Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are most commonly associated with typical and atypical antipsychotics. However, other drugs such as antidepressants, antihistamines, antiepileptics, antiarrhythmics, and gastrointestinal drugs can also cause abnormal involuntary movements. Different types of movement disorders can also occur because of adverse drug reactions. Therefore, the important key to diagnosing DIMDs is a causal relationship between potential offending drugs and the occurrence of abnormal movements. The pathophysiology of DIMDs is not clearly understood; however, many cases of DIMDs are thought to exert adverse mechanisms of action in the basal ganglia. The treatment of some DIMDs is quite challenging, and removing the offending drugs may not be possible in some conditions such as withdrawing antipsychotics in the patient with partially or uncontrollable neuropsychiatric conditions. Future research is needed to understand the mechanism of DIMDs and the development of drugs with better side-effect profiles. This article reviews the phenomenology, diagnostic criteria, pathophysiology, and management of DIMDs.

Lack of Target Engagement Following Low-Frequency Deep Transcranial Magnetic Stimulation of the Anterior Insula.

OBJECTIVE: To evaluate the safety and efficacy of low-frequency, inhibitory, deep rTMS with a novel H-coil specifically designed to stimulate the insula. METHODS: In a randomized, crossover order, 16 healthy volunteers underwent two sessions (sham; active) of 1 Hz repetitive TMS at an intensity of 120% of individual motor threshold, over the right anterior insular cortex localized using a neuronavigation system. Before, immediately after, and one hour after rTMS, subjects performed two tasks that have previously been shown in fMRI experiments to activate insular cortex: A blink suppression task and a forced-choice risk-taking task. RESULTS: No drop-outs or adverse events occurred. Active deep rTMS did not result in decreased urge to blink compared to sham. Similarly, no significant time × condition interaction on risk-taking behavior was found. CONCLUSIONS: Low-frequency deep rTMS using a novel H8 coil was shown to be safe but did not affect any of the behavioral markers, also used to investigate modulation of insula activity. Our findings highlight the challenges of modulating the activity of deep brain regions with TMS. Further studies are necessary to identify effective stimulation parameters for deep targets, and to characterize the effects of deep TMS on overlying cortical regions.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

BACKGROUND: Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. OBJECTIVES: To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. SEARCH METHODS: We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. SELECTION CRITERIA: We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. MAIN RESULTS: Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. AUTHORS' CONCLUSIONS: We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

Parkinsonian syndromes: A review.

Since James Parkinson published his remarkable clinical observations in the "An Essay On The Shaking Palsy" in 1817, the number of diseases included in the spectrum of parkinsonian syndromes (a group of diseases that have some part of their clinical features resembling those seen in Parkinson's disease), are growing. Careful history taking, comprehensive neurological examination, and utilization of proper investigations will lead the physicians to make an accurate diagnosis of the specific disease entity present. In this recent review, we cover the issue of classification of parkinsonian syndromes, and comprehensively review the characteristic features of the commonly encountered diseases that present with this syndrome. The salient aspects of the epidemiology, key clinical features, proper investigations, and possible treatment options of these diseases have also been addressed.

Cerebellar brain inhibition in the target and surround muscles during voluntary tonic activation.

Motor surround inhibition is the neural mechanism that selectively favours the contraction of target muscles and inhibits nearby muscles to prevent unwanted movements. This inhibition was previously reported at the onset of a movement, but not during a tonic contraction. Cerebellar brain inhibition (CBI) is reduced in active muscles during tonic activation; however, it has not been studied in the surround muscles. CBI was evaluated in the first dorsal interosseus (FDI) muscle as the target muscle, and the abductor digiti minimi, flexor carpi radialis and extensor carpi radialis muscles as surround muscles, during rest and tonic activation of the FDI muscle in 21 subjects. Cerebellar stimulation was performed under magnetic resonance imaging-guided neuronavigation targeting lobule VIII of the cerebellar hemisphere. Stimulus intensities for cerebellar stimulation were based on the resting motor cortex threshold (RMT) and adjusted for the depth difference between the cerebellar and motor cortices. We used 90-120% of the adjusted RMT as the conditioning stimulus intensity during rest. The intensity that generated the best CBI at rest in the FDI muscle was selected for use during tonic activation. During selective tonic activation of the FDI muscle, CBI was significantly reduced only for the FDI muscle, and not for the surround muscles. Unconditioned motor evoked potential sizes were increased in all muscles during FDI muscle tonic activation as compared with rest, despite background electromyography activity increasing only for the FDI muscle. Our study suggests that the cerebellum may play an important role in selective tonic finger movement by reducing its inhibition in the motor cortex only for the relevant agonist muscle.

