Dopaminergic versus anticholinergic treatment effects on physiologic complexity of hand tremor in Parkinson's disease: A randomized crossover study.

AIMS: Parkinsonian tremor (PT) is regulated by numerous neurophysiological components across multiple temporospatial scales. The dynamics of tremor fluctuation are thus highly complex. This study aimed to explore the effects of different medications on tremor complexity, and how the underlying factors contribute to such tremor complexity. METHODS: In this study, 66 participants received a 2-mg dose of benzhexol or a pre-determined dose of levodopa at two study visits in a randomized order. Before and after taking the medications, tremor fluctuation was recorded using surface electromyography electrodes and accelerometers in resting, posture, and weighting conditions with and without a concurrent cognitive task. Tremor complexity was quantified using multiscale entropy. RESULTS: Tremor complexity in resting (p = 0.002) and postural condition (p < 0.0001) was lower when participants were performing a cognitive task compared to a task-free condition. After taking levodopa and benzhexol, participants had increased (p = 0.02-0.03) and decreased (p = 0.03) tremor complexity compared to pre-medication state, respectively. Tremor complexity and its changes as induced by medications were significantly correlated with clinical ratings and their changes (ß = -0.23 to -0.39; p = 0.002-0.04), respectively. CONCLUSION: Tremor complexity may be a promising marker to capture the pathophysiology underlying the development of PT, aiding the characterization of the effects medications have on PT regulation.

Trihexyphenidyl in young children with dystonic cerebral palsy: A single arm study.

PURPOSE: The incidence of dystonic cerebral palsy causing significant morbidity is on the rise. There is a paucity of evidence for the management of dystonia in children. METHODS: Forty-one children aged 6 months-5 years with predominantly dystonic cerebral palsy were started on a predetermined protocol of trihexyphenidyl (0.25-0.52 mg/kg) and followed up at 3, 6 and 12 weeks. Dystonia severity, motor function and developmental age at baseline and 12 weeks were compared using the Global Dystonia Scale (GDS), the Gross Motor Function Measure (GMFM), and Fine Motor/Perceptual Subscale of the Early Developmental Profile-2. Thirty-four children completed the entire 12 weeks of intervention. RESULTS: The mean age of participants was 25±11 months. A significant decrease in median total dystonia scores on the GDS was observed post-intervention (74.5 to 59, p < 0.0001), and 64% of participants gained motor milestones. GMFM scores increased significantly from a median of 19.8% pre-intervention to 26.5% post-intervention (p < 0.0001). There was improvement in the fine motor domain as compared to the baseline (p < 0.0001). The number of children classified at Gross Motor Function Classification System levels 1 and 2 increased to 47.05% from 5.88% in the pre-intervention group. CONCLUSION: Trihexyphenidyl significantly improved dystonia, motor function and development in children with dystonic cerebral palsy in this study. Additional studies are needed to clarify its role in larger numbers of children with this condition.

Gabapentin as Add-on Therapy to Trihexyphenidyl in Children with Dyskinetic Cerebral Palsy: A Randomized, Controlled Trial.

OBJECTIVE: To compare the efficacy of gabapentin as add-on therapy to trihexyphenidyl in the treatment of children with dyskinetic cerebral palsy (CP). METHODS: An open-labelled, randomized, controlled trial was conducted among children aged 3-9 y with dyskinetic CP [Gross Motor Functional Classification System (GMFCS) 4-5]. Participants were assigned into two groups: gabapentin with trihexyphenidyl (n = 30) and trihexyphenidyl alone (n = 30). Dyskinesia Impairment Scale (DIS), Dystonia Severity Assessment Plan (DSAP), and International Classification of Functioning, Disability, and Health-Children and Youth Version (ICF-CY) were measured at baseline, 4 and 12 wk. RESULTS: There was significant reduction in baseline dystonia in both the groups (DIS: p < 0.001; DSAP: p = 0.007; ICF-CY: p < 0.001) but when data were compared between the groups, there was no significant difference in the severity of dystonia at 4 wk and at 12 wk (DIS: p = 0.09; DSAP: p = 0.49; ICF-CY: p = 0.25). Constipation was the commonest side effect observed in both the groups [3 (11.5%) vs. 4 (14.3%)]. CONCLUSION: Trihexyphenidyl alone is as effective as combination of gabapentin with trihexyphenidyl in decreasing the severity of dystonia at 12 wk. Hence, there is no added benefit of gabapentin as add-on therapy for dystonia among children with dyskinetic CP. TRIAL REGISTRATION: CTRI/2019/04/018603.

