The cerebellum in dystonia – Help or hindrance?

Sadnicka, Anna; Hoffland, Britt S.; Bhatia, Kailash P.; Warrenburg, B.P.C. van de; Edwards, Mark J.

doi:10.1016/j.clinph.2011.04.027

Cited by 104 publications

(82 citation statements)

References 97 publications

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“…There is evidence that dysfunction of Purkinje cell firing induces dystonic motor behavior in rats (Raike et al, 2012; Todorov et al, 2012), and morphological degeneration of Purkinje neurons has been found postmortem in brains of people who suffered dystonia (Prudente et al, 2013). Pilot studies in our laboratory indicate that noninvasive stimulation to increase excitability of the cerebellum may transiently improve handwriting in people with focal hand and cervical dystonia (Bradnam et al, 2013).…”

Section: A Model Of Craniocervical Dystonia Involving Loss Of Tsnc Inmentioning

confidence: 91%

The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia

Bradnam

Barry²

2013

J. Neurosci.

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Isolated focal dystonia is a neurological disorder that manifests as repetitive involuntary spasms and/or aberrant postures of the affected body part. Craniocervical dystonia involves muscles of the eye, jaw, larynx, or neck. The pathophysiology is unclear, and effective therapies are limited. One mechanism for increased muscle activity in craniocervical dystonia is loss of inhibition involving the trigeminal sensory nuclear complex (TSNC). The TSNC is tightly integrated into functionally connected regions subserving sensorimotor control of the neck and face. It mediates both excitatory and inhibitory reflexes of the jaw, face, and neck. These reflexes are often aberrant in craniocervical dystonia, leading to our hypothesis that the TSNC may play a central role in these particular focal dystonias. In this review, we present a hypothetical extended brain network model that includes the TSNC in describing the pathophysiology of craniocervical dystonia. Our model suggests the TSNC may become hyperexcitable due to loss of tonic inhibition by functionally connected motor nuclei such as the motor cortex, basal ganglia, and cerebellum. Disordered sensory input from trigeminal nerve afferents, such as aberrant feedback from dystonic muscles, may continue to potentiate brainstem circuits subserving craniocervical muscle control. We suggest that potentiation of the TSNC may also contribute to disordered sensorimotor control of face and neck muscles via ascending and cortical descending projections. Better understanding of the role of the TSNC within the extended neural network contributing to the pathophysiology of craniocervical dystonia may facilitate the development of new therapies such as noninvasive brain stimulation.

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Section: A Model Of Craniocervical Dystonia Involving Loss Of Tsnc Inmentioning

confidence: 91%

The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia

Bradnam

Barry²

2013

J. Neurosci.

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“…This localization of dystonia to the basal ganglia does not accommodate a growing body of clinical and experimental evidence of the involvement of other structures, and the concept of dystonia as a network disorder involving multiple brain regions has been proposed [2,3]. The role of the cerebellum in the pathophysiology of dystonia was first noted by Fletcher et al [4] and there is strong evidence of abnormal cerebellar function from pathological, neuroimaging, and neurophysiological studies [2,3,5], particularly in forms of primary dystonia [6][7][8].…”

mentioning

confidence: 99%

Dissecting the Links Between Cerebellum and Dystonia

Malone

Manto²,

Hass

2014

Cerebellum

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Dystonia is a common movement disorder characterized by sustained muscle contractions. These contractions generate twisting and repetitive movements or typical abnormal postures, often exacerbated by voluntary movement. Dystonia can affect almost all the voluntary muscles. For several decades, the discussion on the pathogenesis has been focused on basal ganglia circuits, especially striatal networks. So far, although dystonia has been observed in some forms of ataxia such as dominant ataxias, the link between the cerebellum and dystonia has remained unclear. Recent human studies and experimental data mainly in rodents show that the cerebellum circuitry could also be a key player in the pathogenesis of some forms of dystonia. In particular, studies based on behavioral adaptation paradigm shed light on the links between dystonia and cerebellum. The spectrum of movement disorders in which the cerebellum is implicated is continuously expanding, and manipulation of cerebellar circuits might even emerge as a candidate therapy in the coming years.

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“…However, recent studies have also provided evidence of cerebellar abnormalities in isolated dystonias [6,7]. In humans, THAP1 is widely expressed in the brain and in a wide variety of extraneural tissues such as the liver, kidney, skeletal muscle, thyroid gland and prostate [8].…”

Section: Introductionmentioning

confidence: 99%

DYT6 Dystonia: A Neuropathological Study

Paudel¹,

Li²,

Hardy³

et al. 2015

Neurodegener Dis

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Background: Mutations in the thanatos-associated protein domain containing apoptosis-associated protein 1 gene (THAP1) are responsible for adult-onset isolated dystonia (DYT6). However, no neuropathological studies of genetically proven DYT6 cases have been previously reported. Objective: We report the first detailed neuropathological investigation carried out on two DYT6 brains. Methods: Genetic screening for THAP1 gene mutations using standard Sanger polymerase chain reaction sequencing identified 2 cases, 1 with a known pathogenic mutation and the other with a novel mutation. A detailed neuropathological assessment of the cases was performed. Results: Both DYT6 cases showed no significant neurodegeneration and no specific disease-related pathology. Conclusions: No neuropathological features that could be defined as hallmark features of DYT6 dystonia were identified. Our study supports the notion that in isolated dystonia, there is no significant neurodegeneration or morphological lesions that can be identified using routine methods.

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The cerebellum in dystonia – Help or hindrance?

Cited by 104 publications

References 97 publications

The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia

The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia

Dissecting the Links Between Cerebellum and Dystonia

DYT6 Dystonia: A Neuropathological Study

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