Dystonia is classified along two axes per the 2013 international consensus update:

Axis 1: Clinical Characteristics

Age at Onset

• Infancy: birth–2 years
• Childhood: 3–12 years
• Adolescence: 13–20 years
• Early adulthood: 21–40 years
• Late adulthood: >40 years
• Earlier onset → greater tendency to generalize; later onset → more likely to remain focal

Body Distribution

Temporal Pattern

• Persistent: present throughout the day
• Action-specific: only during specific tasks (e.g., writer’s cramp)
• Diurnal fluctuation: worsens as day progresses (classic for dopa-responsive dystonia)
• Paroxysmal: sudden episodes of dystonia (paroxysmal kinesigenic and non-kinesigenic dystonias)

Associated Features

• Isolated dystonia: dystonia is the only motor feature (with or without tremor)
• Combined dystonia: dystonia + another movement disorder (myoclonus, parkinsonism)

Axis 2: Etiology

• Inherited: autosomal dominant (DYT-TOR1A, DYT-THAP1, DYT-GCH1), autosomal recessive, X-linked, mitochondrial
• Acquired: perinatal brain injury/CP, infection, drugs (tardive), toxins, vascular, neoplastic, brain injury
• Idiopathic: sporadic or familial, no identified cause

DYT-GCH1 (Segawa Disease)

• Gene: GCH1 (GTP cyclohydrolase 1) — rate-limiting enzyme in tetrahydrobiopterin (BH4) synthesis
• Inheritance: autosomal dominant with reduced penetrance; females affected more than males (2.5:1)
• Pathophysiology: BH4 deficiency → decreased tyrosine hydroxylase activity → reduced dopamine synthesis in nigrostriatal pathway; neurons are structurally intact
• Onset: childhood (mean ~6 years); typically begins with foot dystonia causing gait difficulty
• Distribution: starts in lower limbs → may generalize; can be mistaken for cerebral palsy

Key Clinical Features

• Diurnal fluctuation: symptoms worsen as the day progresses and improve after sleep — hallmark feature
• May present with dystonia, parkinsonism, or both
• Hyperreflexia and mild spasticity may be present (mimics diplegic CP)
• Cognition is normal
• DaTSCAN: normal (intact presynaptic dopamine terminals) — distinguishes from juvenile-onset PD (abnormal DaTSCAN)
• CSF: low homovanillic acid (HVA) and biopterin; normal neopterin (distinguishes from other BH4 deficiency causes)

Treatment

• Dramatic, sustained response to LOW-dose levodopa (50–200 mg/day of levodopa) — often described as “miraculous”
• Does NOT develop motor fluctuations or dyskinesias with chronic levodopa use (unlike PD)
• Response persists for decades without dose escalation
• A levodopa trial should be performed in essentially all children and young adults with unexplained dystonia — failure to trial levodopa is a frequently missed diagnosis of a highly treatable condition (DRD / Segawa disease)

Focal dystonias are the most common form of dystonia in adults. Onset is typically in the 4th–6th decade. They remain confined to one body region and rarely generalize.

Sensory Trick (Geste Antagoniste)

• Light touch to the chin, face, or back of head alleviates cervical dystonia in ~70% of patients
• Highly specific for dystonia — rarely seen in other movement disorders
• Mechanism: likely modulation of abnormal sensorimotor integration at the basal ganglia level
• Diminishes over time in many patients

Botulinum Toxin (Focal Dystonia — First-Line)

• Mechanism: cleaves SNARE proteins (synaptobrevin/SNAP-25) → blocks presynaptic acetylcholine release at the neuromuscular junction
• Type A: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin) — cleaves SNAP-25
• Type B: rimabotulinumtoxinB (Myobloc) — cleaves synaptobrevin/VAMP; used when resistance develops to type A
• Onset: 2–5 days; peak effect ~2 weeks; duration 3–4 months; requires repeat injections
• Side effects: local weakness, dysphagia (cervical injections), ptosis (blepharospasm injections)
• Antibody formation: develops in ~5%; results in secondary non-response. IncobotulinumtoxinA (Xeomin) is complexing-protein-free, which may theoretically reduce immunogenicity; for confirmed neutralizing-antibody resistance to type A, switch to type B (rimabotulinumtoxinB)
• EMG or ultrasound guidance improves targeting accuracy for deep or small muscles

Oral Medications

Deep Brain Stimulation (DBS)

• Target: globus pallidus internus (GPi) — standard target for dystonia
• Regulatory status: GPi DBS for chronic, intractable primary dystonia received FDA Humanitarian Device Exemption (HDE) approval in 2003
• Best outcomes: DYT-TOR1A generalized dystonia (>50% improvement in most); DYT-KMT2B also responds well
• Response is gradual (weeks to months) unlike PD DBS (immediate tremor suppression)
• Beneficial for medically refractory generalized, segmental, and cervical dystonia
• Less effective for secondary/acquired dystonias (structural lesions, CP) — though some benefit possible
• Subthalamic nucleus (STN) DBS is an emerging alternative target

Treatment Algorithm Summary

• Step 1: Trial levodopa in ALL young-onset dystonia (rule out DRD)
• Step 2 — Focal: Botulinum toxin (first-line)
• Step 2 — Generalized: Trihexyphenidyl (first-line, especially in children); add baclofen or clonazepam as needed
• Step 3: GPi DBS for medically refractory cases (generalized > segmental > cervical)

