Differential Diagnoses for Altered Mental Status
Most Common Etiologic Categories (in Order of Prevalence)
The differential diagnosis for altered mental status follows a systematic pattern, with neurological causes being most common (30-35%), followed by toxicologic/pharmacologic (20-25%), metabolic/systemic (15-20%), and infectious causes (9-18%). 1, 2
Neurological Causes (30-35%)
- Stroke (ischemic or hemorrhagic) - accounts for the majority of neurological deaths in hospitalized AMS patients 3
- Intracranial hemorrhage (subdural, subarachnoid, intraparenchymal) 4
- Seizures (convulsive or nonconvulsive status epilepticus) 4, 5
- Intracranial mass lesions (tumor, abscess) 4, 2
- Meningitis or encephalitis 4, 2
- Autoimmune encephalitis (paraneoplastic or nonparaneoplastic) 5
- Hydrocephalus 4
- Increased intracranial pressure 4
Toxicologic/Pharmacologic Causes (20-25%)
- Medication side effects or toxicity (opioids, benzodiazepines, gabapentin, anticholinergics) 1, 6
- Alcohol intoxication or withdrawal 1, 6
- Illicit drug use (stimulants, sedatives, hallucinogens) 2
- Serotonin syndrome 7
- Neuroleptic malignant syndrome 7, 8
- Anticholinergic toxicity 4, 8
- Drug-drug interactions 1
Metabolic/Systemic Causes (15-20%)
- Hypoglycemia or hyperglycemia 2, 6
- Electrolyte abnormalities (hyponatremia, hypernatremia, hypercalcemia) 1, 2
- Hepatic encephalopathy (in cirrhotic patients, but remains diagnosis of exclusion) 1, 2
- Uremic encephalopathy 2, 9
- Hypoxia or hypercapnia 10
- Thyroid disorders (myxedema coma, thyroid storm) 4
- Adrenal insufficiency 4
Infectious Causes (9-18%)
- Sepsis (from any source) 2, 9
- Urinary tract infection (especially in elderly) 4, 2
- Pneumonia 4, 2
- Central nervous system infections (meningitis, encephalitis, brain abscess) 4, 2
Psychiatric Causes (3.9%)
- Primary psychosis (schizophrenia, bipolar disorder, schizoaffective disorder) 4
- Depression with psychotic features 4
- However, psychiatric causes should NEVER be attributed without completing full medical workup 1, 2, 7
Other Causes
Initial Management Algorithm
Step 1: Immediate Stabilization (First Priority)
- Secure airway and stabilize vital signs before pursuing diagnostic workup - airway protection prevents aspiration in patients with impaired consciousness 7
- Transfer to ICU-level monitoring immediately if Glasgow Coma Scale <8 or Grade 3-4 altered mental status 1, 7
- Intubate if: inability to maintain airway, massive GI bleeding, or respiratory distress 1, 7
- Use short-acting sedatives (propofol or dexmedetomidine) instead of benzodiazepines to preserve cognitive assessment and reduce ventilation duration 1, 7
Step 2: Rapid Bedside Assessment
- Quantify severity using validated scales (Glasgow Coma Scale, Richmond Agitation Sedation Scale, or West Haven criteria) 4, 2, 7
- Examine for focal neurological deficits - their presence significantly increases likelihood of intracranial pathology requiring immediate neuroimaging 2, 7
- Document vital sign abnormalities (fever suggests infection, hypotension suggests shock, hypertension suggests hypertensive emergency) 2
- Identify toxidromes (serotonin syndrome, neuroleptic malignant syndrome, anticholinergic syndrome) 7
- Assess for signs of trauma, infection sources, and meningismus 1
Step 3: Obtain Comprehensive History
- History and physical examination have 94% sensitivity for identifying medical conditions, compared to only 20% for laboratory testing alone 1, 2
- Obtain medication, drug, and alcohol history to identify toxicologic causes 2
- Interview patient and collateral sources separately when possible 1
- Identify precipitating factors - approximately 90% of patients improve with correction of precipitating factor alone 1, 7
Step 4: Laboratory Investigations
- Obtain comprehensive metabolic panel: complete blood count, electrolytes, glucose, renal function, liver function tests, urinalysis 1, 2
- Perform toxicology screens when substance use is suspected 2
- Do NOT routinely measure ammonia levels in cirrhotic patients - levels are variable, unreliable, and may be elevated in non-hepatic encephalopathy conditions 1, 2, 7
Step 5: Neuroimaging Decision Algorithm
Obtain head CT without contrast immediately if: 2, 7
- First episode of altered mental status
- Focal neurological deficits present
- Seizures occurred
- Increased risk for intracranial bleeding (anticoagulation, trauma, falls)
- Hypertensive emergency
- Known intracranial pathology with worsening mental status
Brain MRI may be appropriate when: CT is negative but clinical suspicion remains high, or inflammatory conditions/encephalitis suspected 2
Routine brain imaging is NOT necessary in clinically stable psychiatric patients (alert, cooperative, normal vitals, noncontributory history/physical) 1
Yield of acute contributory CT findings ranges from 2% to 45% based on risk factors 2
Step 6: Empiric Treatment While Awaiting Diagnostics
- For suspected encephalitis: start IV acyclovir 10 mg/kg three times daily immediately, especially in immunocompromised patients 2, 7
- For suspected hepatic encephalopathy: initiate lactulose or polyethylene glycol; consider rifaximin as add-on therapy 1, 7
- Avoid sedating medications in cirrhotic patients (opioids, benzodiazepines, gabapentin have synergistic sedating effects) 1
- Never delay empiric treatment while awaiting diagnostic results in potentially life-threatening conditions 1, 7
Critical Pitfalls to Avoid
- Never attribute altered mental status solely to psychiatric causes without completing medical workup - this is the most dangerous error 1, 2, 7
- Never rely on ammonia levels alone to diagnose hepatic encephalopathy in cirrhotic patients 1, 2, 7
- Always consider multiple concurrent etiologies, especially in elderly patients where delirium is often multifactorial 1, 2, 7
- Never skip thorough clinical assessment - history and physical have 94% sensitivity versus 20% for labs alone 1, 2, 7
- Mortality doubles if delirium diagnosis is missed 1
Special Population Considerations
Elderly Patients
- Consider multiple concurrent etiologies - delirium is often multifactorial with higher mortality (10.8% vs 6.9% in younger patients) 1, 6
- Infection is the most common precipitating factor (urinary tract infections or pneumonia) 4
- Assess fall risk due to motor instability, somnolence, and orthostatic hypotension from antipsychotics 11, 8
Cirrhotic Patients
- Hepatic encephalopathy remains a diagnosis of exclusion - investigate alternative causes (alcohol intoxication, infections, electrolyte disorders) first 1, 7
- Avoid sedating medications that can worsen encephalopathy 1, 7
ICU Patients
- Delirium may develop in up to 56% of admitted patients, particularly following surgery 4
- Use dexmedetomidine over benzodiazepines to reduce delirium rates 5