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Headache
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Headaches Due to Cerebrovascular Disease Jun Kawamura, MD,* andJohn Stirling Meyer, MDt
Headaches are among the primary symptoms of many different types of cerebrovascular disorders. It is important to determine the correct diagnosis and understand the pathogenesis of the head pain in patients who complain of headache, because many forms of cerebrovascular disease, if untreated, may be fatal; if recognized, they are amenable to medical and surgical treatment. A complete list of the different types of cerebrovascular disorders that may cause headaches is presented in Table 1. Symptoms and signs that are characteristic manifestations of these different cerebrovascular diseases are discussed, and approaches to their diagnosis and management are reviewed. HEADACHES DUE TO INTRACEREBRAL HEMORRHAGE Subarachnoid Hemorrhage Of the different cerebrovascular diseases, subarachnoid hemorrhage is the most common cause of intense and incapacitating headache of abrupt onset. Patients with subarachnoid hemorrhage look sick; may have fever, sweating, and tachycardia; and often have elevated blood pressure. The head pain is produced by three possible mechanisms: chemical irritation by the blood of the intracranial sensory nerves, distortion and stretching of the intracranial meninges and blood vessels, and increased intracranial pressure. Excluding trauma, the majority of subarachnoid hemorrhages result from ruptured saccular aneurysms or arteriovenous malformations. The remainder result from hemorrhagic diatheses, arteritis, brain tumor, spinal subarachnoid hemorrhage, and amyloid angiopathy. Ruptured saccular aneurysms are the most common cause of subarachnoid hemorrhage due to cerebrovascular disease. According to the cooperative study reported by Sahs,26 75% of subarachnoid hemorrhages are caused by ruptured aneurysm. The onset of aneurysmal rupture is characterized by sudden, generalized, and extremely severe headache that often occurs during physical exertion and is accompanied by nausea and vomiting. Several investigations have documented that headache is a relatively constant symptom of ruptured aneurysm, although a few From the Department of Neurology, Baylor College of Medicine; and Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center, Houston, Texas *Research Associate
t Professor; and Director Medical Clinics of North America-Vo!' 75, No. 3, May 1991
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cases of ruptured aneurysm without headache have been observed by Fisher6 (3%) but denied by Gorelick et al. 8 Headache persists for several days and subsides within a week or two. Fisher observed that unilateral headache, which is complained of by 70% of patients with subarachnoid hemorrhage, results from rupture of internal carotid-posterior communicating and middle cerebral aneurysms, whereas bilateral headache occurs with rupture of an anterior communicating artery aneurysm. 6 Adams et at' reviewed the symptoms of 41 patients with subarachnoid hemorrhages who were misdiagnosed, so that treatment was delayed. Although these patients were initially less acutely ill than patients with correct diagnoses, headache was the most common symptom (it was recognized in 35 out of 41 patients) and remained a major complaint even in the presence of other severe symptoms. On neurologic examination, signs of meningeal irritation are present, with stiff neck and limitation of straight leg raising. Absence of meningeal irritation, however, does not exclude subarachnoid hemorrhage, because elicitation of meningeal signs depends on the age of the patient, the state of consciousness, and the skill and experience of the examiner. Signs of increased intracranial pressure may exist, but papilledema may be infrequent at the onset, even in patients with large subarachnoid hemorrhages. Focal neurologic deficits may occur depending on the site of the ruptured aneurysm, although Sacco et al25 found focal neurologic deficits in only 4 out of 36 patients. Deterioration of consciousness occurs transiently or permanently if intracranial pressure becomes increased, or if there is brain-stem compression or ischemia. Thus, headache accompanied by transient loss of consciousness should raise the strong suspicion of subarachnoid hemorrhage until proven otherwise. Patients may experience premonitory headache a few days or weeks before the major aneurysmal rupture. Fisher" reported antecedent headache prior to aneurysmal rupture in about 20% of patients with aneurysm. Gorelick et al8 noted that 31 % of patients experienced headache as a forewarning symptom. The premonitory headache may be similar to that of major rupture, or it may be less severe. In addition to premonitory headache, other signs and symptoms of ocular palsy, neck pain, transient loss of consciousness, visual disturbances, transient motor or sensory disturbances, and vomiting often supervene. The mechanisms responsible for neurologic signs are considered to be mass effects due to vascular disturbance, minor leakages of blood with hematoma formation, and ischemic lesions. 19 The mean interval from onset of early warning signs to aneurysmal rupture is 20 days, but the intervals vary depending on the etiology of the neurologic deficits. Table 1. Types of Cerebrovascular Disorders That May Cause Headache Headaches due to intracranial hemorrhage Subarachnoid hemorrhage Cerebral hemorrhage Cerebellar hemorrhage Subdural and epidural hematoma Headaches due to occlusive cerebrovascular disease Transient ischemic attacks Internal carotid artery occlusion and stenosis Occlusion of middle cerebral artery with infarction and brain swelling Vertebrobasilar arterial occlusion and stenosis Thrombosis of dural sinuses and cerebral veins Dissecting aneurysm of the carotid, vertebral, and middle cerebral arteries Arteritis Fibromuscular dysplasia Hypertensive encephalopathy Carotid endarterectomy and superficial temporal artery-middle cerebral artery bypass surgery
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Although recurrence of headache in patients with ruptured aneurysm virtually always indicates rebleeding, often occurring within 2 and 14 days of the first symptoms, headache also may be caused by acute hydrocephalus, inappropriate secretion of antidiuretic hormone with water intoxication, and cerebral edema. Rupture of an arteriovenous malformation (AVM) is the second most common cause of subarachnoid hemorrhage. 26 Patients with AVM are likely to be younger than those with ruptured berry aneurysm and frequently give a history of recurrent seizures. Subarachnoid hemorrhage from AVM is less massive than that which occurs with ruptured aneurysm because of lower pressure within the AVM compared with arterial pressure in an aneurysm. Therefore, the headache is usually not as severe or prolonged as in ruptured aneurysm. Bleeding into the brain parenchyma associated with AVM produces focal neurologic signs along with the meningeal signs more commonly than with ruptured aneurysm. Intracranial bruit might be heard over the skull of patients with AVM. These features give clues to the differential diagnosis of AVM from ruptured aneurysm. In 10% to 25% of AVMs without bleeding, recurrent headaches occur on the side of the AVM, so that one must be suspicious of the possibility of an underlying AVM when confronted with a case of persistently localized unilateral headache. However, large, unruptured AVMs may exist without headache. Arteriovenous malformations may closely mimic classic, complicated, and common migraine, so that the differentiation is difficult and computed tomography (CT) brain scanning is necessary for adequate differential diagnosis. Diagnosis of the cause. of headache due to subarachnoid hemorrhage is made by CT scanning (Figs. 1 and 2), lumbar puncture, and angiography (Figs. 3 and 4). If CT scanning facilities are available, this procedure should be done first to
Figure 1. Plain, non-iodine contrast computed tomography scan shOWing blood in the third and lateral ventricles in a 63-yearold man with ruptured aneurysm of the anterior communicating artery and dissection into the floor of the third ventricle, resulting in acute hydrocephalus.
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Figure 2. Intravenous iodine contrast -enhanced computed tomography scan made in a 30-yearold man with recurrent headaches due to a large arteriovenous malformation showing a small hematoma in the brain parenchyma plus many dilated thin-walled arteriovenous communications and enlarged torcular herophili (confluens sinuum).
determine whether there is blood in the subarachnoid space and whether intracerebral hematoma is present, which may be a contraindication to lumbar puncture if there is a danger of brain herniation. Apart from excluding intracerebral hematoma, CT scanning will also indicate the presence of brain embolism, tumor, and abscess. One should keep in mind that CT scanning is unable to demonstrate small amounts of subarachnoid hemorrhage. Therefore, if the CT scan fails to confirm subarachnoid hemorrhage in cases of highly suspected subarachnoid hemorrhage, lumbar puncture should be performed. If CT scan shows subarachnoid bleeding, spinal puncture is usually unnecessary. Following confirmation of the presence of blood in the subarachnoid space, cerebral angiography is necessary to identify ruptured aneurysm and AVM prior to subsequent surgical intervention. Although many features of AVM give clues for differentiation of subarachnoid hemorrhages due to ruptured AVM versus ruptured aneurysm, the precise diagnosis of small to moderate AVMs often requires angiography. Large AVMs may be revealed by contrast-enhanced CT. Surgical treatment includes clipping aneurysms and excision of AVMs. Symptomatic treatment of headache often requires meperidine, codeine, and other analgesics and sedatives. Common causes of death and disability among patients with subarachnoid hemorrhage are rebleeding and vasospasm. Rebleeding especially occurs within the first 48 hours following the initial bleeding. Thus, treatment should begin as soon as possible after the initial rupture in order to improve prognosis among patients with ruptured aneurysm. According to Kassell et al,12 however, neurosurgical care after aneurysmal rupture is delayed for a large population of patients, with the median time to referral being 3.6 days. Proper understanding of the signs and symptoms of subarachnoid hemorrhage should avoid these unnecessary delays.
