Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage

Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.

A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage

BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.

BMSCs transplantation inhibits neuronal apoptosis after subarachnoid hemorrhage in rats through activation of AMPK/mTOR signaling pathway-mediated autophagy

Objective:To explore the impacts of bone marrow mesenchymal stem cells(BMSCs)intervention on the neuronal withering and autophagy in rats after subarachnoid hemorrhage(SAH)in rats and its process.Methods:forty-eight SD rats(males),were randomly assigned to the followings:sham surgery(Sham)group,modeling(SAH)group,modeling group+bone marrow mesenchymal stem cells(BMSCs)group,the modeling group+BMSCs+AMPK inhibitor(Compound C)group,twelve rats in each group.Except Sham group,other groups formed SAH samples with intravascular points.Separate groups Compound C and BMSCs,respectively Compound C and 10μL of normal saline were injected into the left lateral ventricle of rats using a stereoscope brain machine 30 minutes before modeling,and 2μL concentration is 1×10^(8)/mL cell suspension was injected into the ventricles of the brain 1 hour after the model was established.Observe whether the rats have severe brain swelling.Garcia were used to test the neural function of rats.TUNEL staining was used to monitor neuronal apoptosis in the rat hippocampal gyrus.Immunohistochemical fluorescence reflected the expression of two proteins,LC3-II and Beclin-1,in rat hippocampal gyrus.Western blotting is applied to measure the expressions of autophagy-associated proteins in the AMPK pathway.Results:Compared with the group undergoing sham-surgery,brain edema worsened in the model group,neuronal apoptosis rate was increased,neural function was weakened,Protein granules decreased(P<0.05)and expression levels of p-AMPK and other proteins decreased(P<0.05);brain swelling and neuronal apoptosis were reduced in the BMSCs group by comparison with the modeling group’s,with substantial elevation in the expression of proteins comprising LC3-Ⅱ,Beclin-1,and p-AMPK.And the standard of p-mTOR protein expression was considerably lessened(P<0.05);rats belonging to group compound C showed increased brain swelling which is relative to that of BMSCs group,increased neuronal apoptosis,decreased neuronal function(P<0.05),increased p-AMPK protein expression,and decreased LC3-Ⅱ,Beclin-1,and p-mTOR protein expression(P<0.05).Conclusion:BMSCs transplantation can reduce neuronal apoptosis after SAH;its principle may be to activate AMPK/mTOR pathway,strengthen autophagy of neurons,and thus inhibit their transformation to apoptosis.

Nontraumatic convexal subarachnoid hemorrhage:A case report

BACKGROUND Nontraumatic convexal subarachnoid hemorrhage(c SAH)is a rare type of atypical subarachnoid hemorrhage.It mainly presents as a focal and transient neurological deficit with similar manifestations as transient ischemic attack.CASE SUMMARY We report a case of a 64-year-old man who visited the hospital with paroxysmal left-sided numbness and weakness is presented in this study.Computed tomography examination indicated a high-density image of the right frontalparietal sulcus.Digital subtraction angiography showed severe stenosis at the right anterior cerebral artery A2-A3 junction(stenosis rate approximately 70%).CONCLUSION The findings of this case indicate that anterior cerebral artery stenosis may lead to the occurrence of c SAH.

Serum Gamma-glutamyl Transferase Levels Predict Functional Outcomes after Aneurysmal Subarachnoid Hemorrhage

Objective We aim to explore the potential association between serum gamma-glutamyl transferase levels and functional outcome after aneurysmal subarachnoid hemorrhage in a Chinese population. Methods A total of 386 aneurysmal subarachnoid hemorrhage patients were included in the study from September 2007 to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month follow-up functional outcomes were determined. A poor outcome was defined as a modified ranking scale score of ≥ 3. The multivariable logistic model was used to analyze the relationship between serum gamma-glutamyl transferase and clinical outcomes after aneurysmal subarachnoid hemorrhage. Results The adjusted poor outcome rates of patients with gamma-glutamyl transferase levels of 〈 30 U/L, 30-50 U/L and ≥ 50 U/L were 16.7%, 19.6%, and 34.4%, respectively （P 〈 0.01）. The age-sex and multivariable adjusted odds ratios （95% confidence intervals） of poor prognosis comparing the top group （≥ 50 U/L） with the lowest group （〈 30 U/L） were 5.76 （2.74-12.13）, 6.64 （2.05-21.52）, and 6.36 （1.92-21.02）. A significant linear trend existed between gamma-glutamyl transferase level and aneurysmal subarachnoid hemorrhage prognosis. This association was also observed among nondrinkers. Conclusion Patients with higher gamma-glutamyl transferase levels were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can be considered to be an independent predictor of functional outcomes after aneurysmal subarachnoid hemorrhage.

