SUPRATENTORIAL STRUCTURAL LESIONS
Subdural hematoma is a collection of blood in the subdural space between the dura mater and the arachnoid. Because subdural hematoma is resectable, it must always be considered early in any comatose patient with a suspected supratentorial mass lesion. Subdural hematoma is more common in older patients, because cerebral atrophy stretches cortical veins bridging the subdural space, rendering them more susceptible to laceration from shearing injury or spontaneous rupture.
Trauma is the most common cause, and in the acute stage after head injury, focal neurologic deficits are often conspicuous. The severity of injury needed to produce a subdural hematoma becomes less with advancing age; in perhaps 25% of cases no history of trauma is present.
The most common clinical features are headache and altered consciousness, but symptoms and signs may be absent, nonspecific, or nonlocalizing, especially with chronic subdural hematomas that appear months or years after injury (Table 3-5). The classic history of waxing and waning signs and symptoms occurs too infrequently to be relied on for diagnosis. Hemiparesis, when present, is contralateral to the lesion in approximately 70% of cases. Pupillary dilation, when present, is ipsilateral in approximately 90% of cases. The frequency of bilateral hematomas may make clinical localization difficult, as may coexisting cerebral contusion.
Table 3-5.Clinical Features of Subdural Hematoma. ||Download (.pdf) Table 3-5. Clinical Features of Subdural Hematoma.
| ||Acute1 (82 Cases) (%) ||Subacute2 (91 Cases) (%) ||Chronic3 (216 Cases) (%) |
|Symptoms || || || |
|Depressed consciousness ||100 ||88 ||47 |
|Vomiting ||24 ||31 ||30 |
|Weakness ||20 ||19 ||22 |
|Confusion ||12 ||41 ||37 |
|Headache ||11 ||44 ||81 |
|Speech disturbance ||6 ||8 ||6 |
|Seizures ||6 ||3 ||9 |
|Vertigo ||0 ||4 ||5 |
|Visual disturbance ||0 ||0 ||12 |
|Signs || || || |
|Depressed consciousness ||100 ||88 ||59 |
|Pupillary inequality ||57 ||27 ||20 |
|Motor asymmetry ||44 ||37 ||41 |
|Confusion and memory loss ||17 ||21 ||27 |
|Aphasia ||6 ||12 ||11 |
|Papilledema ||1 ||15 ||22 |
|Hemianopia ||0 ||4 ||3 |
|Facial weakness ||0 ||3 ||3 |
Diagnosis is by computed tomography (CT) scan or magnetic resonance imaging (MRI) (Figure 3-6).
(A) Subdural hematoma. Unenhanced CT scan showing a large, high-density crescentic mass over the right cerebral hemisphere, with shift of the lateral ventricles across the midline. (B) Epidural hematoma. Unenhanced CT scan showing a large, high-density lens-shaped mass in the right parietooccipital region. Fracture of the occipital bone was seen on bone windows.
Treatment of subdural hematoma causing coma is by surgical evacuation.
Epidural hematoma typically results from head trauma associated with a lateral skull fracture and tearing of the middle meningeal artery and vein. Patients may or may not lose consciousness initially. There is often a lucid interval of several hours before the onset of coma, during which time headache, vomiting, obtundation, seizures, and focal neurologic signs may occur. The diagnosis is made by CT scan or MRI (see Figure 3-6), which classically shows a hyper intense, biconvex, lens-shaped mass compressing the cerebral hemisphere. Prompt surgical evacuation of the hematoma is essential to prevent a fatal outcome.
Cerebral contusion is bruising of the brain caused by head trauma. It may be associated with initial unconsciousness from which the patient recovers. Edema surrounding the contusion may cause the level of consciousness to fluctuate, and seizures and focal neurologic signs may develop. Patients must be carefully monitored for neurologic deterioration related to progressive edema and herniation.
Lumbar puncture is unnecessary and potentially dangerous. CT scan or MRI are the diagnostic procedures of choice. In contrast to subdural and epidural hematomas, cerebral contusions rarely require surgery.
The most common cause of nontraumatic intracerebral hemorrhage is chronic hypertension. This and other causes are discussed in more detail in Chapter 13, Stroke.
