Clinical manifestations

Presentation and course

Stroke can occur during the first minutes of acute intoxication with a drug, in the hours following ingestion, or weeks (rarely months) following intoxication. Recognition of the role of drug use in the pathogenesis of stroke requires familiarity with the acute effects of commonly used recreational drugs and a high index of suspicion. The signs and symptoms of a stroke are not different in the user of recreational drugs unless the user is acutely intoxicated. Rather, the physician must probe for a history of substance abuse from the patient, friends, and family. Given that drugs of abuse are typically produced illegally, there is little assurance that the patient has consumed the agent described and not some substitute drug of abuse. Thus, the clinical history alone must be considered of limited reliability. Identifying agents via toxicology screens or, rarely, analysis of drug samples themselves is important. Suspicion can be confirmed in many cases through prompt urine toxicology screening in patients who present during or soon after acute intoxication. Confirmation of the role of drug abuse as the cause of symptoms weeks and months after acute intoxication depends on a complete history and plausible mechanism of action, for example, a stroke caused by a necrotizing vasculitis due to chronic use of an amphetamine or infective endocarditis with cardioembolic stroke in an intravenous drug user who does not use sterile needles.

Identifying a stroke secondary to ingesting a specific drug permits a directed stroke work-up. For example, angiography may be indicated in patients taking drugs associated with vasculopathy or to search for vascular malformations in certain drug users with intracranial hemorrhage. Recognition that angiographic vasculopathy is due to abuse of a certain agent will prevent initiation of unnecessary treatments with possible morbidity, eg, long-term immunosuppression, which is appropriate for autoimmune but not drug-induced vasculopathy. Thus, familiarity with the cerebrovascular complications of drug abuse guides the patient’s diagnostic evaluation and determines long-term stroke prophylaxis.

Sympathomimetic drugs cause a common profile of acute intoxication. Users of amphetamines, amphetamine derivatives (MDMA, ephedrine, phenylpropanolamine, methylphenidate, etc.), and cocaine experience elation and increased alertness; motor activity, coordination, and physical endurance are increased. Orgasm is reportedly delayed and heightened. Pupils are dilated, systolic blood pressure is elevated, and reflex bradycardia is noted. Blood pressure might be normal in patients by the time they arrive for medical attention unless they are still intoxicated. Higher doses cause agitation, suspiciousness verging on paranoia, and violent acts. Palpitations and stereotyped motor behavior may be present. Chronic use causes labile mood, paranoia, and a frank psychosis resembling schizophrenia. Some users engage in "runs" of iterative drug use for several days, finally stopping because of insurmountable exhaustion, lack of funds, or because they are too disorganized to continue ingesting the drug (usually by injection) (08).

Intoxication with phencyclidine varies with the dose ingested. Lower doses heighten sensory perception and cause euphoria or dysphoria and mood lability. Higher doses increase agitation and induce a state of excited catatonia or frank paranoid psychosis with auditory hallucinations. Bizarre, potentially violent behaviors are seen. Analgesia occurs with higher doses. Phencyclidine intoxication is also associated with elevated systolic pressure, sweating, hypersalivation, miosis, burst-like nystagmus, and ataxia (04; 08).

Acute heroin intoxication causes a pleasant, dream-like euphoria with impaired concentration. Some users experience anxiety rather than drowsiness, and nausea and vomiting may occur. Pupils are small but reactive. Tone is decreased in the face and neck muscles. A dry mouth, difficulty urinating, constipation, and respiratory depression can be seen. Chronic users are often irritable and dysphoric, having developed tolerance to many of the acute effects of heroin use (08).

Cannabis and synthetic cannabis intoxication cause an increased sense of well-being, mild euphoria, and feelings of relaxation. High doses can cause hallucinations and paranoia. Systemic effects include mild reductions in blood pressure, increased heart rate, dry mouth, and dilation of corneal blood vessels.

