Summary Functional (psychogenic) movement disorders (FMD) are part of the wide spectrum of functional neurological disorders, which together account for over 16% of patients referred to neurology ...clinics. FMD have been described as a “crisis for neurology” and cause major challenges in terms of diagnosis and treatment. As with other functional disorders, a key issue is the absence of pathophysiological understanding. There has been an influential historical emphasis on causation by emotional trauma, which is not supported by epidemiological studies. The similarity between physical signs in functional disorders and those that occur in feigned illness has also raised important challenges for pathophysiological understanding and has challenged health professionals' attitudes toward patients with these disorders. However, physical signs and selected investigations can help clinicians to reach a positive diagnosis, and modern pathophysiological research is showing an appreciation of the importance of both physical and psychological factors in FMD.
In each of these instances, there are fundamental clinical and anatomopathological differences (figure). ...patients in whom scenarios 1 and 2 apply will present with neurological manifestations ...generally incompatible with the diagnostic criteria for Parkinson's disease, such as acute onset, myoclonus, cerebellar or pyramidal signs, and scarce or no response to levodopa treatment. ...this classic example of a respiratory virus associated with damage of the substantia nigra triggered a condition clearly different from Parkinson's disease, both clinically and pathologically. ...unlike in Parkinson's disease, hyposmia is reversible in the majority of cases with COVID-19, and whether or not it reflects the ability of the virus to reach the nigrostriatal pathway remains speculative as there is no direct connection between the olfactory bulb and the substantia nigra in primates. ...we could perhaps conclude, on the basis of the limited evidence, that SARS-CoV-2 enters the CNS, but no data support a preferential tropism for the substantia nigra.
Unravelling of the paroxysmal dyskinesias Erro, Roberto; Bhatia, Kailash P
Journal of neurology, neurosurgery and psychiatry,
02/2019, Letnik:
90, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Paroxysmal dyskinesias (PxD) refer to a rare group of clinically and genetically heterogeneous disorders presenting with recurrent attacks of abnormal movements, typically dystonia, chorea or a ...combination thereof, without loss of consciousness. Classically, PxD have been categorised according to their triggers and duration of the attacks, but increasing evidence suggests that there is a certain degree of clinical and genetic overlap and challenges the concept that one phenotype is attributable to one single aetiology. Here we review the increasing spectrum of genetic conditions, as well as of other non-genetic disorders, that might present with PxD, provide criteria for case definition and propose a diagnostic workup to reach a definitive diagnosis, on which treatment is heavily dependent.
Dystonia and Parkinson's disease are closely linked disorders sharing many pathophysiological overlaps. Dystonia can be seen in 30% or more of the patients suffering with PD and sometimes can precede ...the overt parkinsonism. The response of early dystonia to the introduction of dopamine replacement therapy (levodopa, dopamine agonists) is variable; dystonia commonly occurs in PD patients following levodopa initiation. Similarly, parkinsonism is commonly seen in patients with mutations in various DYT genes including those involved in the dopamine synthesis pathway. Pharmacological blockade of dopamine receptors can cause both tardive dystonia and parkinsonism and these movement disorders syndromes can occur in many other neurodegenerative, genetic, toxic and metabolic diseases. Pallidotomy in the past and currently deep brain stimulation largely involving the GPi are effective treatment options for both dystonia and parkinsonism. However, the physiological mechanisms underlying the response of these two different movement disorder syndromes are poorly understood. Interestingly, DBS for PD can cause dystonia such as blepharospasm and bilateral pallidal DBS for dystonia can result in features of parkinsonism. Advances in our understanding of these responses may provide better explanations for the relationship between dystonia and Parkinson's disease.
Speed-accuracy trade-off is an intensively studied law governing almost all behavioral tasks across species. Here we show that motivation by reward breaks this law, by simultaneously invigorating ...movement and improving response precision. We devised a model to explain this paradoxical effect of reward by considering a new factor: the cost of control. Exerting control to improve response precision might itself come at a cost—a cost to attenuate a proportion of intrinsic neural noise. Applying a noise-reduction cost to optimal motor control predicted that reward can increase both velocity and accuracy. Similarly, application to decision-making predicted that reward reduces reaction times and errors in cognitive control. We used a novel saccadic distraction task to quantify the speed and accuracy of both movements and decisions under varying reward. Both faster speeds and smaller errors were observed with higher incentives, with the results best fitted by a model including a precision cost. Recent theories consider dopamine to be a key neuromodulator in mediating motivational effects of reward. We therefore examined how Parkinson’s disease (PD), a condition associated with dopamine depletion, alters the effects of reward. Individuals with PD showed reduced reward sensitivity in their speed and accuracy, consistent in our model with higher noise-control costs. Including a cost of control over noise explains how reward may allow apparent performance limits to be surpassed. On this view, the pattern of reduced reward sensitivity in PD patients can specifically be accounted for by a higher cost for controlling noise.
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•The speed-accuracy trade-off in motor and cognitive control can be broken by reward•Apparent limits of performance can be overcome by motivation•A cost for reducing intrinsic neural noise quantitatively explains such improvements•Reduced reward effects in Parkinson’s disease suggest an increased cost of control
Manohar et al. investigate how motivation by reward can improve both speed and accuracy, apparently exceeding the limits of the speed-accuracy trade-off. They propose a cost for reducing intrinsic neural noise. Optimizing this cost predicts both motor and cognitive performance. The cost of control may be increased in Parkinson’s disease.
In this study, we combined linkage analysis with whole-exome sequencing of two individuals to identify candidate causal variants in a moderately-sized UK kindred exhibiting autosomal-dominant ...inheritance of craniocervical dystonia. Subsequent screening of these candidate causal variants in a large number of familial and sporadic cases of cervical dystonia led to the identification of a total of six putatively pathogenic mutations in ANO3, a gene encoding a predicted Ca2+-gated chloride channel that we show to be highly expressed in the striatum. Functional studies using Ca2+ imaging in case and control fibroblasts demonstrated clear abnormalities in endoplasmic-reticulum-dependent Ca2+ signaling. We conclude that mutations in ANO3 are a cause of autosomal-dominant craniocervical dystonia. The locus DYT23 has been reserved as a synonym for this gene. The implication of an ion channel in the pathogenesis of dystonia provides insights into an alternative mechanism that opens fresh avenues for further research.
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