Neurologic Complications of Hypertension

Keywords

hypertension, stroke, cerebral aneurysm, subarachnoid hemorrhage, intracranial hemorrhage, transient ischemia attack, TIA

Blood pressure was first measured in 1707 by an English divinity student, Stephan Hales, using a glass tube attached directly into the arteries of animals. Methods of measurement improved slowly over the next 200 years, with Nikolai Korotkoff describing the modern cuff-and-stethoscope technique in 1905. Hypertension was recognized as an indicator of poor prognosis by Theodore Janeway, who published a case series of 7,872 hypertensive patients gathered between 1903 and 1912, in which hypertension was defined as a systolic blood pressure greater than 160 mmHg. He found a mean survival of 4 to 5 years after the development of symptoms of hypertension, with stroke being an important cause of death. A tolerable oral agent to treat hypertension was not available until 1957, when chlorothiazide was shown to reduce blood pressure in patients with essential hypertension and rapidly became the most commonly prescribed medication.

Both acute hypertension and chronic hypertension produce neurologic disease. Acute hypertension is associated with hypertensive encephalopathy, an uncommon presentation since the widespread identification and treatment of hypertension. Chronic hypertension is associated with stroke, which is its most important neurologic complication. All stroke subtypes are linked to hypertension, including ischemic infarction, intraparenchymal hemorrhage, and aneurysmal subarachnoid hemorrhage. Chronic hypertension is also associated with dementia.

Epidemiology

Both systolic and diastolic blood pressures are distributed approximately normally in the population. For convenience, physicians have defined pathologic states such as hypertension based on specific blood pressure thresholds, typically a systolic blood pressure of 140 mmHg or greater or a diastolic blood pressure of 90 mmHg or greater, or both. Thus defined, hypertension is common, affecting approximately 78 million adults in the United States. The number of hypertensive adults worldwide is expected to reach 1.54 billion by 2025. In the Framingham study, individuals who were normotensive at age 55 had an approximately 90 percent lifetime risk of developing hypertension.

Despite the frequent division of blood pressure into diagnostic categories such as hypertension and normotension, there is no obvious threshold at which higher blood pressure begins affecting the risk of complications, and even patients with diastolic blood pressures of 80 to 90 mmHg are at increased risk of stroke compared with those with blood pressures of 70 to 80 mmHg ( Fig. 7-1 ). Reflecting a growing awareness of the continuous risk associated with blood pressure, blood pressures in the range of 120–140/80–90 mmHg, once considered to be “normal,” are now labeled as “prehypertensive.”

Pathophysiology

In the brain, the primary pathophysiologic process of hypertension is related to increases in vasomotor tone and peripheral arterial resistance. Acute elevation in blood pressure results in constriction of small arteries in the brain in a compensatory response termed autoregulation. Blood flow to the brain is maintained at a relatively constant level over a range of pressures. At high pressures, vasoconstriction is thought to be protective by reducing pressure at smaller, more distal vessels. Acute severe hypertension overwhelms normal autoregulation at a mean arterial pressure of approximately 150 mmHg, with increased cerebral blood flow occurring above this pressure threshold. Vasoconstriction in acute hypertension is patchy, and some small vessels are exposed to high pressures, which may lead to endothelial injury and focal breakdown of the blood–brain barrier. Acute hypertensive encephalopathy is a fulminant presentation of this process. Fibrinoid necrosis of small vessels may also occur, lowering the threshold for future ischemic and hemorrhagic events.

Chronic hypertension results in cerebral vascular remodeling. The media hypertrophies, and the lumen becomes narrowed. These changes are protective, with reduction in wall tension and shifting of the autoregulation curve to allow compensation at higher blood pressures. However, vascular remodeling is accompanied by endothelial dysfunction, with impaired relaxation and poor compensation for hypoperfusion. The result is greater susceptibility to ischemic injury due to reduced collateral flow.

Hypertension also predisposes to atherosclerosis. Hypertension is proinflammatory and is accompanied by increased plasma oxygen free radicals. Free radicals induce vascular smooth muscle cell proliferation and may oxidize low-density lipoproteins, which in turn promotes macrophage activation and monocyte extravasation. Angiotensin II is elevated in many hypertensive patients and may play a direct role in atherogenesis independent of its effects on blood pressure. It directly stimulates smooth muscle cell growth, hypertrophy, and lipoxygenase activity, with resultant inflammation and low-density lipoprotein oxidation, thus accelerating atherosclerosis.