Central inhibition prevents the in vivo acute toxicity of harmine in mice.

BACKGROUND: Harmine is a ß-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered. PURPOSE: To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity. METHODS: The in vivo toxicity of harmine was assessed from the symptoms, biochemical indices, and cardiovascular effects in mice. The intervention experiments were performed by using anesthetics, central drugs, and peripheral anticholinergics. RESULTS: The acute toxicity of harmine is significantly dose-dependent and the median lethal dose is 26.9 mg/kg in vivo. The typical symptoms include convulsion, tremor, jumping, restlessness, ataxia, opisthotonos, and death; it also changes cardiovascular function. The anesthetics improved the survival rate and abolished the symptoms after harmine poisoning. Two central inhibitors, benzhexol and phenytoin sodium, uniformly improved the survival rates of mice poisoned with harmine. The peripheral anticholinergics didn't show any effects. CONCLUSION: Harmine exposure leads to central neurological symptoms, cardiovascular effects and even death through direct inhibition of the central AChE activity, where the death primarily comes from central neurological symptoms and is cooperated by the secondary cardiovascular collapse. Central inhibition prevents the acute toxicity of harmine, and especially rapid gaseous anesthetics such as isoflurane, might have potential application in the treatment of harmine poisoning.

Botulinum toxin type A versus anticholinergics for cervical dystonia.

BACKGROUND: This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment. OBJECTIVES: To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia. SEARCH METHODS: We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020. SELECTION CRITERIA: Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. MAIN RESULTS: We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness). AUTHORS' CONCLUSIONS: We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.

Pharmacological and neurosurgical interventions for individuals with cerebral palsy and dystonia: a systematic review update and meta-analysis.

AIM: To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia. METHOD: Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE. RESULTS: Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis. INTERPRETATION: Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.

Trihexyphenidyl induced malignant hyperthermia in a patient with Parkinson's disease complicated with pneumonia: A case report.

INTRODUCTION: Drug-induced fever is easy to overlook in respiratory departments. High fever is a rare side effect of trihexyphenidyl, which can be used clinically to treat Parkinson's disease. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a group of clinical syndromes caused by various diseases, resulting in water retention and refractory hyponatremia. However, pneumonia combined with malignant hyperthermia and SIADH has rarely been reported. We describe an unusual case of malignant hyperthermia and refractory hyponatremia due to trihexyphenidyl adverse reaction. PATIENT CONCERNS: Fifty-five-year-old male with pneumonia presented with malignant hyperthermia and refractory hyponatremia has a history of Parkinson's disease. DIAGNOSIS: Early considerations related the described hyperthermia findings to the manifestations of pneumonia. However, the last findings were due to trihexyphenidyl adverse reaction. INTERVENTIONS: Broad-spectrum antibiotics, oral and intravenous supplement of concentrated sodium chloride, drug, and physical cooling. OUTCOMES: The patient survived. During the 3-month follow up, the patient was no recurrence of fever or hyponatremia. CONCLUSION: High fever and SIADH can be a rare adverse reaction to trihexyphenidyl. Therefore, possible drug factors should be considered in the case. Consideration of other possible causes can improve early diagnosis and treatment of patients with fever of unknown origins.

Treatment of Tardive Dyskinesia.

Tardive dyskinesia (TD) is an iatrogenic condition that encompasses a wide phenomenological spectrum of movement disorders caused by exposure to dopamine receptor blocking agents (DRBAs). TD may cause troublesome or disabling symptoms that impair quality of life. Due to frequent, often inappropriate, use of DRBAs, TD prevalence rates among patients exposed to DRBAs continue to be high. The judicious use of DRBAs is key to the prevention of TD, reduction of disease burden, and achieving lasting remission. Dopamine-depleting vesicular monoamine transporter type 2 inhibitors are considered the treatment of choice of TD.

Patient-reported responses to medical treatment in primary dystonia.

