ISSN 0017-8748 doi: 10.1111/head.12319 Published by Wiley Periodicals, Inc.
Headache © 2014 American Headache Society
Brief Communication Reversible Cerebral Vasoconstriction Syndrome After Blood Transfusion Yi-Hsuan Dou, MD; Jong-Ling Fuh, MD; Shih-Pin Chen, MD, PhD; Shuu-Jiun Wang, MD Objectives.—To report 2 cases of reversible cerebral vasoconstriction syndrome (RCVS) with posterior reversible encephalopathy syndrome (PRES) after blood transfusion for severe anemia. Background.—RCVS is presented with recurrent thunderclap headache and reversible constriction of cerebral arteries. PRES is a known complication of RCVS. Blood transfusion for severe anemia could be a cause for PRES in few cases; however, it is seldom mentioned as an etiology for RCVS. Methods.—We report a case series. Results.—We report 2 women presented with RCVS with PRES after blood transfusion for anemia, and reviewed another 4 similar cases reported in the literature. Our 2 patients were middle-aged women, with severe chronic anemia (average hemoglobin: 1.45 g/dL), and received multiple blood transfusions (average: 3250 mL) over a period of 5-7 days. They developed thunderclap headache and other symptoms about 1 week after the last blood transfusion. Cerebral vasoconstrictions were demonstrated by magnetic resonance angiography and transcranial color-coded sonography. PRES was found in both of them using magnetic resonance imaging, and one of them also had cytotoxic edema on diffusion weighted image. Conclusions.—RCVS with PRES is one complication of blood transfusion in patients under chronic severe anemia (especially when hemoglobin level increased for more than 5 g/dL), particularly in Asian women with menorrhagia. Blood pressure surge and the occurrence of severe headaches or other neurological symptoms should be aggressively monitored within 10 days after the last blood transfusion. Key words: reversible cerebral vasoconstriction syndrome, blood transfusion, posterior reversible encephalopathy syndrome, chronic anemia Abbreviations: BP blood pressure, CT computed tomography, FLAIR fluid-attenuated inversion recovery, ICH intracranial hemorrhage, LI Lindegaard Index, MCA middle cerebral artery, MMSE mini-mental status examination, MRA magnetic resonance angiograph, MRI magnetic resonance imaging, PRBC packed red blood cells, PRES posterior reversible encephalopathy syndrome, RCVS reversible cerebral vasoconstriction syndrome, SAH subarachnoid hemorrhage, TCCS transcranial color-coded sonography (Headache 2014;54:736-744) From the Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H. Dou, J.-L. Fuh, S.-P. Chen, and S.-J. Wang); Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (Y.-H. Dou, J.-L. Fuh, S.-P. Chen, and S.-J. Wang); Brain Research Center, National Yang-Ming University, Taipei, Taiwan (J.-L. Fuh, S.-P. Chen, and S.-J. Wang); Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan (S.-J. Wang). Address all correspondence to S.-J. Wang, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei 11217, Taiwan. Accepted for publication December 27, 2013. Conflict of Interest: Dr. Dou reports no disclosures. Dr. Chen received grants from Taipei Veterans General Hospital and National Science Councils, Taiwan. Dr. Jong-Ling Fuh is a member of a scientific advisory board of Elli Lilly and Novartis, and has as well received research support from the Taiwan National Science Council, Taipei-Veterans General Hospital, and Elli Lilly. Dr. Shuu-Jiun Wang has served on the advisory boards of Pfizer, Allergan, and Elli Lilly Taiwan. He has received speaking honoraria from local companies (Taiwan branches) of Pfizer, Elli Lilly, Boehringer Ingelheim, and GSK. He has received research grants from the Taiwan National Science Council, Taipei-Veterans General Hospital, and Taiwan Headache Society.
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Headache Reversible cerebral vasoconstriction syndrome (RCVS) is associated with recurrent thunderclap headache and reversible constriction of the cerebral arteries. RCVS occurs predominantly in females, with a peak prevalence age of about 40-50 years.1-3 Posterior reversible encephalopathy syndrome (PRES) is a known complication of RCVS, with an estimated prevalence of 8-38%.1,3-7 Patients with severe cerebral vasoconstrictions are more likely to develop PRES and even ischemic stroke.2,8 The etiology of RCVS can be either idiopathic or secondary. Estimated frequencies of idiopathic and secondary RCVS are approximately 37-94% and 6-64%, respectively, and vary among different studies or cohorts.1,2 The use of vasoactive substances, such as illicit drugs and selective serotonin-reuptake inhibitors, is the most common secondary cause of RCVS, accounting for one-half of the secondary cases.3,4 The second most common cause is post-partum status, which accounts for an estimated 9% of cases.3,4 Blood transfusion for severe anemia has been associated with PRES in a few cases; however, blood transfusion is seldom mentioned as an etiology for RCVS.9-11 Here, we report the cases of 2 women who presented with RCVS and PRES after blood transfusion for severe anemia.
CASE 1 A previously healthy 50-year-old woman presented with severe anemia (hemoglobin: 1.5 g/dL) due to menorrhagia for the past 1 month. The woman was admitted to the hospital. She was given a blood transfusion of packed red blood cells (PRBCs) at 500 mL/d for 6 days (total of 3000 mL), which increased her hemoglobin level to 12.0 g/dL. On the 7th day after admission, the patient underwent surgery for a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Postoperative findings included uterine leiomyoma, adenomyosis, and cervical polyps. Because of a blood loss of 1700 mL during the surgery, 1 L of PRBCs was subsequently transfused. On the 10th day after admission, the patient experienced a thunderclap headache, ie, a suddenonset severe headache (numerical rating scale 10/10), reaching the maximum within 1 minute and persisting
737 for approximately 15 minutes. The severe headache occurred when she was lying on the bed and improved after administration of acetaminophen (500 mg every 6 hours). The headache was accompanied by a blood pressure (BP) surge, with systolic BP increasing to a maximum of 204 mmHg. The headache was located over the vertex of the head with bursting pain. The patient did not report accompanying nausea, vomiting, photophobia, or phonophobia. Another 5 episodes of thunderclap headaches with elevated BP subsequently occurred. On the 15th day after admission, one episode of generalized tonic clonic seizure was observed. In the following week, elevated BP (systolic BP: 160-180 mmHg) and severe episodic headaches recurred. A T2-weighted magnetic resonance imaging (MRI) scan of the patient’s brain disclosed hyperintense lesions over the bilateral frontal and parietooccipital regions (Fig. 1A,B). T2 fluid-attenuated inversion recovery (FLAIR) revealed focal highintensity signals over the bilateral posterior temporal lobes (Fig. 1C). Magnetic resonance angiography (MRA) demonstrated multiple segmental cerebral vasoconstrictions (Fig. 2A,B). Transcranial colorcoded sonography (TCCS) showed a mean flow velocity in the right M1 segment of the middle cerebral artery (MCA) of 231 cm/second and a Lindegaard Index (LI) of 8.25; the mean flow velocity in the left M1 was 213 cm/second, with an LI of 6.65. The patient’s hemoglobin level at this time was 12.3 g/ dL. RCVS with PRES was diagnosed. Upon administration of nimodipine (60 mg every 4 hours), the patient’s symptoms improved without further incidence of thunderclap headaches. Follow-up brain MRA (Fig. 2C,D) showed significant improvement of vasoconstriction 7 days after the first MRA. The high signal shown in the brain T2-weighted MRI and T2 FLAIR over the bilateral frontal, occipito-parietal, and posterior temporal lobes was shown to be resolved. Repeat tests 20 days after the first TCCS showed a marked decrease of flow velocity.
