...Not unlike you post-call...

Definitions/Epidemiology

• A change in cognitive function or level of consciousness (departure from baseline mental status - includes both changes in content of consciousness as well as level of arousal).

• Encephalopathy is a nonspecific term, often used interchangeably with altered mental status, and implies a diffuse global process resulting in a change in the level of arousal.

  • Recent consensus recommends the term acute encephalopathy to describe a rapidly developing (less than 4 weeks) pathobiological brain process that is expressed clinically as either subsyndromal delirium, delirium, or coma and may have additional features, such as seizures or extrapyramidal signs. 

• Delirium is a more specific term and is defined as an acute change in mental status, characterized by a deficit in attention and awareness with a fluctuating course with either disorganized thinking or change in the level of arousal.  It occurs over hours, tends to fluctuate, and is accompanied by a change in cognition that cannot be explained by a preexisting neurocognitive disorder but rather is a consequence of another medical condition, including intoxication or withdrawal.

•  Subsyndromal delirium is a sudden cognitive change that resembles delirium but does not meet all of its criteria. 

• Coma is a state of severely depressed responsiveness defined by using diagnostic systems such as the Glasgow Coma Scale score or the FOUR score. 

  • Coma is a state of complete behavioral unresponsiveness to external stimulation.

  • Delirium is acute confusional state resulting from diffuse or multifocal cerebral dysfunction and is characterized by relatively rapid reduction in the ability to focus, sustain, or shift attention, a change in cognition, fluctuations in consciousness; disorientation and sometimes hallucinations (visual hallucination are common in delirium).

  • Level of consciousness is severely impaired in damage to brainstem reticular formation, bilateral lesions of cerebral hemispheres, thalami. It may also be mildly impaired in unilateral cortical and thalamic lesions. Toxic and metabolic factors are also common causes of impaired consciousness.

• LOC 

  • • Clouding of consciousness is a very mild form of altered mental status in which the patient has inattention and reduced wakefulness.

      • Confusional state is a more profound deficit that includes disorientation, bewilderment, and difficulty following commands.

      • Lethargy consists of severe drowsiness in which the patient can be aroused by moderate stimuli and then drift back to sleep.

      • Obtundation is a state similar to lethargy in which the patient has a lessened interest in the environment, slowed responses to stimulation, and tends to sleep more than normal with drowsiness in between sleep states.

      • Stupor means that only vigorous and repeated stimuli will arouse the individual, and when left undisturbed, the patient will immediately lapse back to the unresponsive state.

      • Coma is a state of unarousable unresponsiveness

• Altered mental status/change in mental status.  5%-10% of ED consults; 10% - 31% of elderly hospitalized; 80% in ICU. 15% of all neurology consults in a tertiary care center.

• A classic study of admissions to the medical intensive care unit (ICU) found neurologic complications in 12.3% of patients admitted with non-neurologic primary diagnoses.  A 2018 meta-analysis revealed a prevalence of delirium in 31% of adult patients in the ICU and in nearly 80% of mechanically ventilated patients who are formally screened. 

• 14% of patients admitted to neurology service with altered mental status have clinically significant finding on head CT or MRI.

  • Half of patients with significant clinical findings on CT or MRI had no focal neurologic signs.

  • 10% - 19% of patients with unexplained encephalopathy have seizures.

• Most internal medicine hospitalists and emergency department physicians are comfortable performing the initial workup, and neurologists are usually consulted only when a focal lesion is suspected, or no immediate cause can be found. 

Basic Approach to Altered Mental Status:

1. Step 1 (All Patients)

   • Check airway, breathing, and circulation; vital signs; blood glucose level.

     • If glucose is low, administer thiamine and dextrose; consider naloxone in the event of a possible opiate overdose

2. Step 2 (All Patients): History (special attention to baseline cognitive status, medications, symptoms of infection)

   • What are the Pt's VS? 

   • Fever/Septic/immunocompromised

   • What was the reason for admission?

   • What is the baseline mental status and level of functioning?

   • Is there any change in level of consciousness?

   • What is the time course of change from baseline mental status?

   • Any seizure activity? 

   • Any history of prior episodes of altered consciousness?

   • Any head trauma ?

   • Is the Pt diabetic...what's the blood sugar?

   • What are the meds given. Any narcotics or sedatives including benzodiazepines, anticholinergics, or benadryl given? Any herbal or OTC medications or preparations?

   • Any drug paraphernalia on the scene, drugs, pill boxes (OD)?

   • Any h/o psychiatric conditions?

   • H/o alcohol abuse. When was the last drink (withdrawal), Wernicke's encephalopathy?

   • Is the patient in AF?

   • Home or NH or from off the street or prison; locked room (exposure to CO)?

   • Any h/o kidney disease, cirrhosis, HIV, COPD?

