Sex and Gender Differences in Parkinson's Disease.

The lower prevalence of Parkinson disease (PD) in females is not well understood but may be partially explained by sex differences in nigrostriatal circuitry and possible neuroprotective effects of estrogen. PD motor and nonmotor symptoms differ between sexes, and women experience disparities in care including undertreatment with DBS and less access to caregiving. Our knowledge about PD in gender diverse individuals is limited. Future studies should improve our understanding of the role of hormone replacement therapy in PD, address gender-based inequities in PD care and expand our understanding of PD in SGM and marginalized communities.

TikTok Tics: A Pandemic Within a Pandemic.

BACKGROUND: TikTok is a social media platform where users create and share videos. During the COVID-19 pandemic, the use of this site greatly expanded. Tic and Tourette syndrome content also increased dramatically along with the number of patients with tics in neurology clinics. OBJECTIVES: We compared the phenomenology of "TikTok tics" to typical tic disorders. We chose to analyze the most widely viewed videos and therefore focused on the most popular content creators. METHODS: Videos with the keywords "tic," "Tourette," or "tourettes" were reviewed to identify content creators between March 11, 2020 and March 30, 2021. We performed a quantitative assessment of TikTok tics as well as a descriptive analysis of the entire series of videos of each content creator. RESULTS: The mean age of the cohort was 18.8 years old, and the majority were women. Unlike the predominance of facial movements in typical tics, arm movements were most frequent. Average tics per minute was 29, and almost all recorded TikTok tics were severe, causing significant disability. Whereas coprolalia and self-injurious behavior are only infrequently encountered in typical tic disorders, they were present in the overwhelming majority of TikTok subjects. CONCLUSIONS: TikTok tics are distinct from what is typically seen in patients with Tourette syndrome, although share many characteristics with functional tics. We believe this to be an example of mass sociogenic illness, which involves behaviors, emotions, or conditions spreading spontaneously through a group. A modern clinician needs to remain abreast of social media sources as knowledge of media content is essential in managing patients in the current environment.

An Open-Label Phase 2a Study to Evaluate the Safety and Tolerability of Perampanel in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is the most common focal isolated dystonia. Preclinical studies report that AMPA-selective glutamate receptor antagonists improve dystonia. Perampanel is a clinically available, AMPA receptor antagonist that has shown efficacy and safety in epilepsy. OBJECTIVES: To determine safety and tolerability of perampanel in CD. METHODS: We performed a phase 2a, open-label, multicenter study to evaluate tolerability and safety of perampanel in CD. Included subjects had primary CD; those on botulinum toxin were 8 weeks post last injection. All subjects received perampanel 2 mg/day, titrated 2 mg weekly over 6 weeks, to maximum 12 mg/day; maintenance phase was 4 weeks, ending at week 10. Primary endpoints included tolerability, defined as ability to remain on perampanel for the maintenance period, at any dose level and safety, determined from adverse events (AEs) collected at each visit. Secondary exploratory endpoints included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), quality of life (cervical dystonia impact profile [CIDP]-58) and Clinical Global Impression of change (CGI). RESULTS: CD participants (n = 25) were recruited. Eight subjects withdrew; 4 because of AEs, 3 for other reasons and 1 lost to follow up. One subject tolerated 12 mg/day. Eight subjects (30.8%) tolerated 2 mg, whereas 19.2% tolerated 4 mg/day, and 15.4% tolerated 6 mg or 8 mg/day. All subjects experienced AEs. The most common AEs were dizziness, imbalance, and irritability. Exploratory endpoints of TWSTRS showed some improved pain scores and CIDP-58 improved sleep. CONCLUSIONS: Tolerability to perampanel was variable in CD subjects. Lower doses would be considered for future studies in this population.

Multidisciplinary inpatient rehabilitation for Functional Movement Disorders: A prospective study with long term follow up.