CASE 2 A 46-year-old woman was admitted for irregular menstrual cycles, prolonged menstruation periods in
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Fig 1.—(A) Hyperintense lesions were found over bilateral frontal area in brain magnetic resonance image (MRI) T2-weighted image. (B) Brain MRI T2-weighted image showed hyperintense lesions over bilateral posterior parieto-occipital regions. (C) T2 fluid-attenuated inversion recovery (FLAIR) MRI revealed focal high signals over bilateral posterior temporal lobes.
the previous 6 months, and persistent vaginal bleeding for 1 month. She reported a history of uterine leiomyoma without medical treatment for the past 10 years. On arrival, severe microcytic anemia (hemoglobin: 1.4 g/dL) was found. The patient received blood transfusions of 500 mL PRBC for 5 days (total of 2500 mL), after which time the patient’s hemoglobin increased to 10.9 g/dL. A huge uterine leiomyoma (12 × 9.4 cm) was revealed by an abdominal computed tomography (CT) scan. A total abdominal hysterectomy was performed on the 8th day after admission, with an intraoperative blood loss of 250 mL. The patient developed a thunderclap headache, visual field deficits, and cognitive impairment on the 15th day after admission. After the thunderclap headache, she had residual dull headache. No concomitant nausea, vomiting, photophobia, or phonophobia was reported. Examination revealed right homonymous hemianopsia, cognitive impairment (mini-mental status examination [MMSE] score: 19), and apraxia. Elevated BP was noted (162/93 mmHg; patient baseline: 90-100/50-60 mmHg). Brain CT revealed low-density signals over the patient’s left parietal and right medial high frontal regions. Brain MRI showed acute infarctions over the bilateral parasagittal frontoparietal, temporo-
occipital, and left parietal regions (Fig. 3). Multiple segmental narrowings of cerebral arteries were demonstrated by MRA (Fig. 4A,B). TCCS revealed a mean flow velocity in the right M1 of 233 cm/second and an LI of 3.14; the mean flow velocity in the left M1 was 320 cm/second, with an LI of 4.57. The diagnosis of RCVS with PRES and ischemic stroke was made. The patient was treated with 75 mg of clopidogrel per day and 60 mg of nimodipine every 4 hours, and the above symptoms improved gradually. No significant cognitive impairment (MMSE score: 30) and little residual visual deficit remained. A follow-up MRA, performed 25 days after the first, showed recovery of the vasoconstriction (Fig. 4C,D). The mean MCA flow velocities gradually decreased to below 120 cm/second by 27 days after the first TCCS. The mean flow velocities of the right and left M1 were 110 and 111 cm/second, respectively. Some remaining brain infarct lesions were demonstrated by brain MRI T2 FLAIR imaging 40 days after the first MRI (Fig. 3G-I). The patient reported no occurrence of headache after nimodipine use.
DISCUSSION Our cases demonstrate that RCVS with PRES could be a serious complication of blood transfusion in women with severe chronic anemia due to menor-
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Fig 2.—(A and B) Three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) showed multiple segmental narrowings over bilateral anterior cerebral arteries, left middle cerebral artery, and right posterior cerebral artery (arrows). (C and D) 3D TOF MRA obtained after 7 days showed significant improvement of vasoconstriction (arrows).
rhagia. In our case reports, the patients were middleaged women with severe chronic anemia (average hemoglobin: 1.45 g/dL). They each received multiple blood transfusions (average: 3250 mL) over a period of 5-7 days.The patients developed thunderclap headaches and other symptoms approximately 1 week after the last blood transfusion. Recovery of the cerebral vessel constriction was demonstrated by MRA and TCCS. Although the second patient experienced a stroke, this complication could be considered as a more severe form of PRES, with cytotoxic edema, in the MRI findings. Stroke is a common complication in severe RCVS or PRES. Red blood cell transfusion was a known possible trigger factor for cerebral vasoconstriction; however, the headache features were not clearly mentioned.10 Only one case report has mentioned the development of RCVS after blood transfusion; however, the incidence of RCVS was noted 3 months after blood trans-
fusion,9 and the causality was difficult to confirm. Several cases of PRES after blood transfusion have been reported, some of which were also found to have vasoconstriction, although this characteristic was not stressed by the authors.11-14 However, the reversibility of vasoconstriction and thunderclap headache was not clearly described.11-14 The Table summarizes the cases of PRES after blood transfusion that have been described in the literature, including our 2 cases. These cases include exclusively female patients, mostly middle-aged and Asian, with chronic severe anemia (mostly due to menorrhagia). In all cases, blood transfusion increased the hemoglobin level by at least 5 g/dL from baseline (average increase: 8.2 g/dL). Within 10 days of the last blood transfusion, symptoms of severe headache, BP surge, and encephalopathy developed. One patient demonstrated aplastic anemia13 and received a blood transfusion without any surgical
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Fig 3.—(A-C) Hyperintense signals over bilateral parasagittal frontoparietal, temporo-occipital, and left parietal regions in diffusion weighted imaging (DWI). (D-F) The apparent diffusion coefficient (ADC) image showed low signals areas compared with the bright signals in DWI. (G-I) High signals in T2 FLAIR series over bilateral parasagittal frontopareital, temporo-occipital, and left parietal lobes in a 40-day follow-up brain MRI.