Intracerebral hemorrhage usually occurs while the patient is awake. Hemorrhage is not preceded by transient prodromal symptoms, such as the transient ischemic attacks (TIAs) often associated with cerebral infarction (see Chapter 13, Stroke).
Headache occurs in many cases and can be moderate to severe. If present, headache may be localized to the site of hemorrhage or generalized. Nausea and vomiting are common. Altered consciousness may progress steadily to stupor or coma over minutes to hours.
On examination, patients are nearly always hypertensive (blood pressure 170/90 mm Hg or higher), even in the late stages of transtentorial herniation. The funduscopic examination usually shows vascular changes associated with chronic hypertension. Nuchal rigidity is common. Gaze deviation—toward the side of a putaminal or lobar hemorrhage or downward and medially in thalamic hemorrhage—may occur. Hemiparesis is frequent because of the proximity of common hemorrhage sites, such as the basal ganglia and thalamus, to the internal capsule, which conveys descending motor fibers from the cerebral cortex.
Seizures occur in approximately 10% of cases and are often focal. Neurologic deficits do not fluctuate spontaneously.
CT brain scan without contrast or MRI shows intraparenchymal blood and confirms the diagnosis (see Figure 13-20).
Blood pressure—Systolic blood pressure should be reduced to 140 mm Hg or less to limit hematoma expansion, but excessive blood pressure reduction should be avoided, as it may compromise blood flow in brain tissue adjacent to the hemorrhage.
Cerebral edema—The mass effect of intracerebral hemorrhage is typically compounded by progressive cerebral edema, which becomes evident at approximately 24 hours and maximal within 5 to 6 days. Cerebral edema may be treated with mannitol or intravenous hypertonic saline (Table 3-6), but this is usually only useful as a temporizing measure prior to surgery, when indicated, and alone rarely alters the eventual outcome.
Surgical treatment—Evacuation of the clot may be appropriate in cases (approximately 10%) in which hemorrhage is located superficially in the cerebral hemisphere and produces a mass effect. However, most hemorrhages are deep within the brain and less accessible to surgery.
Table 3-6.Drug Therapy for Cerebral Edema. ||Download (.pdf) Table 3-6. Drug Therapy for Cerebral Edema.
|Drug ||Dose ||Route ||Indications and Comments |
|Dexamethasone ||10-100 mg, then 4 mg 4 times daily ||Intravenous or orally || |
Dexamethasone preferred for lowest mineralocorticoid effect.
Antacid treatment indicated.
Effective for edema associated with brain tumor or abscess; not indicated for intracerebral hemorrhage or infarction.
|Prednisone ||60 mg, then 25 mg 4 times daily ||Orally |
|Methylprednisolone ||60 mg, then 25 mg 4 times daily ||Intravenous or orally |
|Hydrocortisone || |
300 mg, then 130 mg
4 times daily
|Intravenous or orally |
|Osmotic diuretic agents |
|Mannitol ||1.5-2 g/kg over 30 min–1 h ||20% intravenous solution ||Effective acutely. Major dehydrating effect on normal tissue; osmotic effect short-lived, and more than two intravenous doses rarely effective. Hypertonic saline has both osmotic and vasoregulatory effects. |
|Hypertonic saline ||3% continuous infusion or 23.4% or 29.2% by 20 mL bolus ||Intravenously ||Continuous infusion of 3% hypertonic saline to target a serum sodium of 145-155 mEq/L; boluses of hypertonic saline may be more effective than other osmotic agents. |
Early mortality from intracerebral hemorrhage is high, with approximately 25% of patients dying within 72 hours. However, those who survive may be left with surprisingly mild deficits as the clot resolves over a period of weeks to months.
Brain abscess is an uncommon disorder, accounting for only 2% of intracranial masses but occurring more frequently in immunosuppressed patients.
The common conditions predisposing to brain abscess, in approximate order of frequency, are blood-borne metastasis from distant systemic (especially pulmonary) infection, direct extension from parameningeal sites (otitis, cranial osteomyelitis, mastoiditis, sinusitis), an unknown source, infection associated with recent or remote head trauma or craniotomy, and infection associated with cyanotic congenital heart disease.