Evaluation and Treatment

The gold standard of blood pressure measurement is auscultation using a mercury sphygmomanometer. Newer devices can provide accurate readings but require calibration. Blood pressure should be measured in the seated position after a 5-minute rest with the patient’s feet resting on the floor and the arm supported at heart level during the measurement. Accurate readings depend on the use of an appropriate-sized cuff with the bladder covering at least 80 percent of the arm. The classification of blood pressure into specific diagnostic categories is based on the average of two or more readings on each of two or more office visits. A complete history and physical examination with basic laboratory measurements are essential to evaluate for identifiable causes of hypertension and assess risk. Several patient characteristics may suggest an identifiable cause of hypertension including young age, severe hypertension, hypertension that is refractory to multiple interventions, and physical or laboratory findings suggestive of endocrinologic disorders, such as truncal obesity or hypokalemia. Abdominal bruits or decreased femoral pulses may also be an indicator of renovascular disease or coarctation of the aorta.

Lifestyle modification is recommended as an initial therapy for patients with blood pressure of 120/80 mmHg or higher. Effective lifestyle interventions include weight loss, limited alcohol intake, aerobic physical activity, adequate potassium intake, reduction in sodium intake, and dietary regimens such as the Dietary Approaches to Stop Hypertension (DASH) eating plan. Antihypertensive medications are recommended in addition to lifestyle measures for patients with blood pressure of 140/90 mmHg or higher, with a lower threshold of 130/80 mmHg or higher in those with diabetes and chronic kidney disease.

For patients without a history of cardiovascular disease or other compelling indication, initiating therapy with a thiazide diuretic such as chlorthalidone is generally recommended. In a trial involving more than 33,000 participants, therapy with chlorthalidone was either equivalent or superior to lisinopril and amlodipine for the primary prevention of cardiovascular end-points, with a particular benefit for African Americans in terms of both safety and efficacy. When the blood pressure is 160/100 mmHg or higher, initiating therapy with two-drug combinations is generally recommended.

There are many benefits to treating hypertension, including a reduction in myocardial infarctions, congestive heart failure, retinopathy, renal failure, and overall mortality. The focus of the remainder of this chapter is on specific neurologic complications of hypertension and the unique aspects of treatment that they necessitate.

Stroke

Of all the identified modifiable risk factors for stroke, hypertension appears to be the most important, owing to its high prevalence and its associated three- to fivefold increase in stroke risk. Based on epidemiologic data, approximately 50 percent of strokes could be prevented if hypertension were eliminated ( Table 7-1 ). Even small reductions in blood pressure result in large reductions in stroke risk. For example, in a meta-analysis of 37,000 hypertensive subjects from 14 studies, a reduction of 5 to 6 mmHg in diastolic blood pressure with active treatment was associated with a 42 percent reduction in stroke risk. The benefits of blood pressure reduction on stroke risk extend similarly to the elderly with isolated elevations in systolic blood pressure. In one trial of 4,736 subjects aged 60 years or more, a 36 percent reduction in stroke was seen with a 12-mmHg decline in systolic pressure, a finding confirmed in other large randomized trials. The best available data suggest that benefits of treating blood pressure in the oldest old (>85 years) are comparable to those seen in younger individuals.

Table 7-1

Estimated Impact of Modifiable Risk Factors on Stroke in the United States *

Adapted from Gorelick PB: Stroke prevention: an opportunity for efficient utilization of health care resources during the coming decade. Stroke 25:220, 1994.

Risk Factor	Percentage Exposed	Relative Risk	Population- Attributable Risk (%)	Projected Number of Strokes Preventable
Hypertension	56	2.7	49	370,000
Cigarette smoking	27	1.5	12	92,000
Atrial fibrillation	4	3.6	9	71,000
Heavy alcohol consumption	7	1.7	5	35,000

* Relative risks are from the Framingham study. Population-attributable risk is the expected decrease in stroke rates if the risk factor were eliminated. Projected number of strokes preventable is based on an estimated 750,000 strokes per year.

The burden of stroke has generally declined in the developed world. Although these historic trends are not entirely explained by better control of blood pressure, the rates of decline have roughly paralleled the increased use of antihypertensive medications. However, hypertension remains the leading risk factor for death globally, and the developing world continues to bear a disproportionate, substantial, and increasing burden of disease from stroke ( Fig. 7-2 ).

