What are the possible causes of involuntary mouth movements (orofacial dyskinesia) in a patient not taking medications known to cause tardive dyskinesia?

Causes of Involuntary Mouth Movements (Non-Medication Related)

Primary Non-Drug Causes to Consider

When involuntary mouth movements occur without antipsychotic or dopamine-blocking medication exposure, the differential diagnosis should focus on autoimmune encephalitis (particularly NMDA receptor and VGKC-complex antibody-associated), structural brain lesions, neurodegenerative disorders, and withdrawal dyskinesia from previously discontinued medications.

Autoimmune Encephalitis

NMDA receptor antibody-associated encephalitis is a critical diagnosis that presents with orofacial dyskinesia and choreoathetosis as hallmark features 1:

• Median age at presentation is 25 years with 2:1 female predominance 1
• The illness progresses in two phases: initial phase with seizures, confusion, amnesia, and psychosis, followed by involuntary movements (classically choreoathetosis and orofacial dyskinesia), fluctuating consciousness, dysautonomia, and central hypoventilation 1
• Associated with ovarian teratomas in 20-50% of female patients; lower tumor rates in men and children 1
• CSF frequently shows lymphocytosis and detectable NMDA antibodies; MRI is normal in approximately 77% of cases 1
• Treatment requires combination immunosuppression with corticosteroids plus either plasma exchange or IVIg, with rituximab or cyclophosphamide for refractory cases 1

VGKC-complex antibody-associated encephalitis presents differently 1:

• Characterized by subacute history, hyponatraemia, and brief dystonic seizures affecting arms and face 1
• MRI shows hippocampal high signal with swelling in approximately 60% (bilateral in most, unilateral in 15%) 1
• Responds well to high-dose oral steroids (0.5 mg/kg/day) with antibody normalization in 3-6 months 1
• This is typically a monophasic illness with rare relapses once antibodies become undetectable 1

Hidden Medication Exposure

Prior dopamine-blocking medication use must be thoroughly investigated, even if not currently prescribed 2:

• Tardive dyskinesia can persist indefinitely after medication discontinuation 2
• Investigate emergency department visits where antipsychotics (haloperidol, droperidol) or antiemetics (metoclopramide) may have been administered 2
• Metoclopramide causes potentially irreversible tardive dyskinesia, particularly in elderly patients, even with short-term use 3
• Trazodone, commonly prescribed for insomnia, has documented cases of causing tardive dyskinesia 4

Withdrawal Dyskinesia

Withdrawal dyskinesia occurs with cessation of neuroleptic agents 2:

• May occur with either gradual or sudden medication cessation 2
• Typically resolves over time, distinguishing it from persistent tardive dyskinesia 2
• Up to 50% of youth receiving neuroleptics may experience some form of tardive or withdrawal dyskinesia 2

Neurological Disorders

Other neurological conditions causing orofacial dyskinesia include 5, 6:

• Huntington's disease and other hereditary choreas 6
• Wilson's disease (must check ceruloplasmin and 24-hour urine copper) 6
• Stroke or structural brain lesions affecting basal ganglia 6
• Parkinson's disease and related syndromes 6
• Seizure disorders 6

Critical Diagnostic Algorithm

Step 1: Obtain comprehensive medication history 2:

• Document ALL medications including over-the-counter antiemetics, antipsychotics (even single doses in emergency settings), and antidepressants like trazodone 2, 4
• Inquire about medications discontinued months to years ago, as tardive dyskinesia persists after drug withdrawal 2

Step 2: Screen for autoimmune encephalitis 1:

• Check serum VGKC-complex antibodies if subacute history, hyponatraemia, or brief dystonic seizures present 1
• Check serum and CSF NMDA receptor antibodies if younger patient with psychiatric symptoms, seizures, or dysautonomia 1
• Perform brain MRI looking for hippocampal signal abnormalities 1
• Screen for tumors (ovarian ultrasound in women, chest CT for thymoma or small cell lung cancer) 1

Step 3: Evaluate for structural/metabolic causes 6:

• Brain MRI to exclude stroke, tumor, or basal ganglia lesions 6
• Ceruloplasmin and 24-hour urine copper for Wilson's disease (especially if age <40) 6
• Thyroid function, glucose, electrolytes 6

Management Approach

For autoimmune encephalitis with confirmed antibodies 1:

• NMDA receptor: Combination therapy with corticosteroids plus IVIg (0.4 g/kg/day) or plasma exchange, with tumor removal if present 1
• VGKC-complex: High-dose oral steroids (0.5 mg/kg/day) tapered over 12 months after antibody normalization 1

For suspected medication-induced dyskinesia despite no current exposure 2, 4:

• Document baseline movements using Abnormal Involuntary Movement Scale (AIMS) 2
• For moderate to severe symptoms, consider VMAT2 inhibitors (valbenazine or deutetrabenazine) as first-line pharmacotherapy 3, 4
• Avoid anticholinergic medications, which are ineffective for tardive dyskinesia and may worsen symptoms 4

Common Pitfalls

• Failing to recognize autoimmune encephalitis: NMDA receptor encephalitis is frequently misdiagnosed as primary psychiatric illness due to prominent behavioral symptoms 1
• Inadequate medication history: Not investigating emergency department visits or discontinued medications from months/years prior 2
• Assuming movements are voluntary or psychiatric: Orofacial dyskinesia in young patients with behavioral changes should prompt autoimmune workup 1
• Using anticholinergics for tardive dyskinesia: These are indicated only for acute dystonia and parkinsonism, not tardive dyskinesia 4