Lobar Hemorrhage Research Articles

Long-term neurodevelopmental outcome of neonates born at term with perinatal haemorrhagic stroke: A population-based study.

AimTo assess the long‐term neurodevelopmental outcome of neonates born at term diagnosed with perinatal haemorrhagic stroke (PHS) and investigate the associations among brain territorial involvement, clinical risk factors, and neurodevelopmental outcomes.MethodWe conducted a population‐based study enrolling 55 neonates born at term with PHS confirmed by magnetic resonance imaging born between 2007 and 2017. Long‐term neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition, the Brunet–Lézine test, and the Stanford–Binet Intelligence Scales, Fifth Edition.ResultsFollow‐up was available in 50 (91%) of the infants, at a median age of 60 months (interquartile range 35–88). Forty per cent of the infants developed according to population norms, and developmental disabilities were diagnosed less frequently among neonates with frontal lobe PHS. In a multivariable model, parietal lobe PHS increased the risk for cerebral palsy (odds ratio [OR] 6.7; 95% confidence interval [CI] 1.1–41.4) and cognitive impairment (OR: 23.6; 95% CI: 2.9–194.9), while the involvement of the thalamus and/or basal ganglia was associated with epilepsy (OR: 7.0; 95% CI: 1.3–37.7). Seizures on admission were associated with epilepsy (OR: 10.8; 95% CI: 1.8–64.3). Patients with PHS affecting multiple lobes had poor prognosis.InterpretationParietal lobe haemorrhage, the involvement of the thalamus/basal ganglia, PHS affecting multiple lobes, and seizures were independent predictors of chronic neurodevelopmental sequelae, suggesting that the stroke territorial involvement and clinical risk factors influence the outcome of PHS.

Neuronal circuits sustaining neocortical-injury-induced status epilepticus

ObjectivesAcute injuries or insults to the cortex, such as trauma, subarachnoid hemorrhage, lobar hemorrhage, can cause seizures or status epilepticus(SE). Neocortical SE is associated with coma, worse prognosis, delayed recovery, and the development of epilepsy. The anatomical structures progressively recruited during neocortical-onset status epilepticus (SE) is unknown. Therefore, we constructed large-scale maps of brain regions active during neocortical SE. MethodsWe used a neocortical injury-induced SE mouse model. We implanted cobalt (Co) in the right supplementary motor cortex (M2). We 16 h later administered a homocysteine injection (845 mg/kg, intraperitoneal) to C57Bl/6 J mice to induce SE and monitored it by video and EEG. We harvested animals for 1 h (early-stage) and 2 h (late-stage) following homocysteine injections. To construct activation maps, we immunolabeled whole-brain sections for cFos and NeuN, imaged them using a confocal microscope and quantified cFos immunoreactivity (IR). ResultsSE in the early phase consisted of discrete, focal intermittent seizures, which became continuous and bilateral in the late stage. In this early stage, cFos IR was primarily observed in the right hemisphere, ipsilateral to the Co lesion, specifically in the motor cortex, retrosplenial cortex, somatosensory cortex, anterior cingulate cortex, lateral and medial septal nuclei, and amygdala. We observed bilateral cFos IR in brain regions during the late stage, indicating the bilateral spread of focal seizures. We found increased cFOS IR in the bilateral somatosensory cortex and the motor cortex and subcortical regions, including the amygdala, thalamus, and hypothalamus. There was noticeably different, intense cFos IR in the bilateral hippocampus compared to the early stage. In addition, there was higher activity in the cortex ipsilateral to the seizure focus during the late stage compared with the early one. ConclusionWe present a large-scale, high-resolution map of seizure spread during neocortical injury-induced SE. Cortico-cortical and cortico subcortical re-entrant circuits sustain neocortical SE. Neuronal loss following neocortical SE, distant from the neocortical focus, may result from seizures.

