Pituitary Apoplexy: Pitfalls in Diagnosis.

Headache is a common presenting complaint in the emergency department. A rare cause is pituitary apoplexy - a complication of pituitary adenoma consisting of hemorrhage or infarction of the primary tumor accounting for approximately 1 % of headaches. A 44-year-old female presented with intractable headache, nausea, photophobia and later - signs of meningeal irritation. Initial imaging demonstrated no mass or hemorrhage, labs showed only leukocytosis and elevated CRP. Patient was started on empiric acyclovir and methylprednisolone. CSF analysis was negative for meningitis, thus MRI of the brain was performed which demonstrated a 2.5 cm suprasellar mass. Initial Pituitary hormone evaluation demonstrated low prolactin, normal TSH and low ACTH thought to be due to steroid use. Repeat laboratory evaluation demonstrated hypopituitarism. Patient underwent resection of the adenoma with pathology consistent with pituitary apoplexy. We highlight the need for careful evaluation of patients presenting with headache and signs of meningeal irritation given 16 % prevalence of pituitary adenoma. CT of the head may not always demonstrate acute infarction, with MRI of the brain remaining the most sensitive imaging modality. Given the common use of methylprednisolone for headache, a pitfall in the diagnosis of pituitary apoplexy includes proper assessment of a pituitary panel prior to initiation of steroids.

A prognostic model incorporating the albumin-corrected anion gap in patients with aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients. Methods: Significant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC). Results: Among 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt-Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt-Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality. Conclusion: The ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies.

Transcranial Doppler in the Detection of Cerebral Vasospasm After Subarachnoid Hemorrhage.

Background Transcranial Doppler (TCD) is a simple, noninvasive, nonionizing, portable technique but not widely practiced to detect cerebral vasospasm after subarachnoid hemorrhage (SAH). Objective The aim of this study was to assess the performance of TCD in the detection of cerebral vasospasm in patients with SAH considering CT angiography (CTA) as a gold standard. Methods and material This cross-sectional study included 50 patients with acute SAH admitted to the National Institute of Neurosciences & Hospital (NINS & H), Dhaka, Bangladesh, from February to June 2021. The neurological status, severity of SAH, and initial CT findings were recorded. All patients were screened for cerebral vasospasm with TCD on the 4th, 7th, 10th, and 14th days after the event. Screening of cerebral vasospasm by CTA was done on the 14th day of the event or earlier if TCD suggested vasospasm. Results The mean age of the participants was 51.4 ±13.4 years (mean ± SD), and females were predominant (N=29, 58%). CTA detected cerebral vasospasm in 18 (36%) participants, but TCD could detect it in only 13 (26%) cases. Among the participants who had no vasospasm by CTA, all but one were also found to have no vasospasm by TCD. The agreement between TCD and CTA in detecting cerebral vasospasm was significant (p<0.001, κ=0.726). TCD shows good specificity (96.9%) and positive predictive value (92.8%), but sensitivity (72.2%) and negative predictive value (81.6%) were comparatively lower. Overall, the diagnostic accuracy of TCD in detecting cerebral vasospasm was 88%. Conclusions Although compared to CTA, TCD is a highly specific but less sensitive tool in detecting vasospasm, TCD remains a reliable screening tool for detecting vasospasm following SAH.

12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.

Background and Purpose: Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus 12/15-LOX is an important target to prevent delayed cerebral ischemia. Methods: SAH was induced in C57BL/6 and 12/15-LOX-/- mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and in vitro. C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day five to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and for development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. Results: In SAH mice, 12/15-LOX was upregulated in brain vascular cells and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Conclusions: Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.

Sex Differences in Outcome of Aneurysmal Subarachnoid Hemorrhage and Its Relation to Postoperative Cerebral Ischemia.

