Dystonia Research Articles

Early onset tardive syndromes associated with Lurasidone in patients with mood disorders: A case series and literature review

• The incidence of tardive syndromes on antipsychotics is cumulative and screening as early as one month may enhance the opportunity for early detection and treatment. This is especially important in patients with mood disorders who can be managed using alternative drug classes and can achieve early and full resolution of the movement disorder without the need for antidyskinetic medications. • Differentiation of tardive dyskinesia from tardive dystonia and tardive akathisia is important as they may have different prognoses and treatment. This can be achieved both by expert clinical assessment and the use of scales that capture nuances in tardive syndromes • Newer antipsychotics such as lurasidone are increasingly used in mood disorders with good efficacy but there is limited data on the risks of tardive syndromes in this population. Further work is necessary to characterize which factors are most associated with early onset tardive syndromes. Tardive syndromes (TS) are a group of movement disorders that typically occur following chronic exposure to Dopamine D2 receptor antagonists. Rarely, these syndromes may occur in less than six months following the initiation of a causative medication. Owing to Lurasidone's recent introduction to the North American market, there is limited literature on its association with tardive syndromes. We describe three cases with mood disorder prospectively and systematically followed for tardive syndromes on Lurasidone and present a literature review of existing data on tardive syndromes associated with Lurasidone in patients with mood disorders. These three cases all developed TS before three months. A single previously published case series included cases of early-onset tardive syndromes following lurasidone use. This is an open case series in a single academic practice focused on mood disorders. There is limited data in the literature for comparison. Lurasidone's common use in patients with vulnerabilities to developing tardive syndromes, such as those with mood disorders, may be an area for clinical concern. Clinicians should strongly consider earlier screening for tardive syndromes in patients with appropriate risk factors.

Paroxysmal Dystonia in a Child with Enoyl-CoA Hydratase Short-Chain 1 (ECHS1) Mutations

Paroxysmal Dystonia in a Child with Enoyl-CoA Hydratase Short-Chain 1 (ECHS1) Mutations

Obsessive–compulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia

We aimed to clarify the correlations between motor symptoms and obsessive–compulsive symptoms and between the volumes of basal ganglia components and obsessive–compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke–Fahn–Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive–compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers’ scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). “Checking” rituals had a strong and significant negative correlation with the Burke–Fahn–Marsden Dystonia Rating Scale (ρ = − 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ρ = 0.72, p = 0.023; left: ρ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive–compulsive disorder and dystonia.

Pallidal deep brain stimulation for tardive dystonia: meta-analysis of clinical outcomes.

Tardive dystonia (TD) is a disabling complication of pharmacological therapy with dopaminergic receptor antagonists, usually resistant to oral medications. Several reports have shown that deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD, but the overall level of evidence remains limited to case reports or small case series. We sought to summarize the collective evidence in support of GPi-DBS for TD using a meta-analytic approach. We searched PubMed for human studies reporting tardive dystonia cases treated with GPi-DBS that reported the validated Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) as outcome measure. Data extracted were reviewed for risk of bias. Then, through linear mixed effects modeling of the percent improvement seen on an individual level, we estimated the average improvement effect varying by study. The searching strategy resulted in a total of n = 78 studies, which were screened for eligibility criteria resulting in the inclusion of n = 14 studies, yielding 134 TD patients for the final analyses. The overall estimate improvement in the BFMDRS after GPi-DBS was 66.88 ± 11.96%. The review of individual case reports indicated rare worsening (n = 4) or lack of improvement (n = 3) following GPi-DBS. Bilateral GPi-DBS can be an effective therapeutic option for severe cases of TD resistant to oral pharmacological therapies, even though rare cases of symptom worsening or lack of improvement have also been reported.

Pharmacokinetics of escalating single-dose administration of cannabidiol to cats.

This study aimed to assess the single-dose pharmacokinetics and tolerability of a cannabidiol (CBD) isolate in sunflower oil with escalating oral doses in eight healthy, purpose-bred cats. Eight cats were randomized into six dosing groups of four cats each. Cats were administered a single 2.5, 5, 10, 20, 40, or 80 mg/kg dose orally with at least a two-week washout in between doses. Behavior scoring, complete blood count, serum biochemistry analysis, physical examination, and CBD plasma levels were evaluated before and after dosing. All cats successfully completed the study. CBD was measured in the plasma of all cats dosed with CBD oil. The Cmax and AUC increased in a dose-proportional fashion across all dosing groups. There were no major bloodwork or behavioral changes although the BUN and creatinine values decreased after treatment across all doses. No adverse effects were observed, and behavioral changes were limited to head shaking, lip smacking, and hypersalivation immediately following dose administration. Single orally administered CBD doses up to 80 mg/kg were safe and well tolerated in this cohort of cats and display dose-proportional pharmacokinetics across a broad concentration.