Prognosis and complications

Patients who use methamphetamine are at risk for systemic vasculopathy. Screening for other organ system dysfunction is warranted. Patients who use cocaine may have myocardial ischemia, cardiac arrhythmias, or sudden death. Screening evaluation is warranted.

The systemic complications of stroke in the setting of acute heroin intoxication include hypotension, increased risk for pulmonary edema, and respiratory depression with possible hypoxia.

The prognosis is largely determined by whether or not the individual user continues to use these drugs. Many of the reported patients are "lost to follow-up," presumably because they have returned to drug use. Users of methamphetamine appear at risk for recurrent stroke due to ongoing vasculopathy.

Biological basis

Etiology and pathogenesis

Cocaine. Cocaine acts as a CNS stimulant by blocking the reuptake of norepinephrine and epinephrine after sympathetic stimulation, thus, potentiating the actions of the sympathetic nervous system. Cocaine reinforces its own use by inhibiting the reuptake of dopamine in the ventral tegmental area of the mesocorticolimbic system. The prolongation of the actions of dopamine in this area "rewards" cocaine use and encourages its reuse. It also acts as a local anesthetic by blocking the initiation or conduction of nerve impulses following local administration (29). Cocaine is ingested in two forms. Cocaine hydrochloride is injected intravenously or snorted intranasally. Alkaloidal (freebase or crack) cocaine is smoked.

Amphetamines. Amphetamines are the most potent CNS stimulants among sympathomimetic drugs. Methamphetamine has the most potent CNS effects of the amphetamines. These drugs facilitate the release of central norepinephrine and dopamine stored in synaptic vesicles. Wakefulness, attention, and the ability to perform simple but not complex mental tasks are improved in sleep-deprived subjects. Athletic performance is enhanced. At higher doses, dopamine is released in the neostriatum, leading to stereotyped behaviors. The release of dopamine in the mesolimbic cortex rewards amphetamine use and encourages its reuse. At the highest doses, they trigger the release of 5-hydroxytryptamine in the mesolimbic cortex, disturbing perception and causing frank psychosis. They may also directly stimulate 5-hydroxytryptamine receptors. They are also anorectic through their actions on the lateral hypothalamic feeding center (29). Amphetamines are taken orally, intravenously, or smoked (crystal methamphetamine). Intravenous formulations may be diluted with talc or cornstarch.

Amphetamine derivatives. Methylphenidate is structurally related to amphetamine but has greater stimulation of mental rather than physical activities. It has the same mechanism of action as the amphetamines. Higher doses are associated with an increased risk of convulsions. Like amphetamines, it is a polar molecule that achieves higher levels in the CNS (29). Methylphenidate is ingested orally; tablets are sometimes crushed and injected intravenously.

Several synthetic sympathomimetics have been employed to treat nasal congestion. Their alpha-agonist activity causes hypertension, and this effect has been invoked to explain acute stroke occurring in some patients using these agents. Ephedrine has both alpha- and beta-adrenergic agonist activity and also enhances the release of norepinephrine from sympathetic neurons. It is a CNS stimulant, although it is less potent than the amphetamines. Pseudoephedrine is a stereoisomer of ephedrine that is used as a nasal decongestant. Phenylpropanolamine is another synthetic sympathomimetic used to treat nasal congestion, but it causes less CNS stimulation (29). These drugs are primarily ingested orally.

Heroin. Heroin binds to mu opioid receptors in the brain. The proscription against legal use of heroin makes access to sterile needles and syringes difficult. Ignorance regarding sterile technique and the temporal exigencies of physical addiction increase the risk of infective endocarditis and its complications, including ischemic stroke via embolism, mycotic cerebral aneurysms, and intracranial hemorrhage.

