Fulminant Reversible Cerebral Vasoconstriction Syndrome: The Other Thunderclap Headache

Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a rare phenomenon that is underdiagnosed in clinical practice [1]. Oftentimes the presenting symptom of RCVS is a thunderclap headache leading to evaluation for cerebral hemorrhage. However, blood work and imaging are usually negative which often leave the physician without answers or down an arbitrary path to treat atypical migraine headache [2]. Classically the symptoms of RCVS improve after approximately 2 months, but given the risk of life altering complications which include cerebral infarction, it is important that RCVS be included high in the differential diagnosis [2,3]. We present a case of a 56 year old female with thunderclap headache who was subsequently diagnosed with RCVS after devastating cerebral infarction.


Introduction
Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a rare phenomenon that is underdiagnosed in clinical practice [1]. Oftentimes the presenting symptom of RCVS is a thunderclap headache leading to evaluation for cerebral hemorrhage. However, blood work and imaging are usually negative which often leave the physician without answers or down an arbitrary path to treat atypical migraine headache [2]. Classically the symptoms of RCVS improve after approximately 2 months, but given the risk of life altering complications which include cerebral infarction, it is important that RCVS be included high in the differential diagnosis [2,3]. We present a case of a 56 year old female with thunderclap headache who was subsequently diagnosed with RCVS after devastating cerebral infarction.
as it presented more suddenly and with greater intensity. She presented to multiple urgent care facilities to seek treatment and multiple Computed Tomographies (CT) of the head with CT Angiography (CTA) were performed throughout the previous week, which were only signifi cant for bilateral intracranial internal carotid artery aneurysm. Her surgical history consists of hysterectomy, C3-C4 cervical fusion, and bilateral rotator cuff repair. Her social history was reviewed and she is a 1 pack per day smoker. Her home medication regimen included atorvastatin 80mg daily, clopidogrel 75mg daily, duloxetine 90mg daily, omeprazole 40mg daily, carvedilol 6.25mg daily, and ranitidine 150mg twice daily, and butalbitalacetaminophen-caffeine 50-325-40mg daily as needed.
On arrival to the hospital, the patient's vital signs revealed a blood pressure of 147/78 mmHg.
Her admission laboratory work was unremarkable with the exception of a glucose of 199 mg/dL. CT of the head and CT angiography of the head and neck were performed promptly upon arrival, which was approximately 1 week after onset of headache, revealing atherosclerotic calcifi cation of the bilateral internal carotid arteries particularly at the level of the cavernous and supraclinoid segments. Two aneurysms measuring 2mm involving the left and right internal carotid arteries were

Discussion
In 2007, multiple unexplained vasculopathies and vasoconstriction syndromes to include CallFleming syndrome, postpartum angiopathy, and acute benign cerebral angiopathy were unifi ed as one clinical syndrome called RCVS [4,5].
Since this time few cases have been reported in the literature of patients with RCVS with poor outcomes and death as it is generally observed to have a self-limiting course [5]. RCVS appears to predominantly affect young females between the ages of 20 to 50 years of age, but according to a single cohort  study, men who present with RCVS are signifi cantly younger and symptoms are often associated with sexual activity [6]. The hallmark of the disease is thunderclap headache as well as reports of photophobia and phonophobia leading the physician to a diagnosis of migraine after cerebral hemorrhage has been ruled out [1,7]. The exact mechanism for this clinical syndrome is unknown, but susceptibility to developing RCVS may be infl uenced by genetics or a potential trigger [8]. Common triggers have been reported to include alcohol, sexual intercourse, triptans, postpartum states, and Valsalva maneuver; however, many patients are diagnosed without a known trigger [2]. Specifi c attention should be paid to the use of triptans as patients are often prescribed this for migraine, which this clinical syndrome is often mistaken for. Previous case reports have linked triptans to induce or at the very least exacerbate RCVS [8]. Our patient was also prescribed triptans which may have contributed to her rapid neurologic decline after hospitalization.
Clinical presentation is misleading as thunderclap headache is the most common clinical presentation of RCVS although it is not specifi c for the syndrome [1,4]. In fact, when physicians encounter thunderclap headache the differential is often limited to subarachnoid hemorrhage, migrainous headache disorder, Primary Angiitis of the Central Nervous System (PACNS), and cervical arterial dissection. More specifi c characteristics of thunderclap headache that are associated with RCVS include a waxing and waning course often that repeats over 1 to 3 weeks [4]. This distinction is particularly important to consider during initial examination in a patient with RCVS as presentation of subarachnoid hemorrhage presents with more abrupt onset.
Seizures can be present at onset as well, but their recurrence is rare [9]. Rapid progression of the disease is very unusual in RCVS [5], but our patient did develop rapid neurological decline after she was hospitalized. This type of fulminant course is encountered in 5-10% of patients with RCVS resulting in permanent disability and death [10].
Diagnostic criteria for RCVS include acute and severe onset headache, with or without additional neurologic signs or symptoms that are uniphasic without new symptoms after 1 month of onset. On cerebrovascular imaging there is evidence of multifocal segmental cerebral artery vasoconstriction without evidence of aneurysmal SAH [4,9]. A clinical and radiologic distinction must be made between RCVS and PRES. In RCVS vasoconstriction on vascular imaging is a distinctive fi nding 6. Our patient demonstrated fi ndings of asymmetric lesions with associated ischemia with vasoconstriction on vascular imaging which is more typical with RCVS. Given results of imaging, a lumbar puncture was performed to exclude pleocytosis in the setting of headache. Infectious workup to include CSF analysis was unremarkable, which was done to exclude infectious as well as paraneoplastic and autoimmune etiology. Most importantly there is reversibility of angiographic abnormalities within 12 weeks after onset of disease, separating it from the etiology and fi ndings in acute ischemia secondary to vascular occlusion from thrombosis or progressive atherosclerosis [4,9]. Infarction on baseline imaging, use of intra-arterial vasodilator therapy, and glucocorticoid therapy may be associated with poor outcomes [10].
There are no clear treatment modalities for the treatment of RCVS and specifi c treatment is based on observational studies and clinical experience. Like any clinical entity with potential triggers, these offending agents must be discontinued [9], such as sumatriptan in our patient. Other pharmacologic agents thought to be potential precipitating factors are triptans, ergotamines, pseudoephedrine, amphetamines, cannabis, cocaine, and bromocriptine [1]. Treatment of the vasospasm should be considered for cerebral vasoconstriction with calcium channel blockers and continued for 4-12 weeks. Our patient was treated with amlodipine and magnesium upon diagnosis which has been used as well in the treatment of acute RCVS with success. The decision to use amlodipine opposed to nimodipine, nicardipine, or verapamil was arbitrary and based off of the attending physician preference. There are no evidence based guidelines regarding calcium channel blockers although nimodipine and verapamil are most common reported in previous cases. Intra-arterial administration of epoprostenol, milrinone, and nimodipine as well balloon angioplasty have all been reported in more severe cases with variable success.
However, this intervention should be utilized based on access to intervention and operator experience as this procedure is higher risk [1,9]. Although magnesium and calcium channel blockers have been used in previous reported cases of RCVS, no standard treatment regimen has been established [1].
However, long term management with neurologic specialists is imperative as symptom recurrence and complications until death may rarely occur [10]. Unfortunately, this leads to prescription of vasoconstrictive drugs which can often worsen RCVS. Through this case it is our goal to bring awareness to RCVS and bring the condition into physicians' differential diagnosis as the other thunderclap headache.