Cerebrovascular Disease a,b, a,b Louis R. Caplan, MD *, D. Eric Searls, MD , c Fong Kwong Sonny Hon, FRCP KEYWORDS Cerebrovascular disease Stroke Intracerebral hemorrhage Subarachnoid hemorrhage Transient ischemic attack AIMS AND QUERIES Effective management of patients who have cerebrovascular disease depends on ac- curate diagnosis. Outpatient ambulatory visits have advantages and disadvantages over inpatient encounters. The office allows more privacy, room, time, and relative freedom from distractions. Seeing the patient and significant others in their usual attire adds information not obtained from seeing the patient in the hospital. The inpatient setting allows for more rapid diagnostic testing, frequent nursing observation, and the possibility of deploying advanced pharmacologic and mechanical therapies for stroke. In ambulatory patients, the key questions are as follows: What is the diagnosis (what and where are the vascular and brain lesions)? How urgent is the problem? Should the patient be hospitalized? What tests should be ordered, and how soon? What treat- ment should be prescribed? What explanations and instructions should be given? These questions must be answered quickly, directly after the outpatient encounter. This article focuses on the first issues—making the diagnosis and planning the evalu- ation of a patient suspected of having cerebrovascular disease. Box 1 lists the data the clinician needs to know.1 Because cerebrovascular disease is so heterogeneous, management of individual patients depends on the type, loca- tion, and severity of the cerebrovascular disease and the presence, severity, and location of the resultant brain injury. Diagnosis and acquisition of data are accom- plished best by a question-driven approach. a Department of Neurology, Cerebrovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215-5400, USA b Cerebrovascular Division, Department of Neurology, Harvard University, School of Medicine, 127 Palmer, 330 Brookline Avenue, Boston, MA 02215, USA c Department of Medicine, Pamela Youde Nethersole Eastern Hospital, 10 Tai Man Road, Hong Kong, China * Corresponding author. Cerebrovascular Division, Department of Neurology, Harvard University, School of Medicine, 127 Palmer, 330 Brookline Avenue, Boston, MA 02215. E-mail address: [email protected] (L.R. Caplan). Med Clin N Am 93 (2009) 353–369 doi:10.1016/j.mcna.2008.09.004 medical.theclinics.com 0025-7125/08/$ – see front matter ª 2009 Elsevier Inc. All rights reserved. 354 Caplan et al Box 1 Data needed to treat a patient with brain ischemia logically Stroke mechanism, ischemic or hemorrhagic, and their subtypes Nature, location, and severity of the causative cardiac-cerebrovascular-hematologic lesions Pathophysiology of the vascular lesion that caused the brain injury-hemorrhage, hypoperfusion, or embolism Nature and function of the key cellular and serologic blood components and any disorder of coagulation State of the brain, whether normal, infarcted, or injured but recoverable From Caplan LR, Hon FK. Clinical diagnosis of patients with cerebrovascular disease. Prim Care 2004;31(1):96; with permission. Does the Patient have Cerebrovascular Disease or a Mimic? Many conditions cause clinical findings that closely resemble cerebrovascular disor- ders. Table 1 lists the most frequent stroke mimics and whether they tend to produce general or focal neurologic symptoms and signs.1 Brain tumors occasionally cause sudden-onset symptoms. Seizures, migraine attacks, and faints sometime are difficult to separate from transient ischemic attacks (TIAs). Table 2 lists the differential diag- nostic features of these common stroke mimics.1 Hypoglycemia, severe hyperglyce- mia, severe hyponatremia, hypocalcemia, and other toxic and metabolic conditions occasionally can cause focal brain symptoms. Diagnosis is based on the presence of risk factors for vascular disease, the tempo of onset, the presence of concurrent conditions, and the clinical course of development of neurologic symptoms and signs. In many patients, recognition that the disorder is not cerebrovascular is based on the neuroimaging presence of another condition, such as a tumor, subdural hematoma, brain abscess, or hemorrhage. Stroke mimics are also diagnosed by blood and Table 1 Frequent stroke mimics and their tendency to produce general versus localized nervous system findings Conditions Focal Symptoms Nonfocal Symptoms Frequent disorders Seizures 11 11 Transient ischemic attacks 1111 Occasionally Migraine 1111 1111 Syncope — 1111 Less frequent disorders Vestibulopathy 11 11 Metabolic 1 111 Neoplasm 111 1 Multiple sclerosis 1111 — Psychiatric 11 11 Peripheral nerves and roots 1111 — From Caplan LR, Hon FK. Clinical diagnosis of patients with