Cannabis. Cannabis contains more than 100 different cannabinoid substances, the two most notable being delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component of cannabis, and CBD is the main nonpsychoactive component. There are two known cannabinoid receptors: CB1R, located in the central nervous system, and CB2R, found peripherally, particularly within immune system tissues. The amount of THC and CBD varies based on the plant, although studies have suggested increasing THC content and decreasing CBD content in recent decades (15). Cannabis can be smoked or ingested orally. It causes a euphoric sensation with reduced anxiety and alertness and altered perception; however, anxiety or dysphoria can occur in some individuals. Synthetic cannabinoids are a heterogeneous group of compounds but generally act at the CB1R receptor and have similar effects as cannabis. Because they can be much more potent than cannabis, they likely have a greater risk of adverse events, including agitated psychosis, hallucinations, and seizures.

The mechanisms by which drug abuse causes stroke are not fully understood but are likely heterogeneous. In this regard, it is useful to distinguish between stroke as a direct or an indirect medical complication of drug abuse. Direct medical complications result from the physiological action of the drug or its toxic effects. For example, it has been proposed that hemorrhagic stroke may be due to the sympathomimetic and hypertensive action of drugs like cocaine, methamphetamine, or amphetamine derivatives. The abrupt rise in sympathetic activity causes a sharp increase in blood pressure, which ruptures an intracerebral artery, causing a "hypertensive" hemorrhage or a vascular malformation or aneurysm, causing lobar or subarachnoid hemorrhage. This explanation is likely too simplistic, and poorly understood factors are likely involved. In general, the mechanisms of ischemic stroke are even less clearly defined.

Indirect complications are not immediately linked to a specific drug or its mechanism of action but, rather, to the means of its administration or to contaminants mixed in with the drug. For example, cardioembolic stroke can be secondary to bacterial endocarditis in an intravenous drug user who employs nonsterile needles. The drug injected is not relevant to the pathogenesis of endocarditis. Additionally, cocaine has been reported to cause myocardial infarctions and cardiomyopathies, creating the potential for cardioembolic stroke (17; 71; 06). Similarly, several drugs intended for intravenous use are mixed with talc or cornstarch, which have been found to occlude arteries, causing stroke. On autopsy, deposits of talc were found occluding the small vessels in the medulla of a young woman who crushed and injected tablets of methylphenidate and suffered a medial medullary stroke (56).

The cerebrovascular complications and specific proposed mechanisms by which they occur for the most commonly implicated drugs are described below.

Cocaine. Stroke following cocaine use typically occurs in the first minutes or hours after ingestion, rarely up to a week later. Headache is common, and seizures have been reported in 20% of patients. Approximately 80% of strokes attributed to the use of cocaine hydrochloride are hemorrhagic (46). Among those undergoing angiographic evaluation, roughly 50% have an underlying aneurysm or arteriovenous malformation (47). Among patients with aneurysmal subarachnoid hemorrhage, one study reported a higher re-rupture rate (7.7% vs. 2.7%, p< 0.05) and a higher rate of in-hospital mortality (26% vs. 17%, p< 0.05) among cocaine users (11). Many of the hemorrhages seen in patients without vascular malformations are deep, similar to hypertensive hemorrhages. In patients using alkaloidal cocaine, approximately half of strokes are ischemic, and 50% are hemorrhagic (47; 27). In a large, population-based case-control study of adults younger than 50 years of age, acute cocaine use, defined as use within 24 hours, was strongly associated with ischemic stroke (age-, sex-, and race-adjusted odds ratio = 6.4, 95% CI 2.2) (14). This study did not report suspected etiology of these infarcts, but a different small study suggested that large artery atherosclerosis is common, occurring in 44% (78). Several mechanisms have been proposed:

(1) Acute hypertension during the sudden surge of sympathetic activity plausibly explains the rupture of small penetrating arterioles in patients with deep hemorrhages or with ischemic strokes in the territories of small penetrating arteries. This would also explain the rupture of saccular aneurysms or arteriovenous malformations.

