Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH. METHODS: Overall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study. Following SAH onset, 136 patients were managed with continuous CSF drainage, whereas 68 were managed with intermittent CSF drainage. Logistic regression analyses were used to calculate the age-adjusted and multivariate odds ratios for the development of sCH. The Cox proportional hazards regression model were used to compare the effects of intermittent and continuous CSF drainage on sCH development. RESULTS: Overall, 96 patients developed sCH among the 204 patients with SAH. In total, 74 (54.4%) of the 136 patients managed with continuous CSF drainage developed sCH, whereas 22 (32.4%) of the 68 patients managed with intermittent CSF drainage developed sCH. This demonstrated that the rate of sCH development was significantly lower among patients managed with intermittent CSF drainage. Compared with continuous CSF drainage, intermittent CSF drainage exhibited a multivariate odds ratio (95% confidential interval) of 0.25 (0.11-0.57) for sCH development. Intermittent CSF drainage was more effective (0.20, 0.04-0.95) in patients with severe-grade SAH than in those with mild-grade SAH (0.33, 0.12-0.95). Intermittent CSF drainage was ineffective in patients with acute hydrocephalus (8.37, 0.56-125.2), but it was effective in patients without acute hydrocephalus (0.11, 0.04-0.31). CONCLUSIONS: Compared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset.

Japanese nationwide questionnaire survey on delayed cerebral infarction due to vasospasm after subarachnoid hemorrhage.

Background and purpose: Various prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021. Methods: In 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan. Of them, 162 hospitals (29% response rate) responded to the questionnaire. Of these, 158 were included in this study, while four hospitals that responded insufficiently were excluded. The efficacy of treatments for reducing DCI were examined through a logistic regression analysis. Results: Among 3,093 patients treated with aneurysmal SAH, 281 patients (9.1%) were diagnosed with DCI related to cerebral vasospasm. Coil embolization had significantly lower DCI frequency (6.9%), compared to microsurgical clipping (11.8%, odds ratio, 0.90; 95% confidential intervals, 0.84-0.96; P, 0.007). In addition, cilostazol administration was associated with significantly lower DCI frequency (0.48; 0.27-0.82; 0.026). The efficacy of cilostazol in reducing DCI remained unchanged after adjustment for covariates. The most effective combination of multiple prophylactic drugs in reducing DCI related to cerebral vasospasm was cilostazol, fasudil, and statin (0.38; 0.22-0.67; 0.005). Conclusions: This study elucidated the trends in prophylactic drugs to prevent cerebral vasospasm and frequency of DCI after aneurysmal SAH in Japan. Coil embolization and cilostazol administration showed effectiveness in reducing DCI related to cerebral vasospasm in 2021.

Secular trends and features of thalamic hemorrhages compared with other hypertensive intracerebral hemorrhages: an 18-year single-center retrospective assessment.

Introduction: Trends regarding the locations of hypertensive cerebral hemorrhages are unclear. To clarify hypertensive hemorrhage trends, we investigated intracerebral hemorrhages (ICHs) over an 18-year period, focusing on thalamic hemorrhages compared with other sites of hemorrhages. Methods: We reviewed the cases of patients hospitalized for hypertensive ICH in 2004-2021 at our hospital; 1,320 eligible patients were registered with a primary ICH/intraventricular hemorrhage. After exclusion criteria were applied, we retrospectively analyzed 1,026 hypertensive ICH cases. Results: The proportions of thalamic and subcortical hemorrhages increased over the 18-year period, whereas putaminal hemorrhage decreased. Multivariate logistic regression analyses revealed that for thalamic hemorrhage, ≥200 mmHg systolic blood pressure (p = 0.031), bleeding <15 mL (p = 0.001), and higher modified Rankin scale (mRS) score ≥ 4 at discharge (p = 0.006) were significant variables in the late period (2013-2021) versus the early period (2004-2012), whereas for putaminal hemorrhage, significant factors in the late period were triglyceride <150 mg/dL (p = 0.006) and mRS score ≥ 4 at discharge (p = 0.002). Among the features of the thalamic hemorrhages in the late period revealed by our group comparison with the putaminal and subcortical hemorrhages, the total and subcortical microbleeds were more notable in the thalamic hemorrhages than in the other two types of hemorrhage, whereas cerebellar microbleeds were more prominent when compared only with subcortical hemorrhages. Discussion: Our findings revealed an increasing trend for thalamic hypertensive hemorrhage and a decreasing trend for putaminal hemorrhage. The thalamic hemorrhage increase was observed in both young and older patients, regardless of gender. The main features of thalamic hemorrhage in the late period versus the early period were decrease in larger hemorrhage (≥15 mL) and an increase in cases with higher systolic blood pressure (at least partially involved a small number of untreated hypertensive patients who developed major bleeding). The total and subcortical microbleeds were more notable in the thalamic hemorrhages of the late period than in the putaminal and subcortical hemorrhages. These results may contribute to a better understanding of the recent trends of hypertensive ICHs and may help guide their appropriate treatments for this condition.