BACKGROUND: Whether there is a sex difference in the outcome of aneurysmal subarachnoid hemorrhage (aSAH) remains controversial, and clarifying the role of women in postoperative cerebral ischemic events can help us to understand its relationship with poor prognosis. Therefore, the purpose of this study was to elucidate the relationship between the three aspects of sex differences, postoperative cerebral ischemia, and poor prognosis after aSAH. METHODS: A total of 472 patients admitted within 72 h after aSAH between January 2018 and December 2022 were included. We systematically analyzed the characteristics of sex differences in aSAH and explored the relationship between delayed cerebral ischemia (DCI), surgery-related cerebral infarction (SRCI), and poor prognosis (modified Rankin Scale > 2). RESULTS: Compared with women, men were in worse condition and had more intracerebral hematoma (p = 0.001) on admission, whereas women were older (p < 0.001) and had more multiple aneurysms (p = 0.002). During hospitalization, men were more likely to experience emergency intubation (p = 0.036) and tracheotomy (p = 0.013). Women achieved functional independence at discharge at a similar rate to men (p = 0.394). Among postoperative complications, the incidence of DCI (22% vs. 12%, p = 0.01) and urinary tract infection (p = 0.022) was significantly higher in women. After adjusting for age, multivariable regression analysis showed that hypertension (odds ratio [OR] 2.139, 95% confidence interval [CI] 1.027-4.457), preoperative rerupture (OR 12.240, 95% CI 1.491-100.458), pulmonary infection (OR 2.297, 95% CI 1.070-4.930), external ventricular drainage placement (OR 4.382, 95% CI 1.550-12.390), bacteremia (OR 14.943, 95% CI 1.412-158.117), SRCI (OR 8.588, 95% CI 4.092-18.023), venous thrombosis (OR 5.283, 95% CI 1.859-15.013), higher modified Fisher grades (p = 0.003), and Hunt-Hess grades (p = 0.035) were associated with poor prognosis, whereas DCI (OR 1.394, 95% CI 0.591-3.292) was not an independent risk factor for poor prognosis. The proportion of patients who fully recovered from cerebral ischemia was higher in the DCI group (p < 0.001) compared with the SRCI group, and more patients were discharged with modified Rankin Scale > 2 in the SRCI group (p = 0.005). CONCLUSIONS: Women have a higher incidence of DCI, but there is no sex difference in outcomes after aSAH, and poor prognosis is associated with worse admission condition and perioperative complications. SRCI is a strong independent risk factor for poor prognosis, whereas DCI is not.

Impact of frailty on post-operative outcomes following subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and morbidity, particularly among elderly patients. The presence of frailty may impact survival rates in patients with SAH. In this study, we aim to investigate the impact of frailty on the clinical outcomes in SAH patients. METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Relevant papers through December 2023 were retrieved from PubMed, Scopus, Web of science, and Embase. RESULTS: A total of 5 studies met inclusion/exclusion criteria with an aggregate 39,221 non-frail patients (mean age 52.4 ± 5.2 yr; 62.1 % Female), and 79,416 frail patients (mean age 61.1 ± 5.4 yr; 69.0 % Female). Frailty was significantly associated with higher mortality ratio (Odds ratio (OR)= 2.09; CI [1.04: 4.20], p= 0.04), and increased length of hospital stay (OR= 1.40; CI [1.07: 1.83], p= 0.015). Additionally, frailty was associated with higher odds of external ventricular drain insertion, the need of tracheostomy/endoscopic gastrostomy, increased risk of deep vein thrombosis, and postoperative neurological complications. CONCLUSION: Frailty is associated with worse clinical outcomes and higher mortality rates in SAH patients. Our findings highlight that frailty, when considered alongside other established prognostic factors, serves as crucial predictor for peri-operative complications and overall hospital course in SAH patients.

Diagnostic value of transcranial doppler to predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : To predict delayed cerebral ischemia.

BACKGROUND: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. METHODS: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. RESULTS: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5. CONCLUSION: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.

Management of external ventricular drain: to wean or not to wean?

