Background: Primary intraventricular hemorrhage is an uncommon cause of stroke and is often associated with longstanding, uncontrolled hypertension. Reversible cerebral vasoconstriction is also an uncommon condition characterized by reversible constriction of intracerebral vessels, which can lead to ischemic or hemorrhagic strokes. Case presentation: We describe a case of isolated primary intraventricular hemorrhage secondary to reversible cerebral vasoconstriction syndrome triggered by pseudoephedrine. Conclusions: Reversible cerebral vasoconstriction syndrome is a rare cause of primary intraventricular hemorrhage and should be considered in the differential in angiography-negative IVH when there is a history of vasoactive substance use. Keywords: Reversible cerebral vasoconstriction syndrome, Pseudoephedrine, Primary intraventricular hemorrhage Background is the first case reported of RCVS causing isolated intraven- Reversible cerebral vasoconstriction syndrome (RCVS) is an tricular hemorrhage. uncommon condition of reversible vasospasm of intracere- bral vessels which manifests as a thunderclap headache, Case presentation focal neurologic deficits and often both ischemic and A 58 year-old woman presented to an outside hospital after hemorrhagic strokes including subarachnoid hemorrhage. It developing the “worst headache of her life” followed by is felt to be secondary to disturbances in vascular tone, and abrupt collapse with convulsive movements. At the out- is often triggered by use of vasoactive substances, though it side hospital, a noncontrast head CT demonstrated may also be seen in the postpartum setting . High cortical IVH (Fig. 1a). Her mental status then deteriorated, re- subarachnoid hemorrhages are commonly reported in quiring emergent intubation, and she was transferred RCVS. However, primary intraventricular hemorrhage has to our hospital. not previously been described as a hemorrhagic manifest- Her past medical history included chronic migraines, de- ation of RCVS. Primary intraventricular hemorrhage (IVH) pression and seasonal allergies. She had no prior surgeries. is a rare cause of intracerebral hemorrhage; it accounts for Her home medications included two antidepressants with 3.1% of hemorrhagic strokes  and 0.31% of all strokes . serotonergic activity, bupropion and sertraline. In the past IVH has only once been previously described in the litera- few weeks prior to presentation, she had been using an ture with regards to reversible cerebral vasoconstriction and over-the-counter decongestant on a daily basis which con- occurred in context of additional ischemic lesions rather tained pseudoephedrine. She had no history of auto- than as an isolated manifestation . To our knowledge, this immune disease, vasculitis, hypertension or stroke. She did not endorse any history of illicit or recreational drug use. Upon arrival to our hospital, she was hypertensive with * Correspondence: firstname.lastname@example.org a systolic blood pressure of 200 mmHg despite no previ- Department of Neurology, Neurosurgery and Medical Education, Rhode ous history of hypertension. Her lab studies on admission Island Hospital/The Warren Alpert Medical School of Brown University, 593 included a negative toxicology screen which excluded Eddy St APC 712, Providence, RI 02903, USA Full list of author information is available at the end of the article presence of amphetamines or cocaine. Platelet count and © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Dakay et al. Chinese Neurosurgical Journal (2018) 4:11 Page 2 of 4 Fig. 1 : Noncontrast head CT demonstrated intraventricular hemorrhage (IVH) a Initial head CT showing diffuse IVH in the bilateral lateral ventricles. b Follow-up head CT showing stable IVH coagulation parameters were within normal limits. Elec- Transcranial Doppler on hospital days five and nine dem- trocardiogram demonstrated sinus rhythm. onstrated normal velocities. Subsequently, conventional The patient’s blood pressure was treated with a con- catheter angiography on day five of admission was ob- tinuous infusion of nicardipine with a goal systolic blood tained which showed multifocal areas of irregular narrow- pressure less than 160 mmHg, and she was admitted to ing in the distal posterior cerebral artery branches and the neurocritical care unit. Repeat noncontrast head CT distal left middle cerebral artery consistent with a vascu- 6 hours after her initial head CT was unchanged (Fig. 1b). lopathy (Fig. 3). CT angiogram of the brain did not demonstrate an under- lying vascular abnormality. The patient was monitored for risk of hydrocephalus, which did not develop. An MRI of the brain performed on the fourth day of admission rede- monstrated the IVH without any intraparenchymal com- ponent or underlying vascular malformation (Fig. 2). Fig. 2 MRI brain [fast low angle shot (FLASH) sequence] demonstrated Fig. 3 Catheter angiography of left vertebral artery demonstrated intraventricular hemorrhage; no causative underlying vascular lesion vasoconstriction. The arrows point to multifocal areas of irregular was identified narrowing of the distal branches of the left posterior cerebral artery Dakay et al. Chinese Neurosurgical Journal (2018) 4:11 Page 3 of 4 The patient improved clinically and was extubated; how- including pseudoephedrine, phenylephrine, and oxymetazo- ever, she continued to have a severe headache. Oral verap- line are commonly available