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Figure 3. Selective internal carotid arteriogram showing giant aneurysm at the junction of the internal carotid and anterior communicating arteries.
Figure 4. Selective left carotid angiogram in a 35-year-old man with headaches and seizures. There is a moderate-sized arteriovenous malformation involving the middle cerebral artery and draining into the superior sagittal sinus. This was successfully removed without residual neurologic deficit.
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Cerebral Hemorrhage The onset of large, parenchymatous cerebral hemorrhages, as a rule, is accompanied by severe and sudden headache with vomiting. The reported frequency of associated headache has varied widely from 23% to 57%.6,17,21 Difference in the frequency of associated headache probably depends on the size and location of the lesion. Fisher" reported that headache occurred in 13% of patients with putaminal hemorrhage, in 32% with thalamic hemorrhage, and more frequently in patients with cerebral lobar hemorrhages, The incidence of headache in patients with lobar hemorrhage was 46%, as reported by Ropper and Davis, and 68%, as reported by Kase et al. 11, 23 Gorelick et alB did not recognize any consistent association between the site of the intracerebral hematoma and location of headache apart from putamenal hemorrhages in which patients reported ipsilateral frontal headache. Regarding lobar hemorrhages, Ropper and Davis23 identified certain characteristic clinical features that correlated with the location of lobar hematomas; however, Kase et al 11 did not find such clinicopathologic confirmation in their series of patients with relatively larger lobar hematoma. If cerebral hemorrhages rupture into the ventricular system and the subarachnoid space, obtundation of consciousness follows, with signs of meningeal irritation, including stiff neck and positive Kernig's sign. With the advent of CT scanners, smaller cerebral hemorrhages are now detected without any associated increases in intracranial pressure and without extension into the subarachnoid space, which are major contributing causes of headache. According to Broderick et al,2 the incidence rate of intracerebral hemorrhage increased from 91100,000 in the period between 1965 and 1974 to 14/100,000 between 1975 and 1984 in the Rochester, Minnesota, population. This increase in the incidence rate of intracerebral hemorrhage was largely due to detection of small hemorrhages by CT. In such cases, headache may be entirely absent. Gorelick et alB stated that premonitory headache occurred in only 14% of patients with intracerebral hemorrhage, although the pathophysiology of premonitory headache has not been established. Headache, with large cerebral parenchymal hemorrhages, is considered to result from traction on major vessels and dural sinuses in much the same way as occurs with brain tumors and other space-occupying lesions of the brain. The majority of cerebral hemorrhages are caused by arterial hypertension, but other causes include hemorrhage into a brain tumor, arteritis, amyloid angiopathy, ruptured AVMs, and blood dyscrasias. Diagnosis is established better by CT scanning of the brain (Fig. 5) than by magnetic resonance imaging. Treatment should be directed toward control of hypertension, reduction of cerebral edema and intracranial pressure, and use of analgesics. Cerebellar Hemorrhage The incidence of headache accompanying cerebellar hemorrhage is much higher than that accompanying hemorrhage into the cerebral hemispheres. Headache occurs in 65% to 80% of cerebellar hemorrhages, according to data analyzed from literatures. 24, 2B, 29 The pain is usually occipital in location, but it may be frontal. The mechanism of the headache may be due to tension on pain-sensitive structures or increases in intracranial pressure as a result of obstruction of the ventricular system. Associated neurologic symptoms at the onset of cerebellar hemorrhage include nausea, vomiting, dizziness, instability of gait, and impairment of consciousness. Neurologic examination reveals conjugate deviation of the eyes to the side opposite from the hemorrhage, plus miosis and ataxia. The region, size, and rate of expansion of cerebellar hematomas decide the severity of clinical symptoms. Computed tomography scanning should be carried out as soon as possible when cerebellar hemorrhage is suspected. Lumbar puncture is extremely risky in cerebellar hem-
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Figure 5. Plain computed tomography scan in a 24-year-old man with severe headache and left hemiparesis secondary to right putamenal hemorrhage with compression of the anterior horn of the lateral ventricle.
orrhage; the risks are similar to those encountered in posterior fossa expanding and space-occupying lesions. Differential diagnoses are ruptured aneurysm of the vertebrobasilar arterial system, brain-stem infarction, and hemorrhage into an angioma of the cerebellum. Van der Hoop et al29 concluded that cerebellar hemorrhage should be surgically removed if the hematoma causes impairment of consciousness in patients whose brain-stem reflexes are still preserved. Small cerebellar hemorrhage without disturbance of consciousness may be treated medically by reducing cerebral edema. Epidural and Subdural Hematoma In patients with epidural hematoma, headache is a prominent and early symptom. Disturbances of consciousness in patients with epidural hematoma are preceded by the well-known asymptomatic lucid interval following the head injury. The pathogenesis of the headache is due to separation of the dura from the skull, with stretching and distortion of pain-sensitive vascular structures. Increasing volume of the hematoma produces progressive impairment of consciousness. The hematoma should be removed surgically as soon as possible and on an emergency basis. Headache is the most common symptom in patients with subdural hematoma. It may be moderate or mild, but it is persistent and troublesome. If the headache is overlooked and the hematoma becomes enlarged enough to compress the brain, nonspecific and nonlocalizing neurologic signs usually become manifest. Trauma is the most probable cause of subdural hematoma, but often, particularly in the elderly and demented patient, it does not elicit attention and is not offered by the patient when giving the history. In elderly patients with subdural hematoma, headache may be masked by other clinical symptoms, such as disturbed consciousness, mental deterioration, and progressive dementia.
