Sudden onset of a new headache may be a symptom of serious intracranial or systemic disease; it must be investigated promptly and thoroughly.
Spontaneous (nontraumatic) subarachnoid hemorrhage (bleeding into the subarachnoid space) is usually the result of a ruptured cerebral arterial aneurysm or an AVM.
Rupture of a saccular (berry) aneurysm accounts for approximately 75% of cases of subarachnoid hemorrhage, with an annual incidence of 6 per 100,000. Most arise sporadically, but some are familial. Families with two or more affected persons should have all members screened. Both autosomal and recessive patterns of inheritance occur.
Rupture occurs most often during the fifth and sixth decades; sex distribution is approximately equal. The risk of rupture of an intracranial aneurysm varies with the patient’s age and the site and size of the aneurysm; approximately 5% of autopsied individuals have cerebral aneurysms, and most have never experienced symptoms. Hypertension has not been conclusively demonstrated to predispose to the development of aneurysms, but acute elevation of blood pressure (eg, at orgasm) may be responsible for aneurysm rupture.
Fusiform aneurysms result from circumferential dilation of a cerebral arterial trunk. In contrast to saccular aneurysms, they are thought to be caused by atherosclerosis or dissection, affect the vertebrobasilar system preferentially, and can present with symptoms of ischemia or mass effect, in addition to rupture.
Intracranial AVMs, a less frequent cause of subarachnoid hemorrhage (10%), occur twice as often in men as in women, and usually bleed in the second to fourth decades, although a significant incidence extends into the sixties. Blood in the subarachnoid space can also result from intracerebral hemorrhage, embolic stroke, and trauma.
Cerebral arterial aneurysms are usually congenital and result from developmental weakness of the vessel wall, especially at sites of branching. They typically arise from intracranial arteries about the circle of Willis at the base of the brain (Figure 6-4), occur in 2% of patients, and are multiple in approximately 20% of cases. Other congenital abnormalities, such as polycystic kidney disease or coarctation of the aorta, may be associated with berry aneurysms.
Frequency distribution of intracranial aneurysms.
Occasionally, systemic infections such as infective endocarditis disseminate to a cerebral artery and cause aneurysm formation; such mycotic aneurysms account for 2% to 3% of aneurysmal ruptures. Mycotic aneurysms are usually more distal along the course of cerebral arteries than are berry aneurysms.
AVMs consist of abnormal vascular communications that permit arterial blood to enter the venous system without passing through a capillary bed. They are most common in the middle cerebral artery distribution.
Rupture of an intracranial artery elevates intracranial pressure and distorts pain-sensitive structures, producing headache. Intracranial pressure may reach systemic perfusion pressure and acutely decrease cerebral blood flow; together with the concussive effect of the rupture, this is thought to cause the loss of consciousness that occurs at the onset in approximately 50% of patients. Rapid elevation of intracranial pressure can also produce subhyaloid retinal hemorrhages (see Figure 6-3).
The classic (but not invariable) presentation of subarachnoid hemorrhage is with the sudden onset of an unusually severe generalized headache, classically described as the worst headache the patient has ever experienced. However, among patients presenting with the abrupt onset of an unusually severe headache, only 8% to 10% will have subarachnoid hemorrhage (see also reversible cerebral vasoconstriction syndrome characterized by recurrent thunderclap headache in Chapter 13). Abrupt onset to maximal intensity is the essential feature of subarachnoid hemorrhage headache. The absence of headache essentially excludes the diagnosis. One-third of patients present with headache alone. In the remainder, loss of consciousness is frequent at onset, as are vomiting and neck stiffness. Symptoms may begin at any time of day and during either rest or exertion.
The most significant feature of the headache is that it is new. Milder but otherwise similar headache (sentinel headache) may have occurred in the weeks prior to the acute event and probably represent small prodromal hemorrhages or aneurysmal stretch.
The headache is not always severe, especially if hemorrhage is from a ruptured AVM rather than an aneurysm. Although the duration of the hemorrhage is brief, the intensity of the headache may remain unchanged for several days and may subside slowly over approximately 2 weeks. Recurrence of the headache usually signifies rebleeding.
