7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Differential diagnosis of transient ischemic attack and acute stroke : Louis R Caplan, MD : Scott E Kasner, MD : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 30, 2021. INTRODUCTION The symptoms of brain ischemia may be transient, lasting seconds to minutes, or can persist for longer periods of time. Symptoms and signs remain indefinitely if the brain becomes irreversibly damaged and infarction occurs. Unfortunately, the presence of neurologic symptoms does not accurately reflect the presence or absence of infarction, and the tempo of the symptoms is not diagnostic for the cause of the ischemia [1,2]. This is a critical issue because treatment depends upon accurately identifying the cause of symptoms, and the nature, location, and severity of causative cardiac, hematologic, and cerebrovascular abnormalities. The differential diagnosis of transient ischemic attack and stroke will be reviewed here. The evaluation of stroke and transient cerebral ischemia are discussed separately. (See "Overview of the evaluation of stroke" and "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) PERSISTENT NEUROLOGIC DEFICITS WITH ABRUPT ONSET Ischemic strokes are characterized by the abrupt or at least very acute onset of focal neurologic symptoms and signs that leave persistent neurologic deficits. Other disorders that have acute onset and cause persistent focal signs should be considered in the differential diagnosis. https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 1/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Intracerebral hemorrhages usually develop during minutes and cause gradually increasing focal signs. Patients with large hemorrhages often develop headache, vomiting, and reduced consciousness; these findings are typically absent in patients with small hemorrhages. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".) Brain tumors can cause an abrupt onset or worsening of symptoms; hemorrhage into a tumor is one mechanism for such a change. In addition, some tumors which are outside the brain (eg, meningiomas) reach a critical mass and can cause abrupt displacement of brain tissue with the sudden onset of symptoms. (See "Overview of the clinical features and diagnosis of brain tumors in adults".) Brain abscesses cause focal neurologic symptoms and signs which can begin abruptly; fever, headache, and seizures are common accompanying signs. (See "Pathogenesis, clinical manifestations, and diagnosis of brain abscess".) Nonketotic hyperglycemic stupor is often associated with focal neurologic signs; there may be a focal region of brain edema on brain imaging tests. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis".) Attacks of multiple sclerosis can begin abruptly and may have paroxysmal transient manifestations (see 'Other causes' below). Most often however, MS attacks develop over 5 to 21 days, a longer period than strokes. MS is most common in the third to fifth decades of life, while the frequency of stroke peaks later. A history of prior attacks is very important in making the diagnosis. (See "Manifestations of multiple sclerosis in adults".) Demyelination can occur around veins after various viral infections which result in the abrupt onset of multifocal signs that develop over days. This disorder is often called acute disseminated encephalomyelitis (ADEM). Other viral infections, particularly cytomegalovirus, can cause focal brain lesions associated with focal neurologic signs. TRANSIENT ISCHEMIC ATTACK Transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. In keeping with this definition of TIA, ischemic stroke is defined as an infarction of central nervous system tissue. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Definition of TIA'.) https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 2/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate The term "transient ischemic attack" was first introduced in the early 1950s based upon the recognition that a transient focal loss of neurologic function often preceded strokes [3]. In the years after this initial description in patients with carotid artery disease, various groups and committees arbitrarily defined TIAs as lasting less than 24 hours [2]. However, this classic definition of TIA was inadequate for several reasons. Most notably, there is risk of permanent tissue injury (ie, infarction) even when focal transient neurologic symptoms last less than one hour. Subsequent data showed that ischemic attacks that last longer than one hour are most often associated with brain infarction [4,5]. Most TIAs last less than one hour [2]. Thus, the benign connotation of TIA has been replaced by an understanding that even relatively brief ischemia can cause permanent brain injury. When strokes develop after a TIA, they almost always have the same cause as the TIA. Strokes occur