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Diagnosis of epidural and subdural hematoma is made by CT or magnetic resonance imaging scanning. Computed tomography scanning before and after intravenous injection of iodine contrast medium is most helpful. Treatment involves neurosurgical removal of the hematoma. HEADACHE IN OCCLUSIVE CEREBROVASCULAR DISEASE Transient Ischemic Attacks Headache is a prominent symptom in about one fourth of patients with transient ischemic attacks (TIAs). Frequencies have been reported by Edmeads et aP (25%), Grindal and Toole 9 (25%), Medina et al 15 (44%), and Portenoy et a{2' (36%). Grindal and Toole 9 mentioned that no distinguishing features according to populations, arteriographic, or prognostic considerations were found among patients whose TIAs were accompanied by headache when compared with those without headache. Two investigations revealed that headache was a more common accompaniment in patients with vertebrobasilar TIA than in those with carotid TIA."' '4 Patients with TIA in the carotid territory are likely to complain of frontal headache, whereas those with vertebrobasilar TIA have occipital headache. The headache is ipsilateral to the involved vessel, and is mild or moderately severe. Two mechanisms are thought to be the cause of headache in patients with TIA. Medina et ai'5 demonstrated a connection between TIA and late-onset vascular headache. Crowell et aP speculated that vasomotor phenomena similar to those operating in migraine may play a major role in the cause of vertebrobasilar arterial insufficiency with transient global amnesia by measurements of cerebral blood flow. On the other hand, Edmeads5 invoked the platelet hypothesis with serotonin release, which could account for the headache in patients with TIAs as well as in patients with ischemic stroke. Although headache associated with TIA does not characterize the TIA, clinical investigation is indicated and should include CT scanning and Doppler sonography to verify atheromatous lesions of carotid artery, echocardiography to detect cardiac sources of emboli, and intravenous subtraction angiography to verify suspected plaques of the aortocranial arterial tree. Internal Carotid Artery Occlusion and Stenosis Patients with occlusion or stenosis of the internal carotid artery complain of frontal or temporal pain and ipsilateral or bilateral headaches. However, the incidence of headache in occlusive disease of the carotid arteries varies according to different investigators. Fisher6 reported headache or parietal discomfort of the head and neck in 31% of patients with internal carotid disease, whereas Mohr et al 17 noted headache in only 9% of such patients. Edmeads5 reported headache in 25% of patients with carotid artery disease. Headaches in occlusive carotid artery disease may precede an ischemic stroke by days, whether or not there are accompanying transient ischemic attacks. The headache is located frontally in most cases, but it may be referred to in fronto-occipital or cervico-occipital regions. The quality of headache varies. Some patients describe the headache as throbbing, but others describe it as steady. The intensity also varies, but the majority of headaches are mild to moderate. The pain is considered to be due to dilatation of the superficial temporal artery and other extracranial vessels that provide the collateral circulation via ophthalmic and other extracranial-intracranial collaterals. However, the headache is too transient to be explained by collateral circulation after occlusion of the internal carotid artery. Analysis of collateral flow by means of arteriography has disclosed no differences between cases with and without headache. Furthermore, ligation of the common
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carotid artery for treatment of intracranial aneurysms did not result in headache, even when cerebral infarction resulted. Platelet aggregation with release of vasoactive substances such as serotonin and prostaglandins probably is the cause of headache in occlusive cerebrovascular disease. 2B Diagnosis should be suspected in any middle-aged or elderly person with risk factors for stroke, including hypertension, diabetes, smoking, and a history of heart disease. A history of previous neurologic deficits and of cervical bruit is also suggestive. Diagnosis is established by Doppler sonography, CT scan, and intravenous subtraction angiography or cerebral angiography. The treatment of headache associated with occlusive carotid artery disease is administration of aspirin orally, with acetaminophen as needed for pain. Endarterectomy should be considered for prevention of further ischemic episodes. Occlusion of the Middle Cerebral Artery According to Fisher's experience,6 headache occurred in 17% of patients with middle cerebral occlusion. The headache is located around the ipsilateral eye. The character of the pain is steady or develops during the stroke. The headache may precede the ischemic event. Embolism of the middle cerebral artery is more likely to cause headache in the ipsilateral temple, although the differentiation of these two causes of middle cerebral artery occlusion is clinically difficult. Diagnosis of occlusion of middle cerebral artery is made by CT scan, magnetic resonance imaging, and cerebral angiography (Fig. 6). The head pain responds to acetaminophen, a drug that does not inhibit prostaglandin synthesis as does aspirin and does not interfere with concomitant daily aspirin therapy. The headache subsides significantly after 7 to 10 days in patients without cerebral edema. Vertebrobasilar Arterial Occlusion and Stenosis Among patients with basilar artery thrombosis or embolism, head pain is occipital, which may be lateralized or bioccipital. Neck pain may occur in patients with occlusion of the cervical portion of vertebral artery occlusion. The incidence of headache in patients with basilar artery occlusion is 44%, according to Fisher. 6 By contrast, the majority of patients with basilar stenosis do not have headache. Diagnosis should be suspected when occipital headache is associated with neurologic symptoms such as visual-field defects, blurred vision, dysphagia, ataxia, and alternating hemiparesis or hemisensory loss. Diagnosis is confirmed by cerebral angiography or intravenous subtraction angiography. Headache is treated with aspirin and acetaminophen. Thrombosis of the Dural Sinus and Cerebral Veins Thrombotic occlusions of the dural sinus and cerebral veins are frequently associated with the early onset of severe headache. Patients with thrombosis of the cerebrovenous system are usually younger than those with atherosclerotic disease. Thrombosis of the superior sagittal sinus produces severe generalized headache, papilledema, and obtundation. The thrombus may spread from the sagittal sinus into the cerebral veins, and hemorrhagic infarction associated with crural diplegia and focal seizures may result. Lateral sinus thrombosis produces increased intracranial pressure without focal neurologic deficit-so-called otitic hydrocephalus. The pain of lateral sinus thrombosis is often masked by the pain of mastoid disease, which predisposes to venous thrombosis. Sometimes, lateral sinus thrombosis may be completely asymptomatic. The symptoms associated with cavernous sinus thrombosis are well known and include pain around the eye and over the forehead, conjunctival congestion, proptosis, facial edema, and ophthalmoplegia. Diagnosis of cerebral venous thrombosis is made by CT scanning with contrast, magnetic resonance imaging, angiography, and venography. Treatment of intracranial venous
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Figure 6. Selective internal carotid angiogram showing stenosis (black arrow) of the left middle cerebral artery in a 60-year-old woman with headaches and transient attacks of right hemiparesis. Daily treatment with aspirin relieved her symptoms.
thrombosis includes control of seizures, reduction of intracranial pressure, and use of anticoagulants and fibrinolytics; it may include use of antibiotics if sinus infection predisposes to thrombosis.
DISSECTING ANEURYSMS OF THE CAROTID, VERTEBRAL, AND MIDDLE CEREBRAL ARTERY Headache is a prominent symptom in patients with spontaneous dissection of the cervical carotid artery before cerebrovascular manifestations appear. Fisher7 concluded that typical headaches in spontaneous dissection involve the ipsilateral forehead with pain of severe or moderately severe intensity, and about half of the patients had neck pain located in the upper part of the internal carotid artery. In addition to headache and neck pain, neurologic symptoms, such as ipsilateral oculosympathctic paresis (Homer's syndrome), subjective bruit, and visual disturbances, are important clues to recognize carotid dissection. Oculosympathetic
