Reversible Cerebral Vasoconstriction Syndrome

Dear editor,

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiological syndrome characterised by the sudden onset of severe headaches and multifocal segmental vasoconstriction of the cerebral arteries. Because of the rapid onset of cephalalgia, it is classified in the thunderclap headache group (this term is being used for severe headaches reaching their maximum intensity within one minute). Cephalalgia in RCVS can appear as a single attack, or it can recur within 1–4 weeks. It is usually bilateral, and it might be accompanied by nausea, vomiting, photophobia and disorientation [1]. In some cases, focal neurological deficit may be present (hemianopsia or cortical blindness, hemiparesis, dysarthria, aphasia or ataxia) [2–4]. Major complications of RCVS involve minor cortical subarachnoid haemorrhage (SAH), intracerebral bleeding, ischemic stroke and, rarely, epileptic seizures [3,4]. RCVS may appear in all age groups with occurrences peaking in the fifth decennium. Women are affected more often [1,5]. The syndrome used to have different eponymous and syndromological denominations in the past. The designation RCVS appears frequently in literature since 2007, when Calabrese et al. used it in a paper that mapped the syndrome cases published previously under various designations [6]. However, this denomination can even be found in 20-year-older literature [7].

A 21-year-old male suffered from an acute onset of a diffuse headache at rest shortly after lunch. After 20 minutes, he also experienced bilateral blindness. During the initial examination at the outpatient department of internal medicine at the regional hospital, the patient was disoriented and could not communicate. The subsequently obtained medical history revealed only the meningitis experienced in childhood; family and pharmacological history were negative. The patient was a non-smoker. Due to the severity of his condition, the patient was transferred to the department of emergency medicine at a university hospital. During transport, the patient vomited repeatedly. On arrival, the blindness and diffuse cephalalgia persisted, but the patient already communicated adequately. He was slightly somnolent and slightly disoriented in time. Other neurological findings were normal. The patient was examined by CT of the brain including CT angiography (CTA) – no pathological findings were detected. Three hours after the onset of the symptoms, cerebrospinal fluid was collected. Its examination, including spectrophotometry, did not show any evidence of neuroinfection or SAH. Blood examination found leucocytosis (16 × 10⁹/L) without an increase in C-reactive protein levels. Toxicologic blood examination of the presence of cannabinoids and amphetamine was negative. Five hours following the onset of the symptoms, the patient was admitted to an intensive care unit at the department of neurology. The cephalalgia was alleviated by the administration of opioids. At that time, the blindness waned, and the patient could distinguish silhouettes. On the next day, completely normal vision was spontaneously restored. On that same day, magnetic resonance imaging (MRI) of the brain was completed, and it did not detect any focal changes of the brain or extracerebral haemorrhage. Intracranial MR angiography (MRA) did not show any arterial stenoses or occlusions, vascular malformations or sinus thromboses. Hypoplasia of the left vertebral artery, the right anterior cerebral artery and the right posterior communicating artery represented irrelevant variant findings. Ophthalmological examination did not document intraocular hypertension or the congestion in ocular fundus. Within the initial two days, attacks of headaches with nausea and vomiting recurred. However, no visual disturbances or any other neurological symptoms were present. Over the next days, the patient had no problems at all. On the fourth day of hospitalisation, transcranial Doppler ultrasonography was performed, and it proved mild vasospasm of the left middle cerebral artery (MCA). Thus, oral administration of nimodipine was initiated. Due to the patient’s relatively low blood pressure, the dose was reduced to 60 mg 4× a day. Follow-up transcranial colour-coded sonography (TCCS) was performed on the 8^th, the 14^th (Fig. 1), the 17^th day and after 3 months. The examinations showed persistence of the mild vasospasms on the left MCA – peak systolic velocity (PSV) values gradually decreased from the peak value of 163 to 137 cm/s. On the 14^th and 17^th day, mild vasospasm was transiently detected also in the right MCA with PSV of 149 and 138 cm/s, respectively (Tab. 1). On the 8^th day and after 3 months, borderline acceleration was detected in the left anterior cerebral artery (PSV 116 and 111 cm/s, respectively). Flow in the other cerebral arteries in the anterior and posterior circulation was normal. After 14 days following the onset of the symptoms, the patient was discharged home from the hospital, still treated with nimodipine. He discontinued the medication by himself after the next two weeks. During all follow-up visits, he had no problems.

Patophysiology of RCVS has not been clarified yet. Presumably, impairment of regulation of the cerebrovascular pressure from increased reactivity of sympathicus has been proposed. Oxidative stress and endothelial dysfunction may play a significant role in the pathophysiology [5,8]. There may be primary (idiopathic) RCVS; however, 25–60% of the appearances is secondary [5,8]. The most common causes of secondary RCVS are represented by the use of vasoactive substances (cannabinoids, ecstasy, cocaine, amphetamine, antidepressants – selective serotonin reuptake inhibitors), the puerperium (after pregnancy complicated by eclampsia or preeclampsia or following an uncomplicated pregnancy), and the use of immunosuppressive drugs [1,5]. Differential diagnosis should focus on intracranial haemorrhage and, particularly, SAH, cerebral sinus thrombosis, dissection of cerebral arteries or meningoencephalitis. In the first place, the diagnosis should be based on the CT of the brain. If negative, cerebrospinal fluid examination including spectrophotometry should follow. In case of normal cerebrospinal fluid examination, cerebral vessel imaging takes place [9]. Multifocal segmental arterial vasoconstriction represents the characteristic finding for RCVS on CTA, MRA or catheterisation angiography. However, the results may be negative during the first days [1,5]. TCCS is suitable for follow-up monitoring of the haemodynamic changes and for predicting the risk of ischemic complications. Interestingly, the peak intracranial flow velocity is often detected in the period around the third week following the onset of RCVS, when the problems of the patient recede or have completely receded [1]. Current guidelines for therapy of RCVS contain analgesic treatment, blood pressure monitoring attempting to maintain normal values and administration of calcium channel blockers. Most often, nimodipine is administered intravenously (0.5–2 mg/h) or orally (30–60 mg every 4 h), usually, for 4–12 weeks [1,4]. Glucocorticoid administration is not recommended [1,4]. Prognosis is good, as the clinical symptoms and vasospasms completely subside most often within three months [1].

We evaluate the presented case as differentially probable diagnosis of primary RCVS. Despite very intensive initial symptoms, early CTA and MRA findings were negative. Vasospasms in the anterior cerebral circulation bilaterally were only confirmed by TCCS, which was also used for monitoring of their dynamics, the peak flow velocities were detected after 2 weeks. To treat RCVS, we prescribed oral nimodipine. The course of the disease was uncomplicated, and the symptoms have subsided completely.

In conclusion, it can be stated that RCVS probably represents under-diagnosed cause of headaches. It is necessary to give it a consideration in cases of thunderclap headaches, if the results of imaging studies and cerebrospinal fluid examination are negative.

MUDr. Libor Šimůnek

Neurologická klinika LF UK a

FN Hradec Králové

Sokolská 581

500 05 Hradec králové

e-mail: libor.simunek@email.cz