Reversible Cerebral Vasoconstriction Syndrome Research Articles

Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.

This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination. The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS2 score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO. Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema. This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.

Reversible Cerebral Vasoconstriction Syndrome With Typical and Atypical Symptoms: A Case Series.

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) is most commonly characterized by focal or diffuse severe thunderclap headache with or without focal neurological deficits and associated transient focal vasoconstriction of the intracerebral arteries lasting up to three months. We present six patients diagnosed as RCVS, with three patients presenting with focal neurological deficits without headache and the remaining three with severe headache alone. Neuroimaging revealed focal subarachnoid bleed with or without segmental intracerebral vasospasm, which resolved over three months. Despite thunderclap headache being the most prevalent symptom associated with RCVS, the absence of this symptom should not preclude the diagnosis, especially in the presence of cortical subarachnoid hemorrhage (SAH) or focal segmental intracerebral arterial narrowing. Methods This case series is a retrospective analysis of all patients diagnosed with RCVS between 2018 and 2022, focusing on clinical symptoms, imaging findings, and management. Results Six patients (three males and three females) were diagnosed with RCVS between 2018 and 2022. Three patients presented with typical symptoms, while the remaining three presented with atypical symptoms. Neuroimaging findings ranged from normal to focal SAH with or without arterial narrowing. Conclusion This case series underscores the diverse clinical presentations of RCVS, emphasizing that while thunderclap headache is the predominant symptom, its absence should not exclude the possibility of RCVS, especially when accompanied by focal neurological deficits or cortical SAH. Neuroimaging played a crucial role in identifying the spectrum of findings. These findings highlight the importance of comprehensive evaluation and consideration of RCVS in patients presenting with neurological symptoms, even in the absence of typical headache features.

Clinical relevance of reversible cerebral vasoconstriction syndrome in pregnant women with posterior reversible encephalopathy syndrome: review of case reports in Japan.

We systematically reviewed case reports of posterior reversible encephalopathy syndrome (PRES), and investigated the characteristics of PRES in pregnant Japanese women and the clinical relevance of reversible cerebral vasoconstriction syndrome (RCVS) in pregnant women with PRES. Articles were collected using the PubMed/Medline and Ichushi-Web databases. This review was ultimately conducted on 121 articles (162 patients). The clinical characteristics of PRES, individual sites of PRES lesions, edema types, and clinical characteristics of RCVS in PRES cases were examined. The most common individual site of PRES lesion was the occipital lobe (83.3%), followed by the basal ganglia, parietal lobe, frontal lobe, brain stem, cerebellum, temporal lobe, thalamus, and splenium corpus callosum (47.5, 42.6, 24.7, 16.1, 9.3, 5.6, 4.3, and 0.0%, respectively). Edema types in 79 cases with PRES were mainly the vasogenic edema type (91.1%), with very few cases of the cytotoxic edema type (3.8%) and mixed type (5.1%). Among 25 PRES cases with RCVS, RCVS was not strongly suspected in 17 (68.0%) before magnetic resonance angiography. RCVS was observed at the same time as PRES in 13 cases (approximately 50%), and between days 1 and 14 after the onset of PRES in the other 12. These results suggest that the basal ganglia is a frequent site of PRES lesions in pregnant women. RCVS may occur at or after the onset of PRES, even if there are no symptoms to suggest RCVS.

Reversible Cerebral Vasoconstriction Syndrome in Children and Adolescents: A Case Series and Literature Review

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical radiographic phenomenon characterized by thunderclap headaches and transient vasoconstriction of cerebral vessels, which typically resolve within 3 months of symptom onset. Although RCVS has been extensively studied in adults, research on this condition in pediatric populations is limited, likely due to its perceived rarity. This comprehensive review aims to bridge the knowledge gap by examining the clinical presentation, diagnostic methods, treatment strategies, and prognostic outcomes of pediatric RCVS cases, including two case reports contributed by the authors. This study demonstrates an inconclusive sex distribution of RCVS in children, attributed to the scarcity of comprehensive studies of this demographic. Additionally, we identified several predictors of adverse neurological outcomes in children with RCVS, including motor deficits, aphasia, hypertension, and renal disease. This study offers a thorough overview of RCVS in the pediatric population, providing valuable insights to inform future research in this area.