(2) Vasospasm has been observed in several angiographic studies done both acutely and subacutely (28; 32; 46; 44) and strongly suggested pathologically in one case (44). The vasospasm has been attributed to the direct effect of noradrenergic innervation of these vessels, but vasospasm has also been documented in vessels with sparse innervation (66). Cocaine-induced vasospasm is mediated by endothelin-1 (25). It has been postulated that vasospasm may be associated with hemorrhage by causing ischemia of the distal vessel wall as well as the cerebral parenchyma, resulting in a sudden rise in blood flow, causing vessel rupture when the vasospasm is relieved (10).

(3) Vasculitis has been suggested in a few cases (41; 48; 58; 53) and generally appears as a non-necrotizing small vessel angiitis involving arterioles and venules without granuloma formation or fibrinous degeneration. Controversy exists as to whether this represents a hypersensitivity angiitis or a true arteritis (08; 58; 53) or even diapedesis of leukocytes through the vessel wall. As a rule, these cases have not fulfilled rigorous pathological criteria for vasculitis. It should be noted that it is usually not seen on angiography because it affects vessels too small to be seen.

(4) Cocaine directly enhances platelet aggregation through increased synthesis of thromboxane A2 and increased responsiveness to arachidonic acid (77); a procoagulant effect via depletion of protein C and antithrombin III has also been proposed (33). This may increase the likelihood of thrombus formation at the site of vasospasm (44).

(5) A moyamoya-type vasculopathy occurring in two chronic cocaine users has been reported. One patient presented with aneurysmal subarachnoid hemorrhage, the other with bilateral ischemic stroke. Both patients had extensive collateral development with lenticulostriate networks (76). Patients with pseudocholinesterase deficiency may be especially vulnerable to cerebrovascular complications of cocaine because they cannot metabolize the drug efficiently (35).

Methamphetamine. Stroke following methamphetamine use can occur after oral, intravenous, or inhalational use. In many cases, stroke occurs within minutes to hours after last use but has been reported weeks and even months after last use (60; 45). Hemorrhagic stroke, including both intraparenchymal and subarachnoid hemorrhage, is more common than ischemic stroke, although both are possible (16; 52; 20; 69; 45).

Methamphetamine may cause stroke through several mechanisms. As a sympathomimetic, methamphetamine can cause acute hypertension and chronic use may cause long-term hypertension. Hypertension is a major risk factor for both ischemic and hemorrhagic stroke. Vasospasm with superimposed thrombosis has also been proposed (65). Chronic administration of methamphetamine has been associated with a necrotizing angiitis involving arterioles and capillaries, which has been likened to polyarteritis nodosa and hypersensitivity angiitis (67; 68; 16; 05; 08). It is also possible that methamphetamine use may lead to accelerated atherosclerosis (31). Affected vessels have been described as beaded with segmental narrowing and aneurysm formation. These abnormalities are not restricted to the central nervous system (16). Finally, there is an increased risk of severe dilated cardiomyopathy in methamphetamine users, which may represent a cardioembolic source of ischemic stroke (34).

Amphetamine derivatives. Intracerebral hemorrhage has been described in patients using "ecstasy", or methylenedioxymethamphetamine, and a vascular malformation was identified in at least one patient (18). Ischemic stroke due to MDMA has also been described (51). Phenylpropanolamine and pseudoephedrine have been linked to deep and lobar hemorrhages occurring a few hours after ingestion (75; 40; 74). Angiography in three cases showed the beading classically associated with amphetamine use (75; 40). A large, case-control study confirmed an association between a first use of phenylpropanolamine and hemorrhagic stroke in women; however, no association was identified with a firstuse of pseudoephedrine (42). Chronic abusers of these substances may be at higher risk. Ephedrine use has been linked to subarachnoid and intracranial hemorrhage and, less commonly, ischemic stroke (82; 75; 07). Angiography disclosed an aneurysm in one patient with subarachnoid hemorrhage and vasculitic changes in two patients with intracerebral hematomas. There have been a number of reports of stroke associated with the use of herbal remedies containing ephedra (70). A case-control study did not confirm an association between ephedra use and hemorrhagic stroke, except possibly with high doses of ephedra (57).