Blood pressure frequently rises precipitously as a result of the hemorrhage. Meningeal irritation may induce temperature elevations up to 39°C (102.2°F) during the first 2 weeks. There is frequently associated confusion, stupor, or coma. Nuchal rigidity and other evidence of meningeal irritation (see Figure 1-5) are common, but may not occur for several hours after the onset of headache. Preretinal globular subhyaloid hemorrhages (found in 20%-40% of cases; see Figure 6-3) are most suggestive of the diagnosis.
With aneurysmal rupture, bleeding occurs mainly in the subarachnoid space rather than within brain parenchyma. Therefore, prominent focal neurologic signs are uncommon, and even when present, they may bear no relationship to the site of the aneurysm. An exception is oculomotor (III) nerve palsy from compression of the nerve ipsilateral to a posterior communicating artery aneurysm. Bilateral extensor plantar responses and abducens (VI) nerve palsy are frequent nonlocalizing signs that result from increased intracranial pressure.
Ruptured AVMs tend to occur within brain tissue and accordingly produce focal neurologic signs, such as hemiparesis, aphasia, or visual field defects.
Patients presenting with subarachnoid hemorrhage are investigated first by computed tomography (CT) scanning (Figure 6-5), which confirms the hemorrhage in more than 90% of patients with aneurysmal rupture and can help identify a focal source. The test is most sensitive in the first six hours after bleeding occurs, when sensitivity approaches 100%. Complications, including intracerebral or intraventricular extension of blood, hydrocephalus, and infarction, can also be identified. Aneurysms themselves may not be evident on CT, but most AVMs can be seen after administration of contrast material. Magnetic resonance imaging (MRI) is especially useful for detecting small AVMs in the brainstem, which are poorly seen on CT scan.
(A) Nonenhanced brain CT scan from a patient with an acute aneurysmal subarachnoid hemorrhage. Areas of high density (arrows) represent blood in the subarachnoid space at the base of the brain (most aneurysms occur in this region about the circle of Willis; see Figure 6-4). (Used with permission from H. Yonas.) (B) A normal nonenhanced brain CT scan of the same region. Interpeduncular cistern, large arrow; suprasellar cistern, small arrow. (Used with permission from C. Jungreis.)
In patients with a normal neurologic examination, a normal CT scan within 6 hours of symptom onset is held by many authorities to exclude subarachnoid hemorrhage. CT scans that are technically inadequate or delayed, or that otherwise fail to confirm the diagnosis of subarachnoid hemorrhage, necessitate lumbar puncture (see Chapter 2, Investigative Studies). The CSF in subarachnoid hemorrhage usually has a markedly elevated opening pressure and is grossly bloody, containing 100,000 to >1 million/μL red blood cells. As heme from these cells is degraded, first (by heme oxygenase) to the green pigment, biliverdin, and then (by biliverdin reductase) to the yellow pigment, bilirubin, the supernatant of the centrifuged CSF becomes yellow-tinged (xanthochromic) within 12 hours after hemorrhage. The pigment can be detected spectrophotometrically. White blood cells are initially present in the CSF in the same proportion to red cells as in the peripheral blood. However, chemical meningitis caused by blood in the subarachnoid space may produce a pleocytosis of several thousand white blood cells during the first 48 hours and a reduction in CSF glucose 4 to 8 days after hemorrhage. In the absence of pleocytosis, CSF glucose after subarachnoid hemorrhage is normal. The peripheral white blood cell count is often modestly elevated but rarely exceeds 15,000/μL.
The electrocardiogram (ECG) may reveal a host of abnormalities, including peaked or deeply inverted T waves, a short PR interval, or tall U waves.
Once the diagnosis of subarachnoid hemorrhage is confirmed by CT or lumbar puncture, four-vessel cerebral arteriography is undertaken. Both the carotid and vertebral arteries should be studied to visualize the entire cerebral vascular anatomy, as multiple aneurysms occur in 20% of patients and AVMs are frequently supplied from multiple vessels. Angiography should be performed at the earliest convenient time, and is a prerequisite to the rational planning of surgical treatment. It is therefore not necessary for patients who are not surgical candidates, such as those who are deeply comatose. CT and magnetic resonance angiography do not yet have the resolution needed to replace conventional catheter angiography.
