Smaller Cerebellar Lobule VIIb is Associated with Tremor Severity in Parkinson's Disease.

Alterations in the cerebellum's morphology in Parkinson's disease (PD) point to its pathophysiological involvement in this movement disorder. Such abnormalities have previously been attributed to different PD motor subtypes. The aim of the study was to relate volumes of specific cerebellar lobules to motor symptom severity, in particular tremor (TR), bradykinesia/rigidity (BR), and postural instability and gait disorders (PIGD) in PD. We performed a volumetric analysis based on T1-weighted MRI images of 55 participants with PD (22 females, median age 65 years, Hoehn and Yahr stage 2). Multiple regression models were fitted to investigate associations between volumes of cerebellar lobules with clinical symptom severity based on MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score and sub-scores for TR, BR, and PIGD; adjusted for age, sex, disease duration, and intercranial volume as cofactors. Smaller volume of lobule VIIb was associated with higher tremor severity (P = 0.004). No structure-function relationships were detected for other lobules or other motor symptoms. This distinct structural association denotes the involvement of the cerebellum in PD tremor. Characterizing morphological features of the cerebellum leads to a better understanding of its role in the spectrum of motor symptoms in PD and contributes further to identifying potential biological markers.

Cerebellar Modulation of Sensorimotor Associative Plasticity Is Impaired in Cervical Dystonia.

BACKGROUND: In recent years, cervical dystonia (CD) has been recognized as a network disorder that involves not only the basal ganglia but other brain regions, such as the primary motor and somatosensory cortex, brainstem, and cerebellum. So far, the role of the cerebellum in the pathophysiology of dystonia is only poorly understood. OBJECTIVE: The objective of this study was to investigate the role of the cerebellum on sensorimotor associative plasticity in patients with CD. METHODS: Sixteen patients with CD and 13 healthy subjects received cerebellar transcranial direct current stimulation (ctDCS) followed by a paired associative stimulation (PAS) protocol based on transcranial magnetic stimulation that induces sensorimotor associative plasticity. Across three sessions the participants received excitatory anodal, inhibitory cathodal, and sham ctDCS in a double-blind crossover design. Before and after the intervention, motor cortical excitability and motor symptom severity were assessed. RESULTS: PAS induced an increase in motor cortical excitability in both healthy control subjects and patients with CD. In healthy subjects this effect was attenuated by both anodal and cathodal ctDCS with a stronger effect of cathodal stimulation. In patients with CD, anodal stimulation suppressed the PAS effect, whereas cathodal stimulation had no influence on PAS. Motor symptom severity was unchanged after the intervention. CONCLUSIONS: Cerebellar modulation with cathodal ctDCS had no effect on sensorimotor associative plasticity in patients with CD, in contrast with the net inhibitory effect in healthy subjects. This is further evidence that the cerebello-thalamo-cortical network plays a role in the pathophysiology of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A case of Huntington's disease with two reduced penetrance alleles.

We present a case of Huntington's Disease (HD) with two reduced penetrance alleles and show that age of onset and motor symptoms are comparable to heterozygous patients with the same number of CAG triplet repeats. We performed a review of the literature on clinical presentation of homozygous HD cases and highlight that, so far, evidence exists that HD is a truly dominant disorder. This has important implications for pathophysiology concepts of the disease.

Fixed endothelial cells exhibit physiologically relevant nanomechanics of the cortical actin web.

It has been unknown whether cells retain their mechanical properties after fixation. Therefore, this study was designed to compare the stiffness properties of the cell cortex (the 50-100 nm thick zone below the plasma membrane) before and after fixation. Atomic force microscopy was used to acquire force indentation curves from which the nanomechanical cell properties were derived. Cells were pretreated with different concentrations of actin destabilizing agent cytochalasin D, which results in a gradual softening of the cell cortex. Then cells were studied 'alive' or 'fixed'. We show that the cortical stiffness of fixed endothelial cells still reports functional properties of the actin web qualitatively comparable to those of living cells. Myosin motor protein activity, tested by blebbistatin inhibition, can only be detected, in terms of cortical mechanics, in living but not in fixed cells. We conclude that fixation interferes with motor proteins while maintaining a functional cortical actin web. Thus, fixation of cells opens up the prospect of differentially studying the actions of cellular myosin and actin.