Melatonin Ameliorates Hemorrhagic Transformation via Suppression of ROS-Induced NLRP3 Activation after Cerebral Ischemia in Hyperglycemic Rats.

Melatonin is a strong antioxidant which beneficially protects against middle cerebral artery occlusion (MCAO) followed by hemorrhagic transformation in rats; protection includes the reduction of neurological deficits, infarction, and hematoma volume. The molecular mechanisms underlying these neuroprotective effects in the MCAO model have not been clearly identified. This study examined the influence and involved mechanism of melatonin on inflammation in hemorrhagic transformation following hyperglycemia MCAO rat model. Compared with the MCAO group, MCAO+dextrose (DX) group showed worse neurological function and higher infarction and hematoma volume. Interestingly, the protein expression of Nod-like receptor protein 3 (NLRP3) inflammasome increased in the MCAO+DX group compared with the MCAO group, which indicated that NLRP3 inflammasome may be involved in the DX-induced hemorrhagic transformation following MCAO. Then, three dosages of melatonin were intraperitoneally injected 2 h after MCAO induction. Melatonin treatment attenuated inflammatory response by inhibiting the reactive oxygen species (ROS) and NLRP3 inflammasome, alleviating neuronal injury, and reducing infarction and hematoma volume, finally improving neurological score. Melatonin also repressed cortical levels of proinflammatory cytokine IL-1ß, which were increased 24 h after hyperglycemia MCAO. In order to identify the potential mechanisms, we further revealed that nigericin administration reversed the neuroprotective effect of melatonin by promoting NLRP3 inflammasome activation. In general, this present study reveals that melatonin prevents the occurrence of hyperglycemia-enhanced hemorrhagic transformation, and this effect might be beneficial to attenuate neurological dysfunction via suppressing the inflammatory response after MCAO which possibly associated with the inhibition of the ROS/NLRP3 inflammasome pathway.

Pial arteriovenous fistula with appearance of hemorrhagic tumor: A case report.

INTRODUCTION: Pial arteriovenous fistula (PAVF) is a rare intracranial vascular disease, and its presentation with a huge tumor-resembling thrombus is rarer. PATIENT CONCERNS: A 38-year-old female patient presented with a sudden left-side motor disorder and loss of consciousness. The patient was otherwise in good health and had no history of hypertension or diabetes. During the physical examination, she appeared lethargic and manifested left limb paralysis with level zero muscle strength and a positive pathological reflex. DIAGNOSES: Because imaging failed to rule out a tumor stroke, an intracranial lesion resection was performed immediately. Because the lesion was considered to be a vascular structure, digital subtraction angiography was undertaken before the surgery, and PAVF was diagnosed. INTERVENTIONS: Endovascular embolization was conducted, followed by PAVF and hematoma resection. OUTCOMES: At the 3-month follow up, her left limb muscle strength was level 4, and she could live on her own (Modified Rankin Scale score = 2). CONCLUSIONS: It is noteworthy that PAVF with a large thrombus may appear as a tumor in the initial diagnosis, and therefore it is necessary to perform an intracranial vascular examination in patients with tumor stroke symptoms.

Lumbar Subdural Hematoma Detected After Surgical Treatment of Chronic Intracranial Subdural Hematoma.

BACKGROUND: Spinal subdural hematoma (SSDH), which can cause lower back pain, leg pain, and leg weakness, is rare and will usually be associated with a bleeding tendency, trauma, spinal vascular malformation, intraspinal tumor, or iatrogenic invasion. Only a few cases of SSDH after intracranial chronic subdural hematoma (CSDH) have been reported. We report a case of lumbar SSDH in the absence of predisposing factors after reoperation for recurrent intracranial CSDH, which improved with conservative treatment. CASE DESCRIPTION: Approximately 1 month after falling, a 63-year-old woman was experiencing left hemiparesis and impaired orientation that was diagnosed as right intracranial CSDH using computed tomography. Surgical treatment of the CSDH led to immediate improvement of her symptoms. On postoperative day 29, the right CSDH had recurred with left hemiparesis, and successful reoperation relieved the symptoms within a few hours postoperatively. However, 1 day after the second operation, very small acute subdural hematomas in regions along the left tentorium cerebelli and left falx cerebri were found on computed tomography. On day 31, she complained of sitting-induced bilateral radiating lower limb pain. Magnetic resonance imaging on day 34 showed an acute SSDH at the L4-L5 level and a sacral perineural cyst filled with hematoma, although her radiating pain was showing improvement. She was treated conservatively and was discharged without symptoms on day 44. CONCLUSIONS: Although SSDH is rare, it is important for neurosurgeons and physicians to consider the possibility of a SSDH when lower limb pain or paresis occurs after procedures that will result in rapid intracranial pressure alterations such as drainage of an intracranial CSDH.