Endoscope-Controlled High Frontal Approach for Dural Arteriovenous Fistula in Anterior Cranial Fossa.

BACKGROUND: Currently, surgical obliterations are a mainstay for treating dural arteriovenous fistula (DAVF) in the anterior cranial fossa (ACF), which has high risks of hemorrhage and functional disorder. By introducing an endoscope into a high frontal approach and utilizing its advantages, we attempted to establish it as a new surgical procedure that eliminates the drawbacks of various approaches that have been used to date. METHODS: By using 30 clinical datasets of venous-phase head computed tomography angiogram, measurements and comparisons on a 3-dimensional workstation were performed to identify the appropriate positioning of keyhole craniotomy for endoscope-controlled high frontal approach (EHFA). Based on these data, a cadaver-based surgery was simulated to verify the feasibility of EHFA and develop an efficient procedure. RESULTS: In EHFA, though raising the position of the keyhole craniotomy made the operative field deeper, significant advantages were obtained in the angle between the operative axis and the medial-anterior cranial base and the amount of bone removal required at the anterior edge of craniotomy. Minimally invasive EHFA, performed through a keyhole craniotomy without opening the frontal sinus, proved to be feasible on 10 sides of 5 cadaver heads. Moreover, 3 patients with DAVF in ACF were successfully treated by clipping the fistula via EHFA. CONCLUSIONS: EHFA, which provided a direct corridor to the medial ACF at the level of the foramen cecum and crista galli and the minimum necessary operative field, was found to be a suitable procedure for clipping the fistula of DAVF in ACF.

Clinical utility of paced finger tapping assessment in idiopathic normal pressure hydrocephalus.

Background: The Finger Tapping (F-T) test is useful for assessing motor function of the upper limbs in patients with idiopathic normal pressure hydrocephalus (iNPH). However, quantitative evaluation of F-T for iNPH has not yet been established. The purpose of this study was to investigate the usefulness of the quantitative F-T test and optimal measurement conditions as a motor evaluation and screening test for iNPH. Methods: Sixteen age-matched healthy controls (mean age 73 ± 5 years; 7/16 male) and fifteen participants with a diagnosis of definitive iNPH (mean age 76 ± 5 years; 8/15 male) completed the study (mean ± standard deviation). F-T performance of the index finger and thumb was quantified using a magnetic sensing device. The performance of repetitive F-T by participants was recorded in both not timing-regulated and timing-regulated conditions. The mean value of the maximum amplitude of F-T was defined as M-Amplitude, and the mean value of the maximum velocity of closure of F-T was defined as cl-Velocity. Results: Finger Tapping in the iNPH group, with or without timing control, showed a decrease in M-Amplitude and cl-Velocity compared to the control group. We found the only paced F-T with 2.0 Hz auditory stimuli was found to improve both M-Amplitude and cl-Velocity after shunt surgery. Conclusion: The quantitative assessment of F-T with auditory stimuli at the rate of 2.0 Hz may be a useful and potentially supplemental screening method for motor assessment in patients with iNPH.

