Core Concepts - Not Just Delirium
- Distinguished from delirium by a clear sensorium and normal level of consciousness. Psychotic symptoms are the core feature, not a consequence of attentional deficits.
- Requires evidence from history, physical exam, or labs that hallucinations/delusions are a direct physiological result of a specific medical condition.
- A close temporal association between the medical illness (onset, exacerbation) and psychotic symptoms is essential for diagnosis.
- Common etiologies:
- Neurologic: Seizures (post-ictal), CNS tumors, stroke, Huntington's disease
- Endocrine: Cushing's syndrome, thyroid/parathyroid disorders
- Autoimmune/Inflammatory: SLE, anti-NMDA receptor encephalitis
⭐ Visual hallucinations are more common than auditory ones, a key feature distinguishing it from primary psychotic disorders like schizophrenia.
Common Culprits - The Body's Rebellion
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Neurologic Causes
- CNS Infections (e.g., HSV encephalitis, neurosyphilis)
- Cerebrovascular Disease (Strokes, vasculitis)
- Degenerative Disorders (Huntington's, Lewy Body Dementia)
- Seizure-related (ictal, post-ictal)
- Space-occupying lesions (neoplasms)
- Autoimmune (e.g., Anti-NMDA receptor encephalitis, SLE cerebritis)
- Traumatic Brain Injury (TBI)
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Endocrine & Metabolic
- Thyroid dysfunction (thyrotoxicosis, myxedema madness)
- Adrenal disorders (Cushing's, Addison's)
- Electrolyte imbalance (↓Na+, ↑Ca2+)
- Hypoglycemia
- Organ failure (uremia, hepatic encephalopathy)
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Systemic & Nutritional
- Infections (HIV, sepsis)
- Vitamin deficiencies (B12, B1, B3)
⭐ Anti-NMDA Receptor Encephalitis: A critical diagnosis to consider in young patients (especially women) with new-onset psychosis, seizures, dyskinesias, and autonomic instability. Frequently paraneoplastic, associated with ovarian teratomas.
Workup & Management - Sleuthing & Soothing
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Core Principle: Identify and treat the underlying medical etiology. Psychosis should resolve as the medical condition improves.
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Initial Workup:
- History & Physical: Focus on new medications, substance use, and systemic signs of illness.
- Labs: CBC, CMP, TSH, Vitamin B12/folate, urinalysis, urine drug screen.
- Targeted Tests: RPR/VDRL (syphilis), HIV screen, ANA (lupus), ceruloplasmin (Wilson's), LP (if CNS infection/inflammation suspected).
- Imaging/Function: Brain CT/MRI, EEG.
- Management:
- Primary: Address the root medical cause (e.g., antibiotics for infection, steroids for autoimmune).
- Symptomatic: Use low-dose, short-term antipsychotics (e.g., Haloperidol, Risperidone) for agitation/psychosis.
- Environment: Ensure patient safety and provide a calm, structured setting.
⭐ Exam Favorite: Always consider anti-NMDA receptor encephalitis in young women presenting with new-onset psychosis, psychiatric symptoms, and subtle neurological signs (e.g., seizures, dyskinesias).

High-Yield Points - ⚡ Biggest Takeaways
- This is a diagnosis of exclusion, requiring a thorough workup to rule out other causes.
- A clear temporal relationship between the general medical condition and the psychosis is essential for diagnosis.
- Be suspicious with atypical features like late age of onset, visual hallucinations, or fluctuating consciousness.
- Key causes include CNS disease (tumors, seizures), endocrinopathies, autoimmune disorders (SLE), and metabolic disturbances.
- Management priority is to treat the underlying medical condition first and foremost.
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