PURPOSE: External ventricular drain (EVD) is one of the most frequent procedures in neurosurgery and around 15 to 30% of these patients require a permanent cerebrospinal fluid (CSF) diversion. The optimal EVD weaning strategy is still unclear. Whether gradual weaning compared to rapid closure, reduces the rate of permanent CSF diversion remains controversial. The aim of this trial is to compare the rates of permanent CSF diversion between gradual weaning and rapid closure of an EVD. METHODS: This was a single-center, retrospective cohort study including patients between 2010 to 2020. Patients were divided into a weaning (WG) and non-weaning (NWG) group. The primary outcome was permanent CSF diversion rates, secondary outcomes included hospitalization time, EVD-related morbidity, and clinical outcome. RESULTS: Out of 412 patients, 123 (29.9%) patients were excluded due to early death or palliative treatment. We registered 178 (61.6%) patients in the WG and 111 (38.4%) in the NWG. Baseline characteristics were comparable between groups. The VPS rate was comparable in both groups (NWG 37.8%; WG 39.9%, p = 0.728). EVD related infection (13.5% vs 1.8%, p < 0.001), as well as non-EVD related infection rates (2.8% vs 0%, p < 0.001), were significantly higher in the WG. Hospitalization time was significantly shorter in the NWG (WG 24.93 ± 9.50 days; NWG 23.66 ± 14.51 days, p = 0.039). CONCLUSION: Gradual EVD weaning does not seem to reduce the need for permanent CSF diversion, while infection rates and hospitalization time were significantly higher/longer. Therefore, direct closure should be considered in the clinical setting.

Identification of metabolites associated with preserved muscle volume after aneurysmal subarachnoid hemorrhage due to high protein supplementation and neuromuscular electrical stimulation.

The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and ß-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.

Partial coil embolization before surgical clipping of ruptured intracranial aneurysms.

OBJECTIVE: Intraoperative rupture (IOR) is the most common adverse event encountered during surgical clip obliteration of ruptured intracranial aneurysms. Besides increasing surgeon experience and early proximal control, no methods exist to decrease IOR risk. Thus, our objective was to assess if partial endovascular coil embolization to protect the aneurysm before clipping decreases IOR. METHODS: We conducted a retrospective analysis of patients with ruptured intracranial aneurysms that were treated with surgical clipping at two tertiary academic centers. We compared patient characteristics and outcomes of those who underwent partial endovascular coil embolization to protect the aneurysm before clipping to those who did not. The primary outcome was IOR. Secondary outcomes were inpatient mortality and discharge destination. RESULTS: We analyzed 100 patients. Partial endovascular aneurysm protection was performed in 27 patients. Age, sex, subarachnoid hemorrhage severity, and aneurysm location were similar between the partially-embolized and non-embolized groups. The median size of the partially-embolized aneurysms was larger (7.0 mm [interquartile range 5.95-8.7] vs. 4.6 mm [3.3-6.0]; P < 0.001). During surgical clipping, IOR occurred less frequently in the partially-embolized aneurysms than non-embolized aneurysms (2/27, 7.4%, vs. 30/73, 41%; P = 0.001). Inpatient mortality was 14.8% (4/27) in patients with partially-embolized aneurysms and 28.8% (21/73) in patients without embolization (P = 0.20). Discharge to home or inpatient rehabilitation was 74.0% in patients with partially-embolized aneurysms and 56.2% in patients without embolization (P = 0.11). A complication from partial embolization occurred in 2/27 (7.4%) patients. CONCLUSIONS: Preoperative partial endovascular coil embolization of ruptured aneurysms is associated with a reduced frequency of IOR during definitive treatment with surgical clip obliteration. These results and the impact of preoperative partial endovascular coil embolization on functional outcomes should be confirmed with a randomized trial.

Association of hemoglobin drift and outcomes in patients with aneurysmal subarachnoid hemorrhage.