Serial lumbar puncture reduces cerebrospinal fluid (CSF) infection during removal of hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling

The present study aimed to compare the complications and clinical outcomes of serial lumbar puncture（LP） and lumbar cerebrospinal fluid（CSF） drainage（LD） of patients with aneurysmal subarachnoid hemorrhage and provide more evidence to guide clinical management.In this retrospective study,41 and 39 aneurysmal subarachnoid hemorrhage patients were enrolled in the LP and LD group,respectively.Clinical outcomes,including CSF infection,intracerebral hemorrhage,vasospasm,hydrocephalus,death,length of stay,duration of drainage and the Glasgow Outcome Scale score were compared between the two groups.By comparing with the LP group,the LD group showed a significantly higher rate of CSF infection（P= 0.029） and shorter duration of drainage（P〈 0.001）.Both groups displayed similar rates of vasospasm,hydrocephalus,intracerebral hemorrhage,the Glasgow Outcome Scale score one month after endovascular coiling and length of stay（P〉 0.05,respectively）.In conclusion,both LD and serial LP are effective methods in the treatment of aneurysmal subarachnoid hemorrhage; besides,serial LP can reduce the incidence of CSF infection in draining hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling.

D-dimer may predict poor outcomes in patients with aneurysmal subarachnoid hemorrhage: a retrospective study

Serum biomarkers may play a reliable role in predicting the outcomes of patients with aneurysmal subarachnoid hemorrhage. This study retrospectively analyzed the relationship between serum biomarkers on admission and outcomes in patients with aneurysmal subarachnoid hemorrhage. We recruited 146 patients with aneurysmal subarachnoid hemorrhage who were treated in Renmin Hospital of Wuhan University of China between 1 May 2014 and 30 March 2016. There were 57 males and 89 females included and average age of included patients was 57.03 years old. Serum samples were taken immediately on admission（within 48 hours after initial hemorrhage） and the levels of serum biomarkers were detected. Baseline information, complications, and outcomes at 6 months were recorded. Univariate and multivariate logistic regression analyses were used to explore the relationship between biomarkers and clinical outcomes. Receiver operating characteristic curves were obtained to investigate the possibility of the biomarkers predicting prognosis. Of the 146 patients, 102 patients achieved good outcomes and 44 patients had poor outcomes. Univariate and multivariate analyses showed that high World Federation of Neurosurgical Societies grade, high serum D-dimer levels, and high neurological complications were significantly associated with poor outcomes. Receiver operating characteristic curves verified that D-dimer levels were associated with poor outcomes. D-dimer levels strongly correlated with neurological complications. In conclusion, we suggest that D-dimer levels are a good independent prognostic factor for poor outcomes in patients with aneurysmal subarachnoid hemorrhage.

Matricellular proteins as possible biomarkers for early brain injury after aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia（DCI）,being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.

Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage

Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage（SAH）, and Toll-like receptor（TLR） 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor（NF）-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury（EBI） such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.

Cerebral venous thrombosis presenting with headache only and misdiagnosed as subarachnoid hemorrhage

INTRODUCTION Patients with headache constitute up to 4.5%of emergency department(ED)visits.[1]Cerebral venous thrombosis(CVT)is an important cause of the headache that is more common than once suspected.The diagnosis of CVT is often missed or delayed because of non-

Encephalic hemodynamic phases in subarachnoid hemorrhage:how to improve the protective effect in patient prognoses

Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemo- dynamic phases were identified during subarachnoid hemorrhage： oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses.