Hypertension contributes to each of the major intermediate causes of both ischemic and hemorrhagic stroke including carotid stenosis, intracranial atherosclerosis, small-vessel arteriosclerosis, and both macroscopic and microscopic aneurysms. Each of these conditions is considered separately in this chapter.

In the acute phase of cerebral ischemia, hypertension may play a compensatory role in maintaining cerebral perfusion to viable but threatened areas of the brain. Loss of normal cerebral autoregulation has been demonstrated in areas of ischemic brain. When autoregulation is lost, blood flow to the brain becomes directly proportional to mean arterial pressure and therefore, in theory, pharmacologic increases in blood pressure could have salutatory effects in preserving hypoperfused regions of the brain. In some small studies, rapid pharmacologic reductions in blood pressure have predicted worse outcomes, and there are numerous anecdotal reports of the recrudescence of stroke symptoms after a decrease in blood pressure. Therefore, most stroke guidelines recommend withholding or reducing pharmacologic treatments of blood pressure in acute ischemic stroke in the absence of acute end-organ injury or administration of thrombolytics, unless the blood pressure exceeds 220/120 mmHg.

There is overwhelming evidence to support the use of pharmacologic interventions to lower blood pressure for secondary stroke prevention. In 6,105 subjects with a history of stroke, one study demonstrated a 43 percent relative risk reduction for secondary stroke prevention when subjects were randomized to the combination of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the thiazide diuretic indapamide. Combination therapy with the ACE inhibitor and thiazide, which resulted in a mean blood pressure reduction of 12.3/5 mmHg, produced a substantially more robust benefit for stroke prevention than monotherapy with ramipril (relative risk reduction, 5%), which produced only a 4.9/2.8-mmHg average reduction in blood pressure ( P for heterogeneity between treatments<0.001). Combination therapy with an ACE inhibitor and a thiazide diuretic is now commonly recommended for secondary stroke prevention, with benefits appearing to be similar regardless of whether measured blood pressure is above or below the traditional cut points for hypertension. Although other studies have supported the finding that therapy with renin-angiotensin system antagonists and diuretics provides especially strong benefits for stroke prevention, particularly when compared with β-blockers, the degree of hypertension control that is achieved is usually the best predictor of protection against recurrent stroke. Therefore, response to therapy and other comorbidities, such as heart failure, diabetes, asthma, and arrhythmia, should be considered when deciding on an appropriate antihypertensive drug regimen. The Scandinavian Acute Stroke Trial (SCAST) of 2,029 patients suggested no benefit (hazard ratio for vascular death, MI, or stroke=1.09) and possible harm (adjusted hazard ratio for 6-month functional outcome=1.17) with acute blood pressure lowering with candesartan for 7 days after stroke, though starting antihypertensive therapy before hospital discharge may improve initial patient adherence.

Cerebral Aneurysms

Cerebral aneurysms are focal dilatations of blood vessels. Subarachnoid hemorrhage, an important form of hemorrhagic stroke, occurs when a cerebral aneurysm ruptures ( Fig. 7-3 ). Hypertension is associated with cerebral aneurysm formation and with subarachnoid hemorrhage. In a large sample of Medicare patients, hypertension was listed as a secondary diagnosis in 43 percent of patients admitted with unruptured aneurysms and in 34 percent of hospitalized control subjects. In a meta-analysis, the risk of subarachnoid hemorrhage was 2.8 times greater in those with a history of hypertension.

The cause of the development and rupture of cerebral aneurysms is probably multifactorial. Epidemiologic studies have found several environmental risk factors for subarachnoid hemorrhage other than hypertension. Cigarette smoking increases the risk of subarachnoid hemorrhage by 100 percent or more, perhaps by increasing the release of proteolytic enzymes that affect blood-vessel integrity. Heavy alcohol consumption increases subarachnoid hemorrhage risk with a pooled odds ratio of 1.5 in case control studies and a relative risk of 4.7 in cohort studies. Alcohol-induced hypertension, relative anticoagulation, or increased cerebral blood flow may be responsible. Oral contraceptives are associated with a small but significant excess risk of subarachnoid hemorrhage, with a relative risk of 1.4 in current and past users.

