Movement disorders of the mouth: a review of the common phenomenologies.

Movement disorders of the mouth encompass a spectrum of hyperactive movements involving the muscles of the orofacial complex. They are rare conditions and are described in the literature primarily in case reports originating from neurologists, psychiatrists, and the dental community. The focus of this review is to provide a phenomenological description of different oral motor disorders including oromandibular dystonia, orofacial dyskinesia and orolingual tremor, and to offer management strategies for optimal treatment based on the current literature. A literature search of full text studies using PubMed/Medline and Cochrane library combined with a manual search of the reference lists was conducted until June 2021. Results from this search included meta-analyses, systematic reviews, reviews, clinical studies, case series, and case reports published by neurologists, psychiatrists, dentists and oral and maxillofacial surgeons. Data garnered from these sources were used to provide an overview of most commonly encountered movement disorders of the mouth, aiding physicians in recognizing these rare conditions and in initiating appropriate therapy.

The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.

Biallelic GBA mutations cause Gaucher disease (GD), and heterozygous carriers are at risk for synucleinopathies. No founder GBA mutations in French-Canadians are known. GBA was fully sequenced using targeted next generation and Sanger sequencing in French-Canadian Parkinson disease (PD) patients (n = 436), rapid eye movement (REM)-sleep behavior disorder (RBD) patients (n = 189) and controls (n = 891). Haplotype, identity-by-descent (IBD) and principal component analyses (PCA) were performed using single nucleotide polymorphism-chip data. Data on GD patients from Toronto and Montreal were collected from patients' files. A GBA p.Trp378Gly mutation was identified in two RBD and four PD patients (1% of all patients combined), and not in controls. The two RBD patients had converted to DLB within 3 years of their diagnosis. Haplotype, IBD and PCA analysis demonstrated that this mutation is from a single founder. Out of 167 GD patients screened, 15 (9.0%) carried the p.Trp378Gly mutation, all in trans with p.Asn370Ser. Three (20%) of the GD patients with the p.Trp378Gly mutation had developed Parkinsonism, and 11 patients had family history of PD. The p.Trp378Gly mutation is the first French-Canadian founder GBA mutation to be described, which leads to synucleinopathies and to GD type 1 when in compound heterozygosity with p.Asn370Ser.

Repetitive transcranial magnetic stimulation plus standardized suggestion of benefit for functional movement disorders: an open label case series.

BACKGROUND: We studied suggestion of benefit combined with motor cortex and premotor cortex repetitive transcranial magnetic stimulation (rTMS) in chronic (>2 years) FMDs. METHODS: Patients were identified from our patient records who had clinically definite FMDs and had undergone neuropsychiatric evaluation. Those with chronic FMDs were offered open-label rTMS over the dominant motor cortex. If they failed to improve they received dominant premotor cortex rTMS. The primary outcome was change from baseline to post-rTMS in quality of life measured by the World Health Organization Quality of Life Brief (WHOQOL-BREF) scale. Secondary outcomes were subject and investigator global impression of change (GIC), blinded Rush psychogenic movements rating scale, Barbers suggestibility scale, baseline expectation of benefit scale, and adverse effects. RESULTS: Six subjects were enrolled. For the primary outcome, there was significant improvement in the physical domain scores but significant reduction in psychological domain scores after premotor cortex rTMS compared to baseline and after motor cortex rTMS. There was no significant change between baseline and motor cortex rTMS or in any other domain after premotor cortex rTMS. Secondary outcome measures showed no meaningful change. Transient headache and worsening of FMD symptoms were the most common adverse effects observed. CONCLUSION: rTMS combined with strong suggestion of benefit provided dissonant results after premotor cortex rTMS with improvement in physical quality of life but reduction in psychological quality of life. These results serve to underscore the complex nature of FMDs where the overt physical manifestation is but one part of a comprehensive neuropsychological syndrome.

Molecular chaperones as rational drug targets for Parkinson's disease therapeutics.

Parkinson's disease is a neurodegenerative movement disorder that is caused, in part, by the loss of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia. The presence of intracellular protein aggregates, known as Lewy bodies and Lewy neurites, within the surviving nigral neurons is the defining neuropathological feature of the disease. Accordingly, the identification of specific genes mutated in families with Parkinson's disease and of genetic susceptibility variants for idiopathic Parkinson's disease has implicated abnormalities in proteostasis, or the handling and elimination of misfolded proteins, in the pathogenesis of this neurodegenerative disorder. Protein folding and the refolding of misfolded proteins are regulated by a network of interactive molecules, known as the chaperone system, which is composed of molecular chaperones and co-chaperones. The chaperone system is intimately associated with the ubiquitin-proteasome system and the autophagy-lysosomal pathway which are responsible for elimination of misfolded proteins and protein quality control. In addition to their role in proteostasis, some chaperone molecules are involved in the regulation of cell death pathways. Here we review the role of the molecular chaperones Hsp70 and Hsp90, and the cochaperones Hsp40, BAG family members such as BAG5, CHIP and Hip in modulating neuronal death with a focus on dopaminergic neurodegeneration in Parkinson's disease. We also review current progress in preclinical studies aimed at targetting the chaperone system to prevent neurodegeneration. Finally, we discuss potential future chaperone-based therapeutics for the symptomatic treatment and possible disease modification of Parkinson's disease.