Altered Mental Status

Marissa Beal, DO, Yelena Gimelshteyn, M.D., Peter V. Rabins, M.D., M.P.H.

DEFINITION

  • “Altered mental status” is a vague, often misleading description that encompasses a host of presentations that include changes in cognition, mood, behavior and/or level of arousal such as:
    • Coma
    • Stupor
    • Delirium and/or encephalopathy
    • Dementia or other neurocognitive disorders
    • Acute worsening of psychiatric illness
  • There is a spectrum of acute brain dysfunction including coma, stupor, and delirium which include impairment of consciousness[1].
  • Consciousness is further delineated into content (cognitive function mediated by cortical brain areas) and arousal (wakefulness mediated by reticular activating system)[2].

EPIDEMIOLOGY

  • 5-10% of patients presenting to emergency departments have a chief complaint of "altered mental status"[3][4].
    • Half of these patients are admitted to the hospital[3].
  • Most of the patients seen for "altered mental status" are diagnosed with delirium. 8-10% of elderly patients in the ED are diagnosed with delirium and 5-9% with stupor or coma[1].
  • “Altered mental status” occurs at any age with a possible bimodal distribution of the young adult and elderly adult[4][5].
  • Most common etiologies include neurologic and toxicologic[4].

DIFFERENTIAL DIAGNOSIS

ADULT

  • Abrupt changes in mental function occurring over hours to days include:
    • Delirium and/or encephalopathy
      • These are the preferred terms to use when identifying “altered mental status”[6].
      • Delirium is defined as concurrent disturbances of both consciousness and cognition resulting in disturbances of attention (and additional memory, visuospatial and/or executive dysfunction) often accompanied by changes in psychomotor behavior, perception, emotion, and sleep-wake cycle.
      • Encephalopathy, a term favored by neurologists, encompasses clinical presentations representative of global brain dysfunction (which may include delirium) due to a particular etiology. For example, hepatic encephalopathy may present acutely with coma, stupor, delirium or psychomotor retardation.
      • By definition, this disturbance is a direct physiological consequence of a medical condition or conditions, including intoxication or withdrawal, and requires the diagnosis and treatment of the underlying cause.
  • Slowly progressing cognitive changes (seen over months to years):
    • Neurocognitive disorders (NCDs ) include dementing illness and are characterized by a significant decline from baseline in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor skills, or social cognition).
    • By definition, these impairments significantly impair the patient’s function in multiple areas of life[7].
    • Diagnosis is based on history, including information obtained from collateral informants and standardized testing or clinical assessment[7].
  • Change in cognition/attention/mood/behavior that can be attributed to a psychiatric illness:
    • Primary psychiatric illness should be considered if criteria for the illness are met and medical causes for change in mental status are ruled out.
    • This is particularly important in patients with a history of psychiatric illness or a family history of psychiatric illness.
    • Generally, patients with primary psychiatric illness do not have disturbances in attention or sensorium. This is more challenging to discern in patients with catatonia or severe disorganization. Standardized cognitive screening, such as MMSE or 4AT, can be useful to identify delirium and differentiate symptoms from a primary psychiatric illness. In catatonia, these cognitive exams should be done after a high dose benzodiazepine trial.
    • Collateral is also vital to determine if current presentation is similar to previous episodes of change in behavior.
    • Normal background rhythm on EEG and absence of other abnormalities on medical work-up can help point to a primary psychiatric diagnosis.
  • Commonly cited etiologies of altered mental status[8][9]:
    • Vascular:
      • e.g., ischemic stroke, intracerebral or subarachnoid hemorrhage.
    • Infectious:
      • e.g., urinary tract infection, pneumonia, sepsis, encephalitis, or meningitis.
    • Toxic:
      • e.g., intoxications, overdoses, withdrawal syndromes, or adverse reactions to medications, including prescription/over-the-counter/supplements.
    • Traumatic:
      • e.g., concussion or subdural hematoma.
    • Autoimmune:
      • e.g., vasculitis, Behcet syndrome, acute disseminated encephalomyelitis, Hashimoto encephalopathy, or autoimmune limbic encephalitis.
    • Metabolic:
      • Electrolyte abnormalities (e.g., hypo- and hypernatremia, hypo- or hypercalcemia, hypo- or hypermagnesemia, hypo- or hyperphosphatemia).
      • Endocrine problems (e.g., hypo- and hyperthyroidism, hypo- and hypercortisolism, hypo- and hyperglycemia).
      • Liver failure, kidney failure, acute pancreatitis
      • Hypoxia and hypercarbia
      • Hypo- and hyperthermia
      • Thiamine, vitamin B12, and folate deficiencies
      • Porphyria
      • Marchiafava Bignami disease
    • Iatrogenic causes:
      • Use of deliriogenic medications (e.g., anticholinergics, benzodiazepines, opiates, antihistamines, muscle relaxants, antiepileptics, dopamine agonists, MAOIs, steroids, fluoroquinolones, cephalosporin antibiotics, beta blockers, digitalis, lithium, or calcineurin inhibitors).
      • Recent surgery or multiple procedures in patients with or at high risk of delirium.
      • Use of restraints or urinary catheters
      • Untreated pain
      • Sleep deprivation
    • Neoplastic:
      • e.g., large brain tumors, carcinomatous meningitis, or paraneoplastic limbic encephalitis.
    • Seizure-related:
      • e.g., post-ictal state and nonconvulsive status epilepticus.
    • Structural:
      • e.g. hydrocephalus.
    • Degenerative:
    • Psychiatric illness-related conditions

