Correspondence *Oxford Kidney Unit, Churchill Hospital, Oxford OX3 7LJ, UK

Email claremacewen@doctors.org.uk

The case

A 40-year-old man presented to the emergency department of a district general hospital with writhing movements of his limbs, slurred speech and diplopia, all of which had developed shortly after waking that morning. He had been well the previous evening and had no history of trauma. The patient was agitated and uncooperative, with a Glasgow Coma Score (GCS) of 14. He had gaze paresis to the left hand side and athetosis of his left arm and leg. There was some spontaneous movement of his right limbs, and a neurological examination revealed bilateral upgoing plantar reflexes. The patient was apyrexial, with a blood pressure of 120/80, a regular pulse of 96 bpm, and a blood oxygen saturation of 100% on breathing room air. A cardiorespiratory examination was unremarkable.

The patient was unable to provide a history, but his medical notes revealed that he had sustained a right cerebellar infarct several years earlier, at which point a magnetic resonance angiogram (MRA), a transthoracic echocardiogram and a thrombophilia screen had been unremarkable. The patient had declined further investigation and had made a complete recovery. Otherwise, he had no medical problems, took no medication, and had no relevant family history of disease. He smoked 20 cigarettes a day and drank alcohol in moderation. His family were unaware of any illicit drug use.

An urgent CT scan of the patient's head revealed an old right cerebellar infarct and a basilar artery hyperdensity, consistent with basilar artery thrombosis (Figure 1). The 3-hour window for thrombolysis had already passed, and so the patient was given a loading dose of aspirin and was managed supportively. Over the next few hours, however, he deteriorated rapidly, and his GCS dropped to 8. He was intubated, sedated and ventilated, and he was transferred to a stroke unit. A repeat CT brain scan showed extension of the clot, but, importantly, no brainstem infarction. Angiography confirmed basilar artery occlusion extending distally from the mid-portion of the vessel (Figure 2a). There was some filling of the distal basilar artery from both posterior communicating arteries, and there was no evidence of dissection or atherosclerosis.

Figure 1 Brain CT scan in a patient with cocaine-induced basilar artery thrombosis.

The scan shows opacity in the basilar artery (arrow).

Full figure and legend (15K)Figures & Tables indexDownload Power Point slide (72K)

Figure 2 Angiography in a patient with cocaine-induced basilar artery thrombosis.

(A) Angiography of right vertebral artery showing basilar artery occlusion (arrow). (B) Recanalization of basilar artery after intra-arterial thrombolytic therapy and mechanical aspiration. The left posterior cerebral artery remains occluded (arrow).

Full figure and legend (17K)Figures & Tables indexDownload Power Point slide (73K)

At 11 hours after symptom onset, a decision was made to attempt recanalization through mechanical aspiration plus intra-arterial thrombolysis (recombinant tissue plasminogen activator 70 mg administered intravenously). Repeat angiography after intra-arterial thrombolysis showed recanalization of the basilar artery, but persistent occlusion of the left posterior cerebral artery (Figure 2B). The antiplatelet agent abciximab was administered intravenously at a dose of 5 mg, and a follow-up angiogram revealed that the occlusion was cleared.

The following day, the sedation that had been administered at the time of intubation was reduced, and the patient was able to open his eyes in response to commands and follow simple instructions. A dense left hemiplegia was apparent, with midline ocular bobbing and downbeat nystagmus. A repeat CT scan showed a right pontine infarct. Aspirin (150 mg once daily) and simvastatin (20 mg once daily) administration was initiated. Extubation proved difficult owing to recurrent apneic episodes and the patient's inability to protect the airway, both of which were attributed to brainstem dysfunction, and a tracheostomy was required to wean the patient from the ventilator.

Once the patient was off respiratory support, investigations began into the cause of this second ischemic stroke in a young man. A transesophageal echocardiogram with bubble contrast was obtained and was unremarkable. Repeat MRA showed a slightly narrow right vertebral artery, but no evidence of dissection. When the patient was well enough to communicate fully, his social history was explored further, and it was established that he regularly used cocaine. Both strokes had occurred following acute cocaine intake. It was agreed that cocaine was certainly the precipitating factor, and it was decided not to anticoagulate or investigate further.

After a week on neurointensive care, the patient was transferred to a specialist stroke unit, where he made excellent progress; by 5 weeks after the event, he had regained four-fifths the power in his left limbs, such that he could walk with assistance, and had only a mild scanning dysarthria. Nine months later, he is living independently at home with his family and is planning to return to work. His only complaint is of a mild loss of dexterity in his left hand and some residual difficulty in balance.

Discussion of diagnosis

Cocaine is an alkaloid prepared from the leaves of the Erythroxylon coca plant. Its main pharmacological mechanism of action is inhibition of norepinephrine reuptake by sympathetic neurons, although it also inhibits the reuptake of 5-hydroxytryptamine and dopamine. This results in a potentiation of sympathetic activity, leading to tachycardia, hypertension and vasospasm. Cocaine is also a local anesthetic, blocking fast sodium channels in excitable cells. Cocaine toxicity has a wide variety of manifestations, most of which are cardiovascular in nature (Box 1).