The sudden onset of severe headache, with confusion or obtundation, nuchal rigidity, absence of focal neurologic deficits, and bloody spinal fluid is highly specific for subarachnoid hemorrhage.
Other disorders can also produce obtundation and bloody spinal fluid, but are distinguished by additional findings, such as prominent focal neurologic deficits (hypertensive intracerebral hemorrhage) or signs of endocarditis (ruptured mycotic aneurysm) or a presenting history of head trauma.
Traumatic lumbar puncture can be excluded as the cause of bloody CSF by comparing red blood cell counts in the first and last tubes of CSF obtained and by examination of the centrifuged CSF specimen. Blood clears as fluid is removed after a traumatic tap, but not after subarachnoid hemorrhage. Because blood introduced by traumatic lumbar puncture does not have time to undergo enzymatic breakdown to bilirubin, centrifugation of the specimen reveals a colorless supernatant.
Bacterial meningitis is excluded by the presence of blood in the CSF or on CT scan.
A. Recurrence of Hemorrhage
Recurrence of aneurysmal hemorrhage occurs in approximately 20% of patients over 10 to 14 days. It is the major acute complication and roughly doubles the mortality rate. Acute recurrence of hemorrhage from AVM is less common.
B. Intraparenchymal Extension of Hemorrhage
Although hemorrhages from an AVM commonly involve the brain parenchyma, this is far less common with aneurysmal hemorrhage. However, rupture of an aneurysm of the anterior cerebral or middle cerebral artery may direct a jet of blood into the brain with resultant intracerebral hematoma producing hemiparesis, aphasia, and sometimes transtentorial herniation.
Delayed arterial narrowing (vasospasm) occurs in vessels surrounded by subarachnoid blood and is associated with ischemic neurologic deficits in more than one-third of cases. Clinical ischemia typically does not appear before day 4 after the hemorrhage, peaks at day 7 to 8, and then resolves spontaneously. The diagnosis can be confirmed by transcranial Doppler or cerebral angiography (see Chapter 2, Investigative Studies). The severity of vasospasm is related to the amount of subarachnoid blood, and vasospasm is less common when less blood is present, such as after traumatic subarachnoid hemorrhage or rupture of an AVM. Vasospasm appears to be only one element in the genesis of delayed ischemic neurologic deficits following subarachnoid hemorrhage, as one-third of patients with delayed ischemia clinically do not have demonstrable vasospasm.
D. Acute or Subacute Hydrocephalus
Acute or subacute hydrocephalus may develop during the first three days—or after several weeks—as a result of impaired CSF absorption in the subarachnoid space. Progressive somnolence, nonfocal findings, and impaired upgaze due to downward pressure on the midbrain should suggest the diagnosis.
Seizures occur in fewer than 10% of cases and only after damage to the cerebral cortex. Decorticate or decerebrate posturing is common acutely and may be mistaken for seizures.
Although inappropriate secretion of antidiuretic hormone and resultant diabetes insipidus can occur, they are uncommon.
Medical treatment is directed toward preventing elevation of arterial or intracranial pressure that might re-rupture the aneurysm or AVM. Typical measures include absolute bed rest with the head of the bed elevated 15 to 20 degrees, mild sedation, and analgesics for headache (antiplatelet drugs should be avoided). Because patients who are hypertensive on admission have increased mortality, reducing blood pressure (to approximately 160/100 mm Hg) is prudent, but bed rest and mild sedation are often adequate in this regard.
Fever is common and worsens outcome. Induced normothermia is essential (infusion of 4° C NaCl is suggested). Hypotension should be prevented to ensure adequate cerebral perfusion, but intravenous fluids should be isosmotic (normal saline) and should be administered with care, as overhydration can exacerbate cerebral swelling. Hyponatremia is frequently seen and should be managed by oral administration of NaCl, or intravenous 3% normal saline, rather than by fluid restriction.
