Project description:There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders.
Project description:Emerging studies indicate that striatal cholinergic interneurons play an important role in synaptic plasticity and motor control under normal physiological conditions, while their disruption may lead to movement disorders. Here we discuss the involvement of the cholinergic system in motor dysfunction, with a focus on the role of the nicotinic cholinergic system in Parkinson's disease and drug-induced dyskinesias. Evidence for a role for the striatal nicotinic cholinergic system stems from studies showing that administration of nicotine or nicotinic receptor drugs protects against nigrostriatal degeneration and decreases L-dopa-induced dyskinesias. In addition, nicotinic receptor drugs may ameliorate tardive dyskinesia, Tourette's syndrome and ataxia, although further study is required to understand their full potential in the treatment of these disorders. A role for the striatal muscarinic cholinergic system in movement disorders stems from studies showing that muscarinic receptor drugs acutely improve Parkinson's disease motor symptoms, and may reduce dyskinesias and dystonia. Selective stimulation or lesioning of striatal cholinergic interneurons suggests they are primary players in this regulation, although multiple central nervous systems appear to be involved.ImplicationsAccumulating data from preclinical studies and clinical trials suggest that drugs targeting CNS cholinergic systems may be useful for symptomatic treatment of movement disorders. Nicotinic cholinergic drugs, including nicotine and selective nAChR receptor agonists, reduce L-dopa-induced dyskinesias, as well as antipsychotic-induced tardive dyskinesia, and may be useful in Tourette's syndrome and ataxia. Subtype selective muscarinic cholinergic drugs may also provide effective therapies for Parkinson's disease, dyskinesias and dystonia. Continued studies/trials will help address this important issue.
Project description:Background:Functional movement disorders (FMDs) have been rarely described in the elderly population. Methods:This is a retrospective chart review of elderly patients with FMDs (onset >60 years) attending the movement disorders clinic at a tertiary care teaching institute in India. Results:Out of 117 patients diagnosed with FMD at our center, 18 patients had an onset after the age of 60 years. The male-to-female ratio was 10:8 and the duration of symptoms ranged from 1 day to 5 years. Social (10/18) and physical factors (5/18) with an evident temporal relationship with the onset of FMD were identified in 15 out of 18 patients. Six of them had a past history of depression, anxiety, or other psychiatric illnesses. The tremor was the most frequent phenomenology seen in 11 (61.1%) patients, followed by dystonia in seven (38.8%), choreoballism and tics in two each, and hemifacial spasm and functional gait in one each. Seven patients had more than one phenotype. Discussion:Tremor was the most frequent movement disorder seen in our patients with FMD. Surprisingly, tics (n = 2) and choreoballistic (n = 2) movements were also found in our patients with FMD, which has not been reported previously in an elderly population. Both physical and social factors were identified preceding the development of FMDs in majority of our patients.
Project description:Background:Functional neurological disorders are generally more common in females than males, but the reason for this gender difference is not well understood. Objectives:In this study, we aim to compare the clinical and demographic features of functional movement disorders (FMDs) between males and females. Methods:We examined clinical data and video-recordings of patients with FMDs evaluated at the Baylor College of Medicine Movement Disorders Clinic. Results:Of the 196 patients with FMDs, males represented only 30% (n = 59) of the entire cohort. Men had an older age at onset: 40.5 versus 34.1?years (P =?0.026) and an older age at evaluation: 43.8 versus 38.1?years (P =?0.041) compared to women. Functional dystonia was more frequently observed in women: 47.5 versus 20.3% (P <?0.001), but there was a trend for higher frequency of functional gait disorder in men: 44 versus 30% (P =?0.056). Females were particularly over-represented (73.7%) in children and adolescents; but the genders were equally represented in patients aged ?50?years. Conclusions:Female patients are over-represented in FMDs, except in individuals aged ?50?years. Compared to female patients, males with FMDs present later in life and are less likely to have functional dystonia.
Project description:Functional (psychogenic) movement disorders are a common source of disability and distress. Despite this, little systematic evidence is available to guide treatment decisions. This situation is likely to have been influenced by the "no man's land" that such patients occupy between neurologists and psychiatrists, often with neither side feeling a clear responsibility or ability to direct management. The aim of this narrative review is to provide an overview of the current state of the evidence regarding management of functional movement disorders. This reveals that there is some evidence to support the use of specific forms of cognitive behavioral therapy and physiotherapy. Such treatments may be facilitated in selected patients with the use of antidepressant medication, and may be more effective for those with severe symptoms when given as part of inpatient multidisciplinary rehabilitation. Other treatments, for example hypnosis and transcranial magnetic stimulation, are of interest, but further evidence is required regarding mechanism of effect and long-term benefit. Though prognosis is poor in general, improvement in symptoms is possible in patients with functional movement disorders, and there is a clear challenge to clinicians and therapists involved in their care to conduct and advocate for high-quality clinical trials.
