression of Change (CGIC, PGIC), TWSTRS subscale scores, and safety. Multiplicity-adjusted intent-to-treat hypothesis tests with multiple imputation were performed using ANCOVA and Cochran-Mantel-Haenszel analyses. RESULTS: Of 444 individuals screened, 301 were randomized to DAXI 125U (n = 125) or 250U (n = 130) or placebo (n = 46). DAXI 125U and 250U significantly improved the mean TWSTRS total score vs placebo (least squares mean [standard error] difference vs placebo: DAXI 125U, -8.5 [1.93], p < 0.0001; DAXI 250U, -6.6 [1.92], p = 0.0006). The median duration of effect (time from treatment until loss of ≥80% of the peak improvement in average TWSTRS total score achieved at weeks 4 and 6) was 24.0 (95% confidence interval 20.3-29.1) weeks with DAXI 125U and 20.3 (16.7-24.0) weeks with DAXI 250U. Significant improvements were also observed with DAXI in CGIC and PGIC responder rates and TWSTRS subscales. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.6% of participants with DAXI 125U, 23.8% with DAXI 250U, and 17.4% with placebo, with injection site pain being the most common overall. The most frequently reported treatment-related TEAEs of interest in DAXI 125U, DAXI 250U, and placebo, respectively, were muscular weakness (4.8%, 2.3%, 0%), musculoskeletal pain (2.4%, 3.1%, 0%), and dysphagia (1.6%, 3.8%, 0%). DISCUSSION: This study demonstrated that DAXI, at doses of 125U and 250U, is an effective, safe, long-acting, and well-tolerated treatment for CD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier (NCT03608397, submitted July 11, 2018) and EU Clinical Trials Register (ClinicalTrialsRegister.eu EudraCT identifier 2018-000446-19, submitted September 13, 2018). First participant enrolled on June 11, 2018. Trial registration was performed in accordance with the Food and Drug Administration Amendments Act (FDAAA 801), which stipulates that the responsible party register an applicable clinical trial not later than 21 calendar days after enrolling the first human participant (42 CFR 11.24). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in adults with moderate-to-severe idiopathic cervical dystonia, DAXI reduces dystonia more effectively than placebo.

Improvement of obsessive-compulsive disorder after pallidothalamic tractotomy for cervical dystonia.

A 30-year-old woman with tardive dystonia in the cervical region from long-term antipsychotic meds was treated with radiofrequency ablation of the right pallidothalamic tract in the fields of Forel. The patient showed improvement in both cervical dystonia and obsessive-compulsive disorder after the procedure, with 77.4% improvement in cervical dystonia and 86.7% improvement in obsessive-compulsive disorder. Although the treatment site in this case was intended to treat cervical dystonia, the lesion was located in the optimal stimulation network for both obsessive-compulsive disorder and cervical dystonia, suggesting that neuromodulation of this region could potentially treat both simultaneously.

[Focal or Segmental Dystonia Resistant to Botulinum Toxin: How Do You Treat Patients in Whom Botulinum Toxin Treatment Has No Effect?]

Botulinum toxin treatment is most commonly used for blepharospasm, spastic torticollis, upper limb dystonia, and local dystonia in Japan. Botulinum toxin treatment is the first choice in these conditions. However, it has the disadvantages that the therapeutic effect is transient, that there are cases in whom the treatment is ineffective, and a high cost. In ineffective cases, botulinum toxin treatment involves medication and rehabilitation. Various medications have been used for the treatment of focal dystonia mainly in open trials. As these treatments have low evidence levels, each case should be dealt with individually. Operative treatment should be considered for severe cases.

Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy.

OBJECTIVE: To investigate the risk factors of neutralizing antibody (NAB)-induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. METHODS: This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. RESULTS: Treatment duration was 9.8 ± 6.2 years (range, 0.5-30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3-112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1-14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. CONCLUSIONS: We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.

Quetiapine-induced cervical dystonia.

OBJECTIVE: Our objective was to report and describe a case of quetiapine-induced dystonia in an older lady with psychosis. Quetiapine is a second-generation antipsychotic and known to be rare in causing extrapyramidal side effects with rates similar to placebo. CONCLUSIONS: There have been few documented cases of quetiapine-induced dystonia. It is important to be vigilant and consider the development of dystonia in patients who may not fit the typical risk profile.

Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration.

Extrapyramidal symptoms are an uncommon but well-recognized side effect after the administration of general anesthesia in patients without a significant neurologic history. Several case reports implicate propofol as the likely causative agent producing these symptoms, which include ballismus, dystonia, choreoathetosis, and opisthotonus. Currently, there is no clear consensus on first-line treatment of these symptoms. In each of the published cases, anticholinergic medications and benzodiazepines were central to initial management, although the speed and extent of symptom resolution were variable. Here we present a case of a 17-year-old boy with ulcerative colitis who presented with ballismus, torticollis, tongue thrusting, and oculogyric movements after colonoscopy under general anesthesia with propofol. The patient responded promptly to treatment with diphenhydramine. This is the first reported case in which diphenhydramine was successfully used as the primary treatment of severe extrapyramidal symptoms in a pediatric patient after propofol administration.

The occurrence of lateral shift in cervical dystonia.

Aim of this study is to identify factors contributing the occurrence of neck lateral shift (LS) in patients with cervical dystonia (CD). A retrospective analysis focused on the treatment with botulinum toxin (BTX) was conducted on 38 consecutive idiopathic CD patients comparing subjects with and without LS. The main result was the evidence of a significantly higher BTX inter-side dose difference in patients with LS suggesting that this uncommon phenotype may be an artifact of chronic therapy with BTX.

Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy.

We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.

Spasmodic torticollis associated with sertraline in a child and an adolescent.

Movement disorders or extrapyramidal symptoms (EPS) associated with selective serotonin reuptake inhibitors (SSRIs) have been reported. Although akathisia was found to be the most common EPS, and fluoxetine was implicated in the majority of the adverse reactions, there were also cases with EPS due to sertraline treatment. We present a child and an adolescent who developed torticollis (cervical dystonia) after using sertraline. To our knowledge, the child case is the first such report of sertraline-induced torticollis, and the adolescent case is the third in the literature.

Mioclonias cervicales en paciente en tratamiento con etanercept / Myoclonus in patients treated with etanercept

No disponible

Acute cervical dystonia after the first dose of butamirate citrate.

Butamirate citrate is a central-acting antitussive drug and is widely used in clinical practice in childhood. It is thought that to be centrally active antitussive drugs act through receptors in the brainstem to inhibit cough, and these findings were based on the evidence of animal models. Central nervous system adverse effects of cough suppressants are rare and include irritability, lethargy, hallucinations, and dystonic reactions. In this report, we present the first patient who developed cervical dystonia shortly after the first dose of butamirate citrate, and the patient's symptoms improved immediately after a single intramuscular dosage of biperiden.

Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata.

GABAergic neurons of the substantia nigra pars reticulata (SNpr) and globus pallidus pars interna (GPi) constitute the output pathways of the basal ganglia. In monkeys, choreiform limb dyskinesias have been described after inhibition of the GPi, but not the SNpr. Given the anatomical and functional similarities between these structures, we hypothesized that choreiform dyskinesias could be evoked by inhibition of an appropriate region within the SNpr. The GABAA receptor agonist, muscimol, was infused into various sites within the SNpr and the adjacent STN of freely moving macaques. The effect of the GABAA antagonist, bicuculline (BIC), was also examined. Muscimol (MUS) in SNpr evoked the following: (1) choreiform dyskinesias of the contralateral arm and/or leg from central and lateral sites; (2) contralaterally directed torticollis from central and posterior sites; and (3) contraversive quadrupedal rotation from anterior and lateral sites. MUS infusions into the adjacent SN pars compacta or STN were without effect, ruling out a contribution of drug spread to adjacent structures. BIC in SNpr induced ipsiversive postures without choreiform dyskinesia or torticollis, whereas in the STN, it evoked ballistic movements. This is the first report of choreiform dyskinesia evoked by inhibition of the SNpr. This highly site-specific effect was obtained from a restricted region within the SNpr distinct from that responsible for inducing torticollis. These results suggest that overactivity of different SNpr outputs mediates choreiform dyskinesia and torticollis. These abnormalities are symptoms of dystonia, Huntington's disease, and iatrogenic dyskinesias, suggesting that these conditions may result, in part, from a loss of function in SNpr efferent projections.