From the Guidelines
Dystonia is primarily caused by abnormal functioning of the basal ganglia, a region of the brain responsible for controlling movement, and can be classified as primary (genetic or idiopathic) or secondary (acquired) 1. This neurological disorder can result from various factors, including genetic mutations, brain injury, stroke, oxygen deprivation, infections, drug reactions, poisoning, or as a symptom of other neurological conditions such as Parkinson's disease, Huntington's disease, or Wilson's disease. The fundamental problem involves disrupted communication between neurons, leading to excessive muscle contractions that cause abnormal postures or repetitive movements.
Causes of Dystonia
- Primary dystonia often has a genetic basis, with mutations in genes like DYT1/TOR1A being well-documented causes
- Secondary dystonia can result from brain injury, stroke, oxygen deprivation, infections like encephalitis, drug reactions (particularly to antipsychotics), poisoning from substances like carbon monoxide or manganese
- Dystonia can also develop following physical trauma, particularly in cases of cervical dystonia
- In many cases, especially in adults with focal dystonia, the exact cause remains unknown despite the clear dysfunction in brain circuitry regulating movement
Treatment Approaches
- Treatment approaches vary based on the underlying cause, with options including oral medications, botulinum toxin injections, physical therapy, and in some cases, deep brain stimulation 1
- Clinicians should offer, or refer to someone who can offer, botulinum toxin injections for the treatment of dysphonia caused by spasmodic dysphonia and other types of laryngeal dystonia 1
From the Research
Causes of Dystonia
- Dystonia is a neurological condition characterized by abnormal involuntary movements or postures owing to sustained or intermittent muscle contractions 2
- The condition can be caused by various factors, including genetic mutations, and can affect all age groups, leading to substantial disability and impaired quality of life 2, 3
- Genetic mutations, such as those in the TOR1A, THAP1, GCH1, and KMT2B genes, have been linked to the development of dystonia, and can affect transcriptional regulation, striatal dopaminergic signalling, and synaptic plasticity 2, 3
Pathophysiology of Dystonia
- Dystonia is thought to result from a dysfunctional network involving the basal ganglia, cerebellum, thalamus, and cortex 3
- Abnormalities in gene transcription during neurodevelopment, calcium homeostasis, striatal dopamine signaling, and endoplasmic reticulum stress response have been implicated in the pathogenesis of dystonia 3
- Shared pathophysiological pathways and molecular mechanisms, including abnormalities in the dopaminergic system, mitochondrial function, and calcium regulation, have been identified in etiologically-diverse dystonias 4
Genetic Factors
- Genetic mutations are a significant cause of dystonia, and can be used to guide treatment selection and response 5
- Different forms of dystonia can be molecularly grouped, which may facilitate treatment development in the future 3
- The discovery of genes underlying the mendelian forms of isolated or combined dystonia has led to a better understanding of its pathophysiology 2