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There are many approaches to altered mental status (AMS). Here is one of them:

  • Step 1: First assess for acute/emergent situations

    • - Is the patient protecting their airway? If not, intubate.

    • - Does the patient have signs of elevated intracranial pressure (ICP) such as acute loss of brainstem reflexes, particularly with fixed and dilated pupils? If so, perform NCHCT and consult neurosurgery stat. Consider the need for intubation, mannitol, hypertonic saline.

    • - Concern for opioid overdose? Administer naloxone.

    • - Check a fingerstick glucose? If <70 mg/dL, administer D50 and thiamine.

  • Step 2: Consider the differential diagnosis using the mnemonic “MISTO”:

    • - Metabolic:

      • Electrolyte abnormalities: Check sodium, calcium

      • Endocrine abnormalities: Check TSH, glucose (hypoglycemia or hyperglycemia [consider DKA/HHS])

      • Organ dysfunction: Kidney, liver, heart (ACS), lung (low oxygen, high CO2)

      • Vitamin deficiencies: B1 (thiamine), B12

      • Other: Urinary retention, constipation

    • - Infection:

      • CNS infection: Meningitis, encephalitis, abscess

      • Non-CNS infection: UTI, pneumonia, bacteremia

    • - Structural/seizure:

      • Structural: Stroke, hemorrhage, tumor

      • Seizure

    • - Toxin:

      • Medications

        • - Perform a complete medication reconciliation; polypharmacy is a common cause of AMS in elderly patients

        • - Consider drug overdose, drug withdrawal, associated syndromes (e.g., serotonin syndrome)

      • Alcohol/substances

        • - Check serum alcohol level and serum osms

        • - Check urine toxicology screen

    • - Oxygenation:

      • Low O2

      • High CO2

  • Step 3: Based on this differential, perform diagnostic tests to further evaluate. Diagnostics to consider:

    • - Labs: CBC, BMP, LFTs, TSH, serum alcohol level, serum osms, ABG/VBG, ammonia, Utox

    • - Imaging: Choose based on differential diagnosis – NCHCT, contrast-enhanced head CT, MRI brain


  • Step 1: Delineate neurologic versus non-neurologic causes of weakness and take a detailed history

    • - Non-neurologic causes of weakness:

      • Generalized weakness/deconditioning from prolonged bedrest or systemic illness

      • Asthenia (motor impairment due to pain or joint dysfunction)

      • Functional/psychogenic weakness – diagnosis of exclusion!

    • - History of present illness:

      • Be specific! Describe the weakness; are there specific tasks the patient has difficulty performing? Are they limited by fatigue, shortness of breath, joint pain, etc.?

      • Tempo: Hyperacute, acute, subacute, chronic, episodic, fatigable?

      • Distribution: Generalized, proximal vs. distal, unilateral vs bilateral, symmetric vs. asymmetric?

      • Progression over time: Have symptoms remained localized? Or have they spread over time?

      • Sensory involvement: Numbness, paresthesia, allodynia

      • Autonomic symptoms: Orthostasis, palpitations, bowel/bladder dysfunction, pupil abnormalities

      • Associated symptoms: Recent fever, URI, gastroenteritis, or vaccinations (rarely trigger Guillain-Barré), neck/back pain, spine trauma, tenderness, breathing difficulties

    • - Review other history/comorbidities:

      • Medications: Perform a complete medication reconciliation. In particular, ask about medications which may contribute to weakness (e.g., statins, colchicine)

      • Past medical history: Certain medical conditions can contribute to weakness (e.g., DM, thyroid disease, HIV, syphilis, B12 deficiency)

      • Social history: Ask about alcohol use, recreational drug use

      • Family history: Ask about family history of neuromuscular disorders, such as myopathy, ALS, multiple sclerosis

  • Step 2: Localize the lesion. See Table 12.2 and the following information about CNS and PNS ...

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