What are the differential diagnoses for altered mental status?

Differential Diagnoses for Altered Mental Status

The most common differential diagnoses for altered mental status include underlying medical conditions, substance use/intoxication/withdrawal, mental disorders, delirium, and primary neurologic insults, with delirium being the most frequent presentation in older patients presenting to the emergency department. 1

Primary Diagnostic Categories

Most Common Etiologies (in order of frequency)

• Neurological disorders (35%): Stroke, intracranial hemorrhage, seizures, traumatic brain injury, mass lesions, and infections 2
• Pharmacological and toxicological causes (23%): Drug intoxication, medication side effects (including cephalosporins like cefdinir), drug withdrawal (especially alcohol and benzodiazepines), and toxin exposure 2, 3
• Systemic and organic dysfunction (14.5%): Hepatic encephalopathy, renal failure, respiratory failure, and cardiac dysfunction 2
• Infectious causes (9.1%): Sepsis, urinary tract infections, pneumonia, and encephalitis 2
• Endocrine/metabolic disorders (7.9%): Hypoglycemia, hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state, electrolyte abnormalities (hyponatremia, hypercalcemia), and thyroid disorders 1, 2
• Psychiatric conditions (3.9%): Primary psychiatric disorders, though these remain diagnoses of exclusion 2
• Traumatic causes (2.1%): Head trauma with or without intracranial bleeding 2

Critical Delirium Subtype

Delirium represents a medical emergency and is the most common presentation in elderly patients with altered mental status, occurring in 10-31% at admission and developing in up to 56% of hospitalized patients. 1

Key Features of Delirium

• Cardinal feature: Inattention with fluctuating course throughout the day with lucid intervals 1
• Precipitating factors: Another medical condition, intoxication, or withdrawal 1
• Mortality risk: Twice as high if diagnosis is missed, with overall mortality of 8.1% in altered mental status patients (significantly higher in elderly) 1

Psychosis as a Distinct Subtype

New-onset psychosis differs from other altered mental status presentations because level of consciousness and awareness remain intact. 1

Primary vs Secondary Psychosis

• Primary psychosis: Related to underlying psychiatric disorders (dementia, schizophrenia, bipolar disorder, schizoaffective disorder, depression with psychotic features) 1
• Secondary psychosis: Directly related to medical causes including:
  • Endocrine disorders 1
  • Autoimmune diseases 1
  • Neoplasms and paraneoplastic processes 1
  • Neurologic disorders 1
  • Infections 1
  • Genetic or metabolic disorders 1
  • Nutritional deficiencies 1
  • Drug-related effects (intoxication, withdrawal, side effects, toxicity) 1

Special Population: Cirrhosis Patients

In patients with cirrhosis, hepatic encephalopathy is a common cause but remains a diagnosis of exclusion after ruling out other etiologies. 1

Specific Differentials in Cirrhotic Patients

• Alcohol intoxication and withdrawal 1
• Drug-related causes 1
• Infections 1
• Diabetic ketoacidosis and hyperosmolar hyperglycemic state 1
• Electrolyte disorders 1
• Intracranial bleeding 1
• Nonepileptic seizures 1
• Psychiatric disorders 1

Important caveat: Several of these conditions can coexist with hepatic encephalopathy and synergize to worsen mental status 1

High-Risk Presentations Requiring Immediate Consideration

Conditions Requiring Urgent Neuroimaging

• First episode of altered mental status 1
• Focal neurological signs or deficits 4
• Seizures 1, 4
• Increased risk for intracranial bleeding 4
• Hypertensive emergency 4
• Unsatisfactory response to treatment of precipitating factors 1

Life-Threatening Reversible Causes (Require Immediate Intervention)

• Hypoglycemia 5
• Hypoxia 5
• Hypotension/shock 5
• Hypertensive emergency 4
• Intracranial hemorrhage 2
• Status epilepticus 5
• Meningitis/encephalitis 4
• Severe electrolyte abnormalities 1

Critical Pitfalls to Avoid

• Never attribute altered mental status solely to psychiatric causes without adequate medical workup, as this can miss life-threatening conditions 1
• Do not rely on ammonia levels alone to diagnose hepatic encephalopathy in cirrhotic patients; a low ammonia level should prompt investigation of other etiologies 1
• Avoid delaying empiric treatment while awaiting diagnostic results in potentially life-threatening conditions 4
• Do not miss delirium in elderly patients, as mortality doubles when diagnosis is missed 1
• Remember that multiple etiologies can coexist, particularly in elderly and critically ill patients 1