Ischemic stroke has been reported in users of prescription amphetamines and methylphenidate for attention deficit hyperactivity disorder (72). Large population studies, however, have failed to detect an increased risk of stroke in patients receiving pharmacotherapy for attention deficit hyperactivity disorder (30; 49). These studies may be limited by healthy user bias, but nonetheless, they are reassuring that these medications appear safe when used at typical doses in otherwise healthy subjects. Similarly, case reports of ischemic stroke possibly associated with phentermine have been described (43), but a large case-control study of an obese population did not identify an association between phentermine and stroke (21). These data highlight that there may be important differences across amphetamine derivative drugs that impact whether or not they present a risk for stroke.

Heroin. Heroin use most commonly causes stroke through complications of its intravenous injection. The use of nonsterile needles causes infective endocarditis and septic embolization. The mitral, aortic, and tricuspid valves are involved with varying frequencies (08; 55). Septic embolization and the rupture of mycotic aneurysms have been associated with ischemic stroke, subarachnoid hemorrhage, and diffuse vasculitis.

Peripheral thrombophlebitis secondary to repeated use of nonsterile needles may cause stroke through paradoxical embolism in a patient with a right-to-left intracardiac shunt. Foreign body embolization of talc and cornstarch admixed with heroin has also been documented. Rare cases of what is presumed to be a hypersensitivity angiitis have been reported in heroin users. Angiography in these cases demonstrated a small vessel arteritis or diffuse angiitis (08).

Cannabis and synthetic cannabinoids. There are case reports of stroke temporally associated with the use of both cannabis and synthetic cannabinoids (26; 03). Topical reviews have concluded that cannabis may increase stroke risk (81; 38), and proposed stroke mechanisms include cardiac arrhythmia, systemic hypotension, cerebral vasospasm, platelet aggregation, or oxidative stress (83; 02; 80; 15). Both cannabis and synthetic cannabis have also been suggested as causes of reversible cerebral vasoconstriction syndrome, which can present with subarachnoid hemorrhage, intraparenchymal hemorrhage, and ischemic stroke (22; 64). Data from the Behavioral Risk Factor Surveillance System, from the U.S. Centers for Disease Control, have found that frequent marijuana users have almost twice the risk of myocardial infarction and stroke compared to nonusers (63; 73). Additionally, a longitudinal cohort study of medical cannabis users found that cannabis users were at an increased risk of acute coronary syndrome or stroke compared to matched population-based controls (adjusted HR 1.44, 95% CI 1.08-1.93) (84).

Given the wide use of cannabis and the methodologic limitations of existing literature, it is difficult to establish a causal link between cannabis use and stroke. Multiple case-control studies have failed to detect an association between cannabis and stroke, including a large study that included 751 cases and 813 controls (01; 81; 23). Another large population-based cohort study from Sweden did not find an association between cannabis use and stroke before 45 years of age (24). A scientific statement from the American Heart Association published in 2020 found that “overall, evidence is still inconclusive for cannabis use and adverse cardiovascular outcomes” (62).

Hallucinogens. As mentioned earlier, several case reports link PCP to hemorrhagic stroke (04; 08). Data associating other hallucinogens (eg, LSD) with stroke are limited.

Barbiturates, other sedatives, and inhalants. No clear data associate these agents with stroke.