Following definitive surgical treatment of the ruptured aneurysm and in the absence of other aneurysms, vasospasm can be treated by induced hypertension with phenylephrine or dopamine. The calcium channel antagonist nimodipine, 60 mg orally (or by nasogastric tube) every 4 hours for 21 days, reduces delayed ischemic neurologic deficits in patients with a ruptured aneurysm through neuroprotective mechanisms rather than by a direct effect on vasospasm. Seizures are uncommon after aneurysmal rupture, but the hypertension accompanying an acute seizure increases the risk of re-rupture. Accordingly, prophylactic administration of an anticonvulsant (eg, phenytoin, 300 mg/d) is recommended in the perioperative period and then is discontinued following definite treatment.
Aneurysm—Definitive surgical therapy of a ruptured aneurysm consists of clipping the neck of the aneurysm or endovascular placement of a coil to induce clotting.
The neurologic examination is used to grade the patient’s surgical candidacy (Table 6-2). In patients who are fully alert (Hunt and Hess grades I and II) or only mildly confused (grade III), surgery has been shown to improve the clinical outcome. In contrast, stuporous (grade IV) or comatose (grade V) patients do not appear to benefit.
As rebleeding is maximal within the first 24 hours following aneurysmal rupture, early surgical intervention is indicated. This approach reduces the period at risk for rebleeding and permits aggressive treatment of vasospasm with volume expansion and pharmacologic elevation of blood pressure.
Treatment of associated unruptured aneurysms is individualized. Surgery is favored by young age, previous rupture, family history of aneurysmal rupture, observed aneurysm growth, and low operative risk. Decreased life expectancy and asymptomatic small (<7-mm diameter) aneurysms favor conservative management.
AVM—Surgically accessible AVMs may be removed by en-bloc resection or obliterated by ligation of feeding vessels or by embolization with a local intra-arterial catheter. Because the risk of an early second hemorrhage is much less with AVMs than with aneurysms, surgical treatment can be undertaken electively at a convenient time after the bleeding episode.
Table 6-2.Clinical Grading of Patients With Aneurysmal Subarachnoid Hemorrhage. ||Download (.pdf) Table 6-2. Clinical Grading of Patients With Aneurysmal Subarachnoid Hemorrhage.
|Grade ||Level of Consciousness ||Associated Clinical Features ||Surgical Candidate |
|I ||Normal ||None or mild headache and stiff neck ||Yes |
|II ||Normal ||Moderate headache and stiff neck; minimal neurologic deficit (eg, cranial nerve palsy) in some cases ||Yes |
|III ||Confusional state ||Focal neurologic deficits in some cases ||Yes |
|IV ||Stupor ||Focal neurologic deficits in some cases ||No |
|V ||Coma ||Decerebrate posturing in some cases ||No |
The mortality rate from aneurysmal subarachnoid hemorrhage is high. Approximately 20% of patients die before reaching a hospital, 25% die subsequently from the initial hemorrhage or its complications, and 20% die from rebleeding prior to surgical correction. Most deaths occur in the first few days after the hemorrhage.
The probability of survival after aneurysmal rupture is related to the patient’s state of consciousness and the time elapsed since rupture. On day 1, the probability of survival is 60% for symptom-free and 30% for somnolent patients; at 1 month, these groups have survival probabilities of 90% and 60%, respectively. Among survivors of aneurysmal subarachnoid hemorrhage, approximately one-half have permanent brain injury.
Nearly 90% of patients recover after subarachnoid hemorrhage from ruptured AVM. Although recurrent hemorrhage remains a danger, conservative management compares favorably with surgery.
OTHER CEREBROVASCULAR DISORDERS
Intracerebral hemorrhage commonly presents with headache, vomiting, altered consciousness, and focal neurologic deficits. Headache in this setting results from compression of pain-sensitive structures by the hematoma. The most common cause of nontraumatic intracerebral hemorrhage is hypertension, but AVMs and bleeding into tumors can present in a similar manner. The CT scan shows a hematoma, which is usually located in the basal ganglia, thalamus, cerebellum, pons, or subcortical white matter. Intracerebral hemorrhage is discussed in more detail in Chapter 13, Stroke.
Headache occurs at onset of stroke or TIA in one-third of patients and may persist for hours to several days. The association of headache is independent of stroke etiology (thrombotic, embolic, lacunar), stroke severity, or hypertension. Headache is more common with younger age, female gender, cerebellar location, and a history of migraine.