The relationship between in-hospital hemoglobin (Hb) drift and outcomes in patients undergoing surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH) is not well studied. This study aims to investigate the association between Hb drift and mortality in this patient population. We conducted a cohort study encompassing adult patients diagnosed with aSAH who were admitted to a university hospital. These patients were stratified into distinct groups based on their Hb drift levels. We employed logistic and Cox proportional hazard models to assess the relationship between Hb drift and outcomes. Additionally, propensity score matching (PSM) was utilized to ensure comparability between patient groups. The discriminative performance of different models was evaluated using C-statistics, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Overall, our cohort comprised 671 patients, of whom 165 (24.6%) demonstrated an in-hospital Hb drift exceeding 25%. The analyses revealed elevated Hb drift was independently associated with higher likelihood of follow-up mortality (aOR: 3.29, 95% CI: 1.65 to 6.56; P = 0.001) and in-hospital mortality (aOR: 3.44, 95% CI: 1.55 to 7.63; P = 0.002). PSM analysis yielded similar results. Additionally, patients with Hb drift exhibited a notable decrease in survival rate compared to those without Hb drift (aHR: 3.99, 95% CI 2.30 to 6.70; P < 0.001). Furthermore, the inclusion of Hb drift significantly improved the C-statistic (P = 0.037), IDI (2.78%; P = 0.004) and NRI metrics (41.86%; P < 0.001) for mortality prediction. In summary, our results highlight that an in-hospital Hb drift exceeding 25% serves as an independent predictor of mortality in patients who have undergone surgical clipping for aSAH.

Intermediate catheter use is associated with intraprocedural rupture during coil embolization of ruptured intracranial aneurysms: a retrospective propensity score-matched study.

Introduction: An intermediate catheter (IMC) may pose a risk of intraprocedural rupture (IPR) during coil embolization of ruptured intracranial aneurysms (RIAs), because the pressure on the microcatheter and coil might be more direct. To verify this hypothesis, this study explored whether use of an IMC might correlate with an increased rate of IPR during coil embolization for RIAs. Methods: We retrospectively reviewed 195 consecutive aneurysms in 192 patients who underwent initial coil embolization for saccular RIAs at our institution between January 2007 and December 2023. Patients were divided into two groups with aneurysms treated either with an IMC (IMC group) or without an IMC (non-IMC group). To investigate whether IMC use increased the rate of IPR, a propensity score-matched analysis was employed to control for age, sex, maximal aneurysm size, neck size, bleb formation, aneurysm location, proximal vessel tortuosity, balloon-assisted coiling, type of microcatheter, and type of framing coil. Results: Ultimately, 43 (22%) coil embolization used IMC. In univariate analysis, the incidence of IPR was significantly higher in the IMC group compared with the non-IMC group (14.0 vs. 3.3%, p = 0.016). Propensity score matching was successful for pairs of 26 aneurysms in the IMC group and 52 aneurysms in the non-IMC group. The incidence of IPR was still significantly higher in the IMC group than in the non-IMC group (23.1 vs. 3.8%, p = 0.015). No significant differences in the incidences of ischemic complications and IMC-related parent artery dissection were observed between the two groups. Discussion: When using IMC for coil embolization of RIAs, the surgeons should be more careful and delicate in manipulating the microcatheter and inserting the coils to avoid IPR.

Subarachnoid Intra-cranial Lipiodol Deposits.

Lipiodol, an oil-based contrast medium first introduced in 1944, was commonly used for various radiological exams until the 1980s, when it was replaced by water-soluble contrast media due to complications such as arachnoiditis and chronic irritations. Due to its slow resorption rate, asymptomatic lipiodol deposits can occasionally be found incidentally. This case report describes a 93-year-old man who presented to the emergency department after a fall. A non-contrast head CT scan, performed to rule out subarachnoid hemorrhage, revealed numerous hyperdense droplets in the subarachnoid spaces of the brain, primarily around the temporal lobes. Further investigation uncovered a previous pelvic X-ray showing similar hyperdense droplets around the cauda equina. The patient's history indicated a lipiodol myelography performed 51 years earlier. Lipiodol deposits are generally found in the lumbar region, making an intra-cranial location particularly rare. When present, these deposits are visible as radiopaque droplets on X-rays, hyperdense droplets on CT scans, and hyper-T1 on MRI, though the T2 signal is variable. Though lipiodol deposits are generally left untreated, symptomatic spinal deposits may be surgically removed. This rare case underscores the importance of thorough patient history in diagnosing subarachnoid lipiodol deposits, a condition relevant only in older patients who underwent myelography before the 1980s.

Uncommon Cause, Critical Consequence: Vertebral Artery Aneurysm Resulting in Intraventricular Hemorrhage.