Genetic factors are also important to aneurysm formation and subarachnoid hemorrhage. The risk of subarachnoid hemorrhage is three to seven times greater in patients with an affected first-degree relative, and the prevalence of unruptured aneurysms is probably at least twice as high when a family history of aneurysm is present. Females are nearly twice as likely as males to have an aneurysm or to present with subarachnoid hemorrhage. African Americans have twice the rate of subarachnoid hemorrhage as whites. Polycystic kidney disease, Ehlers–Danlos syndrome type 4, and α ₁-antitrypsin deficiency are also associated with increased risk.

Unruptured Cerebral Aneurysms

Estimates of the prevalence of unruptured aneurysms vary widely. A meta-analysis of 68 studies estimated that overall prevalence would be 3.2 percent in a population without comorbidities, with a mean age of 50 years, and consisting of 50 percent males. In a prior meta-analysis, approximately 90 percent of aneurysms were less than 10 mm in diameter, and 70 percent were less than 6 mm. Based on these estimates, 11 million American adults have an unruptured aneurysm. These aneurysms are being detected more frequently as imaging technology improves and as imaging studies are applied more frequently. The annual cost for unruptured aneurysms in the United States was estimated at $522 million in the 1980s and is significantly greater now.

Unruptured aneurysms are often asymptomatic, discovered incidentally in the work-up for an unrelated problem. Some aneurysms produce symptoms by compressing neighboring structures. Presentation with a new cranial neuropathy is considered a worrisome sign of imminent rupture and often prompts urgent treatment. New headaches are also a presenting sign of unruptured aneurysm. Although migraine may simply represent an unrelated occurrence that prompts head imaging, some headaches may be due to the aneurysm itself. A sudden, severe “thunderclap” headache may herald rapid aneurysm growth or a small leak without evidence of subarachnoid hemorrhage.

Catheter angiography remains the gold standard for detection of aneurysms. Magnetic resonance (MR) angiography is approximately 85 percent sensitive for detecting aneurysms larger than 3 mm, with 85 percent specificity. Head computed tomography (CT) does not reliably detect unruptured aneurysms, though CT angiography may be useful to identify certain aneurysms, particularly those that are larger than 3 mm.

Prognosis of unruptured aneurysms, as reflected in the rate of rupture, is a subject of controversy. In the largest prospective cohort study, 1,692 subjects with unruptured aneurysms who did not undergo surgery or endovascular treatment were followed prospectively for an average of 4.1 years. The size of the aneurysm (≥7 mm in maximum diameter) and location at the basilar tip or posterior communicating artery were independent predictors of hemorrhage. Among 1,077 subjects with no history of subarachnoid hemorrhage, the annual risk of hemorrhage for an aneurysm less than 7 mm in diameter in the anterior circulation was essentially 0 percent; it was 0.5 percent when the aneurysm was located in the posterior circulation.

The standard of care for treatment of aneurysms has historically been surgical clipping, in which a metal clip is placed over the neck of the aneurysm, isolating it from the circulation. Coil embolization is an alternative therapy that involves packing platinum coils into an aneurysm through a microcatheter in an angiographic endovascular procedure. This approach has been widely applied and appears to be a generally safer approach when technically feasible.

Whether a given aneurysm requires treatment depends on the anticipated rupture rate and procedural risks. For asymptomatic aneurysms smaller than 7 mm with no history of subarachnoid hemorrhage, treatment may not be justified, particularly when in the anterior circulation, given the risks of surgery and endovascular therapy. Treatment of unruptured aneurysms appears to be cost-effective when they are larger or symptomatic or when there is a history of subarachnoid hemorrhage from a different aneurysm.

Controlling or eliminating risk factors, such as hypertension, smoking, and alcohol abuse, may reduce rupture rates, but this has not been systematically studied.

Subarachnoid Hemorrhage

Subarachnoid hemorrhage accounts for approximately 5 percent of all strokes, but it tends to occur at a younger age than other stroke subtypes, with median age at death being 59 years for subarachnoid hemorrhage, 73 years for intracerebral hemorrhage, and 81 years for ischemic stroke. Subarachnoid hemorrhage accounts for nearly one-third of the years of potential life lost before age 65 due to stroke. Case fatality rates approach 50 percent, and another 10 to 20 percent remain disabled and dependent at follow-up. Approximately 30,000 Americans present with subarachnoid hemorrhage each year, with total costs estimated at well over $5.6 billion.

