What are the next steps in evaluating a patient with altered mental status after a normal CT head?

Next Steps After Normal CT Head in Altered Mental Status

After a normal CT head, immediately pursue metabolic workup (glucose, sodium, pregnancy test if applicable), assess for infection/sepsis with lumbar puncture if febrile or immunocompromised, and consider MRI brain if symptoms persist or clinical suspicion remains high for stroke, encephalitis, or other occult pathology. 1

Immediate Laboratory Evaluation

Essential metabolic studies must be obtained:

• Serum glucose and sodium levels are Level B recommendations for all patients with altered mental status who have returned to baseline 1
• Pregnancy test for all women of childbearing age 1
• Complete metabolic panel to identify hypoglycemia, hyperglycemia, hyponatremia, hypoxia, hypothermia, or other metabolic derangements 1

Lumbar Puncture Indications

Perform lumbar puncture in specific high-risk scenarios:

• Immunocompromised patients require LP after CT head to evaluate for CNS infection, even with normal CSF white cell count 1
• Febrile patients with altered mental status warrant LP to exclude meningitis or encephalitis 1
• Alert, oriented, afebrile, non-immunocompromised patients without focal deficits do not require routine LP 1

Critical caveat: In immunocompromised patients, CSF may be acellular despite active CNS infection, so LP should be performed regardless of clinical appearance 1

Advanced Imaging with MRI

MRI brain should be pursued as second-line imaging when:

• Initial CT is negative but symptoms persist or worsen, as MRI has superior sensitivity for ischemia (70% of missed strokes present as altered mental status rather than focal deficits), encephalitis, subtle subarachnoid hemorrhage, and small infarcts 1, 2
• Known malignancy, HIV, or endocarditis exists, where MRI without and with contrast is preferred 1
• Suspected posterior reversible encephalopathy syndrome, Wernicke encephalopathy, or metabolic disorders (noncontrast MRI typically sufficient) 1
• MRI changed clinical management in 76% of ICU patients with disorders of consciousness, including revised diagnoses in 20% 2

Specific Infectious/Inflammatory Workup

For immunocompromised patients, obtain comprehensive CSF studies:

• CSF PCR for HSV-1/2, VZV, enteroviruses, EBV, CMV 1
• Acid-fast bacillus staining and culture for tuberculosis 1
• CSF and blood culture for Listeria monocytogenes 1
• Indian ink staining and/or cryptococcal antigen testing 1
• Toxoplasma antibody testing with CSF PCR if positive 1
• Syphilis serology 1

Electroencephalography

Consider EEG for suspected seizure activity:

• Nonconvulsive seizures can present as isolated altered mental status 1
• EEG is complementary to imaging and should be obtained when seizure is in the differential 1

Risk Stratification for Persistent Symptoms

High-risk features requiring aggressive workup despite normal CT:

• Focal neurologic deficits (even subtle) 2, 3
• Anticoagulation or antiplatelet therapy 2, 3
• History of malignancy 1, 2
• Persistent headache, nausea, or vomiting 2, 3
• Glasgow Coma Scale <15 3
• Age >40-41 years with acute change 1, 2

Important pitfall: Normal neurological examination cannot exclude serious intracranial pathology—18.4% of mild head injury patients have intracranial lesions on CT despite near-normal exams 2

Systemic Evaluation Beyond Neuroimaging

Complete evaluation includes:

• Chest radiography for pneumonia 1
• Electrocardiogram for myocardial ischemia 1
• Blood cultures if sepsis suspected 1
• Toxicology screening if drug/alcohol intoxication suspected 1
• Thyroid function, liver function, ammonia level depending on clinical context 1

Clinical Decision Algorithm

1. Normal CT obtained → Proceed with metabolic panel (glucose, sodium, comprehensive metabolic panel) 1
2. Assess infection risk → If febrile, immunocompromised, or signs of meningismus → Lumbar puncture 1
3. Evaluate for occult pathology → If symptoms persist, high clinical suspicion, or risk factors present → MRI brain 1, 2
4. Consider seizure → If witnessed seizure activity or unexplained altered mental status → EEG 1
5. Systemic workup → Chest X-ray, ECG, blood cultures as clinically indicated 1

The diagnostic yield of CT in altered mental status is only 11% overall, but missing treatable causes like stroke, infection, or metabolic disorders carries significant morbidity and mortality risk. 1, 4 Therefore, systematic evaluation beyond imaging is essential even when CT is normal.