intervention. Another patient who developed RCVS 3 months after receiving a blood transfusion was the only patient who also received hormonal therapy9; therefore, this case was omitted from the table. Around 87% of patients with PRES demonstrate cerebral vasoconstriction or focal vasculopathy.15
Some shared potential causes between RCVS and PRES include hypertension, eclampsia or preeclampsia, autoimmune diseases, and immunosuppressants.16 RCVS and PRES share many features, such as similar background characteristics, predisposing factors, clinical presentations, and clinical courses
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Fig 4.—(A) Three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) showed multiple shortsegmental narrowings over bilateral middle cerebral arteries and anterior cerebral arteries (arrows). (B) 3D TOF MRA revealed severe constriction over left posterior cerebral artery and short segmental narrowing over right posterior cerebral artery (arrows). (C and D) 3D TOF MRA obtained after 25 days showed recovery of vasoconstriction (arrows).
and outcomes, which suggests overlapping pathophysiological mechanisms. Thus, RCVS and PRES may be included in an overlapping disease spectrum with variable involvement. The mechanisms behind RCVS and PRES development are still unknown. A proposed pathophysiologic mechanism is dysautoregulation of the cerebral endothelium under specific predisposing factors, resulting in dysregulation of cerebral vascular tone.17 No case report exists regarding RCVS due to transfused blood products under conditions of acute blood loss. It has been suggested that chronic anemia may result in a compensatory cerebral vasodilatation.18 We hypothesize that when patients with chronic anemia receive blood transfusions, the resulting rapid increase in cerebral blood flow and viscosity may result in a loss of vasodilation, increase in vascular resistance, and ultimately, overwhelming cerebral vessel constriction, which resembles cerebral hyper-
perfusion syndrome in carotid revascularization surgery associated with carotid stenting and endarterectomy.19,20 Factors related to vasospasm in aneurysmal subarachnoid hemorrhage (SAH) (catecholamines, endothelin-1, calcium, serotonin, nitric oxide, and prostaglandins) might play some role in the vasoconstriction in RCVS, although it had no direct evidence.21 The latencies from autoregulation breakthrough to symptom onset and overt vasoconstriction of major cerebral arteries may depend on the patients’ conditions, underlying diseases, blood transfusion amount, and duration. Another explanation for the delayed onset of vasoconstrictions might be related to the temporal course of centripetal progression of the vasoconstrictions.1 The deranged cerebral vasomotor control might first involve small distal arteries that are beyond the resolution of imaging studies. Furthermore, case reports have been published of patients with chronic anemic conditions (eg, end-stage renal
Menometrorrhagia (uterine myoma)
48/F
47/F
32/F
50/F
46/F
Boughammoura et al11
Heo et al13
Huang et al14
Dou et al case 1
Dou et al case 2 Headache, visual deficit, elevated BP and cognitive impairment
Headache, dizziness, nausea, GTCS, and consciousness disturbance Headache, nausea, vomiting, blurred vision and GTCS Headache, BP surge and GTCS
Status epilepticus and consciousness disturbance
Headache, nausea, GTCS, and BP surge
Symptoms
2500
3000 + 1000‡
1600
Unknown†
1000
800
BT Volume of PRBCs (mL)
10
3
5
7
6
2
Symptoms Onset After Last BT (days)
1.4/10.9
1.5/12.0
5.7/12.5
1.5/10.9
3.0/8.0
2.0/10.0
Hb**** (g/dL)
6.8/33.7
5.7/36.3
22.6/43.4
4.2/31.6
13/29
9.0/31
Hct**** (%)
5 days
6 days + 1 day‡
20 hours
4 days
7 hours
14 days
Period of BT
Bilateral frontoparietal, left parietal, left, and temporo-occipital regions acute infarction
Bilateral occipital lobes T2 hyperintensities Bilateral parietal lobes T2 FLAIR hyperintensities
Bilateral parietooccipital white matter T2 hyperintensities Bilateral small fronto-parietal cortical and subcortical T2 FLAIR hyperintensities Bilateral parietooccipital T2 hyperintensities
Brain Imaging
Diffuse proximal
Diffuse proximal and distal
Left PCA
Diffuse proximal and distal
Diffuse proximal and distal
Distal PCAs
Vasoconstriction
Mean flow velocities of bilateral MCA > 120 cm/second Mean flow velocities of bilateral MCA > 120 cm/second
Nil
Increased left MCA peak systolic velocity (140 cm/ second) Nil
Nil
TCD
Nil
Nil
Right homonymous inferior quadrantanopia Nil
Nil
Nil
Complications§
****Data before/after blood transfusion. †Filtrated red blood cells, platelet concentrates, and fresh frozen plasma. ‡6 days were presurgery, 1 day for surgical blood loss during the operation. §Complications of the reversible cerebral vasoconstriction syndrome (RCVS) with posterior reversible encephalopathy syndrome (PRES). BP = blood pressure; BT = blood transfusion; F = female; FLAIR = fluid-attenuated inversion recovery; GTCS = generalized tonic-clonic seizure; Hb = hemoglobin; Hct = hematocrit; MCA = middle cerebral artery; PCA = posterior cerebral artery; PRBC = packed red blood cell; TCD = transcranial Doppler ultrasound.
Menometrorrhagia (uterine leiomyoma)
Menorrhagia (uterine leiomyoma and adenomyosis)
Menorrhagia (uterine myoma)
Aplastic anemia
Menometrorrhagia (uterine myoma)
45/F
Causes of Anemia
Ito et al12
Study
Age (years)/ Gender
Table.—Cases of Reversible Vasoconstriction Syndrome With Posterior Reversible Encephalopathy Syndrome After Blood Transfusion
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Headache diseases and sickle-cell anemia) who developed PRES, with or without cerebral vasoconstriction, after blood transfusion.22-24 Damage related to reperfusion may release free radicals and trigger dysfunction of the cerebral endothelium, which may further aggravate cerebral vasoconstriction and damage to the vasculoendothelial system, leading to a vicious cycle. This hypothesis is supported by our recent study, in which we showed that oxidative stress is associated with cerebral vasoconstriction in RCVS.25 Nimodipine has been listed as a possible treatment for RCVS.26 The favorable response to nimodipine may be partly due to its role in preventing vasospasm or its effect on the endothelium.27 In line with our cases, a recent case report suggested that nimodipine may be used to prevent and treat recurrent PRES.26 Thus, in RCVS with PRES, nimodipine might be worthy of further investigation. In case 1, BP surge was found. After nimodipine (60 mg every 4 hours) treatment, her BP returned to normal. We could not conclude if BP management could prevent the development of RCVS. In case 2, clopidogrel was given because of acute cerebral infarction. It is estimated that the frequency of intracranial hemorrhages (ICHs) as complications of RCVS was about 28%.1 In fact, complications of RCVS differ in different time course. Cerebral hemorrhages (such as cortical SAH and ICH) are early events occurring during the first week. The ischemic complications occur later, usually during the second week.1 This patient developed cerebral infarction during the second week. In our opinion, the benefit of administering clopidogrel for secondary stroke prevention might outweigh the risk of hemorrhage.
