Reversible cerebral vasoconstriction syndrome in association with fingolimod use

Background: Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is characterized by thunderclap headaches, non-aneurysmal segmental cerebral vasoconstriction seen on arteriogram, and spontaneously resolves within 12 weeks. Fingolimod has been reported to cause posterior reversible encephalopathy syndrome (PRES) and one case of RCVS. Objective: We report a case of RCVS possibly related to fingolimod use, and compare to cases of adverse outcomes in fingolimod use. Methods: This is a single observational study without controls; therefore, level of evidence is IV. A literature review in pubmed with keywords, fingolimod, vasospasm, RCVS, Call-Fleming, stroke, PRES and hemorrhage. Results: One case of RCVS on fingolimod in the post-partum period. Two other cases in the literature were found one with hemorrhagic encephalitis and the other critical vasospasm in the upper extremity associated with fingolimod 1.25 mg daily in the FREEDOMS II trial and TRANSFORMS study, respectively. Additionally, Novartis reports nine cases of PRES related to fingolimod use. Conclusion: Fingolimod has the potential to cause vasoconstriction however appears to be rare and more likely on doses higher than 0.5 mg daily. Fingolimod may be associated in RCVS and should be considered in patients with severe headache on fingolimod.     

PRES and RCVS: Two Distinct Entities or a Spectrum of the Same Disease?

ObjectivesTo report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities.Materials and MethodsWe conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS.ResultsPRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS.ConclusionsPRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.     

Reversible cerebral vasoconstriction syndrome identification of prognostic factors

Object

: Reversible cerebral vasoconstriction syndrome (RCVS) is described as a clinical and radiological entity characterized by thunderclap headaches, a reversible segmental or multifocal vasoconstriction of cerebral arteries with or without focal neurological deficits or seizures. The purpose of this study is to determine risk factors of poor outcome in patients presented a RCVS.

Methods

A retrospective multi-center review of invasive and non-invasive neurovascular imaging between January 2006 and January 2011 has identified 10 patients with criterion of reversible segmental vasoconstriction syndrome. Demographics data, vascular risks and evolution of each of these patients were analyzed.

Results

Seven of the ten patients were females with a mean age of 46 years. In four patients, we did not found any causative factors. Two cases presented RCVS in post-partum period between their first and their third week after delivery. The other three cases were drug-induced RCVS, mainly vaso-active drugs. Cannabis was found as the causative factor in two patient, Sumatriptan identified in one patient while cyclosporine was the causative agent in also one patient. The mean duration of clinical follow-up was 10.2 months (range: 0–28 months). Two patients had neurological sequelae: one patient kept a dysphasia and the other had a homonymous lateral hemianopia. We could not find any significant difference of the evolution between secondary RCVS and idiopathic RCVS. The only two factors, which could be correlated to the clinical outcome were the neurological status at admission and the presence of intraparenchymal abnormalities (ischemic stroke, hematoma) in brain imaging.

Conclusions

Fulminant vasoconstriction resulting in progressive symptoms or death has been reported in exceptional frequency. Physicians had to remember that such evolution could happen and predict them by identifying all factors of poor prognosis (neurological status at admission, the presence of intraparenchymal abnormalities).     

A pediatric case of reversible cerebral vasoconstriction syndrome with cortical subarachnoid hemorrhage

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare disorder characterized by acute onset, severe headache, with reversible vasoconstriction of cerebral arteries often accompanied by additional neurological symptoms. This syndrome is seen mainly in middle-aged adults, predominantly women. Herein, we report on a pediatric case of RCVS with cortical subarachnoid hemorrhage (SAH). A 12-year-old boy developed acute, severe headache with paralysis of lower extremities causing gait disturbance after administration of eletriptan. Brain magnetic resonance angiography (MRA) revealed multifocal narrowing of the cerebral arteries, whereas magnetic resonance imaging (MRI) demonstrated sulcal hyperintensity on fluid-attenuated inversion recovery, consistent with cortical SAH. The patient's clinical symptoms resolved spontaneously after a few days and the MRI and MRA findings disappeared 3months later, suggesting a diagnosis of RCVS. Eletriptan might cause vasoconstriction of cerebral arteries. Although most patients with RCVS are adults and pediatric cases are rare, RCVS should be considered in a child complaining of severe headache.     

