By Dr Nicolas Martinez-Majander, Department of Neurology, Helsinki University Hospital, Finland
A 38-year-old man was admitted to our hospital with a thunderclap headache and a transient left upper limb paresis. He was a non-smoker with no comorbidities or prior medications. He also reported having such headaches repeatedly during the previous two weeks, always associated with physical exercise. Initial non-contrast CT showed no ischemia or intracranial hemorrhage. However, on CT angiography we saw multiple arterial abnormalities with smooth narrowings followed by abnormal dilated segments especially in the more distal branches. There were no abnormalities of cerebrospinal fluid (CFS), and aneurysmal subarachnoid haemorrhage and infections of central nervous system were considered unlikely. Toxicology and infection screen were negative and the patient remained normoglycemic, normotensive, and no epileptic seizures emerged. Brain MRI the second day, however, revealed a small ischemic lesion in the right MCA territory. The patient was suspected of suffering from reversible cerebral vasoconstriction syndrome (RCVS) and treatment with nimodipine was started. In a control imaging at four weeks CT angiography abnormalities had resolved completely and the patient had a full recovery.
RCVS (sometimes also called Call-Fleming syndrome) is a vasculopathy syndrome with segmental constrictions of cerebral arteries that should resolve within three months.1 Typical symptoms and findings include a thunderclap headache, often with a paroxysmal occurrence. However, there are exceptions since up to 20% of cases can have only subacute headaches that are less severe and reoccur over the course of several weeks.2 Patients can develop intracranial hemorrhage, ischemic disturbance of the cerebral circulation, hypertensive encephalopathy (PRES) or epileptic seizures as complications. Associated symptoms might include focal neurological deficits, nausea, and vomiting.
These patients also tend to be younger than average patients with stroke and may have less cardiovascular risk factors. However, more than half the cases occur postpartum, after exposure to adrenergic or serotonergic drugs, or other triggers such as immunosuppressive drugs (tacrolimus and cyclophosphamide) and illicit drugs (cocaine, ecstasy, and marijuana).3
The onset of headache itself is usually triggered by e.g. physical exertion, sex, and sneezing. Transient or persistent neurological deficits are reported in 8-43% of cases, and up to one third of patients present with an intracranial haemorrhage, most frequently convexity subarachnoid haemorrhage (SAH) that is usually smaller than aneurysmal SAHs. The prevalence of intracerebral bleedings and ischemic strokes are estimated to be around 12-20% and 6-39%, respectively.4,5
Diagnostic work-up should include at least brain CT/MRI, CT/MR angiography of cerebral arteries and a lumbar puncture. Arterial imaging should be repeated if suspicion of RCVS is strong and the initial CTA/MRA remains unremarkable. It should also be repeated later to confirm that the arterial abnormalities are indeed reversible within 12 months. Transcranial doppler can be used in the follow-up of the arterial vasoconstriction as well. Also in RCVS, there might be slight abnormalities in the CSF sample, such as presence of small numbers of white blood cells (usually less than 10/ml), elevated protein levels, and erythrocytes (with SAHs caused by vasoconstriction).6 Diagnostic criteria for RCVS have been proposed previously,7,8 and the most important differential diagnoses include aneurysmal SAH, cervical artery dissection, cerebral venous thrombosis, migraine, and primary angiitis of the central nervous system (PACNS).
Treatment of RCVS included pain relief, blood pressure management especially in cases with intracranial haemorrhage, and treatment of seizures if present. Vasoactive agents (if used prior to RCVS) should be paused or stopped. Thus far, since RCVS is often self-limiting and since there are no randomized controlled trials showing superiority of any specific agents, treatment is still empirical guided by observational studies and expert opinions. Nimodipine is the most commonly used calcium channel blocker, but also verapamil and magnesium sulfate can be considered. These agents can be discontinued after resolution of symptoms and/or angiographic findings. The overall prognosis of RCVS is good and long-term morbidity and mortality low, mainly determined by the occurrence of stroke.1
- Ducros et al. Reversible cerebral vasoconstriction syndrome. Lancet Neurology 2012;11:906-917.
- Robert T et al. Reversible cerebral vasoconstriction syndrome identification of prognostic factors. Clin Neurol Neurosurg 2013;115:2351–2357.
- Singhal AB et al. Postpartum angiopathy and other cerebral vasoconstriction syndromes. Neurocrit Care 2005;3:91-97.
- Singhal AB et al. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol 2011;68:1005–1012.
- Ducros A et al. Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome: frequency, features, and risk factors. Stroke 2010; 41:2505–2511.
- Ducros A et al. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain 2007;130:3091–3101.
- Headache classification subcommittee of the International Headache Society. The international classification of headache disorders. Cephalalgia. 2004;24:1-160.
- Calabrese LH et al. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med. 2007;146:34-44.