What is confusing about many of these cases is the normal angiographic appearance in many instances and large vessel occlusions in others, in contrast to the pathologic changes, which are concentrated in small cortical vessels. Many cases seem to be of an entirely different type, displaying long segments of vascular attenuation in the angiogram and no evidence of an inflammatory process in biopsy or autopsy material. The correct treatment, aside from lowering the blood pressure, is uncertain. A similar apparently vasospastic disorder is emerging from the use of high-potency cannabinoids (e.g., K-2, “spice”), including strokes.
Singhal and colleagues and others have brought to attention that serotonergic drugs may produce reversible multifocal vasospasm, severe headache, and stroke. One of their patients was using the antimigraine medicine sumatriptan; others were using serotonin reuptake inhibitor antidepressants and, in addition, had taken over-the-counter cold remedies that included pseudoephedrine and dextromethorphan; we are aware of other similar cases. These authors proposed that in these cases a “serotonin syndrome” had occurred, similar to what has been seen with overdoses of this class of antidepressants.
A drug-induced vasculitis, typical of the ingestion of sympathomimetic compounds, is difficult to distinguish from a more common state of focal or diffuse vasospasm that may also be induced by these same agents. The nature of this process is indeterminate but may be related to the deposition of circulating immune complexes in the walls of cerebral vessels.
Whether there is an increased incidence of arteriovenous malformation and cerebral aneurysm in patients who have cerebral hemorrhages after ingestion of cocaine, as suggested in several articles, is uncertain but this, in any case, suggests that sympathomimetic drugs can precipitate hemorrhage from an underlying developmental vascular lesion (Fessler et al).
Crack cocaine may also cause a choreiform disorder (“crack dancing”), not unlike that associated with antiphospholipid antibody but generalized rather than focal (see further on); usually there are small infarctions in the basal ganglia, but an immune mechanism has also been suggested.
The nature of diffuse vasospasm when there is no hyperadrenergic precipitant, trauma, or arterial dissection, is unknown. This was the process noted by Call et al. A relationship to hypertensive encephalopathy or to delayed postpartum eclampsia has been suggested because of the aforementioned widespread cerebral vasospasm that may be seen in eclamptic women, even those with marginally elevated blood pressures. Two of our patients have been in the postpartum period and other such patients have been described in the first 3 weeks after delivery. In an autopsy studied case, Kheir and coworkers found, in addition to fatal cerebral edema, a range of vascular cerebral parenchymal changes, mostly fibrinoid necrosis, perivascular hemorrhage, and exudates, all features found in hypertensive encephalopathy.
Treatment, alluded to above, has been difficult to establish. Systemic administration of calcium channel blockers or magnesium has given mixed results but is often used. Some groups have resorted to intrarterial injection of these agents. Stellate sympathetic block has been tried. Systemic glucocorticoids have been tried but retrospective one single center series suggested they may be detrimental (Singhal and Topcuoglu). A review of the subject is given by Ducros. The relationship of this process to a true vasculitis of cerebral vessels, most often from drug exposure, is uncertain and discussed separately below under “Arteritis Symptomatic of Underlying Systemic Disease and Sympathomimetic Drug Ingestion.”