The most frequently cultured organisms are Streptococcus species (30%), Staphylococcus species (20%) (local rates of methicillin-resistant staph vary widely), and gram-negative enteric bacteria (15%). Abscess formation in neurosurgical or head trauma patients is more likely to be staphylococcal, and abscess from infections promoting contiguous spread (otitis, sinusitis) is more commonly streptococcal. Multiple organisms are present in the majority of abscesses. Patients immunocompromised by HIV coinfection are subject to Toxoplasma gondii and tuberculosis abscess; solid organ or stem cell transplant patients are at risk for fungal brain abscess, mainly Aspergillus and Candida species.
The course is that of an expanding mass lesion, usually presenting with headache and focal neurologic deficits in a conscious patient with a mean symptom duration of approximately one week. Presentation with seizure occurs in 25% of patients. Coma may develop over days and rarely over hours. Common presenting signs and symptoms are shown in Table 3-7. It is important to note that common correlates of infection may be absent: Temperature is normal in 40% of patients, and the peripheral white blood cell count is below 10,000/μL in 20%.
Table 3-7.Brain Abscesses: Presenting Features in 123 Cases. ||Download (.pdf) Table 3-7. Brain Abscesses: Presenting Features in 123 Cases.
|Fever ||58% |
|Headache ||55% |
|Disturbed consciousness ||48% |
|Hemiparesis ||48% |
|Nausea, vomiting ||32% |
|Nuchal rigidity ||29% |
|Dysarthria ||20% |
|Seizures ||19% |
|Sepsis ||17% |
|Visual disturbances ||15% |
The diagnosis is strongly supported by finding a mass lesion with a contrast-enhanced rim on CT scan or MRI or an avascular mass on angiography. Diffusion-weighted MRI differentiates abscess from tumor. A single abscess, most commonly in the frontal or temporal lobe, occurs in 80% of patients. CSF reveals an increased opening pressure in 75% of patients, pleocytosis of 25 to 500 or more white cells/μL (depending on the proximity of the abscess to the ventricular surface and its degree of encapsulation), and elevated protein level (45-500 mg/dL) in approximately 60% of patients. CSF and blood cultures are each positive in a quarter of cases. Marked clinical deterioration may follow lumbar puncture in patients with brain abscess; therefore, lumbar puncture should not be performed if brain abscess is suspected based on other studies.
Treatment of pyogenic brain abscess can be with antibiotics alone or combined with surgical drainage. Surgical therapy should be strongly considered when there is a significant mass effect or the abscess is near the ventricular surface, because catastrophic rupture into the ventricular system may occur.
Medical treatment alone is indicated for surgically inaccessible, multiple, or early abscesses. If the causal organism is unknown, broad-spectrum antibiotic coverage is indicated. The first-line recommendation in North America is a third-generation cephalosporin plus metronidazole. If staphylococcal infection is suspected, vancomycin should be added. Glucocorticoids (see Table 3-6) are commonly used to reduce edema surrounding the abscess. The response to medical treatment should be assessed by clinical examination and serial CT or MRI scans. When medically treated patients do not improve, needle aspiration of the abscess is indicated to identify the organisms present.
STROKE (CEREBRAL INFARCTION)
Embolic or thrombotic occlusion of one carotid artery does not cause coma directly, because bilateral hemispheric lesions are required for consciousness to be lost. However, cerebral edema after massive hemispheric infarction can compress the contralateral hemisphere or cause transtentorial herniation, either of which can produce coma. Edema becomes maximal within 48 to 72 hours after infarction, and may cause progression of the original neurologic deficit and ultimately stupor and coma. Cerebral hemorrhage is excluded by CT scan or MRI.
The use of corticosteroids and dehydrating agents to treat cerebral edema associated with stroke has produced no clear benefit. Stroke is discussed in more detail in Chapter 13, Stroke.
Primary or metastatic brain tumors (see Chapter 6, Headache & Facial Pain) rarely present with coma, although they can do so when hemorrhage into the tumor or tumor-induced seizures occur. More often, coma occurs late in the clinical course of brain tumor, and there is a history of headache, focal neurologic deficits, and altered consciousness. Papilledema is a presenting sign in 25% of cases.
