[Reversible cerebral vasoconstriction syndrome : A rare cause of stroke]. / Reversibles zerebrales Vasokonstriktionssyndrom : Eine seltene Schlaganfallursache.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex and etiologically diverse neurovascular disorder that typically presents with severe thunderclap headaches (TCH) as the primary symptom, accompanied by reversible vasoconstriction of the cerebral arteries. The clinical course may include focal neurological deficits or epileptic seizures. There are two types: idiopathic RCVS and secondary RCVS, the latter triggered by various substances, medical interventions, or diseases. In clinical practice, various medical specialists may initially encounter this condition, underscoring the importance of accurate recognition and diagnosis of RCVS. The clinical course often appears monophasic and self-limiting, with recurrences reported in only 1.7% of cases annually. Complications such as cerebral hemorrhages and cerebral ischemia can lead to death in 5-10% of cases. This article utilizes a case study to explore RCVS, its complications, and the diagnostic procedures involved.

CT Imaging Computed Tomography/Computed Tomography Angiography/Perfusion in Acute Ischemic Stroke and Vasospasm.

Computed tomography (CT), CT angiography (CTA), and CT perfusion (CTP) play crucial roles in the comprehensive evaluation and management of acute ischemic stroke, aneurysmal subarachnoid hemorrhage (SAH), and vasospasm. CTP provides functional data about cerebral blood flow, allowing radiologists, neurointerventionalists, and stroke neurologists to more accurately delineate the volume of core infarct and ischemic penumbra allowing for patient-specific treatment decisions to be made. CTA and CTP are used in tandem to evaluate for vasospasm associated with aneurysmal SAH and can help provide an insight into the physiologic impact of angiographic vasospasm, better triaging patients for medical and interventional treatment.

A Case of Pregnancy-Induced Hereditary Thrombotic Thrombocytopenic Purpura Complicated by Cerebral Vasospasm.

BACKGROUND: The aim was to explore the treatment of a case of congenital thrombotic thrombocytopenic purpura induced by pregnancy complicated with cerebral vasospasm. METHODS: We present a case study of congenital TTP where disease onset occurred during two separate pregnancies. Interestingly, the disease course exhibited distinct differences on each occasion. Additionally, following plasma transfusion therapy, there was a transient occurrence of cerebral vasospasm. RESULTS: In this case, ADAMTS13 levels reached their lowest point three days after delivery during the first pregnancy, triggering morbidity. Remarkably, a single plasma transfusion of 400 mL sufficed for the patient's recovery. Nonetheless, a recurrence of symptoms transpired during her second pregnancy at 24 weeks of gestation. Plasma transfusions were administered during and after delivery. Sudden convulsions developed. ADAMTS13 ac-tivity returned to normal, but cranial MRA revealed constrictions in the intracranial segments of both vertebral arteries, the basilar artery, and the lumen of the anterior, middle, and posterior cerebral arteries. A subsequent cranial MRA conducted a month later showed no lumen stenosis, indicating spontaneous recovery. CONCLUSIONS: These findings highlight the importance of careful consideration when administering plasma transfusions in congenital TTP during pregnancy. Moreover, the development of novel therapeutic approaches such as recombinant ADAMTS13 is crucial for minimizing complications and optimizing patient care.

Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review.

Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.

Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review.

BACKGROUND: Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models. METHODS AND RESULTS: We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016-2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri-interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used. CONCLUSIONS: Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.

Split-brain syndrome after subarachnoid haemorrhage.

We present the case of a patient with extensive ischaemia of the corpus callosum (CC) including all its anatomical subdivisions, caused by a ruptured aneurysm of the anterior cerebral artery (ACA). This resulted in subarachnoid haemorrhage (SAH) and subsequently in cerebral vasospasm. The aneurysm was coiled, the vasospasm treated with repetitive intra-arterial spasmolysis and the patient then received intensive neurorehabilitative care. The case is an example of ischaemic infarction, which happens rarely in the CC after SAH, and even more rarely affects the CC along its entire length. The case is further remarkable for the resulting nearly complete and isolated split-brain syndrome: CC disconnection syndromes are only exceptionally seen after vascular callosal damage because they are most often overshadowed by symptoms resulting from coaffected adjacent brain areas.