The vertebrobasilar system is made up of the two vertebral arteries that unite to form the basilar artery near the base of the skull. Aneurysms in the vertebrobasilar system are distinct from other cerebral aneurysms due to their unique morphologic characteristics. They can be large and bulging (massive), pressing on the brainstem. Alternatively, they might be weak and splitting apart (dissecting) or have an elongated shape (fusiform). On the other end of the spectrum, Vertebral artery aneurysms (VAAs) can also be small and rounded (saccular). These aneurysms can occur at the vertebral artery itself or where it joins the posterior inferior cerebellar artery (PICA). Anatomically, they are situated near the brainstem and cranial nerves, deep within the posterior fossa. The cerebrospinal fluid is kept in transit and flux by the ventricular system's chambers circulating the fluid within themselves. An intraventricular hemorrhage (IVH) can occasionally result from vertebral artery aneurysmal ruptures that result in bleeding into the subarachnoid space and then extravasate into the ventricles. Persistent and poorly controlled hypertension affects about 50% of individuals with IVH. In this case report, we study a 74-year-old woman who complained of a sudden onset headache that had been bothering her for three days at the medical emergency room. She had been diagnosed with systemic hypertension eight years prior and had not taken her medicines as prescribed. She was discovered to have rigidity in her neck and a blood pressure reading of 170/100 mmHg, which had been followed by an episode of vomiting. Radiological investigations revealed a VAA that had a high risk of rupturing and causing an IVH.

A High-grade Aneurysmal Subarachnoid Hemorrhage in the Peripartum Period.

Aneurysmal subarachnoid hemorrhage (aSAH) is a rare but devastating complication with increased morbidity and mortality. It is still unclear whether the incidence is increased during pregnancy and in the peripartum period. However, the incidence of cerebral aneurysmal rupture is higher during the third trimester than in the first trimester. The risk of aneurysmal rupture and subarachnoid hemorrhage (SAH) during general anesthesia or spinal anesthesia is unclear. We report a case of left supraclinoid aneurysm rupture after spinal anesthesia for Low Segment Caesarean Section (LSCS) in the immediate postpartum period causing high-grade aSAH.

Protective effects of flavonoids against intracerebral and subarachnoid hemorrhage (Review).

Intracerebral hemorrhage (ICH), known as non-traumatic cerebrovascular rupture and hemorrhage, often occurs in the deep basal brain segment. It is known for its high morbidity and mortality rates. Subarachnoid hemorrhage (SAH) is a clinical syndrome caused by the rupture of blood vessels at the base or surface of the brain that allows blood to flow directly into the subarachnoid space. It progresses quickly and typically manifests at younger ages compared with ICH. ICH and SAH are both devastating events in the category of hemorrhagic strokes and are attracting increasing attention from researchers. Flavonoids, being important natural molecules, have remarkable anti-inflammatory and antioxidant effects. Flavonoids have extensive biological activities in inflammation and oxidative stress (OS), and have protective effects in vascular function associated with cerebrovascular diseases. They have an impact on the onset of ICH and SAH by targeting various pathways, including the suppression of inflammation and OS. Recently, the role of flavonoid compounds in ICH and SAH has also received increasing interest. Thus, to serve as a resource for the prevention and treatment of ICH and SAH, the present review provided an overview of the research on flavonoid compounds in the prevention of brain damage after these two conditions have occurred.

Meteorological factors and risk of ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage: a time stratified case-crossover study.