   • Physical examination (special attention to signs of infection; careful neurologic examination to rule out a focal deficit)

   • Complete blood count, electrolyte panel including calcium, magnesium, and phosphorus, Liver and kidney function tests, including albumin, Urinalysis and culture, urine toxicology screen, CK

   • Chest radiograph

   • ECG

3. Step 3 (Guided by Findings on the Initial Evaluation)

   • Brain imaging with CT followed by MRI with diffusion and gadolinium if the cause remains unclear.

   • Lumbar puncture (perform immediately after CT if meningitis is suspected; probably underused in patients presenting to medical care with altered mental status; usually not necessary for hospital-acquired encephalopathy unless the patient is immunocompromised or neurosurgical)

4. Step 4 (Guided by Findings on the Initial Evaluation)

   • Serum ammonia, thyroid function tests, morning cortisol, vitamin B12, arterial blood gas

   • Sedimentation rate, autoimmune serologies including antinuclear antibodies, thyroperoxidase, and thyroglobulin antibodies

   • Blood cultures

   • Extended toxicology screen, GCMS.

   • EEG (perform sooner if high suspicion for status epilepticus)

Major causes of Acute Altered Mental Status (Delirium, Stupor, Coma)

1. Intracranial lesion

   • Stroke

     • Hemorrhage

       • Epidural hematoma

       • SDH

       • SAH

       • IPH

       • Intraventricular

     • Infarction

   • Trauma

   • Infection

   • Seizures

   • Neoplasm

   • Brain edema

2. Toxic/metabolic disorders

   • Exogenous

     • Alcohol

     • Barbiturates

     • Salicylates

     • Psychotropics

     • Street drug

     • Insulin

   • Endogenous

     • Hyperglycemia

       • Ketotic

       • Non-ketotic

     • Hypoglycemia

     • Uremia

     • Hepatic

     • Electrolyte abnormalities

       • Dehydration

       • Heat stroke

     • Endocrine disorders

       • Pituitary

       • Thyroid

       • Adrenal

3. Anxoia

   • Pulmonary disease

   • CO

4. Ischemia

   • Shock

     • Blood loss

     • Anaphylaxis

     • Hypovolemia

   • Heart failure

5. Mental illness

   • Feigned

   • Hysteria

   • Psychosis.

MS changes: AEIOU TIPS. - 

• • Alcohol 

  • Encephalopathy (metabolic, hypoxic or hypercapnic respiratory failure, uremia, hepatic) Endocrine: hypothyroidism, hyperthyroidism, hyperadrenocorticism, adrenal insufficiency; Epilepsy (post-ictal)

  • Infection: UTI, pneumonia, sepsis, meningitis, brain abscess, lyme disease, line sepsis

  • ODs or withdrawal: opiates, benzodiazepines, toxic ingestions, other medications (methyldopa, BB, TCA, lithium, phenothiazines, MAO-I, SSRIs, steroids, cimetidine, antihistamines, anticholinergics, NSAIDs)

  • Uremia

  • Trauma: head injury

  • Insulin: hyperglycemia - DKA, hypoglycemia 2° excess insulin dosing

  • Psychiatric: dementia (DAT, VaD, Parkinson's, NPH), delirium, schizophrenia, mania, depression

  • Stroke: CVA, TIA SAH, SDH, ICH, brain tumor; SLE, PAN.

  • Structural lesions, supra- or infratentorial: abscess, epidural/subdural hematoma, H'ge, aneurysm, hydrocephalus, stroke, tumor, venous occlusion

Things not to miss

• • • Sepsis or meningitis 

    • Intracranial mass or increased intracranial pressure, ICH, stroke.

    • Alcohol withdrawal (DTs)

    • Intoxications

    • Hypoglycemia

    • Hypotension, hypoxia

    • Liver and/or kidney failure

    • Traumatic ICH

Sundowning:

This is a common call overnight. The patient can present with confusion, disorientation, or combativeness in the evening hours. Associated with dementia, delirium, and unfamiliar environments. Things to consider:

• • Identifying and treat any underlying conditions that could be contributing.

  • Provide frequent reorientation; family members can be helpful.  

  • Maintenance of a familiar environment.

  • Increased lighting.

  • Maintain a quiet structured environment to help calm down the patient.

  • If all else fails:

    • Minimize sedation. If absolutely necessary, haloperidol (Haldol), 0.25 mg PO/IM qd; increase to 1 - 5 mg as needed.

    • Quetiapine 25 mg po bid, Respiridone 0.25 - 1.5 mg qd or olanzapine, 2.5-10 mg qd for agitation, hallucinations or delusions

    • Citalopram 10-30 mg/dL for antidepressants

History: 

• • Seek information from primary or admitting team, EMS, Pt's family and friends, NH staff with the goal to review the medical information in general and events that may have lead to the current state?

  • What was the patient baseline mental status/premorbid state: Awake, alert, and oriented - walking, eating, talking, peeing, and pooping...?

  • Check BP, pulse, respirations, oxygen sats., temperature, and blood sugar.

  • Quickly look at the patient and review the chart.

    • Why was the patient admitted?

    • UTI and pneumonia commonly produce delirium in elderly or demented patient, especially in combination with new medications, fever, or sleep deprivation.