Project description:The aim of this study was to assess cerebrospinal fluid (CSF) concentrations of specific amino acids using a high-performance liquid chromatography system in a sample of patients with functional movement disorders (FMDs) and in a sample of controls. CSF levels of glutamate were significantly lower in patients with FMD than in controls. This finding argues in favor of glutamatergic dysfunction in the pathophysiology of FMD.
Project description:Making the diagnosis of functional movement disorders can be challenging. Identifying positive physical signs and diagnostic maneuvers is critical to this process. Distractibility, entrainability, and variability are examples of classic physical findings in these patients. In this case series, we identify and characterize another phenomenon observed in some of these patients. In this phenomenon, movement suppression of one body part is followed by immediate reemergence of movement in another. We propose that this phenomenon be referred to as the "whack-a-mole" sign. This name is derived from the arcade game whack-a-mole, in which a mole, when hit into its original hole, re-emerges elsewhere. We present a case series of 4 patients with functional movement disorders who exhibit this sign.
Project description:Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This can make the diagnostic process time-consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next-generation sequencing, post-sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs. WHAT THIS PAPER ADDS: An up-to-date description and diagnostic framework for testing of paediatric movement disorders is presented. The framework helps to determine which patients will benefit from next-generation sequencing.
Project description:BackgroundMovement disorders can be associated with anti-neuronal antibodies.MethodsWe conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospinal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variable selection and recursive partitioning and regression trees for the creation of a data-driven decision algorithm, integrated with expert's clinical feedback.ResultsThree hundred and seventy-seven studies met eligibility criteria, totaling 844 patients and 13 antibodies: amphiphysin, GAD, GlyR, mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, NMDAR, LGI-1, CRMP5/CV2, ANNA-1/Hu, IgLON5, and DPPX. Stiffness/rigidity/spasm spectrum symptoms were more frequently associated with amphiphysin, GAD, and GlyR; ataxia with mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, and ANNA-1/Hu; dyskinesia with NMDAR and paroxysmal movement with LGI1; chorea/choreoathetosis with CRMP5/CV2, IgLON5, and NMDAR; myoclonus with GlyR and DPPX; tremors with ANNA2/Ri and anti-DPPX; and parkinsonism with IgLON5 and NMDAR. Data-driven classification analysis determined the following diagnostic predictions (with probability selection): psychiatric symptoms and dyskinesia predicted NMDAR (71% and 87%, respectively); stiffness/rigidity/spasm and ataxia, GAD (67% and 47%, respectively); ataxia and opsoclonus, ANNA-2/Ri (68%); chorea/choreoathetosis, CRMP5/CV2 (41%). These symptoms remained the top predictors in random forests analysis. The integration with an expert opinion analysis refined the precision of the approach. Breast and lung tumors were the most common tumors. On neuroimaging, cerebellar involvement was associated with GAD and Yo/PCA-1; temporal involvement with Caspr2, LGI-1, ANNA-1/Hu.ConclusionSelected movement disorders are associated with specific anti-neuronal antibodies. The combination of data-driven and expert opinion approach to the diagnosis may assist early management efforts.
Project description:A large body of evidence using experimental animal models shows that the nicotinic cholinergic system is involved in the control of movement under physiological conditions. This work raised the question whether dysregulation of this system may contribute to motor dysfunction and whether drugs targeting nicotinic acetylcholine receptors (nAChRs) may be of therapeutic benefit in movement disorders. Accumulating preclinical studies now show that drugs acting at nAChRs improve drug-induced dyskinesias. The general nAChR agonist nicotine, as well as several nAChR agonists (varenicline, ABT-089 and ABT-894), reduces l-dopa-induced abnormal involuntary movements or dyskinesias up to 60% in parkinsonian nonhuman primates and rodents. These dyskinesias are potentially debilitating abnormal involuntary movements that arise as a complication of l-dopa therapy for Parkinson's disease. In addition, nicotine and varenicline decrease antipsychotic-induced abnormal involuntary movements in rodent models of tardive dyskinesia. Antipsychotic-induced dyskinesias frequently arise as a side effect of chronic drug treatment for schizophrenia, psychosis and other psychiatric disorders. Preclinical and clinical studies also show that the nAChR agonist varenicline improves balance and coordination in various ataxias. Lastly, nicotine has been reported to attenuate the dyskinetic symptoms of Tourette's disorder. Several nAChR subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including ?4?2*, ?6?2* and ?7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.