Validation of external and internal exposome of the findings associated to cerebral small vessel disease: A Mendelian randomization study

The exposome characterizes all environmental exposures and their impact on a disease. To determine the causally-associated components of the exposome for cerebral small vessel disease (CSVD), we performed mendelian randomization analysis of 5365 exposures on six clinical and subclinical CSVD measures. We found statistically significant evidence (FDR-corrected P < 0.05) that hypertension, high cholesterol, longer television-watching time, lower educational qualifications, younger age of first sexual intercourse, smoking, reduced pulmonary function, higher subjective overall health rating, and frequent tiredness were associated with increased risk of intracerebral hemorrhage or small vessel stroke. Adiposity, diabetes, frequent alcoholic drinks, higher white blood cell count and neutrophil count were significantly associated with higher risk of non-lobar hemorrhage or small vessel stroke, but not lobar hemorrhage. Hypertension, higher arm or leg fat-free mass and higher sitting height were significantly associated with higher white matter hyperintensities. The results were robust to sensitivity analyses and showed no evidence of horizontal pleiotropy. We also identified 41 exposures suggestively associated (uncorrected P < 0.05) with multiple CSVD measures as the “the CSVD exposome”. This exposome-wide association study provides insight into CSVD development and prevention.

Prognostication in Acute Neurological Emergencies

BackgroundFor patients with acute, serious neurological conditions presenting to the emergency department (ED), prognostication is typically based on clinical experience, scoring systems and patient co-morbidities. Because estimating a poor prognosis influences caregiver decisions to withdraw life-sustaining therapy, we investigated the consistency of prognostication across a spectrum of neurology physicians. MethodsFive acute neurological presentations (2 with large hemispheric infarction; 1 with brainstem infarction, 1 with lobar hemorrhage, and 1 with hypoxic-ischemic encephalopathy) were selected for a department-wide prognostication simulation exercise. All had presented to our tertiary care hospital's ED, where a poor outcome was predicted by the ED neurology team within 24 hours of onset. Relevant clinical, laboratory and imaging data available before ED prognostication were presented on a web-based platform to 120 providers blinded to the actual outcome. The provider was requested to rank-order, from most to least likely, the predicted 90-day modified Rankin Scale (mRS) score. To determine the accuracy of individual outcome predictions we compared the patient's the actual 90-day mRS score to highest ranked predicted mRS score. Additionally, the group's “weighted” outcomes, accounting for the entire spectrum of mRS scores ranked by all respondents, were compared to the actual outcome for each case. Consistency was compared between pre-specified provider roles: neurology trainees versus faculty; non-vascular versus vascular faculty. ResultsResponses ranged from 106-110 per case. Individual predictions were highly variable, with predictions matching the actual mRS scores in as low as 2% of respondents in one case and 95% in another case. However, as a group, the weighted outcome matched the actual mRS score in 3 of 5 cases (60%). There was no significant difference between subgroups based on expertise (stroke/neurocritical care versus other) or experience (faculty versus trainee) in 4 of 5 cases. ConclusionAcute neuro-prognostication is highly variable and often inaccurate among neurology providers. Significant differences are not attributable to experience or subspecialty expertise. The mean outcome prediction from group of providers (“the wisdom of the crowd”) may be superior to that of individual providers.

Efficacy of arterial spin labeling for detection of the ruptured micro-arteriovenous malformation: illustrative cases.