    • New meds or narcotics, medication changes.

      • Anticholinergics

      • Dopaminergic

    • H/o seizures, hepatic, renal, CNS (strokes, brain damage, neurosurgical procedures), diabetes, cardiac disease, psychiatric illness.

    • H/o alcohol abuse, alcohol or drug use.

    • Check for abnormal admission labs: metabolic abnormalities, ABGs (hypercapnia, hypoxia), anemia, uremia, alcohol level (high or low), vit B12 def, leukocytosis, leukopenia (HIV?), LFTs (hepatic encephalopathy, Reye's syndrome), high med level (lithium, anticonvulsants, digoxin), endocrine (TSH, adrenal, pituitary dysfx), sz (EEG triphasic waves), CT of head (H'ge, mass, infarct, hydrocephalus), MRI, LP

    • Any gait problems, urine incontinence, personality changes, headaches.

    • Sleep pattern while in hospital?  Sundowning (the nocturnal exacerbation of confusion).

  • Confirm no falls or trauma.

  • Sudden onset: trauma, seizure, stroke, toxic, metabolic. 

    • CO poisoning

  • Seizures can cause confusion. 

    • Check for prior EEG

    • Check for prior MRI for brain abnormality

    • Partial complex sz are the most common type of focal seizures that can cause confusion.

    • Epilepsia patialis continua is a focal motor epilepsy where clonic movements of the face, arm, and leg recur intermittently for long periods of time.

    • Generalized seizures can cause confusion or postconvulsive encephalopathy

    • Absence seizures are generalized seizures that induce brief lapses of consciousness with prominent automatisms.

• If occurred 48-72 hr after hospitalization, think withdrawal (alcohol or drugs), toxic/metabolic.

  • Similar episodes occurred before (hypoglycemia, porphyria)

  • Gradual onset: expanding CNS lesions, signs of systemic illness associated with coma (cirrhosis, HD, shunt, rash of meningococcemia, hypoxemic or hypercapneic respiratory failure, electrolyte abnormalities, uremia, hyperosmolar states), dementia.

• Fluctuating course of confusional state: metabolic, chronic sedative intoxication, trauma

  • Progressive course: Alzheimer's disease.

  • Step-wise deterioration: VaD, multi-infarct dementia.

  • Did the patient receive potentially sedating or paralytic pharmacologic agents during management and transport to hospital? 

  • STIs, HIV

  • FH of Huntington disease, Wilson disease

Clinical features helpful in the DDx of Acute confusional states.

Headache:  if acute is suggestive of head trauma, meningitis, SAH, ICH, cortical venous sinus thrombosis, and migraine.   If progressive or gradual over period of time: CNS neoplasm, infection, or hydrocephalus.

Language and speech: Inability to recognize both written and oral language, interpret its meaning and produce speech- change in content of consciousness without affecting the level of arousal indicate focal lesion in the left temporal and frontal lobes (dominant hemisphere).

Level of arousal is affected in focal lesions in brainstem, hypothalamus, basal forebrain, and bilateral thalamus, ascending reticular activating system (ARAS), both cerebral hemispheres when affectedcan lead to changes in level of arousal.

Focal deficits and delirium:  Basilar meningitis or a large hematoma with mass effect leading to hemiparesis and decreased responsiveness.  It is important to emphasize that strokes in the ICU may present with acute onset delirium rather than focal deficits; hence, a careful evaluation for subtle signs of focality or a history of cerebrovascular risk factors should be considered when formulating a diagnostic approach. 

Altered mental status in the absence of focal deficits: Paramedian thalamic infarcts, press, nondominant parietal lobe infarcts, watershed infarcts.

Vital signs:

• Fever: Infectious meningitis, anticholinergic intoxication, withdrawal from EtOH or sedative drugs, or sepsis.

• Hypothermia: Intoxication with EtOH and sedative drugs, hepatic encephalopathy, hypoglycemia, hypothyroidism, adrenal insufficiency, or sepsis.

• Hyperthermia:  Sepsis, serotonin syndrome, or NMS.

• Hypertension: Anticholinergic intoxication, withdrawal from EtOH or sedative drugs, hypertensive encephalopathy, SAH, or  sympathomimetic intoxication.

• Tachycardia: Anticholinergic intoxication, withdrawal from EtOH or sedative drugs, thyrotoxicosis, or sepsis.

• Bradycardia: Hypothyroidism

• Hyperventilation: Hepatic encephalopathy, hyperglycemia, or sepsis.

General examination

• Meningismus: Meningitis, SAH.

• Skin rash: Meningococcal meningitis

• Tetany: Hypocalcemia

• Abulia: Orbitofrontal lobe lesions, thalamic lesions.

• Agitation: PCA infarcts involving nondominant parietal lobe.

• Wernicke's aphasia: Left MCA infarcts.  May be initially mistaken for psychosis or delirium.

• Coma: Basilar artery occlusion.

Cranial nerves

• Papilledema: Hypertensive encephalopathy and intracranial mass.

