Structural abnormalities in the cerebellum and sensorimotor circuit in writer's cramp
ABSTRACT Structural abnormalities were detected in bilateral primary sensorimotor areas in writer's cramp. Evidence in other primary dystonia, including blepharospasm and cervical dystonia, suggest that structural abnormalities may be observed in other brain areas such as the cerebellum in writer's cramp.
To test the hypothesis that structural abnormalities are present along the sensorimotor and cerebellar circuits in patients with writer's cramp.
Using voxel-based morphometry, the authors compared the brain structure of 30 right-handed patients with writer's cramp with that of 30 healthy control subjects matched for gender, age, and handedness.
Gray matter decrease was found in the hand area of the left primary sensorimotor cortex, bilateral thalamus, and cerebellum (height threshold p < 0.01, cluster significant at p < 0.05 corrected for multiple comparisons).
These results demonstrate in writer's cramp the presence of structural abnormalities in brain structures interconnected within the sensorimotor network including the cerebellum and the cortical representation of the affected hand. These abnormalities may be related to the pathophysiology of writer's cramp, questioning the role of the cerebellum, or to maladaptive plasticity in a task-related dystonia.
- SourceAvailable from: Viviana Ponzo
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- "Recent evidence suggested that cerebellar circuits may play a prominent role in the pathophysiology of dystonia  . For instance, patients affected by primary dystonia have structural, metabolic and functional changes of cerebellar circuits, and MRI investigations revealed that patients with writer's cramp show a gray matter decrease in cerebellum . Indeed, changes in microstructural imaging and metabolic activity of cerebellarthalamo-cortical (CTC) pathways have been observed in primary torsion dystonia  and in hereditary dystonia . "
ABSTRACT: Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.Brain Stimulation 05/2014; 7(4). DOI:10.1016/j.brs.2014.05.002 · 5.43 Impact Factor
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- "Recent evidence also suggests a role for the cerebellum in the pathophysiology of some forms of dystonia (Lehericy et al., 2013). For example, a reduction in cerebellar gray matter has been described in patients with focal dystonia (Delmaire et al., 2007), and cerebellar dysfunction appears to be the primary cause for dystonia in patients who display marked dystonia affecting the neck, vocal cords, face, and upper and lower limbs, and face (Le Ber et al., 2006). Moreover, patients with primary dystonia have increased metabolic activity in the cerebellum (Eidelberg et al., 1998) and imaging studies of patients with the most common inherited form of dystonia, DYT1, have revealed abnormalities in cerebellar outflow (Argyelan et al., 2009). "
ABSTRACT: Recent evidence suggests that dystonia, a movement disorder characterized by sustained involuntary muscle contractions, can be associated with cerebellar abnormalities. The basis for how functional changes in the cerebellum can cause dystonia is poorly understood. Here we identify alterations in physiology in Atcay(ji-hes) mice which in addition to ataxia, have an abnormal gait with hind limb extension and toe walking, reminiscent of human dystonic gait. No morphological abnormalities in the brain accompany the dystonia, but partial cerebellectomy causes resolution of the stiff-legged gait, suggesting that cerebellar dysfunction contributes to the dystonic gait of Atcay(ji-hes) mice. Recordings from Purkinje and deep cerebellar nuclear (DCN) neurons in acute brain slices were used to determine the physiological correlates of dystonia in the Atcay(ji-hes) mice. Approximately 50% of cerebellar Purkinje neurons fail to display the normal repetitive firing characteristic of these cells. In addition, DCN neurons exhibit increased intrinsic firing frequencies with a subset of neurons displaying bursts of action potentials. This increased intrinsic excitability of DCN neurons is accompanied by a reduction in after-hyperpolarization currents mediated by small-conductance calcium-activated potassium (SK) channels. An activator of SK channels reduces DCN neuron firing frequency in acute cerebellar slices and improves the dystonic gait of Atcay(ji-hes) mice. These results suggest that a combination of reduced Purkinje neuron activity and increased DCN intrinsic excitability can result in a combination of ataxia and a dystonia-like gait in mice.Neurobiology of Disease 04/2014; 67. DOI:10.1016/j.nbd.2014.03.020 · 5.20 Impact Factor
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- "Similar to the case for the basal ganglia, autopsy and clinical imaging studies have linked some subtypes of dystonia with focal lesions of cerebellar circuits (Neychev et al., 2011; Zoons and Tijssen, 2013), and recent studies have shown subtle defects in cerebellar Purkinje cells in autopsy specimens from patients with cervical dystonia (Ma et al., 2012; Prudente et al., 2012). The same functional imaging studies that revealed abnormalities in the basal ganglia very frequently simultaneously revealed abnormalities in the cerebellum, and in some cases the cerebellar changes were greater than those in the basal ganglia (Odergren et al., 1998; Hutchinson et al., 2000; Delmaire et al., 2007; Thobois et al., 2008; Argyelan et al., 2009). These cerebellar abnormalities originally were interpreted as secondary compensatory changes to causal pathology in the basal ganglia, but more recent re-interpretations suggest the cerebellar abnormalities may be causal (Argyelan et al., 2009; Carbon and Eidelberg, 2009). "
ABSTRACT: The dystonias are a group of disorders defined by sustained or intermittent muscle contractions that result in involuntary posturing or repetitive movements. There are many different clinical manifestations and causes. Although they traditionally have been ascribed to dysfunction of the basal ganglia, recent evidence has suggested dysfunction may originate from other regions, particularly the cerebellum. This recent evidence has led to an emerging view that dystonia is a network disorder that involves multiple brain regions. The new network model for the pathogenesis of dystonia has raised many questions, particularly regarding the role of the cerebellum. For example, if dystonia may arise from cerebellar dysfunction, then why are there no cerebellar signs in dystonia? Why are focal cerebellar lesions or degenerative cerebellar disorders more commonly associated with ataxia rather than dystonia? Why is dystonia more commonly associated with basal ganglia lesions rather than cerebellar lesions? Can answers obtained from animals be extrapolated to humans? Is there any evidence that the cerebellum is not involved? Finally, what is the practical value of this new model of pathogenesis for the neuroscientist and clinician? This article explores potential answers to these questions.Neuroscience 01/2014; 260:23–35. · 3.33 Impact Factor