BACKGROUNDDiagnosis of a microarteriovenous malformation (micro-AVM) is difficult, especially in the acute stage of rupture because of the small size of the nidus and the existence of hematoma. We report two cases of ruptured micro-AVMs detected by arterial spin labeling (ASL).OBSERVATIONSIn one case, a 45-year-old male was transported with a complaint of right hemiparesis. Computed tomography (CT) revealed a right parietal lobar hemorrhage. Standard magnetic resonance imaging (MRI) showed no abnormal findings as the cause of the hemorrhage. ASL 23 days after the onset demonstrated high signals on the medial wall of the hematoma. Digital subtraction angiography (DSA) showed a micro-AVM in accordance with the site of high signals on ASL. In another case, a 38-year-old female was transported with a complaint of left hemianopsia. CT on admission revealed a right parietal lobar hemorrhage. Standard MRI showed no abnormal findings as the cause of the hemorrhage. ASL 15 days after the onset demonstrated high signals on the internal wall of the hematoma. DSA showed micro-AVM in accordance with the site of high signaling on ASL. Both cases were successfully treated with open surgery.LESSONSASL can manifest micro-AVMs as high signals within the hematoma. ASL is a useful less-invasive screening tool for the detection of ruptured micro-AVMs.

Trigger Factors for Spontaneous Intracerebral Hemorrhage: A Case-Crossover Study.

Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge on the pathophysiology of ICH. We assessed potential trigger factors and their risk for ICH onset. We included consecutive patients diagnosed with ICH between July 1, 2013, and December 31, 2019. We interviewed patients on their exposure to 12 potential trigger factors (eg, Valsalva maneuvers) in the (hazard) period soon before onset of ICH and their normal exposure to these trigger factors in the year before the ICH. We used the case-crossover design to calculate relative risks (RR) for potential trigger factors. We interviewed 149 patients (mean age 64, 66% male) with ICH. Sixty-seven (45%) had a lobar hemorrhage, 60 (40%) had a deep hemorrhage, 19 (13%) had a cerebellar hemorrhage, and 3 (2%) had an intraventricular hemorrhage. For ICH in general, there was an increased risk within an hour after caffeine consumption (RR=2.5 [95% CI=1.8-3.6]), within an hour after coffee consumption alone (RR=4.8 [95% CI=3.3-6.9]), within an hour after lifting >25 kg (RR=6.6 [95% CI=2.2-19.9]), within an hour after minor head trauma (RR=10.1 [95% CI=1.7-60.2]), within an hour after sexual activity (RR=30.4 [95% CI=16.8-55.0]), within an hour after straining for defecation (RR=37.6 [95% CI=22.4-63.4]), and within an hour after vigorous exercise (RR=21.8 [95% CI=12.6-37.8]). Within 24 hours after flu-like disease or fever, the risk for ICH was also increased (RR=50.7 [95% CI=27.1-95.1]). Within an hour after Valsalva maneuvers, the RR for deep ICH was 3.5 (95% CI=1.7-6.9) and for lobar ICH the RR was 2.0 (95% CI=0.9-4.2). We identified one infection and several blood pressure related trigger factors for ICH onset, providing new insights into the pathophysiology of vessel rupture resulting in ICH.

Clinical features of intracerebral hemorrhage in patients with colorectal cancer and its underlying pathogenesis.

BACKGROUNDThe diagnosis of both cancer and intracerebral hemorrhage (ICH) in the same patient is not uncommon, but the clinical features and pathogenesis of patients with colorectal cancer (CRC) and ICH are still not well known.AIMTo investigate the clinical features and underlying pathogenesis of ICH in patients with CRC. METHODSA retrospective review of CRC patients complicated with ICH from three centers between January 2014 and December 2020 was performed. Clinical data such as laboratory examinations, imaging features, prognosis, and underlying pathogenesis were analyzed.RESULTSOf 16673 identified CRC patients, 20 (0.12%) suffered from ICH. There were 13 males and 7 females, with an average age (mean ± SD) of 68.45 ± 10.66 years. Fourteen patients (70%) had distant metastases and most patients (85%) showed an elevation of one or more cancer biomarkers. The hemorrhagic lesions in 13 patients (65%) were in the intracerebral lobe. Four patients were completely dependent and 4 died within 30 days after hemorrhage. Intratumoral hemorrhage (50%) and coagulopathy (50%) accounted for the majority of hemorrhages.CONCLUSIONPatients with ICH and CRC often have clinical features with lobar hemorrhage, distant metastases and poor prognosis. Intratumoral hemorrhage and coagulopathy are the main causes of ICH in patients with CRC.

