Delmaire, C. et al. Structural abnormalities in the cerebellum and sensorimotor circuit in writer's cramp. Neurology 69, 376-380

INSERM U610, Groupe Hôpitalier Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France.
Neurology (Impact Factor: 8.29). 08/2007; 69(4):376-80. DOI: 10.1212/01.wnl.0000266591.49624.1a
Source: PubMed


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.

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    • "Imaging studies strongly implicate BG circuits in the pathophysiology of dystonia. Though generally considered a disorder of abnormal function of motor circuits (as opposed to structure), consistent changes in the volume of motor-related areas (motor cortex, BG, and cerebellum) have been found in both focal and generalized primary dystonias (Delmaire et al., 2007; Draganski, Thun-Hohenstein, Bogdahn, Winkler, & May, 2003; Egger et al., 2007; Garraux et al., 2004). Some of these changes are specific to patients manifesting dystonia, while others also occur in mutation carriers. "
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    ABSTRACT: This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role-Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function.
    Current Topics in Developmental Biology 06/2014; 109:97-169. DOI:10.1016/B978-0-12-397920-9.00001-9 · 4.68 Impact Factor
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    • "Recent evidence suggested that cerebellar circuits may play a prominent role in the pathophysiology of dystonia [7] [8]. 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 [9]. Indeed, changes in microstructural imaging and metabolic activity of cerebellarthalamo-cortical (CTC) pathways have been observed in primary torsion dystonia [10] and in hereditary dystonia [11]. "
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    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 · 4.40 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). "
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    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.
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