over-the-counter without a pre- amil resulted in mild improvement. Subsequently, 2 g of scription and used to treat allergies, sinus congestion, and intravenous magnesium were administered followed by occasionally epistaxis. oral magnesium gluconate; the patient reported a dra- Primary IVH is a rare cause of intracerebral hemorrhage matic improvement in her headache and was discharged. and typically presents either with abrupt sudden coma The diagnosis on the basis of the history of vasoactive followed by signs of brainstem dysfunction or a waxing substance use, severe acute headache, and characteristic and waning headache followed by nausea, vomiting and a angiography findings was a primary IVH secondary to progressive confusional state. One striking feature differ- RCVS. The trigger was felt to be pseudoephedrine with entiating primary IVH from other types of intracerebral possible contributing factors being the use of bupropion hemorrhage is either a lack of, or very minimal, focal and sertraline, leading to altered vascular tone. Vasculitis neurologic deficits. Hypertension is a common risk factor was felt to be unlikely given the abrupt onset of symp- for IVH. However, angiography is recommended given the toms and rapid clinical improvement. Bupropion, sertra- potential for underlying vascular malformations. line and pseudoephedrine were held throughout her In the discussed case, angiography was undertaken given hospitalization and discontinued upon discharge. The the risk of an underlying causative vascular malformation, patient presented to clinic follow-up 2 months later and which has been reported to be as high as 56% when com- reported resolution of symptoms; thus, follow-up vascu- bining various case studies . However, catheter angiog- lar imaging was deferred. She has not had any recur- raphy yielded no evidence of aneurysm or arteriovenous rence of thunderclap headaches since discharge. malformation, but instead demonstrated beading and dila- tation of the distal vessels suggestive of vasculopathy. Discussion and conclusions Given the rapid improvement in clinical status after with- RCVS is a clinical syndrome characterized by acute drawal of the offending substances and initiation of cal- thunderclap headache with nausea and vomiting often cium channel blocker medication as well as magnesium, mimicking aneurysmal subarachnoid hemorrhage. It is the overall clinical picture supported a diagnosis of RCVS. more common in women than in men . Its defining Though head CT can be normal in RCVS, common im- features include findings of segmental vasoconstriction aging abnormalities seen include ischemic stroke, high on angiography, lack of aneurysmal source, normal or cortical subarachnoid hemorrhage, vasogenic edema, and near normal cerebrospinal fluid, thunderclap headache, lobar hemorrhage [1, 9]. One large case series reported and reversibility of the lesion . It is felt to be due to that 43% of patients with RCVS have hemorrhagic compli- alterations in vascular tone and likely affects the distal cations . Subdural hemorrhage is rarely seen but has vasculature primarily, progressing more proximally to- been reported. Two previous case studies have reported wards the vessels of the Circle of Willis . These IVH in the setting of RCVS [4, 11], indicating that it is a rare changes are often not seen on noninvasive vessel im- phenomenon. In one case, an patient with RCVS triggered aging. Likewise, in our case, a CT angiogram of the brain by phenylephrine developed an intraparenchymal hematoma did not show the typical diffuse stenoses and dilatation which extended into the subarachnoid and intraventricular of vessels characteristic of RCVS, but these findings spaces ; however, in this situation, the IVH was second- were very apparent on catheter angiography. ary to a primary intraparenchymal hematoma. A second RCVS is often triggered by vasoactive substances in- case demonstrated a primary IVH secondary to reversible cluding selective serotonin reuptake inhibitors and sym- cerebral vasoconstriction which occurred in the context of pathomimetic medications; illicit substances including the nasal decongestant oxymetazoline; in this situation pre- cocaine, ecstasy, and marijuana have also been impli- pontine cisternal and fourth ventricular hemorrhages were cated . In our patient, pseudoephedrine, which has demonstrated, but occurred in the context of multifocal is- previously been described as a precipitant, was felt to be chemic strokes more typical of that seen in RCVS . The the primary causative factor given the temporal relation- mechanism by which RCVS leads to hemorrhagic complica- ship of the usage to the development of symptoms. tions, including intraventricular hemorrhage is not well- However, bupropion and sertraline both have serotonin elucidated; however, it is postulated that rapid changes in reuptake inhibition activity and were also identified as vascular caliber due to vasoconstriction and subsequent possible precipitating factors. The mechanism by which vasodilatation can lead to reperfusion injury and subsequent sympathomimetic overactivity leads to RCVS is not known, hemorrhage . To our knowledge, our case is the first of however, one theory is that genetically susceptible patients an isolated primary IVH without additional lesions. may develop microvascular inflammation in response to Treatment of RCVS involves withdrawal of the offend- sympathetic