Primary Headache Associated with Sexual Activity: A Review of the Literature.

This review summarizes the evolution in diagnosis, evaluation, and treatment of primary headache associated with sexual activity (PHASA). Despite increased access to patient information and advances in imaging, the pathophysiology of PHASA remains not fully understood. There are many secondary headaches that may present with headache during sexual activity, and a thorough workup is indicated to rule out potentially life-threatening etiologies. Many recent case series discuss the efficacy of known treatments of PHASA, as well as suggest other potential therapies for this condition including the newer CGRP-targeted therapies. Headaches during sexual activity can be worrisome events which necessitate urgent evaluation, particularly when presenting with sudden-onset and severe "thunderclap" headaches. A thorough workup including imaging should be conducted to rule out etiologies such as subarachnoid hemorrhage, reversible cerebral vasoconstrictive syndrome (RCVS),vasospasm, and dissection. PHASA is commonly comorbid with migraine, tension-type headache, exertional headache, and hypertension. PHASA can present as a dull headache that progresses with sexual excitement, or an explosive headache at or around orgasm. Pain is primarily occipital, diffuse, and bilateral. The headaches are discrete, recurrent events with bouts that typically self-resolve, but may also relapse and remit or continue chronically in some patients. PHASA can be treated preemptively with indomethacin and triptans administered prior to sexual activity, or treated prophylactically with beta-blockers, topiramate, and calcium channel blockers. CGRP-targeted therapies may provide relief in PHASA based on a few case reports, but there are no randomized controlled trials looking at specific efficacy for these therapies.

Reversible Cerebral Vasoconstriction Syndrome and Female Sex: A Narrative Review.

Reversible cerebral vasoconstriction syndrome (RCVS) refers to segmental, multifocal constriction of intracranial arteries along with acute headache and resolves within weeks. It occurs more commonly in women, and 1 well-known manifestation of RCVS is postpartum angiopathy. Furthermore, the female sex is included in scoring systems designed to assist with diagnosing RCVS. Nonetheless, the literature is mixed regarding the true role of female and pregnancy-related factors in the pathophysiology of RCVS, and it is similarly unclear whether management of this disorder differs by sex. Given the association of RCVS with female sex and the importance of highlighting, recognizing, and managing stroke etiologies in women, herein, the author reviews what is currently known and unknown about the topic of RCVS in women.

DIAGNOSTIC CHALLENGE IN MIDDLE-AGED WOMAN WITH RECURRENT ISCHEMIC STROKES: A CASE OF PRIMARY CENTRAL NERVOUS SYSTEM VASCULITIS AND LITERATURE REVIEW

Primary vasculitides of the central nervous system are rare vascular disorders whose pathophysiology involves inflammatory infiltration exclusively in the vessels of the central nervous system. Its spectrum extends from primary angiitis of the central nervous system to cerebral amyloid angiopathy. This case portrays a 46-year-old woman with a history of multiple strokes. History of multiple comorbidities such as systemic arterial hypertension, prediabetes, and smoking. During follow-up after the second ischemic event, a patent foramen ovale was detected with positive microbubbles stand. Therefore, she was using oral anticoagulants. Transthoracic echocardiogram and magnetic resonance angiography without relevant changes. However, she resorted to the neurological deficit three more times. Cerebrospinal fluid (CSF) analysis was done twice; both were normal. Cerebral angiography was performed at the time of the last stroke and revealed suggestive signs of vasculitis. Discrimination of angiitis and reversible cerebral vasoconstriction syndrome was challenging and based on the demographic and clinical features of the patient. The characteristics of this case that corroborate the hypothesis of angiitis are the patient's age, which is in the median age range (40-60 years), chronic headache, and focal symptoms not temporally associated with the headache. Intravenous methylprednisolone pulse therapy (one gram/day) was performed for five days. Evolved with progressive improvement of the motor deficit. On hospital discharge, it was prescribed prednisone, and after ten days, Azathioprine 2.5mg/Kg/day was started. Diagnosis of primary central nervous system vasculitis requires high clinical suspicion due to the low specificity of the clinical features. This report reinforces the importance of investigating CNS vasculitis in young patients with a history of recurrent stroke.

Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome.

The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30days) and remission (≥ 90days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). A total of 138 RCVS patients (mean age, 46.8years ± 11.8; 128 women) and 42 HCs (mean age, 46.0years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.

Abstract WP271: Marijuana Use and Stroke: A Systematic Review and Meta-Analysis

Introduction: The prevalence of stroke among young adults has been on the rise, along with a similar rising trend in marijuana use. Ischemic strokes, intracerebral hemorrhage (ICH), reversible cerebral vasoconstriction syndrome (RCVS), and subarachnoid hemorrhage (SAH) are among the commonly reported neurovascular events associated with marijuana use. We attempted to systematically review the literature and find an association between marijuana use and stroke. Methods: We searched data from PubMed/Medline, SCOPUS and studies that met the inclusion criteria were selected and Review Manager 5.4.1 was used for statistical analysis of data. Twenty six studies with a total of 13,550 patients were selected of which 11 were included in the meta analysis. Results: The pooled odds of cannabis use in ischemic stroke patients was statistically significant at 1.16 (95% CI: 1.07-1.25). Among patients with undefined stroke, pooled odds of cannabis use were 0.86 (0.43, 1.72). Meta-analysis for the SAH subgroup could not be done due to varying outcome measures. Overall, upon combining all the subgroups, the odds of cannabis use among stroke patients was not significant (OR: 0.96; 0.77,1.20, I2-100%). High heterogeneity might be the pooling of studies with different stroke types and individual study variations. Conclusions: Cannabis use was significantly associated with ischemic stroke although this significance was not maintained among other stroke subgroups and with overall analysis. Further research should be done to assess the association of dose, chronicity and frequency of cannabis on stroke to further delineate the true association.

Abstract WP121: Cerebral Hemodynamics in the First Week Postpartum in Healthy Women and Women With Preeclampsia

Objective: Standard adult normative data for transcranial Doppler (TCD)-based cerebral hemodynamic measures, such as mean and peak cerebral blood flow velocity (mCBFV, pCBFV), are used to identify pathological conditions such as postpartum angiopathy. However, little is known about cerebral hemodynamics during the early postpartum period, particularly in patients with preeclampsia (PEC). We characterized cerebral hemodynamics using TCD in the first week postpartum in patients with and without PEC. Methods: We prospectively recruited women with PEC and normotensive pregnant women delivering at an urban academic medical center. We measured CBFV in the bilateral middle cerebral arteries with TCD and calculated systolic mCBFV and pCBFV as well as pulsatility index (PI) and PI-derived noninvasive intracranial pressure (nICP). We compared systolic mCBFV and pCBFV between postpartum women with and without PEC, and historical data from non-pregnant young adult female controls. Results: Subjects were 51 women with PEC, 19 normotensive postpartum women, and 28 non-pregnant historical controls. In the PEC group, median mCBFV was 75.0 cm/s (IQR 65.2-99.1) and median pCBFV was 106.9 cm/s (IQR 92.7-130.8). In the normotensive postpartum group, median mCBFV was 77.1 cm/s (IQR 66.0-92.3) and median pCBFV was 107.9 cm/s (IQR 96.6-127.4). In the non-pregnant female control group, median mCBFV was 62.0 cm/s (IQR 48.5-67.9) and median pCBFV was 83.6 cm/s (IQR 69.3-95.2) (p&lt;0.0001 for mean and peak 3-way comparisons; see Figure). PI and nICP were within normal range in both postpartum groups and did not differ significantly between groups. Conclusion: Postpartum women with and without PEC had mCBFV and pCBFV significantly higher than non-pregnant controls, and many fell outside the standard normal range for healthy adults, but PI and nICP were within normal range. Standard ranges of CBFV for healthy adults may not apply in the postpartum period.