Presentation with subarachnoid hemorrhage generally involves the sudden onset of severe headache, sometimes accompanied by neck pain. Alteration of consciousness occurs in a minority of patients, but it may be severe enough to produce coma or sudden death outside the hospital. Head CT often shows blood surrounding the base of the brain. Intraventricular and intraparenchymal hemorrhage may be present and can provide clues as to the location of the ruptured aneurysm. Lumbar puncture may rarely show signs of hemorrhage when there is no evidence of it on head CT. Blood in the spinal fluid that does not clear is suggestive of subarachnoid hemorrhage. Xanthochromia is present in nearly all cases and may persist for more than 3 weeks, but its appearance is delayed by more than 12 hours in 10 percent of cases. Angiography is required for the characterization of the aneurysm and to plan treatment.

Prognosis depends on the ability to treat the underlying aneurysm and on the patient’s condition at presentation. Recurrent hemorrhage occurs in more than 4 percent of untreated patients during the first day and then in 1 to 2 percent per day for the next 2 weeks and is associated with even greater fatality and morbidity than primary rupture. Regardless of treatment and recurrent hemorrhage, the level of consciousness at presentation is the major predictor of mortality ( Table 7-2 ). The World Federation of Neurological Surgeons developed a Universal Subarachnoid Hemorrhage Grading Scale, similar to the older Hunt and Hess scale, which has been widely adopted but offers little advantage over determinations based on level of consciousness alone.

Table 7-2

Overall Outcome after Subarachnoid Hemorrhage by Consciousness Level on Admission *

From Kassell NF, Torner JC, Haley EC, et al: The International Cooperative Study on the timing of aneurysm surgery. J Neurosurg 73:18, 1990, with permission.

Consciousness Level	Good Recovery		Moderately Disabled		Severely Disabled		Vegetative Survival		Dead		Totals
Consciousness Level	Number	Percent	Number	Percent	Number	Percent	Number	Percent	Number	Percent	Number	Percent
Alert	1,279	74.3	130	7.5	70	4.1	18	1.0	225	13.1	1,722	100.0
Drowsy	608	53.5	125	11.0	71	6.3	19	1.7	313	27.6	1,136	100.0
Stuporous	105	30.2	48	13.8	28	8.0	15	4.3	152	43.7	348	100.0
Comatose	35	11.1	17	5.4	25	7.9	11	3.5	227	72.1	315	100.0
Totals	2,027	57.6	320	9.1	194	5.5	63	1.8	917	26.0	3,521	100.0

* Percentages are of row totals. Relationship between admission level of consciousness and outcome: χ ²=720.5; P <0.001.

To reduce the risk of recurrent hemorrhage, ruptured aneurysms should be identified rapidly and repaired with surgical clipping or endovascular coil embolization as early as feasible. Hydrocephalus from obstruction of the cerebral aqueduct or the meninges by blood clot may require external drainage. Vasospasm is a common complication that produces cerebral ischemia due to blood-vessel constriction in areas exposed to subarachnoid blood. It becomes symptomatic in one-third of cases, usually 3 to 14 days after hemorrhage, and results in cerebral infarction or death in 15 to 20 percent. Transcranial Doppler ultrasonography can detect vasospasm before it becomes symptomatic. Oral nimodipine, a calcium-channel antagonist, reduces poor outcomes from vasospasm and is generally given for the first 21 days after the initial bleed. Hypertension induced with pressors and hydration with intravenous fluids may reduce the risk of infarction, but these measures have never been studied in trials. They should not be used in patients with untreated aneurysms because of the risk of precipitating further episodes of bleeding. Vasodilatation through angioplasty or intra-arterial verapamil (or other vasodilators) immediately reverses angiographic vasospasm in many cases, but clinical benefits have not been definitely demonstrated.

Intracerebral Hemorrhage

Bleeding directly into the substance of the brain is termed intraparenchymal or intracerebral hemorrhage ( Fig. 7-4 ). It may occur as a complication of ischemic stroke, termed hemorrhagic conversion , or as the primary injury without preceding ischemia. Hypertension is the most important identified risk factor for intracerebral hemorrhage. More than 70 percent of patients with intracerebral hemorrhage have a history of hypertension, and the risk of hemorrhagic stroke is elevated 9.5-fold in the highest compared with the lowest quintile of systolic blood pressure.