Reversible Cerebral Vasoconstriction Syndrome And Fibromuscular Dysplasia: An Epiphenomenon Or A Causal Relationship?

Fibromuscular dysplasia (FMD) is a rare non-atherosclerotic arterial disease that primarily affects middle-aged Caucasian women. Carotid web (CW) is a variant of FMD characterized by a nonatheromatous, membrane-like tissue protrusion into the carotid bulb. Reversible cerebral vasoconstriction syndrome (RCVS) is defined by severe headaches and reversible narrowing of cerebral arteries, which typically resolves within three months. While most RCVS cases have identifiable triggers, a significant portion occurs without known causes. Recent studies have reported a high prevalence of neurovascular abnormalities in RCVS patients. We present a case of a thirty-year-old woman with a sudden-onset severe headache, diagnosed with RCVS associated with carotid web. The patient had no ischemic involvement and responded well to flunarizine treatment. Follow-up imaging showed no stenosis. This case highlights a potential association between carotid web and RCVS, suggesting that FMD may contribute to vascular hyperreactivity and presents as a risk factor for RCVS. Further investigations are needed to understand the underlying mechanisms connecting these two vascular disorders. Keywords: reversible vasoconstriction syndrome; fibromuscular dysplasia; carotid web; structural abnormalities; vascular hyperreactivity.

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

BACKGROUND: Half 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. METHODS: A 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. RESULTS: Forty-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. CONCLUSIONS: Dysfunctional 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.

Investigation of the effect of carnitine on cerebral vasospasm in experimental subarachnoid hemorrhage model.

The vasospasm, which develops after subarachnoid hemorrhage (SAH), is an unenlightened table in terms of etiology and results. It is usually associated with decreased perfusion, which is associated with decreased blood flow distal to the affected artery and can be demonstrated radiologically. Acetyl-L-carnitine (ALCAR) can be found in brain tissue and easily crosses the blood-brain barrier. Therefore, in this study, we aimed to investigate the therapeutic efficacy of ALCAR, which is an effective antioxidant amine, on vasospasm development after experimental SAH. In our study, 35 adults male Wistar RATs weighing between 235-250 g were used. These RATs were divided into five groups with n = 7. Group 1 Control group, Group 2 SAH + SF (carrier solution), Group 3 SAH + ALCAR 50 mg\kg intraperitoneally, Group 4 SAH + ALCAR 100 mg\kg intraperitoneally and Group 5 SAH. Subarachnoid hemorrhage was induced by giving autologous arterial blood to the cisterna magna of the animals in groups 2, 3, 4, and 5. At 0.-12.- 24.- 36.- 48.- 60. and 72. h, Group 2 was injected with SF, Group 3 with intraperitoneally ALCAR 50 mg\kg, and Group 4 with intraperitoneally ALCAR 100 mg\kg, respectively. Following perfusion and fixation, the animals were subjected to a wide craniectomy, and the brain, cerebellum, and brain stems were removed globally. Then, sections were taken from the basilar arteries of all animals and photographed at 40X magnification. Basilar artery lumen cross-sectional areas, basilar artery areas, and wall thicknesses were measured from these sections. The basilar artery lumen cross-sectional area was found to be significantly larger in the groups in which SAH was formed and ALCAR 50 mg\kg and ALCAR 100 mg\kg were given compared to the group with only SAH and SAH + SF (p = 0.0408). Basilar artery wall thickness increased in all groups except the control group (p < 0.05). In light of all these findings, it was concluded in our study that Carnitine was effective in the resolution of vasospasm in the experimental SAH model.

