Dystonia

Abstract

Dystonia is a neurological condition characterized by abnormal involuntary movements or postures owing to sustained or intermittent muscle contractions. Dystonia can be the manifesting neurological sign of many disorders, either in isolation (isolated dystonia) or with additional signs (combined dystonia). The main focus of this Primer is forms of isolated dystonia of idiopathic or genetic aetiology. These disorders differ in manifestations and severity but can affect all age groups and lead to substantial disability and impaired quality of life. The discovery of genes underlying the mendelian forms of isolated or combined dystonia has led to a better understanding of its pathophysiology. In some of the most common genetic dystonias, such as those caused by TOR1A, THAP1, GCH1 and KMT2B mutations, and idiopathic dystonia, these mechanisms include abnormalities in transcriptional regulation, striatal dopaminergic signalling and synaptic plasticity and a loss of inhibition at neuronal circuits. The diagnosis of dystonia is largely based on clinical signs, and the diagnosis and aetiological definition of this disorder remain a challenge. Effective symptomatic treatments with pharmacological therapy (anticholinergics), intramuscular botulinum toxin injection and deep brain stimulation are available; however, future research will hopefully lead to reliable biomarkers, better treatments and cure of this disorder.

Diverse Mechanisms Lead to Common Dysfunction of Striatal Cholinergic Interneurons in Distinct Genetic Mouse Models of Dystonia

“…Although the majority of cases are sporadic, recent work has uncovered a number of genetically determined forms; Ͼ20 dystonia-causing mutations have been established to date (Lohmann and Klein, 2017). However, even in these genetic forms in which the proximate cause is known, the neural mechanism(s) are still for the most part unknown (Breakefield et al, 2008;Balint et al, 2018). These limitations have made it difficult to develop targeted treatments for dystonia.…”

Paroxysmal Asymmetric Dystonic Arm Posturing—A Less Recognized but Characteristic Manifestation of ATP1A3‐related disease

“…Reduced α3 activity has also been suggested to interfere with reuptake of neurotransmitters such as glutamate, γ‐aminobutyric acid (GABA), and dopamine . Hence, it is conceivable that structures and neurotransmitters known to be involved in dystonia can be affected in ATP1A3 mutation carriers . Similar to other paroxysmal dyskinesias (e.g., those caused by PRRT2 mutations), the marked asymmetry and often alternating manifestation of signs remain a mystery.…”

Syringomyelia‐Associated Dystonia: Case Series, Literature Review, and Novel Insights

“…Including the cases reported on herein, 18 cases of dystonia associated with syringomyelia have now been described (summarized in Table ), though it is possible that some remain undiagnosed (cord imaging not being routine in most dystonic conditions) and unreported. The association of these conditions does not necessarily imply causality, and indeed given that most patients with syringomyelia do not develop dystonia, the presence of a syrinx may only be pathophysiologically relevant in otherwise predisposed individuals . Nevertheless, critical appraisal of these cases adds to the current scant literature on the subject and provides insights into possible pathophysiological underpinnings of syringomyelia‐associated dystonia (SAD).…”