most often within days or weeks after the TIA. Symptoms of TIA Transient ischemic attacks are caused by decreased blood flow to a local portion of the brain. Decreased perfusion can be due to blockage of blood flow to a brain region from an in-situ occlusion of a supply artery, or from embolism to that artery. Symptoms are focal, suggesting that they relate to dysfunction of a localized area of the brain. Symptoms are also transient when the arterial blockage passes (eg, following dissolution or distal passage of an embolus) or when collateral circulation is able to restore adequate perfusion to the region of ischemia. The symptoms and signs may fluctuate depending upon the adequacy of perfusion, which is in turn related to systemic factors (eg, blood volume, cardiac output, blood pressure, blood viscosity) and local factors (eg, propagation and embolization of clot, development of collateral circulation). The symptoms of TIAs depend upon the underlying vascular cause ( table 1) [6]. When ischemia is caused by penetrating artery disease, for example, the symptoms are usually stereotyped (eg, numbness of the face, arm, and leg on one side of the body, or hemiparesis). In contrast, attacks due to large artery occlusive disease have different symptoms in different attacks: When the carotid artery is narrowed or occluded, patients may have monocular blindness on the side of the occlusive lesion, weakness of the contralateral hand, or aphasia [3]. Occlusive lesions of the internal carotid artery in the neck or head, or of its major intracranial branches, the middle and anterior cerebral arteries, cause loss of cerebral hemisphere functions. Occlusive lesions of the vertebral arteries in the head and neck and of the basilar artery cause brainstem and cerebellar symptoms and deficits. https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 3/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Occlusive disease of the posterior cerebral arteries (PCAs) causes visual and somatosensory symptoms due to loss of function in the lateral thalamus and occipital lobe regions supplied by the PCAs. Thus, some TIAs, such as those causing transient monocular blindness, diplopia, and aphasia, are very specific for one vascular territory, while others, such as limb weakness or numbness, are compatible with a number of different territories. The occurrence of a TIA is not helpful in predicting the presence of brain damage, the cause and mechanism of the ischemia, or the prognosis [1,2]. Transient brain ischemia can be caused by a variety of different conditions (see "Definition, etiology, and clinical manifestations of transient ischemic attack"): Brain embolism arising from the heart, aorta, or proximal arterial vessels. Occlusive lesions of either large extracranial or intracranial arteries. These large artery lesions are associated with intermittent hypoperfusion of the symptomatic regions of the brain, or with embolization of fibrin-platelet (white thrombi) or erythrocyte-fibrin (red thrombi) clots into the distal brain circulation. Emboli often break up or pass through the vasculature, explaining the transiency of the neurologic symptoms. Occlusive lesions (either lipohyalinosis or atheromatous branch disease) of small microscopic-sized intracranial arteries and arterioles. Hypercoagulability and diseases that cause thrombosis of small vessels (eg, thrombotic thrombocytopenic purpura). TRANSIENT NEUROLOGIC EVENTS The differential diagnosis of TIAs includes all other causes of transient "spells." The Australians often use the nonspecific word "turns" for such transient episodes of neurologic dysfunction. In addition to TIAs, the most important and frequent causes of discrete self-limited attacks include ( table 2): Seizure Migraine aura Syncope Some disorders mentioned above cause focal abnormalities of brain function, while others cause dysfunction that is either widespread or difficult to localize to any one anatomic region https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 4/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate ( table 3). Certain disorders may also cause both focal and nonfocal attacks. Seizures, for example, can begin and remain focal or can be generalized. Similarly, patients with hypoglycemia usually have global deficits in alertness and cognition, but on occasion can have focal symptoms such as hemiplegia [7]. The term "transient neurological attack" (TNA) has been proposed to describe sudden neurologic symptoms that completely resolve within 24 hours, with no clear evidence to support a diagnosis of migraine, epilepsy, M ni re disease, hyperventilation, cardiac syncope, hypoglycemia, or orthostatic hypotension [8]. The symptoms of TNAs can be focal, nonfocal, or mixed. In this classification, focal TNAs represent TIAs, while TNAs with nonfocal or mixed symptoms are heterogeneous in terms of