Causes of Walking Dystonia
Walking dystonia is primarily caused by genetic factors, particularly mutations in genes like PRRT2, PNKD, SLC2A1, SCN8A, KCNMA1, KCNA19, and DEPDC5, with PRRT2 being the major causative gene for paroxysmal kinesigenic dyskinesia (PKD), a common form of walking dystonia. 1
Primary Causes
Genetic Factors
- Hereditary primary dystonias:
Neurophysiological Mechanisms
- Abnormalities in brain motor networks 2
- Loss of inhibition at neuronal circuits 3
- Abnormalities in transcriptional regulation 3
- Striatal dopaminergic signaling dysfunction 3
- Altered synaptic plasticity 3
Secondary Causes
Neurological Conditions
- Demyelinating diseases, especially multiple sclerosis (most common cause of secondary PKD) 1, 4
- Parkinson's disease 4
- Amyotrophic lateral sclerosis 4
- Essential tremor 4
Vascular and Structural
- Cerebrovascular diseases 1
- Traumatic brain injury 1
- Lesions involving the thalamus, lenticular nucleus, globus pallidus, and internal capsule 1
Metabolic Disorders
- Hyperthyroidism 1, 4
- Calcium-phosphate metabolism disorders:
- Glucose metabolism disorders 1
- Wilson's disease 4
Other Medical Conditions
Medication-Induced
- High-potency typical antipsychotics 4
- Antiemetics (e.g., prochlorperazine and metoclopramide) 4
- Certain antidepressants 4
- Risk factors: young age, male gender 4
Psychological Factors
- Psychological disorders can mimic or exacerbate dystonia 1
- Features suggesting psychological origin: distractibility, variable presentations, suggestibility 1
- Red flags: adult onset, altered consciousness during attacks, additional psychogenic signs 1
Clinical Classification
By Distribution
- Focal (affecting one body region)
- Segmental (affecting adjacent body regions)
- Multifocal (affecting non-adjacent body regions)
- Generalized (affecting multiple body regions) 2
By Presentation
- Pure form: Only kinesigenic involuntary movements 1
- Complicated type: Kinesigenic dyskinesia plus other neurological symptoms 1
- May include benign familial infantile epilepsy, febrile convulsion, migraine, hemiplegic migraine, episodic ataxia, or epilepsy 1
By Trigger
- Paroxysmal kinesigenic dyskinesia (PKD): Triggered by sudden voluntary actions 1
- Paroxysmal non-kinesigenic dyskinesia (PNKD): Triggered by non-movement factors like caffeine, alcohol, stress 1
- Paroxysmal exercise-induced dyskinesia (PED): Triggered by prolonged exercise 1
- Task-specific dystonia: Occurs only during specific activities 2
Diagnostic Considerations
Key Clinical Features
- Attacks presenting as dystonia, chorea, ballism, or combinations 1
- Preserved consciousness during attacks 1
- Presence of aura (numbness, tingling, muscle weakness) in 78-82% of PKD patients 1
- Attack duration typically <1 minute for PKD 1
- Good response to sodium channel blockers (carbamazepine/oxcarbazepine) in PKD 1
Red Flags for Secondary Causes
- Duration of attacks >1 minute 1
- Age of onset over 20 years 1
- Abnormal brain imaging 1
- No response to appropriate medications 1
- Abnormal interictal examinations 1
Differential Diagnosis
- Epilepsy (especially frontal lobe epilepsy) 1
- Tics (typically shorter in duration) 1
- Hyperekplexia (excessive startle response) 1
- Sandifer syndrome (in children with gastroesophageal reflux) 1
- Benign paroxysmal torticollis (in infants) 1
- Transient dystonia of infancy 1
- Benign myoclonus of early infancy 1
Understanding the specific cause of walking dystonia is crucial for appropriate treatment selection, which may include botulinum toxin injections, oral medications (anticholinergics, benzodiazepines, baclofen), or surgical interventions like deep brain stimulation in refractory cases 4, 3, 2.