Uso de simvastatina en la prevención de la isquemia cerebral en la hemorragia subaracnoídea aneurismática / Use of simvastatin in brain ischemia prevention in aneurysmal subarachnoid hemorrhage

Introducción: El vasoespasmo cerebral es una complicación temida y aun no resuelta en los pacientes que cursan con hemorragia subaracnoídea neurismática (HSA), y que significa una importante morbi-mortalidad en dichos pacientes. Material y métodos: Se revisaron los registros de 161 pacientes ingresados en el Hospital Carlos Van Buren de Valparaíso por HSA entre entre Mayo de 2007 y Agosto de 2009, comparando la aparición de complicaciones isquémicas y resultados funcionales, según fuesen o no tratados con Simvastatina (40 mg/día). Resultados: El grupo de pacientes tratados con Simvastatina presentó significativamente menos infartos cerebrales (9,30 por ciento vs. 24,58 por ciento, p=0,02) y menos mortalidad intrahospitalaria (1,24 por ciento vs. 11,80 por ciento, p=0,04). Conclusiones: Si bien el diseño del estudio impide atribuir las diferencias encontradas al uso de Simvastatina, dado el contexto del mismo, es muy probable que así sea. El uso de estatinas en la hemorragia subaracnoídea aneurismática, como profilaxis del vasoespasmo es aún un tema controversial y promisorio, que se encuentra en plena etapa de estudio y desarrollo.

Background: Vasospasm is a feared complication in patients who present with aneurysmal subarachnoid hemorrhage (SAH) and that means significant morbidity and mortality in these patients. Material and methods: We reviewed the records of 161 patients admitted to the Hospital Carlos Van Buren with SAH between May 2007 and August 2009, comparing the occurrence of ischemic complications and functional results as they were or not treated with simvastatin (40mg/day). Results: The patient group treated with simvastatin had significantly fewer strokes (p = 0.02) and fewer hospital mortality (p = 0.04). Conclusions: Although the study design precludes attributing the differences found when using simvastatin, given the context, it is likely to be so. The use of statins in aneurismal subarachnoid hemorrhage for vasospasm prophylaxis is still a controversial and promising topic, wich is under full development and study.

Reversible cerebral vasoconstriction syndrome / Síndrome de vasoconstricción cerebral reversible

Background: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache associated with multifocal vasoconstriction of cerebral arteries in patients without aneurysmal subarachnoid hemorrhage (SAH). The vasoconstriction reverts within three months. We report a 44-year-old man who had a thunderclap headache during sexual intercourse. A similar episode occurred at rest 36 hours later. The patient had already experienced a thunderclap headache 10 years earlier, during coitus. There were no abnormalities on examination. His brain computed tomography scan was normal and cerebrospinal fluid analysis showed no xanthochromia, 15 WBC/mm³ and 10 RBC/mm³. Lumbar puncture was repeated two days later (WBC = 3/mm³ and RBC = 43/mm³). An initial digital cerebral angiography showed a diffuse segmental intracerebral vasospasm. A new angiography after 15 days was normal. He remains headache-free after twenty six months. In conclusion, patients who have thunderclap headache with normal brain CT and cerebrospinal fluid without xantochromia should be investigated for this syndrome.

El síndrome de vasoconstricción cerebral reversible se caracteriza por una cefalea lancinante asociada a una vasoconstricción multifocal de las arterias cerebrales, en pacientes sin hemorragia subaracnoidea causada por aneurismas. La vasoconstricción se revierte en un plazo de tres meses. Presentamos un paciente varón de 44 años que experimentó una cefalea lancinante durante el acto sexual. Un episodio similar repitió 36 horas después, pero mientras estaba en reposo. El paciente había sufrido una cefalea lancinante durante el coito, 10 años antes. El examen físico fue normal. La tomografía cerebral estaba normal y el líquido cefalorraquídeo era claro, con 15 leucocitos y 10 eritrocitos por mm³. Una angiografía cerebral digital mostró un vasoespasmo intracerebral difuso segmentario. Una nueva angiografía, efectuada 15 días después, fue normal. El paciente está libre de cefaleas después de 26 meses de seguimiento.