Influence of hypertension classification on hypertensive intracerebral hemorrhage location.

The authors sought to explore whether hypertension classification was risk factor for lobar and non‐lobar hypertensive intracerebral hemorrhage (HICH) and the prognosis in patients with hematoma. This retrospective cohort study was conducted on HICH patients admitted at the First Affiliated Hospital of Soochow University. Observations with first‐ever intracerebral hemorrhage (ICH) were recruited. The authors divided the brain image into three groups according to the location of ICH to predict whether there were significant differences between lobar and non‐lobar ICH. A Mann‐Whitney U test was used and this retrospective trial also compared the operation and mortality rates. Our cohort included 209 patients (73.7% male; median age:60.5±16.7). The overall incidence of lobar HICH was less than non‐lobar HICH (24.4% vs. 68.4%), 7.2% cases of mixed HICH was included in this analysis. In a Mann‐Whitney U test analyze, it indicated that there were significant differences in hypertension classification between lobar and non‐lobar HICH (Z = ‐3.3, p<.05). And the percentage of hematoma in lobar areas with relatively slightly high blood pressure (BP) (high normal and grade 1 hypertension) accounts for 52.9% versus 30.1% in non‐lobar areas. The increasing trends of the prevalent rate of lobar ICH with BP rising were not remarkable. The non‐lobar HICH showed a sharper increase in the condition of grade 3 hypertension compared with lobar HICH. During the period of research, the fatality of lobar hemorrhage was 2.9% versus 7.7% (non‐lobar). Besides, the fatality incidence of HICH with relatively slightly high BP (high normal and grade 1 hypertension) was lower than poorly controlled hypertensive patients (grade 2 and grade 3 hypertension). (8.0% vs. 15.7%). The increase of hypertension classification will aggravate the occurrence of non‐lobar ICH and positively corrected with BP, but not in lobar areas. It is essential to understand the distinction influence of hypertension classification between lobar and non‐lobar ICH.

POCUS OBTAINED OPTIC NERVE SHEATH DIAMETER IN PATIENTS PRESENTING WITH INTRACEREBRAL HEMORRHAGE

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: Intracerebral hemorrhage (ICH) results in spontaneous bleeding into the brain. This accounts for 10-15% of all strokes in the United States and has poor outcomes due to death or disability. An ICH can result in increased intracranial pressure due to blood occupying extra space. Optic nerve ultrasonography has emerged as a quick noninvasive procedure to detect increased intracranial pressure. A question that has not been answered is whether there is a specific correlation between the size of hematoma in the brain and the optic nerve sheath diameter (ONSD). The optic nerve is wrapped by a sheath derived from the meninges. Cerebrospinal fluid (CSF) can transfer freely between the intracranial and intraorbital spaces. METHODS: 23 patients were recruited into this study. Each of these patient’s received the diagnosis of ICH and admitted to the neuro intensive care unit (NICU). Ultrasound of the optic nerve was performed using a Sonosite machine and the high frequency probe. The exam was performed upon admission to the NICU. Both eyes were scanned in two planes, longitudinal and transverse. Once the ONSD measurements were recorded, the volume of the ICH was noted on initial head CT. RESULTS: The average ICH score was 1.35 and the average APACHE IV score was 27.35. In addition, the average GCS on admission was 13. The most common cause of ICH was hypertension. The most common location for the ICH was lobar hemorrhage. 8 out of 23 patients had midline shift on their initial head CT. 4 out of 23 patients underwent some sort of surgical intervention. The smallest average combined ONSD was 4.43cm. The longest average combined ONSD was 8.03cm. The minimum hemorrhage volume was 0.20cm3. The maximum was 60.0cm3. A moderate, positive correlation was detected between average optic nerve size and hemorrhage volume (correlation=0.5262; p-value=0.0099). A weak positive correlation was detected between APACHE IV and average ONSD (correlation=0.2052; p-value=0.3476). A weak-moderate positive correlation was detected between ICH score and average ONSD. (correlation=0.3622; p-value=0.0895). Those who experienced a midline shift had significantly higher averaged ONSD compared to those who did not. CONCLUSIONS: This study determined there was a moderate positive correlation between the ONSD and volume of hematoma. From a pathophysiological standpoint, conditions like ICH lead to cerebral parenchyma swelling which is transmitted to the optic nerves through the meninges. Additionally, our study revealed a significant difference in average ONSD and midline shift observed on CT scan. In settings where no invasive monitoring is available, ONSD enlargement may be a useful technique for monitoring midline shift. CLINICAL IMPLICATIONS: There are already established prognostic indicators for ICH including an ICH volume of 60cm3or greater on initial CT along with a GCS of 9 or less which predict a 30 day mortality of 19%. ONSD has a role in prognostication. Growth of the hematoma in the first 24 hours is an independent predictor of mortality and poor outcome. Serial exams of a patients ONSD can be applied to indirectly monitor any expanding hematoma. Given the positive correlation between ONSD and hematoma volume, I would be interested in ONSD and the degree of disability scores such as the modified rankin scale. DISCLOSURES: No relevant relationships by Braden Anderson, source=Web Response No relevant relationships by Shekhar Ghamande, source=Web Response No relevant relationships by Sarita Kambhampati, source=Web Response No relevant relationships by Matthew Lohse, source=Web Response No relevant relationships by Alireza Nathani, source=Web Response