Cocaine is the second most commonly used illicit drug in both the US and the UK, after cannabis. The Home Office 2006–2007 British Crime Survey found that 2.6% of respondents between the ages of 16 and 59 years admitted to using cocaine at least once in the preceding year.¹ The prevalence was highest among those between 16 and 24 years old (6.1%). This represents a statistically significant increase from the previous decade. Stroke precipitated by cocaine is a therefore a phenomenon that doctors are encountering with increasing frequency, but no consensus has yet been reached on optimal management.

Between 25% and 60% of cocaine-induced strokes are ischemic in nature,^{2, 3} and the principal mechanism is vasospasm of large cerebral arteries. There is evidence, however, that cocaine causes thrombosis, possibly because vasospasm leads to secondary endothelial dysfunction and platelet aggregation. This might explain the accelerated atherosclerosis seen in cocaine users.⁴ In addition, cocaine can cause cerebral vasculitis, thereby predisposing the individual to thrombosis, although this mechanism remains controversial.^{5, 6} Cardioembolic ischemic stroke in patients with cocaine-induced cardiomyopathy has also been described.⁷ A rationale exists, therefore, for administering thrombolysis as a therapeutic intervention in certain patients.

It is vital that a diagnosis of ischemic stroke secondary to thrombus is made quickly and reliably in patients presenting with a neurological deficit after cocaine use. Thrombus can be distinguished from hemorrhage or vasospasm on CT, which can demonstrate a hyperdensity in the relevant cerebral vessel, as in the present case. Angiography is the gold standard investigation; it can provide a definitive diagnosis and can rule out associated dissection or cerebral aneurysms. In addition, this method enables radiological intervention and a direct assessment of the success of reperfusion therapy. It is not, however, readily available in some smaller centers.

Treatment and management

Cocaine-induced stroke has traditionally been managed supportively. In cases of confirmed thrombotic or thromboembolic stroke, the aim of treatment should be to establish reperfusion before irreversible ischemia occurs. There are two case reports to date in the literature describing intervention to achieve recanalization in cocaine-induced ischemic stroke. Vallee et al. described successful thromboaspiration in a young patient with a basilar artery clot induced by cocaine and ecstasy.⁸ Konzen et al. described a patient with carotid artery embolism following cocaine use who made a good recovery after carotid thrombectomy.⁹

In the present case, a decision was made to administer thrombolysis 11 hours after symptom onset—long after the standard 3-hour window for thrombolysis had passed. The rationale for this decision was that the window for thrombolysis is often longer in posterior circulation strokes than in anterior circulation strokes; the presence of collaterals can delay the development of irreversible ischemia, and the risk of hemorrhagic transformation is reduced owing to smaller volumes of infarcted tissue.¹⁰ MRI diffusion and perfusion weighted imaging is the best way to image the ischemic penumbra in such late presentations, in order to identify threatened but salvageable tissue that might benefit from thrombolysis.¹¹ In the present patient, however, the dire prognosis of complete basilar artery occlusion leading to coma,¹² combined with the reassuring appearance of the repeat CT brain scan, convinced the clinicians that expedient intervention without further imaging was the best management strategy.

The present patient was also treated with the antiplatelet agent abciximab when angiography revealed persistent occlusion of the left posterior cerebral artery after thrombolysis. Products of fibrinolysis paradoxically activate platelets, and there is some evidence that glycoprotein IIb-IIIa inhibitors such as abciximab increase recanalization rates when used as an adjunct to intra-arterial thrombolysis.¹³

To our knowledge, thrombolysis has not previously been reported as a treatment for cocaine-associated ischemic stroke. There might be several reasons for this. First, in the absence of timely imaging and skilled reporting, it might be assumed that the underlying pathology of neurological deficit after cocaine use is hemorrhage or vasospasm, rather than thrombosis. This highlights the importance of conducting an urgent CT head scan in all such patients. Second, information regarding illicit drug use might be unavailable, or not sought, as with the present patient's first stroke. As cocaine abuse becomes increasingly widespread, it is imperative to ask all patients specifically about illicit drug use, regardless of age or background.

Most importantly, the safety of thrombolytics in cocaine users has been questioned, following a report of fatal intracerebral hemorrhage as a complication of intravenous thrombolysis in a patient with cocaine-induced myocardial infarction (MI).¹⁴ There has been speculation that hypertension, vasculitis and mycotic aneurysms associated with cocaine use might translate into an increased rate of hemorrhagic complications.¹⁴ A retrospective cross-sectional survey by Hollander et al. found no evidence to support this, however, and the authors concluded that thrombolysis is a safe option in cocaine-induced MI.¹⁵ This does not mean that there is evidence of efficacy, which would require a much larger study, only that there is no evidence of harm. This safety data should be applicable to ischemic stroke in the same patient subgroup. Intravenous thrombolysis is more readily available than interventional angiography and might be a useful therapeutic option in certain individuals with cocaine-induced ischemic stroke.

