Altered Mental Status

1. Sean Ruland, D.O. Professor Department of Neurology Altered Mental Status

2. Outline • Terminology • Diagnosis • Work-up • Specific etiologies and treatments • Appropriate consultation

3. Terminology and Definition • Encephalopathy • Diffuse cerebral dysfunction • Acute (onset hours to days) encephalopathy = delirium = acute confusional state

4. Clinicoanatomical Correlation • Ascending reticular activating system impairment (ARAS) • Impaired arousal (hypoactive delirium) • Occasionally agitated delirium

5. History • Collateral sources of information often necessary • Define temporal course • Past medical and surgical history • DM; hepatic, renal, and thyroid disorders; and mental illness • Comprehensive medication reconciliation • ETOH and illicit substance use • Baseline cognitive function

6. General Examination • ABCs • Intubation may be required • Respiratory rate, depth, and pattern • Autonomic dysregulation • Core temperature • Inspection • Signs of trauma, jaundice, petechial hemorrhage, ecchymosis, spider angiomata, needle tracks and evidence of skin popping, pressure ulcers (prolonged immobility) • Breath odor • ETOH, acetone (ketoacidosis), fetid (uremia) • Palpation • Hepatomegaly, nodular liver, ascites

7. Neurologic Examination • Altered sensorium • Ranges from mild inattention to coma (waxes and wanes) • Pitfall—eye opening apraxia • Impaired cognition • Meningeal signs • Papilledema • Pupillary function • Mydriasis—central herniation, HIE, anticholinergic or sympathomimetic exposure • Miosis—opioid or organophosphate exposure, pontine injury, advanced age • Asymmetry—uncal herniation, previous ocular injury, midbrain damage, Horner syndrome

8. Neurologic Examination • Eye movements • Dysconjugate gaze but typically oculocephalic and oculovestibular reflexes present • Decreased saccades, nystagmus, frank ophthalmoplegia • Corneal and pharyngeal reflexes typically present unless severe • Motor • Asterixis, diffuse myoclonus, extrapyramidal signs, symmetrical posturing, upgoing plantar responses

9. Structural • Trauma • Diffuse axonal injury • Unilateral or bilateral extracerebral hematoma • Prefrontal mass lesions • Neoplasm • Pyogenic brain abscess • Subdural hematoma • Acute obstructive hydrocephalus • Scattered infarctions due to multiple emboli, vasculitis/vasculopathy • Requires brain imaging to assess

10. Seizures/Status Epilepticus • Cause and/or effect of underlying problem • Seizure description may help determine etiology • Focal onset vs generalized • May require continuous EEG monitoring • Treatment depends on etiology

11. Infectious • Meningoencephalitis • Meningeal signs not invariably present • CSF analysis may be required • Septic encephalopathy • Complex mechanism and may involve multiple organ systems • Hypoxia and/or hypercapnea with pneumonia • Decreased toxin and/or medication clearance due to hepatic and/or renal dysfunction • Microvascular thrombosis (e.g. DIC) • Brain suppression due to endotoxin and inflammatory mediators • Secondary effects (e.g. septic emboli, brain abscess, vasculitis, etc.) • Neurotoxic effects of antibiotics • Antibiotic-associated neurotoxicity • 4th generation cephalosporins and carbapenems

12. Toxic Encephalopathy • Clinical signs • Depressed LOC or agitated delirium including hallucinations • Seizures (toxic or withdrawal state) • Nystagmus, dysarthria, incoordination, tremor, ataxia, extrapyramidal features (rigidity, choreoathetosis, akathisia) • Decreased muscle tone, depressed muscle stretch reflexes, posturing (rarely) • Autonomic and thermal dysregulation

13. Toxic Encephalopathy • Offending agents • ETOH and illicits • Sedative-hypnotics and narcotic analgesics • Benzos and barbs may cause acute respiratory failure • Flumazenil (caution as may cause seizures) • Opiates (pinpoint pupils, respiratory depression—naloxone) • Neuroleptics (neuroleptic malignant syndrome) • Rigidity, hyperpyrexia, elevated CK and transaminases, leukocytosis • Dopamine agonist and dantrolene • Anti-seizure medication • Cerebellar syndrome • Levetiracetam (agitated delirium) • Valproic acid (hyperammonemia) • Acute phenytoin exposure (ophthalmoplegia, extrapyramidal signs) • Barbiturates (cardiotoxicity, hypothermia) • Antidepressants (serotonin syndrome) • Similar to NMS with tremor, myoclonus, and/or hyperreflexia • Anticholinergic medication (H1 and H2 blockers) • Immunosuppressants • CSA and tacrolimus (PRES—visual changes, seizures, impaired consciousness, MRI findings) • Iodinated contrast-induced encephalopathy (PRES)

14. Posterior Reversible Encephalopathy Syndrome (PRES)

15. Hypoxic Ischemic Encephalopathy • Selective vulnerability • Hippocampus (CA1 region) • Purkinje cells • Basal ganglia • Deep layers cerebral cortex • Etiologies • Cardiopulmonary arrest • Carbon monoxide exposure (headache, mild confusion >>> coma, cherry red lips and mucous membranes) • Hyperbaric O2 • Methemoglobinemia (topical anesthetics, nitrates, and cyanide can induce iron oxidation within Hgb) • Methylene blue • High altitude sickness (headache, confusion, sleep disturbance, papilledema, uni/bilateral 6th nerve palsy, coma) • Descent, acetazolamide, dexamethasone may be preventive • Subclinical partial arylsulfatase A deficiency (predispose to delayed encephalopathy following mild hypoxia) • Manifestations • Seizures • Myoclonic jerking • Short term memory loss • Cerebellar dysfunction • Extrapyramidal signs • Cognitive impairment • Coma and absent brainstem reflexes