Camptocormia in Parkinson's disease: definition, epidemiology, pathogenesis and treatment modalities.

Camptocormia is an axial postural deformity characterised by abnormal thoracolumbar spinal flexion. The symptom usually presents while standing, walking or exercising and is alleviated while sitting, lying in a recumbent position, standing against a wall or using walking support. There is no consensus on the degree of thoracolumbar flexion to define camptocormia. However, most authors usually use an arbitrary number of at least 45° flexion of the thoracolumbar spine when the individual is standing or walking. Aetiologies of camptocormia are heterogeneous, and Parkinson's disease (PD) is one of its many causes. The prevalence of camptocormia in PD ranges from 3% to 18%. Central and peripheral mechanisms might both contribute to its pathogenesis. Although there is no established consensus for treatment of camptocormia in PD, there are non-pharmacological, pharmacological and surgical approaches that can be used.

Inducing LTD-Like Effect in the Human Motor Cortex with Low Frequency and Very Short Duration Paired Associative Stimulation: An Exploratory Study.

Introduction. Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency of PAS10 ms protocols in human M1. Methods. Six protocols of low frequency PAS10 ms (ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applying PAS10 ms up to 30 minutes. After we found PAS10 ms protocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects. Results. One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes. Conclusion. Low frequency and very short duration of PAS10 ms potentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort.

Differences in active range of motion measurements in the upper extremity of patients with writer's cramp compared with healthy controls.

STUDY DESIGN: Exploratory case-control study. INTRODUCTION: Writer's cramp (WC) is a type of focal hand dystonia. The central nervous system plays a role in its pathophysiology, but abnormalities in the affected musculoskeletal components may also be relevant. PURPOSE OF THE STUDY: We compared the active range of motion (ROM) in patients with WC and healthy volunteers (HVs) and correlated the findings with disease duration and severity. METHODS: Affected limb joints were measured with goniometers. Patients were assessed at least 3 months after their last botulinum toxin (botulinum neurotoxin) injection, and strength was clinically normal. t tests were used to compare the ROMs of WC with matched HVs. The Spearman correlation coefficient assessed the relationship of active ROMs to the disease duration and handwriting subscore of the Dystonia Disability Scale. RESULTS: ROMs of D1 metacarpophalangeal (MCP) joint extension as well as D2 and D5 MCP flexion were significantly smaller in WC, and distal interphalangeal joint extension in D3 and D5 was significantly greater compared with HVs. There were negative correlations between D2 MCP flexion and disease duration and with Dystonia Disability Scale. DISCUSSION: Abnormalities in ROMs in WC were found. Severity and disease duration correlated with reduced D2 MCP flexion. This may be related to intrinsic biomechanical abnormalities, co-contraction of muscles, or a combination of subclinical weakness and atrophy from repeated botulinum neurotoxin injections. CONCLUSIONS: Hand biomechanical properties should not be ignored in the pathophysiology of WC. LEVEL OF EVIDENCE: 2c.

Evaluation of sleep disorders in Parkinson's disease: a comparison between physician diagnosis and self-administered questionnaires.