It might be possible to predict which individuals are most at risk of developing hemorrhagic complications and to avoid thrombolysis in these patients. One study found that 48% of intracerebral hemorrhages and 78% of subarachnoid hemorrhages following cocaine use occurred in patients with an underlying vascular abnormality.¹⁶ Such abnormalities could potentially be detected by angiography, if available, before administering thombolysis. In addition, the risk of hemorrhage is increased by hypertensive cardiovascular disease.¹⁷

Conclusions

Medical practitioners are witnessing the use of cocaine and its devastating consequences with increasing frequency; therefore, it is important to ask about cocaine exposure as part of a routine cardiovascular history. Traditionally, cocaine-induced ischemic stroke has been managed supportively, with only two reported cases of mechanical thrombectomy.^{8, 9} An opportunity has now emerged to consider thrombolysis in certain individuals.

Extrapolating from safety data in patients with cocaine-induced MI, there is no reason to suppose that patients with cocaine-induced ischemic stroke would show increased hemorrhagic complications of thrombolysis. We believe that all patients with acute neurological deficit in the context of cocaine abuse should be investigated urgently with a CT head scan, and, if available, angiography, in order to elucidate the etiology of the stroke. In patients with confirmed thrombus and controlled blood pressure, intravenous or intra-arterial thrombolysis, with or without mechanical clot aspiration, should be considered as a therapeutic option. To date, there is only anecdotal evidence to support this approach, but the growing awareness of the role of cocaine in ischemic stroke should generate a sufficient number of cases to enable assessement of this treatment's efficacy.

Acknowledgments

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

References

1. Nicholas S. et al (Eds; online July 2007) Home Office Statistical Bulletin: Crime in England and Wales 2006/07, edn 4 [http://www.homeoffice.gov.uk/rds/pdfs07/hosb1107.pdf] (accessed 27 June 2008)
2. Daras M et al. (1994) Neurovascular complications of cocaine. Acta Neurol Scand 90: 124–129 | PubMed | ChemPort |
3. Levine SR et al. (1990) Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine. N Engl J Med 323: 699–704 | PubMed | ChemPort |
4. Treadwell SD et al. (2007) Cocaine use and stroke. Postgrad Med J 83: 389–393 | Article | PubMed | ChemPort |
5. Krendel DA et al. (1990) Biopsy-proven cerebral vasculitis associated with cocaine abuse. Neurology 40: 1092–1094 | PubMed | ChemPort |
6. Fredericks RK et al. (1991) Cerebral vasculitis associated with cocaine use. Stroke 22: 1437–1439 | PubMed | ChemPort |
7. Sauer CM (1991) Recurrent embolic stroke and cocaine-related cardiomyopathy. Stroke 22: 1203–1205 | PubMed | ChemPort |
8. Vallee JN et al. (2003) Basilar artery occlusion treated by thromboaspiration in a cocaine and ecstasy abuser. Neurology 61: 839–841 | PubMed |
9. Konzen P et al. (1995) Vasospasm and thrombus formation as possible mechanisms of stroke related to alkaloidal cocaine. Stroke 26: 1114–1118 | PubMed | ADS |
10. Brandt T (2002) Diagnosis and thrombolytic therapy of acute basilar artery occlusion: a review. Clin Exp Hypertens 24: 611–622 | Article | PubMed |
11. Gregory WA (1999) Expanding the window for thrombolytic therapy in acute stroke. Stroke 30: 2230–2237 | PubMed | ISI | ChemPort |
12. Voetsch B et al. (2004) Basilar artery occlusive disease in the New England Medical Center Posterior Circulation Registry. Arch Neurol 61: 496–504 | Article | PubMed |
13. Eckert B et al. (2003) Acute basilar artery occlusion treated with combined intravenous abciximab and intra-arterial tissue plasminogen activator. Stroke 33: 1424–1427 | Article |
14. Bush SH (1998) Cocaine-associated myocardial infarction—a word of caution about thrombolytic therapy. Chest 94: 878 | Article |
15. Hollander J et al. (1995) Cocaine-associated myocardial infarction: clinical safety of thrombolytic therapy: Cocaine Associated Myocardial Infarction (CAMI) Study Group. Chest 107: 1237–1241 | Article | PubMed | ChemPort |
16. Green RM et al. (1990) Multiple intracerebral haemorrhages after smoking crack cocaine. Stroke 21: 657–672
17. Kibayashi K et al. (1995) Cocaine-induced intracerebral haemorrhage: analysis of predisposing factors and mechanisms causing haemorrhagic strokes. Hum Pathol 26: 659–663 | Article | PubMed | ChemPort |

Contact the journal about this article

Subject areas under which this article appears: Stroke | Brain imaging