etiology. Like TIAs, both nonfocal and mixed TNAs appear to be associated with an increased risk of stroke [8]. In addition, some patients diagnosed with TNAs by experienced stroke neurologists have evidence of acute ischemic brain lesions on diffusion-weighted MRI [9]. This finding suggests that clinical features alone do not always distinguish TIA from TNA. Seizure An epileptic seizure refers to a transient occurrence of signs and/or symptoms due to abnormally excessive neuronal activity of the brain. Seizures, especially repeated focal seizures, can be followed by postictal paralysis or loss of other functions. (See "Evaluation and management of the first seizure in adults", section on 'Postictal period'.) Nonepileptic seizures are characterized by sudden changes in behavior that resemble epileptic seizures but are not associated with the typical neurophysiological changes that characterize epileptic seizures. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".) The symptoms of seizures and nonepileptic paroxysmal events are diverse. These are discussed in detail separately. (See "Evaluation and management of the first seizure in adults", section on 'Initial evaluation' and "Nonepileptic paroxysmal disorders in adolescents and adults".) Migraine aura Migraine aura is the complex of neurologic symptoms that often accompanies migraine headache. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Migraine aura'.) An aura presents as a progressive neurologic deficit or disturbance with subsequent complete recovery. Auras are thought to be caused by cortical spreading depression occurring in regions of the cortex that correspond to the clinical manifestations of the aura. Patients often have a history of migraine or migraine with auras that dates back years, sometimes beginning in childhood and adolescence. This contrasts with TIAs, which seldom recur over more than a few months. https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 5/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Auras typically occur before the onset of migraine headache, and the headache usually begins simultaneously with or just after the end of the aura phase. However, headache onset can rarely occur an hour or more after the end of the aura phase. Although atypical, an aura can develop during or after the onset of headache, and many patients have migraine aura with only a minimal or no headache. Most migraine auras resolve in 20 to 30 minutes and seldom last more than one hour. Typical auras may involve one or more of visual disturbances, sensory symptoms, motor weakness, or speech disturbances. Visual disturbances are the most common type of aura. Visual auras usually begin with seeing a small formed object or objects. The objects vary; stars, circles, squares, zig-zags, pointed lines, fire-flies, lightning bolts, heat waves, pinwheels, rods, beads are a few of the names given by patients. At times, the forms are linear and have angles and straight edges. The resemblance of the edges and lines to forts led to frequent use of the term "fortifications" and fortification spectra to describe this visual experience. Often the forms are bright and may be colored, especially red, green, blue, extra white, or purple. Migraineurs usually describe some type of motion, both in place and across the visual field. In-place motion is often described as flickering, shimmering, rotating, oscillating, or like a kaleidoscope. A key feature of the visual symptoms is buildup of the visual forms. The forms often become brighter, larger, and more objects may appear with time. Characteristically, the forms often move slowly across the visual field leaving a void or darkness (ie, a scotoma) in their wake. Often, as the forms move, the scotoma enlarges. In some patients, the predominant symptom is loss of vision without illusory forms. This can take the form of a black spot, but, more often, the visual loss is that of a hemianopia. Altitudinal or quadrantic visual field defects occur occasionally but are not common. The visual field loss is usually binocular and very similar in the two eyes. It may begin abruptly or progress over a few minutes. Total obscuration of vision with dimness or blackness also occurs. In most patients, the visual symptoms are the only aura symptom. In some patients, the visual symptoms are followed by paresthesias or other sensory phenomena. Less often, the attacks begin or consist solely of somatosensory symptoms. Somatosensory symptoms are the second most common type of migraine aura. Tingling, prickling, pins-and-needles, and numbness are the most common descriptions used to describe sensory phenomena. They may begin anywhere but probably favor the face and hand (cheiro-oral). A march, spread, or buildup of the somatosensory symptoms is https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 6/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate characteristic. At times, the paresthesia spread from one finger to the next, gradually spreading up the hand to the wrist, then to the arm, and then to the shoulder. Most often the initial symptoms are "positive," that is, paresthesia and other spontaneous abnormal sensations rather than a loss of feeling. When the paresthesia move up a limb, they often leave a numbness and loss of feeling in their wake. The parallel between the visual and somatosensory symptoms is clear. A spread or march of positive phenomena (eg, scintillations, sparkles, paresthesias) followed in the wake of the slow spread by negative phenomena (eg, loss of vision, scotomas, and numbness). Like the visual scintillations, the march of paresthesias is relatively slow, much slower than in a seizure, in which the sensory march usually takes seconds. Some patients only note numbness and have no paresthetic symptoms. When visual symptoms precede sensory symptoms, the visual symptoms usually, but not always, clear before the sensory symptoms begin. The march of symptoms includes not only gradual spread within each modality, such as vision and sensation, but also a gradual changeover from one modality to another. Late-life migraine accompaniments are symptoms related to the onset of migraine aura without headache in patients who are 50 years of age or older. The most common symptoms are visual auras, followed by sensory auras (paresthesia), speech disturbances, and motor auras (weakness or paralysis). (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Late-life migraine accompaniments'.) The relationship between migraine and ischemic stroke is discussed in detail separately. (See "Migraine-associated stroke: risk factors, diagnosis, and prevention".) Syncope Syncope is the abrupt and transient loss of consciousness associated with absence of postural tone, followed by a rapid and usually complete recovery. Syncope is caused by an interruption of energy sources to the brain, usually because of a sudden reduction of cerebral perfusion. Common types of syncope include: Neurocardiogenic (vasovagal) syncope Situational syncope (during or immediately after urination, defecation, cough, or swallowing) Orthostatic syncope (associated with orthostatic hypotension) Syncope related to cardiac ischemia or cardiac arrhythmia https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 7/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate These are reviewed in detail elsewhere. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".) Transient global amnesia Transient global amnesia (TGA) is reviewed here briefly and discussed in detail separately. (See "Transient global amnesia".) Briefly, TGA is a syndrome characterized by the acute onset of severe anterograde amnesia accompanied by retrograde amnesia, without other cognitive or focal neurologic impairment. The amnesia resolves within 24 hours. Most patients are middle aged or older adults. Episodes are usually not recurrent, but some patients have infrequent attacks that recur over several years. The etiology of TGA is uncertain. Most TGA episodes are probably related to vasoconstriction, but some may be caused by transient ischemia or complex partial seizures. TGA can be associated with small focal abnormalities on diffusion-weighted MRI, but the significance of these remains unclear. Other causes Less frequent causes of transient neurologic events include the following: Metabolic perturbations, such as hypoglycemia, can be associated with focal neurologic deficits. Multiple sclerosis occasionally can cause paroxysmal attacks, particularly of ataxia and dysarthria. (See "Manifestations of multiple sclerosis in adults", section on 'Paroxysmal symptoms'.) Brain tumors can occasionally result in transient neurologic symptoms; the mechanism in these cases is thought to involve mechanical changes that result in pressure on structures adjacent to the tumor. (See "Overview of the clinical features and diagnosis of brain tumors in adults".) Subdural hematomas may cause attacks of transient neurologic dysfunction, again due to mechanical changes that result in pressure on structures adjacent to the hematoma. (See "Subdural hematoma in adults: Etiology, clinical features, and diagnosis".) Intracerebral hemorrhage can rarely present with rapidly resolving symptoms and signs that resemble transient ischemic attacks [10]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".) https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 8/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Cerebral amyloid angiopathy, better known as a cause of intracerebral hemorrhage, may also cause transient neurologic symptoms. Affected patients complain of recurrent, brief (minutes), often stereotyped spells of weakness, numbness, paresthesias, or other cortical symptoms that can spread smoothly over contiguous body