INTRODUCTION: Functional Movement Disorders (FMDs) are challenging to treat. We assessed the effect of multidisciplinary inpatient rehabilitation, involving motor retraining, psychotherapy and psychotropic medication on FMD patient function and maintenance of improvement after one year. METHODS: FMD patients in a movement disorders clinic were referred for inpatient rehabilitation. Baseline, discharge and one year follow-up measures included: Clinical Global Impression (CGI-severity, CGI-change); Depression and Somatic Symptom Scale (DSSS); Generalized Anxiety Disorder-7 (GAD-7); Patient Health Questionnaire-9 (PHQ-9); Post-traumatic stress disorder check-list for DSM-5 (PCL-5). Outcomes were analyzed with non-parametric models. RESULTS: Seventeen patients completed rehabilitation. Thirteen completed one-year follow-up. Median CGI-severity was "markedly ill." At discharge, movement disorder improved in 93% (median CGI-change = 2, "much improved") as assessed by neurologist and patient. Psychiatrist ratings showed improvement among 86.7%; physiatrist and psychologist ratings were 66.7% and 53.3%, respectively. Symptoms improved on DSSS (Wilcoxon Z = -2.914, p ≤ 0.004); GAD-7 (Z = -3.045, p ≤ 0.002); PHQ-9 (Z = -3.415, p ≤ 0.01) but not PCL-5 (Z = -1.506, p = 0.132). At 1 year, 54% maintained at least minimal improvement by neurologist rating and 77% by patient rating (median CGI-change = 3, "minimally improved"). Improvement was not maintained for DSSS (Wilcoxon Z = -0.385. p = 0.701), GAD-7 (Z = -0.943, p = 0.357) or PHQ-9 (Z = -0.55, p = 0.582). CONCLUSIONS: Multidisciplinary inpatient rehabilitation improved FMD patient function, depression, anxiety and somatic symptoms. One-year follow-up demonstrated minimal sustained improvement and worsening psychopathology, reflecting chronic debility despite initial rehabilitative success.

Clinical Features of Tourette Syndrome.

Tourette syndrome is a multifaceted disorder characterized by multiple motor and at least one vocal tics that start in childhood, persist for at least 1 year, and cannot be attributed to another medical condition or exposure to medications/drugs. Clinical diagnostic criteria are available, and identification of tics is typically straightforward based on characteristic appearance and features. Diagnostic uncertainty can rarely arise in cases of mild tics, atypical features, certain psychiatric comorbidities, and other non-tic movement disorders. Comorbid psychopathology, including attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive behaviors/obsessive-compulsive disorder, affects the majority of patients and is correlated with disease severity and the presence of additional psychiatric behaviors. The severity of tics often improves after adolescence, whereas psychiatric symptoms typically persist. The subset of patients in whom tics persist into adulthood experience higher rates of anxiety, and lower self-esteem, socioeconomic status, and quality of life; the relative contribution of motor tics and psychopathology is not fully understood. This article summarizes the clinical features of Tourette syndrome, including major diagnostic criteria, unique features of tics, and key aspects that differentiate tics from common mimics and chameleons. Comorbid psychiatric conditions and their impact on phenotype and quality of life are described. Finally, current understanding of the natural history is summarized, including limited research in adults with Tourette syndrome.

Mortality and morbidity among hospitalized adult patients with neurological diseases in Cameroon.

BACKGROUND: There is inadequate information on the morbidity and mortality (M&M) from neurological diseases in sub-Saharan Africa. OBJECTIVE: To record the M&M from neurological diseases in adults in Cameroon from 2013 to 2015 using a registry and surveillance from two urban health care centers. METHODS: Records from all adult admissions from two urban hospitals over a two year period were reviewed. Adult cases with neurological diagnosis as the main cause for admission were identified. The neurological diagnosis was made by a neurologist in all cases. Variables analyzed were: demographics, neurological diagnosis, medical history, medical center characteristics, morbidity and mortality (M&M). Neurological diseases were classified according to ICD-10. RESULTS: Among the 2225 neurological admissions of adults, death from neurological disease was recorded in 423 patients (19.01%), and disability in 819 of the survivors (53.6%). The factors that were significantly associated with death in the multivariate analysis were age, history of ischemic cardiac disease, and neurological diagnoses of CNS infection, cerebrovascular disease, and CNS tumor. Similarly, factors associated with disability were medical history of HIV, and cerebrovascular disease, and neurological diagnoses of cerebrovascular disease and CNS tumor. Higher educational level and epilepsy were associated with less disability. CONCLUSIONS: As expected in this sample, older patients with neurological diseases had more M&M. Morbidity was inversely associated with education, which given that cerebrovascular disease is by far the most common cause of morbidity, indicates the power of risk factor control in preventing neurological disability.