Tenascin-C in aneurysmal subarachnoid hemorrhage: deleterious or protective?

Subarachnoid hemorrhage（SAH）caused by the rupture of a cerebral aneurysm is a well-known devastating cerebrovascular disease.Post-SAH brain is vulnerable,associated with early brain injury（EBI;Suzuki,2015）.

Unusual neural connection between injured cingulum and brainstem in a patient with subarachnoid hemorrhage

The human brain is known to have six cholinergic nudei （Selden et al., 1998; Nieuwenhuys et al., 2008）. The cerebral cortex obtains cholinergic innervation mainly from the basalis nucleus of Meynert （Ch 4） in the bas- al forebrain through the medial and lateral cholinergic pathways （Selden et al., 1998; Mesulam et al., 1983）. The cingulum, the neural fiber bundle connecting the basal forebrain and the medial temporal lobe, contains the medial cholinergic pathway （Selden et al., 1998; Hong and Jang, 2010）.

Effectiveness and Influencing Factors of Comprehensive Rehabilitation Therapy in Patients with Aneurysmal Subarachnoid Hemorrhage

This study aimed to determine the effectiveness of comprehensive rehabilitation for patients with aneurysmal subarachnoid hemorrhage (aSAH) and to explore the factors influencing the prognosis of rehabilitation. This was a retrospective study. Twenty-five patients with aSAH were treated with physical therapy, occupational therapy, speech therapy, cognitive therapy, music therapy, Chinese acupuncture, hyperbaric oxygen, and transcranial magnetic stimulation. The general data of all patients were collected, and the functional scores at admission were compared with those at discharge. The Mini Mental State Examination, Fugl-Meyer Assessment Scale (FMAS) for motor and balance assessment, Holden Functional Ambulation Classification (FAC), modified Rankin Scale, National Institute of Health Stroke Scale, Modified Barthel Index for activities of daily living (ADL), and Glasgow Outcome Scale were significantly improved among 25 patients with aSAH after 1 month of comprehensive rehabilitation training. Hydrocephalus was an independent factor of the ability to perform ADLs (odds ratio, 0.29;95% confidence interval, 2.03. 3.15;p = 0.000). The improvement of ADLs in aSAH patients was not related to sex, surgical method, aneurysm location, age, or smoking status. Comprehensive and professional rehabilitation is effective for the cognition, movement, walking, ADLs, and functional prognosis of patients with aSAH, while early hydrocephalus may be a risk factor for poor ADLs.

Recurrent perimesencephalic nonaneurysmal subarachnoid hemorrhage within a short period of time: A case report

BACKGROUND Spontaneous subarachnoid hemorrhage(SAH)is primarily caused by a ruptured intracranial aneurysm.Perimesencephalic nonaneurysmal SAH(PNSAH)accounts for approximately 5%of all spontaneous SAH.PNSAH displays favorable prognosis.The risk of hemorrhage recurrence is low.We report a case of PNSAH recurrence,occurring within a short time after the initial episode in a patient not receiving antithrombotic or antiplatelet drugs.CASE SUMMARY A 66-year-old male,without any history of recent trauma or antithrombotic/antiplatelet medication,suffered two similar episodes of sudden onset of severe headache,nausea,and vomiting.A plain head computed tomography(CT)scan showed subarachnoid blood confined to the anterior part of the brainstem.Platelet count and coagulation function were normal.PNSAH was diagnosed by repeated head CT,magnetic resonance imaging,and cerebral angiography,none of which revealed the source of SAH.The patient was discharged without focal neurological deficits.At 6-mo follow-up,the patient had experienced no sudden onset of severe headache and presented favorable clinical outcome.Studies have reported a few patients with recurrent PNSAH,originating frequently from venous hemorrhage and conventionally associated with venous abnormalities.PNSAH recurs within a short time following the initial onset of symptoms,although the possibility of re-hemorrhage is extremely rare.CONCLUSION PNSAH recurrence should arouse vigilance;however,the definite source of idiopathic SAH in this case report deserves further attention.