What this paper adds
- • RCVs should be considered in acute headache and stroke syndromes featuring prominent, recurrent headache.
- • The evolving pathology may lead to discrepancies in serial imaging.
Reversible cerebral vasoconstriction syndrome (RCVS) is a clinicoradiological diagnosis comprising ‘thunderclap’ headaches and reversible segmental vasoconstriction of cerebral arteries, occasionally complicated by ischaemic or haemorrhagic stroke. We report a case of RCVS in a 13-year-old male with severe thunderclap headaches and no focal neurological signs. Brain imaging showed multiple posterior circulation infarcts; cerebral computed tomography, magnetic resonance imaging, and catheter angiography showed multifocal irregularity and narrowing, but in different arterial segments. Laboratory studies did not support a diagnosis of vasculitis. Symptoms resolved over 3 weeks; magnetic resonance angiography 3 months later was normal and remained so after 2 years. We highlight the typical clinical features of RCVS in this case and suggest that the diagnosis should be considered in children with thunderclap headaches or stroke syndromes where headache is a prominent feature, especially if cerebrovascular imaging studies appear to be evolving or discrepant.
Magnetic resonance angiography
Reversible cerebral vasoconstriction syndrome
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute ‘thunderclap’ (sudden and severe) headache with imaging evidence of segmental cerebral arterial vasoconstriction and dilatation that completely resolves over a period of months. Most cases resolve spontaneously, but arterial ischaemic stroke and intracerebral and subarachnoid haemorrhages complicate a minority. Here we report a paediatric case of RCVS to highlight this as a potential differential diagnosis for both acute childhood headache and stroke. Parental written consent was given for the anonymized publication of this case.
A 13-year-old male developed a sudden severe headache, without other neurological deficits, after swimming in cold seawater. Migraine was diagnosed and he was given sumatriptan. Three days later he presented with an unprovoked severe diffuse headache, only partially controlled with intravenous opiates. Cardiovascular, neurological, and systemic examination was normal. He had a history of uncomplicated migraine, with infrequent mild headache. He was on no medication and denied alcohol, tobacco, or substance misuse. Family history was negative for headache, migraine, or premature vascular disease.
Unenhanced head computed tomography (CT) at initial presentation was normal. Cerebrospinal fluid examination showed normal opening pressure, normal protein and glucose, and no cells or xanthochromia. Brain magnetic resonance imaging (MRI) on day 12 showed multiple acute infarcts in the occipital and parietal cortices, left cerebellar hemisphere, and posterior deep white matter (Fig. 1), all within the territory of the posterior circulation. Time-of-flight magnetic resonance angiography (MRA) of the cervical and intracranial arteries showed a diffusely small right vertebral artery, with marked attenuation of flow in its V3 segment; there was also turbulent flow in both proximal middle cerebral arteries with preservation of distal filling (Fig. 2). Abnormality of the right vertebral artery was also identified on cervical T1-weighted fat-saturated MRI. The right vertebral artery findings were felt to be suggestive, but not diagnostic, of arterial dissection. CT angiography of the cervical and intracranial circulation was undertaken as it was felt that an endoluminal technique might be conclusive; this confirmed the diffusely small (likely normal and non-dominant) right vertebral artery with a more focal distal stenosis, as well as stenosis of the right middle cerebral arteries (Fig. 2).
Catheter cerebral angiography was undertaken on day 18 in an attempt to make a definitive diagnosis. This was markedly abnormal, with extensive abnormalities identified in the right vertebral artery, bilateral posterior cerebral arteries, internal carotid arteries, and middle cerebral arteries (Fig. 3), consisting of extensive segments of alternating increased and reduced calibre or beading. Visceral angiography was normal. Serology demonstrated normal inflammatory markers, autoimmune profile, complement, immunoglobulin levels, and procoagulant screen.
Severe headache recurred daily for the first 2 weeks with no neurological deficits evident. Subsequently, both headache frequency and severity reduced. Five weeks after initial presentation, repeat intracranial and cervical MRA showed resolution of the internal carotid arteries changes previously observed on catheter angiography. The patient was discharged on amitriptyline and aspirin. Repeat brain MRI and MRA after 3 months showed maturation of the previous infarcts; MRA from the aortic arch to the circle of Willis showed a diffusely smaller right vertebral artery only; the previously noted abnormalities on all vascular imaging modalities had reversed. Further repeat MRI and MRA after 2 years remained unchanged.