CONCLUSION Our case reports suggest that RCVS with PRES is one complication of blood transfusion (especially when the hemoglobin level increases by >5 g/dL) in patients experiencing chronic severe anemia – in particular,Asian women with menorrhagia. BP surge and the occurrence of severe headaches or other neurological symptoms should be aggressively monitored, especially within the first 10 days after the last blood transfusion.
743 Acknowledgments: This study was supported by grants from the National Science Council of Taiwan (NSC 100-2314-B-010-019-MY2, NSC 100-2314-B010-018-MY3), Taipei-Veterans General Hospital (VGHUST102-G7-6-1, V102C-118, V102E9-001), NSC support for Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan (NSC 101-2911-I-008-001), Brain Research Center, National Yang-Ming University, and a grant from Ministry of Education, Aim for the Top University Plan. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Shih-Pin Chen (b) Acquisition of Data Yi-Hsuan Dou (c) Analysis and Interpretation of Data Shuu-Jiun Wang, Jong-Ling Fuh, Shih-Pin Chen, Yi-Hsuan Dou Category 2 (a) Drafting the Manuscript Yi-Hsuan Dou (b) Revising It for Intellectual Content Shuu-Jiun Wang, Jong-Ling Fuh, Shih-Pin Chen Category 3 (a) Final Approval of the Completed Manuscript Shuu-Jiun Wang, Jong-Ling Fuh, Shih-Pin Chen, Yi-Hsuan Dou
REFERENCES 1. Ducros A, Boukobza M, Porcher R, Sarov M, Valade D, Bousser MG. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain. 2007;130:3091-3101. 2. Chen SP, Fuh JL, Wang SJ, et al. Magnetic resonance angiography in reversible cerebral vasoconstriction syndromes. Ann Neurol. 2010;67:648656.
744 3. Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. Reversible cerebral vasoconstriction syndromes: Analysis of 139 cases. Arch Neurol. 2011;68:10051012. 4. Ducros A, Fiedler U, Porcher R, Boukobza M, Stapf C, Bousser MG. Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome: Frequency, features, and risk factors. Stroke. 2010;41: 2505-2511. 5. Singhal AB. Postpartum angiopathy with reversible posterior leukoencephalopathy. Arch Neurol. 2004; 61:411-416. 6. Fugate JE, Ameriso SF, Ortiz G, et al. Variable presentations of postpartum angiopathy. Stroke. 2012; 43:670-676. 7. Dodick DW, Eross EJ, Drazkowski JF, Ingall TJ. Thunderclap headache associated with reversible vasospasm and posterior leukoencephalopathy syndrome. Cephalalgia. 2003;23:994-997. 8. Chen SP, Fuh JL, Chang FC, Lirng JF, Shia BC, Wang SJ. Transcranial color Doppler study for reversible cerebral vasoconstriction syndromes. Ann Neurol. 2008;63:751-757. 9. Braun CN, Hughes RL, Bosque PJ. Reversible cerebral vasoconstriction syndrome 3 months after blood transfusion. J Stroke Cerebrovasc Dis. 2012; 21:e911-e915. 10. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: Reversible cerebral vasoconstriction syndromes. Ann Intern Med. 2007;146:3444. 11. Boughammoura A, Touze E, Oppenheim C, Trystram D, Mas JL. Reversible angiopathy and encephalopathy after blood transfusion. J Neurol. 2003;250:116-118. 12. Ito Y, Niwa H, Iida T, et al. Post-transfusion reversible posterior leukoencephalopathy syndrome with cerebral vasoconstriction. Neurology. 1997;49:11741175. 13. Heo K, Park S, Lee JY, Lee BI, Lee SK. Posttransfusion posterior leukoencephalopathy with cytotoxic and vasogenic edema precipitated by vasospasm. Cerebrovasc Dis. 2003;15:230-233. 14. Huang YC, Tsai PL, Yeh JH, Chen WH. Reversible posterior leukoencephalopathy syndrome caused by blood transfusion: A case report. Acta Neurol Taiwan. 2008;17:258-262.
April 2014 15. Bartynski WS, Boardman JF. Catheter angiography, MR angiography, and MR perfusion in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol. 2008;29:447-455. 16. Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012;11:906-917. 17. Chen SP, Fuh JL, Wang SJ. Reversible cerebral vasoconstriction syndrome: Current and future perspectives. Expert Rev Neurother. 2011;11:1265-1276. 18. Medel R, Crowley RW, Dumont AS. Hyperperfusion syndrome following endovascular cerebral revascularization. Neurosurg Focus. 2009;26:E4. 19. McCabe DJ, Brown MM, Clifton A. Fatal cerebral reperfusion hemorrhage after carotid stenting. Stroke. 1999;30:2483-2486. 20. Ballesteros-Pomar M, Alonso-Argueso G, TejadaGarcia J, Vaquero-Morillo F. Cerebral hyperperfusion syndrome in carotid revascularisation surgery. Rev Neurol. 2012;55:490-498. 21. Singhal AB. Cerebral vasoconstriction syndromes. Top Stroke Rehabil. 2004;11:1-6. 22. Kolovou V, Zampakis P, Ginopoulou A, Varvarigou A, Kaleyias J. Reversible posterior leukoencephalopathy syndrome after blood transfusion in a pediatric patient with sickle cell disease. Pediatr Neurol. 2013;49:213-217. 23. Raj S, Killinger J, Overby P. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES). J Child Neurol. 2013;28:1284-1286. 24. Sato Y, Hirose M, Inoue Y, et al. Reversible posterior leukoencephalopathy syndrome after blood transfusion in a patient with end-stage renal disease. Clin Exp Nephrol. 2011;15:942-947. 25. Chen SP, Chung YT, Liu TY, Wang YF, Fuh JL, Wang SJ. Oxidative stress and increased formation of vasoconstricting F2-isoprostanes in patients with reversible cerebral vasoconstriction syndrome. Free Radic Biol Med. 2013;61C:243-248. 26. Lu SR, Liao YC, Fuh JL, Lirng JF, Wang SJ. Nimodipine for treatment of primary thunderclap headache. Neurology. 2004;62:1414-1416. 27. Matias-Guiu JA, Garcia-Ptacek S, Ordas CM, Marcos-Dolado A, Porta-Etessam J. Recurrent reversible posterior encephalopathy syndrome with a response to nimodipine. Neurologia. 2012;27:378380.
