Genetic updates on paroxysmal dyskinesias.

The paroxysmal dyskinesias are a diverse group of genetic disorders that manifest as episodic movements, with specific triggers, attack frequency, and duration. With recent advances in genetic sequencing, the number of genetic variants associated with paroxysmal dyskinesia has dramatically increased, and it is now evident that there is significant genotype-phenotype overlap, reduced (or incomplete) penetrance, and phenotypic variability. In addition, a variety of genetic conditions can present with paroxysmal dyskinesia as the initial symptom. This review will cover the 34 genes implicated to date and propose a diagnostic workflow featuring judicious use of whole-exome or -genome sequencing. The goal of this review is to provide a common understanding of paroxysmal dyskinesias so basic scientists, geneticists, and clinicians can collaborate effectively to provide diagnoses and treatments for patients.

Neuroleptic-induced Parkinsonism: Clinicopathological study.

BACKGROUND: Drug-induced parkinsonism is a well-known complication of several different drugs--the most common being neuroleptic-induced parkinsonism. However, very few autopsies have been reported in such cases. METHODS: Patients assessed at Movement Disorders Clinic Saskatchewan are offered brain autopsy. Detailed clinical records are kept. RESULTS: Brains were obtained from 7 drug-induced parkinsonism patients with parkinsonian symptom onset coinciding with use of drugs known to produce parkinsonism. Six were on antipsychotics and 1 was on metoclopramide. Three cases were treated with levodopa for parkinsonism. In two cases, parkinsonian features reversed after stopping the offending agent. Both had autopsy evidence of preclinical PD. In 4 of the remaining 5, dopamine-blocking drugs were continued until death. In 4 of those 5, brain histology revealed no cause for the parkinsonism, but 1 had mild SN neuronal loss without Lewy bodies. CONCLUSION: This study shows that reversal of parkinsonism after discontinuing offending drugs does not indicate absence of underlying pathology. Neuroleptics can unmask preclinical PD in patients with insufficient SN damage for the disease to manifest clinically. Though the mechanism of sustained parkinsonian features after discontinuing neuroleptics remains to be established, it is unlikely that dopamine receptor block leads to retrograde SN neuronal degeneration. Furthermore, L-dopa does not appear to be toxic to SN.

The selfie sign in the diagnosis of functional tremor.

Functional tremor (FT) is the most common phenotype of functional movement disorders (FMD). Its diagnosis can often be challenging. While positive signs such as tremor variability, distractibility, and entrainment support a diagnosis of FT, these diagnostic clues may not always be present and can be challenging to assess. In this case series, we identify another examination technique which could be of value when assessing FT. In our Movement Disorders clinic, charts were retrospectively reviewed for relevant clinical information. Video examinations were conducted. Obtained videos were either synchronous, via the use of screen recording software during telehealth visits or asynchronous, from self-recorded home videos. In both settings, patients were instructed to self-record their tremor using their phone cameras. Three patients with FT or comorbid FT were identified as demonstrating a unique examination sign. Videos showed an improvement or suppression of the tremor when the phone was held by the affected hand. When compared to a patient with tremor-dominant Parkinson's disease serving as a control, this "selfie sign" was not observed. These observations are preliminary and larger studies are needed to confirm the usefulness of the selfie sign in diagnosing FT. Patient-recorded videos of their tremor can be a convenient and practical way of evaluating suspected FT, especially when paroxysmal or variable symptoms limit the usefulness of classic signs often assessed in the clinic.