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paresis occurs as a result of involvement of the pericarotid sympathetic plexus. Focal neurologic deficits may result if the lumen is occluded or if cerebral embolization arises from the distal portion of the dissection. Similar headache in the occipital region occurs in dissection of the vertebral arteries and is associated with symptoms of vertebrobasilar arterial insufficiency. Often patients report a history of previous trauma to neck or head. Differential diagnosis includes cluster headache and migraine with pupillary dysfunction. DiagnOSis is confirmed by angiography. Conservative treatment with analgesics is indicated. Several physicians recommend the administration of anticoagulants to intervene cerebral embolism. According to the report of Mokri et al,'8 subsequent angiography after 3 to 6 months in the patients without surgical intervention showed complete or partial resolution of the angiographic abnormalities. External carotidinternal carotid bypass surgery has been performed in the patients with arterial occlusion caused by carotid dissection. ARTERITIS Arteritis involving cerebral vessels includes temporal arteritis (giant cell arteritis), periarteritis nodosa, Takayasu's disease, and other collagen diseases. They are regularly associated with headache. The headache is considered to result from inflammation of adjacent meninges, irritation of involved vessels, and cerebral infarction. Temporal arteritis is the most common. The characteristic symptoms of temporal arteritis are unilateral tenderness of the superficial temporal and OCCipital arteries with local headache that has a deep, aching quality and is throbbing in nature. Abnormal laboratory findings include elevated sedimentation rates and elevated gamma-globulin levels. Diagnosis is made by temporal artery biopsy. As soon as the diagnosis is made, administration of prednisone or other corticosteroids is the treatment of choice. FIBROMUSCULAR DYSPLASIA Fibromuscular dysplasia (FMD) is a well-known vascular disorder that can involve the cerebral arteries as well as large or medium-sized arteries of other organs. A study of819 routine autopsies revealed nine patients with FMD, indicating the incidence to be about 1%.10 The diagnosis of FMD in most cases is made accidentally, with angiography being performed for some other reason. Patients with FMD have a history of multiple recurrent symptoms, of which headache is the most common. Mettinger and Ericson '6 reported headache in 25 out of 32 (78%) FMD patients, and 5 patients (16%) had recurrent or persistent pain of one side of the neck. Other frequent clinical complaints consist of tinnitus, vertigo, syncope, and TIAs, corresponding to the widespread FMD lesions of the arterial system. Cerebral angiography is required to confirm the diagnosis. In approximately 80% of patients with FMD, multiple irregularly spaced concentric constrictions with normal or dilated intervening segments are seen in the involved vessel. These are the so-called string of beads seen angiographically. 20 The mechanism of the headache is not clear, and it is difficult to treat efficiently. Fibromuscular dysfunction may cause hemorrhagic as well as ischemic cerebral lesions. Vascular surgery and balloon angioplasty using various techniques and administration of antiplatelet agents are recommended in the treatment of FMD. HYPERTENSIVE ENCEPHALOPATHY Hypertensive encephalopathy is seldom seen nowadays because of the availability of improved medications for the control of hypertension. Headache occurred
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in 85% of patients with hypertensive encephalopathy in Fisher's study.6 Headache may precede the development of symptoms such as vomiting, vertigo, generalized weakness, irritability, and generalized seizure and consciousness disturbance. Increased intracranial hypertension produces papilledema and retinal vasospasm or bleeding in almost all the cases. Cardiac and renal failure are ordinarily present. Untreated hypertensive encephalopathy is a medical emergency, because intracerebral hemorrhage often results. Treatment is vigorous, with immediate administration of antihypertensive drugs, such as calcium-channel blockers, beta-blockers, or intravenous sodium nitroprusside. CAROTID ENDARTERECTOMY AND SUPERFICIAL TEMPORAL ARTERY-MIDDLE CEREBRAL ARTERY BYPASS SURGERY Following carotid endarterectomy, severe headache localized to the side of the endarterectomy is common for the first few days. Leviton et al l3 postulated that the headaches were related to loss of autoregulation. Other investigators reported patients with headache and seizures after endarterectomy and related their postoperative dysfunctions to cerebral hyperperfusion. 4 . 22 Schroeder et al27 revealed an initial increase in blood flow of greater than 200%, with values gradually returning to normal after endarterectomy. Occasionally, cerebral hyperperfusion following endarterectomy gives rise to focal and generalized seizures, transient neurologic deficits, and intracerebral hemorrhage. Furthermore, cerebral hyperperfusion is usually considered to result from cerebral microembolization, which is the most common complication of endarterectomy. Headache after endarterectomy is managed easily with analgesics, but further evaluation and careful treatment are required in cases with severe unilateral headache. Computed tomography scanning and an electroencephalogram should be done, and systemic blood pressure and seizures should be controlled. Headache has not often been reported in the literature as a result of superficial temporal artery-middle cerebral artery anastomosis. However, Edmeads 5 reported that headache was common in the first few days after such bypass surgery. The headache is localized to the side of the anastomosis, and the pain is more severe than that following simple craniotomy. The headaches usually disappear completely in 2 to 5 days if the shunt remains patent and the scalp vessels continued to dilate. Edmeads hypothesized that platelet aggregation with serotonin release plays an important role in the occurrence of headache. SUMMARY Subarachnoid hemorrhage causes sudden, severe headache and requires immediate medical and surgical diagnosis and treatment. A CT scan is the first choice for correct diagnosis. In order to prevent rebleeding, delays in treatment should be avoided. Intraparenchymal cerebral hemorrhage is now often recognized by means ofCT scanning and sometimes is a cause of headache. Cerebellar hemorrhage commonly causes occipital headache and is an indication for immediate surgical intervention, although small cerebellar hemorrhages can be treated conservatively. Ischemic cerebrovascular disease is frequently accompanied by headache, but its etiology remains uncertain. Thrombosis of the cerebrovenous system is a less frequent cause of head pain than that of the arterial system, but it usually shows characteristic neurologic signs. Following carotid endarterectomy or superficial temporal artery-middle cerebral artery bypass surgery, the patient may have
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moderate to severe unilateral headaches, probably as a result of platelet aggregation and serotonin release.
REFERENCES 1. Adams HP, Jergenson DD, Kassell NF, et al: Pitfalls in the recognition of subarachnoid hemorrhage. JAMA 244:794-796, 1980 2. Broderick JP, Phillips SJ, Whisnant JP, et al: Incidence rates of stroke in the eighties: The end of the decline in stroke? Stroke 20:577-583, 1989 3. Crowell CF, Stump DA, Biller J, et al: The transient global amnesia-migraine connection. Arch NeuroI4l:75-79, 1984 4. Dolan JC, Mushlin AI: Hypertension, vascular headaches, and seizures after carotid endarterectomy: Case report and therapeutic considerations. Arch Intern Med 144:1489-1491, 1984 5. Edmeads J: The headaches of ischemic cerebrovascular disease. Headache 19:345-349, 1979 6. Fisher CM: Headache in cerebrovascular disease. In Vinken PJ, Bruyn CW (eds): Headache. (Handbook of Clinical Neurology, vol 5.) Amsterdam, North-Holland Publishing Company, 1968, pp 124-156 7. Fisher CM: The headache and pain of spontaneous carotid dissection. Headache 22:6065, 1982 8. Corelick PB, Hier DB, Caplan LR, et al: Headache in acute cerebrovascular disease. Neurology 36:1445-1450, 1986 9. Crindal AB, Toole JF: Headache and transient ischemic attack. Stroke 5:603-606, 1974 10. Heffelfinger MJ, Holley KE, Harrison EC Jr, et al: Arterial fibromuscular dysplasia studied at autopsy. Am J Clin Pathol 54:274, 1970 11. Kase CS, Williams JP, Wyatt DA, et al: Lobar intracerebral hematomas: Clinical and CT analysis of 22 cases. Neurology 32: 1146-1150, 1982 12. Kassell NF, Kongable CL, Torner JC, et al: Delay in referral of patients with ruptured aneurysms to neurosurgical attention. Stroke 16:587-590, 1985 13. Leviton A, Caplan L, Salzman E: Severe headache after carotid endarterectomy. Headache 15:207-209, 1975 14. Loeb C, Candolfo C, Dall'Agata 0: Headache in transient ischemic attacks (TIA). Cephalalgia 5: 17-19, 1985 15. Medina JL, Diamond S, Rubino FA: Headache in patients with transient ischemic attacks. Headache 15:194-197, 1975 16. Mettinger KL, Ericson K: Fibromuscular dysplasia and the brain. Observations on angiographic, clinical and genetic characteristics. Stroke 13:46-52, 1982 17. Mohr JP, Caplan LR, Melski JW, et al: The Harvard Cooperative Stroke Registry: A prospective registry. Neurology 28:754-762, 1978 18. Mokri B, Sundt TM Jr, Houser OW: Spontaneous internal carotid dissection, hemicrania, and Horner's syndrome. Arch Neurol 36:677-680, 1979 19. Okawara S: Warning signs prior to rupture of an intracranial aneurysm. J Neurosurg 38:575-580, 1973 20. Osborn AC, Anderson RE: Angiographic spectrum of cervical and intracranial fibromuscular dysplasia. Stroke 8:617-626, 1977 21. Portenoy RK, Abissi CL Lipton RB, et al: Headache in cerebrovascular disease. Stroke 15:1009-1012, 1984 22. Reigel MM, Hollier LH, Sundt TM, et al: Cerebral hyperperfusion syndrome: A cause of neurologic dysfunction after carotid endarterectomy. J Vasc Surg 5:628-634, 1987 23. Ropper AH, Davis KR: Lobar cerebral hemorrhages: Acute clinical syndromes in 26 cases. Ann Neurol 8:141-147, 1980 24. Rosenberg CA, Kaufman OM: Cerebellar hemorrhage: Reliability of clinical evaluation. Stroke 7:332-336, 1976 25. Sacco RL, Wolf PA, Bharucha NE, et al: Subarachnoid and intracerebral hemorrhage: Natural history, prognosis, and precursive factors in the Framingham study. Neurology 34:847-854, 1984 26. Sahs AL: Subarachnoid hemorrhage. In Harrison MJC, Dyken ML (eds): Cerebral Vascular Disease. London, Butterworths, 1983, pp 354-402
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27. Schroeder T, Holstein PE, Engell HC: Hyperfusion following endarterectomy [letter]. Stroke 15:758, 1984 28. Scotti C, Spinnler H, Sterzi R, et al: Cerebellar softening. Ann Neurol 8:133-140, 1980 29. van der Hoop RC, Vermeulen M, van Cijn J: Cerebellar hemorrhage: Diagnosis and treatment. Surg Neurol 29:6-10, 1988
Address reprint requests to John Stirling Meyer, MD Cerebrovascular Research Laboratories Department of Veterans Affairs Medical Center 2002 Holcombe Boulevard Houston, TX 77211
Headache
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Headaches Due to Cerebrovascular Disease Jun Kawamura, MD,* andJohn Stirling Meyer, MDt