Bilateral Renal Cortical Necrosis and Reversible Cerebral Vasoconstriction Syndrome in a Case of Severe Postpartum Haemorrhage

Bilateral Renal Cortical Necrosis (BRCN) is a rare but serious condition characterised by the ischaemic necrosis of both kidneys’ cortical tissues. Concurrently, Reversible Cerebral Vasoconstriction Syndrome (RCVS) manifests as a transient constriction of cerebral blood vessels. The fusion of these two rare entities within the context of severe Postpartum Haemorrhage (PPH) poses a unique diagnostic and therapeutic dilemma for healthcare practitioners. This case study documents the intricate and severe complications experienced by a 32-year-old primiparous woman following abruptio placenta with Intrauterine Foetal Death (IUFD). The patient presented with massive vaginal bleeding, leading to an emergency Lower Segment Caesarean Section (LSCS) where bilateral uterine artery ligation and bilateral internal iliac artery ligation were performed to control haemorrhage. Despite initial interventions, the patient’s condition deteriorated, leading to signs of shock, haemoperitoneum, sepsis, Acute Kidney Injury (AKI), and cerebral complications. The medical journey unfolded with an urgent re-laparotomy, draining haemoperitoneum and conducting a subtotal hysterectomy. This case highlights the critical importance of a multidisciplinary approach involving obstetrics, nephrology, and intensive care, in managing such complex postpartum complications. Vigilant monitoring, collaborative decision-making, and meticulous postoperative care played pivotal roles. The successful outcome was attributed to early recognition, aggressive supportive measures, and timely interventions, including haemodialysis. The challenges faced underscore the need for accessible obstetric care, awareness about antenatal complications, and community-focused initiatives. Further research is warranted to unravel the intricate connections between PPH, RCVS, and associated complications, enhancing our understanding and improving patient outcomes in similar critical cases.

Reversible cerebral vasoconstriction syndrome developed during treatment of Parkinson's disease with rasagiline mesylate: A case report

Background Rasagiline mesylate, a monoamine oxidase-B inhibitor, is used in Parkinson's disease (PD) treatment. We report a case of reversible cerebral vasoconstriction syndrome (RCVS) developed after rasagiline mesylate initiation. Case presentation A 59-year-old woman was diagnosed with PD at the age of 54 years. She experienced frequent episodes of nausea after increasing the dose of levodopa-carbidopa hydrate, and her nausea worsened with the addition of rasagiline mesylate. Three months later, the patient experienced recurrent thunderclap headaches. Brain imaging revealed subarachnoid hemorrhage with segmental vasoconstriction in the main trunks of multiple cerebral arteries. The subsequent clinical course was consistent with RCVS. Her headache and nausea were completely resolved by the discontinuation of rasagiline mesylate and addition of verapamil hydrochloride. Discussion Worsened nausea was the only sign implicating the elevated monoamine levels, potentially linked to the development of RCVS. RCVS should be considered when a patient taking rasagiline mesylate experiences thunderclap headache.