Intracranial hemorrhage is responsible for 10 to 15 percent of all stroke deaths but for more than one-third of the years of life lost before age 65 due to the younger age distribution of intra- cerebral hemorrhage. Case fatality rates are high, with 35 to 50 percent dead at 1 month and only 20 percent returning to independence at 6 months. In the United States, an estimated 37,000 cases of intracerebral hemorrhage occur each year, with the total estimated cost of care exceeding $6 billion annually.

Other risk factors for intracerebral hemorrhage include age, race, substance abuse, anticoagulation, platelet dysfunction, and vascular and structural anomalies. Rates of intracerebral hemorrhage increase with age. African Americans have rates that are 40 percent higher than those of whites, with larger differences at younger ages. Cocaine and amphetamine use is associated with increased risk, particularly acutely, possibly because of transient severe hypertension. Abnormalities in clotting may account for an increased incidence of intracerebral hemorrhage with heavy alcohol use. Excessive anticoagulation and antiplatelet therapy also increase the risk of intracerebral hemorrhage. Thrombolytic agents used for ischemic stroke and myocardial infarction cause intracerebral hemorrhage in some cases. It may also occur with severe thrombocytopenia and platelet dysfunction.

Intracerebral hemorrhage may result from and occur in brain tumors, such as glioblastoma multiforme and in metastatic melanoma, choriocarcinoma, renal cell carcinoma, and bronchogenic carcinoma. Cerebral amyloid angiopathy, a vasculopathy common in the elderly, is associated with lobar hemorrhages, often centered at the gray-white junction. Other punctate hemorrhages may be apparent on gradient-echo MR images ( Fig. 7-5 ), supporting the diagnosis. Arteriovenous malformations, abnormal complexes of arteries and veins in brain parenchyma, account for 5 percent of intracerebral hemorrhages. Cavernous malformations are dense collections of thin-walled vascular channels and appear to be the cause of intracerebral hemorrhage in 5 percent of autopsies ; they are not apparent on angiography but have a “popcorn” appearance on MR images, with a hyperintense core surrounded by hypointense hemosiderin from previous small hemorrhages ( Fig. 7-6 ). Aneurysms may produce intracerebral hemorrhages when blood is directed into the brain, and these rarely are mistaken for primary hypertensive hemorrhages.

Primary hypertensive intracerebral hemorrhage was thought to be caused by chronic vascular injury, resulting in formation of microscopic aneurysms, first characterized by Charcot and Bouchard in 1868. Advances in pathologic tissue preparation have raised doubts about the frequency and importance of microscopic aneurysms, which may actually represent complex vascular coils. More recently, fibrinoid necrosis of small arteries has been proposed as the initial step in intracerebral hemorrhage. Brain injury occurs because of compression of surrounding tissue and from the direct toxic effects of blood. Mass effect from the hematoma may lead to uncal, subfalcine, tonsillar, or transtentorial herniation, depending on location, and death may ensue.

Clinical presentation depends on the location and size of the hemorrhage ( Table 7-3 ). Nearly all intracerebral hemorrhage is characterized by the sudden onset of neurologic deficits, progressing over minutes and accompanied by headache, often with alteration of consciousness. Deterioration due to surrounding edema, hydrocephalus, or continuing or recurrent hemorrhage often occurs within the first 24 hours but may be delayed by days.

Table 7-3

Clinical Presentation of Intracerebral Hemorrhage

Adapted from Thrift AG, Donnan GA, McNeil JJ: Epidemiology of intracerebral hemorrhage. Epidemiol Rev 17:361, 1995.

Location	Occurrence	Clinical Signs	Nonhypertensive	Mortality
Putamen	28–42%	Motor and sensory deficit; depressed consciousness	10%	20%
Thalamus	10–26%	Sensory and motor deficit; depressed consciousness; homonymous hemianopia	10%	40%
Subcortical white matter (lobar)	19–30%	Higher incidence of seizures; coma unlikely; other symptoms depend on involved lobe	65%	20%
Cerebellum	8–15%	Ataxia, cranial neuropathies;±depressed consciousness	15%	Coma 75% Other 17%
Brainstem	4–11%	Coma, decerebrate posturing, pinpoint reactive pupils, cranial neuropathies	30%	85%

Prognosis is multifactorial. Hemorrhage volume, most easily measured by halving the product of the length, width, and depth on axial head CT images, is a powerful predictor of mortality, with 80 percent 30-day mortality in those with volumes greater than 60 ml, and 22 percent mortality in hemorrhages less than 30 ml. Mortality is much greater in those with intraventricular extension of blood. Hydrocephalus due to intraventricular extension or cerebrospinal fluid (CSF) outflow obstruction predicts in-hospital mortality: 51 percent of those with and 2 percent of those without hydrocephalus died in one series. Lower Glasgow Coma Scale scores, greater age, location, and blood pressure or pulse pressure are other independent predictors of mortality. Simple multivariable prediction models have been developed and validated.