Epidemiology

The peak ages of patients with stroke related to drug abuse are in the third and fourth decades. The relative risk of stroke in drug users is 6.5 (95% confidence interval: 3.1 to 13.6) relative to nonusers after controlling for other stroke risk factors. When restricted to those under 35, it is 11.7 (confidence interval: 3.2 to 42.5) (39). Epidemiologic evidence suggests that stroke associated with drug abuse has been increasing and contributes to the increasing incidence of stroke in young adults (19; 50). Few data are available regarding the risk of stroke related to specific drugs of abuse; however, a study of hospital discharges in the United States found that there has been an increase in stroke related to infective endocarditis, from 2.4 to 18.8 hospitalizations per 10 million United States residents from 1993 to 2015 (61). The data in table 2 summarize estimates (%) of drug use in the past year during 2019 and 2020 in different age categories (79).

Table 2. Types of Illicit Drug Use in the Past Month (Percentages) 2019-2020

Prevention

Illicit drug use appears to wax and wane in cycles as a function of many factors, including availability, perceived risk to personal health, psychosocial status of the individual drug, and treatment efficacy.

Availability refers to accessibility within a given geographical location and actual cost as a percentage of disposable income. Geographic availability means users can easily purchase a drug within their neighborhood. Theoretically, this can be reduced by interdicting drug transportation before local delivery and sale. Successful interdiction may reduce drug use through the resulting increase in cost passed on by distributors to consumers to cover losses. Popularity is also affected by the cost per dose, which may rise with reduced availability. Attempted interdiction has been stymied in many cases because drug production is ubiquitous; arresting one trafficker or destroying one region of cultivation does not sufficiently reduce availability.

Perceived risk refers to the health risks associated with drug use. The clearest example is the decline in intravenous drug use after it was linked to the intravenous transmission of HIV and AIDS. The popularity of heroin subsequently fell until the purity of street heroin was sufficient to afford a "high" with inhalational ingestion.

Psychosocial status refers to the perception of the ill effects of single or chronic use of an individual drug within the community. Crack cocaine use fell when communities saw its disastrous effects on users due to its addictive potential. Crack users seemed willing to sacrifice anything to obtain their next dose. Phencyclidine use fell when people noted the prevalence of "bad highs" characterized by paranoia and violence. Psychosocial status also refers to whether a community tolerates drug use among its members. Social stigmatization may reduce the likelihood of initial experimentation in the individual user. This is only effective when community attitudes are conveyed to the potential drug user. Initial experimentation appears to begin among preadolescents and adolescents. Community attitudes have less effect when this age group has little parental or adult supervision. When illicit drug use is assigned low psychosocial status among all age groups, the demand for these substances will decline.

Treatment efficacy refers to the availability of treatment to help illicit drug users break their habit. It entails medical care through the withdrawal syndrome (if present) and psychological counseling to deal with factors underlying psychological addiction.

Differential diagnosis

Stroke related to drug use should be considered in all young patients with stroke, particularly in the absence of traditional vascular risk factors. Stroke in the young has many mechanisms, including premature atherosclerosis, arterial dissection, cardioembolism, prothrombotic states, and infection, and these should also be considered.

Diagnostic workup

Drug use should be suspected in any young person (under 55 years of age) who presents with a stroke. It should be remembered that drug use encompasses not only illegal substances like cocaine, methamphetamine, and heroin, but also diet pills, over-the-counter decongestants, prescription drugs, synthetic cannabinoids, and amphetamine derivatives. A detailed history should be sought from the patient, friends, and family. Urine toxicology screens should be sent immediately. They can be positive as early as 1 hour after ingestion and remain positive for 2 to 3 days. Chronic users may have positive toxicology screens for longer periods. Importantly, synthetic cannabinoids and amphetamine derivatives are not tested for in routine urine toxicology screens.