Update on the efficiency and safety of orally administered nasal decongestants

Nasal congestion leading to obstruction is one of the main symptoms in acute rhinosinusitis (common cold), other upper respiratory infections and allergic rhinitis. The EPOS 2020 guidelines place oral decongestants as an efficient therapy for the relief of nasal obstruction. In Romania, there are more than 50 available nasal decongestants, so it is very important for practitioners from all medical domains to be aware of recent data regarding their effectiveness and safety profile. Recent concerns raised by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regarding the efficacy and safety of pseudoephedrine (PSE) and phenylephrine (PHE) emphasize the need for informed decision-making in prescribing. Notably, there were concerns raised about the association between PSE, reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES). EMA’s safety committee, Pharmacovigilance Risk Assessment Committee (PRAC), recently recommended measures to minimize risks of serious side effects when using medicines containing PSE. PRAC recommends that medicines containing PSE should not be used in patients with severe or uncontrolled hypertension and severe acute or chronic kidney disease or failure. Additionally, PRAC recommends healthcare professionals to counsel patients to discontinue the use of such medicines promptly and seek medical assistance if they experience symptoms suggesting PRES or RCVS, such as sudden onset of severe headache, confusion, vomiting, visual disturbances or seizures. While effectiveness of oral PSE is confirmed by clinical studies, expert consensus is unfavorable to PHE. Both in vitro and in vivo clinical pharmacology data indicate that neither the recommended doses nor higher doses of oral PHE demonstrate efficacy in alleviating symptoms of nasal congestion.

Atypical Manifestation of Zoster Meningitis Presented with Headache and Multiple Cerebral Vasoconstrictions

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by headaches and multiple transient cerebral vasoconstrictions. Central nervous system (CNS) infections related to the varicella zoster virus (VZV) can complicate various neurological disorders, including cerebral vasculopathy. We present the case of a patient who complained of a severe headache without any other symptoms or focal neurological signs. Brain magnetic resonance angiography showed multiple focal stenoses, especially in the right middle cerebral artery (MCA), and transcranial Doppler sonography revealed increased velocities in the MCA and right anterior cerebral artery. Initially, the headache was attributed to RCVS, and nimodipine infusion was initiated; however, the headache worsened. A cerebrospinal fluid study showed pleocytosis, increased protein levels, and positive polymerase chain reaction markers for VZV. No skin lesions or fever were observed during treatment. Our case emphasizes considering VZV meningitis as a cause of cerebral vasoconstriction, even in the absence of typical signs of CNS infection.

The Music Within: A Doppler Harmonic Pattern Report in Non-Subarachnoid Hemorrhage Related Cerebral Vasospasm

A 40-year-old male presented an episode of severe thunderclap headache with right hemiparesis. Imaging revealed severe stenosis in the left middle cerebral artery, associated with increased mean velocities detected by Transcranial Doppler Ultrasound (TCD). Notably, a distinctive "tin whistle" sound, known as a doppler harmonic effect, near the highest velocity point was observed during the examination. Extensive workup was performed, including CSF analysis and laboratory investigations, and the diagnosis of Reversible Cerebral Vasoconstriction Syndrome (RCVS) was established. Treatment involving medication and daily monitoring led to a decline in the left MCA's velocity, enabling the patient's discharge with no recurrent headaches or neurological deficits. Notably, a follow-up MRI exhibited the disappearance of the left MCA stenosis. This report discusses the rare occurrence of "musical murmurs" in cerebrovascular diseases, underscoring the potential for early diagnosis using techniques like TCD in emergency settings, particularly in conditions like RCVs.

Association between impaired dynamic cerebral autoregulation and BBB disruption in reversible cerebral vasoconstriction syndrome

BackgroundHalf of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption.MethodsA cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption.ResultsForty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index.ConclusionsDysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure.Graphical

Reversible cerebral vasoconstriction syndrome: A systematic review of reports and case series

Reversible cerebral vasoconstriction syndrome: A systematic review of reports and case series

When less is more: A case of reversible cerebral vasoconstriction syndrome

When less is more: A case of reversible cerebral vasoconstriction syndrome

Post blood transfusion reversible cerebral vasoconstriction syndrome in sickle cell disease: Two case reports

Post blood transfusion reversible cerebral vasoconstriction syndrome in sickle cell disease: Two case reports

Transfusion-Associated Reversible Cerebral Vasoconstriction Syndrome in Pediatrics: A Case Report and Review of Literature

