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Published: June 2012

Reversible Cerebral Vasoconstriction Syndrome - Medicine Induced?

Prescriber Update 33(2): 14-15
June 2012

A recent Medsafe review confirmed that cases of Reversible Cerebral Vasoconstriction Syndrome (RCVS) have been reported in association with the use of the serotonergic medicines. Cases of RCVS have been reported with duloxetine, sertraline, citalopram, paroxetine, fluoxetine and sumatriptan. However, this data is currently inadequate to confirm a causal association.

RCVS should be considered in the differential diagnosis of thunderclap headaches when other causes have been excluded.

RCVS is thought to be under-reported for many reasons including lack of awareness of the condition and difficulties in confirming the diagnosis. The current data on RCVS comes primarily from case series conducted in Taiwan, France and the US1-3. The case series included 262 patients who experienced RCVS.

Medsafe has added 'thunderclap headache/RCVS with serotonin reuptake inhibitors or triptans' to the M² logo monitoring scheme. Prescribers are asked to report all cases of recurrent thunderclap headaches or suspected RCVS associated with these medicines to the Centre for Adverse Reactions Monitoring (CARM). Prescribers should report cases even if an angiogram has not been performed.

What is RCVS?

RCVS is a unifying term used to describe a diverse range of conditions characterised by recurrent thunderclap headaches and reversible segmental cerebral arterial vasoconstriction on angiogram. Conditions include Call-Fleming syndrome, benign angiopathy of the CNS, postpartum angiopathy or idiopathic thunderclap headache.

Clinical Presentation4

RCVS classically presents with sudden-onset and severe headaches that recur over a 1–3 week period. The headaches may be accompanied by nausea, vomiting and photophobia. Most headaches are bilateral and involve the occipital region. Patients with a history of headaches (including migraines) describe the headache as different from their usual headache.

Table 1: Vasoactive substances associated with the development of RCVS4

Serotonergic drugs Selective serotonin reuptake inhibitors and triptans
Illicit drugs Cannabis, cocaine, ecstasy, amphetamines and LSD
Ergots Ergotamine, methergine, lisuride and bromocriptine
Sympathomimetic drugs Ephedrine and diet pills
Immunosuppressants Tacrolimus, cyclophosphamide and interferon-α
Others Nicotine patches, ginseng, indomethacin, binge drinking and oral contraceptive pills


Neurological complications occur in up to 50% of patients. Complications include seizures, cortical subarachnoid haemorrhage, ischaemic stroke and intra-cerebral haemorrhage.

RCVS is more common in women and in middle aged people (median age of 40–60 years). Up to 80% of patients have identifiable triggers such as exertion, cough, defecation or sexual activity.

Diagnosis of RCVS

The diagnosis of RCVS should be made by a specialist. All three of the following events are required for the diagnosis of RCVS.

  1. History of multiple thunderclap headaches.
  2. Demonstration of segmental vessel constriction (string and beads appearance) of the cerebral arteries and its reversibility (complete or marked normalisation of arteries within 12 weeks of onset by initial and repeated cerebral angiography).
  3. Exclusion of other causes of thunderclap headaches such as aneurysmal subarachnoid haemorrhage, cervicocerebral arterial dissection or primary angiitis of the CNS.

In patients presenting with thunderclap headaches, a normal CT scan and lumbar puncture does not exclude RCVS. If the patient presents with unexplained recurrent headaches and is using a vasoactive agent, a CT angiography (CTA) or magnetic resonance angiography (MRA) may be necessary to further investigate the cause.

Possible causes of RCVS1-3

Although RCVS can occur spontaneously, a number of potential secondary causes have also been identified. Vasoactive substances (50% of cases) and the post-partum state (9% of patients) are the secondary causes most commonly implicated (Table 1).

Treatment options

There is general agreement that all patients require supportive care, withdrawal or correction of possible secondary causes and avoidance of further triggers.

Prognosis

The majority of patients recover fully. However, neurological deficits were found to be permanent in 3–9% of patients in a prospective case series5.

References
  1. Chen SP, Fuh JL, Lirng JF, et al. 2006. Recurrent primary thunderclap headache and benign CNS angiopathy: spectra of the same disorder? Neurology 67: 2164-9.
  2. Ducros A, Boukobza M, Porcher R, et al. 2007. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain 130: 3091-101.
  3. Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. 2011. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Archives of Neurology 68: 1005-12.
  4. Chen SP, Fuh JL, Wang SJ. 2010. Reversible cerebral vasoconstriction syndrome: an under-recognized clinical emergency. Therapeutic Advances in Neurological Disorders 3: 161-71.
  5. Sattar A, Manousakis G, Jensen MB. 2010. Systematic review of reversible cerebral vasoconstriction syndrome. Expert Review of Cardiovascular Therapy 8: 1417-21.

 

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