• Dilated pupils: Head trauma, anticholinergic intoxication, withdrawal from alcohol or sedative drugs, sympathomimetic intoxication.

• Constricted pupils: Opioid intoxication.

• Nystagmus/ophthalmoplegia: Intoxication with alcohol, sedative drugs, or phencyclidine, vertebrobasilar ischemia, or Wernicke's encephalopathy.

Motor

• Tremor: Withdrawal from alcohol, sedative drugs, sympathomimetic intoxication, or thyrotoxicosis.

• Asterixis: Metabolic encephalopathy-hepatic, renal, pulmonary, or drug intoxication.

• Myoclonus: Rapid shocklike muscle contractions, seen in uremia, cerebral hypoxia, HHNK states, CJD, or HIV-associated dementia.

• Hemiparesis: Cerebral infarction, head trauma, hyperglycemia, or hypoglycemia.

Others

• Seizures: Withdrawal from ethanol or sedative drugs, head trauma, hyperglycemia, hypoglycemia.

• Ataxia: Intoxication with ethanol or sedative drugs, Wernicke's encephalopathy.

• Unprotected sexual intercourse, intravenous drug use, hemophilia or blood transfusions: HIV-associated dementia.

• Family history of Huntington's disease or Wilson disease.

Physical examination: 

The physical examination is tailored to the restrictions created by a typically bedbound patient, sedation, mechanical ventilation, and invasive monitoring devices. 

Diagnostic testing typically feasible in a stable inpatient may not always be possible in critically ill patients.  In such settings, clinical localization by bedside examination, triage of imaging based on urgency and impact on immediate management, and discussion with the critical care team on the overall clinical priorities of neurologic management become key pillars of providing an effective neurology consultation in these difficult conditions. 

Traditional localization to a central nervous system disorder with further delineation of cortical, subcortical, brainstem, or localization in spinal cord (spinal cord syndromes) or peripheral nervous system disorder with further delineation of AHC, roots, plexus, nerve, NMJ, and muscle is still applicable to evaluation in the ICU. Additionally, a pathology-based localization paradigm assigning the cause of symptoms to structural, electrophysiologic, perfusion-related, or neurochemistry-related issues akin to the components of a house can help prioritize the diagnostic evaluation. 

If able to do so safely, the examiner should pause any sedating medications before the neurologic examination.  

n. Patients with neuromuscular paralysis caused by the use of cisatracurium may be examined 30 minutes after stopping the infusion because of its short half-life.  Nondepolarizing neuromuscular blockers, such as rocuronium or vecuronium, used for intubation have longer clearance times and may need reversal with sugammadex. 

A peripheral nerve stimulator called a train-of-four monitor can be used to assess neuromuscular transmission when neuromuscular blocking agents are given.  Typically, the stimulator is applied on the median nerve while twitches in the thumb are observed.  Four twitches, hence the train-of-four, reflect intact neuromuscular transmission and clearance of neuromuscular blocking agents. 

Focused Examination

• • General: How distressed or sick the patient appears? GCS. Odor of alcohol or fetor hepaticus, fruity odor (acetone breath in DKA). 

  • VS: Temp, HR, RR, pulse ox, BP. Shock

  • Skin: warmth, pallor, capillary refill, jaundice, diaphoresis, cyanosis, needle track marks, skin "popping", rash, hirsutism, hyperpigmentation, scaly dermatitis, Janeway lesions, spider nevi

  • Nails: splinter H'ges.

  • Respiratory rate and pattern: 

    • Cheyne-Stokes respirations (rhythmic crescendo-decrescendo hyperpnea alternating with periods of apnea) occur in metabolic acidosis, supratentorial lesions, COPD, and CHF.

    • Hyperventilation usually as signs of metabolic acidosis, hypoxemia, pneumonia, or other pulmonary disease may also be caused by upper brainstem injury.

    • Apneustic breathing (long pauses after inspiration), Cluster breathing (breathing in short bursts). Ataxic breathing (irregular breathings without pattern) are all signs of impending respiratory arrest.

      • Apneustic breathing, classically associated with bilateral pontine injury, can also be caused by excessive ventilatory support, leading to hypocapnia-induced pauses in respiratory drive.

  • HEENT: Icteric sclera, signs of trauma like ecchymoses, abrasions, or lacerations, bony deformities, epistaxis, CSF rhinorrhea and/or otorrhea, gray and immobile TM, facial and sinus tenderness, nasal septum erosion from cocaine snorting, hemotympanum, anisocoria,  Check pupil size, symmetry, reaction to light, papilledema, Check postauricular for Battle's sign, the bulb of VP shunt - malfunction > raised ICP. Check buccal muosa and tongue for lacerations or abrasions - seizures.

  • Neck: nuchal rigidity. Meningeal signs: Check for meningeal signs (Kernig's and Brudzinski's). 

  • Cardiovascular: Listen for irregular heart rhythm and for murmurs; suggest valvular heart disease or endocarditis.