If brain tumor is suspected, a head CT scan or MRI should be obtained. It may or may not be possible to determine the nature of the tumor by its imaging appearance alone; biopsy may be required. Chest X-ray or CT scan is useful, because lung carcinoma is the most common source of intracranial metastasis and because other tumors that metastasize to the brain commonly involve the lungs first.
In contrast to their lack of therapeutic effect on cytotoxic edema resulting from cerebral ischemia, corticosteroids (see Table 3-6) are often remarkably effective in reducing tumor-associated vasogenic brain edema from leaking capillaries with resultant improvement in related neurologic deficits. Specific approaches to the treatment of tumors include excision, radiotherapy, and chemotherapy, depending on the site and nature of the lesion.
SUBTENTORIAL STRUCTURAL LESIONS
BASILAR ARTERY THROMBOSIS OR EMBOLIC OCCLUSION
These relatively common vascular syndromes (discussed in more detail in Chapter 13, Stroke) produce coma by impairing blood flow to the brainstem reticular activating system. Patients are typically middle-aged to elderly and often have a history of hypertension, atherosclerotic vascular disease, or TIAs. Thrombosis usually affects the middle portion, and embolic occlusion the top, of the basilar artery. Virtually all patients present with some alteration of consciousness, and 50% are comatose at presentation. Focal neurologic signs are present from the outset.
Pupillary abnormalities vary with the site of the lesion and include midsized fixed pupils with midbrain involvement and pinpoint pupils with pontine lesions. Vertically skewed deviation of the eyes is common, and horizontal eye movements may be absent or asymmetric during doll’s-head or cold-water caloric testing. Conjugate eye deviation, if present, is directed away from the side of the lesion and toward the hemiparesis (see Figure 7-17). Vertical eye movements may be impaired or intact. Symmetric or asymmetric signs, such as hemiparesis, hyperreflexia, and Babinski responses, may be present. There is no blood in the CSF.
Conventional treatment involves antiplatelet agents or anticoagulation for progressive subtotal basilar artery thrombosis, despite the absence of clear evidence of efficacy for either strategy. The prognosis depends directly on the degree of brainstem injury as represented by depth of decreased consciousness or coma. Eligible patients should be treated with intravenous t-PA. For complete occlusion, endovascular thrombectomy should be considered, and some patients with prolonged symptoms (even beyond 6 hours from onset) may benefit, especially if symptoms have been progressive or fluctuating.
Additional discussion is found in Chapter 13, Stroke.
Pontine hemorrhage occurs almost exclusively in hypertensive patients, but only approximately 6% of hypertensive intracerebral hemorrhages are at this site. The sudden, “apoplectic” onset of coma is the hallmark of this syndrome. Physical examination reveals many of the findings noted in basilar artery infarction, but preceding transient ischemic episodes do not occur. Features especially suggestive of pontine involvement include pinpoint pupils, loss of horizontal eye movements, and ocular bobbing (spontaneous, brisk, periodic, mainly conjugate, downward movements of the eyes, with slower return to the primary position). Hyperthermia, with temperature elevations to 39.5°C (103°F) or more, occurs in most patients who survive for more than a few hours. The diagnosis is made by CT scan or MRI. CSF is grossly bloody and under increased pressure, but lumbar puncture is not indicated. There is no effective treatment. Pontine hemorrhage is considered in greater detail in Chapter 13, Stroke.
CEREBELLAR HEMORRHAGE OR INFARCTION
The clinical presentation of cerebellar hemorrhage or infarction ranges from sudden onset of coma with rapid evolution to death to a syndrome in which headache, dizziness, vomiting, and inability to stand progress to coma over hours or even several days. Acute deterioration may occur without warning; this emphasizes the need for careful observation and early treatment of all patients. CT scan or MRI confirms the diagnosis.
Surgical decompression may produce dramatic reduction of symptoms, and with proper surgical treatment, lethargic or even stuporous patients may survive with minimal or no residual deficits and intact intellect. Current treatment guidelines emphasize surgical hematoma evacuation in potentially salvageable patients, and this includes those in deep coma. Salvageability likely decreases with longer duration of coma.