overstimulation, leading to disruption in arteri- ing substance and supportive care. While there are no olar tone . It is important to note that sympathomimetics randomized controlled trials supporting the efficacy of Dakay et al. Chinese Neurosurgical Journal (2018) 4:11 Page 4 of 4 calcium channel blockers, several case series have re- Author details Department of Neurology, Rhode Island Hospital/The Warren Alpert Medical ported improvement in symptoms with usage of these School of Brown University, Providence, RI, USA. Departments of Radiology, agents and they are currently recommended on this Neurology, and Neurosurgery, Rhode Island Hospital/The Warren Alpert basis . Steroids were associated with a trend towards Medical School of Brown University, Providence, RI, USA. Department of Neurology, Neurosurgery and Medical Education, Rhode Island Hospital/The poor outcome in one two-center case series though in- Warren Alpert Medical School of Brown University, 593 Eddy St APC 712, terpretation is limited as the series was retrospective. Providence, RI 02903, USA. The outcome of RCVS is generally favorable , though Received: 22 June 2017 Accepted: 25 April 2018 hemorrhage increases the risk of disability . Fortu- nately, the patient described in our case was asymptom- atic at follow-up several weeks after discharge. References 1. Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Yang D, et al. RCVS may be a potential culprit in cases of primary Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch IVH in which a causative aneurysm or arteriovenous Neurol. 2011;68:1005–12. malformation cannot be identified. Our case study was 2. Darby DG, Donnan GA, Saling MA, Walsh KW, Bladin PF. Primary intraventricular hemorrhage: clinical and neuropsychological findings in a limited in the sense that the patient did not have follow- prospective stroke series. Neurology. 1988;38:68–75. up imaging, as the additional radiation was felt to be un- 3. Arboix A, Garcia-Eroles L, Vicens A, Oliveres M, Massons J. Spontaneous necessary due to the complete resolution of symptoms. primary intraventricular hemorrhage: clinical features and early outcome. ISRN Neurol. 2012;2012:498303. It is also not possible to prove the sequence of the vaso- 4. Wilson D, Marshall CR, Solbach T, Watkins L, Werring DJ. Intraventricular constriction and the hemorrhage, as vessel imaging was hemorrhage in reversible cerebral vasoconstriction syndrome. J Neurol. obtained only after the patient was found to have a 2014;261:2221–4. 5. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible hemorrhage, although the diffuse nature of the vasocon- cerebral vasoconstriction syndromes. Ann Intern Med. 2007;146:34–44. striction was felt to more likely represent the cause of 6. Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. the intraventricular hemorrhage rather than an effect. 2012;11:906–17. 7. Cappelen-Smith C, Calic Z, Cordato D. Reversible cerebral vasoconstriction However, the important point in this case is the poten- syndrome: recognition and treatment. Curr Treat Options Neurol. 2017;19:21. tial serious consequences of vasoactive substances such 8. Flint AC, Roebken A, Singh V. Primary intraventricular hemorrhage: yield of as over-the-counter decongestants, which have been as- diagnostic angiography and clinical outcome. Neurocrit Care. 2008;8:330–6. 9. Ducros A, Fiedler U, Porcher R, Boukobza M, Stapf C, Bousser MG. sociated with triggering RCVS. Because these substances Hemorrhagic manifestations of reversible cerebral vasoconstriction are readily available without a prescription, it is import- syndrome: frequency, features, and risk factors. Stroke. 2010;41:2505–11. ant to inquire about the use of these substances, as 10. Topcuoglu MA, Singhal AB. Hemorrhagic reversible cerebral vasoconstriction syndrome: features and mechanisms. Stroke. 2016;47:1742–7. prompt identification and withdrawal of the offending 11. Tark BE, Messe SR, Balucani C, Levine SR. Intracerebral hemorrhage agent reduces the risk of further neurologic decline. associated with oral phenylephrine use: a case report and review of the literature. J Stroke Cerebrovasc Dis. 2014;23:2296–300. Abbreviations RCVS: Reversible cerebral vasoconstriction syndrome; IVH : Intraventricular hemorrhage; CT : Computerized tomography; MRI : Magnetic resonance imaging Availability of data and materials Data sharing not applicable to this article as no datasets were generated or analyzed. Authors’ contributions KD drafted the manuscript; LW assisted in review of literature and preparation of manuscript; SY assisted in editing the manuscript; MJ and RM assisted in preparation and interpretation of the figures; all authors read and approved the final manuscript. Ethics approval and consent to participate The institutional review board at Lifespan exempted this case report from formal review as per the Human Research Protection Program Policy and Procedure Manual, as it does not meet the Common Rule definition for research. The patient consented for the preparation and submission of this manuscript. Consent for publication Written consent has been obtained from the patient involved in this case report, and the patient has agreed to her clinical information being published. Competing interests The authors declare that they have no competing interests.
Chinese Neurosurgical Journal – Springer Journals
Published: Jun 4, 2018
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