Headache © 2014 American Headache Society
Brief Communication Reversible Cerebral Vasoconstriction Syndrome After Blood Transfusion Yi-Hsuan Dou, MD; Jong-Ling Fuh, MD; Shih-Pin Chen, MD, PhD; Shuu-Jiun Wang, MD Objectives.—To report 2 cases of reversible cerebral vasoconstriction syndrome (RCVS) with posterior reversible encephalopathy syndrome (PRES) after blood transfusion for severe anemia. Background.—RCVS is presented with recurrent thunderclap headache and reversible constriction of cerebral arteries. PRES is a known complication of RCVS. Blood transfusion for severe anemia could be a cause for PRES in few cases; however, it is seldom mentioned as an etiology for RCVS. Methods.—We report a case series. Results.—We report 2 women presented with RCVS with PRES after blood transfusion for anemia, and reviewed another 4 similar cases reported in the literature. Our 2 patients were middle-aged women, with severe chronic anemia (average hemoglobin: 1.45 g/dL), and received multiple blood transfusions (average: 3250 mL) over a period of 5-7 days. They developed thunderclap headache and other symptoms about 1 week after the last blood transfusion. Cerebral vasoconstrictions were demonstrated by magnetic resonance angiography and transcranial color-coded sonography. PRES was found in both of them using magnetic resonance imaging, and one of them also had cytotoxic edema on diffusion weighted image. Conclusions.—RCVS with PRES is one complication of blood transfusion in patients under chronic severe anemia (especially when hemoglobin level increased for more than 5 g/dL), particularly in Asian women with menorrhagia. Blood pressure surge and the occurrence of severe headaches or other neurological symptoms should be aggressively monitored within 10 days after the last blood transfusion. Key words: reversible cerebral vasoconstriction syndrome, blood transfusion, posterior reversible encephalopathy syndrome, chronic anemia Abbreviations: BP blood pressure, CT computed tomography, FLAIR fluid-attenuated inversion recovery, ICH intracranial hemorrhage, LI Lindegaard Index, MCA middle cerebral artery, MMSE mini-mental status examination, MRA magnetic resonance angiograph, MRI magnetic resonance imaging, PRBC packed red blood cells, PRES posterior reversible encephalopathy syndrome, RCVS reversible cerebral vasoconstriction syndrome, SAH subarachnoid hemorrhage, TCCS transcranial color-coded sonography (Headache 2014;54:736-744) From the Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H. Dou, J.-L. Fuh, S.-P. Chen, and S.-J. Wang); Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (Y.-H. Dou, J.-L. Fuh, S.-P. Chen, and S.-J. Wang); Brain Research Center, National Yang-Ming University, Taipei, Taiwan (J.-L. Fuh, S.-P. Chen, and S.-J. Wang); Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan (S.-J. Wang). Address all correspondence to S.-J. Wang, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei 11217, Taiwan. Accepted for publication December 27, 2013. Conflict of Interest: Dr. Dou reports no disclosures. Dr. Chen received grants from Taipei Veterans General Hospital and National Science Councils, Taiwan. Dr. Jong-Ling Fuh is a member of a scientific advisory board of Elli Lilly and Novartis, and has as well received research support from the Taiwan National Science Council, Taipei-Veterans General Hospital, and Elli Lilly. Dr. Shuu-Jiun Wang has served on the advisory boards of Pfizer, Allergan, and Elli Lilly Taiwan. He has received speaking honoraria from local companies (Taiwan branches) of Pfizer, Elli Lilly, Boehringer Ingelheim, and GSK. He has received research grants from the Taiwan National Science Council, Taipei-Veterans General Hospital, and Taiwan Headache Society.
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Headache Reversible cerebral vasoconstriction syndrome (RCVS) is associated with recurrent thunderclap headache and reversible constriction of the cerebral arteries. RCVS occurs predominantly in females, with a peak prevalence age of about 40-50 years.1-3 Posterior reversible encephalopathy syndrome (PRES) is a known complication of RCVS, with an estimated prevalence of 8-38%.1,3-7 Patients with severe cerebral vasoconstrictions are more likely to develop PRES and even ischemic stroke.2,8 The etiology of RCVS can be either idiopathic or secondary. Estimated frequencies of idiopathic and secondary RCVS are approximately 37-94% and 6-64%, respectively, and vary among different studies or cohorts.1,2 The use of vasoactive substances, such as illicit drugs and selective serotonin-reuptake inhibitors, is the most common secondary cause of RCVS, accounting for one-half of the secondary cases.3,4 The second most common cause is post-partum status, which accounts for an estimated 9% of cases.3,4 Blood transfusion for severe anemia has been associated with PRES in a few cases; however, blood transfusion is seldom mentioned as an etiology for RCVS.9-11 Here, we report the cases of 2 women who presented with RCVS and PRES after blood transfusion for severe anemia.
CASE 1 A previously healthy 50-year-old woman presented with severe anemia (hemoglobin: 1.5 g/dL) due to menorrhagia for the past 1 month. The woman was admitted to the hospital. She was given a blood transfusion of packed red blood cells (PRBCs) at 500 mL/d for 6 days (total of 3000 mL), which increased her hemoglobin level to 12.0 g/dL. On the 7th day after admission, the patient underwent surgery for a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Postoperative findings included uterine leiomyoma, adenomyosis, and cervical polyps. Because of a blood loss of 1700 mL during the surgery, 1 L of PRBCs was subsequently transfused. On the 10th day after admission, the patient experienced a thunderclap headache, ie, a suddenonset severe headache (numerical rating scale 10/10), reaching the maximum within 1 minute and persisting
737 for approximately 15 minutes. The severe headache occurred when she was lying on the bed and improved after administration of acetaminophen (500 mg every 6 hours). The headache was accompanied by a blood pressure (BP) surge, with systolic BP increasing to a maximum of 204 mmHg. The headache was located over the vertex of the head with bursting pain. The patient did not report accompanying nausea, vomiting, photophobia, or phonophobia. Another 5 episodes of thunderclap headaches with elevated BP subsequently occurred. On the 15th day after admission, one episode of generalized tonic clonic seizure was observed. In the following week, elevated BP (systolic BP: 160-180 mmHg) and severe episodic headaches recurred. A T2-weighted magnetic resonance imaging (MRI) scan of the patient’s brain disclosed hyperintense lesions over the bilateral frontal and parietooccipital regions (Fig. 1A,B). T2 fluid-attenuated inversion recovery (FLAIR) revealed focal highintensity signals over the bilateral posterior temporal lobes (Fig. 1C). Magnetic resonance angiography (MRA) demonstrated multiple segmental cerebral vasoconstrictions (Fig. 2A,B). Transcranial colorcoded sonography (TCCS) showed a mean flow velocity in the right M1 segment of the middle cerebral artery (MCA) of 231 cm/second and a Lindegaard Index (LI) of 8.25; the mean flow velocity in the left M1 was 213 cm/second, with an LI of 6.65. The patient’s hemoglobin level at this time was 12.3 g/ dL. RCVS with PRES was diagnosed. Upon administration of nimodipine (60 mg every 4 hours), the patient’s symptoms improved without further incidence of thunderclap headaches. Follow-up brain MRA (Fig. 2C,D) showed significant improvement of vasoconstriction 7 days after the first MRA. The high signal shown in the brain T2-weighted MRI and T2 FLAIR over the bilateral frontal, occipito-parietal, and posterior temporal lobes was shown to be resolved. Repeat tests 20 days after the first TCCS showed a marked decrease of flow velocity.