Headaches are among the primary symptoms of many different types of cerebrovascular disorders. It is important to determine the correct diagnosis and understand the pathogenesis of the head pain in patients who complain of headache, because many forms of cerebrovascular disease, if untreated, may be fatal; if recognized, they are amenable to medical and surgical treatment. A complete list of the different types of cerebrovascular disorders that may cause headaches is presented in Table 1. Symptoms and signs that are characteristic manifestations of these different cerebrovascular diseases are discussed, and approaches to their diagnosis and management are reviewed. HEADACHES DUE TO INTRACEREBRAL HEMORRHAGE Subarachnoid Hemorrhage Of the different cerebrovascular diseases, subarachnoid hemorrhage is the most common cause of intense and incapacitating headache of abrupt onset. Patients with subarachnoid hemorrhage look sick; may have fever, sweating, and tachycardia; and often have elevated blood pressure. The head pain is produced by three possible mechanisms: chemical irritation by the blood of the intracranial sensory nerves, distortion and stretching of the intracranial meninges and blood vessels, and increased intracranial pressure. Excluding trauma, the majority of subarachnoid hemorrhages result from ruptured saccular aneurysms or arteriovenous malformations. The remainder result from hemorrhagic diatheses, arteritis, brain tumor, spinal subarachnoid hemorrhage, and amyloid angiopathy. Ruptured saccular aneurysms are the most common cause of subarachnoid hemorrhage due to cerebrovascular disease. According to the cooperative study reported by Sahs,26 75% of subarachnoid hemorrhages are caused by ruptured aneurysm. The onset of aneurysmal rupture is characterized by sudden, generalized, and extremely severe headache that often occurs during physical exertion and is accompanied by nausea and vomiting. Several investigations have documented that headache is a relatively constant symptom of ruptured aneurysm, although a few From the Department of Neurology, Baylor College of Medicine; and Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center, Houston, Texas *Research Associate
t Professor; and Director Medical Clinics of North America-Vo!' 75, No. 3, May 1991
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cases of ruptured aneurysm without headache have been observed by Fisher6 (3%) but denied by Gorelick et al. 8 Headache persists for several days and subsides within a week or two. Fisher observed that unilateral headache, which is complained of by 70% of patients with subarachnoid hemorrhage, results from rupture of internal carotid-posterior communicating and middle cerebral aneurysms, whereas bilateral headache occurs with rupture of an anterior communicating artery aneurysm. 6 Adams et at' reviewed the symptoms of 41 patients with subarachnoid hemorrhages who were misdiagnosed, so that treatment was delayed. Although these patients were initially less acutely ill than patients with correct diagnoses, headache was the most common symptom (it was recognized in 35 out of 41 patients) and remained a major complaint even in the presence of other severe symptoms. On neurologic examination, signs of meningeal irritation are present, with stiff neck and limitation of straight leg raising. Absence of meningeal irritation, however, does not exclude subarachnoid hemorrhage, because elicitation of meningeal signs depends on the age of the patient, the state of consciousness, and the skill and experience of the examiner. Signs of increased intracranial pressure may exist, but papilledema may be infrequent at the onset, even in patients with large subarachnoid hemorrhages. Focal neurologic deficits may occur depending on the site of the ruptured aneurysm, although Sacco et al25 found focal neurologic deficits in only 4 out of 36 patients. Deterioration of consciousness occurs transiently or permanently if intracranial pressure becomes increased, or if there is brain-stem compression or ischemia. Thus, headache accompanied by transient loss of consciousness should raise the strong suspicion of subarachnoid hemorrhage until proven otherwise. Patients may experience premonitory headache a few days or weeks before the major aneurysmal rupture. Fisher" reported antecedent headache prior to aneurysmal rupture in about 20% of patients with aneurysm. Gorelick et al8 noted that 31 % of patients experienced headache as a forewarning symptom. The premonitory headache may be similar to that of major rupture, or it may be less severe. In addition to premonitory headache, other signs and symptoms of ocular palsy, neck pain, transient loss of consciousness, visual disturbances, transient motor or sensory disturbances, and vomiting often supervene. The mechanisms responsible for neurologic signs are considered to be mass effects due to vascular disturbance, minor leakages of blood with hematoma formation, and ischemic lesions. 19 The mean interval from onset of early warning signs to aneurysmal rupture is 20 days, but the intervals vary depending on the etiology of the neurologic deficits. Table 1. Types of Cerebrovascular Disorders That May Cause Headache Headaches due to intracranial hemorrhage Subarachnoid hemorrhage Cerebral hemorrhage Cerebellar hemorrhage Subdural and epidural hematoma Headaches due to occlusive cerebrovascular disease Transient ischemic attacks Internal carotid artery occlusion and stenosis Occlusion of middle cerebral artery with infarction and brain swelling Vertebrobasilar arterial occlusion and stenosis Thrombosis of dural sinuses and cerebral veins Dissecting aneurysm of the carotid, vertebral, and middle cerebral arteries Arteritis Fibromuscular dysplasia Hypertensive encephalopathy Carotid endarterectomy and superficial temporal artery-middle cerebral artery bypass surgery
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Although recurrence of headache in patients with ruptured aneurysm virtually always indicates rebleeding, often occurring within 2 and 14 days of the first symptoms, headache also may be caused by acute hydrocephalus, inappropriate secretion of antidiuretic hormone with water intoxication, and cerebral edema. Rupture of an arteriovenous malformation (AVM) is the second most common cause of subarachnoid hemorrhage. 26 Patients with AVM are likely to be younger than those with ruptured berry aneurysm and frequently give a history of recurrent seizures. Subarachnoid hemorrhage from AVM is less massive than that which occurs with ruptured aneurysm because of lower pressure within the AVM compared with arterial pressure in an aneurysm. Therefore, the headache is usually not as severe or prolonged as in ruptured aneurysm. Bleeding into the brain parenchyma associated with AVM produces focal neurologic signs along with the meningeal signs more commonly than with ruptured aneurysm. Intracranial bruit might be heard over the skull of patients with AVM. These features give clues to the differential diagnosis of AVM from ruptured aneurysm. In 10% to 25% of AVMs without bleeding, recurrent headaches occur on the side of the AVM, so that one must be suspicious of the possibility of an underlying AVM when confronted with a case of persistently localized unilateral headache. However, large, unruptured AVMs may exist without headache. Arteriovenous malformations may closely mimic classic, complicated, and common migraine, so that the differentiation is difficult and computed tomography (CT) brain scanning is necessary for adequate differential diagnosis. Diagnosis of the cause. of headache due to subarachnoid hemorrhage is made by CT scanning (Figs. 1 and 2), lumbar puncture, and angiography (Figs. 3 and 4). If CT scanning facilities are available, this procedure should be done first to
Figure 1. Plain, non-iodine contrast computed tomography scan shOWing blood in the third and lateral ventricles in a 63-yearold man with ruptured aneurysm of the anterior communicating artery and dissection into the floor of the third ventricle, resulting in acute hydrocephalus.
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Figure 2. Intravenous iodine contrast -enhanced computed tomography scan made in a 30-yearold man with recurrent headaches due to a large arteriovenous malformation showing a small hematoma in the brain parenchyma plus many dilated thin-walled arteriovenous communications and enlarged torcular herophili (confluens sinuum).
determine whether there is blood in the subarachnoid space and whether intracerebral hematoma is present, which may be a contraindication to lumbar puncture if there is a danger of brain herniation. Apart from excluding intracerebral hematoma, CT scanning will also indicate the presence of brain embolism, tumor, and abscess. One should keep in mind that CT scanning is unable to demonstrate small amounts of subarachnoid hemorrhage. Therefore, if the CT scan fails to confirm subarachnoid hemorrhage in cases of highly suspected subarachnoid hemorrhage, lumbar puncture should be performed. If CT scan shows subarachnoid bleeding, spinal puncture is usually unnecessary. Following confirmation of the presence of blood in the subarachnoid space, cerebral angiography is necessary to identify ruptured aneurysm and AVM prior to subsequent surgical intervention. Although many features of AVM give clues for differentiation of subarachnoid hemorrhages due to ruptured AVM versus ruptured aneurysm, the precise diagnosis of small to moderate AVMs often requires angiography. Large AVMs may be revealed by contrast-enhanced CT. Surgical treatment includes clipping aneurysms and excision of AVMs. Symptomatic treatment of headache often requires meperidine, codeine, and other analgesics and sedatives. Common causes of death and disability among patients with subarachnoid hemorrhage are rebleeding and vasospasm. Rebleeding especially occurs within the first 48 hours following the initial bleeding. Thus, treatment should begin as soon as possible after the initial rupture in order to improve prognosis among patients with ruptured aneurysm. According to Kassell et al,12 however, neurosurgical care after aneurysmal rupture is delayed for a large population of patients, with the median time to referral being 3.6 days. Proper understanding of the signs and symptoms of subarachnoid hemorrhage should avoid these unnecessary delays.