parts. (See "Cerebral amyloid angiopathy", section on 'Transient focal neurologic episodes'.) Hepatic, renal, and pulmonary encephalopathies can produce temporary aberrations in alertness, behavior and movement. Compressive myelopathy [11] and spinal dural arteriovenous fistulas [12,13] may occasionally present with sudden transient sensory changes and motor deficits, especially in the bilateral lower limbs. Pressure- or position-related peripheral nerve or nerve root compression can cause transient paresthesias and numbness. Peripheral vestibulopathies can cause transient episodic dizziness. (See "Approach to the patient with dizziness" and "Evaluation of the patient with vertigo".) Hysteria and other psychiatric disorders may underlie attacks that include swoons, falls, and episodic blindness, deafness, and paralysis, which can be confused with organic loss of function. DISTINGUISHING TRANSIENT ATTACKS The history is important in distinguishing the various causes of transient attacks. Useful historical features include ( table 2): The focal or nonfocal nature of attacks The nature of the symptoms and their progression The duration and timing of symptoms Associated symptoms during and after the attacks The evaluation of a patient presenting with acute symptoms suggestive of TIA or ischemic stroke is outlined in the algorithm ( algorithm 1) and discussed in detail separately. (See "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) Nature of symptoms Symptoms can be categorized using Jacksonian terminology as either "positive" or "negative." https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 9/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Positive symptoms indicate active discharge from central nervous system neurons. Typical positive symptoms can be visual (eg, bright lines, shapes, objects), auditory (eg, tinnitus, noises, music), somatosensory (eg, burning, pain, paresthesia), or motor (eg, jerking or repetitive rhythmic movements). Negative symptoms indicate an absence or loss of function, such as loss of vision, hearing, feeling, or ability to move a part of the body. Seizures and migraine auras characteristically (but not always) begin with positive symptoms, while TIAs invariably are characterized by negative symptoms. Seizures occasionally cause paralytic attacks but, on close observation, there are usually features of the history and physical examination that suggest the presence of a seizure disorder such as minor twitching of a finger or toe or a tingling sensation in the affected limb [14]. Progression and course The progression and course of the symptoms are also helpful in the differential diagnosis. Migraine aura often progresses slowly within one modality. As an example, scintillations or bright objects tend to move slowly across the visual field. Paresthesia may gradually progress from one finger, to all the digits, to the wrist, forearm, shoulder, trunk, and then the face and leg. This progression normally occurs over minutes. After the positive symptoms move, they are often followed by loss of function. The moving train of visual scintillations may end in a scotoma or visual field defect. Similarly, as paresthesia travel centripetally, they may leave the initial areas of skin numb and devoid of feeling. Migrainous aura typically progresses from one modality to another; after the visual symptoms clear, paresthesia begins. When paresthesia clear, aphasia or other cortical function abnormalities may develop [15-17]. In contrast to migraine: Seizures usually consist of positive phenomena in one modality which progress very quickly over seconds. TIA symptoms are negative; when more than one modality or function is involved, all are affected at about the same time. Loss of consciousness is very common in seizures and syncope, which usually produce relatively stereotyped attacks; in comparison, loss of consciousness is rare in TIAs, and symptoms can be stereotyped or different in various TIAs. Duration and tempo The duration and tempo of attacks also are useful in predicting the cause: https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 10/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Migrainous auras characteristically last 20 to 30 minutes, although they may persist for hours TIAs are usually fleeting, usually lasting less than one hour Seizures last on average about 30 seconds to 3 minutes; some seizures, including absence attacks, atonic seizures and myoclonic jerks, are shorter in duration Syncope is very brief (seconds) unless the patient is artificially propped up or otherwise cannot obtain a supine position Seizures occur sporadically over the years but sometimes appear in flurries. In comparison, TIAs usually cluster during a finite period of time and can occur as frequent "shotgun"-like attacks, and syncopal attacks are scattered over years. Attacks that are scattered