Writing tremor in Parkinson's disease: frequency and associated clinical features.

Action tremor in Parkinson's disease may present in up to 46% of patients, either as postural or kinetic tremor. How action tremor may affect handwriting has been the object of some investigations; however, clinical features of writing tremor in Parkinson's disease are still not well-characterised. One hundred consecutive patients with idiopathic Parkinson's disease were included in the study. Demographic and clinical data were collected through a standardized questionnaire. Patients were assessed for the presence of rest, action and writing tremor in on condition. The effect of a standardised sensory trick (gently touching the wrist of the upper limb manifesting tremor with the contralateral hand) was also investigated in all patients with action tremor. Writing tremor was found in 10% of patients (26% of patients with postural/kinetic tremor, either alone or in combination with rest tremor). Severity of writing tremor did not correlated with that of the other tremor variants and to the other clinical variables. Writing tremor was task-specific in 4/10 patients, no task-specific in 6/10. Sensory trick was effective on writing tremor in two patients but did not improve action tremor in any of the study patients. Results showed that writing tremor in Parkinson's disease is less common than other tremor variants, may be associated with other forms of action tremor, and may sometimes have dystonic features, including task-specificity and sensitivity to sensory trick.

PSII-7 Feed Intake and Behavioral Responses of Mature Rams Provided Feed Containing Phenylthiocarbamide

Abstract Bitter taste perception has been studied in various species, including humans, using the synthetic compound phenylthiocarbamide (PTC). Human perception of PTC is linked to the ability to taste bitter foods. Sheep express varying levels of aversion to PTC delivered in drinking water. The objective of this study was to determine the effects of PTC delivered in feed on dietary intake and behavior in mature rams. We hypothesized that rams previously classified into PTC-taster categories using PTC-spiked drinking water would rank similarly when PTC was added to feed. Mature Targhee, Rambouillet, Polypay, and composite-breed rams, previously classified as either super- (n = 3), intermediate- (n = 5), or non-PTC tasters (n = 4), were subjected to 4-d acclimation and 6-d test phases. Alfalfa (70%), corn (15%), and beat pulp (15%) meal were mixed with ethanol (150 g/kg, as fed) only (control) or PTC solubilized in ethanol (150 g/kg, as fed) to create three pelleted (6.3 mm) test diets (110, 220 and 330 mg PTC/kg feed, as fed). Rams received control and PTC diets (0.87% BW) daily for 30 min in a side-by-side presentation, which was replicated for each PTC concentration. Feeding duration, number of bucket approaches and switches, sniffs, drinks, lip smacks and licks, and head bobs, jerks, and shakes were recorded throughout the trial using video surveillance. For each PTC concentration, consumption of PTC and control diets was similar (P = 0.22) when measured as a percentage of total diet (control + PTC) consumed. Individual PTC diet intakes ranged from 1.5 to 89.8% of total diet consumed. The CV for intake of 110, 220 and 330 mg/kg diets increased from 22.4 to 34.1 to 36.1%, respectively. Intake of total diet offered decreased (P = 0.01) between 110 mg/kg (80.9 ± 3.2%) and 330 mg/kg (72.3 ± 3.2%), while 220 mg/kg (78.4 ± 3.2%) was intermediate (P ≥ 0.06). Rams were classified by average PTC diet consumption relative to ± 1.0 SD of the population mean (50.2 ± 7.5%). Using this method, only 7 of the 12 rams were classified similarly to the former classification established when PTC was added to drinking water. Total feeding duration was less (P ≤ 0.03) when rams were offered 330 mg/kg (805.4 ± 18.2 s) compared with 110 (858.1 ± 19.3 s) and 220 mg/kg (862.7 ± 19.5 s). Rams switched between the control and PTC diets more (P ≤ 0.02) when offered 110 mg/kg (21.2 ± 10.0) than the 220 (16.4 ± 7.8) and 330 mg/kg (18.4 ± 8.4). These results suggest that sheep perceive and exhibit variable responses to PTC when incorporated into a pelleted feed. More research is needed to identify mechanisms by which sheep perceive bitter-tasting feeds.

Comment les Annales Médico-Psychologiques parlaient-elles de l’encéphalite léthargique voici cent ans ?