OBJECTIVE: The objective of the present study was to compare a physician's diagnosis of sleep disorders in patients with Parkinson's disease (PD) during clinical evaluation of sleep disorders diagnosed by validated questionnaires. MATERIAL AND METHOD: Patients with PD at the Parkinson's clinic at Siriraj Hospital were included in this prospective cross-sectional study. Patients completed the Modified Parkinson's Disease Sleep Scale (MPDSS), Thai Epworth Sleepiness Scale (Thai-ESS), Scales for Outcomes in Parkinson's Disease-Sleep Scale questionnaire (SCOPA), Berlin questionnaire (Thai version), and Siriraj sleep questionnaire (SSQ). Thereafter, attending physicians diagnosed sleep disorders based on patient evaluation. RESULTS: One hundred twenty patients with PD participated in the present study. Among them, 73 (60.8%) were males, the mean age was 61.5 +/- 12.0 years, and the mean body mass index (BMI) was 22.7 +/- 3.5 kg/m2 (BMI > or = 30 kg/m2 in 1.7% of patients). The study demonstrated a prevalence of overall sleep disorders in 59.2% of patients based on physician diagnosis and 81.7% of patients based on the MPDSS questionnaire. The ESS was > 10 in 29.2% of the patients. High risk for obstructive sleep apnea was observed in 28.3% (Berlin) and 42% (MPDSS) of patients (15% by both). SSQ detected all sleep disorders in 86.7% of the population, and its results correlated with the MPDSS. CONCLUSION: Sleep disorders are common in patients with PD but remain underestimated because they are not routinely screened in clinical practice. This study demonstrates the use of validated questionnaires to efficiently detect and classify patients with PD at risk for common sleep disorders.

The effect of a home-based exercise program on gait characteristics in an individual with Parkinson's disease over a one-year period: A case study.

BACKGROUND: The COVID-19 pandemic has placed a restriction on physiotherapy clinical visits for supervised exercise. It is important that individuals with Parkinson's Disease (PD) continue an exercise regime at home during the pandemic and also in normal situations. OBJECTIVE: The purpose of this study was to explore the case history of an individual with PD who used a developed home-based exercise programme for one year during the COVID-19 pandemic. METHODS: A 67 year-old married woman was diagnosed with PD stage 2.5 on the modified Hoehn and Yahr (HY) scale. Gait characteristics and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scores were assessed at baseline, 10 weeks, and 12 months. The home-based exercise program included breathing exercises, posture correction, stretching exercises, rotation of the axial segments, balance training, and task-specific gait training. RESULTS: After 12 months, her MDS-UPDRS motor scores decreased when compared to baseline and 10 weeks, and gait characteristics at 12 months showed an increase in the degree of foot rotation, step length, cadence, and gait speed when compared to baseline and 10 weeks. CONCLUSION: This case study showed that improvements in MDS-UPDRS and gait characteristics can continue over a 12 month period as a result of a home-based exercise programme. Therefore, home-based exercise programs should be encouraged with weekly monitoring, especially in individuals with gait disorders which show deterioration.

Prevalence of Thai patients with advanced Parkinson's disease and external validation of the 5-2-1 Criteria and the CDEPA Questionnaire: A single-centered, cross-sectional study.

BACKGROUND: Advanced stage of Parkinson's disease (APD) diagnosis is challenging for general neurologists. The 5-2-1 Criteria and the Cuestionario De Enfermedad de Parkinson Avanzada (CDEPA) have been validated for screening for APD. OBJECTIVE: This article reports the period-prevalence of APD defined by a movement disorder expert, the 5-2-1 Criteria, and CDEPA and to improve the screening performance of the 5-2-1 Criteria METHODS: A cross-sectional retrospective study at the Parkinson's disease (PD) clinic of a tertiary hospital in Bangkok, Thailand amongst all PD patients aged ≥ 18 years was performed from January 2016 to January 2020. We compared the characteristics of APD and non-APD patients. We externally validated the 5-2-1 Criteria and CDEPA. We explored improving the 5-2-1 Criteria. RESULTS: Of 480 PD patients with complete data, the period-prevalence of APD by the movement disorder expert, the 5-2-1 Criteria and CDEPA were 37.1 %, 48.5 %, and 27.5 %, respectively. Adding requiring help with an activity of daily living and freezing of gait to the original 5-2-1 Criteria enhanced the sensitivity from 86.5 % (95 %CI 80.6, 91.2) to 94.9 % (95 %CI 90.6, 97.7) and negative predictive value (NPV) from 90.3 % (95 %CI 85.9, 93.7) to 96 % (95 %CI 92.6, 98.2). However, the CDEPA had a sensitivity of 62.9 % (95 %CI 55.4, 70) and NPV of 81.0 (95 %CI 76.5, 85). CONCLUSION: The 5-2-1 Criteria had a good screening tool performance for general neurologists to refer APD patients for optimal treatments. The modified 5-2-1 Criteria had better performance than the original one. External validation is needed.