over many years are almost always either faints, migraines, or seizures; TIAs almost never continue over this time span. Precipitating factors Precipitants often give clues to the cause of attacks. Activation of seizures may occur in some patients after stroboscopic stimulation, hyperventilation, stopping antiseizure medications, fever, and alcohol or drug withdrawal. In some patients, TIAs occur when blood pressure is reduced, or upon sudden standing or bending. Dizziness and vertigo in patients with peripheral vestibulopathies are often triggered by sudden movements and positional changes. The "classical" or "typical" presentation of vasovagal syncope refers to syncope triggered by emotional or orthostatic stress, painful or noxious stimuli, fear of bodily injury, prolonged standing, heat exposure, or after physical exertion. As examples, vasovagal syncope commonly occurs when patients see blood, have or are about to have phlebotomy or other medical procedures, see an electric saw poised to remove a plaster cast on their arm or leg, stand up for a long time in church, or when a dental drill is aimed directly at their open mouth by a dentist. Hypovolemia also frequently precipitates syncope. Associated symptoms Non-neurologic associated symptoms can be characteristic of certain disorders. Headache is common after migraine aura and following a seizure. Headache can also occur during a TIA, but rarely at the same time or directly after neurologic symptoms. A bitten tongue, incontinence, and muscle aches are frequently associated with seizure. Vomiting is common after migraine and occasionally follows syncope, but is rare after or during https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 11/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate TIA and rare in relation to seizure. In the latter circumstance, vomiting may develop after the patient has lost consciousness; patients do not recall vomiting unless they see the vomitus when they awaken. Nausea and a need to urinate or defecate often precede or follow syncope; sweating and pallor are other common features of syncope. Age and sex of patient Demographic information may be helpful but there is substantial overlap ( table 2). Seizures occur at any age, while TIAs are not very common in young individuals, particularly those who do not have prominent risk factors for vascular disease (eg, hypertension, diabetes, smoking, cardiac disease, sickle cell disease, etc). In otherwise healthy women who are pregnant, transient focal neurologic symptoms are often related to migraine with aura, and usually have a benign outcome [18]. Syncope has little predilection for age, but is more common in women. TIAs and strokes are somewhat more common in men, although after menopause the frequencies are nearly equal in the two sexes. Seizures have no strong sex predilection. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Beyond the Basics topics (see "Patient education: Transient ischemic attack (Beyond the Basics)" and "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)") https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 12/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate SUMMARY Ischemic stroke is characterized by the abrupt or at least very acute onset of focal neurologic symptoms and signs that leave persistent neurologic deficits. Other disorders that have acute onset and cause persistent focal signs should be considered in the differential diagnosis, including intracerebral hemorrhage, brain tumor, brain abscess, nonketotic hyperglycemic stupor, attacks of multiple sclerosis, and acute disseminated encephalomyelitis (ADEM). (See 'Persistent neurologic deficits with abrupt onset' above.) Transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Ischemic stroke is defined as an infarction of central nervous system tissue. The symptoms of TIAs are typically focal and depend upon the underlying vascular cause ( table 1). (See 'Transient ischemic attack' above.) In addition to TIA, the most important and frequent causes of discrete self-limited attacks include seizure, migraine aura, and syncope ( table 2). Transient global amnesia or TGA is an uncommon syndrome characterized by the acute onset of temporary but severe anterograde amnesia accompanied by retrograde amnesia, without other cognitive or focal neurologic impairment. (See 'Transient neurologic events' above.) Other less frequent causes of transient neurologic events include hypoglycemia, multiple sclerosis, brain tumor, subdural hematoma, cerebral amyloid angiopathy, various toxic or metabolic encephalopathies, compressive myelopathy, nerve root compression, peripheral vestibulopathies, and psychogenic etiologies. (See 'Other causes' above.) Useful features for distinguishing the various causes of transient attacks include the focal or nonfocal nature of attacks, the nature of the symptoms