A century ago, when the so-called Spanish flu epidemic was spreading, René Cruchet in France and Constantin von Economo in Austria drew the attention of military and civilian physicians to the existence of another pandemic, encephalitis lethargica. After a more or less prolonged phase of irrepressible drowsiness, those who survived progressively developed permanent sequelae, i.e. parkinson’ syndrome, or various types of paroxysmal dystonia. The patients were often children and young adults. From 1920 to 1946, the Société Médico-Psychologique devoted twenty sessions to the study of the neuropsychiatric sequelae of these encephalitides. In addition to abnormal movements, psychiatrists treated hallucinatory delusions, violent and aggressive behaviors with sexual disinhibition, myoclonic epilepsy, etc. The clinical presentations summarized here seem to demonstrate that this pandemic allowed psychiatrists to relate psychiatric deterioration to diencephalic and mesencephalic lesions in a way that they had never done before. The current etiological hypothesis concludes this presentation.

PO014 / #468 PRE AND POST OPERATIVE CLINICAL ASSESSMENT OF PATIENTS SUFFRING FOR DYSTONIA: E-POSTER VIEWING

Dystonia is a syndrome characterized by involuntary sustained muscle contractions that result in twisting, repetitive movement and abnormal posture. Dystonia is typically classified by age of onset, origin, and affected body region. When the cause is not defined or unknown, the dystonia is referred to as idiopathic or primary dystonia. Primary dystonia can be familial. Deep brain stimulation is an effective treatment of generalized dystonia.

PO042 / #960 CASE REPORT OF 21 Y/O. PATIENT WITH 9 YEARS OF DBS IN DYSTONIA HISTORY AND SOCIOECONOMIC OUTCOME: E-POSTER VIEWING

Subject was diagnosed General dystonia, and undergone GPi DBS surgery in Tyumen Federal Center of Neurosurgery, Russia. Examined through 9 (2013-2021) years after surgery. The long follow-up period and geographic difference between his city Krasnodar and Tyumen (2835) km. made it impractical to perform consistent in-person evaluations every 3 month as we planned. Social media allowed doctors to contact patient and to achieve a high responder rate.

A novel SYNJ1 homozygous variant causing developmental and epileptic encephalopathy in an Afro-Caribbean individual.

SYNJ1 encodes Synaptojanin-1, a dual-function poly-phosphoinositide phosphatase that is expressed in the brain to regulate neuronal synaptic vesicle dynamics. Biallelic SYNJ1 variants cause a spectrum of clinical manifestations, from early onset parkinsonism to developmental and epileptic encephalopathy. Proband-only exome sequencing was used to identify a homozygous SYNJ1 pathogenic variant in an individual with epileptic encephalopathy. Sanger sequencing was used to confirm the variant. We present an Afro-Caribbean female who developed uncontrollable seizures shortly after birth, accompanied by developmental delay and severe generalized dystonia. She had homozygosity for a novel c.242-2A > G variant in SYNJ1 with both parents being heterozygous carriers. An older sister was reported to have had a similar presentation but was not examined. Both siblings died at an approximate age of 16 years. We report a novel pathogenic variant in SYNJ1 present in homozygosity leading to developmental and epileptic encephalopathy. Currently, there are only 4 reports describing 10 individuals with SYNJ1-related developmental and epileptic encephalopathy. This case expands the clinical knowledge and the allelic heterogeneity associated with SYNJ1 variants.

TU-200. Pathophysiological mechanisms underlying sensory trick in cervical dystonia: An electroencephalogram-electromyography study

TU-200. Pathophysiological mechanisms underlying sensory trick in cervical dystonia: An electroencephalogram-electromyography study

Direct cerebello-striatal loop in dystonia as a possible new target for deep brain stimulation: A revised view of subcortical pathways involved.

Dystonia is the second most common movement disorder next to tremor, but its pathophysiology remains unsettled. Its therapeutic measures include anti-cholingerics and other medications, in addition to botulinum neurotoxin injections, and stereotaxic surgery including deep brain stimulation (DBS), but there still remain a number of patients resistant to the therapy. Evidence has been accumulating suggesting that basal ganglia in association with the cerebellum are playing a pivotal role in pathogenesis. Clinical observations such as sensory tricks and the effects of muscle afferent stimulation and blockage suggest the conflict between the cortical voluntary motor plan and the subcortical motor program or motor subroutine controlling the intended action semi-automatically. In this review, the current understanding of the possible pathways or loops involved in dystonia is presented, and we review promising new targets for Deep Brain Stimulation (DBS) including the cerebellum.