  • Respiratory: Tachypnea indicates hypoxia or metabolic acidosis. Crackles or decreased breath sounds may help diagnose or pneumonia., CHF, cardiac tamponade, pneumonia →→ hypoxia contributing to delirium.

  • Abdomen: Look for signs of ascites, jaundice, splenomegaly, caput medusae. Abdominal tenderness (RUQ - cholecystitis, VP shunt patients can have shunt infection with peritonitis), CVA tenderness.

  • Extremities: Look for clubbing as a sign of chronic pulmonary disease, peripheral edema as a sign of cardiorenal failure, splinter hemorrhages as a sign of emboli. Asterixis is a sign of metabolic encephalopathy especially from renal or hepatic failure. 

  • Neurologic: 

    • Mental Status:

      • GCS. Attention (inability to maintain attention - hallmark of delirium).  Ask patient to count days of the week forward and backward or to count backward from 20 to 1.

      • Orientation to person is usually intact. Disoriented to place, and time. 

      • Arousal: Changes in levels of arousal from coma, drowsiness, lethargy, hypervigilance to agitated.

      • Memory usually not testable, if inattentive.  Because registration depends on the ability to focus attention, delirious patients frequently are unable to form new memories and do so only during lucid periods.

      • Perception: Hallucinations - visual or auditory. Illusions and delusions.

      • TP is abnormal. Incongruent, not goal-directed. Cognitive impairment.

      • Emotional lability and inappropriate emotional responses occur frequently.

      • Language abnormalities: Incoherent and rambling speech.

      • Nonspecific signs and symptoms of increased ICP: HA, N/V, HTN, bradycardia, papilledema, CN VI palsy, transient visual obscurations, irregular respirations, and alterations in consciousness.

      • The mental status examination is tailored to the patient’s level of consciousness.  At a minimum, the examiner should assess the level of arousal by evaluating whether the patient’s eyes open spontaneously to voice, gentle touch, or noxious stimulation.  The examiner should call the patient’s attention to both sides of the room to seek evidence of neglect.  Some patients who do not voluntarily open their eyes may attend or track if the examiner opens their eyes for them, indicating bilateral ptosis or apraxia of eye-opening.

      • The examiner should evaluate language comprehension by asking the patient to follow both axial and appendicular commands. Intubated awake patients may also be able to read to follow commands and write to allow a more complete language assessment. 

    • Cranial nerves:

      • For cranial nerve assessment, the pupillary reflex, corneal reflex, facial asymmetry in response to pain, and cough and gag reflexes are usually the most common tests to allow assessment of cranial nerves II, III, V, VII, IX, and X.  High doses of sedatives or hypothermia can abolish these reflexes, and they can be temporarily absent in patients for several hours after cardiac arrest.  Visual field testing can be performed by checking for the blink-to-visual-threat reflex.  Anisocoria may be physiologic in up to 20% of patients in the general population or caused by the administration of anticholinergics such as nebulized ipratropium or scopolamine patches.  Pupillary pathways are typically resistant to changes in metabolism, and pupillary reflexes are typically not affected by pharmacologic neuromuscular paralysis.  This makes them very sensitive markers of uncal herniation.  In patients with eyelid swelling or orbital trauma impairing access to the pupil, ultrasonography can be used to assess the consensual pupillary reflex. 

      • Papilledema: ▲ ICP, HTN encephalopthy. Absence does not rule out increased ICP.

      • Pupillary changes:

      • Unilateral dilated pupil (blown out pupil) with or without other components of CN III (down-and-out sign) palsy is a sign of herniation. This is a neurological emergency.

        • Anisocoria (assymetric pupils) in a patient with altered mental status requires immediate diagnosis and treatment, or exclusion, of possible herniation. It may be physiological or produced by mydriatics (e.g., scopolamine, atropine).

        • Small but reactive pupils are seen in narcotic overdose (<2 mm), metabolic encephalopathy, and thalamic or pontine lesions.

        • Midposition or fixed pupils imply midbrain lesions and occur in transtentorial herniation.

        • Bilaterally fixed and dilated pupils are seen in anoxic encephalopathy, hypoglycemia, or intoxication with drugs such as scopolamine, atropine, glutethimide, or methyl alcohol

        • Enlarged but reactive pupils: increased sympathetic activity, intoxication with cocaine, amphetamines, therapeutic use of epinephrine, pressors, ipratopium.

      • EOM:

        • Upgaze palsy: dorsal upper midbrain lesion or compression (Parinaud's?) due to hydrocephalus.

        • Unilateral failure of eye to adduct (with pupillary dilatation) and diminished level of consciousness - herniation, neurological emergency.

        • Absence of all eye movements indicates a bilateral pontine lesion or drug-induced ophthalmoplegia (e.g., barbiturates, phenytoin, paralytics).

        • Dysconjugate gaze in the horizontal plane may occur in intoxication or drowsiness, whereas dysconjugate gaze in the vertical plane results from pontine or cerebellar lesions.