Estimated creatinine clearance and cognitive impairment in Thai older adults: a pilot study from the dementia and disability project in Thailand.

BACKGROUND: Chronic kidney disease and dementia are the two common conditions in the older adults. The recent study from the US older adult populations has shown that the lower levels of kidney function are associated with increased prevalence of cognitive impairment. OBJECTIVE: Exploring the relationship between levels of kidney function and cognitive function in Thai community base older adults and finding the threshold of kidney function for which general practitioner should screen for cognitive impairment. MATERIAL AND METHOD: Bangkok community dwelling older adults were recruited during 2004-2006. Serum creatinine and cognitive function were measured. Kidney function was represented in estimated creatinine clearance (eCrCl), calculated by Cockcroft-Gault formula. Cognitive function assessment was evaluated by Mini Mental State Exam Thai version (TMSE). The participants were divided into 4 groups, Model 1, those stratified by level of eCrCl; > or = 90 60-89, 30-59 and < 30 mL/min respectively. Unfortunately, after the authors categorized eCrCl as a Model 1, the number of participants are largely unequally distributed among the 4 groups. Therefore, the authors developed Model 2. In Model 2, eCrCl was divided, by tertile, into 3 groups; eCrCl > 65, 48-65 and < 48 mL/min respectively. Participants with TMSE < 24 were considered to have cognitive impairment. The association between kidney function and cognitive impairment was determined by univariable and multivariable logistic regression models. RESULTS: 317 participants were enrolled, 65.71% (n = 207) were women. The mean age was 71.13 years (SD = 7.99). In Model 1, the authors found a trend which indicated that eCrCl < 30 mL/min increased the prevalence of cognitive impairment when compared with eCrCl > or = 90 mL/min (adjusted odds ratio 3.82; 95% CI 0.90-16.19, p-value = 0.07). In Model 2, the authors also found that populations ofeCrCl < 48 mL/min had a trend to increase the prevalence of cognitive impairment when compared with eCrCl > 65 mL/min (adjusted odds ratio 1.76; 95% CI 0.99-3.12, p-value = 0.052). CONCLUSION: In the present study, the authors could not demonstrate any statistical significant of an association between the lower eCrCl and cognitive impairment. However the authors found that eCrCl < 48 mL/min may have a trend to associate with cognitive impairment. Therefore, the authors may use this eCrCl level for screening prevalence of cognitive impairment in the older adult population.

Validity and Reliability of the Thai Version of the Freezing of Gait Questionnaire in Individuals With Parkinson's disease.

OBJECTIVE: To evaluate the validity and reliability of the Thai version of the Freezing of Gait Questionnaire (FOG-Q) in individuals with Parkinson's disease (PD). METHODS: The FOG-Q was translated into Thai according to the standard process. Fifty-six individuals with PD participated in the study. The content validity was assessed using the content validity index (CVI). The construct validity was evaluated by correlating Thai FOG-Q with Thai version of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) items 2.13 and 3.11, Thai version of the Falls Efficacy Scale-International (FES-I), Timed Up and Go test (TUG) and Berg Balance Scale (BBS) using Spearman's correlation coefficient (rS). The correlation between Thai FOG-Q and clinical characteristics, for example, duration of PD and modified Hoehn and Yahr (mH&Y) stage was evaluated. Internal consistency and test-retest reliability were evaluated with Cronbach's alpha (Cα) and intraclass correlation coefficient (ICC), respectively. RESULTS: The Thai FOG-Q had high content validity (CVI=0.96). The mean FOG-Q score was 9.0±4.9. The construct validity showed a strong positive correlation with MDS-UPDRS item 2.13 (rS=0.81), and moderate correlations with MDS-UPDRS item 3.11, FES-I, and TUG (rS=0.42-0.60). A negative correlation with BBS was found (rS=-0.32). It had a moderate correlation with mH&Y stage (rS=0.40). The Thai FOG-Q had good internal consistency (Cα=0.87) with excellent test-retest reliability (ICC=0.91). CONCLUSION: The Thai FOG-Q has excellent validity and reliability. It is a useful instrument for the evaluation of FOG in individuals with PD.

Movement Disorders and Musculoskeletal System: A Reciprocal Relationship.

