Editors: Foster, Corey; Mistry, Neville F.; Peddi, Parvin F.

; Sharma, Shivak Title: Washington Manual of Medical Therapeutics, The, 33rd Edition Copyright 2010 Lippincott Williams & Wilkins Table of Contents 23 - Neurologic Disorders Victoria Sharma Beau Ances Alterations in Consciousness GENERAL PRINCIPLES Definition

Coma is a state of complete behavioral unresponsiveness to external stimulation. Because some causes of coma may lead to irreversible brain damage, expeditious evaluation and treatment should be performed concurrently. The need for neurosurgical intervention must be determined promptly. Acute confusional state (delirium) results 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.

Epidemiology

About 30% of older patients (>60 years old) experience delirium at some time during hospitalization. Patients who experience delirium may have prolonged hospitalizations, more rapid functional decline, and are at higher risk for long-term institutionalization.

Etiology

Coma results from diffuse or multifocal dysfunction within cerebral hemispheres or the reticular activating system in the brainstem. Etiologies for delirium are listed in Table 1. Mild systemic illness (i.e., UTI) commonly produces delirium in an elderly or demented patient, especially in combination with new medications, fever, or sleep deprivation.

Risk Factors Can be divided into those that increase vulnerability (underlying neurodegenerative disorder or stroke) and precipitating event (trauma or toxin ingestion). DIAGNOSIS

Initial assessment should focus on recognizing the development and progression of altered consciousness. Examiner should query for history of trauma, seizures, medication changes, alcohol or drug use, and existing medical conditions as possible etiologies. 1

If trauma has or may have occurred, immobilize the spine immediately while arranging radiographs to identify or exclude fracture or instability.

Clinical Presentation Physical Examination

Search for signs of systemic illness associated with coma (e.g., cirrhosis, hemodialysis shunt, rash of meningococcemia) or signs of head trauma (e.g., lacerations, periorbital or mastoid ecchymosis, hemotympanum). The physical and neurologic examination may reveal systemic illness (e.g., pneumonia) or neurologic signs (meningismus or paralysis) to narrow the differential diagnosis. The diagnosis of brain herniation must be recognized and treated immediately (serial examinations should be performed to detect and intervene if clinical deterioration occurs). Neurologic examination should focus on the ability of the patient to focus, sustain, or shift attention. Repeated neurologic examination may be required due to fluctuations in status. Level of consciousness can be assessed semiquantitatively and followed by all levels of caregivers with the Glasgow Coma Scale. Scores range from 3 (unresponsive) to 15 (normal). Respiratory rate and pattern o Cheyne-Stokes respirations (rhythmic crescendo-decrescendo hyperpnea alternating with periods of apnea) occur in metabolic coma and supratentorial lesions, as well as in chronic pulmonary disease and congestive heart failure (CHF). o Hyperventilation is usually a sign of metabolic acidosis, hypoxemia, pneumonia, or other pulmonary disease but may be caused by upper brainstem injury. o Apneustic breathing (long pauses after inspiration), cluster breathing (breathing in short bursts), and ataxic breathing (irregular breaths without pattern) are signs of brainstem injury and warn of impending respiratory arrest. Pupil size and light reactivity o Anisocoria (asymmetric pupils) in a patient with altered mental status requires immediate diagnosis and treatment, or exclusion, of possible herniation. Anisocoria may be physiologic or produced by mydriatics (e.g., scopolamine, atropine). o Small but reactive pupils are seen in narcotic overdose, metabolic encephalopathy, and thalamic or pontine lesions. o Midposition fixed pupils imply midbrain lesions and occur in transtentorial herniation. o Bilaterally fixed and dilated pupils are seen with severe anoxic encephalopathy or intoxication with drugs such as scopolamine, atropine, glutethimide, or methyl alcohol. Eye movements o The oculocephalic (doll's eyes) test is performed (if no cervical injury is present) by quickly turning the head laterally or vertically. In coma with 2