Cerebral Amyloid Angiopathy Pathology and Its Association With Amyloid-β PET Signal.

To determine the contribution of cerebral amyloid angiopathy (CAA) to Pittsburgh compound B (PiB)-PET tracer retention. Participants from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer's Disease Research Center with antemortem PiB-PET imaging for β-amyloid (Aβ) who later underwent autopsy were included in this study. Pathologic regional leptomeningeal, parenchymal, capillary CAA, and Aβ plaque burden were calculated from one hemisphere. Regional lobar amyloid standardized uptake value ratio (SUVR) on PET was calculated from the same hemisphere sampled at autopsy. Single- and multiple-predictor linear regression models were used to evaluate the relative contributions of pathologically determined regional CAA and Aβ plaques to antemortem PiB-PET SUVR. Forty-one participants (30 male, 11 female) with a mean (SD) age at death of 75.7 (10.6) years were included. Twenty-seven (66%) had high PiB signal with a mean (SD) of 2.3 (1.2) years from time of PET scan to death; 24 (59%) had a pathologic diagnosis of Alzheimer disease. On multivariate analysis, CAA was not associated with PiB-PET SUVR, while plaques remained associated with PiB-PET SUVR in all regions (all p < 0.05). In patients without frequent amyloid plaques, CAA was not associated with PiB-PET in any region. We did not find evidence that pathologically confirmed regional CAA burden contributes significantly to proximal antemortem regional PiB-PET signal, suggesting that amyloid PET imaging for measurement of cortical amyloid burden is unconfounded by CAA on a lobar level. Whether CAA burden contributes to PiB-PET signal in patients with severe CAA phenotypes, such as lobar hemorrhage, requires further investigation.

Clinical and radiological features of cerebral amyloid angiopathy-related inflammation.