Initial vasodilatation in a child with reversible cerebral vasoconstriction syndrome

We describe the case of a 10-year-old boy who developed reversible cerebral vasoconstriction syndrome (RCVS) after cerebellitis. He received intravenous immunoglobulin and methylprednisolone to treat the cerebellitis. However, he then presented with a sudden severe headache, vomiting, and generalized tonic-clonic seizure. Brain magnetic resonance angiography (MRA) initially revealed diffuse cerebral vasodilatations, and diffuse multifocal segmental vasoconstrictions developed several days later. His clinical symptoms gradually resolved after several days, in the absence of any specific therapy. MRA performed 46 days after symptom onset showed that the multifocal segmental vasoconstrictions had resolved, suggesting a diagnosis of RCVS. The imaging features of RCVS include multifocal segmental vasoconstriction. However, our case suggests that diffuse cerebral vasodilatation may in fact be evident during the early stage of disease.     

Epilepsy after neuroimaging normalization in a woman with tacrolimus-related posterior reversible encephalopathy syndrome

Posterior reversible encephalopathy syndrome (PRES) is known to occur after solid organ transplantation, and is caused by immunosuppressive agents such as tacrolimus. PRES onset usually occurs within the first 2 months after liver transplantation. Clinical findings include seizures, headache, focal neurological deficits, visual disturbances, and altered mental status. These are associated with characteristic imaging features of subcortical white matter lesions on brain MRI. Atypical localizations of this posterior leukoencephalopathy have been reported. Expeditious recognition of the syndrome may lead to a complete recovery. Abnormalities of EEG during follow-up might be associated with unfavorable seizure outcome, even when neuroimaging changes resolve. We report a case of late-onset PRES with atypical localization following liver transplantation. The patient developed epilepsy despite resolution of MRI lesions at 8 months of follow-up. EEG was a prognostic factor of seizure persistence, suggesting an incomplete recovery of brain lesions in contrast to neuroimaging findings.     

Reversible cerebral vasoconstriction following carotid endarterectomy

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by the triad of severe "thunderclap" headaches, neurological symptoms and transient segmental cerebral arterial vasoconstriction. We report a patient with RCVS following carotid endarterectomy and review the literature on RCVS following carotid revascularisation.     

Recurrent and atypical posterior reversible encephalopathy syndrome in a child with hypertension

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiologic entity with typical symptoms including headache, seizures, visual disturbance, altered mental status, vomiting, nausea and focal neurologic signs. In this article, we report recurrent and atypical PRES in a child with hypertension due to end-stage renal disease (ESRD) who was on a peritoneal dialysis program for 6 months. After the second hypertension attack, PRES findings did not recover and persisted as encephalomalacia. As far as we know, this case is the first child with ESRD who developed encephalomalacia after recurrent episodes of PRES. When a patient with a history of PRES presented with new clinical and neuroradiological findings, recurrent PRES should be considered.     

可逆性后部脑病综合征MRI脑水肿与血清乳酸脱氢酶及脑钠肽的关系

目的 探讨可逆性后部脑病综合征(PRES)患者的MRI影像学特点,进一步分析发病时患者脑水肿程度与血清乳酸脱氢酶(LDH)、脑钠肽(BNP)的关系.方法 回顾性分析17例PRES患者的临床资料及MRI影像学特征,依据FLAIR、DWI及ADC图评价患者脑水肿类型及程度,分析脑水肿评分与LDH、BNP的相关性.结果 MR...     

