Project description:Despite recent advances in tremor and dystonia classification, it remains difficult to discriminate essential tremor from dystonic tremor as they are similar in appearance and no biomarker exists. Further, tremor can appear in the same or a different body part than the dystonia. The aim of the current study was to better understand the differential pathophysiology of these tremors. We designed a cross-sectional case-control study and recruited 16 patients with essential tremor, 16 patients with dystonic tremor, and 17 age-matched healthy volunteers. We used multi-modal imaging combining resting-state functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy. We measured functional connectivity of resting-state fMRI to assess connectivity in the tremor network, fractional anisotropy and mean diffusivity with diffusion tensor imaging, and GABA+, Glutamate/Glutamine, Choline, and N-Acetylaspartate with spectroscopy (adjusted to Creatine). Our results showed reduced functional connectivity of resting-state fMRI between the cerebellum and dentate nucleus bilaterally for the essential tremor group, but not the dystonic tremor group, compared to healthy volunteers. There was higher fractional anisotropy in the middle cerebellar peduncle bilaterally for the dystonic tremor group compared to the essential tremor group as well as for essential tremor group compared to healthy volunteers. There was also higher fractional anisotropy in the red nucleus and corticospinal tract for essential tremor and dystonic tremor groups compared to healthy volunteers. We also showed reduced mean diffusivity in the cerebellum of both essential tremor and dystonic tremor groups compared to healthy volunteers. Finally, we found elevated GABA+/Cr in the cerebellum of the essential tremor and dystonic tremor groups compared to healthy volunteers, but no difference emerged between essential tremor and dystonic tremor groups. We did not find group differences in the other metabolites. Our results indicate cerebellar alterations in essential tremor and dystonic tremor patients compared to healthy volunteers, and further changes in the cerebellum network for the dystonic tremor patients. suggesting that the cerebellum is affected differently in both tremors.

Project description:Dystonia is a movement disorder characterized by involuntary muscle co-contractions that give rise to disabling movements and postures. A recent expert consensus labelled the incidence of tremor as a core feature of dystonia that can affect body regions both symptomatic and asymptomatic to dystonic features. We are only beginning to understand the neural network-level signatures that relate to clinical features of dystonic tremor. At the same time, clinical features of dystonic tremor can resemble that of essential tremor and present a diagnostic confound for clinicians. Here, we examined network-level functional activation and connectivity in patients with dystonic tremor and essential tremor. The dystonic tremor group included primarily cervical dystonia patients with dystonic head tremor and the majority had additional upper-limb tremor. The experimental paradigm included a precision grip-force task wherein online visual feedback related to force was manipulated across high and low spatial feedback levels. Prior work using this paradigm in essential tremor patients produced exacerbation of grip-force tremor and associated changes in functional activation. As such, we directly compared the effect of visual feedback on grip-force tremor and associated functional network-level activation and connectivity between dystonic tremor and essential tremor patient cohorts to better understand disease-specific mechanisms. Increased visual feedback similarly exacerbated force tremor during the grip-force task in dystonic tremor and essential tremor cohorts. Patients with dystonic tremor and essential tremor were characterized by distinct functional activation abnormalities in cortical regions but not in the cerebellum. We examined seed-based functional connectivity from the sensorimotor cortex, globus pallidus internus, ventral intermediate thalamic nucleus, and dentate nucleus, and observed abnormal functional connectivity networks in dystonic tremor and essential tremor groups relative to controls. However, the effects were far more widespread in the dystonic tremor group as changes in functional connectivity were revealed across cortical, subcortical, and cerebellar regions independent of the seed location. A unique pattern for dystonic tremor included widespread reductions in functional connectivity compared to essential tremor within higher-level cortical, basal ganglia, and cerebellar regions. Importantly, a receiver operating characteristic determined that functional connectivity z-scores were able to classify dystonic tremor and essential tremor with 89% area under the curve, whereas combining functional connectivity with force tremor yielded 94%. These findings point to network-level connectivity as an important feature that differs substantially between dystonic tremor and essential tremor and should be further explored in implementing appropriate diagnostic and therapeutic strategies.

Project description:Dystonic tremor syndromes are highly burdensome and treatment is often inadequate. This is partly due to poor understanding of the underlying pathophysiology. Several lines of research suggest involvement of the cerebello-thalamo-cortical circuit and the basal ganglia in dystonic tremor syndromes, but their role is unclear. Here we aimed to investigate the contribution of the cerebello-thalamo-cortical circuit and the basal ganglia to the pathophysiology of dystonic tremor syndrome, by directly linking tremor fluctuations to cerebral activity during scanning. In 27 patients with dystonic tremor syndrome (dystonic tremor: n = 23; tremor associated with dystonia: n = 4), we used concurrent accelerometery and functional MRI during a posture holding task that evoked tremor, alternated with rest. Using multiple regression analyses, we separated tremor-related activity from brain activity related to (voluntary) posture holding. Using dynamic causal modelling, we tested for altered effective connectivity between tremor-related brain regions as a function of tremor amplitude fluctuations. Finally, we compared grey matter volume between patients (n = 27) and matched controls (n = 27). We found tremor-related activity in sensorimotor regions of the bilateral cerebellum, contralateral posterior and anterior ventral lateral nuclei of the thalamus (VLp and VLa), contralateral primary motor cortex (hand area), contralateral pallidum, and the bilateral frontal cortex (laterality with respect to the tremor). Grey matter volume was increased in patients compared to controls in the portion of contralateral thalamus also showing tremor-related activity, as well as in bilateral medial and left lateral primary motor cortex, where no tremor-related activity was present. Effective connectivity analyses showed that inter-regional coupling in the cerebello-thalamic pathway, as well as the thalamic self-connection, were strengthened as a function of increasing tremor power. These findings indicate that the pathophysiology of dystonic tremor syndromes involves functional and structural changes in the cerebello-thalamo-cortical circuit and pallidum. Deficient input from the cerebellum towards the thalamo-cortical circuit, together with hypertrophy of the thalamus, may play a key role in the generation of dystonic tremor syndrome.

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Helmet Tremor: A Rare Dystonic Tremor

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