Additional discussion of these disorders can be found in Chapter 13, Stroke.
POSTERIOR FOSSA SUBDURAL & EPIDURAL HEMATOMAS
These very uncommon lesions have similar clinical pictures and are important to recognize because they are treatable. Occipital trauma typically precedes the onset of brainstem involvement by hours to many weeks. Physical findings result from extra-axial (extrinsic) compression of the brainstem and include ataxia, nystagmus, vertigo, vomiting, and progressive obtundation. Nuchal rigidity may be present, as may papilledema in more chronic cases. CT scans of the skull often reveal a fracture line crossing the transverse or sigmoid sinus. The source of the hematoma is the traumatic tearing of these vessels. Examination of the CSF is not helpful. Treatment is by surgical decompression.
MENINGITIS & ENCEPHALITIS
Meningitis and encephalitis may be manifested by an acute confusional state (Chapter 4) or coma and are characteristically associated with fever and headache. In meningitis, signs of meningeal irritation are also typically present and should be sought meticulously so that lumbar puncture, diagnosis, and treatment can be undertaken promptly. These signs include resistance of the neck to full forward flexion, knee flexion during passive neck flexion, and flexion of the neck or contralateral knee during passive elevation of the extended straight leg (see Figure 1-5). Meningeal signs may be absent in encephalitis without meningeal involvement and in meningitis occurring at the extremes of age, in patients who are deeply comatose, or in those who are immunosuppressed. Findings on neurologic examination are usually symmetric, but focal features may be seen in certain infections, such as herpes simplex encephalitis or bacterial meningitis complicated by vasculitis. CSF findings and treatment are considered in Chapter 4, Confusional States. If signs of meningeal irritation are present, CSF examination should not be delayed in order to obtain a CT scan.
In subarachnoid hemorrhage, discussed in detail in Chapter 6, Headache & Facial Pain, symptoms begin suddenly and almost always include headache, which is typically, but not invariably, severe. Consciousness is frequently lost, either transiently or permanently, at onset. Decerebrate posturing or, rarely, seizures may occur at this time. Other than oculomotor (III) or abducens (VI) nerve palsies, prominent focal neurologic signs are uncommon, although bilateral extensor plantar responses occur frequently. Subarachnoid blood causes meningeal irritation and meningeal signs. Examination of the optic fundi may show acute hemorrhages from suddenly increased intracranial pressure or the more classic superficial subhyaloid hemorrhages (see Figure 6-3). The CSF is bloody and the CT brain scan shows blood in the subarachnoid space (see Figure 6-5).
Hypoglycemic encephalopathy and coma usually result from insulin overdose. Other causes include alcoholism, severe liver disease, oral hypoglycemic agents, insulin-secreting neoplasms (insulinoma), and large retroperitoneal tumors.
As the blood glucose level declines, signs of sympathetic nervous system hyperactivity (tachycardia, sweating, and anxiety) appear and may warn patients of hypoglycemia. These prodromal symptoms may be absent, however, in patients with diabetic autonomic neuropathy. Neurologic findings in hypoglycemia include seizures, focal neurologic signs that may alternate sides, delirium, stupor, and coma. Progressive hypothermia is common.
There is no precise correlation between blood glucose levels and symptoms; thus, a level of 30 mg/dL can be associated with coma in one patient, delirium in a second, and hemiparesis with preserved consciousness in a third. Coma, stupor, and confusion have been reported with blood glucose concentrations of 2 to 28, 8 to 59, and 9 to 60 mg/dL, respectively.
Permanent brain damage from hypoglycemia can be avoided if glucose is rapidly administered intravenously, orally, or by nasogastric tube. Because hypoglycemia is so easily treated and because a delay in treatment can have tragic consequences, every patient presenting with altered consciousness (acute confusional state, coma, or psychosis) should have blood drawn for subsequent glucose determination and immediately receive 50 mL of 50% dextrose intravenously. This allows blood to be analyzed without delaying therapy.