TREATMENT

  • Acute "altered mental status" is an emergency.
    • Initial basic approach to work-up[8][9]:
      • Medical stabilization:
        • Ensure airway, breathing, and circulation.
        • Obtain vital signs and measure glucose level.
          • If glucose is low, administration of thiamine and dextrose is indicated to avoid precipitation of Wernicke’s encephalopathy.
        • Administer naloxone if opioid overdose is suspected.
      • Information gathering:
        • Gather information from patient and collateral sources to focus on changes in cognition, perceptual experiences, and behavior.
        • With history, also establish baseline functioning and timing of change from baseline (acute vs chronic).
        • Review current medications and recent changes (including over-the-counter and illicit substances).
        • Review past medical history, including history of comorbid conditions (cirrhosis, chronic kidney disease, chronic obstructive pulmonary disease, epilepsy, immune compromise and psychiatric illness), and history of previous, similar episodes.
      • Physical exam:
        • Cognitive assessment may reveal fluctuation in level of consciousness, difficulty maintaining attention, disorientation, and/or impaired memory and is best evaluated using a cognitive screening tool such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA).
        • Assess for withdrawal or other toxidrome via vital signs and physical exam (looking for tremor, mydriasis/miosis, nystagmus, myoclonus, hyperreflexia).
        • Conduct a complete neurological exam; rule-out focal deficits, asterixis, and meningismus. Identify soft neurological signs such as the unilateral palmomental, grasp, snout, and glabellar reflexes[10].
        • Assess for signs of infection, head trauma, and decompensated chronic conditions.
      • Labs and other Investigations:
        • Complete blood count with differential (leukopenia or leukocytosis may indicate infection or severe inflammatory process).
        • Comprehensive metabolic panel (identify electrolyte abnormalities, assess renal and liver function).
        • Magnesium, phosphorus, and albumin levels
        • Urinalysis and urine culture
        • Urine and blood toxicology screens
        • Arterial blood gas (rule-out hypoxia or hypercarbia, as well as elevated bicarbonate suggesting chronic respiratory acidosis).
        • Thyroid stimulating hormone (TSH), vitamin B12, folate and rapid plasma reagin (RPR).
        • Chest x-ray (rule-out acute lung process).
        • Electrocardiogram (evaluate for a large myocardial infarction).
    • Steps to take when guided by findings on earlier evaluation:
      • Brain imaging:
        • A computed tomography (CT) examination of the head should be done if the patient’s source of "altered mental status" is not obvious from the information above.
        • A head CT is mandatory in situations of "altered mental status" with focal neurological deficits, prior to lumbar puncture when focal deficits are suspected, and in the context of an increased likelihood of intracranial pathology (previous brain lesions, recent head trauma, HIV or other immunocompromised state).
        • Head CT is usually followed with magnetic resonance imaging (MRI) of the brain with diffusion and gadolinium if the cause remains unclear.
        • MRI of the brain is diagnostic if posterior reversible encephalopathy syndrome (PRES) is suspected.
        • Vascular imaging with CT angiography or MRI angiogram should be performed if large-vessel occlusion is suspected.
      • Lumbar puncture (LP):
        • Should be performed if meningitis or encephalitis is suspected, or if the patient is immunocompromised or just had neurosurgery.
        • Never rest solely on the presence or absence of meningismus, as these signs are insensitive.
        • Head CT prior to LP is recommended, particularly if there is concern about focal lesions, to avoid brain herniation.
      • Electroencephalography (EEG):
        • Recommended, particularly if there is suspicion of status epilepticus.
        • It is also helpful in delirium.
      • Other laboratory tests as guided by initial evaluation:
        • Ammonia level
        • HIV
        • Additional thyroid function tests
        • Morning cortisol
        • ESR and CRP
        • Autoimmune serologies (e.g., antinuclear antibodies, thyroperoxidase, and thyroglobulin antibodies)
        • Blood cultures
        • Extended toxicology screen
        • Heavy metal screening
    • Subsequent evaluation of "altered mental status": additional work-up may be necessary if initial work-up is not revealing.
      • Caution: additional testing may be expensive and cause iatrogenic complications.
      • These evaluations should be done in the context of specific clinical suspicion.