ObjectivesWe want to report the clinical and radiological features of our cohort of patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-RI) according to the Boston Criteria and additionally to disclose some atypical clinical characteristics observed in some of them to provide more knowledge about this novel entity.MethodsWe describe 5 patients with probable CAA-RI according to a validation study of proposed criteria for the diagnosis of CAA-RI at University Hospital Josep Trueta of Girona. We consider some clinical characteristics which include the response to immunotherapy, CSF findings, and MRI features. The patient’s neurologic outcomes were assessed using the modified Rankin Scale (mRS).ResultsWe collected 5 patients admitted for probable CAA-RI. Most were women and the median age was 72 years. The median mRS score at the onset of disease was 1. Parietal lobes were most affected clinically as well as radiologically. Two patients had intracranial hemorrhage. Decreased levels of CSF amyloid beta 42 and 40 protein were observed. Corticosteroids were used in four patients and a remarkable improvement was observed in all of them.ConclusionsCAA-RI is a condition that predominantly affects parietal lobes according to our case series and this involvement seems to be directly related to a greater burden of microbleeds, cortical siderosis, WMH, and lobar hemorrhages on these lobes. Decreased levels of CSF amyloid beta protein plus increased total tau protein should be considered as part of the diagnostic criteria of CAA-RI. We recommend corticosteroids using, as they have been demonstrated to be very effective in managing CAA-RI.

Association of early glycemic change with short-term mortality in lobar and non-lobar intracerebral hemorrhage

The association between early glycemic change and short-term mortality in non-diabetic patients with acute intracerebral hemorrhage (ICH) is unclear. We retrospectively investigated non-diabetic patients with lobar (n = 262) and non-lobar ICH (n = 370). Each patient had a random serum glucose test on hospital admission and a fasting serum glucose test within the following 48 h. Hyperglycemia was defined as serum glucose ≥ 7.8 mmol/l. Four patterns were determined: no hyperglycemia (reference category), persistent hyperglycemia, delayed hyperglycemia, and decreasing hyperglycemia. Associations with 30-day mortality were estimated using Cox models adjusted for major features of ICH severity. Persistent hyperglycemia was associated with 30-day mortality in both lobar (HR 3.00; 95% CI 1.28–7.02) and non-lobar ICH (HR 4.95; 95% CI 2.20–11.09). In lobar ICH, 30-day mortality was also associated with delayed (HR 4.10; 95% CI 1.77–9.49) and decreasing hyperglycemia (HR 2.01, 95% CI 1.09–3.70). These findings were confirmed in Cox models using glycemic change (fasting minus random serum glucose) as a continuous variable. Our study shows that, in non-diabetic patients with ICH, early persistent hyperglycemia is an independent predictor of short-term mortality regardless of hematoma location. Moreover, in non-diabetic patients with lobar ICH, both a positive and a negative glycemic change are associated with short-term mortality.

Impact of Increased Hemoglobin on Spontaneous Intracerebral Hemorrhage

BackgroundStudies of the impact of increased hemoglobin on spontaneous intracerebral hemorrhage (ICH) are limited. The present study aimed to explore the effect of increased hemoglobin on ICH.MethodsA retrospective single-center study using medical records from a database processed by univariate and multivariate analyses was performed in the People’s Hospital of Tibet Autonomous Region in Lhasa, Tibet, China.ResultsThe mean hemoglobin level in 211 patients with ICH was 165.03 ± 34.12 g/l, and a median hematoma volume was 18.5 ml. Eighty-eight (41.7%) patients had large hematomas (supratentorial hematoma ≥ 30 ml; infratentorial hematoma ≥ 10 ml). No differences in ICH risk factors between the groups with different hemoglobin levels were detected. Increased hemoglobin was independently associated with large hematomas [odds ratio (OR) 1.013, P = 0.023]. Increased hemoglobin was independently associated with ICH with subarachnoid hemorrhage (OR 1.014, P = 0.016), which was more pronounced in men (OR 1.027, P = 0.002). Increased hemoglobin was independently associated with basal ganglia hemorrhage and lobar hemorrhage in men (OR 0.986, P = 0.022; OR 1.013, P = 0.044, respectively) but not in women (P > 0.1).ConclusionsIncreased hemoglobin was independently associated with large hemorrhage volume. Increased hemoglobin was independently associated with lobar hemorrhage in men and ICH with subarachnoid hemorrhage, which was more pronounced in men. Additional studies are needed to confirm our findings and explore potential mechanisms.

