Alcohol improves cerebellar learning deficit in myoclonus–dystonia: A clinical and electrophysiological investigation

Weissbach, Anne; Werner, Elisa; Bally, Julien; Tunc, Sinem; Löns, Sebastian; Timmann, Dagmar; Zeuner, Kirsten E.; Tadić, Vera; Brüggemann, Norbert; Lang, Anthony E.; Klein, Christine; Münchau, Alexander; Bäumer, Tobias

doi:10.1002/ana.25035

Cited by 43 publications

(44 citation statements)

References 47 publications

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“…16,17 In addition, the partial alleviation of symptoms of DYT11 with alcohol, to which the cerebellum is highly sensitive, is often taken as a clinical marker of potential cerebellar involvement. 8,17 The causative mutation of DYT11 dystonia, ϵ-sarcoglycan, is expressed in multiple nonneural and neural regions throughout development. 18 Importantly, brain-specific isoforms demonstrate high expression in the Purkinje cells and neurones of the dentate nucleus, 8 in motor learning on a beam-walking test have been observed in a Purkinje cell-specific conditional knockout for ϵ-sarcoglycan.…”

Section: Discussionmentioning

confidence: 99%

“…6 In humans with DYT11 dystonia, imaging studies have revealed metabolic changes in the cerebellum (in conjunction with other regional abnormalities) 7 and impaired saccadic adaptation has been taken as one of the first functional markers of cerebellar dysfunction in the disease. 9 Results with another associative cerebellar learning paradigm, eye blink conditioning, have to date been mixed (one study showing normal acquisition, 4 the other impaired acquisition) 17 . Whether the subclinical deficit in saccadic adaption was indicative of a more general deficit in adaptation was the core experimental question explored in this paper.…”

Section: Discussionmentioning

confidence: 99%

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Delineating cerebellar mechanisms in DYT11 myoclonus‐dystonia

et al. 2018

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Background Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus‐dystonia syndrome as a result of mutations in the ɛ‐sarcoglycan gene (DYT11). Specifically, a cerebellar‐dependent saccadic adaptation task is dramatically impaired in this patient group. Objectives The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions. Methods Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged‐matched controls. Results Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions. Conclusions DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study. © 2018 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Delineating cerebellar mechanisms in DYT11 myoclonus‐dystonia

et al. 2018

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“…This suggests that dysfunction of the striato‐pallido‐thalamo‐cortical network is critically involved in the generation of this motor phenotype . Metabolic neuroimaging and various neurophysiological studies point to a dysfunctional cerebello‐thalamo‐cortical pathway . Similar to other dystonic syndromes, abnormal sensorimotor integration with hypoactivity within the premotor, sensory, and parietal cortices and the cerebellum has been shown in DYT‐ SGCE .…”

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confidence: 90%

Visual Sensory Processing is Altered in Myoclonus Dystonia

et al. 2019

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Background Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes. Objective To investigate visual sensory processing in DYT‐SGCE and identify its structural correlates. Methods DYT‐SGCE patients without DBS (DYT‐SGCE‐non‐DBS) and with DBS (DYT‐SGCE‐DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with μ parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold. Results Twenty‐four DYT‐SGCE‐non‐DBS, 13 DYT‐SGCE‐DBS, and 25 healthy volunteers were included in the study. In DYT‐SGCE‐DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (μ) was lower in DYT‐SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT‐SGCE‐non‐DBS compared to healthy volunteers, which also correlated with lower μ in temporal discrimination threshold (P = 0.029). In DYT‐SGCE‐non‐DBS, myoclonus severity also correlated with a lower μ in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022). Conclusion In DYT‐SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. © 2019 International Parkinson and Movement Disorder Society

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“…© 2018 International Parkinson and Movement Disorder Society crucial role of the cerebellothalamic pathways in the generation of these motor symptoms, as well as objective improvement after alcohol intake. 6 The disease typically starts with action myoclonus, which is, in fact, the most disabling manifestation based on our clinical experience, and is followed by focal or segmental dystonia of the upper body. The clinical picture also includes a broad spectrum of neuropsychiatric symptoms, mostly anxiety-related disorders and obsessive-compulsive disorder, and an increased risk of alcoholism.…”

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confidence: 95%

“…The brain‐specific function of the gene is not completely elucidated, but it is a part of the dystrophin‐associated membrane complex . Histopathological, neurophysiological, and imaging studies point to a crucial role of the cerebellothalamic pathways in the generation of these motor symptoms, as well as objective improvement after alcohol intake …”

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confidence: 99%

Long‐term GPi‐DBS improves motor features in myoclonus‐dystonia and enhances social adjustment

et al. 2018

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Background Good short‐term results of pallidal deep brain stimulation have been reported in myoclonus‐dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long‐term clinical outcome, quality of life, and social adjustment of GPi‐DBS in patients with ε‐sarcoglycan (DYT11)‐positive myoclonus‐dystonia. Methods Consecutive myoclonus‐dystonia patients with ε‐sarcoglycan mutations who underwent GPi‐DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke‐Fahn‐Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video‐protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. Results Nine patients (5 women) with long‐term GPi‐DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. Conclusions GPi‐DBS seems to be a safe and efficacious treatment for medically refractory ɛ‐sarcoglycan myoclonus‐dystonia, with sustained motor benefit, good quality of life, and social adjustment in long‐term follow‐up. © 2018 International Parkinson and Movement Disorder Society

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Alcohol improves cerebellar learning deficit in myoclonus–dystonia: A clinical and electrophysiological investigation

Cited by 43 publications

References 47 publications

Delineating cerebellar mechanisms in DYT11 myoclonus‐dystonia

Delineating cerebellar mechanisms in DYT11 myoclonus‐dystonia

Visual Sensory Processing is Altered in Myoclonus Dystonia

Long‐term GPi‐DBS improves motor features in myoclonus‐dystonia and enhances social adjustment

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