The Prevalence of Idiopathic or Inherited Isolated Dystonia: A Systematic Review and Meta‐Analysis

ABSTRACTBackgroundA systematic review of epidemiological studies of primary dystonia from 1985 and 2010 found an overall prevalence of 16.43 per 100,000 (95% CI = 12.09–22.32).MethodsWe performed a systematic review of studies from 2010 and 2022 to determine if there are important differences in epidemiology between these time periods.ResultsNineteen studies were included. Incidence of cervical dystonia, blepharospasm, and oromandibular dystonia were each reported in one study; one study reported incidence for all adult onset idiopathic focal dystonias combined. Using data from 11 studies, we performed random effects meta‐analyses of the prevalence of cervical dystonia (9.95 per 100,000; 95% CI = 3.51–28.17), blepharospasm (2.82 per 100,000; 95% CI = 1.12–7.12), laryngeal dystonia (0.40 per 100,000; 95% CI = 0.09–1.83), upper limb dystonia (1.27 per 100,000; 95% CI = 0.36–4.52), oromandibular dystonia (0.57 per 100,000; 95% CI = 0.15–2.15), and idiopathic or inherited isolated dystonia all subtypes combined (30.85 per 100,000; 95% CI = 5.06–187.74). All studies reported more cases of dystonia in females. There was no significant difference in prevalence by subgroup analysis based on time of study publication (1985–2010 vs. 2010–2022). Subgroup analysis of differences in prevalence by dystonia subtype by continent using all studies published (1985–2022) revealed significant regional differences in the prevalence of cervical and laryngeal dystonia.ConclusionThe incidence and prevalence of idiopathic or inherited isolated dystonia in the last decade was not significantly different from earlier reports. Population‐based studies across multiple geographic areas are needed to obtain a clearer understanding of the epidemiology of this condition.

MRM2 variants in families with complex dystonic syndromes: evidence for phenotypic heterogeneity

BackgroundDystonia involves repetitive movements and muscle contractions leading to abnormal postures. We investigated patients in two families, DYAF11 and M, exhibiting dystonic or involuntary movement disorders.MethodsClinical investigations were performed for...

A Japanese family with dystonia due to a pathogenic variant in SGCE

Dystonia (DYT) is a heterogeneous neurological disorder, and there are many types of DYT depending on the responsible genes. DYT11 is an autosomal dominant DYT caused by functional variants in the SGCE gene. We examined a Japanese patient with myoclonic dystonia. By using exome analysis, we identified a rare variant in the SGCE gene, NM_003919.3: c.304C > T [Arg102*], in this patient. Therefore, this patient has been molecularly diagnosed with DYT11. By Sanger sequencing, we confirmed that this variant was paternally inherited in this patient. By allele-specific PCR, we confirmed that the maternally inherited normal allele of SGCE was silenced, and only the paternally inherited variant allele was expressed in this patient. Despite the pathogenicity, identical variants have been recurrently reported in eight independent families from different ethnicities, suggesting recurrent mutations at this mutational hotspot in SGCE.

A Clinical Approach to Focal Dystonias

Dystonia is a hyperkinetic movement disorder (HMD), characterised by sustained or intermittent involuntary muscle contractions resulting in abnormal postures and/or movements [1]. Although primary dystonia has an estimated prevalence of 16 per 100,000 [2], the diagnosis may be delayed, due to its clinical heterogeneity, the lack of objective biomarkers and the potential for pseudodystonic conditions to mimic it [1,3]. We provide an overview of the classification and common subtypes of focal dystonia, focusing on the clinical phenomenology and diagnosis.

Extrapyramidal syndrome in a breastfed child, relevance of toxicological analysis