Urgent head CT is required in patients with suspected intracerebral hemorrhage. MRI is as sensitive as CT for detecting hemorrhage and is more sensitive for detecting an underlying structural etiology, but the rapidity, availability, and ease of interpretation of CT favor its initial use. Contrast-enhanced head CT scan may show evidence of persistent hemorrhage at the time of presentation, a sign associated with poor prognosis. Vascular imaging is required whenever aneurysmal subarachnoid hemorrhage is possible, such as in cases with a large amount of subarachnoid blood, and should be considered for all patients without a clear etiology who would be surgical candidates. Early MRI may be indicated if a structural etiology is suspected, but findings are often obscured by the hemorrhage, and a scan delayed by 4 to 8 weeks may provide more useful information if urgent diagnosis is unnecessary. MRI is useful in diagnosing cavernous malformations and may suggest cerebral amyloid angiopathy.

Treatment is generally supportive, although surgical intervention is indicated in some cases. Severe hypertension is common after intracerebral hemorrhage, in part because it is a response to elevated intracranial pressure and brain injury. In patients with a systolic blood pressure of 150 to 220 mmHg, acute lowering of systolic blood pressure to 140 mmHg is probably safe. Current consensus guidelines suggest treating with antihypertensive medications for systolic blood pressure greater than 180 mmHg or mean arterial pressure greater than 130 mmHg, though clinical trials to determine optimal blood pressure control after intracerebral hemorrhage are ongoing. Increased intracranial pressure may lead to coma and is treated with extraventricular drainage, osmotherapy, or hyperventilation.

Surgical evacuation of primary intracerebral hemorrhages is commonly performed when there is posterior fossa hemorrhage with a risk of brainstem compression or when there is evolving neurologic deterioration in patients with lobar hemorrhages and other prognostic signs are favorable. A large, international trial randomized 1,033 subjects with supratentorial hemorrhage to receive early surgical evacuation of the hematoma or initial conservative treatment followed by surgical evacuation only if it was necessitated by neurologic deterioration. There was a favorable outcome at 6 months in 26 percent of those allocated to early surgery as compared with 24 percent in those allocated to initial conservative treatment ( P =0.89). In subgroup analysis, it appeared that early surgery was more effective than conservative therapy when the hematoma was 1 cm or less from the cortical surface. Additional trials will be needed to resolve the issue of early surgical benefit for superficial hematomas.

After the acute period, aggressive treatment of hypertension is indicated. In addition to reducing cardiovascular disease and ischemic stroke, one study has shown that treating hypertension reduces the risk of intracerebral hemorrhage by more than 50 percent.

Lacunar Infarct

The term lacune was first introduced in 1843 by M. Durand-Fardel to describe small, subcortical areas lacking gray and white matter. These lesions were attributed to infarct and associated with particular clinical presentations by Marie and Ferrand more than 50 years later. In the 1950s, Miller Fisher reintroduced the term into modern neurology. In a rapid succession of articles, he described the clinical and pathologic presentation, recognized the importance of hypertension as an etiology, and developed a theory of pathogenesis that survives today.

Less than 2 cm in diameter, lacunes are small infarcts that result from occlusion of small penetrating branches arising from large arteries ( Fig. 7-7 ). There is general agreement about the definition of lacune, but much argument about the interrelationship between lacunar infarcts, lacunar strokes (symptomatic lacunes), lacunar syndromes (symptom complexes often associated with lacunar strokes), and lacunar disease (lacunes due to intrinsic small-vessel changes). Arguments arise from imperfect correlations between these entities. First, not all lacunes produce lacunar strokes because some are silent. Second, lacunar syndromes are sometimes associated with large-vessel strokes. Third, lacunes are produced by intrinsic small-vessel disease and by other etiologies.