The term ‘reversible cerebral segmental vasoconstriction’ was first used in 1988 by Call et al.,1 who collated data on a series of patients with headache and similar radiological features. Now termed reversible cerebral vasoconstriction syndrome (RCVS), current diagnostic criteria are (1) acute severe headache; (2) monophasic course without new symptoms more than 1 month after onset; (3) segmental cerebral arterial vasoconstriction; (4) exclusion of aneurysmal subarachnoid haemorrhage; (5) normal cerebrospinal fluid; and (6) complete or marked normalization of arterial changes after 12 weeks.2 The pathogenic mechanism is thought to be a transient dysregulation of arterial tone secondary to sympathetic overactivity.3,4 A centripetal pattern of involvement has been described, with initial disturbance of small peripheral arteries, often missed by early imaging.5,6 Abrupt stretching of the arterial wall is thought to be responsible for the typical ‘thunderclap’ headache and can lead to early complications including cerebral haemorrhage (parenchymal and subarachnoid) and seizures. This is followed by more proximal medium to large artery involvement with an increased risk of cerebral ischaemia in the second week.4
A recent systematic review6 identified over 200 cases of RCVS in the literature; eight children have been described here7–10 (see Table I). The majority of the children are male, in contrast to a female preponderance in adult cases. Paediatric arterial ischaemic stroke also favours males, which has been attributed to increased testosterone levels in affected patients.11 It is unknown whether a similar association is present in cases of RCVS.
|Study||Age (y)||Sex||Potential triggers||Neurological deficit||Brain imaging||Cerebrovascular imaging||Treatment||Outcome|
|Kirton et al.7||13||M||Deep diving||None||CT normal (day 1 and 5). MRI normal (day 5)||Smooth narrowing of multiple bilateral proximal vessels (day 6)||None||Normal angiography 16 days after original headache. Headache free >18 months|
|Liu et al.8||10||M||Nasal spray (fluticasone); bath related; hypertension||None||Hyperintense lesion of left occipital region and hyperintensity of sulci on MRI FLAIR images (day 12). No prior images described||Multiple segmental narrowing in MCA and PCA bilaterally (day 4)||Nimodipine, nicardipine||MRA on day 44 showed resolution. Persistent lesion on MRI. Headache free >3 months|
|Liu et al.8||16||M||Defaecation; hypertension||None||Not described||Multiple segmental narrowing in bilateral PCA and irregularity of left MCA||Nimodipine||Normal MRA after 2 months Headache free >2 years|
|Liu et al.8||10||M||Hit by football; sneezing||None||Not described||Multisegmental narrowing of bilateral MCA, PCA||Nimodipine||MRA on day 31 improved. Headache free >2 years|
|Ghosh et al.3||15||M||Hypertension||None||CT and MRI normal (day 2)||Multifocal vascular irregularities of posterior and anterior circulation (days 4 and 6)||Verapamil||MRA at 6 weeks showed complete resolution. Headache free >3 months|
|Yoshioka et al.9||12||M||Eletriptan||Paralysis of lower extremities, gait disturbance||CT (day 1) normal. Cortical SAH over right occipital, left frontal, and bilateral parietal lobes on MRI (day 5)||Multifocal narrowing of cerebral arteries (day 5)||None||MRI and MRA findings resolved 3 months later Headache free >3 months|
|Kazato et al.10||7||F||Immunosuppressants; hypertension||Loss of consciousness||CT (day 2) parenchymal haemorrhage between occipital and parietal lobes. No change on MRI (day 28)||Diffuse cerebral vasoconstriction (day 28)||Nicardipine||MRA day 60 resolution of vascular changes|
|Probert et al. 2012 (present study)||13||M||Swimming in cold water; sumatriptan||None||Normal CT (day 5). Multiple acute infarcts in territory of posterior circulation on MRI (day 12)||Beading and stenosis of both VAs, ICAs, and MCAs (day 18)||None||MRA at 5 weeks showed resolution of vascular changes. No new lesions on MRI. Headache free >3 years|
Between 25% and 60% of cases are thought to be secondary to vasoactive substances (particularly drugs of abuse and serotonergic drugs) or the postpartum period.5 Triptans have been associated with RCVS and had been prescribed to the patient in our case study. Where antecedent drug ingestion has been reported previously, the interval between drug exposure and symptoms has been variable. Precipitants (including immersion in cold water) are reported in 20% to 30% of cases.7 Other associations include vascular lesions (dissection/aneurysms), catecholamine-secreting tumours, trauma, and neurosurgical procedures. Hypertension is commonly observed and is thought to reflect the disturbance of sympathetic tone.4