BACKGROUND: Stroke risks associated with rapid climate change remain controversial due to a paucity of evidence. AIMS: To examine the risk of subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), and ischemic stroke (IS) associated with meteorological parameters. METHODS: In this time-stratified case-crossover study, adult patients hospitalized for their first stroke between 2011 and 2020 from the insurance claims data in Taiwan were identified. The hospitalization day was designated as the case period, and three or four control periods were matched by the same day of the week and month of each case period. Daily mean and 24-hour variations in ambient temperature, relative humidity, air pressure, and apparent temperature were measured. Conditional logistic regression models were applied to assess the risk of stroke associated with exposure to weather variables, using the third quintile as a reference, controlling for air pollutant levels. RESULTS: There were 7161 patients with SAH, 40,426 patients with ICH, and 107,550 patients with IS. There was an inverse linear relationship between mean daily temperature and apparent temperature with ICH. Elevated mean daily atmospheric pressure was associated with an increased risk of ICH. A greater decrease in apparent temperature over a 24-hour period was associated with increased risk of ICH but decreased risk of IS (odds ratio [95% confidence interval] for the first vs. third quintile of changes in apparent temperature, 1.141 [1.053-1.237] and 0.946 [0.899-0.996], respectively). CONCLUSIONS: There were considerable differences in short-term associations between meteorological parameters and three main pathological types of strokes.Data access statement: The authors have no permission to share the data.

Visualization of Cerebrospinal Fluid Outflow and Egress along the Nerve Roots of the Lumbar Spine.

Intrinsic cerebrospinal fluid (CSF) dynamics in the brain have been extensively studied, particularly the egress sites of tagged intrinsic CSF in the meninges. Although spinal CSF recirculates within the central nervous system (CNS), we hypothesized that CSF outflows from the lumbar spinal canal. We aimed to visualize and semi-quantify the outflow using non-contrast MRI techniques. We utilized a 3 Tesla clinical MRI with a 16-channel spine coil, employing time-spatial labeling inversion (Time-SLIP) with tag-on and tag-off acquisitions, T2-weighted coronal 2D fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal 3D centric ky-kz single-shot FSE (cSSFSE). Images were acquired using time-spatial labeling inversion pulse (Time-SLIP) with tag-on and tag-off acquisitions with varying TI periods. Ten healthy volunteers with no known spinal diseases participated. Variations in tagged CSF outflow were observed across different thoracolumbar nerve root segments in all participants. We quantified CSF outflow at all lumbar levels and the psoas region. There was no significant difference among the ROIs for signal intensity. The tagged CSF outflow from the spinal canal is small but demonstrates egress to surrounding tissues. This finding may pave the way for exploring intrathecal drug delivery, understanding of CSF-related pathologies and its potential as a biomarker for peripheral neuropathy and radiculopathy.

Longitudinal Genome-Wide Association Study of Cognitive Impairment after Subarachnoid Hemorrhage.

OBJECTIVES: The occurrence of cognitive deficits after subarachnoid hemorrhage (SAH) is highly possible, leading to vascular dementia. We performed a novel longitudinal genome-wide association study (GWAS) to identify genetic modifications associated with cognitive impairment following SAH in a long-term prospective cohort study. MATERIALS AND METHODS: This GWAS involved 153 patients with SAH sharing 5,971,372 markers after high-throughput imputation. Genome-wide Cox proportional hazard regression testing was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Subsequently, a weighted polygenetic risk score (wPRS) was determined, based on GWAS-driven loci and risk stratification. RESULTS: Cognitive impairment was observed in 65 patients (42.5%) during a mean follow-up of 37.7 ± 12.4 months. Five genome-wide signals, including rs138753053 (PDCD6IP-LOC101928135, HR = 28.33, p = 3.4 × 10-8), rs56823384 (LINC00499, HR = 12.47, p = 2.8 × 10-9), rs145397166 (CASC15, HR = 11.16, p = 1.7 × 10-8), rs10503670 (LPL-SLC18A1, HR = 2.88, p = 4.0 × 10-8), and rs76507772 (IRS2, HR = 5.99, p = 3.5 × 10-8), were significantly associated with cognitive impairment following SAH. In addition, the well-constructed wPRS containing five markers showed nominal ability to predict cognitive impairment (AUROC = 0.745, 95% CI: 0.667-0.824). Tertile stratification showed a higher effectiveness in predicting cognitive impairment, especially in those with haptoglobin 2-1 (HR = 44.59, 95% CI: 8.61-231.08). CONCLUSIONS: Our study revealed novel susceptible loci for cognitive impairment, longitudinally measured in patients with SAH. The clinical utility of these loci will be evaluated in further follow-up studies.