Acute Dystonic Reaction

• Onset: within hours to days of starting a dopamine receptor blocker — classically neuroleptics (haloperidol) or antiemetics (metoclopramide, prochlorperazine)
• Risk factors: young males at highest risk; high-potency typical antipsychotics; first exposure
• Presentation: oculogyric crisis (forced sustained upward gaze), torticollis, retrocollis, trismus, tongue protrusion; laryngospasm is potentially life-threatening
• Treatment: IM/IV diphenhydramine 25–50 mg or benztropine 1–2 mg — rapid resolution (often within minutes)
• Consider continued oral anticholinergic for 24–48 hours to prevent recurrence; reassess offending agent

Tardive Dystonia

• Caused by chronic dopamine receptor blocker exposure (antipsychotics, metoclopramide)
• More disabling than tardive dyskinesia; retrocollis and trunk extension (opisthotonus) are characteristic
• May occur in isolation or combined with tardive dyskinesia
• Treatment: stop/reduce offending agent if possible; VMAT2 inhibitors (valbenazine, deutetrabenazine) may be beneficial, though evidence is stronger for tardive dyskinesia than for tardive dystonia; botulinum toxin for focal components is generally first-line for tardive dystonia; trihexyphenidyl may help (unlike in tardive dyskinesia, where anticholinergics worsen the movement)
• May persist indefinitely even after offending agent is discontinued

Wilson Disease

• Always consider in any patient <50 years with unexplained dystonia
• Autosomal recessive; ATP7B gene; copper accumulation in liver and brain (especially basal ganglia)
• Dystonia is the most common movement disorder in neurological Wilson disease; may also cause tremor (“wing-beating”), parkinsonism, chorea
• Kayser-Fleischer rings: slit-lamp examination; present in ~95% with neurologic involvement
• Workup: low ceruloplasmin, elevated 24-hour urine copper, liver function tests, brain MRI (“face of the giant panda” sign in midbrain; “face of the miniature panda” sign in pontine tegmentum)
• Treatment: D-penicillamine or trientine (copper chelation); zinc (blocks intestinal absorption); liver transplant for fulminant hepatic failure

Other Acquired Causes

• Post-stroke dystonia: delayed onset (weeks to months); contralateral hemidystonia; basal ganglia or thalamic lesions
• Cerebral palsy: most common cause of secondary dystonia in children; basal ganglia injury from perinatal asphyxia; may have delayed onset
• Structural lesions: tumors, AVM, abscess involving basal ganglia or thalamus → contralateral hemidystonia
• Post-traumatic: head injury with basal ganglia contusion; delayed onset common
• Autoimmune: anti-NMDA receptor encephalitis (orofacial dyskinesias/dystonia); anti-basal ganglia antibodies
• Toxic/metabolic: manganese exposure, carbon monoxide poisoning, methanol → basal ganglia necrosis with dystonia

• PRRT2 mutations also cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis (ICCA syndrome)
• SLC2A1 (GLUT1 deficiency): low CSF glucose (CSF:serum glucose ratio <0.4); also causes epilepsy, intellectual disability, acquired microcephaly

• Definition: severe, progressively worsening generalized dystonia with sustained, increasingly frequent, and disabling spasms — a movement disorder emergency with potentially life-threatening systemic complications
• Triggers: infection, drug changes (especially abrupt withdrawal of antidystonic medications or intrathecal baclofen), trauma, surgery, metabolic derangement; more common in patients with underlying genetic or secondary dystonia (DYT-TOR1A, CP, PKAN)
• Complications:
  • Rhabdomyolysis → acute renal failure
  • Hyperthermia
  • Respiratory compromise (chest wall and laryngeal involvement)
  • Autonomic instability; metabolic acidosis; bulbar failure
• Management ladder (escalate as needed):
  1. Identify and treat trigger; ICU admission; supportive care (hydration, cooling, electrolyte correction, monitoring of CK/renal function)
  2. Benzodiazepines (clonazepam, diazepam, midazolam) — first-line pharmacologic step
  3. Sedation/anesthesia: propofol or midazolam continuous infusion; may require intubation
  4. Intrathecal baclofen (bolus or pump)
  5. Emergent GPi DBS for refractory cases — can be life-saving

Hemifacial spasm (HFS) is NOT a true dystonia — it is a peripherally generated cranial nerve hyperexcitability syndrome. It is included here because it is commonly confused with blepharospasm and other cranial dystonias on board questions.

• Etiology: vascular compression of the facial nerve (CN VII) root exit zone — typically an AICA or PICA loop; less commonly tumors, AVMs, or MS plaque
• Presentation: unilateral involuntary tonic and clonic contractions involving orbicularis oculi initially, spreading to lower facial muscles (orbicularis oris, platysma) over time; often persists during sleep (a useful distinguishing feature from most dystonias and tics, which abate in sleep)
• “Other-Babinski sign” (Babinski-2 sign): synkinetic elevation of the ipsilateral eyebrow with forced eye closure — helps distinguish HFS from blepharospasm (where the brow descends)
• Distinguishing features vs. blepharospasm: HFS is unilateral and involves lower facial muscles; blepharospasm is bilateral and confined to periocular muscles
• Workup: MRI/MRA of the brain with attention to the CN VII root exit zone to identify the offending vascular loop or alternative structural cause
• Treatment:
  • Botulinum toxin to orbicularis oculi and involved lower facial muscles — first-line, repeat every 3–4 months
  • Microvascular decompression (Jannetta procedure) — curative; Teflon pledget placed between offending vessel and CN VII at root exit zone
  • Oral agents (carbamazepine, baclofen) of limited benefit