The duration of hypoglycemia that will result in permanent damage to the brain is variable. Hypoglycemic coma may be tolerated for 60 to 90 minutes, but once the stage of flaccidity with hyporeflexia has been reached, glucose must be administered within 15 minutes if recovery is to be expected. If the brain has not been irreparably damaged, full recovery should occur within seconds after intravenous administration of glucose and within 10 to 30 minutes after nasogastric administration. Rapid and complete recovery is the rule, but improvement to full normality may sometimes take hours to several days. Any lingering signs or symptoms suggest irreversible brain damage from hypoglycemia or an additional neuropathologic process.
Global cerebral ischemia produces encephalopathy and coma, which occur most often after cardiac arrest. The pupils dilate rapidly, and there may be tonic, often opisthotonic, posturing with a few seizure-like tonic–clonic movements. Fecal incontinence is common.
If cerebral perfusion is promptly reestablished, recovery can occur and begins at the brainstem level with the return of reflex eye movements and pupillary function. Reflex motor activity (extensor or flexor posturing) then gives way to purposive movements, and consciousness is regained.
Prognosis is related to the rapidity with which brain function returns (Table 3-8). Patients without pupillary reactivity within 1 day—or those who fail to regain consciousness within 4 days—have a poor prognosis.
Table 3-8.Prognostic Signs in Normothermic Coma From Global Cerebral Ischemia. ||Download (.pdf) Table 3-8. Prognostic Signs in Normothermic Coma From Global Cerebral Ischemia.
|Probability of Recovering Independent Function (%) |
| || Time Since Onset of Coma (days) |
|Sign ||0 ||1 ||3 ||7 |
|No verbal response ||13 ||8 ||5 ||6 |
|No eye opening ||11 ||6 ||4 ||0 |
|Unreactive pupils ||0 ||0 ||0 ||0 |
|No spontaneous eye movements ||6 ||5 ||2 ||0 |
|No caloric responses ||5 ||6 ||6 ||0 |
|Extensor posturing ||18 ||0 ||0 ||0 |
|Flexor posturing ||14 ||3 ||0 ||0 |
|Absent motor responses ||4 ||3 ||0 ||0 |
Persistent impairment of brainstem function (unreactive pupils) in adults after the return of cardiac function essentially precludes meaningful recovery. Incomplete recovery may occur, leading to the return of brainstem function and wakefulness (ie, eye opening with sleep–wake cycles) without higher-level intellectual functions. The condition of such patients—awake but not aware—has been termed persistent vegetative state (see later). Although such an outcome is possible after other major brain insults such as trauma, bihemispheric stroke, or subarachnoid hemorrhage, global ischemia is the most common cause.
The advent of therapeutic hypothermia (now termed Targeted Temperature Management [TTM]) to treat patients in coma after resuscitation from cardiac arrest has improved prognosis but has also required a reassessment of the prognostic indicators summarized in Table 3-8 for normothermic patients. Debate exists about whether prognostic assessment at 72 hours after rewarming (therefore 96 hours post-arrest) allows sufficient time for accurate assessment, and many advocate a longer observation period. Loss of pupillary light reflex remains a grave prognostic sign, while motor responsiveness, prognostic in normothermic anoxia 3 days out, is of uncertain significance in hypothermia-treated patients. A combination of brainstem signs, EEG findings, and the results of somatosensory-evoked potential studies is increasingly used for prognostication in many centers.
Sedative drug overdose is the most common cause of coma in many series; barbiturates and benzodiazepines are the prototypical drugs.
Coma is preceded by a period of intoxication marked by prominent nystagmus in all directions of gaze, dysarthria, and ataxia. Shortly after consciousness is lost, the neurologic examination may briefly suggest a structural lesion affecting motor pathways, with hyperreflexia, ankle clonus, extensor plantar responses, and (rarely) decorticate or decerebrate posturing. However, the characteristic feature of sedative-hypnotic overdose is the absence of eye movements on doll’s-head or cold-water caloric testing, with preserved pupillary reactivity. Rarely, concentrations of barbiturates or other sedative drugs sufficient to produce severe hypotension and respiratory depression requiring pressors and ventilatory support can also compromise pupillary reactivity, resulting in pupils 2 to 3 mm in diameter that are nonreactive to light. Bullous skin eruptions and hypothermia are also characteristic of barbiturate-induced coma.