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Figure 3. Selective internal carotid arteriogram showing giant aneurysm at the junction of the internal carotid and anterior communicating arteries.
Figure 4. Selective left carotid angiogram in a 35-year-old man with headaches and seizures. There is a moderate-sized arteriovenous malformation involving the middle cerebral artery and draining into the superior sagittal sinus. This was successfully removed without residual neurologic deficit.
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Cerebral Hemorrhage The onset of large, parenchymatous cerebral hemorrhages, as a rule, is accompanied by severe and sudden headache with vomiting. The reported frequency of associated headache has varied widely from 23% to 57%.6,17,21 Difference in the frequency of associated headache probably depends on the size and location of the lesion. Fisher" reported that headache occurred in 13% of patients with putaminal hemorrhage, in 32% with thalamic hemorrhage, and more frequently in patients with cerebral lobar hemorrhages, The incidence of headache in patients with lobar hemorrhage was 46%, as reported by Ropper and Davis, and 68%, as reported by Kase et al. 11, 23 Gorelick et alB did not recognize any consistent association between the site of the intracerebral hematoma and location of headache apart from putamenal hemorrhages in which patients reported ipsilateral frontal headache. Regarding lobar hemorrhages, Ropper and Davis23 identified certain characteristic clinical features that correlated with the location of lobar hematomas; however, Kase et al 11 did not find such clinicopathologic confirmation in their series of patients with relatively larger lobar hematoma. If cerebral hemorrhages rupture into the ventricular system and the subarachnoid space, obtundation of consciousness follows, with signs of meningeal irritation, including stiff neck and positive Kernig's sign. With the advent of CT scanners, smaller cerebral hemorrhages are now detected without any associated increases in intracranial pressure and without extension into the subarachnoid space, which are major contributing causes of headache. According to Broderick et al,2 the incidence rate of intracerebral hemorrhage increased from 91100,000 in the period between 1965 and 1974 to 14/100,000 between 1975 and 1984 in the Rochester, Minnesota, population. This increase in the incidence rate of intracerebral hemorrhage was largely due to detection of small hemorrhages by CT. In such cases, headache may be entirely absent. Gorelick et alB stated that premonitory headache occurred in only 14% of patients with intracerebral hemorrhage, although the pathophysiology of premonitory headache has not been established. Headache, with large cerebral parenchymal hemorrhages, is considered to result from traction on major vessels and dural sinuses in much the same way as occurs with brain tumors and other space-occupying lesions of the brain. The majority of cerebral hemorrhages are caused by arterial hypertension, but other causes include hemorrhage into a brain tumor, arteritis, amyloid angiopathy, ruptured AVMs, and blood dyscrasias. Diagnosis is established better by CT scanning of the brain (Fig. 5) than by magnetic resonance imaging. Treatment should be directed toward control of hypertension, reduction of cerebral edema and intracranial pressure, and use of analgesics. Cerebellar Hemorrhage The incidence of headache accompanying cerebellar hemorrhage is much higher than that accompanying hemorrhage into the cerebral hemispheres. Headache occurs in 65% to 80% of cerebellar hemorrhages, according to data analyzed from literatures. 24, 2B, 29 The pain is usually occipital in location, but it may be frontal. The mechanism of the headache may be due to tension on pain-sensitive structures or increases in intracranial pressure as a result of obstruction of the ventricular system. Associated neurologic symptoms at the onset of cerebellar hemorrhage include nausea, vomiting, dizziness, instability of gait, and impairment of consciousness. Neurologic examination reveals conjugate deviation of the eyes to the side opposite from the hemorrhage, plus miosis and ataxia. The region, size, and rate of expansion of cerebellar hematomas decide the severity of clinical symptoms. Computed tomography scanning should be carried out as soon as possible when cerebellar hemorrhage is suspected. Lumbar puncture is extremely risky in cerebellar hem-
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Figure 5. Plain computed tomography scan in a 24-year-old man with severe headache and left hemiparesis secondary to right putamenal hemorrhage with compression of the anterior horn of the lateral ventricle.
orrhage; the risks are similar to those encountered in posterior fossa expanding and space-occupying lesions. Differential diagnoses are ruptured aneurysm of the vertebrobasilar arterial system, brain-stem infarction, and hemorrhage into an angioma of the cerebellum. Van der Hoop et al29 concluded that cerebellar hemorrhage should be surgically removed if the hematoma causes impairment of consciousness in patients whose brain-stem reflexes are still preserved. Small cerebellar hemorrhage without disturbance of consciousness may be treated medically by reducing cerebral edema. Epidural and Subdural Hematoma In patients with epidural hematoma, headache is a prominent and early symptom. Disturbances of consciousness in patients with epidural hematoma are preceded by the well-known asymptomatic lucid interval following the head injury. The pathogenesis of the headache is due to separation of the dura from the skull, with stretching and distortion of pain-sensitive vascular structures. Increasing volume of the hematoma produces progressive impairment of consciousness. The hematoma should be removed surgically as soon as possible and on an emergency basis. Headache is the most common symptom in patients with subdural hematoma. It may be moderate or mild, but it is persistent and troublesome. If the headache is overlooked and the hematoma becomes enlarged enough to compress the brain, nonspecific and nonlocalizing neurologic signs usually become manifest. Trauma is the most probable cause of subdural hematoma, but often, particularly in the elderly and demented patient, it does not elicit attention and is not offered by the patient when giving the history. In elderly patients with subdural hematoma, headache may be masked by other clinical symptoms, such as disturbed consciousness, mental deterioration, and progressive dementia.
