Stroke after Marijuana smoking in a teenager with factor V Leiden mutation.

ABSTRACT: Factor V Leiden is a well-recognized etiology of venous thrombosis, but reports of stroke in patients with this mutation are few. Marijuana smoking has rarely been associated with thrombosis of cerebral and renal arteries and may be due to a direct toxic effect on the endothelium. Reported here is the case of a previously healthy young man who smoked marijuana on a daily basis and had an occipital lobe stroke; he was found to be heterozygous for factor V Leiden. This case suggests that marijuana smoking may increase the risk of arterial thrombosis in otherwise healthy individuals who are heterozygous for factor V Leiden.

STROKE IN YOUNG PATIENTS has various etiologies, including cardiac, vascular, and hypercoagulable disorders. The factor V Leiden mutation is a common cause of unprovoked venous thrombosis in the white population. Use of oral contraceptives may increase the risk of cerebral venous thrombosis in women who carry this mutation. However, few cases of factor V Leiden mutation associated with cerebral arterial thrombosis and stroke have been reported. (1) Some studies have found an increased risk of cerebral arterial thrombosis in patients with this mutation, but other reports are conflicting. Reported here is the case of a young man who regularly smoked marijuana, had an occipital lobe stroke, and was found to be heterozygous for factor V Leiden.

CASE REPORT

A previously healthy 18-year-old man had acute loss of vision involving the left visual field. The symptoms persisted for several hours, and he received the diagnosis of complicated migraine at a local emergency department. The visual loss persisted, and the patient was referred by his local physician to an ophthalmologist, who noted significant left homonymous hemianopsia on visual field testing. Magnetic resonance imaging revealed an acute infarction of the right occipital lobe involving the calcarine cortex (Figure). The patient was hospitalized for further evaluation.

The patient admitted to smoking several marijuana cigarettes daily for many years and that he had been smoking marijuana the day of symptom onset. He denied use of other drugs or alcohol. Physical examination was notable for homonymous hemianopsia. A chest radiograph and transesophageal echocardiogram appeared normal. Magnetic resonance angiography showed occlusion of the right posterior cerebral artery without evidence of arterial dissection. Urine drug screen was positive for cannabinoids. The following blood studies yielded normal or negative results: hemoglobin, platelet count, white blood cell count, partial thromboplastin time, creatinine, liver enzymes, cholesterol, erythrocyte sedimentation rate, rapid plasma reagin, fibrinogen, proteins C and S, antithrombin III, homocysteine, antinuclear antibody, rheumatoid factor, protein electrophoresis, lupus anticoagulant, and anticardiolipin antibodies. Polymerase chain reaction revealed heterozygosity for factor V Leiden. The patient was treated with warfari n and told to avoid marijuana.

DISCUSSION

Factor V Leiden mutation has been reported only rarely as a cause of ischemic stroke in cases without other obvious etiologies. (1,2) The patient in this report was young and had no traditional risk factors for vascular disease, such as cigarette smoking, diabetes mellitus, hypertension, or hyperlipidemia. Extensive evaluation failed to reveal a cardiac source of embolism or other hypercoagulable disorders. Marijuana smoking has been rarely associated with stroke, and such occurrences may be due to cerebral vasospasm or transient systemic hypertension caused by marijuana or its metabolites. (3,4) Renal infarction due to renal artery thrombosis was reported in a patient who smoked marijuana on a daily basis and who had no other predisposing risk factors. (5) Cannabanoids may result in endothelial cell disruption and necrotizing vasculitis, which may lead to vascular thrombosis and end-organ ischemia or infarction. (5)

The factor V Leiden mutation prevents proteolytic cleavage of factor V by protein C, which leads to resistance of activated protein C. This confers a hypercoagulable state and increases the risk of venous thrombosis. However, a recent study (6) showed an increased risk of transient ischemic attack and stroke in patients younger than 50 years of age with heterozygous factor V Leiden mutation. Previous reports of cerebral infarction also suggest small vessel thrombosis may lead to stroke. (1,7) The patient in this report had thrombosis of the posterior cerebral artery and subsequent occipital infarction, which was possibly caused by a combination of hypercoagulability from factor V Leiden mutation and direct vascular damage from marijuana use. Clinicians should consider testing for factor V Leiden mutation in young patients with ischemic stroke and should specifically inquire about marijuana use if no other cause is apparent.

References

(1.) Marinella MA, Greene K: Bilateral thalamic infarction in a patient with factor v Leiden mutation. Mayo Clin Proc 1999; 74:795-797

(2.) Orlandi G, Pellegrinetti A, Fioretti C, et al: Factor V Leiden mutation in a case with ischemic stroke: which relationship? Angiology 1998; 49:79-82

(3.) Zachariah SB: Stroke after heavy marijuana smoking. Stroke 1991; 22:406-409

(4.) Barnes D, Palace I, O'Brien MD: Stroke following marijuana smoking (Letter). Stroke 1992; 23:1381

(5.) Lambrecht GLY, Malbrain MLNG, Coremans P, et al: Acute renal infarction and heavy marijuana smoking. Nephron 1995; 70:494-496

(6.) Bontempo FA, Hassett AC, Faruki H, et al: The factor V Leiden mutation: spectrum of thrombotic events and laboratory evaluation. J Vasc Surg 1997; 25:271-275

(7.) Yossepowitch O, Chajek-Shaul T, Rubinow A, et al: Resistance to activated protein C: arterial thrombosis associated with autoimmune features. Eur J Med Res 1997; 2:355-357

RELATED ARTICLE: KEY POINTS

* Stroke in young patients without evidence of structural abnormalities of the cerebral vessels or heart should be evaluated for systemic hypercoagulable conditions.

* Stroke in young patients without evidence of structural abnormalities of the cerebral vessels or heart should be evaluated for systemic hypercoagulable conditions.

* Marijuana smoking may lead to cerebral arterial thrombosis in patients heterozygous for factor V Leiden.