Posterior reversible encephalopathy syndrome

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological entity with typical symptoms and symmetric high-signal intensity lesions in the bilateral parieto-occipital lobes on T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. We described three patients with PRES of varied etiologies. Patient 1 was a young man with severe hypertension who presented with headache and visual disturbance. Patient 2 had leukemia and was receiving umbilical cord blood cell transplantation with immunosuppressant, and developed PRES with convulsions. Patient 3 was a pregnant woman with renal failure, who repeatedly developed PRES with convulsions. FLAIR and apparent diffusion coefficient mapping were useful in detecting PRES lesions in our patients, although diffusion-weighted imaging and CT scans had limited use in the diagnosis. Adequate and prompt treatment with antihypertensive medication immediately ameliorated the symptoms, with improvement of abnormal MRI findings. In previous reports, delayed diagnosis might have affected the prognosis. Further work on the clinical manifestations of PRES and its therapy is required.     

Posterior reversible encephalopathy syndrome induced by intracranial hypotension in a postpartum patient

Abstract

Objective: A number of hormonal, physiologic, immunologic, and hemodynamic changes can cause a series of central nervous system-related problems in pregnant and postpartum women. Posterior reversible encephalopathy syndrome (PRES) is commonly seen in these conditions. However, PRES during pregnancy and the postpartum period are not always due to pregnancy.

Methods: We describe a patient who presented with headache followed by an epileptic seizure after cesarean section and whose computed tomography (CT) showed bilateral low-density lesions in the frontal lobe. To explore the pathogenesis, we further examined the patient with brain magnetic resonance imaging (MRI) and lumbar puncture.

Results: Brain MRI revealed vasogenic edema in the frontal lobe and temporal-occipital regions of both hemispheres. MRI of the brain with contrast showed diffuse enhancement of the supratentorial dura mater and decreased of bilateral lateral ventricles. There was no abnormality in brain magnetic resonance angiography and magnetic resonance venography. Bloody cerebrospinal fluid flowed very slowly during lumbar puncture.

Conclusion: These findings suggest that, although rare, intracranial hypotension in postpartum patients may be a cause of PRES.     

Unexpected Seizure Attack in a Patient with Spinal Metastasis Diagnosed as Posterior Reversible Encephalopathy Syndrome

Seizure is a foreseeable risk in patients with brain lesion. However, seizure during treating non-brain lesion is not a familiar situation to neurosurgeon. Posterior reversible encephalopathy syndrome (PRES) is a relatively common situation after systemic chemotherapy. The aim of this study is to make neurosurgeons aware of this potential medical problem. A 52-year-old woman with advanced gastric cancer, presented with low back pain due to spinal metastasis at the 4th lumbar vertebra. Ten cycles of chemotherapy with FOLFOX (5-Fluoruracil/Oxaliplatin) had been completed 23 days ago. Two days before the planned operation, a generalized tonic clonic seizure occurred. She did not have a history of hypertension or seizure. The seizure was stopped with lorazepam 4mg. The brain magnetic resonance (MR) imaging showed high signal changes in both parieto-occipital lobes on the T2-weighted images, and these were partially enhanced, suggesting PRES. The surgery was preceded by treatment with an antiepileptic drug. The MR images, taken 1.5 months after the seizure, showed that the lesion was no longer present. At 3 month follow-up, no additional seizure attack occurred without any seizure medication. The possibility of a seizure attack should be considered if the patient has a history of chemotherapy.     

External carotid artery branches involvement in reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasoconstriction and dilatation of intracranial arteries, usually revealed by headaches, which spontaneously resolve in few weeks. We report a patient with RCVS, revealed by thunderclap headaches, involving both internal and external carotid artery (ECA). She received fluoxetin for depression and took a great amount of cannabis in the last months. While angio-MR, transcranial Doppler and CSF analysis were normal, cerebral angiography disclosed stenoses and dilatations of the middle cerebral artery. It also showed an involvement of maxillary arteries. Fluoxetin and cannabis were stopped. After few days, she had no more headaches. At 8th week, angiography was normalized confirming the RCVS. ECA angiogram may help reaching a diagnosis in patients with suspected RCVS when intracerebral abnormalities are minor or absent.     