CASE 2 A 46-year-old woman was admitted for irregular menstrual cycles, prolonged menstruation periods in
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Fig 1.—(A) Hyperintense lesions were found over bilateral frontal area in brain magnetic resonance image (MRI) T2-weighted image. (B) Brain MRI T2-weighted image showed hyperintense lesions over bilateral posterior parieto-occipital regions. (C) T2 fluid-attenuated inversion recovery (FLAIR) MRI revealed focal high signals over bilateral posterior temporal lobes.
the previous 6 months, and persistent vaginal bleeding for 1 month. She reported a history of uterine leiomyoma without medical treatment for the past 10 years. On arrival, severe microcytic anemia (hemoglobin: 1.4 g/dL) was found. The patient received blood transfusions of 500 mL PRBC for 5 days (total of 2500 mL), after which time the patient’s hemoglobin increased to 10.9 g/dL. A huge uterine leiomyoma (12 × 9.4 cm) was revealed by an abdominal computed tomography (CT) scan. A total abdominal hysterectomy was performed on the 8th day after admission, with an intraoperative blood loss of 250 mL. The patient developed a thunderclap headache, visual field deficits, and cognitive impairment on the 15th day after admission. After the thunderclap headache, she had residual dull headache. No concomitant nausea, vomiting, photophobia, or phonophobia was reported. Examination revealed right homonymous hemianopsia, cognitive impairment (mini-mental status examination [MMSE] score: 19), and apraxia. Elevated BP was noted (162/93 mmHg; patient baseline: 90-100/50-60 mmHg). Brain CT revealed low-density signals over the patient’s left parietal and right medial high frontal regions. Brain MRI showed acute infarctions over the bilateral parasagittal frontoparietal, temporo-
occipital, and left parietal regions (Fig. 3). Multiple segmental narrowings of cerebral arteries were demonstrated by MRA (Fig. 4A,B). TCCS revealed a mean flow velocity in the right M1 of 233 cm/second and an LI of 3.14; the mean flow velocity in the left M1 was 320 cm/second, with an LI of 4.57. The diagnosis of RCVS with PRES and ischemic stroke was made. The patient was treated with 75 mg of clopidogrel per day and 60 mg of nimodipine every 4 hours, and the above symptoms improved gradually. No significant cognitive impairment (MMSE score: 30) and little residual visual deficit remained. A follow-up MRA, performed 25 days after the first, showed recovery of the vasoconstriction (Fig. 4C,D). The mean MCA flow velocities gradually decreased to below 120 cm/second by 27 days after the first TCCS. The mean flow velocities of the right and left M1 were 110 and 111 cm/second, respectively. Some remaining brain infarct lesions were demonstrated by brain MRI T2 FLAIR imaging 40 days after the first MRI (Fig. 3G-I). The patient reported no occurrence of headache after nimodipine use.
DISCUSSION Our cases demonstrate that RCVS with PRES could be a serious complication of blood transfusion in women with severe chronic anemia due to menor-
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Fig 2.—(A and B) Three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) showed multiple segmental narrowings over bilateral anterior cerebral arteries, left middle cerebral artery, and right posterior cerebral artery (arrows). (C and D) 3D TOF MRA obtained after 7 days showed significant improvement of vasoconstriction (arrows).
rhagia. In our case reports, the patients were middleaged women with severe chronic anemia (average hemoglobin: 1.45 g/dL). They each received multiple blood transfusions (average: 3250 mL) over a period of 5-7 days.The patients developed thunderclap headaches and other symptoms approximately 1 week after the last blood transfusion. Recovery of the cerebral vessel constriction was demonstrated by MRA and TCCS. Although the second patient experienced a stroke, this complication could be considered as a more severe form of PRES, with cytotoxic edema, in the MRI findings. Stroke is a common complication in severe RCVS or PRES. Red blood cell transfusion was a known possible trigger factor for cerebral vasoconstriction; however, the headache features were not clearly mentioned.10 Only one case report has mentioned the development of RCVS after blood transfusion; however, the incidence of RCVS was noted 3 months after blood trans-
fusion,9 and the causality was difficult to confirm. Several cases of PRES after blood transfusion have been reported, some of which were also found to have vasoconstriction, although this characteristic was not stressed by the authors.11-14 However, the reversibility of vasoconstriction and thunderclap headache was not clearly described.11-14 The Table summarizes the cases of PRES after blood transfusion that have been described in the literature, including our 2 cases. These cases include exclusively female patients, mostly middle-aged and Asian, with chronic severe anemia (mostly due to menorrhagia). In all cases, blood transfusion increased the hemoglobin level by at least 5 g/dL from baseline (average increase: 8.2 g/dL). Within 10 days of the last blood transfusion, symptoms of severe headache, BP surge, and encephalopathy developed. One patient demonstrated aplastic anemia13 and received a blood transfusion without any surgical
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Fig 3.—(A-C) Hyperintense signals over bilateral parasagittal frontoparietal, temporo-occipital, and left parietal regions in diffusion weighted imaging (DWI). (D-F) The apparent diffusion coefficient (ADC) image showed low signals areas compared with the bright signals in DWI. (G-I) High signals in T2 FLAIR series over bilateral parasagittal frontopareital, temporo-occipital, and left parietal lobes in a 40-day follow-up brain MRI.