Arbitrary Ca2+ regulation for endothelial nitric oxide, NFAT and NF-κB activities by an optogenetic approach.

Modern western dietary habits and low physical activity cause metabolic abnormalities and abnormally elevated levels of metabolites such as low-density lipoprotein, which can lead to immune cell activation, and inflammatory reactions, and atherosclerosis. Appropriate stimulation of vascular endothelial cells can confer protective responses against inflammatory reactions and atherosclerotic conditions. This study aims to determine whether a designed optogenetic approach is capable of affecting functional changes in vascular endothelial cells and to evaluate its potential for therapeutic regulation of vascular inflammatory responses in vitro. We employed a genetically engineered, blue light-activated Ca2+ channel switch molecule that utilizes an endogenous store-operated calcium entry system and induces intracellular Ca2+ influx through blue light irradiation and observed an increase in intracellular Ca2+ in vascular endothelial cells. Ca2+-dependent activation of the nuclear factor of activated T cells and nitric oxide production were also detected. Microarray analysis of Ca2+-induced changes in vascular endothelial cells explored several genes involved in cellular contractility and inflammatory responses. Indeed, there was an increase in the gene expression of molecules related to anti-inflammatory and vasorelaxant effects. Thus, a combination of human blue light-activated Ca2+ channel switch 2 (hBACCS2) and blue light possibly attenuates TNFα-induced inflammatory NF-κB activity. We propose that extrinsic cellular Ca2+ regulation could be a novel approach against vascular inflammation.

Differential Methylation Signatures in Severely Calcified Carotid Plaques by Genome-Wide Comprehensive Analysis.

BACKGROUND: The precise cellular behaviors of calcification, including its molecular and genetic activities, have not yet been fully established for carotid plaques. OBJECTIVE: We sought specific genes with tissue-specific differential methylation associated with carotid calcification status. METHODS: We classified eight plaques from carotid endarterectomy patients as high- or low-calcified based on their Agatston calcium scores. We analyzed differential DNA methylation and performed bioinformatics data mining. RESULTS: A high correlation of average methylation levels (ß-values) in promoter regions between high- and low-calcified plaque groups was observed. A principal component analysis of DNA methylation values in promoters of specimens revealed two independent clusters for high- and lowcalcified plaques. Volcano plots for methylation differences in promoter regions showed that significantly hypomethylated probes were more frequently found for high-calcified plaques than more methylated probes. Differential hypomethylation of receptor activity-modifying protein 1 (RAMP1) in high-calcified plaques was commonly extracted in both the promoter region and the cytosinephosphate- guanine (CpG) island shore region, where differential methylation had been reported to be more tissue-specific. Kyoto Encyclopedia of Genes and Genomes pathway analysis annotated a pathway associated with vascular smooth muscle contraction in the differentially methylated genes of the promoter and CpG island shore regions in high-calcified plaques. CONCLUSION: Among the extracted differentially methylated genes, hypomethylated genes were more dominant than more methylated genes. The augmentation of RAMP1 by hypomethylation may contribute to the enhancement of anti-atherosclerotic effects and hence stability in high-calcified plaques. These results contribute to our understanding of the genetic signatures associated with calcification status and cellular activity in carotid plaques.

A Case of Sarcoidosis-lymphoma Syndrome: Importance of Brain Biopsy.

Sarcoidosis is occasionally associated with malignant lymphoma. Cases of sarcoidosis associated with malignant lymphoma are called sarcoidosis-lymphoma syndrome. We report a 63-year-old man with sarcoidosis associated with primary central nervous system lymphoma (PCNSL). Definitive diagnosis by clinical and radiological findings was difficult. Finally, brain biopsy could produce the correct diagnosis. We could provide appropriate treatment for PCNSL and the patient has survived over 2 years. Thus, it is very important to make an early definitive diagnosis by biopsy for intracranial lesion, because it can prolong survival in patients with sarcoidosis.