Background Reversible cerebral vasoconstriction syndrome (RCVS) is a rare complication of packed red blood cell (pRBC) transfusion primarily reported in adults with severe chronic anemia due to menorrhagia. It is characterized by a triad of rapidly changing and reversible segmental cerebral artery narrowing and dilatation, thunderclap headache, and benign cerebrospinal fluid findings. 1,2 More than 50% of patients experience blurring of vision or cortical vision loss, and a subset of patients develop hemiparesis or aphasia. 1 There are emerging case reports of RCVS in pediatric patients, however the literature examining this transfusion complication in children is limited. The rarity and potential severity of RCVS warrants better understanding by pediatric hematology and transfusion providers. Results We describe a previously healthy 4 year-old male who presented with pallor and laboratory parameters consistent with severe iron deficiency anemia. Chest x-ray showed cardiomegaly, and echocardiogram demonstrated pericardial effusion, moderate left ventricular dilation, and moderate coronary artery dilatation. His history was notable for an extremely selective diet and at least 50 ounces of cow's milk daily. The patient was admitted, and over the course of 3 days, he received a total of 43 mL/kg of pRBCs (602 mL total) in 8 aliquots, and his hemoglobin (Hgb) increased from 1.4 g/dL to 11.4 g/dL (Fig. 1). He then re-presented 5 days after discharge with altered mental status and malignant hypertension. Brain MRI/MRA was consistent with RCVS, with luminal irregularities in multiple anterior and posterior circulation intracranial arteries creating a beaded appearance. He was treated supportively with aggressive blood pressure control and made a complete neurologic recovery 8 days after presentation. At hematology clinic follow-up 2 months post-discharge, he remained at his typical neurologic baseline. Conclusions The connection between blood transfusion and RCVS is postulated to be due to a rapid increase in hematocrit and blood viscosity, which alters cerebral autoregulation and leads to hypertensive encephalopathy despite systemic normotension. 3 The increased viscosity may also lead to vasospasm. 3 When a patient with severe chronic anemia receives a pRBC transfusion, there is increased cerebral blood flow and viscosity, resulting in decreased vasodilation, increased vascular resistance, and cerebral vessel constriction. However, these are hypothesized mechanisms with little supportive experimental data. Vasculopathies and vasoconstrictive medications 2 are also risk factors for RCVS. There are 4 previous reported cases of pediatric RCVS associated with pRBC transfusion. 2 patients were acutely ill with complications of sickle cell anemia. 7,9 Another case occurred in a patient with systemic lupus erythematosus 8, and the fourth occurred in the setting of severe iron deficiency anemia. 5 Several features of our patient's clinical course are similar to the reported cases of transfusion-related RCVS 5 and warrant highlighting: 1) severe chronic anemia with cardiac dysfunction and 2) the large volume of transfused pRBCs over a short period resulting in a significant increase in Hgb. However, our patient developed symptoms of RCVS sooner than other published cases and did not have seizure or stroke. Pediatric guidelines recommend pRBC transfusion for Hgb levels between 5-10 g/dL, depending on the clinical scenario. 4 There are few data to guide Hgb targets for pediatric patients presenting with severe anemia. Over-transfusion does not offer physiological benefit and poses risk of transfusion-related adverse events. A case report from Dou et al 6 proposed that a &amp;gt;5 g/dL Hgb increase was associated with a greater likelihood of developing RCVS. For this patient with cardiac dysfunction and social concerns including lack of primary care, the potential benefits of achieving a higher Hgb with pRBC transfusions were prioritized. RCVS should be considered in pediatric and adult patients recently transfused for chronic severe anemia presenting with headaches or other neurological symptoms. Prompt recognition of RCVS may prevent unnecessary treatment and potentially limit risk of neurologic compromise. The role of the volume and rapidity of the pRBC transfusions in the development of RCVS warrants further study. Fig 1. Timeline of initial presentation, detailing blood transfusions