Impaired white matter integrity between premotor cortex and basal ganglia in writer’s cramp

Abstract

IntroductionWriter’s cramp (WC) as a focal hand dystonia is characterized by abnormal postures of the hand during writing. Impaired inhibition and maladaptive plasticity in circuits linking the basal ganglia and sensorimotor cortices have been described. In particular, a dysfunction of lateral premotor cortices has been associated with impaired motor control in WC. We applied diffusion tensor imaging to identify changes in white matter connectivity between premotor regions and important cortical and subcortical structures.MethodsWhole brain white matter tracts were reconstructed in 18 right‐handed WC patients and 18 matched controls, using probabilistic fiber tracking. We restricted our analyses to left‐hemispheric fibers between the middle frontal gyrus (MFG) and basal ganglia, thalamus, primary motor, and sensory cortex. Diffusion parameters (fractional anisotropy and linear anisotropy) were compared between both groups.ResultsA significant reduction in fractional anisotropy values was shown for patients (mean ± SD: 0.37 ± 0.02) vs. controls (0.39 ± 0.03) regarding fibers between the left‐sided MFG and the putamen (p < 0.05). The same applied for linear anisotropy values in this connection (p < 0.05).ConclusionsOur results suggest an impaired structural connectivity between the left‐hemispheric MFG and putamen with a loss of equally aligned fibers in WC patients. This could reflect a structural basis for functional findings interpreted as altered inhibition and plasticity, both within the premotor cortex and the basal ganglia, that at last lead to the clinical symptoms of WC.

Structure-function abnormalities in cortical sensory projections in embouchure dystonia

“…Brain γ-aminobutyric acid reductions as a potential correlate of impaired inhibitory projections have been observed both in the lentiform nucleus and in the primary sensorimotor cortex of the affected hemisphere in focal hand dystonia patients using magnetic resonance spectroscopy ( Levy and Hallett, 2002 ). While the significant cortico-subcortical tract abnormality reported in this work was confined to sensory trajectories, data in writer’s cramp similarly showed a reduction in axial diffusivity in the trajectory connecting the middle frontal gyrus and the putamen (together with fractional anisotropy) ( Berndt et al, 2018 ). This may indicate that other non-sensory cortices undergo comparable changes, though potential FD subtype-associated differences cannot be excluded ( Bianchi et al, 2019 , Ramdhani et al, 2014 ).…”

Dystonia-specific mutations in THAP1 alter transcription of genes associated with neurodevelopment and myelin

“… 81 , 82 , 83 , 84 Although overt demyelination has not been specifically documented in dystonia, neuroimaging studies have reported white matter abnormalities in multiple forms of the disease, including (1) syndromes associated with genetic variation in TOR1A , THAP1 , SGCE (MIM: 604149 , DYT11 [MIM: 159900 ]), TAF1 , KMT2B , and COL6A3 (MIM: 120250 , DYT27 [MIM: 616411 ]) 20 , 69 , 85 , 86 , 87 , 88 , 89 and (2) idiopathic cases of cervical dystonia, writer’s cramp, laryngeal dystonia, and blepharospasm. 90 , 91 , 92 , 93 The mechanisms underlying these disturbances in white matter tracts are not known, and further investigation is needed to determine whether they reflect common defects in any of the pathways perturbed by genetic variation in THAP1 .…”

Dystonia-specific mutations in THAP1 alter transcription of genes associated with neurodevelopment and myelin

“…[81][82][83][84] Although overt demyelination has not been specifically documented in dystonia, neuroimaging studies have reported white matter abnormalities in multiple forms of the disease, including: (1) syndromes associated with genetic variation in TOR1A, THAP1, SGCE, TAF1, KMT2B, and COL6A3 20,69,[85][86][87][88][89] ; and (2) idiopathic cases of cervical dystonia, writer's cramp, laryngeal dystonia, and blepharospasm. [90][91][92][93] The mechanisms underlying these disturbances in white matter tracts are not known, and further investigation is needed to determine if they reflect common defects in any of the pathways perturbed by genetic variation in THAP1.…”