The Association of Poor Academic Performance with Tic Disorders: A Longitudinal, Mainstream School-Based Population Study.

BACKGROUND: Little is known about the academic performance of students with tic disorders (TD). Our aim was to investigate the association of TD and poor academic performance over time. METHODS: Longitudinal, observational study of mainstream schoolchildren comparing grade retention (GR) and learning disorders (LD) in students with vs. without TD between 2010 and 2014. Students with vs. without TD based on DSM-IV-TR criteria, or with vs. without GR and LD were compared in terms of comorbidities, school, and environmental characteristics. The association of TD with GR was analyzed using hazard ratios (HRs) with 95% CIs, and with LD using logistic regression analysis [Odds ratio (OR)]. RESULTS: Two hundred fifty-eight students were included (mean age 14.0 ± 1.71 years, 143 [55.4%] males). The incident rate for TD and GR was 2.6 and 3.3 per 100 persons-year, respectively. LD found in 21 (9.9%) students was associated with TD (OR 11.62, 95% CI 2.21-60.90, p = 0.004), and attention deficit hyperactivity disorder (ADHD; OR 6.63, 95% CI 1.55-28.37, p = 0.01). Low psychological support (HRs 12.79, 95% CI 3.39-48.17) and low sport participation (HRs 6.41, 95% CI 1.54-26.78) were risk factors for GR. CONCLUSIONS: TD was associated with academic difficulties, namely, LD in conjunction with ADHD but not GR. The diagnosis of TD and comorbidities, and the initiation of proper treatment could have a favorable impact on school performance, and consequently on social development.

The Burden of Movement Disorders in Cameroon: A Rural and Urban-Based Inpatient/Outpatient Study.

BACKGROUND: Because of rapid demographic changes, the prevalence of movement disorders (MDs) is expected to increase in Africa. The objective of this study was to estimate the prevalence of MDs in an inpatient/outpatient-based study of rural and urban health care centers in Cameroon. METHODS: In this retrospective medical chart review, the inpatient/outpatients settings covered an urban population (3,000,000) and a rural population (380,276). Neurological diseases were classified according to the International Statistical Classification of Diseases-Related Health Problems, 10th revision (ICD-10). Crude prevalence was calculated per 100 with 95% confidence intervals (CIs). RESULTS: Of 20,131 medical charts reviewed (13% from the rural area), 4187 patients (20.8%) with neurological complaints were identified. MDs were diagnosed exclusively from urban centers in 134 patients (3.2%): the mean patient age was 48.6 ± 18.6 years, and 54.7% were women. The most prevalent MDs were hyperkinetic movements (tremor, myoclonus, and drug-induced MDs [ICD-10 code G25]; prevalence, 1.19%; 95% CI, 1.192-1.194%), Parkinson's disease (ICD-10 code G20; prevalence, 0.78%; 95% CI, 0.785-0.787%), dystonia (ICD-10 code G24; prevalence, 0.61%; 95% CI, 0.612-0.613%), secondary parkinsonism (ICD-10 code G21; prevalence, 0.56%; 95% CI, 0.564-0.565%), Huntington's disease (ICD-10 code G10; prevalence, 0.09%; 95% CI, 0.091-0.092%), and ataxia (ICD-10 code R29; prevalence, 0.04%; 95% CI, 0.0451-0.0456). CONCLUSION: Although the burden of MDs is expected to increase, MDs are likely underdiagnosed in rural areas. High-quality movement disorder training is essential to tackle this need.

Sources of Disability in Tourette Syndrome: Children vs. Adults.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and neuropsychiatric co-morbidities like Obsessive Compulsive Disorder (OCD) and Attention Deficit Disorder (ADHD), among others. In many instances tics get better with age but this is not always true regarding the psychiatric co-morbidities. METHODS: This manuscript reviews the disease-specific Quality of Life (QOL) instruments used to measure disability in TS and the existing literature on sources of functional impairment in children and adults with TS. RESULTS: Traditionally, disability in TS has been recorded using objective measures. In recent years there has been a development of disease-specific instruments to measure subjectively the impact of the different aspects of TS on the patient's daily function. The differential impact of tics vs. the psychiatric co-morbidities in children with TS is an issue of debate in the existing literature. In adults with TS, the literature is scant, therefore the sources of disability in this group are even less defined compared to children. DISCUSSION: As clinicians, we need to focus on determining the sources of disability in children and adults with TS so we can target our interventions successfully.