Fulminant Reversible Cerebral Vasoconstriction Syndrome in Breakthrough COVID 19 Infection

COVID 19 infection continues to afflict people worldwide. Neurological complications of COVID infection are common. We report a case of fulminant reversible cerebrovascular constriction syndrome (RCVS) in a patient with breakthrough COVID 19 infection who was fully vaccinated. A 64 year old lady, fully vaccinated 2 months back, presented with headache, drowsiness, partial seizures, visual impairment and quadriplegia. Her nasopharyngeal swab was tested positive for SARS COV2 on real time PCR assay. MRI brain FLAIR images showed multifocal hyperintensities with MR angiogram showing arterial vasoconstriction suggestive of RCVS. Despite initiation of nimodipine, patient's symptoms worsened and she succumbed to sepsis. RCVS following COVID infection has been reported to have a benign outcome. However, despite vaccination, fulminant RCVS following a breakthrough COVID infection was observed in our patient.     

Progressive Manifestations of Reversible Cerebral Vasoconstriction Syndrome Presenting with Subarachnoid Hemorrhage,Intracerebral Hemorrhage,and Cerebral Infarction

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset headache with focal neurologic deficit and prolonged but reversible multifocal narrowing of the distal cerebral arteries. Stroke, either hemorrhagic or ischemic, is a relatively frequent presentation in RCVS, but progressive manifestations of subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction in a patient is seldom described. We report a rare case of a 56-year-old woman with reversible cerebral vasoconstriction syndrome consecutively presenting as cortical subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction. When she complained of severe headache with subtle cortical subarachnoid hemorrhage, her angiography was non-specific. But, computed tomographic angiography showed typical angiographic features of this syndrome after four days. Day 12, she suffered mental deterioration and hemiplegia due to contralateral intracerebral hematoma, and she was surgically treated. For recurrent attacks of headache, medical management with calcium channel blockers has been instituted. Normalized angiographic features were documented after 8 weeks. Reversible cerebral vasoconstriction syndrome should be considered as differential diagnosis of non-aneurysmal subarachnoid hemorrhage, and repeated angiography is recommended for the diagnosis of this under-recognized syndrome.     

Repetitive use of intra-arterial verapamil in the treatment of reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) typically presents with recurrent thunderclap headaches and neurological deficits that are usually self-limiting. The intra-arterial (IA) use of vasodilators for RCVS has been reported for severe cases. Patients with RCVS have the potential for serious and permanent neurological deficits. It is a rare disorder, with a recent surge in the number of reports, and probably continues to be under-diagnosed. We report two patients with RCVS with severe neurological sequelae, treated in a large tertiary hospital. Both patients received high-dose cortico steroids due to the possibility of angiitis of the central nervous system, but they deteriorated neurologically, which suggests that steroids may have a deleterious effect in RCVS. Treatment with IA verapamil resulted in reversal of vasoconstriction, but multiple treatments were necessary. Therefore, IA administration of verapamil is a possible treatment for severe RCVS, but there is only limited sustained improvement in vasodilation that may require repetitive treatments with a currently undetermined optimal treatment interval.     

Atraumatic nonaneurysmal sulcal subarachnoid hemorrhages: a diagnostic workup based on a case series