In the absence of pathogenesis-targeted therapy in most types of primary dystonia, the current management strategy is largely symptomatic. Our aim was to comparatively evaluate the patients' perception of symptomatic benefits with the medical treatment of primary dystonia. We reviewed the medical records of 206 patients who received medical treatment upon diagnosis of primary dystonia. The patients were prescribed five different dystonia medications: clonazepam, trihexyphenidyl, nortriptyline, baclofen, and levodopa. Patients tried one type of medicine during each following week and whether each medication was beneficial was recorded in a binary fashion. Subgroups analysis was performed according to the body distribution, duration, ages at onset and treatment of dystonia. A total of 172 patients were included in the analysis. The majority (84%) had focal dystonia, most frequently cervical dystonia and blepharospasm. Clonazepam received the most favorable response (40%), followed by baclofen (20%) and trihexyphenidyl (20%). Patients with focal limb dystonia gave higher rate of positive responses to levodopa (24%) compared to other focal dystonia subgroups. Clonazepam, followed by baclofen and trihexyphenidyl is a useful pharmacologic option for primary dystonia. Levodopa can be considered for isolated limb dystonia.

Anticholinergic medications for reducing drooling in children with developmental disability.

AIM: To determine: the effectiveness of three anticholinergic medications in reducing drooling in children with developmental disabilities (such as cerebral palsy, intellectual disability, and autism spectrum disorder), the frequency and nature of side effects, and their impact on treatment discontinuation. METHOD: After prescription of benzhexol hydrochloride, glycopyrrolate, or scopolamine patches at a tertiary saliva control clinic, all carers of 110 consecutive, eligible patients were recruited over a 5-year period. They provided data for 52 weeks, or until drug discontinuation, on compliance, drooling, adverse effects, and reasons for cessation. We evaluated and compared best drooling response, side effects, and drug cessation rates using survival analysis, and the effect of baseline variables on the discontinuation rate using proportional hazards regression. RESULTS: Among 110 participants (71 males, 39 females; mean age 8y 5mo [SD 4y 3mo], range 1y 11mo-18y 11mo), benzhexol, glycopyrrolate, and scopolamine were prescribed 81, 62, and 17 times respectively, with respective response rates of 85%, 75%, and 65%. Poor head control and poor oromotor function were predictive of poor response. Side effects frequently prompted drug cessation in males more than females (hazard ratio 1.8 [95% confidence interval 1.0-3.2], p=0.048). Glycopyrrolate had the fewest side effects. INTERPRETATION: Benzhexol, glycopyrrolate, and scopolamine reduce drooling, but improvement is offset by adverse side effects. Overall, glycopyrrolate performs best. WHAT THIS PAPER ADDS: In drooling, glycopyrrolate produced the greatest improvement with fewer side effects compared with benzhexol and scopolamine. Poor head control and poor oromotor function were associated with poor response. Medication side effects were common and often led to treatment discontinuation. Behavioural issues instigated cessation of benzhexol more often in males than females.

MEDICAMENTOS ANTICOLINÉRGICOS PARA REDUCIR EL BABEO EN NIÑOS CON TRASTORNOS DEL DESARROLLO: OBJETIVO: Determinar: la eficacia de tres medicamentos anticolinérgicos en la reducción del babeo en niños con trastornos del desarrollo (como parálisis cerebral, discapacidad intelectual y el trastorno del espectro autista), la frecuencia y la naturaleza de los efectos secundarios y su impacto en la interrupción del tratamiento. MÉTODO: Después de la prescripción de trihexifenidilo, glicopirrolato o parches de escopolamina en una clínica terciaria de control de saliva, fueron reclutados los cuidadores de 110 pacientes elegibles durante un período de 5 años. Estos proporcionaron datos sobre el cumplimiento, babeo, efectos adversos y razones para el cese, durante 52 semanas o hasta la interrupción del medicamento. Se evaluó y comparó la mejor respuesta al babeo, efectos secundarios y tasas de cese de drogas, utilizando el análisis de supervivencia y el efecto de las variables basales en la tasa de interrupción utilizando el modelo de riesgos proporcionales. RESULTADOS: Entre 110 participantes (71 varones y 39 mujeres; edad promedio de 8 años 5 meses [DE 4 años 3 meses], con rango de 1 año 11 meses - 18 años 11 meses), se prescribió trihexifenidilo, glicopirrolato y escopolamina, 81, 62, y 17 veces respectivamente, con tasas de respuesta respectivas de 85%, 75% y 65%. El pobre control cefálico y la mala función oromotora eran predictores de una respuesta deficiente. Los efectos secundarios provocaron el cese de las drogas con más frecuencia en los varones que en las mujeres (relación de riesgo 1,8 [intervalo de confianza del 95% 1,0-3,2], p 0,048). Glicopirrolato tuvo el menor número de efectos adversos INTERPRETACIÓN: El trihexifenidilo, el glicopirrolato y la escopolamina reducen el babeo, sin embargo, la mejora se contrarresta por los efectos secundarios. En general, el glicopirrolato tiene mejores resultados.