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740714.

Immediate vs. delayed treatment of psychogenic movement disorders with short term psychodynamic psychotherapy: randomized clinical trial.

OBJECTIVE: In subjects with psychogenic movement disorders (PMDs), we conducted a 6 month randomized, cross-over design study to assess the effect of 3 months of psychodynamic psychotherapy followed by observation by the neurologist vs. observation by the neurologist, then 3 months of psychiatric intervention. BACKGROUND: PMDs are often disabling but no uniformly successful treatment strategies have been identified. Short term, open label psychodynamic psychotherapy has been successful in improving PMDs but whether PMDs improve equally well with neurological observation and support has not been tested. DESIGN: Fifteen patients with PMDs were randomized to immediate vs. delayed (after 3 months) weekly psychodynamic psychotherapy for 12 weeks. During the phase without psychiatric intervention, they were monitored by the treating neurologist. Patients were assessed at baseline, 3 and 6 months. Change in their movement disorder was assessed using a clinical global impression scale change (CGI-c), depression and anxiety using the Hamilton Depression Scale (HAM-D) and Beck Anxiety Inventory (Beck-A). RESULTS: Fourteen women and one man, age 42.3 ± 11, disease duration 63.2 ± 73 months, were randomized to immediate (7 patients) or delayed (8 patients) treatment. Over the six month study, PMDs, depression and anxiety were significantly improved but time was the determinant factor without an independent effect of treatment assignment. CONCLUSION: In this group of PMD patients, where patients were kept within the medical system and involved in a research program, PMDs as well as depression and anxiety improved, but without specific benefit time-linked to psychotherapy as opposed to neurological observation and support.

Impact of placebo assignment in clinical trials of tic disorders.

BACKGROUND: Understanding the impact of placebo treatment is pivotal to the correct interpretation of clinical trials. The aim of present study was to examine the placebo effect in tic disorders. METHODS: Raw data were obtained for 6 placebo-controlled parallel and cross-over trials that involved medical interventions for tic disorders. Tic severity was measured using the Yale Global Tic Severity Scale. Placebo effect was defined as an improvement of at least 30% over baseline scores in the total tic score and was considered clinically relevant when at least 10% of patients in the placebo-arm met that benchmark. RESULTS: In total, 91 placebo-treated patients (80% males; mean age, 16.5 years; standard deviation, 10.5 years) were included. Although there was a trend toward improvement in the total tic scores after placebo administration (P=0.057), the magnitude of the placebo effect was small (Cohen's d=0.16) but relevant (19% of the sample). Females were more likely than males to have a placebo effect. CONCLUSIONS: The magnitude of the placebo effect in tic disorders appeared to be small. Further longitudinal studies using objective assessments for tic disorders are warranted to confirm the current results. © 2013 Movement Disorder Society.

Association of tic disorders with poor academic performance in central Spain: a population-based study.

OBJECTIVE: To analyze the association between tic disorders and poor academic performance in school-aged children. STUDY DESIGN: This was a cross-sectional, observational study conducted in a randomly selected sample of mainstream school-aged children (aged 6-16 years). The sampling frame included different types of schools and educational levels. Children with poor academic performance (eg, repeating a grade, special needs), and tic disorders (defined based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria) were identified. Children with and without tics and children with and without poor academic performance were compared in terms of clinical features (ie, medical history and neurologic and psychiatric comorbidities), school, and environmental characteristics. Logistic regression analyses were performed using school performance (dependent variable) and tic disorders (independent variable), after adjusting for confounding variables. RESULTS: The study cohort comprised 1867 children (mean age, 10.9 + 2.9 years; 1007 males [53.9%]). Tics were present in 162 children (8.6%), and poor academic performance was noted in 223 (11.9%). Overall poor academic performance was associated with age (OR, 1.71; P < .0001), television viewing (OR, 5.33; P = .04), attention deficit hyperactivity disorder (OR, 1.38; P < .0001), and family history of school dysfunction (OR, 2.43; P = .02) and was negatively associated with higher IQ score (OR, 0.90; P < .0001) and tic disorders (OR, 0.29; P = .01). CONCLUSION: After adjusting for other covariates, the presence of tic disorders was not associated with poor academic performance in our cohort. Early academic support and modification of environmental characteristics are needed for children at higher risk for school dysfunction, to enhance academic performance.

