Cocaine
About 70% of strokes arising with intranasal and intravenous use are caused by haemorrhage rather than infarction. However, the pattern of stroke may depend upon the preparation used and upon its mode of administration, since infarcts are as likely as haemorrhages when alkaloidal cocaine, “crack”, is smoked. This may be due to a complex interplay of pharmacokinetic and pharmacodynamic factors, as well as the concentration and type of contaminants, and whether there has been coincidental alcohol use (which more commonly accompanies intranasal cocaine use). These factors may all change the half lives of cocaine metabolites, their metabolic pathways, and their effects on the blood vessels. The liver metabolises cocaine with a half life of only about one hour, but its major metabolites last much longer, sometimes days, and they too have vasoconstrictive actions. The pharmacokinetics of cocaine and its metabolites show large inter-individual variation and there is evidence for prolongation of action in chronic cocaine abusers, which may also occur when alcohol is consumed simultaneously. This may explain why most strokes occur in chronic users and/or with alcohol use.
Haemorrhages may be intracerebral (basal ganglia, thalamic, lobar, or brainstem), intraventricular or subarachnoid. They may occur especially in individuals with pre-existing vascular malformations such as aneurysms and arteriovenous malformations (accounting for up to 50% of intracranial haemorrhage with cocaine). Most strokes tend to occur within an hour of use, especially for crack and intravenous cocaine, and most of the others within three hours. The surge in blood pressure is thought to be to blame for acute rupture. Blood pressure may no longer be elevated by the time of presentation, or alternatively, the hypertension may be wrongly attributed at presentation to the haemorrhage itself. Vasospasm has also been postulated to contribute to aneurysm rupture. In injecting addicts, with or without demonstrable infective endocarditis, septic arteritis and/or mycotic aneurysms need consideration as alternative causes of intracranial haemorrhage. Haemorrhagic transformation of infarcts is another cause. The possibility of cerebral vasculitis is often mentioned, but this is usually because of irregularity of arteries seen on angiography (see below). However histological proof is very seldom provided (a handful of cases only), especially in cases involving abuse of cocaine alone. No cases of vasculitis were found in several larger postmortem series of patients dying of intracranial haemorrhages. If vasculitis does occur in pure cocaine abuse, it must be very rare. Cerebral biopsy specimens examine only small vessels but in the few cases that have revealed vasculitis at postmortem, it is limited to these small vessels and spares the larger ones and would not be seen on angiography.
Infarction of brain, cord (usually anterior spinal artery syndromes) or retina is less common than haemorrhage, but may be particularly associated with smoking crack cocaine. There may be preceding transient ischaemic attacks (TIAs) in 10% of crack related infarcts. Patients tend to develop their infarct within a few hours of use, or wake up with a deficit the morning after. Imaging usually shows infarcts involving cortical or deep penetrating arteries. They often occur in individuals without conventional risk factors and through a variety of potential mechanisms, though again proof is seldom possible.
Cocaine and its metabolites do undoubtedly have major effects on cerebral (and other) arteries. The acute vasospasm has been demonstrated in animals, and by magnetic resonance angiography (MRA) and transcranial Doppler in human volunteers, and occurs in large and medium sized arteries, probably mediated by endothelin 1. In patients, angiography may show beading and focal stenosis, and there may also be associated large vessel occlusion. Such abnormalities may arise through vasospasm caused by the drug itself but the possibility of additional subarachnoid haemorrhage needs excluding. Postmortem specimens in a few patients have shown that arteries may sustain damage to the media and elastic lamina, but no abnormality has been detectable in most studies and in some patients no vasculopathy can be demonstrated (other than aneurysms and AVMs in cases with intracranial haemorrhage).
In half the cases of cocaine infarcts, angiography is unremarkable and does not show the above abnormalities. Occasionally intraluminal clot is seen in the internal carotid artery, perhaps possibly because of “stasis” distant to extracranial carotid artery spasm. Artery-to-artery embolism is therefore another possible mechanism for vessel occlusion, in addition to spasm, in situ thrombosis, and embolism from the heart.
lol