The passage of drugs in breast milk may be responsible for toxicity in breastfed children. We report here a case of passage of metoclopramide, an antiemetic neuroleptic, in breast milk, causing an extrapyramidal syndrome in the child, revealed in blood and hair. Case: a 21-week-old child was brought by his parents to the pediatric neurology department for consultation following two episodes of unexplained extrapyramidal syndrome. The little G., fed by mixed breastfeeding, presented a first episode of unexplained acute dystonia (generalized hypertonia with legs in extension and arms flexed against the chest, ceiling gaze, opisthonos) and two weeks later, a new episode of acute extrapyramidal syndrome, which resolved in a few hours. Both events required emergency hospitalization. During the second episode, diazepam 0.5 mg/kg IV was initiated, unsuccessfully. The anamnesis revealed that the mother had taken a rectal suppository of metoclopramide (10 mg) 48 hours before the first episode. An MRI was performed on arrival at the emergency room. Blood toxicology analysis was performed two days after the first episode. A 3-cm strand of brown hair was collected one month after the second episode. The entire sample (13 mg) was analyzed without segmentation. It should also be noted that the father had retractile capsulitis, treated with codeine paracetamol, and that the child had received paracetamol for teething. The child had no further episodes of dystonia since the second event. The MRI was normal. The child's blood toxicology analysis revealed the presence of metoclopramide at a concentration of 8 ng/mL. Hair analysis revealed metoclopramide at a relatively high concentration (1058 pg/mg), as well as paracetamol (31 ng/mg), lidocaine (34 pg/mg), diazepam (3 pg/mg) and its metabolite nordazepam (5 pg/mg), and codeine (16 pg/mg) in the analyzed hair of child G. The presence of diazepam and its metabolite can be explained by medical care. The low concentration of codeine without its metabolite morphine, may suggest an external contamination by the environment, contact with people who had consumed this molecule (bedding, caressing, etc.), especially the child's father. The presence of metoclopramide in the blood and hair is compatible with a passage of breast milk to the child. According to the literature, less than 5% of the maternal dose is found in the child. Adverse effects such as intestinal disorders, drowsiness, agitation, hypertonia have already been described in breastfed children (EMA. Metoclopramide Assessment report, 2013). This case illustrates the passage into breast milk of rectally administered metoclopramide in the mother and the toxic effects of this molecule in the child. The interpretation of hair analysis in infants remains nevertheless delicate to discriminate consumption from environmental contamination.

The epidemiology of dystonia: the Hannover epidemiology study

The prevalence of dystonia has been studied since the 1980s. Due to different methodologies and due to varying degrees of awareness, resulting figures have been extremely different. We wanted to determine the prevalence of dystonia according to its current definition, using quality-approved registries and based on its relevance for patients, their therapy and the health care system. We applied a service-based chart review design with the City of Hannover as reference area and a population of 525,731. Barrier-free comprehensive dystonia treatment in few highly specialised centres for the last 30 years should have generated maximal dystonia awareness, a minimum of unreported cases and a high degree of data homogeneity. Prevalence [n/1mio] and relative frequency is 601.1 (100%) for all forms of dystonia, 251.1 (42%) for cervical dystonia, 87.5 (15%) for blepharospasm, 55.2 (9%) for writer’s cramp, 38.0 (6%) for tardive dystonia, 32.3 (5%) for musician’s dystonia, 28.5 (5%) for psychogenic dystonia, 26.6 (4%) for generalised dystonia, 24.7 (4%) for spasmodic dysphonia, 20.9 (3%) for segmental dystonia, 15.2 (3%) for arm dystonia and 13.3 (2%) for oromandibular dystonia. Leg dystonia, hemidystonia and complex regional pain syndrome-associated dystonia are very rare. Compared to previous meta-analytical data, primary or isolated dystonia is 3.3 times more frequent in our study. When all forms of dystonia including psychogenic, generalised, tardive and other symptomatic dystonias are considered, our dystonia prevalence is 3.7 times higher than believed before. The real prevalence is likely to be even higher. Having based our study on treatment necessity, our data will allow better allocation of resources for comprehensive dystonia treatment.

Combined thalamic and pallidal deep brain stimulation for dystonic tremor

BackgroundDeep brain stimulation (DBS) has been proposed to treat disabling dystonic tremor (DT), but there is debate about the optimal target. DBS of the globus pallidus interna (GPi) may be insufficient to control tremor, and DBS of the ventral intermediate thalamic nucleus (VIM) may inadequately control dystonic features, raising the question of combining both targets. ObjectivesTo report the respective effects on DT symptoms of high-frequency stimulation of the VIM, the GPi and both targets simultaneously stimulated. MethodsThree patients with DT treated by bilateral high frequency DBS of 2 targets (VIM and GPi) were assessed 12 months after surgery in 4 conditions (VIM and GPi-DBS; GPi-DBS only; VIM-DBS only; DBS switched Off for both targets) by 3 independent movement disorders specialists blinded to the condition. ResultsThe Fahn-Tolosa-Marin-tremor-rating-scale (FTM-TRS) and Burke-Fahn-Marsden-dystonia-rating-scale (BFM-DRS) scores were more improved by combined DBS than VIM alone or GPi alone. Compared to Off/Off condition, mean total FTM-TRS score decrease was 34%, 42% and 63% respectively with VIM only, GPi only and combined VIM and GPi stimulation. Mean total BFM-DRS score decrease was 34%, 37% and 60% respectively with VIM only, GPi only and combined VIM and GPi stimulation, compared to Off/Off condition. Improvement concerned both motor, functional and activities of daily living sub-scores. No complications or adverse events were observed. ConclusionCombined VIM- and GPi-DBS, by modulating the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network, both involved in DT pathophysiology, may be more efficient than single DBS targeting only one of them.