Age-Related Parkinsonian Signs in Microdeletion 22q11.2.

BACKGROUND: The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition. OBJECTIVES: We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD. METHODS: We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia. RESULTS: Median MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%. CONCLUSIONS: Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Clozapine Monotherapy as a Treatment for Antipsychotic-Induced Tardive Dyskinesia: A Meta-Analysis.

OBJECTIVE: Tardive dyskinesia (TD) is an antipsychotic-induced movement disorder that typically occurs after long-term exposure to antipsychotic drugs. There is evidence that switching to clozapine reduces TD. This meta-analysis reviews the effect of switching to clozapine on the severity of TD. DATA SOURCES: The PubMed, PsycINFO, and Embase databases were searched for clozapine, tardive dyskinesia, and related keywords. The search was restricted to articles written in English and Dutch, and it was last updated on October 13, 2015. STUDY SELECTION: Sixteen studies were included in the meta-analysis. Inclusion criteria were a diagnosis of schizophrenia or a related disorder, a switch to clozapine monotherapy, and reports of scores on a TD rating scale before and after the switch to clozapine. DATA EXTRACTION: Two independent investigators extracted the data. Data were converted to standardized mean change scores and analyzed in a random-effects model. RESULTS: A random-effects model showed that the overall effect of switching to clozapine was a significant reduction in TD (npatients = 1,060, d = -0.40, P < .01), especially in the 4 studies that investigated the severity of TD as a primary outcome (npatients = 48, d = -2.56, P = .02). CONCLUSIONS: The overall results show that clozapine treatment can yield a slight reduction in TD. The severity of TD was reduced greatly in patients with moderate to severe TD. In patients with minimal to mild TD, switching to clozapine seldom worsens TD and a trend toward reduction is seen. These results support that a switch to clozapine should be considered for patients with moderate to severe TD and/or patients who experience substantial discomfort due to TD.

High Incidence and Prevalence of Drug-Related Movement Disorders in Young Patients With Psychotic Disorders.

BACKGROUND: Drug-related movement disorders (DRMDs) reduce quality of life and contribute to medication noncompliance of patients with psychotic disorders. Little is known about the epidemiology of DRMDs in relatively young patients a few years after onset of psychosis. This is an important period to study, as the impact of the antipsychotic treatment on the long-term potentiation of the neural pathways associated with psychotic disorders and DRMDs is still minimal. This study investigated the prevalence, incidence, persistence, and clinical correlates of DRMDs in patients during their first years after disease onset. METHODS: The Genetic Risk and Outcome of Psychosis study is a longitudinal study of 1120 relatively young patients with nonaffective psychosis and a mean age and illness duration of 27 and 4 years, respectively. The following drug-related movement disorders were assessed at baseline and at the 3-year follow-up: parkinsonism, akathisia, tardive dyskinesia, and tardive dystonia. We determined prevalence, incidence, and persistence and investigated clinical correlates at and over the baseline and follow-up assessment. RESULTS: Patients' mean age and illness duration at baseline were 27.1 and 4.3 years, respectively. In 4 patients, 1 developed a DRMD over the 3-year study period. Prevalence, incidence, and persistence rates were highest for parkinsonism (32%, 21%, and 53%) followed by akathisia (9%, 5%, and 17%) and tardive dyskinesia (4%, 3%, and 20%). Significant associations were found between DRMDs and the patients' age, IQ, and psychopathology. CONCLUSIONS: The prevalence, persistence, and incidence of DRMDs in this sample were high despite the relatively young age, recent onset of the disorder, and treatment primarily with second-generation antipsychotics. These findings emphasize that screening, diagnosis, and treatment of DRMDs are still important.

Reliability and validity of an instrument for the assessment of bradykinesia.

Bradykinesia is associated with reduced quality of life and medication non-compliance, and it may be a prodrome for schizophrenia. Therefore, screening/monitoring for subtle bradykinesia is of clinical and scientific importance. This study investigated the validity and reliability of such an instrument. Included were 70 patients with psychotic disorders. Inertial sensors captured mean cycle duration, amplitude and velocity of four movement tasks: walking, elbow flexion/extension, forearm pronation/supination and leg agility. The concurrent validity with the Unified Parkinson's Disease Rating Scale (UPDRS) bradykinesia subscale was determined using regression analysis. Reliability was investigated with the intra-class correlation coefficient. The duration, amplitude and velocities of the four tasks measured by the instrument explained 67% of the variance on the UPDRS bradykinesia subscale. The instrument test-retest reliability was high. The instrument investigated in this study is a valid and reliable alternative to observer-rated scales. It is an ideal tool for monitoring bradykinesia as it requires little training and experience to achieve reliable results.

Instrumental Assessment of Bradykinesia: A Comparison Between Motor Tasks.

Bradykinesia, a common symptom in psychiatry, is characterized by reduced movement speed and amplitude. Monitoring for bradykinesia is important, as it has been associated with reductions in quality of life and medication compliance. Subtle forms of bradykinesia have been associated with treatment response in antipsychotic-naïve first episode patients. Therefore, accurate and reliable assessment is of clinical importance. Several mechanical and electronic instruments have been developed for this purpose. However, their content validity is limited. This study investigated which tasks, or combinations thereof, are most suitable for assessing bradykinesia instrumentally. Eleven motor tasks were assessed using inertial sensors. Their capability of distinguishing bradykinetic patients with schizophrenia ( n = 6) from healthy controls ( n = 5) was investigated. Seven tasks significantly discriminated patients from controls. The combination of tasks considered most feasible for the instrumental assessment of bradykinesia was the gait, pronation/supination, leg agility and flexion/extension of elbow tasks (effect size = 2.9).