A Scarlet Enemy of the Brain – A Practical Approach to Diagnosis and Management of Cerebral Amyloid Angiopathy

We present two cases of elderly patients admitted with neurological dysfunction due to isolated focal cortical subarachnoid bleeding and intracerebral lobar haemorrhage, respectively. We discuss the distinguishing features in their clinical and radiological presentations which led to their diagnosis of probable cerebral amyloid angiopathy (CAA). In the hope of encouraging thoughtful learning, we have designed a series of case-based questions with accompanying answers to explain the investigative pathways and management strategies in suspected cases of CAA.

Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18F-THK5351 Positron Emission Tomography: A Case Report

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Arterial Spin Labeling Imaging Assessment of Cerebrovascular Reactivity in Hypertensive Small Vessel Disease.

Objective: Cerebrovascular reactivity (CVR) represents the phenomenon where cerebral vessels dilate or constrict in response to vasoactive stimuli. CVR impairment may contribute to brain injury due to cerebral small vessel disease (SVD). We aimed to determine the CVR in hypertensive intracerebral hemorrhage (ICH) and to identify its vascular dysfunction.Methods: A total of 21 patients with spontaneous hypertensive ICH (strictly deep or mixed deep and lobar hemorrhages, mean age 62.5 ± 11.3 years) and 10 control subjects (mean age 66.1 ± 6.0 years) were enrolled for CVR measurement at least 3 months after the symptomatic ICH event. Each participant underwent a brain MRI study, and CVR was calculated as the cerebral blood flow (CBF) reduction using arterial spin labeling (ASL) between baseline and 10 min after an intravenous dipyridamole injection (0.57 mg/kg). Traditional MRI markers for SVD were also evaluated, including cerebral microbleed, white matter hyperintensity, lacune, and MRI-visible enlarged perivascular space, which were used to determine the total small vessel disease score.Results: Compared to control subjects, hypertensive ICH patients showed reduced CVR in the basal ganglia (CBF reduction 22.4 ± 22.7% vs. 41.7 ± 18.3, p = 0.026), the frontal lobe (15.1 ± 11.9 vs. 26.6 ± 9.9, p = 0.013), and the temporal lobe (14.7 ± 11.1 vs. 26.2 ± 10.0, p = 0.010). These differences remained significant in multivariable models after adjusting for age and sex. Within ICH groups, the CBF reduction in the basal ganglia was significantly correlated with the total small vessel disease score (R = 0.58, p = 0.006), but not with individual MRI markers.Conclusion: Patients with advanced hypertensive SVD demonstrated impaired vasoconstriction after dipyridamole challenge in the basal ganglia and the frontal and temporal lobes. Our findings provide safe approaches for whole-brain CVR mapping in SVD and identify a potential physiological basis for vascular dysfunction in hypertensive SVD.

Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials.

The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n=84) were compared to STICH II all lobar cases (n=259) for volumetric analyses. All MISTIE III surgical patients (n=240) were compared to both STICH I and II (n=722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. End-of-treatment ICH volume ≤28.8mL in MISTIE III and ≤30.0mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180d (P=.01 and P=.003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180d with STICH I and II (P=.0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.

Acute intracerebral haemorrhage and diffusion-weighted imaging lesions: A meta-analysis.