        • Eye movement abnormalities are common in patients in the ICU, including ocular bobbing (rapid, conjugate downward movements followed by a slow return to the primary position), ocular dipping (slow downward movement followed by a rapid return to the primary position), ping-pong gaze (horizontal conjugate deviation of the eyes that alternates every few seconds), and periodic alternating gaze deviation (horizontal conjugate deviation of the eyes that alternates on a scale of minutes).  These do not always localize precisely or reflect structural changes.  Latent phorias may be unmasked in critical illness; hence, knowing if a patient has a preexisting history of strabismus can be useful. 

      • Facial asymmetry: Flattened nasolabial fold or a wider palpebral fissure may be a subtle sign of intraparenchymal mass or stroke. 

      • Assess swallowing capacity and gag reflex.

      • Motor Exam:

        • Quadriparesis delirious - think CPM, PML, ADEM.

        • Paraparesis delirious - think cryptococcosis, vitamin B12 def, and ADEM.

        • Proximal muscle weakness: hypokalemia, Cushing's disease

        • Rigidity: Neuroleptic malignant syndrome or serotonin syndrome, which can be distinguished by the presence of hyperreflexia in the serotonin syndrome.  Paratonic rigidity is common in metabolic encephalopathies.

        • Recrudescence of old deficits:  A review of the neurologic history and imaging, if available, can help determine if focal weakness discovered on examination represents an acute change or the recrudescence of chronic pathology.  Risk factors for worsening of preexisting deficits include infection, hyponatremia, hypoglycemia, hypotension, and benzodiazepines. Although metabolic encephalopathies typically present with a gradual onset of delirium or coma, the recrudescence of focal findings usually occurs abruptly giving an impression of stroke.   

        • Abnormal limb movement:

          • Tremor: Coarse tremor which is irregular, most prominent in fingers of extended arms and absent at rest.

            • Withdrawal from EtOH, benzo

            • Thyrotoxicosis

            • Sympathomimetic intoxications (cocaine, amphetamine, phencyclidine)

            • Barbiturate and benzodiazepine withdrawal.

          • Myoclonus: asynchronous irregular twitching of a single muscle, groups of muscles, or entire limbs, usually with proximal predominance. 

            • Metabolic abnormalities

            • Hypoxic-ischemic encephalopathy

            • Lithium intoxication

            • CNS infections: CJD, HIV.

          • Asterixis: recurrent brief lapses of posture observed with arms raised and elbows and wrists extended (stop-traffic action). Flaps.

            • Hepatic encephalopathy, uremia.

          • Chorea: Huntington disease

        • Gait:

          • Apraxia: magnetic gait -  NPH

          • Gait ataxia is common in intoxication, vitamin B12 deficiency, neurosyphilis, and Wernicke's encephalopathy.

        • Uncal herniation is caused by unilateral supratentorial lesions that progress rapidly. 

          • Earliest sign is dilated pupil ipsilateral to the mass, diminished consciousness, and hemiparesis, first contralateral to the mass and later ipsilateral to the mass (Kernohan notch phenomenon as the cerebral peduncle opposite to the herniating mass is compressed).

      • Sensory Exam:

        • Polyneuropathy with hyporeflexia: neurosyphilis, vitamin B12 deficiency, HIV associated dementia.

      • Reflexes:  Attention must be paid to the asymmetry of reflexes or any upper motor neuron signs, such as the Babinski sign or Hoffman sign, because these may be subtle indicators of central nervous system pathology.

Labs

• • Blood sugar check.

  • CBC, electrolytes, ABGs, LFTs including Hepatitis profile, aPTT, PT, Sr. Osm, Urine Osm, ABGs including arterial lactic acid, arterial ammonia, TSH, FT4, cortisol, CRP, ESR, ANA, ENA scr, amylase, lipase, troponin T, N-terminal pro-BNP, UA, Urine C&S, Vit B12, ECG, CXR. 

  • LP (cell count, differential, gram stain, cultures, viral cultures, AFB, TB PCR, VDRL, HSV 1&2 PCR, VZV PCR, enterovirus, JC virus, cytology, glutamine - for hepatic encephalopathy, CrAg, lyme, WNV - IgG and IgM, histoplasma antigen, coccidioides immunodiffusion or complement fixation, St. Louis encephalitis), HIV, serum CrAg, Bacterial PCRs (T. whippelii, bartonella, ricketssia).

    • Never perform a LP if you suspect a mass lesion or raised ICP, until a CT is obtained or a funduscopic examination is performed. Check for mass or midline shift on CT.

    • LP in patients with fever and headaches or those with high risk of infection. Also in patients suspected of SAH in whom the CT of head is negative.

  • Patients with malignancy (CSF cytology and flow cytometry)

  • CSF glutamine (elevated if serum ammonia is normal). Seen in patients taking valproate and topiramate.

• anti-TPO, anti-thyroglobulin for SREAT (Hashimoto encephalitis).

  • UDS, blood alcohol, ethylene glycol, methanol, VRDL, FOBT, ceruloplasmin, copper, FTA-Ab or MHA-TP, cortisol stimulation test.