WHEN TO REFER

  • A referral to an outpatient psychiatrist is appropriate if one is fairly certain that a patient’s "altered mental status" may be secondary to a neuropsychiatric illness, including dementia.
  • Specialists from Consultation-liaison Psychiatry, Geriatrics or Neurology can provide recommendations for delirium and untreated, partially treated, or decompensated psychiatric illness.

References

  1. Han JH, Wilber ST. Altered mental status in older patients in the emergency department. Clin Geriatr Med. 2013;29(1):101-36.  [PMID:23177603]
  2. Posner JB, Plum F., Saper CB, & Schiff N. (2007). Plum and Posner’s diagnosis of stupor and coma (Vol. 71). OUP USA.
  3. Douglas VC, Josephson SA. Altered mental status. Continuum (Minneap Minn). 2011;17(5 Neurologic Consultation in the Hospital):967-83.  [PMID:22809977]
  4. Kanich W, Brady WJ, Huff JS, et al. Altered mental status: evaluation and etiology in the ED. Am J Emerg Med. 2002;20(7):613-7.  [PMID:12442240]
  5. Xiao HY, Wang YX, Xu TD, et al. Evaluation and treatment of altered mental status patients in the emergency department: Life in the fast lane. World J Emerg Med. 2012;3(4):270-7.  [PMID:25215076]
  6. Slooter AJC, Otte WM, Devlin JW, et al. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020;46(5):1020-1022.  [PMID:32055887]
  7. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing
  8. Neufeld KJ, Thomas C. Delirium: definition, epidemiology, and diagnosis. J Clin Neurophysiol. 2013;30(5):438-42.  [PMID:24084176]
  9. LaHue SC, Douglas VC. Approach to Altered Mental Status and Inpatient Delirium. Neurol Clin. 2022;40(1):45-57.  [PMID:34798974]
  10. Nicolson SE, Chabon B, Larsen KA, et al. Primitive reflexes associated with delirium: a prospective trial. Psychosomatics. 2011;52(6):507-12.  [PMID:22054619]
Last updated: May 11, 2022