and their progression, the duration and timing of symptoms, and associated symptoms during and after the attacks ( table 2). Some disorders cause focal abnormalities of brain function, while others cause dysfunction that is either widespread or difficult to localize to any one anatomic region ( table 3). Certain disorders may cause both focal and nonfocal attacks. (See 'Distinguishing transient attacks' above.) The evaluation of a patient presenting with acute symptoms suggestive of TIA or ischemic stroke is outlined in the algorithm ( algorithm 1) and discussed in detail separately. (See "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 13/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Caplan LR. TIAs: we need to return to the question, 'What is wrong with Mr. Jones?'. Neurology 1988; 38:791. 2. Caplan LR. Transient ischemic attack: definition and natural history. Curr Atheroscler Rep 2006; 8:276. 3. FISHER M. Occlusion of the internal carotid artery. AMA Arch Neurol Psychiatry 1951; 65:346. 4. Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack proposal for a new definition. N Engl J Med 2002; 347:1713. 5. 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Vascular malformations of the spinal cord and dura. Neurosurg Clin N Am 1990; 1:631. 13. Krings T, Geibprasert S. Spinal dural arteriovenous fistulas. AJNR Am J Neuroradiol 2009; 30:639. 14. Villani F, D'Amico D, Pincherle A, et al. Prolonged focal negative motor seizures: a video-EEG study. Epilepsia 2006; 47:1949. 15. Fisher CM. Transient paralytic attacks of obscure nature: the question of non-convulsive seizure paralysis. Can J Neurol Sci 1978; 5:267. https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 14/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate 16. Fisher CM. Migraine accompaniments versus arteriosclerotic ischemia. Trans Am Neurol Assoc 1968; 93:211. 17. Caplan LR. Nonatherosclerotic vasculopathies. In: Caplan's Stroke: A Clinical Approach, 4th e d, Saunders, Philadelphia 2009. p.389. 18. Liberman A, Karussis D, Ben-Hur T, et al. Natural course and pathogenesis of transient focal neurologic symptoms during pregnancy. Arch Neurol 2008; 65:218. Topic 1137 Version 19.0 https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 15/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate GRAPHICS Symptoms of transient ischemic attacks and the vascular territories involved ICA/MCA VA/BA PCA SVD Visual abnormalities Transient ++++ monocular blindness Hemianopia + +++ Blindness ++ ++ Motor abnormalities Hemiparesis + + ++ Quadriparesis ++++ Single part weakness Face + ++ + Arm/hand +++ + Thigh/leg/foot ++ + + Crossed weakness* ++++ Limb ataxia/weakness ++ ++ Gait ataxia +++ + Sensory abnormalities Hemisensory + ++ ++ Single part sensory Face + ++ + ++ Arm/hand ++ ++ + Thigh/leg/foot + + + + Crossed sensory* ++++ Cognitive abnormalities Aphasia ++++ + https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 16/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Amnesia + +++ Alexia +++ +++ Abulia ++ + + Brainstem and cranial nerve symptoms Dizziness/vertigo + +++ Diplopia ++++ Dysarthria + ++ ++ Dysphagia ++ ++ Tinnitus/hearing loss ++++ ICA: internal carotid arteries; MCA: middle cerebral arteries; VA: vertebral arteries; BA: basilar artery; PCA: posterior cerebral arteries; SVD: small vessel disease. Crossed weakness or crossed sensory refers to one side of the cranial structures and the opposite side limbs and trunk. Graphic 71676 Version 5.0 https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke/print 17/24 7/5/23, 12:38 PM Differential diagnosis of transient ischemic attack and acute stroke - UpToDate Clinical features of seizures, syncope, and other paroxysmal neurologic events in adults Clinical Recall of the Diagnostic Duration features event tools Focal seizure Initial symptoms depend on location in brain; Usually <2 minutes; can be difficult to Variable depending on whether EEG may show interictal spikes (poor sensitivity); motor and visual symptoms usually "positive" (eg, shaking, jerking, flashing lights, or visual distortion); distinguish ictal from postictal phase consciousness is impaired ambulatory EEG if episodes are frequent enough; MRI may show structural lesion may have anatomic "march" over seconds; some progress rapidly to GTC Generalized seizure Sudden alteration or loss of <5 minutes (for GTC); <1 minute Complete amnesia; patient EEG may show generalized spike- consciousness without warning; some have myoclonic jerks or staring; tongue- biting and urinary incontinence may for absence may recall initial focal symptoms and-wave characteristic of specific syndrome; MRI usually normal for generalized epilepsy occur (for GTC) syndromes, may show structural lesion if focal onset Psychogenic nonepileptic seizure Fluctuating, asynchronous motor activity, Rarely <1 minute; often prolonged (>30 minutes)