intact brainstem oculomotor function, eyes move conjugately opposite the direction of head movement. o The oculovestibular (cold caloric) test is used if cervical trauma is suspected or if eye movements are absent with the oculocephalic test. Verify intact tympanic membrane and patent auditory canal. Elevate the head 30 degrees above horizontal, with the patient supine. Lavage external auditory canal with 10 to 50 mL of ice water. In coma with intact brainstem oculomotor function, eyes move conjugately toward the lavaged ear. Vertical gaze can be assessed with simultaneous lavage of both ears (cold water eyes depress, warm water eyes elevate). o Absence of all eye movements indicates a bilateral pontine lesion or drug-induced ophthalmoplegia (e.g., barbiturates, phenytoin, paralytics). o Disconjugate gaze suggests a brainstem lesion. o A gaze preference conjugately to one side suggests a unilateral pontine or frontal lobe lesion. An associated hemiparesis and oculocephalic and oculovestibular tests help localize the lesion. In pontine lesions, gaze preference is toward the paretic side, and eyes may move toward but do not cross midline. In frontal lobe lesions, gaze preference is away from the paresis, and eyes move conjugately across midline to both sides. o Impaired vertical eye movement occurs in midbrain lesions and central herniation. Conjugate depression and impaired elevation suggest a tectal lesion (pinealoma) or hydrocephalus. Motor responses help to assess the level of impaired consciousness. Asymmetric motor responses (spontaneous or stimulus induced) have localizing value. Herniation occurs when mass lesions or edema cause shifts in brain tissue. Prompt diagnosis and treatment are necessary to prevent irreversible brain damage and death. o Nonspecific signs and symptoms of increased intracranial pressure include headache, nausea, vomiting, hypertension, bradycardia, papilledema, sixth nerve palsy, transient visual obscurations, and alterations in consciousness. o Uncal herniation is caused by unilateral supratentorial lesions and may progress rapidly. The earliest sign is a dilated pupil ipsilateral to the mass, diminished consciousness, and hemiparesis, first contralateral to the mass and later ipsilateral to the mass (Kernohan notch syndrome). o Central herniation is caused by medial or bilateral supratentorial lesions. Signs include progressive alteration of consciousness, Cheyne-Stokes or normal respirations followed later by central hyperventilation, midposition and unreactive pupils, loss of upward gaze, and posturing of the extremities. o Tonsillar herniation occurs when pressure in the posterior fossa forces the cerebellar tonsils through the foramen magnum, compressing the medulla. Signs include altered level of consciousness and respiratory irregularity or apnea.

Table 1 Causes of Altered Mental Status Metabolic derangements/diffuse etiologies Hyper/hyponatremia Hypercalcemia Hyper/hypoglycemia Hyper/hypothyroidism Acute intermittent porphyria Hypertensive encephalopathy Hypoxia/hypercapnia Global cerebral ischemia from hypotension Infections Meningitis/encephalitis Sepsis Systemic infectious with spread to CNS Drugs/toxins/poisons Prescription medications and side effects of medications Drugs of abuse Withdrawal situations Medication side effects Inhaled toxins Inborn errors of metabolism Nutritional deficiency (i.e., thiamine) Seizures Subclinical seizures Postictal state Head trauma Structural Ischemic stroke (only certain stroke locations cause altered mental status) Hemorrhage Hydrocephalus Tumor Systemic organ failure Hepatic failure Renal failure Psychiatric Diagnostic Testing Laboratories Obtain serum electrolytes, creatinine, glucose, calcium, complete blood count, and urinalysis. Drug levels should be ordered if appropriate. Toxic screen of blood and urine should be considered. Imaging A head CT should be obtained to evaluate for structural abnormalities. Diagnostic Procedures

Lumbar puncture (LP) should be considered in patients with fever and headaches or those at high risk of infection. Electroencephalography (EEG) can be considered to rule out seizures, or confirm the diagnosis of certain metabolic or infectious encephalopathies. These include periodic lateralized epileptiform discharges (PLEDs) in encephalitis 4

(e.g., herpes simplex virus [HSV]), triphasic waves in hepatic or uremic encephalopathy, and activity or voltage suppression in barbiturate or other sedative intoxications. TREATMENT

Ensure adequate airway and ventilation, administer oxygen as needed, and maintain normal body temperature. Establish secure IV and adequate circulation. Arterial, central venous, and intracranial pressures may need to be monitored and treated depending on clinical circumstances. Make repeated attempts to reorient the patient and possibly 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. If restraints are needed they should be carefully adjusted and checked periodically to prevent excessive constriction.

Medications

IV thiamine (100 mg), followed by dextrose (50 mL of 50% dextrose in water = 25 g dextrose), should be administered. Thiamine is administered first because dextrose administration in thiamine-deficient patients may precipitate Wernicke's encephalopathy. IV naloxone (opiate antagonist), 0.01 mg/kg, should be administered if opiate intoxication is suspected (coma, respiratory depression, small reactive pupils). Naloxone may provoke opiate withdrawal syndrome in addicted patients. Flumazenil (benzodiazepine antagonist), 0.2 mg IV, may reverse benzodiazepine intoxication, but its duration of action is short, and additional doses may be needed. Flumazenil can cause seizures. In delirious patients, sedatives should be avoided if possible, but if necessary low doses of lorazepam (1 mg) or chlordiazepoxide (25 mg) can be used.