MEDICAÇÕES ANTICOLINÉRGICAS PARA REDUZIR SIALORRÉIA EM CRIANÇAS COM DEFICIÊNCIAS DESENVOLVIMENTAIS: OBJETIVO: Determinar: a efetividade de três medicações anticolinérgicas na redução da sialorréia em crianças com deficiências desenvolvimentais (como paralisia cerebral, deficiência intelectual, e transtorno do espectro autista), a frequência e natureza dos efeitos colaterais, e seu impacto na descontinuação do tratamento. MÉTODO: Após prescrição de hidroclorido benzexol, glicopirrolato, ou faixas de escopolamina em uma clínica terciária de controle da salivação, todos os cuidadores de 110 pacientes elegíveis consecutivos foram recrutados em um período de 5 anos. Eles forneceram dados de 52 semanas, ou até a descontinuação da medicação, sobre adesão, sialorréia, efeitos adversos, e razões para interrupção. Avaliamos e comparamos a melhor resposta para salivação, efeitos colaterais e interrupção da medicação usando análise de sobrevivência, e o efeito das variáveis na linha de base na taxa de descontinuação usando regressão de riscos proporcionais. RESULTADOS: Entre 110 participantes (71 do sexo masculino, 39 do sexo feminino; média de idade 8a 5m [DP 4a 3m], variação 1a 11m-18a 11m), benzexol, glicopirrolato, e escopolamina foram prescritos 81, 62, e 17 vezes respectivamente, com as respectivas taxas de resposta de 85%, 75%, and 65%. Pouco controle de cabeça e função oromotora foram preditivos de pior resposta. Efeitos colaterais mais frequentemente causaram interrupção da medicação em meninos do que em meninas (taxa de risco 1,8 [intervalo de confiança a 95% 1,0-3,2], p=0,048). Glicopirrolato teve menos efeitos colaterais. INTERPRETAÇÃO: Benzexol, glicopirrolato, ou escopolamina reduzem a sialorréia, mas as melhoras são atenuadas pelos efeitos colaterais. Em geral, glicopirrolato teve o melhor desempenho.

Effects of Muscarinic Acetylcholine m1 and m4 Receptor Blockade on Dyskinesia in the Hemi-Parkinsonian Rat.

Standard treatment for Parkinson's disease (PD) is L-DOPA, but with chronic administration the majority of patients develop L-DOPA-induced dyskinesia (LID). Emerging evidence implicates the cholinergic system in PD and LID. Muscarinic acetylcholine receptors (mAChR) are known to modulate movement and of late have been implicated as possible targets for LID. Therefore the current study investigated the role of M1 and M4 mAChRs in LID, on motor performance following L-DOPA treatment, and sought to identify brain sites through which these receptors were acting. We first administered M1R-preferring antagonist trihexyphenidyl (0, 0.1, and 1.0 mg/kg, i.p.) or the M4R-preferring antagonist tropicamide (0, 10, and 30 mg/kg, i.p.) before L-DOPA, after which LID and motor performance were evaluated. Both compounds worsened and extended the time course of LID, while M1R blockade improved motor performance. We then evaluated the effects of tropicamide and trihexyphenidyl on dyskinesia induced by D1R agonist SKF81297 or D2R agonist quinpirole. Surprisingly, both M1R and M4R antagonists reduced D1R agonist-induced dyskinesia but not D2R agonist-induced dyskinesia, suggesting that mAChR blockade differentially affects MSN firing in the absence of postsynaptic DA. Finally, we evaluated effects of striatum- or PPN-targeted tropicamide microinfusion on LID and motor performance. Despite prior evidence, M4R blockade in either site alone did not affect the severity of LID via local striatal or PPN infusions. Taken together, these data suggest M4R as a promising therapeutic target for reducing LID using more selective compounds.