The electroencephalogram (EEG) may be flat—and in overdose with long-acting barbiturates may remain isoelectric for 24 hours or more—yet full recovery will occur with support of cardiopulmonary function.
Treatment should be supportive, centered on maintaining adequate ventilation and circulation. Barbiturates are dialyzable, but with shorter-acting barbiturates, morbidity and mortality rates are lower in more conservatively managed patients. The benzodiazepine-receptor antagonist flumazenil (0.2-0.3 mg intravenously, repeated once, then 0.1-mg intravenous dosing to maximum of 1 mg) can be used to reverse sedative drug intoxication in some cases, but can precipitate status epilepticus by unmasking tricyclic antidepressant–induced seizures in patients with mixed overdose.
Ethanol overdose produces a syndrome similar to that seen with sedative drug overdose, although nystagmus during wakefulness, early impairment of lateral eye movements, and progression to coma are not as common. Peripheral vasodilation is prominent, as are tachycardia, hypotension, and hypothermia. Stupor is typically associated with blood ethanol levels of 250 to 300 mg/dL and coma with levels of 300 to 400 mg/dL, but alcoholic patients who have developed tolerance to the drug may remain awake and even apparently sober with considerably higher levels.
Opioid overdose is characterized by pupillary constriction (which can also be produced by miotic eye drops, pontine hemorrhage, Argyll Robertson pupils, and organophosphate poisoning). The diagnosis of opioid intoxication is confirmed by rapid pupillary dilation and awakening after intravenous administration of 0.4 to 1.2 mg of the opioid antagonist naloxone. The duration of action of naloxone is typically 1 to 4 hours. Repeated doses may therefore be necessary after intoxication with long-acting opioids such as methadone.
Hepatic encephalopathy leading to coma can occur in patients with severe liver disease, especially those with portacaval shunting. Jaundice need not be present. Coma may be precipitated by an acute insult, especially gastrointestinal hemorrhage. The production of ammonia by colonic bacteria may contribute to coma pathogenesis. Neuronal depression may result from multiple pathophysiologic mechanisms: an increase in inhibitory γ-aminobutyric acid-mediated neurotransmission from elevated levels of endogenous benzodiazepine-receptor agonists in the brain, perhaps via neuroinflammation and by way of brain edema in fulminant (acute) hepatic failure. As in other metabolic encephalopathies, the patient presents with either somnolence or delirium. Asterixis may be especially prominent. Muscle tone is often increased, hyperreflexia is common, and alternating hemiparesis and decorticate or decerebrate posturing have been described. Generalized and focal seizures occur but are infrequent. More details are provided in Chapter 4, Confusional States.
A helpful diagnostic clue is the nearly invariable presence of hyperventilation with resultant respiratory alkalosis; however, serum bicarbonate levels are rarely depressed below 16 mEq/L. The CSF is usually normal but may appear yellow (xanthochromic) in patients with serum bilirubin levels greater than 4 to 6 mg/dL. The diagnosis is confirmed by an elevated CSF glutamine concentration. Coma is usually associated with concentrations above 50 mg/dL but may occur with values as low as 35 mg/dL. Hepatic encephalopathy is treated by controlling gastrointestinal bleeding or systemic infection, decreasing protein intake to less than 20 g/d, and decreasing intracolonic pH with lactulose (30 mg orally 2-3 times per day or titrated to produce 2-4 bowel movements daily). Abdominal cramping may occur during the first 48 hours of lactulose treatment. Production of ammonia by colonic bacteria may be reduced with neomycin 6 g/d orally in three or four divided doses. Rifaximin, a nonabsorbable antibiotic, can be used as a lactulose adjunct to attenuate ammonia from colonic bacteria.
Coma with focal seizures is a common presentation of the hyperosmolar state, which is most often associated with nonketotic hyperglycemia. Hyperosmolar nonketotic hyperglycemia is discussed in Chapter 4, Confusional States.
