Clinical Worsening in Reversible Cerebral Vasoconstriction Syndrome

Abstract

eversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches, radiographic evidence of vasoconstriction with subsequent resolution, and a normal or near-normal cerebrospinal fluid profile. More than one-half of cases of RCVS occur postpartum or in association with exposure to serotonergic or adrenergic medications. 1 The syndrome is considered relatively rare, but its exact incidence is unknown. Because cerebral angiography-a requisite for diagnosis-is not always performed in symptomatic patients with recurrent thunderclap headache and/or transient neurological symptoms, the disorder is probably underrecognized. A high index of suspicion is necessary to diagnose RCVS, especially on initial presentation. The initial presentation of RCVS is not limited to recurrent thunderclap headache but can also include encephalopathy and seizures. Brain imaging can show cortical subarachnoid hemorrhage, intraparenchymal hemorrhage, or vasogenic edema. 1-6 Reversible cerebral vasoconstriction syndrome is traditionally considered to have a monophasic and benign clinical course. However, the clinical course after the establishment of the diagnosis has not been thoroughly studied. Previous reports detail transient ischemic attacks and cerebral infarction occurring as late as 2 weeks after the diagnosis of RCVS, some-IMPORTANCE Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches and evidence of vasoconstriction with subsequent resolution. The clinical course of RCVS is traditionally considered monophasic and benign. However, recurrent episodes of focal neurological symptoms have been described after initial presentation. OBJECTIVE To define the frequency, timing, and consequences of clinical worsening in patients with diagnosis of RCVS. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of consecutive patients with RCVS at 2 referral institutions for neurological disease. MAIN OUTCOME AND MEASURE Clinical worsening after diagnosis of RCVS. We defined clinical worsening as new permanent or transient neurological deficits (compared with presenting signs and symptoms) or new onset of seizures. We performed a logistic regression analysis to assess associations between patient characteristics and clinical worsening. Functional outcome was assessed at 1 to 3 months using the modified Rankin score. RESULTS We identified 59 patients (median age, 47 years; interquartile range, 32-54 years) with RCVS. Twenty patients (34%) experienced clinical worsening after a median of 2.5 days (range, several hours to 14 days). Eight of the 20 patients who worsened had permanent deficits, including 4 who died. We did not find an association between age, sex, smoking, migraine, acute or chronic hypertension, peripartum state, or use of serotonergic drugs with clinical worsening. Clinical worsening was associated with radiological infarction (P = .001) and worse functional outcome (P < .004). Functional outcome was favorable (modified Rankin score...

Reversible Cerebral Vasoconstriction Syndrome, Part 1: Epidemiology, Pathogenesis, and Clinical Course

“…2,3,6,11,23,[28][29][30][31][32][33][34][35][36][37][38] However, the association of RCVS with the most commonly reported triggers is more compelling, including the use of vasoactive drugs and the postpartum state, which together account for more than half of cases in most published series (approximately 50% and 9%-10% of cases respectively). 7,17,39 Sympathomimetic drugs commonly taken over the counter for upper respiratory tract infections, including phenylpropanolamine and pseudoephedrine, as well as antimigrainous medications, have historically been associated with subarachnoid hemorrhage and ischemic stroke in rare cases, which in retrospect likely reflects the sequelae of drug-induced RCVS. 40,41 The association between RCVS and the postpartum state is thought to possibly reflect increased levels of both pro-and antiangiogenic factors, some of which have also been associated with eclampsia, such as placental growth factor.…”

“…2,6,8,12,13,20,23,39,[57][58][59] In her meta-analysis of 3 large case series of patients with RCVS, Ducros 19 found that focal neurologic deficits were present in 8%-43% of patients, seizures in 1%-17%, cortical subarachnoid hemorrhage in 30%-34% (1 study had hemorrhage as an exclusion criterion and was not included), cerebral infarction in 6%-39%, and concomitant PRES in 9%-38% (Fig 2). This wide range in reported incidence of various sequelae of RCVS may reflect recruitment bias, with more ill patients being more likely to present for medical care; selection criteria; and the clinical context in which patients were encountered.…”

“…The syndrome typically follows a self-limiting, monophasic course, with resolution of symptoms by 3 weeks, and no new symptoms after 1 month. 1,13,17,23,39,57,77 By definition, resolution of vasoconstriction should occur by 3 months. However, a minority of patients will demonstrate delayed clinical worsening in the first few weeks following symptoms onset, most often due to the development of an ischemic infarct.…”

“…However, a minority of patients will demonstrate delayed clinical worsening in the first few weeks following symptoms onset, most often due to the development of an ischemic infarct. 39,42,43,77 A more fulminant course of RCVS leading to permanent disability or death can be encountered in 5%-10% of patients. 1,2,6,12,43,60,77 Recurrence of RCVS appears to be rare, though some patients may have chronic mild headaches and fatigue on follow-up.…”

“…2,42,43,78 RCVS encountered in the postpartum period deserves special attention because it has been reported to be more likely to follow a fulminant course, with multifocal infarct, intracranial hemorrhage, extensive vasogenic edema, and death. 1,39,60 When Fugate et al 33 evaluated patients with postpartum angiopathy in a small retrospective series (n ϭ 18), they found focal neurologic deficits in 50%, visual disturbances in 44%, encephalopathy in 33%, sei- zure in 28%, intracranial hemorrhage in 39%, vasogenic edema in 35%, and infarction in 35%. Somewhat unusual for RCVS, only slightly less than half of patients in this small series achieved a complete recovery, while the remaining patients either died or were left with significant neurologic deficits.…”