Migraine is a distinct entity but may be associated. A retrospective analysis of 139 predominately adult patients reported a history of migraine in up to 40% of the participants.2 Additionally, migraine has been linked with an increased risk of haemorrhage in patients with RCVS.12
Headache is a common symptom associated with arterial ischaemic stroke, subarachnoid haemorrhage, central nervous system vasculitis, arterial dissection, and intracerebral infections, which should be excluded by appropriate imaging and laboratory investigations. However, the sudden, severe, and recurrent nature of the headache in RCVS is distinctive and reliably reported in 94% of patients.13 Associated features are nausea, vomiting, photophobia, confusion, and blurred vision. Severe headaches rarely continue beyond 3 weeks but mild headaches may be more persistent.5 Cerebrospinal fluid examination, serological tests, and brain/temporal artery biopsies characteristically show no abnormalities, whilst angiography demonstrates segmental arterial dilatation and stenosis. Focal neurological signs are suggestive of secondary complications including arterial ischaemic stroke or intracranial haemorrhage. Transient ischaemic attacks may be seen and most frequently present with transient visual loss.6 Non-cephalgic cases are thought to exist, characterized by otherwise unexplained cerebral infarction following a recognized trigger for RCVS and the characteristic arterial changes on imaging.
CT is usually normal and most MRI is also normal during the first week of presentation. Around 10% of cases are associated with imaging changes compatible with posterior reversible encephalopathy syndrome. Twenty per cent of individuals with RCVS demonstrate a non-aneurysmal subarachnoid haemorrhage and 10% demonstrate evidence of an intraparenchymal haemorrhage.6 MRA or CTA identify arterial abnormalities in up to 90% of patients with RCVS6 but there is an additional yield from catheter angiography, which, although comparatively invasive, remains the criterion standard. Transcranial Doppler ultrasonography may have a role in the serial monitoring of cases and demonstrates that arterial abnormalities often persist well beyond resolution of clinical symptoms.5,6,8 The diagnosis is confirmed by demonstrations of reversal of the vascular abnormalities 1 to 3 months after initial presentation. Evident in this case were the difficulties in interpreting a dynamic disease process on serial imaging modalities. Whilst early imaging was entirely normal, later images revealed unexpected and seemingly inconsistent findings. There was initial debate about the potential artefacts generated from each technique but in retrospect the discrepant findings were likely to be because of the evolving pathology.
Central nervous system (CNS) vasculitis is an important differential diagnosis as, although RCVS by definition reverses spontaneously, vasculitis has a progressive or recurrent course that necessitates immunosuppression and long-term follow-up. CNS vasculitis is notoriously difficult to identify, and it is well recognized that blood and cerebrospinal fluid studies may be negative in biopsy-proven cases.14 The sudden and severe nature of the headache in RCVS is helpful in contrasting with the insidious headache of CNS vasculitis. The clinical picture of CNS vasculitis is more often dominated by cognitive deficits, seizures, or focal neurology. Brain abnormalities on MRI are more commonly seen in vasculitis and notably, are usually evident on scans at presentation compared with early scans in RCVS, which are often normal.6 A recent paper15 has suggested that demonstration of vessel wall enhancement on high-resolution MRI may enable differentiation between CNS vasculitis and RCVS, but this requires corroboration before diagnostic use.
The presence of posterior circulation infarcts in a child necessitates consideration of arterial dissection. More common than previously thought, and often lacking a history of preceding trauma, the diagnosis should be suspected particularly if neck pain is reported. MRA detects the majority of cases but can miss intimal flaps or double lumens of dissection, and thus there remains a clear rationale for catheter angiography in cases of diagnostic doubt.
Treatment of RCVS includes pain relief and removal of potential triggers. Nimodipine may be used with careful monitoring of blood pressure as in some instances its use has been associated with cerebral ischaemic symptoms. Other calcium channel antagonists, such as nicardipine or verapamil, have also been used. Recurrent attacks are rare and all paediatric cases to date have shown complete resolution of symptoms. Stroke, reported in up to 9% of adult cases, is the most significant determinant of morbidity,6,13 with neurological sequelae persisting after the vasculature has normalized.