Other Nonoperative Therapies

If herniation is identified or suspected, treatment consists of measures to lower intracranial pressure while surgically treatable etiologies are identified or excluded. All of the listed measures are only temporizing methods. Consultation with neurosurgery should be performed concurrently. o Endotracheal intubation is usually performed to enable hyperventilation to a PCO2 of 25 to 30 mm Hg, which reduces intracranial pressure within minutes by cerebral vasoconstriction. Bag-mask ventilation can be performed if manipulation of the neck is precluded by possible or established spinal instability. Reduction of PCO2 below 25 mm Hg is not recommended because it may reduce cerebral blood flow excessively. Administration of mannitol IV, 1 to 2 g/kg over 10 to 20 minutes, osmotically reduces free water in the brain via elimination by the kidneys. This effect peaks at 90 minutes. 5

Dexamethasone, 10 mg IV, followed by 4 mg IV q6h, reduces the edema surrounding a tumor or an abscess. Coagulopathy should be corrected if intracranial hemorrhage is diagnosed and before surgical treatment or invasive procedures (e.g., LP) are performed. Each patient's circumstances should be carefully assessed before therapeutic anticoagulation is reversed.

Surgical Management Surgical evacuation of epidural, subdural, or intraparenchymal (e.g., cerebellar) hemorrhage, shunting for acute hydrocephalus, may be lifesaving, but clinical circumstances dictate the need for, and urgency of, intervention. Some structural lesions are not amenable to surgical treatment. SPECIAL CONSIDERATIONS

Brain death occurs from irreversible brain injury sufficient to permanently eliminate all cortical and brainstem functions. Because the vital centers in the brainstem sustain cardiovascular and respiratory functions, brain death is incompatible with survival despite mechanical ventilation and cardiovascular and nutritional supportive measures. Brain death is distinguished from persistent vegetative state, in which the absence of higher cortical function is accompanied by intact brainstem function. Patients in a persistent vegetative state are unable to think, speak, understand, or meaningfully respond to visual, verbal, or auditory stimuli, yet with nutritional and supportive care their cardiovascular and respiratory functions can sustain viability for many years. o Brain death criteria vary somewhat by institution. Refer to your institution's policy for details. Alcohol withdrawal typically occurs when illness or hospitalization interrupts alcohol intake. o Tremulousness, irritability, anorexia, and nausea characterize minor alcohol withdrawal. Symptoms usually appear within a few hours after reduction or cessation of alcohol consumption and resolve within 48 hours. Treatment includes a well-lit room, reassurance, and the presence of family or friends. Thiamine, 100 mg IM/IV, followed by 100 mg PO daily; multivitamins containing folic acid; and a balanced diet as tolerated should be administered. Chlordiazepoxide (25 to 100 mg PO q6h) with dosage adjusted until the patient is calm may reduce the incidence of seizures and delirium tremens. Serial evaluation for signs of major alcohol withdrawal is essential. o Alcohol withdrawal seizures, typically one or a few brief generalized convulsions, occur 12 to 48 hours after cessation of ethanol intake. Antiepileptic drugs (AEDs) are not indicated for typical alcohol withdrawal seizures. Other causes for seizures (see Seizures) must be excluded. If hypoglycemia is present, thiamine should be administered before glucose. o Severe withdrawal or delirium tremens consists of tremulousness, hallucinations, agitation, confusion, disorientation, and autonomic hyperactivity (fever, tachycardia, diaphoresis), typically occurring 72 to 96 hours after cessation of drinking. Symptoms generally resolve within 3 to 5 days. Delirium tremens complicates 5% to 10% of cases of alcohol 6

withdrawal, with mortality up to 15%. Other causes of delirium must be considered in the differential diagnosis (see Table 1). One should administer supportive management as follows: Chlordiazepoxide is an effective sedative for delirium tremens, 100 mg IV or PO q2-6h as needed (maximum dose, 500 mg in the first 24 hours). One-half the initial 24-hour dose can be administered over the next 24 hours; the dosage can be reduced by 25 to 50 mg/d each day thereafter. Longer-lasting benzodiazepines facilitate smoother tapering, but shorter-acting agents (i.e., lorazepam, 1 to 2 mg PO or IV q6-8h as needed) may be desirable in older patients and those with reduced drug clearance. In patients with severe hepatic failure, oxazepam (15 to 30 mg PO, q6-8h as needed), which is excreted by the kidney, can be used instead of chlordiazepoxide. Maintenance of fluid and electrolyte balance is important. Alcoholic patients are susceptible to hypomagnesemia, hypokalemia, hypoglycemia, and fluid losses, which may be considerable due to fever, diaphoresis, and vomiting.