Headaches associated with ischemic stroke are typically mild to moderate in intensity, and nonthrobbing in character. Their location is determined by the pain projection sites of the involved arteries and is most often, but not invariably, ipsilateral to the ischemic hemisphere. Carotid lesions usually produce frontal (trigeminal distribution) pain, whereas posterior fossa strokes usually present with occipital headache. Headache accompanying retinal artery embolism or posterior cerebral artery spasm or occlusion may be erroneously diagnosed as migraine because of the associated visual impairment.
Headache also occurs as part of the cerebral hyperperfusion syndrome after carotid endarterectomy and may be associated with hypertension, focal sensory or motor signs, seizures, and altered consciousness. This syndrome occurs on the second or third postoperative day and typically produces intense throbbing anterior headache on the operated side, often associated with nausea. The cause is thought to be impaired autoregulation of cerebral blood flow.
Headache associated with cerebral infarction may require analgesics for symptomatic relief.
Cerebral ischemia is discussed in more detail in Chapter 13, Stroke.
MENINGITIS OR ENCEPHALITIS
Patients with infection of the meningeal covering of the brain (meningitis) present with a combination of new headache (87%), neck stiffness (83%), fever (77%), and altered mental state (69%). Infection involving brain parenchyma (encephalitis) presents similarly with headache (81%), fever (90%), and altered consciousness (97%), but seizures are frequent (67% in encephalitis while only 5% in meningitis).
Headache is a prominent feature of inflammation of the brain (encephalitis) or its meningeal coverings (meningitis) caused by bacterial, viral, or other infections, as well as granulomatous processes, neoplasms, or chemical irritants. The pain is caused by inflammation of intracranial pain-sensitive structures, including blood vessels at the base of the brain.
The headache is commonly throbbing in character, bilateral, and occipital or nuchal in location. Its severity is increased by sitting upright, moving the head, compressing the jugular vein, or performing other maneuvers (eg, sneezing, coughing) that transiently increase intracranial pressure. Photophobia may be prominent. The headache rarely presents suddenly, developing instead over hours to days.
Neck stiffness and other signs of meningeal irritation (see Figure 1-5) must be sought with care, as they may not be obvious early in the course or in encephalitis. Fever and lethargy or confusion are often, but not always, prominent features.
Mental status abnormalities accompany most cases of bacterial but few cases of aseptic meningitis. Changes may evolve rapidly and vary in severity from mild confusion to coma. Their duration at presentation is less than 24 hours in about 50% of cases of bacterial meningitis. The clinical and laboratory findings in bacterial meningitis are summarized in Table 4-8.
The diagnosis of bacterial meningitis is suggested by a CSF examination that shows an increased white blood cell count (pleocytosis) and low glucose concentration (hypoglycorrhachia) (see Table 4-9). Bacterial, syphilitic, tuberculous, viral, fungal, and parasitic infections may be distinguished by CSF glucose, Gram stain, acid-fast stain, India ink preparation, cryptococcal antibody assays, Venereal Disease Research Laboratory (VDRL), and cultures (see Table 4-5). Treatment of meningitis and encephalitis is discussed in detail in Chapter 4, Confusional States.
Encapsulated pus from contiguous or hematogenous sources produces an expanding mass resulting in headache, change in mental status, focal neurologic defects, and fever. Seizures are the presenting event in 20% to 25% of cases. Headache is a frequent presentation (see Table 3-7) but the classic triad of headache with fever and focal neurologic signs occurs in less than 20%. Progression is rapid with a mean interval of 8.3 days between symptom onset and hospital admission. MRI and CT scanning differentiate abscess from primary or metastatic cancers. Etiology, clinical findings, evaluation, and treatment are discussed in Chapter 3, Coma.
OTHER CAUSES OF ACUTE HEADACHE
Preictal, ictal, and postictal headaches occur but only the latter are common; they are associated most often with generalized tonic-clonic seizures but also occur following seizures of simple and complex partial phenomenology. Migrainous features (throbbing, nausea and vomiting, photophobia, phonophobia) are common and similar to patients’ non-ictal headaches. It may be important to differentiate these headaches from those of subarachnoid hemorrhage or meningitis. If doubt exists about the cause, lumbar puncture can be undertaken: seizures may produce a mild CSF pleocytosis (up to approximately 10 cells/μL after single seizures or up to approximately 100 cells/μL after status epilepticus), but CSF glucose content is normal.