• Patients who are immunocompromised (CMV PCR, HHV6, JCV, galactomannan if aspergillosis is suspected).

• Ab against VGKC, LGl1, NMDA rcp, AMPA rcp, GABAb rcp, anti-GAD. Abs against Ma1, Hu, CV2/CRMP5, Tr. OGB, IgG index (in patients suspected with paraneoplastic/autoimmune encephalitis).

  • Critically ill patients with fluctuating mental status or those whose disorder of consciousness seems out of proportion to their primary diagnosis should be evaluated for the possibility of nonconvulsive seizures or status epilepticus.   EEG (LTR or cEEG) to rule out seizures, or confirm the diagnosis of certain metabolic or infectious encephalopathies. These include periodic lateralized epileptiform discharges (PLEDs) in encephalitis (e.g., herpes simplex virus), triphasic waves in hepatic or uremic encephalopathy, posterior dominant rhythm frequency of <8 Hz or relative decrease from an alpha wave of 12 - 10 Hz (in mild encephalopathy).  As the encephalopathy worsens, the background becomes disorganized, and high-voltage theta and and delta activity (slowing) appears with loss of EEG reactivity at frequencies less than 5 - 6 Hz. 

  • EMG and nerve conduction studies, including repetitive nerve stimulation, should be considered for all critically ill patients who have unexplained persistent severe weakness with suspected neuromuscular origin. 

  • X-ray spine if trauma has occurred.

  • ECG for cardiac arrhythmia - AF, TCA OD. QTc prolongation.

  • CT/MRI w/wo contrast (seizure protocol/stroke protocol = coronal thin slices, DWI/ADC, GRE) for structural lesions, bleeds, basilar artery thrombosis.

  • Use of iodinated contrast in patients with renal dysfunction is unlikely to substantially contribute to acute kidney injury, even in critically ill patients,20,21 and CT angiography should not be deferred, especially in patients who may be candidates for thrombectomy.

  • MRV or CTV

    • Check Cr. for contrast nephropathy (CTA). 

    • If Pt. is ESRD on HD, gadolinium contrast may cause nephrogenic systemic sclerosis. Coordinate to get MRI with contrast during day of HD, prior to HD.

  • Angiography: aneurysm, AVM, CNS vasculitis

  • Brain bx: rarely indicated in evaluation of delirium. 

    • Brain tumor for histologic typing

    • CNS vasculitis: leptomeningeal bx

ABGs in acute confusional states:

• • AGMA: DKA, lactic acidosis (post-ictal, shock, sepsis), toxins (methanol, ethyelene glycol, salicylates, paraldehyde), uremia

  • Respiratory alkalosis: Hepatic encephalopathy, pulmonary insufficiency, salicylates, sepsis. 

  • Respiratory acidosis: Pulmonary insufficiency, sedative drug overdose. 

Management:

• • Airway obstruction: Remove debris, suction vomitus. Put an airway so that the tongue does not obstruct the airway. Jaw thrust. 

  • Breathing. Apnea requires immediate intervention with BVM, tracheal intubation, and mechanical ventilaton

  • Circulation. Skin pallor, diaphoresis, BP, capillary refill, UO, .

  • Maintain normal body temperature.

  • Establish secure IV

  • Arterial, central venous, and ICP monitoring may be needed depending on circumstances.

  • If trauma has or may have occurred, immobilize the spine immediately.

  • Based on exam findings and lab results.

  • If meningitis is suspected start empiric ABX, neurology consult, ID consult.

  • Reorient patient and have a sitter present if patient remains confused.

  • A quiet well lit room with close observation is necessary. Physical restraints should be used only as a last resort and with appropriate documentation in the medical record. Adjust and check periodically to prevent excessive constriction. D/C if not needed.

  • Alcohol withdrawal needs to be treated urgently with benzodiazepines, usually chlordiazepoxide (Librium) or lorazepam (Ativan). 

  • Thiamine, 100 mg IV, followed by glucose (50 mL of 50% dextrose in water = 25 g dextrose) is administered. 

  • IV naloxone, 0.01 mg/kg, (0.4 - 2 mg IV or IM) should be administered in opiate intoxication, especially in opiate naieve patients. It may provoke opiate withdrawal syndrome in addicted patients.

  • Lactulose

  • Flumazenil, 0.2 mg IV, may reverse benzodiazepine intoxication, but its duration is short, and additional doses may be needed. Flumazenil can cause seizures.

  • Avoid sedation in delirious patients if possible, but if necessary low dose lorazepam (1 mg) or chlordiazepoxide 25 mg can be used.

  • If patient is hemodynamically unstable - admit to ICU.

    • Haloperidol, 0.25 - 5 mg PO, and 2 - 5 mg IV or IV q30 - 60 min till effect desired.  0.25 mg in elderly patients.  Sedation is achieved with 10-20 mg PO or IM.  IV infusions, 1 - 40 mg/hr.  Compared to other antipsychotic have fewer active metabolites and fewer anticholinergic, sedative, and hypotensive efffects, although it may have more extrapyramidal side effects.