Psychogenic movement disorders.

Psychogenic movement disorders are common, but the diagnosis may be difficult. Visual appearance alone is typically not sufficient to make a diagnosis, but such information is certainly important. That a movement is bizarre can be helpful, but still must be considered thoughtfully since organic movement disorders can have endless variety. The diagnosis should rest on positive findings such as paroxysmal nature, maximum severity at or near onset, variability of tremor direction, frequency and amplitude, entrainment of tremor, distractability and suggestibility, and wildly swaying gait and balance problems with no falling. Psychogenic parkinsonism often poses a problem because of the relatively high frequency of overlap of psychogenic and organic disease. In regard to psychogenic parkinsonism, there are special features to look for. There might be tremor with kinetic movement as well as rest and posture, and finger tremor might be absent. With sequential movements, the sequence effect is typically lacking. Extreme slowness and grunting with great effort may be seen. Improvement in arm swing while running, a feature of organic parkinsonism, may not be seen.

Association between antipsychotics and body mass index when treating patients with tics.

OBJECTIVE: Treatment with antipsychotics can be associated with weight gain, and second-generation (atypical) antipsychotics (SGAs) can increase the risk for diabetes and dyslipidemia. These risks have not been assessed in patients with tics, who receive lower doses than those used to treat psychosis. The objective of this study is to investigate the relationship between antipsychotic use and weight in tic patients and compare the effects of SGAs to first-generation (typical) antipsychotics (FGAs). METHODS: We studied the association between antipsychotic use and body mass index (BMI) in consecutive patients with tics seen in a specialty Movement Disorders clinic. RESULTS: Height and weight were recorded on 198 patients, average age 19.9 years+/-14.0 years, 128 treated and 70 not treated with antipsychotics. Standardized measures of BMI were significantly higher in the antipsychotic-treated patients compared to the untreated patients (0.56+/-1.10) treated vs. untreated (-0.31+/-0.82). This difference remained significant after controlling for age, gender, stimulant medications, and co-morbidities such as attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Concomitant medications did not independently influence weight, and there was no difference between FGAs and SGAs. Antipsychotic dose, expressed in chlorpromazine (CPZ) equivalents, and treatment duration did not influence weight. CONCLUSION: Patients with tics on either FGAs or SGAs have higher BMI values compared to patients on no antipsychotics. Better knowledge of this risk should guide physician decision making when treating patients with tics.

Complementary and alternative medicine use in Gilles de la Tourette syndrome.

The aim of this study was to describe the use of complementary and alternative medicine (CAM) in patients with Tourette syndrome (TS) and explore associations with CAM use. In recent years CAM use has increased, but rates of CAM use in TS patients are not reported. Consecutive TS patients or their parent(s), seen in an academic movement disorder center, completed a questionnaire regarding their use of CAM. One hundred TS patients or parents completed the questionnaire, mean age 21.5 +/- 13.5, 76 males, 87 Caucasians. Sixty four patients had used at least one CAM modality. CAM treatments used were prayer (28), vitamins (21), massage (19), dietary supplements (15), chiropractic manipulations (12), meditation (10), diet alterations (nine), yoga (nine), acupuncture (eight), hypnosis (seven), homeopathy (six), and EEG biofeedback (six). Fifty six percent of patients using CAM reported some improvement. Users paid out of pocket for 47% of treatments pursued, and 19% of these payers received partial reimbursement by third party payer. Users and non-users did not differ in age, gender, race, income, educational level, general health, tic severity, medication use for TS, current satisfaction from medications or experience of side effects from medications. CAM use was associated with the presence of affective disorder (P = 0.004), but not with either ADHD or OCD. Among CAM users, 80% initiated CAM without informing their doctor. CAM is commonly used in children and adults with TS, and often without the neurologist's knowledge. Physicians should inquire about CAM to understand the spectrum of interventions that patients with TS use.