Hyponatremia can cause neurologic symptoms if serum sodium levels fall below 120 mEq/L, especially when the serum sodium level falls rapidly. Delirium and seizures are common presenting features. Hyponatremia is considered in detail in Chapter 4, Confusional States.
All patients with temperatures below 26°C (79°F) are comatose, whereas mild hypothermia (>32.2°C [90°F]) does not cause coma. Causes of coma with hypothermia include hypoglycemia, drug intoxication (sedatives, tricyclics, phenothiazines), Wernicke encephalopathy, hypothyroidism (myxedema), and in the elderly, hypothermia associated with sepsis. Exposure can also produce hypothermia, such as may occur when a structural brain lesion causes acute coma out of doors or in another unheated area; therefore, structural lesions should not be excluded from consideration in the differential diagnosis of coma with hypothermia.
On physical examination, the patient is obviously cold to the touch but may not be shivering (which ceases at temperatures <32.5°C [90.5°F]). Neurologic examination shows the patient to be unresponsive to pain, with diffusely increased muscle tone. Pupillary reactions may be sluggish or even absent.
The ECG may show prolonged PR, QRS, and QT intervals; bradycardia; and characteristic J-point elevation (Osborn waves). Serum creatine kinase may be elevated in the absence of myocardial infarction. Arterial blood gas values and pH must be corrected for temperature, otherwise, falsely high PO2 and PCO2 and falsely low pH values will be reported. EEG shows burst suppression at 22°C (71°F) and is isoelectric at 18-20°C (64-68°F).
Treatment is aimed at the underlying disease responsible for hypothermia and at restoration of normal body temperature. The optimal method and speed of rewarming are controversial, but passive rewarming with blankets in a warm room is an effective and simple treatment. Ventricular fibrillation may occur during rewarming. Because warming produces vasodilation and can lead to hypotension, intravenous fluids may be required.
Most patients who recover from hypothermia do so without neurologic sequelae. Except in myxedema, there is no direct correlation between recorded temperature and survival. Death, when it occurs, is caused by the underlying disease process responsible for hypothermia or by ventricular fibrillation, to which the human myocardium becomes especially susceptible at temperatures less than 30°C (86°F); myocardial sensitivity is maximal below 21 to 24°C (70-75°F).
At body temperatures exceeding 42 to 43°C (107.6-109.4°F), the brain’s metabolic activity cannot meet the increased energy demands, and coma ensues. There is associated multi-organ system immunological and inflammatory involvement. The most common cause of hyperthermia is exposure to elevated environmental temperatures with or without associated exertion (heat stroke). Additional causes include status epilepticus, idiosyncratic reactions to halogenated inhalational anesthetics (malignant hyperthermia) or antipsychotic drugs (neuroleptic malignant syndrome), anticholinergic drugs, hypothalamic damage, and delirium tremens. Patients surviving pontine hemorrhage for more than a few hours have centrally mediated temperature elevations ranging from 38.5 to 42.8°C (101.3-109°F).
The neurologic examination in hyperthermia reveals reactive pupils and a diffuse increase in muscle tone, as well as coma. Tonic/clonic seizures can occur.
Treatment is immediate reduction of body temperature to 39°C (102.2°F) by sponging the patient with ice water and alcohol and using an electric fan or cooling blanket. Care must be taken to prevent overhydration, because cooling results in vasoconstriction that may produce pulmonary edema in volume-expanded patients.
SEIZURE OR PROLONGED POSTICTAL STATE
Status epilepticus should always be considered in the differential diagnosis of coma. Motor activity may be restricted to repetitive movements of part of a single limb or one side of the face. Although these signs of seizure activity can be subtle, they must not escape notice: Status epilepticus requires urgent treatment (see Chapter 12, Seizures & Syncope).
Coma may also be due to a prolonged postictal state, which is also discussed in Chapter 12.
OTHER DIFFUSE ENCEPHALOPATHIES
Rare causes of coma include multifocal disorders that present as metabolic coma because of their diffuse effect upon the brain: disseminated intravascular coagulopathy, sepsis, pancreatitis, vasculitis, thrombotic thrombocytopenic purpura, fat emboli, hypertensive encephalopathy, and diffuse micrometastases.