      • Prolonged QTc >450 msec → torsades de pointes may be seen with high dose IV therapy.  Check QTc and electrolytes (potassium and magnesium).  D/c if QTc >450 msec or 25% above baseline.

      • Postural hypotension

        • IVF, Pt. in Trendelenberg position. 

        • Give vasopressors such as epinephrine or phenylephrine

        • No dopamine as it may exacerbate the psychotic state.

      • Neuroleptic malignant syndrome is infrequent, potentially lethal complication.  Rigidity, akinesia, altered sensorium, fever, tachycardia, labile BP, rhabdomyolysis, AKI.  Labs: ▲ CK, LFTs, and WBC

    • Lorazepam, 0.5 - 2 mg IV.  Short duration, fewer active metabolites.  Limited by excess sedation, respiratory depression, and the potential to precipitate agitation in the elderly and in patients with liver disease and low albumin.

      • Versed (mdiazolam), 1-2 mg IV/PO

    • Newer-generation antipsychotics (risperidone, olanzapine (zyprexa), 5-10 mg PO/IM daily, quetiapine (seroquel), 2-50 mg PO, clozapine, ziprasidone) are alternative agents that may lead to decreased incidence of extrapyramidal symptoms.

Other nonoperative therapies:

• • If herniation is identified or suspected, treatment consists of measures to lower ICP while surgically treatable etiologies are identified or excluded. Consult with Neurosurgery ASAP.

    • ETT, hyperventilation to a PCO2 of 25 - 30 mm Hg, reduces ICP within minutes by cerebral vasoconstriction.

    • BVM ventilation if C-spine immobilized.

    • Don't reduce PCO2 < 25 mm Hg as it may reduce CBF excessively.

    • Administer hypertonic saline: NaCl 23.4% of 30 mL vial, IVP over 30 minutes through central line. Follow up maintenance with hpertonic saline 3% @ 1kg/cc/hr 

    • Dexamethasone, 10 mg IV, followed by 4 mg IV q6hr, reduces edema surrounding tumor on an abscess.

    • Coagulopathy should be corrected if ICH is diagnosed and before surgical treatment or invasive procedures (e.g., LP).

Differences between acute confusional sates and dementia

Differential Diagnosis:

Young pregnant woman with subacute progressive encephalopathy, headache and fever.  She has generalized dystonia and hyperreflexia, and dysautonomia, and history of exposure to serotoninergic and neuroleptic d rugs,

• Infectious encephalitis should be the first diagnosis to exclude. 

• Substance abuse. 

• Autoimmune encephalitis.

• Vascular neurologic conditions associated with pregnancy

  • Cerebral venous thrombosis, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome.

• CNS vasculitis, both primary (primary angiitis of the CNS) and secondary (systemic inflammatory diseases). 

• Susac syndrome (SuS) is a rare cause of encephalopathy that may also present with migrainous headache and pyramidal signs, and must not be forgotten, despite the absence of the complete triad (encephalopathy, sensorineural hearing loss, and branch retinal artery occlusions [BRAOs]). 

• Multiple sclerosis and acute disseminated encephalomyelopathy. 

• Taking into account her generalized dystonia and hyperreflexia, fever, and dysautonomia, after exposure to serotoninergic and neuroleptic drugs, the serotoninergic and neuroleptic malignant syndromes should also be acknowledged.

Template:

I discussed my concerns with the hospitalist to order: 

Evaluate for infectious etiology: CBC with differential, CMP, urine toxicology screen, blood alcohol concentration, LFTs, serum ammonia, serum copper, serum ceruloplasmin, TSH, vitamin B12, folate, ABG with lactate. 

Chest x-ray, CT head, MRI of the brain with and without contrast. 

ECG, troponin, BNP. 

Serum: ANA, ENA screen C-ANCA, p-ANCA, RF, CCP, ESR, CRP, acute hepatitis panel, HIV, cardiolipin antibody, syphilis panel, fractionated porphyrin urine heavy metal screen celiac panel, GAD65, anti-TPO, anti-TG, lupus, ACL, listeria. paraneoplastic panel, special lab test: Autoimmune/Paraneoplastic Evaluation, Serum (Mayo): TEST ID : ENS2 (includes CASPR2-ab, LGI1-ab, NMDA-R-ab, and others.

CSF analysis.  Include Encephalopathy, special CSF test: Autoimmune/Paraneoplastic Evaluation, Spinal Fluid (Mayo): Test ID: ENC2.  Also to the cerebrospinal fluid add: JC virus DNA detector in the CSF analysis 14-3-3 protein, S100b protein, RT-QUIC assay, amyloid beta protein (1–42), total tau cerebrospinal fluid

cvEEG (LTM) to check for subclinical/electrographic seizures.

Further recommendations can be made based on results of the above test. 

I also discussed following exclusion of infectious etiologies a trial of Solu-Medrol 500 mg every 12 hours IV infusion for 3 days can be tried to see for any clinical response