The final blink: intact cerebellar associative learning in isolated dystonia

Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia. However, the results from individual studies are conflicting and underpowered. This collaborative project collated all published data and systematically re-examined the contribution of the predictors dystonia and its subtypes within a statistical model which controlled for the co-variates age and sex. Original neurophysiological data were shared and a sex and age matched control group were collected (dystonia n=52, controls n=50). Two raters blinded to participant identity rescored all recordings (6732 trials). After high inter-rater agreement was confirmed, mean conditioning per block was entered into a mixed repetitive measures model to evaluate the influence of sex, age, dystonia subtype (focal hand dystonia, cervical dystonia, DYT-TOR1A and DYT-THAP1) and clinical features such as tremor. There was a wide range of conditioning behavior across individuals in both groups. Young age (p=0.031) was associated with higher conditioning. All dystonia versus controls showed no difference in conditioning (p=0.517). Analysis of dystonia subgroup, with age and sex as co-variates, showed that conditioning in cervical dystonia, focal hand dystonia and DYT-TOR1A was comparable to controls. DYT-THAP1 was characterized by high levels of conditioning. Clinical features such as tremor did not significantly influence conditioning. Sample size estimates for future work are provided based on the variance observed. Eyeblink conditioning, a proxy for cerebellar function, appears intact in the subtypes of isolated dystonia examined. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains elusive.

The Genetic Landscape of Parkinsonism-Related Dystonias and Atypical Parkinsonism-Related Syndromes

In recent decades, genetic research has nominated promising pathways and biological insights contributing to the etiological landscape of parkinsonism-related dystonias and atypical parkinsonism-related syndromes. Several disease-causing mutations and genetic risk factors have been unraveled, providing a deeper molecular understanding of the complex genetic architecture underlying these conditions. These disorders are difficult to accurately diagnose and categorize, thus making genetics research challenging. On one hand, dystonia is an umbrella term linked to clinically heterogeneous forms of disease including dopa-responsive dystonia, myoclonus-dystonia, rapid-onset dystonia-parkinsonism and dystonia-parkinsonism, often viewed as a precursor to Parkinson’s disease. On the other hand, atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration, are rare in nature and represent a wide range of diverse and overlapping phenotypic variabilities, with genetic research limited by sample size availability. The current review summarizes the plethora of available genetic information for these diseases, outlining limits and future directions.

Personality Profile in Focal Hand Dystonia: A Cross-Sectional Study

It has been suggested that focal hand dystonia (FHD) should be viewed as a neuropsychiatric disorder rather than as a pure movement disorder. We aimed to compare the personality factors that are common to people with FHD and evaluate how personality factors could affect the functionality of the upper limbs and community participation. We conducted a cross-sectional case–control study in which 12 people with FHD were matched with 12 age and gender matched healthy control participants. The Big Five Questionnaire; the Quick Disabilities, Arm, Shoulder, and Hand questionnaire; and the Jebsen–Taylor Test of Hand Function were used as assessment measures. Control of emotions was the only variable for which a significant difference was found, with participants with FHD displaying lesser control. Correlations were not observed between different personality profiles, the functionality of the upper limb,s and the perceived participation of people with FHD in activities of daily living. People with FHD may present with low emotional stability, but this does not have a negative impact on the functionality of the upper limbs and activities of daily living. These findings have clinical implications to be considered for interventions, as they suggest that personality aspects, such as extraversion, may not predict for better functionality and perceived participation in activities of daily living.

Use of non-invasive stimulation in movement disorders: a critical review

Background: Noninvasive stimulation has been widely used in the past 30 years to study and treat a large number of neurological diseases, including movement disorders. Objective: In this critical review, we illustrate the rationale for use of these techniques in movement disorders and summarize the best medical evidence based on the main clinical trials performed to date. Methods: A nationally representative group of experts performed a comprehensive review of the literature in order to analyze the key clinical decision-making factors driving transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in movement disorders. Classes of evidence and recommendations were described for each disease. Results: Despite unavoidable heterogeneities and low effect size, TMS is likely to be effective for treating motor symptoms and depression in Parkinson’s disease (PD). The efficacy in other movement disorders is unclear. TMS is possibly effective for focal hand dystonia, essential tremor and cerebellar ataxia. Additionally, it is likely to be ineffective in reducing tics in Tourette syndrome. Lastly, tDCS is likely to be effective in improving gait in PD. Conclusions: There is encouraging evidence for the use of noninvasive stimulation on a subset of symptoms in selected movement disorders, although the means to optimize protocols for improving positive outcomes in routine clinical practice remain undetermined. Similarly, the best stimulation paradigms and responder profile need to be investigated in large clinical trials with established therapeutic and assessment paradigms that could also allow genuine long-term benefits to be determined.

Muscle Tone Physiology and Abnormalities

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.