What are the potential causes and management options for subacute onset dystonia in a 40-year-old individual over 2 months?

Subacute Onset Dystonia in a 40-Year-Old: Diagnostic Approach

In a 40-year-old presenting with subacute dystonia over 2 months, antibody-mediated encephalitis (particularly VGKC-complex antibody-associated encephalitis) must be prioritized as it is treatable and has poor outcomes if missed, followed by systematic exclusion of secondary causes including metabolic disorders, structural lesions, and medication effects. 1

Critical Red Flags Requiring Immediate Investigation

The subacute presentation itself is a red flag that demands urgent evaluation for autoimmune encephalitis. 1 Specific clinical features that strongly suggest antibody-mediated disease include:

• Faciobrachial dystonic seizures (brief dystonic movements of arm and face) - this is pathognomonic for VGKC-complex antibody encephalitis and may precede full encephalitis by weeks 1
• Hyponatremia (present in ~60% of VGKC-complex cases) 1
• Profound confusion, disorientation, or memory impairment accompanying the dystonia 1
• Seizures, particularly if intractable 1
• Orofacial dyskinesia or choreoathetosis 1

Immediate Diagnostic Workup

First-Line Testing

Serum antibody testing should be ordered immediately if any features above are present:

• VGKC-complex antibodies (LGI1, CASPR2) 1
• NMDA receptor antibodies 1
• Other paraneoplastic/autoimmune panels 1

Brain MRI is essential and may show:

• Bilateral hippocampal high signal with swelling (~60% of VGKC cases) 1
• Unilateral hippocampal changes (15% of cases) 1
• Structural lesions suggesting cerebrovascular disease, demyelination, or mass lesions 1

Laboratory evaluation to exclude metabolic causes:

• Serum sodium, calcium, phosphate, magnesium 1
• Thyroid function (hyperthyroidism) 1
• Parathyroid hormone levels 1
• Glucose metabolism assessment 1
• Ceruloplasmin and 24-hour urinary copper (Wilson's disease) 2

Additional Testing

• EEG - may show generalized slowing with or without ictal focus in autoimmune encephalitis 1
• CSF analysis - though CSF antibodies are not always detectable in VGKC encephalitis, CSF is frequently abnormal in NMDA receptor encephalitis 1
• Neoplasm screening - all patients with proven VGKC-complex or NMDA receptor antibody encephalitis require tumor screening (thymoma, small cell lung cancer for VGKC; ovarian teratoma for NMDA) 1

Secondary Causes to Systematically Exclude

Age of onset over 20 years is itself a red flag for secondary dystonia. 1 The following must be ruled out:

Structural/Vascular

• Cerebrovascular disease 1
• Demyelinating disease, especially multiple sclerosis 1
• Brain trauma history 1

Metabolic Disorders

• Calcium-phosphate metabolism disorders (hypoparathyroidism, pseudoparathyroidism, primary familial brain calcification) 1
• Hyperthyroidism 1
• Glucose metabolism disorders 1

Medication-Induced

• Recent antipsychotic exposure (though acute dystonia typically occurs within hours to days, not months) 3
• Other dopamine receptor antagonists 3

Genetic Considerations

• While genetic forms (TOR1A, THAP1, GCH1, KMT2B) typically present earlier, they should be considered if other causes are excluded 4
• In 22q11.2 deletion syndrome, dystonia should prompt consideration of related diseases like CEDNIK or TANGO2-related disease 1

Treatment Approach Based on Etiology

If Antibody-Mediated Encephalitis Confirmed

Immediate immunosuppression is critical as early treatment significantly improves outcomes: 1

• High-dose oral steroids (0.5 mg/kg/day prednisolone) with antibody levels normalizing in 3-6 months, then taper over 12 months 1
• For acutely unwell patients: IV immunoglobulin (0.4 g/kg/day) or plasma exchange in conjunction with steroids to accelerate improvement 1
• Tumor removal if identified 1

Regular IVIg alone without steroids may be less effective at reducing antibody levels with poorer clinical outcomes. 1

If Primary/Idiopathic Dystonia

Botulinum toxin injections are first-line for focal/segmental dystonia: 5

• AboBoNT-A (Dysport) and rimaBoNT-B (Myobloc) have strongest evidence 5
• OnaBoNT-A (Botox) and incoBoNT-A (Xeomin) also effective 5
• Symptom control lasts 3-6 months, requiring repeated injections 5

Oral medications for generalized or refractory cases:

• Anticholinergics 4, 6
• Gabapentinoids (pregabalin, gabapentin) for pain and spasm control 5, 2
• Duloxetine for neuropathic pain 5, 2

Deep brain stimulation should be considered for generalized primary dystonia 5, 6

Common Pitfalls to Avoid

• Missing autoimmune encephalitis due to focusing solely on the dystonia without recognizing the subacute presentation pattern and associated features 1
• Delaying immunosuppression in suspected autoimmune cases while waiting for antibody results - treatment should begin based on clinical suspicion 1
• Assuming primary dystonia without excluding secondary causes, particularly in adult-onset cases 1
• Using serial casting or excessive splinting which can worsen symptoms and cause complex regional pain syndrome 5

Documentation and Follow-Up

Document resolution, improvement, or worsening of dystonic symptoms and quality of life after each intervention using validated patient-reported outcome measures. 5, 2 Follow patients until dystonia has improved, resolved, or the underlying condition has been appropriately managed. 5, 2

For autoimmune encephalitis, confusion and seizures typically improve rapidly with immunosuppression, sodium normalizes, but memory improvement may take months to years. 1 This is usually a monophasic illness with relapse uncommon once antibodies become undetectable. 1