Diffusion-weighted imaging lesions in intracerebral haemorrhage are related to a higher risk of recurrent intracerebral haemorrhage, cognitive damage, and mortality. However, it has been reported that the relationship between the risk of diffusion-weighted imaging lesions and intracerebral haemorrhage subtype or the risk factors for diffusion-weighted imaging lesions is variable. This meta-analysis was performed to evaluate this relationship. A systematic literature search up-to August 2020 was performed and 12 studies included 2815 subjects at the baseline with intracerebral haemorrhage. They were reporting relationships between the diffusion-weighted imaging lesions and intracerebral haemorrhage subtype or investigated the risk factors for diffusion-weighted imaging lesions. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of diffusion-weighted imaging lesions and intracerebral haemorrhage subtype and investigated the risk factors for diffusion-weighted imaging lesions using the dichotomous and continuous method with a random or fixed-effect model. Lobar intracerebral haemorrhage was not significantly related to a higher rate of diffusion-weighted imaging lesions (OR, 1.01; 95% CI, 0.75-1.36, P=.94) compared to the non-lobar intracerebral haemorrhage. Also, history of diabetes mellitus (OR, 1.15; 95% CI, 0.83-1.60, P=.39); history of smoking (OR, 0.95; 95% CI, 0.68-1.33, P=.76); history of hypercholesterolaemia (OR, 1.04; 95% CI, 0.73-1.48, P=.83) and history of ischaemic stroke (OR, 1.63; 95% CI, 0.57-4.66, P=.36) were not significantly related to higher rate of diffusion-weighted imaging lesions compared to no history of those factors. However, the history of hypertension was significantly related to a higher rate of diffusion-weighted imaging lesions (OR, 1.33; 95% CI, 1.04-1.70, P=.02) compared to no history of hypertension. Also, Subjects with diffusion-weighted imaging lesions had a greater decrease in systolic pressure in the acute phase of the intracerebral haemorrhage (OR, 10.23; 95% CI, 7.41-13.06, P<.001) compared to without diffusion-weighted imaging lesions. Based on this meta-analysis, the history of hypertension may have an independent risk relationship with a higher rate of diffusion-weighted imaging lesions. Also, subjects with diffusion-weighted imaging lesions had a greater decrease in systolic pressure in the acute phase of the intracerebral haemorrhage compared to those without diffusion-weighted imaging lesions. This relationship forces us to recommend that identification of diffusion-weighted imaging lesions might add appreciated evidence to evaluate the progression of the underlying micro-angiopathy especially in subjects with a history of hypertension. Though further studies are needed to define the mechanisms by which these lesions may lead to cognitive damage and stroke reappearance.

Cerebral Amyloid Angiopathy-Related Inflammation/Vasculitis

Cerebral amyloid angiopathy (CAA) is a disorder characterized by the deposition of amyloid in the leptomeningeal and cortical blood vessels. Sporadic amyloid β (Aβ)-type CAA is the most common form of CAA. Although CAA is a well-known cause for recurrent cerebral lobar hemorrhage, inflammation, and vasculitis, CAA-related inflammation/vasculitis (CAA-ri/vasculitis) induced by Aβ deposition on vessel walls is emerging as a treatable condition. The estimated total number of cases of and prevalence of CAA-ri/vasculitis in Japan were 170 and 0.13 per 100 000 population, respectively. Patients with CAA-ri/vasculitis show acute or subacute-onset of cognitive impairment, behavioral changes, and headache. Brain magnetic resonance imaging, showing asymmetrical white matter abnormalities and occasional meningeal enhancement, is a useful tool for the diagnosis of CAA-ri/vasculitis. Moreover, elevation of anti-Aβ antibodies and inflammatory markers in the cerebrospinal fluid can help in clinical diagnosis. Although several clinical diagnostic criteria have been proposed, neuropathological examination of a brain biopsy remains the gold standard for detecting severe Aβ deposition and vasculopathic changes with lymphocytic infiltrations and/or granulomatous vasculitis. No validated treatment regimen has been established to date. Nearly 80% patients with CAA-ri/vasculitis improved after immunosuppressant therapy with corticosteroid and/or cyclophosphamide. Early treatment is essential to prevent irreversible sequelae in the brain.

The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage

Introduction: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. Methods: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. Results: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59–79] years; National Institutes of Health Stroke Scale score 9 [17][3–17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19–1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19–2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44–0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01–1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55–0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73–1.14, p = 0.395). Conclusion: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.