cerebrovascular disease. Prim Care 2004;31(1):96; with permission. Cerebrovascular Disease 355 Table 2 Differential diagnostic features Seizures TIAs Migraine Syncope Demographics Any age Older patients Younger age Any age Children are Stroke risk Women>men Often younger common factors present Women>men Men>women Central nervous Aura preceding Negative First positive Light-headed, system Positive symptoms: symptoms, dim vision, symptoms symptoms: numbness, then negative distant noises, limb jerking, weakness, symptoms in decreased head turning, aphasia, visual same modality alertness eye deviation, loss, ataxia Scintillating Transient loss of loss of All sensory scotomas and consciousness consciousness modalities paresthesias Negative affected most frequent symptoms: simultaneously Second sensory (weakness) modality is may develop involved after postictally the first clears Timing 20–180 sec Usually <1 h Usually 30 min to Usually a few Absence, atonic several h seconds seizures & Intermittent Sporadic attacks myoclonic daily, weekly, during years jerks briefer monthly, or yearly Associated Tongue biting, — Headache, Diaphoresis, symptoms incontinence, vomiting, pallor, nausea automatisms photophobia, Headache, phonophobia myalgias postictally Adapted from Caplan LR, Hon FK. Clinical diagnosis of patients with cerebrovascular disease. Prim Care 2004;31(1):97; with permission. cerebrospinal fluid testing that shows a toxic, metabolic, or infectious process and does not show brain infarction or hemorrhage. Does the Patient have Cerebrovascular Disease or a Seizure? Differentiating between strokes and seizures is important (although some stroke pa- tients have seizures at the onset of their stroke). Incorrect diagnosis can lead to the wrong management and can have severe, even life-threatening consequences for the patient. Table 2 lists common features of seizures.1 Once a seizure has concluded (the postictal period), it can be especially difficult to discern between the two condi- tions. During the postictal period, the patient may develop headache or muscle sore- ness. The patient may have focal weakness, such as a monoparesis or hemiparesis (otherwise known as a postictal paresis). This weakness can last from several hours to a day after the seizure’s termination. Postictal paresis can easily be mistaken for the effects of a stroke. Although diagnosing a seizure is based on the clinical picture, ancillary testing (electroencephalogram) can be helpful and may confirm the diagnosis. 356 Caplan et al If the Disorder is Cerebrovascular, is the Problem Hemorrhage or Ischemia? Differentiation into hemorrhagic and ischemic conditions is an important initial step. These two mechanisms are diametrically opposite. In intracranial hemorrhage, there is leakage or rupture of a blood vessel that results in blood in the brain tissue, ventri- cles, subarachnoid space, or epidural space, whereas in ischemia, blood cannot per- fuse brain tissue. The brain tissue is starved of vital nutrients and energy. For patients who have ischemic brains, the aim is to restore blood flow and thereby increase de- livery of oxygen and other nutrients. In hemorrhage patients, however, the aim is to stop the bleeding and prevent further hemorrhages. About 85% of strokes are ische- mic, and about 15% are hemorrhagic.2,3 Separation between bleeding and ischemia is based on the clinical history and examination, but corroboration is always necessary by brain imaging that shows either subarachnoid or intraparenchymatous blood, a brain infarct, or the absence of bleeding without infarction. In some patients, spinal puncture is necessary to document bleeding into the subarachnoid space because brain imaging in these patients sometimes does not show hemorrhage, especially if the hemorrhage was small or occurred days before imaging.4 The absence of bleeding and important nonvascular pathology on brain neuroimaging in patients with acute- onset focal brain symptoms is usually sufficient evidence that the problem is brain ischemia, especially when the patient has stroke risk factors and cardiac or cerebro- vascular lesions shown by vascular imaging and cardiac evaluation. What if the Problem is Hemorrhage? Is the Bleeding Subarachnoid or Intracerebral? Hemorrhagic conditions should be separated into subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). These two subtypes of hemorrhage have different causes, different clinical findings, and different treatment strategies. About 5% of all strokes are due to SAH, and about 10% are due to ICH, depending on age, sex, ed- ucational and social status, and racial composition of patients studied.2,3 Subarachnoid bleeding usually occurs rapidly over several seconds. In some pa- tients,