In general, evaluation of the young stroke patient in the setting of drug abuse is similar to that of a patient without a history of drug use. In particular, it should be noted that patients with intracranial or subarachnoid hemorrhage associated with drug abuse are no less likely to harbor underlying vascular lesions than other patients. Head CT is done in all patients. A lumbar puncture is needed in patients with suspected subarachnoid hemorrhage when the CT scan is negative. MRI may be helpful to identify patterns of ischemic stroke. MR or CT angiography may help identify underlying vascular abnormalities (vasospasm, stenosis, occlusion, vascular malformations, aneurysms). Transcranial Doppler may also be useful in identifying vasospasm. Conventional angiography may be necessary to exclude the presence of aneurysms or vascular malformations in patients with subarachnoid or intracranial hemorrhage and may reveal evidence of vasculitis or vasospasm in patients with ischemic stroke due to cocaine, amphetamine, or amphetamine-like agents. Blood cultures and transesophageal echocardiography should be performed to exclude endocarditis in stroke patients who have used drugs intravenously. Finally, as drug abusers represent a high-risk population, patients should be tested for HIV, syphilis, and other infectious diseases for which clinical suspicion exists. In a series of 42 patients with cocaine-related stroke, three had HIV, three had hepatitis, two had syphilis, and one had tuberculosis (59).

Management

Acute therapy for stroke in patients with suspected drug abuse generally should be similar to the care provided to all stroke patients, including adequate hydration, close neurologic monitoring, and attention to preventing medical complications. The role of tissue plasminogen activator in ischemic stroke due to drug abuse likely depends on the presumed mechanism. In the case of stroke associated with cocaine use, evidence suggests a combination of vasospasm and superimposed thrombosis may occur; in such cases, thrombolysis may be a reasonable therapeutic option. A small cohort study of acute ischemic stroke patients treated with thrombolysis comparing 29 cocaine-positive to 75 cocaine-negative patients found no increased risk of treatment complications in the cocaine-positive group and similar outcomes between the two groups (54). Ischemic stroke due to infective endocarditis, on the other hand, is associated with a high risk of hemorrhagic transformation, and tissue plasminogen activator is not recommended in this setting. Mechanical thrombectomy should be considered in acute stroke due to drug abuse when a large vessel occlusion is present.

In hemorrhagic stroke associated with acutely elevated blood pressure due to drug use, it may be reasonable to be somewhat more aggressive than usual in reducing blood pressure. Ideal therapy for ongoing vasculitis among users of methamphetamine has not been identified, partly because the pathogenesis of the vasculitis is unclear. Steroid therapy has been used in some patients on a short-term basis, but there is little evidence to suggest if this is beneficial. Calcium channel blockers, in particular the dihydropyridine agents (nifedipine, amlodipine, isradipine), have been advocated for the treatment of stroke in cocaine users, but no formal data exist regarding efficacy (37). Vascular malformations and aneurysms should be treated similarly to those occurring in patients without a history of drug abuse.

Patients should be closely monitored for symptoms of drug withdrawal and appropriate therapy instituted if necessary (eg, methadone in opiate addiction). As many abusers of illicit drugs also abuse alcohol, a low threshold should exist for initiating benzodiazepines for symptoms suggestive of alcohol withdrawal.

Long-term secondary stroke prevention strategies should obviously include cessation of the identified abused drug. Hypertension should be identified and treated. Antiplatelet therapy is probably indicated for patients with ischemic stroke, though there are limited data specifically applicable to stroke in the setting of drug abuse.

Special considerations

Pregnancy

Neonatal cerebral infarction, both ischemic and hemorrhagic, has been reported in infants born to mothers who had used cocaine within 2 to 3 days of delivery (12; 13). Elevated blood pressure and cerebral blood flow during the first 24 hours of life in these neonates may increase the risk of intracerebral hemorrhage.

Anesthesia

Anesthetic risks vary depending on the drug ingested and the cumulative effects of chronic drug use on health in general. Acute intoxication requires identification of the responsible agent before anesthesia or invasive procedures can be safely undertaken. A persistent prothrombotic state has been reported in some users of cocaine, methamphetamine, amphetamine derivatives, or other sympathomimetics. Angiography in these patients has been complicated by spontaneous intra-arterial thrombosis and cerebral infarction (82).