Introduction: Atraumatic and nonaneurysmal sulcal subarachnoid hemorrhage (sSAH) is a rare type of cerebrovascular disease with various etiologies previously reported in small case reports. In this study, we propose to analyze clinical presentations, imaging patterns and etiologies in a large case series of such patients in order to propose a diagnostic workup. Methods: We retrospectively analyzed clinical and radiological data of consecutive patients with a diagnosis of atraumatic and nonaneurysmal sSAH, admitted to our institution between 2008 and 2011. All patients had both computed tomography (CT) and magnetic resonance imaging (MRI) as a part of their initial evaluation. Results: 30 patients (18 women and 12 men, mean age: 60 years) were identified. The main clinical symptoms at presentation were focal and transient neurological deficit (n = 22) and thunderclap headache (n = 10). Four patients had progressive headache and 4 other had partial or generalized epileptic seizures. MRI abnormalities associated with sSAH were prior hemorrhages, microbleeds, severe leukoencephalopathy and hemosiderosis suggesting cerebral amyloid angiopathy (CAA; n = 9), vasogenic edema in parieto-occipital areas compatible with a posterior reversible encephalopathy syndrome (PRES; n = 3), cortical venous thrombosis (n = 2) and concomitant acute cortical stroke (n = 3). Other underlying causes of sSAH, not diagnosed on MRI, were reversible cerebral vasoconstriction syndrome (RCVS) based on clinical criteria and conventional angiography (n = 4), angiitis diagnosed by skin biopsy (n = 1), vascular malformation diagnosed on CT and digital subtraction angiographies (n = 3), and overanticoagulation (n = 1). Four cases remained unresolved. Conclusion: This study confirmed that sSAH is a rare condition related to a wide spectrum of etiologies. Combination of brain MRI and magnetic resonance angiography and eventually digital subtraction angiography allowed the identification of an underlying etiology for 87% of patients. CAA, RCVS and PRES represented more than 50% of the etiological mechanisms. Among older patients, sSAH was mainly related to CAA while in younger patients, RCVS represented the most frequent etiology.     

可逆性脑血管收缩综合征临床及影像学特点

目的探讨可逆性脑血管收缩综合征(RCVS)的临床、影像学特点,以提高对该病的认识。方法总结3例RCVS患者的临床及影像学资料并复习相关文献。结果本组3例患者均以剧烈头痛为首发症状,其中1例伴有双下肢无力,1例伴视物模糊、右侧肢体轻偏瘫。TCD检查均提示不同血管不同程度的血流速度增快,头颅MRI及MRA检查提示部分血管痉挛,典型者呈"串珠样"改变;2例脑内有病灶。脑脊液等相关检查无特异性,经钙离子拮抗剂等治疗后临床症状逐渐消失,1~7个月超声影像学复查完全恢复正常,临床呈单相病程,预后良好。结论临床表现为"雷击样、撕裂样"头痛的患者伴或不伴有神经系统定位体征,影像学检查有血管痉挛表现,在排除其他疾病后应考虑RCVS的可能。     

Reversible cerebral vasoconstriction syndrome

ABSTRACT

Reversible cerebral vasoconstriction syndrome (RCVS) is a relatively rare, non-progressive angiopathy frequently heralded by severe thunderclap headache. It is characterised by vasoconstriction of cerebral arteries which usually resolves within three months of onset. Transient focal neurological signs may occur, and persistent deficits associated with haemorrhagic comorbidities have been reported in a small percentage of individuals. In this paper we report the case of RH, a 36-year-old woman who presented at a university teaching hospital in Sydney with a clinical history and radiological evidence consistent with RCVS. There were no haemorrhagic events during the course of her illness, and vasoconstriction resolved within a few days, following treatment with verapamil. Neuropsychological evaluation 16 months later revealed significant deficits in autobiographical memory, verbal and non-verbal new learning and active delayed recall, cognitive flexibility, abstraction and (to a lesser extent) immediate attention span and information processing speed. RH’s case was unusual because the “trigger” for RCVS (Ear, Nose and Throat surgery) has not been previously reported, and because despite there being no haemorrhagic complications during the course of RCVS and no subsequent radiological abnormalities, she had significant cognitive impairment. To date, persistent neuropsychological deficits have not been recognised as a feature of RCVS.     

Reversible Vasoconstriction Syndrome with Bilateral Basal Ganglia Hemorrhages

Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly recognized acute cerebrovascular condition that may produce myriad transient and sustained neurologic deficits as well as a host of radiologic features. We report the case of a woman with RCVS and a severe clinical syndrome with bilateral basal ganglia hemorrhages, cerebral infarctions, and marked vascular abnormalities. The patient made a near complete clinical recovery, representing an extreme and illustrative form of RCVS.