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Diagnosis of epidural and subdural hematoma is made by CT or magnetic resonance imaging scanning. Computed tomography scanning before and after intravenous injection of iodine contrast medium is most helpful. Treatment involves neurosurgical removal of the hematoma. HEADACHE IN OCCLUSIVE CEREBROVASCULAR DISEASE Transient Ischemic Attacks Headache is a prominent symptom in about one fourth of patients with transient ischemic attacks (TIAs). Frequencies have been reported by Edmeads et aP (25%), Grindal and Toole 9 (25%), Medina et al 15 (44%), and Portenoy et a{2' (36%). Grindal and Toole 9 mentioned that no distinguishing features according to populations, arteriographic, or prognostic considerations were found among patients whose TIAs were accompanied by headache when compared with those without headache. Two investigations revealed that headache was a more common accompaniment in patients with vertebrobasilar TIA than in those with carotid TIA."' '4 Patients with TIA in the carotid territory are likely to complain of frontal headache, whereas those with vertebrobasilar TIA have occipital headache. The headache is ipsilateral to the involved vessel, and is mild or moderately severe. Two mechanisms are thought to be the cause of headache in patients with TIA. Medina et ai'5 demonstrated a connection between TIA and late-onset vascular headache. Crowell et aP speculated that vasomotor phenomena similar to those operating in migraine may play a major role in the cause of vertebrobasilar arterial insufficiency with transient global amnesia by measurements of cerebral blood flow. On the other hand, Edmeads5 invoked the platelet hypothesis with serotonin release, which could account for the headache in patients with TIAs as well as in patients with ischemic stroke. Although headache associated with TIA does not characterize the TIA, clinical investigation is indicated and should include CT scanning and Doppler sonography to verify atheromatous lesions of carotid artery, echocardiography to detect cardiac sources of emboli, and intravenous subtraction angiography to verify suspected plaques of the aortocranial arterial tree. Internal Carotid Artery Occlusion and Stenosis Patients with occlusion or stenosis of the internal carotid artery complain of frontal or temporal pain and ipsilateral or bilateral headaches. However, the incidence of headache in occlusive disease of the carotid arteries varies according to different investigators. Fisher6 reported headache or parietal discomfort of the head and neck in 31% of patients with internal carotid disease, whereas Mohr et al 17 noted headache in only 9% of such patients. Edmeads5 reported headache in 25% of patients with carotid artery disease. Headaches in occlusive carotid artery disease may precede an ischemic stroke by days, whether or not there are accompanying transient ischemic attacks. The headache is located frontally in most cases, but it may be referred to in fronto-occipital or cervico-occipital regions. The quality of headache varies. Some patients describe the headache as throbbing, but others describe it as steady. The intensity also varies, but the majority of headaches are mild to moderate. The pain is considered to be due to dilatation of the superficial temporal artery and other extracranial vessels that provide the collateral circulation via ophthalmic and other extracranial-intracranial collaterals. However, the headache is too transient to be explained by collateral circulation after occlusion of the internal carotid artery. Analysis of collateral flow by means of arteriography has disclosed no differences between cases with and without headache. Furthermore, ligation of the common
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carotid artery for treatment of intracranial aneurysms did not result in headache, even when cerebral infarction resulted. Platelet aggregation with release of vasoactive substances such as serotonin and prostaglandins probably is the cause of headache in occlusive cerebrovascular disease. 2B Diagnosis should be suspected in any middle-aged or elderly person with risk factors for stroke, including hypertension, diabetes, smoking, and a history of heart disease. A history of previous neurologic deficits and of cervical bruit is also suggestive. Diagnosis is established by Doppler sonography, CT scan, and intravenous subtraction angiography or cerebral angiography. The treatment of headache associated with occlusive carotid artery disease is administration of aspirin orally, with acetaminophen as needed for pain. Endarterectomy should be considered for prevention of further ischemic episodes. Occlusion of the Middle Cerebral Artery According to Fisher's experience,6 headache occurred in 17% of patients with middle cerebral occlusion. The headache is located around the ipsilateral eye. The character of the pain is steady or develops during the stroke. The headache may precede the ischemic event. Embolism of the middle cerebral artery is more likely to cause headache in the ipsilateral temple, although the differentiation of these two causes of middle cerebral artery occlusion is clinically difficult. Diagnosis of occlusion of middle cerebral artery is made by CT scan, magnetic resonance imaging, and cerebral angiography (Fig. 6). The head pain responds to acetaminophen, a drug that does not inhibit prostaglandin synthesis as does aspirin and does not interfere with concomitant daily aspirin therapy. The headache subsides significantly after 7 to 10 days in patients without cerebral edema. Vertebrobasilar Arterial Occlusion and Stenosis Among patients with basilar artery thrombosis or embolism, head pain is occipital, which may be lateralized or bioccipital. Neck pain may occur in patients with occlusion of the cervical portion of vertebral artery occlusion. The incidence of headache in patients with basilar artery occlusion is 44%, according to Fisher. 6 By contrast, the majority of patients with basilar stenosis do not have headache. Diagnosis should be suspected when occipital headache is associated with neurologic symptoms such as visual-field defects, blurred vision, dysphagia, ataxia, and alternating hemiparesis or hemisensory loss. Diagnosis is confirmed by cerebral angiography or intravenous subtraction angiography. Headache is treated with aspirin and acetaminophen. Thrombosis of the Dural Sinus and Cerebral Veins Thrombotic occlusions of the dural sinus and cerebral veins are frequently associated with the early onset of severe headache. Patients with thrombosis of the cerebrovenous system are usually younger than those with atherosclerotic disease. Thrombosis of the superior sagittal sinus produces severe generalized headache, papilledema, and obtundation. The thrombus may spread from the sagittal sinus into the cerebral veins, and hemorrhagic infarction associated with crural diplegia and focal seizures may result. Lateral sinus thrombosis produces increased intracranial pressure without focal neurologic deficit-so-called otitic hydrocephalus. The pain of lateral sinus thrombosis is often masked by the pain of mastoid disease, which predisposes to venous thrombosis. Sometimes, lateral sinus thrombosis may be completely asymptomatic. The symptoms associated with cavernous sinus thrombosis are well known and include pain around the eye and over the forehead, conjunctival congestion, proptosis, facial edema, and ophthalmoplegia. Diagnosis of cerebral venous thrombosis is made by CT scanning with contrast, magnetic resonance imaging, angiography, and venography. Treatment of intracranial venous
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Figure 6. Selective internal carotid angiogram showing stenosis (black arrow) of the left middle cerebral artery in a 60-year-old woman with headaches and transient attacks of right hemiparesis. Daily treatment with aspirin relieved her symptoms.
thrombosis includes control of seizures, reduction of intracranial pressure, and use of anticoagulants and fibrinolytics; it may include use of antibiotics if sinus infection predisposes to thrombosis.
DISSECTING ANEURYSMS OF THE CAROTID, VERTEBRAL, AND MIDDLE CEREBRAL ARTERY Headache is a prominent symptom in patients with spontaneous dissection of the cervical carotid artery before cerebrovascular manifestations appear. Fisher7 concluded that typical headaches in spontaneous dissection involve the ipsilateral forehead with pain of severe or moderately severe intensity, and about half of the patients had neck pain located in the upper part of the internal carotid artery. In addition to headache and neck pain, neurologic symptoms, such as ipsilateral oculosympathctic paresis (Homer's syndrome), subjective bruit, and visual disturbances, are important clues to recognize carotid dissection. Oculosympathetic