Post-lumbar-puncture headache is diagnosed by a history of a dural puncture (eg, spinal tap, spinal anesthesia) and is characteristically a postural headache, with marked increase in pain in the upright position and relief with recumbency. The pain is typically occipital, comes on within 48 to 72 hours after the procedure, and lasts 1 to 2 days. Nausea and vomiting may occur. Headache is caused by persistent leak of CSF from the spinal subarachnoid space, with resultant traction on pain-sensitive structures at the base of the brain.
The risk of this complication can be reduced by using a small-gauge needle (22 gauge or smaller) for the puncture. Lying flat afterward, for any length of time, does not lessen the risk.
Low-pressure headache syndromes are usually self-limited. When this is not the case, they may respond to the administration of caffeine sodium benzoate, 500 mg intravenously, which can be repeated after 45 minutes if headache persists or recurs upon standing. In persistent cases, the subarachnoid rent can be sealed by injection of autologous blood into the epidural space at the site of the puncture; this requires an experienced anesthesiologist.
Spontaneous intracranial hypotension can produce headache similar in character to that caused by lumbar puncture. T1-weighted, gadolinium-enhanced MRI may show smooth enhancement of the pachymeninges and a “sagging brain” (Figure 6-6); the enhancement may be confused with that associated with meningitis. Low CSF pressure can produce the same MRI picture in the absence of headache. Autologous blood patch injection may produce immediate relief.
Spontaneous intracranial hypotension in a 27-year-old woman presenting with severe postural headaches. Sagittal and axial T1-weighted images obtained after gadolinium injections show features of “sagging brain”: downward displacement of the cerebellar tonsils into the foramen magnum (arrows, left image), effacement of the brainstem cisterns (left image; compare with normal sagittal MRI in Figure 2-6), and diffuse dural enhancement (arrows, right image). MRI abnormalities and symptoms reversed following an epidural blood patch. (Used with permission from H.A. Rowley.)
Headache may be due to a sudden elevation in blood pressure caused by pheochromocytoma, sexual intercourse, the combination of monoamine oxidase inhibitors and tyramine-containing foods such as cheddar cheese, or—the most important cause—malignant hypertension. Blood pressures of 250/150 mm Hg or higher—characteristic of malignant hypertension—produce cerebral edema and displace pain-sensitive structures. The induced pain is described as severe and throbbing. Other signs of diffuse or focal central nervous system dysfunction are also present, such as lethargy, hemiparesis, or focal seizures; on CT or MRI, posterior white matter changes may be seen (see Figure 4-21). Treatment is with antihypertensive drugs (see Chapter 4, Confusional States), but care must be taken to avoid hypotension, which can produce cerebral ischemia and cause stroke.
Most coital headaches are benign. Men are more often affected than women. The pain may be either a dull, bilateral pain occurring during sexual excitement or a severe, sudden headache occurring at the time of orgasm, presumably caused by a marked increase in systemic blood pressure. Persistent headache after orgasm—worse in the upright posture—has also been described, is reminiscent of post-lumbar-puncture headache, and is associated with low opening pressures at lumbar puncture. Each of these headaches is benign and subsides over minutes to days.
Patients reporting severe headache in association with orgasm should be evaluated for possible subarachnoid hemorrhage (see earlier discussion). If no hemorrhage is found, prophylactic treatment with indomethacin, 50 to 100 mg orally 30 to 60 minutes prior to intercourse, may be effective.
Pain about the eye may occur in migraine and cluster headache and is also the presenting feature of iritis and glaucoma. Acute iritis produces extreme eye pain with photophobia. The diagnosis is confirmed by slit lamp examination; acute management involves pharmacologic dilatation of the pupil. Angle-closure glaucoma produces pain within the globe that radiates to the forehead. When it occurs after middle age, such a pain syndrome should prompt diagnostic tonometry.