Pharmacological management of abnormal tone and movement in cerebral palsy.

BACKGROUND: The evidence base to guide the pharmacological management of tone and abnormal movements in cerebral palsy (CP) is limited, as is an understanding of routine clinical practice in the UK. We aimed to establish details of motor phenotype and current pharmacological management of a representative cohort across a network of UK tertiary centres. METHODS: Prospective multicentre review of specialist motor disorder clinics at nine UK centres, collecting data on clinical features and pharmacological management of children and young people (CYP) with CP over a single calendar month. RESULTS: Data were collected from 275 CYP with CP reviewed over the calendar month of October 2017. Isolated dystonia or spasticity was infrequently seen, with a mixed picture of dystonia and spasticity ± choreoathetosis identified in 194/275 (70.5%) of CYP. A comorbid diagnosis of epilepsy was present in 103/275 (37.4%). The most commonly used medications for abnormal tone/movement were baclofen, trihexyphenidyl, gabapentin, diazepam and clonidine. Medication use appeared to be influenced separately by the presence of dystonia or spasticity. Botulinum toxin use was common (62.2%). A smaller proportion of children (12.4%) had undergone a previous neurosurgical procedure for tone/movement management. CONCLUSIONS: CYP with CP frequently present with a complex movement phenotype and comorbid epilepsy. They have multiple therapy, medical and surgical management regimens. Future trials of therapeutic, pharmacological or surgical interventions in this population must adequately encompass this complexity in order to be translatable to clinical practice.

Off-Label Use of Antipsychotic Agents in Dementia: Evidence for the Revision of the Reimbursement Policy.

BACKGROUND: Harmonized requirements apply for the marketing authorization of medicinal products in the EU Member States. On the contrary, the national legislations on the drug reimbursement are not harmonized. The aim of this study was to find out if they are robust enough to ensure high standards of public health protection with focus on the symptomatic treatment of dementia in the elderly. METHODS: A computerized search of authorized therapeutic indications of haloperidol and trihexyphenidyl in the national databases of 8 EU member states and an analysis of the national legislation on reimbursement policies in Lithuania and Latvia was performed. RESULTS: There is a discrepancy in the decisions on the marketing authorization vs the reimbursement in Lithuania and Latvia (reimbursement of haloperidol and trihexyphenidyl for the off-label treatment of dementia). CONCLUSIONS: National legislation on the drug reimbursement in Lithuania and Latvia does not provide safeguards for public health at the same level as the marketing authorization does. Absence of a revision of former decisions in the light of new evidence is a critical weakness of the drug reimbursement in Lithuania and Latvia. Reimbursement for the off-label indications may pose a risk to public health.

Tremor during orthostatism as the initial symptom of Machado-Joseph disease.

A 60-year-old man was admitted to our hospital. He had mild tremor in his four extremities when supine or sitting, which was markedly exacerbated when standing. We diagnosed him with Machado-Joseph disease according to the genetic test. His tremor improved with clonazepam, trihexyphenidyl, and a rotigotine patch.

Trihexyphenidyl for dystonia in cerebral palsy.