intervention. Another patient who developed RCVS 3 months after receiving a blood transfusion was the only patient who also received hormonal therapy9; therefore, this case was omitted from the table. Around 87% of patients with PRES demonstrate cerebral vasoconstriction or focal vasculopathy.15
Some shared potential causes between RCVS and PRES include hypertension, eclampsia or preeclampsia, autoimmune diseases, and immunosuppressants.16 RCVS and PRES share many features, such as similar background characteristics, predisposing factors, clinical presentations, and clinical courses
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Fig 4.—(A) Three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) showed multiple shortsegmental narrowings over bilateral middle cerebral arteries and anterior cerebral arteries (arrows). (B) 3D TOF MRA revealed severe constriction over left posterior cerebral artery and short segmental narrowing over right posterior cerebral artery (arrows). (C and D) 3D TOF MRA obtained after 25 days showed recovery of vasoconstriction (arrows).
and outcomes, which suggests overlapping pathophysiological mechanisms. Thus, RCVS and PRES may be included in an overlapping disease spectrum with variable involvement. The mechanisms behind RCVS and PRES development are still unknown. A proposed pathophysiologic mechanism is dysautoregulation of the cerebral endothelium under specific predisposing factors, resulting in dysregulation of cerebral vascular tone.17 No case report exists regarding RCVS due to transfused blood products under conditions of acute blood loss. It has been suggested that chronic anemia may result in a compensatory cerebral vasodilatation.18 We hypothesize that when patients with chronic anemia receive blood transfusions, the resulting rapid increase in cerebral blood flow and viscosity may result in a loss of vasodilation, increase in vascular resistance, and ultimately, overwhelming cerebral vessel constriction, which resembles cerebral hyper-
perfusion syndrome in carotid revascularization surgery associated with carotid stenting and endarterectomy.19,20 Factors related to vasospasm in aneurysmal subarachnoid hemorrhage (SAH) (catecholamines, endothelin-1, calcium, serotonin, nitric oxide, and prostaglandins) might play some role in the vasoconstriction in RCVS, although it had no direct evidence.21 The latencies from autoregulation breakthrough to symptom onset and overt vasoconstriction of major cerebral arteries may depend on the patients’ conditions, underlying diseases, blood transfusion amount, and duration. Another explanation for the delayed onset of vasoconstrictions might be related to the temporal course of centripetal progression of the vasoconstrictions.1 The deranged cerebral vasomotor control might first involve small distal arteries that are beyond the resolution of imaging studies. Furthermore, case reports have been published of patients with chronic anemic conditions (eg, end-stage renal
Menometrorrhagia (uterine myoma)
48/F
47/F
32/F
50/F
46/F
Boughammoura et al11
Heo et al13
Huang et al14
Dou et al case 1
Dou et al case 2 Headache, visual deficit, elevated BP and cognitive impairment
Headache, dizziness, nausea, GTCS, and consciousness disturbance Headache, nausea, vomiting, blurred vision and GTCS Headache, BP surge and GTCS
Status epilepticus and consciousness disturbance
Headache, nausea, GTCS, and BP surge
Symptoms
2500
3000 + 1000‡
1600
Unknown†
1000
800
BT Volume of PRBCs (mL)
10
3
5
7
6
2
Symptoms Onset After Last BT (days)
1.4/10.9
1.5/12.0
5.7/12.5
1.5/10.9
3.0/8.0
2.0/10.0
Hb**** (g/dL)
6.8/33.7
5.7/36.3
22.6/43.4
4.2/31.6
13/29
9.0/31
Hct**** (%)
5 days
6 days + 1 day‡
20 hours
4 days
7 hours
14 days
Period of BT
Bilateral frontoparietal, left parietal, left, and temporo-occipital regions acute infarction
Bilateral occipital lobes T2 hyperintensities Bilateral parietal lobes T2 FLAIR hyperintensities
Bilateral parietooccipital white matter T2 hyperintensities Bilateral small fronto-parietal cortical and subcortical T2 FLAIR hyperintensities Bilateral parietooccipital T2 hyperintensities
Brain Imaging
Diffuse proximal
Diffuse proximal and distal
Left PCA
Diffuse proximal and distal
Diffuse proximal and distal
Distal PCAs
Vasoconstriction
Mean flow velocities of bilateral MCA > 120 cm/second Mean flow velocities of bilateral MCA > 120 cm/second
Nil
Increased left MCA peak systolic velocity (140 cm/ second) Nil
Nil
TCD
Nil
Nil
Right homonymous inferior quadrantanopia Nil
Nil
Nil
Complications§
****Data before/after blood transfusion. †Filtrated red blood cells, platelet concentrates, and fresh frozen plasma. ‡6 days were presurgery, 1 day for surgical blood loss during the operation. §Complications of the reversible cerebral vasoconstriction syndrome (RCVS) with posterior reversible encephalopathy syndrome (PRES). BP = blood pressure; BT = blood transfusion; F = female; FLAIR = fluid-attenuated inversion recovery; GTCS = generalized tonic-clonic seizure; Hb = hemoglobin; Hct = hematocrit; MCA = middle cerebral artery; PCA = posterior cerebral artery; PRBC = packed red blood cell; TCD = transcranial Doppler ultrasound.
Menometrorrhagia (uterine leiomyoma)
Menorrhagia (uterine leiomyoma and adenomyosis)
Menorrhagia (uterine myoma)
Aplastic anemia
Menometrorrhagia (uterine myoma)
45/F
Causes of Anemia
Ito et al12
Study
Age (years)/ Gender
Table.—Cases of Reversible Vasoconstriction Syndrome With Posterior Reversible Encephalopathy Syndrome After Blood Transfusion
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Headache diseases and sickle-cell anemia) who developed PRES, with or without cerebral vasoconstriction, after blood transfusion.22-24 Damage related to reperfusion may release free radicals and trigger dysfunction of the cerebral endothelium, which may further aggravate cerebral vasoconstriction and damage to the vasculoendothelial system, leading to a vicious cycle. This hypothesis is supported by our recent study, in which we showed that oxidative stress is associated with cerebral vasoconstriction in RCVS.25 Nimodipine has been listed as a possible treatment for RCVS.26 The favorable response to nimodipine may be partly due to its role in preventing vasospasm or its effect on the endothelium.27 In line with our cases, a recent case report suggested that nimodipine may be used to prevent and treat recurrent PRES.26 Thus, in RCVS with PRES, nimodipine might be worthy of further investigation. In case 1, BP surge was found. After nimodipine (60 mg every 4 hours) treatment, her BP returned to normal. We could not conclude if BP management could prevent the development of RCVS. In case 2, clopidogrel was given because of acute cerebral infarction. It is estimated that the frequency of intracranial hemorrhages (ICHs) as complications of RCVS was about 28%.1 In fact, complications of RCVS differ in different time course. Cerebral hemorrhages (such as cortical SAH and ICH) are early events occurring during the first week. The ischemic complications occur later, usually during the second week.1 This patient developed cerebral infarction during the second week. In our opinion, the benefit of administering clopidogrel for secondary stroke prevention might outweigh the risk of hemorrhage.