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paresis occurs as a result of involvement of the pericarotid sympathetic plexus. Focal neurologic deficits may result if the lumen is occluded or if cerebral embolization arises from the distal portion of the dissection. Similar headache in the occipital region occurs in dissection of the vertebral arteries and is associated with symptoms of vertebrobasilar arterial insufficiency. Often patients report a history of previous trauma to neck or head. Differential diagnosis includes cluster headache and migraine with pupillary dysfunction. DiagnOSis is confirmed by angiography. Conservative treatment with analgesics is indicated. Several physicians recommend the administration of anticoagulants to intervene cerebral embolism. According to the report of Mokri et al,'8 subsequent angiography after 3 to 6 months in the patients without surgical intervention showed complete or partial resolution of the angiographic abnormalities. External carotidinternal carotid bypass surgery has been performed in the patients with arterial occlusion caused by carotid dissection. ARTERITIS Arteritis involving cerebral vessels includes temporal arteritis (giant cell arteritis), periarteritis nodosa, Takayasu's disease, and other collagen diseases. They are regularly associated with headache. The headache is considered to result from inflammation of adjacent meninges, irritation of involved vessels, and cerebral infarction. Temporal arteritis is the most common. The characteristic symptoms of temporal arteritis are unilateral tenderness of the superficial temporal and OCCipital arteries with local headache that has a deep, aching quality and is throbbing in nature. Abnormal laboratory findings include elevated sedimentation rates and elevated gamma-globulin levels. Diagnosis is made by temporal artery biopsy. As soon as the diagnosis is made, administration of prednisone or other corticosteroids is the treatment of choice. FIBROMUSCULAR DYSPLASIA Fibromuscular dysplasia (FMD) is a well-known vascular disorder that can involve the cerebral arteries as well as large or medium-sized arteries of other organs. A study of819 routine autopsies revealed nine patients with FMD, indicating the incidence to be about 1%.10 The diagnosis of FMD in most cases is made accidentally, with angiography being performed for some other reason. Patients with FMD have a history of multiple recurrent symptoms, of which headache is the most common. Mettinger and Ericson '6 reported headache in 25 out of 32 (78%) FMD patients, and 5 patients (16%) had recurrent or persistent pain of one side of the neck. Other frequent clinical complaints consist of tinnitus, vertigo, syncope, and TIAs, corresponding to the widespread FMD lesions of the arterial system. Cerebral angiography is required to confirm the diagnosis. In approximately 80% of patients with FMD, multiple irregularly spaced concentric constrictions with normal or dilated intervening segments are seen in the involved vessel. These are the so-called string of beads seen angiographically. 20 The mechanism of the headache is not clear, and it is difficult to treat efficiently. Fibromuscular dysfunction may cause hemorrhagic as well as ischemic cerebral lesions. Vascular surgery and balloon angioplasty using various techniques and administration of antiplatelet agents are recommended in the treatment of FMD. HYPERTENSIVE ENCEPHALOPATHY Hypertensive encephalopathy is seldom seen nowadays because of the availability of improved medications for the control of hypertension. Headache occurred
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in 85% of patients with hypertensive encephalopathy in Fisher's study.6 Headache may precede the development of symptoms such as vomiting, vertigo, generalized weakness, irritability, and generalized seizure and consciousness disturbance. Increased intracranial hypertension produces papilledema and retinal vasospasm or bleeding in almost all the cases. Cardiac and renal failure are ordinarily present. Untreated hypertensive encephalopathy is a medical emergency, because intracerebral hemorrhage often results. Treatment is vigorous, with immediate administration of antihypertensive drugs, such as calcium-channel blockers, beta-blockers, or intravenous sodium nitroprusside. CAROTID ENDARTERECTOMY AND SUPERFICIAL TEMPORAL ARTERY-MIDDLE CEREBRAL ARTERY BYPASS SURGERY Following carotid endarterectomy, severe headache localized to the side of the endarterectomy is common for the first few days. Leviton et al l3 postulated that the headaches were related to loss of autoregulation. Other investigators reported patients with headache and seizures after endarterectomy and related their postoperative dysfunctions to cerebral hyperperfusion. 4 . 22 Schroeder et al27 revealed an initial increase in blood flow of greater than 200%, with values gradually returning to normal after endarterectomy. Occasionally, cerebral hyperperfusion following endarterectomy gives rise to focal and generalized seizures, transient neurologic deficits, and intracerebral hemorrhage. Furthermore, cerebral hyperperfusion is usually considered to result from cerebral microembolization, which is the most common complication of endarterectomy. Headache after endarterectomy is managed easily with analgesics, but further evaluation and careful treatment are required in cases with severe unilateral headache. Computed tomography scanning and an electroencephalogram should be done, and systemic blood pressure and seizures should be controlled. Headache has not often been reported in the literature as a result of superficial temporal artery-middle cerebral artery anastomosis. However, Edmeads 5 reported that headache was common in the first few days after such bypass surgery. The headache is localized to the side of the anastomosis, and the pain is more severe than that following simple craniotomy. The headaches usually disappear completely in 2 to 5 days if the shunt remains patent and the scalp vessels continued to dilate. Edmeads hypothesized that platelet aggregation with serotonin release plays an important role in the occurrence of headache. SUMMARY Subarachnoid hemorrhage causes sudden, severe headache and requires immediate medical and surgical diagnosis and treatment. A CT scan is the first choice for correct diagnosis. In order to prevent rebleeding, delays in treatment should be avoided. Intraparenchymal cerebral hemorrhage is now often recognized by means ofCT scanning and sometimes is a cause of headache. Cerebellar hemorrhage commonly causes occipital headache and is an indication for immediate surgical intervention, although small cerebellar hemorrhages can be treated conservatively. Ischemic cerebrovascular disease is frequently accompanied by headache, but its etiology remains uncertain. Thrombosis of the cerebrovenous system is a less frequent cause of head pain than that of the arterial system, but it usually shows characteristic neurologic signs. Following carotid endarterectomy or superficial temporal artery-middle cerebral artery bypass surgery, the patient may have
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moderate to severe unilateral headaches, probably as a result of platelet aggregation and serotonin release.
REFERENCES 1. Adams HP, Jergenson DD, Kassell NF, et al: Pitfalls in the recognition of subarachnoid hemorrhage. JAMA 244:794-796, 1980 2. Broderick JP, Phillips SJ, Whisnant JP, et al: Incidence rates of stroke in the eighties: The end of the decline in stroke? Stroke 20:577-583, 1989 3. Crowell CF, Stump DA, Biller J, et al: The transient global amnesia-migraine connection. Arch NeuroI4l:75-79, 1984 4. Dolan JC, Mushlin AI: Hypertension, vascular headaches, and seizures after carotid endarterectomy: Case report and therapeutic considerations. Arch Intern Med 144:1489-1491, 1984 5. Edmeads J: The headaches of ischemic cerebrovascular disease. Headache 19:345-349, 1979 6. Fisher CM: Headache in cerebrovascular disease. In Vinken PJ, Bruyn CW (eds): Headache. (Handbook of Clinical Neurology, vol 5.) Amsterdam, North-Holland Publishing Company, 1968, pp 124-156 7. Fisher CM: The headache and pain of spontaneous carotid dissection. Headache 22:6065, 1982 8. Corelick PB, Hier DB, Caplan LR, et al: Headache in acute cerebrovascular disease. Neurology 36:1445-1450, 1986 9. Crindal AB, Toole JF: Headache and transient ischemic attack. Stroke 5:603-606, 1974 10. Heffelfinger MJ, Holley KE, Harrison EC Jr, et al: Arterial fibromuscular dysplasia studied at autopsy. Am J Clin Pathol 54:274, 1970 11. Kase CS, Williams JP, Wyatt DA, et al: Lobar intracerebral hematomas: Clinical and CT analysis of 22 cases. Neurology 32: 1146-1150, 1982 12. Kassell NF, Kongable CL, Torner JC, et al: Delay in referral of patients with ruptured aneurysms to neurosurgical attention. Stroke 16:587-590, 1985 13. Leviton A, Caplan L, Salzman E: Severe headache after carotid endarterectomy. Headache 15:207-209, 1975 14. Loeb C, Candolfo C, Dall'Agata 0: Headache in transient ischemic attacks (TIA). Cephalalgia 5: 17-19, 1985 15. Medina JL, Diamond S, Rubino FA: Headache in patients with transient ischemic attacks. Headache 15:194-197, 1975 16. Mettinger KL, Ericson K: Fibromuscular dysplasia and the brain. Observations on angiographic, clinical and genetic characteristics. Stroke 13:46-52, 1982 17. Mohr JP, Caplan LR, Melski JW, et al: The Harvard Cooperative Stroke Registry: A prospective registry. Neurology 28:754-762, 1978 18. Mokri B, Sundt TM Jr, Houser OW: Spontaneous internal carotid dissection, hemicrania, and Horner's syndrome. Arch Neurol 36:677-680, 1979 19. Okawara S: Warning signs prior to rupture of an intracranial aneurysm. J Neurosurg 38:575-580, 1973 20. Osborn AC, Anderson RE: Angiographic spectrum of cervical and intracranial fibromuscular dysplasia. Stroke 8:617-626, 1977 21. Portenoy RK, Abissi CL Lipton RB, et al: Headache in cerebrovascular disease. Stroke 15:1009-1012, 1984 22. Reigel MM, Hollier LH, Sundt TM, et al: Cerebral hyperperfusion syndrome: A cause of neurologic dysfunction after carotid endarterectomy. J Vasc Surg 5:628-634, 1987 23. Ropper AH, Davis KR: Lobar cerebral hemorrhages: Acute clinical syndromes in 26 cases. Ann Neurol 8:141-147, 1980 24. Rosenberg CA, Kaufman OM: Cerebellar hemorrhage: Reliability of clinical evaluation. Stroke 7:332-336, 1976 25. Sacco RL, Wolf PA, Bharucha NE, et al: Subarachnoid and intracerebral hemorrhage: Natural history, prognosis, and precursive factors in the Framingham study. Neurology 34:847-854, 1984 26. Sahs AL: Subarachnoid hemorrhage. In Harrison MJC, Dyken ML (eds): Cerebral Vascular Disease. London, Butterworths, 1983, pp 354-402
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27. Schroeder T, Holstein PE, Engell HC: Hyperfusion following endarterectomy [letter]. Stroke 15:758, 1984 28. Scotti C, Spinnler H, Sterzi R, et al: Cerebellar softening. Ann Neurol 8:133-140, 1980 29. van der Hoop RC, Vermeulen M, van Cijn J: Cerebellar hemorrhage: Diagnosis and treatment. Surg Neurol 29:6-10, 1988
Address reprint requests to John Stirling Meyer, MD Cerebrovascular Research Laboratories Department of Veterans Affairs Medical Center 2002 Holcombe Boulevard Houston, TX 77211