BACKGROUND: Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder amongst those with cerebral palsy is dystonia: sustained or intermittent involuntary muscle spasms and contractions that cause twisting, repetitive movements and abnormal postures. The involuntary contractions are often very painful and distressing and cause significant limitations to activity and participation.Oral medications are often the first line of medical treatment for dystonia. Trihexyphenidyl is one such medication that clinicians often use to treat dystonia in people with cerebral palsy. OBJECTIVES: To assess the effects of trihexyphenidyl in people with dystonic cerebral palsy, according to the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) domains of impairment, activity and participation. We also assessed the type and incidence of adverse effects in people taking the drug. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, eight other databases and two trials registers in May 2017, and we checked reference lists and citations to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials comparing oral trihexyphenidyl versus placebo for dystonia in cerebral palsy. We included studies in children and adults of any age with dystonic cerebral palsy, either in isolation or with the associated movement disorders of spasticity, ataxia, chorea, athetosis and/or hypotonia. We included studies regardless of whether or not the study authors specified the method used to diagnose dystonia in their study population. Primary outcomes were change in dystonia and adverse effects. Secondary outcomes were: activity, including mobility and upper limb function; participation in activities of daily living; pain; and quality of life. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified one study, which was set in Australia, that met the inclusion criteria. This was a randomised, double-blind, placebo-controlled, cross-over trial in 16 children (10 boys and 6 girls) with predominant dystonic cerebral palsy and a mean age of 9 years (standard deviation 4.3 years, range 2 to 17 years). We considered the trial to be at low risk of selection, performance, detection, attrition, reporting and other sources of bias. We rated the GRADE quality of the evidence as low.We found no difference in mean follow-up scores for change in dystonia as measured by the Barry Albright Dystonia Scale (BADS), which assesses eight body regions for dystonia on a 5-point scale (0 = none to 4 = severe), resulting in a total score of 0 to 32. The BADS score was 2.67 points higher (95% confidence interval (CI) -2.55 to 7.90; low-quality evidence), that is, worse dystonia, in the treated group. Trihexyphenidyl may be associated with an increased risk of adverse effects (risk ratio 2.54, 95% CI 1.38 to 4.67; low-quality evidence).There was no difference in mean follow-up scores for upper limb function as measured by the Quality of Upper Extremity Skills Test, which has four domains that collectively assess 36 items (each scored 1 or 2) and produces a total score of 0 to 100. The score in the treated group was 4.62 points lower (95% CI -10.98 to 20.22; low-quality evidence), corresponding to worse function, than in the control group. We found low-quality evidence for improved participation (as represented by higher scores) in the treated group in activities of daily living, as measured by three tools: 18.86 points higher (95% CI 5.68 to 32.03) for the Goal Attainment Scale (up to five functional goals scored on 5-point scale (-2 = much less than expected to +2 = much more than expected)), 2.91 points higher (95% CI 1.01 to 4.82) for the satisfaction subscale of the Canadian Occupational Performance Measure (COPM; satisfaction with performance in up to five problem areas scored on a 10-point scale (1 = not satisfied at all to 10 = extremely satisfied)), and 2.24 points higher (95% CI 0.64 to 3.84) for performance subscale of the COPM (performance in up to five problem areas scored on a 10-point scale (1 = not able to do to; 10 = able to do extremely well)).The study did not report on pain or quality of life. AUTHORS' CONCLUSIONS: At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.

Velopharyngeal Dystonia: An Unusual Focal Task-specific Dystonia?

BACKGROUND: Velopharyngeal dysfunction produces a nasal speech pattern because of the inability to close the nasal airway during speech, most often associated with anatomical abnormalities of the palate. CASE REPORT: We describe two cases of possible velopharyngeal dystonia, a task-specific movement disorder causing a speech pattern similar to velopharyngeal dysfunction. Both patients experienced treatment response with anticholinergic medication. DISCUSSION: Dystonia affecting speech via involvement of the pharyngeal musculature may be an unrecognized etiology of voice disorders.

Chewing-induced facial dystonia: a rare presentation of task-specific dystonia.

This case is an addition to scarce literature available for a rare condition, chewing-induced task-specific dystonia. The patient was a 63-year-old woman who presented with a 4-year history of progressive difficulty in eating food only during chewing associated with abnormal facial grimaces without any difficulty in drinking, swallowing, speaking or singing. Examination revealed dystonia of facial muscles every time she chewed but absent during drinking and speaking. As movements were consistent and reproducible with the specific task, other differential diagnosis like motor tics, psychogenic disorder, tardive dystonia and parkinsonism syndrome were excluded leading to a diagnosis of task-specific facial dystonia triggered by chewing. Treatment was started with trihexyphenidyl and later on tetrabenazine was also added but she got only mild relief of symptoms. As she did not agreed for botulinum toxin therapy, so we continued with the same treatment without much improvement.

Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms.

Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia-related brain abnormalities. Participants included 16 patients with CD and 16 healthy age-matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1-weighted MRI scans from which we calculated free-water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2-mg dose of trihexyphenidyl. Severity of dystonia was assessed pre- and post-drug using the Burke-Fahn-Marsden Dystonia Rating Scale. Motor-related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post-treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563-4573, 2017. © 2017 Wiley Periodicals, Inc.