The association of movement disorders (MDs) with musculoskeletal (MSK) disorders is observed in two principal scenarios. First, MDs patients may present with MSK issues. This phenomenon is primarily observed in parkinsonian syndromes, but may also be seen in patients with dystonia, Tourette syndrome, and some gene-related MDs. Second, there are MSK disorders that may produce or mimic MDs. Important primary MSK disorders producing MDs are joint hyperlaxity syndrome, non-traumatic craniovertebral junction anomalies, congenital muscular torticollis, and rheumatoid arthritis. Peripheral trauma to the MSK system may also lead to MDs commonly referred to as peripherally induced MDs. The exact pathogenesis of these disorders is not clear, however many patients have associated sensory phenomena such as complex regional pain syndrome. Herein, we provide an overview of disorders that may manifest with a combination of MSK and MDs, as detailed above. The most common MDs are discussed in each section, along with important clinical points, suggested diagnostic workups, and possible differential diagnoses.

Benefits of task-specific movement program on en bloc turning in Parkinson's disease: A randomized controlled trial.

INTRODUCTION: En bloc turning highlights a lack of rotational intersegmental coordination, which commonly impacts turning ability in people with Parkinson's disease (PD). Whilst this turning deficit responds fairly well to medical treatment, it may be further mitigated by performing specific exercise training. Thus, the present study aimed to examine the effects of a 4-week exercise program, which focused on task-specific movements (TSM program) on turning ability and clinical outcomes in people with PD. METHODS: Twenty-two adults (67 ± 6 years) with early-to-mid-stage idiopathic PD were randomly assigned to an experimental group (EG; n = 11) or a control group (CG; n = 11). The exercise group (EG) group received a 60-min per session TSM program for 4 weeks (a total of 15 sessions), while the CG group performed their routine rehabilitation program (a total of 12 sessions). Inertial measurement units were used to measure turning kinematics including; onset latency of body segments and stepping characteristics. Clinical outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS), functional reach test (FRT), and fall efficacy scale international (FES-I). Assessments were conducted at baseline and after 4 weeks. RESULTS: In the EG, turning kinematics, UPDRS scores, FRT, and FES-I scale, were improved at the end of the 4-week program compared with the CG (all p < 0.05). IMPACT STATEMENT: A 4-week TSM program could be a promising alternative rehabilitation program for improving "en bloc" turns and clinical outcomes in PD patients.

An investigation of the contribution of different turn speeds during standing turns in individuals with and without Parkinson's disease.

Issues around turning can impair daily tasks and trigger episodes of freezing of gait in individuals with Parkinson's disease (PD). Slow speeds associated with aging produce a more en-bloc movement strategy which have been linked with falls while turning. However, the influence of speed of turning on the complex whole-body coordination considering eye movements, turning kinematics, and stepping characteristics during turning has not been examined. The aim of this study was to investigate if individuals with PD have a different response to changes in turning speed compared to healthy older adults during 180° standing turns. 20 individuals with PD and 20 healthy age matched adults participated in this study. Data were collected during clockwise and counter-clockwise turns at three self-selected speeds in a randomised order: (a) normal; (b) faster than normal; and (c) slower than normal. Eye movement and turning kinematics were investigated using electrooculography and Inertial Measurement Units. Mixed Model Analysis of Variance (MM ANOVA) tests with post hoc pairwise comparisons were performed to assess the differences between groups and turning speed. In addition, further post hoc Repeated Measures ANOVA (RM ANOVA) tests were performed if any significant interactions were seen between groups and turning speed. Significant interaction effects were found in eye movement and turning kinematics, and the RM ANOVA showed significant main effects for turning speeds within the PD and the control groups. Turning slowly resulted in similar alterations in eye movement, turning kinematics and stepping characteristics in the PD group and the healthy controls. However, individuals with PD showed a different response to the healthy controls, with a greater delay in eye movement and onset latency of segments in turning kinematics and step variables between the different speeds. These findings help our understanding regarding the turning strategies in individuals with PD. The incorporation of guidance with regard to faster turning speeds may be useful in the management of individuals with PD. Clinical training using different turn directions and speeds may improve coordination, increase confidence and reduce the risk of falling.

Validation of the Thai Version of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale.

OBJECTIVE: This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). METHODS: The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing. RESULTS: The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions. CONCLUSION: The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.