CONCLUSION Our case reports suggest that RCVS with PRES is one complication of blood transfusion (especially when the hemoglobin level increases by >5 g/dL) in patients experiencing chronic severe anemia – in particular,Asian women with menorrhagia. BP surge and the occurrence of severe headaches or other neurological symptoms should be aggressively monitored, especially within the first 10 days after the last blood transfusion.
743 Acknowledgments: This study was supported by grants from the National Science Council of Taiwan (NSC 100-2314-B-010-019-MY2, NSC 100-2314-B010-018-MY3), Taipei-Veterans General Hospital (VGHUST102-G7-6-1, V102C-118, V102E9-001), NSC support for Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan (NSC 101-2911-I-008-001), Brain Research Center, National Yang-Ming University, and a grant from Ministry of Education, Aim for the Top University Plan. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Shih-Pin Chen (b) Acquisition of Data Yi-Hsuan Dou (c) Analysis and Interpretation of Data Shuu-Jiun Wang, Jong-Ling Fuh, Shih-Pin Chen, Yi-Hsuan Dou Category 2 (a) Drafting the Manuscript Yi-Hsuan Dou (b) Revising It for Intellectual Content Shuu-Jiun Wang, Jong-Ling Fuh, Shih-Pin Chen Category 3 (a) Final Approval of the Completed Manuscript Shuu-Jiun Wang, Jong-Ling Fuh, Shih-Pin Chen, Yi-Hsuan Dou
REFERENCES 1. Ducros A, Boukobza M, Porcher R, Sarov M, Valade D, Bousser MG. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain. 2007;130:3091-3101. 2. Chen SP, Fuh JL, Wang SJ, et al. Magnetic resonance angiography in reversible cerebral vasoconstriction syndromes. Ann Neurol. 2010;67:648656.
744 3. Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. Reversible cerebral vasoconstriction syndromes: Analysis of 139 cases. Arch Neurol. 2011;68:10051012. 4. Ducros A, Fiedler U, Porcher R, Boukobza M, Stapf C, Bousser MG. Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome: Frequency, features, and risk factors. Stroke. 2010;41: 2505-2511. 5. Singhal AB. Postpartum angiopathy with reversible posterior leukoencephalopathy. Arch Neurol. 2004; 61:411-416. 6. Fugate JE, Ameriso SF, Ortiz G, et al. Variable presentations of postpartum angiopathy. Stroke. 2012; 43:670-676. 7. Dodick DW, Eross EJ, Drazkowski JF, Ingall TJ. Thunderclap headache associated with reversible vasospasm and posterior leukoencephalopathy syndrome. Cephalalgia. 2003;23:994-997. 8. Chen SP, Fuh JL, Chang FC, Lirng JF, Shia BC, Wang SJ. Transcranial color Doppler study for reversible cerebral vasoconstriction syndromes. Ann Neurol. 2008;63:751-757. 9. Braun CN, Hughes RL, Bosque PJ. Reversible cerebral vasoconstriction syndrome 3 months after blood transfusion. J Stroke Cerebrovasc Dis. 2012; 21:e911-e915. 10. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: Reversible cerebral vasoconstriction syndromes. Ann Intern Med. 2007;146:3444. 11. Boughammoura A, Touze E, Oppenheim C, Trystram D, Mas JL. Reversible angiopathy and encephalopathy after blood transfusion. J Neurol. 2003;250:116-118. 12. Ito Y, Niwa H, Iida T, et al. Post-transfusion reversible posterior leukoencephalopathy syndrome with cerebral vasoconstriction. Neurology. 1997;49:11741175. 13. Heo K, Park S, Lee JY, Lee BI, Lee SK. Posttransfusion posterior leukoencephalopathy with cytotoxic and vasogenic edema precipitated by vasospasm. Cerebrovasc Dis. 2003;15:230-233. 14. Huang YC, Tsai PL, Yeh JH, Chen WH. Reversible posterior leukoencephalopathy syndrome caused by blood transfusion: A case report. Acta Neurol Taiwan. 2008;17:258-262.
April 2014 15. Bartynski WS, Boardman JF. Catheter angiography, MR angiography, and MR perfusion in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol. 2008;29:447-455. 16. Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012;11:906-917. 17. Chen SP, Fuh JL, Wang SJ. Reversible cerebral vasoconstriction syndrome: Current and future perspectives. Expert Rev Neurother. 2011;11:1265-1276. 18. Medel R, Crowley RW, Dumont AS. Hyperperfusion syndrome following endovascular cerebral revascularization. Neurosurg Focus. 2009;26:E4. 19. McCabe DJ, Brown MM, Clifton A. Fatal cerebral reperfusion hemorrhage after carotid stenting. Stroke. 1999;30:2483-2486. 20. Ballesteros-Pomar M, Alonso-Argueso G, TejadaGarcia J, Vaquero-Morillo F. Cerebral hyperperfusion syndrome in carotid revascularisation surgery. Rev Neurol. 2012;55:490-498. 21. Singhal AB. Cerebral vasoconstriction syndromes. Top Stroke Rehabil. 2004;11:1-6. 22. Kolovou V, Zampakis P, Ginopoulou A, Varvarigou A, Kaleyias J. Reversible posterior leukoencephalopathy syndrome after blood transfusion in a pediatric patient with sickle cell disease. Pediatr Neurol. 2013;49:213-217. 23. Raj S, Killinger J, Overby P. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES). J Child Neurol. 2013;28:1284-1286. 24. Sato Y, Hirose M, Inoue Y, et al. Reversible posterior leukoencephalopathy syndrome after blood transfusion in a patient with end-stage renal disease. Clin Exp Nephrol. 2011;15:942-947. 25. Chen SP, Chung YT, Liu TY, Wang YF, Fuh JL, Wang SJ. Oxidative stress and increased formation of vasoconstricting F2-isoprostanes in patients with reversible cerebral vasoconstriction syndrome. Free Radic Biol Med. 2013;61C:243-248. 26. Lu SR, Liao YC, Fuh JL, Lirng JF, Wang SJ. Nimodipine for treatment of primary thunderclap headache. Neurology. 2004;62:1414-1416. 27. Matias-Guiu JA, Garcia-Ptacek S, Ordas CM, Marcos-Dolado A, Porta-Etessam J. Recurrent reversible posterior encephalopathy syndrome with a response to nimodipine. Neurologia. 2012;27:378380.