Fatal Acute Intracranial Subdural Hematoma After Spinal Anesthesia for Cesarean Delivery: Case Report and Review of the Literature.

The authors report on the autopsy case of a 40-year-old primigravida without either coagulation disorders or anticoagulant/antiplatelet therapy, who developed a fatal intracranial subdural hematoma after spinal anesthesia (SA) for elective cesarean delivery for tocophobia.Intracranial subdural hematoma is the most dreaded complication of SA and is often misdiagnosed with postdural puncture headache.In this article, the authors discuss pathophysiological mechanisms and risk factors for the development of an intracranial subdural hematoma after SA and review the pertinent literature.

Aspirin treatment does not increase microhemorrhage size in young or aged mice.

Microhemorrhages are common in the aging brain and are thought to contribute to cognitive decline and the development of neurodegenerative diseases, such as Alzheimer's disease. Chronic aspirin therapy is widespread in older individuals and decreases the risk of coronary artery occlusions and stroke. There remains a concern that such aspirin usage may prolong bleeding after a vessel rupture in the brain, leading to larger bleeds that cause more damage to the surrounding tissue. Here, we aimed to understand the influence of aspirin usage on the size of cortical microhemorrhages and explored the impact of age. We used femtosecond laser ablation to rupture arterioles in the cortex of both young (2-5 months old) and aged (18-29 months old) mice dosed on aspirin in their drinking water and measured the extent of penetration of both red blood cells and blood plasma into the surrounding tissue. We found no difference in microhemorrhage size for both young and aged mice dosed on aspirin, as compared to controls (hematoma diameter = 104 +/- 39 (97 +/- 38) µm in controls and 109 +/- 25 (101 +/- 28) µm in aspirin-treated young (aged) mice; mean +/- SD). In contrast, young mice treated with intravenous heparin had an increased hematoma diameter of 136 +/- 44 µm. These data suggest that aspirin does not increase the size of microhemorrhages, supporting the safety of aspirin usage.

Development of a Model of Hemispheric Hypodensity ("Big Black Brain").

Subdural hematoma (SDH) is the most common finding after abusive head trauma (AHT). Hemispheric hypodensity (HH) is a radiological indicator of severe brain damage that encompasses multiple vascular territories, and may develop in the hemisphere(s) underlying the SDH. In some instances where the SDH is predominantly unilateral, the widespread damage is unilateral underlying the SDH. To date, no animal model has successfully replicated this pattern of injury. We combined escalating severities of the injuries and insults commonly associated with HH including SDH, impact, mass effect, seizures, apnea, and hypoventilation to create an experimental model of HH in piglets aged 1 week (comparable to human infants) to 1 month (comparable to human toddlers). Unilateral HH evolved over 24 h when kainic acid was applied ipsilateral to the SDH to induce seizures. Pathological examination revealed a hypoxic-ischemic injury-type pattern with vasogenic edema through much of the cortical ribbon with relative sparing of deep gray matter. The percentage of the hemisphere that was damaged was greater on the ipsilateral versus contralateral side and was positively correlated with SDH area and estimated seizure duration. Further studies are needed to parse out the pathophysiology of this injury and to determine if multiple injuries and insults act synergistically to induce a metabolic mismatch or if the mechanism of trauma induces severe seizures that drive this distinctive pattern of injury.

Intracranial subdural hematomas with elevated rivaroxaban concentration and subsequently detected spinal subdural hematoma: A case report.

A 79-year-old lean man with a height of 157cm and weight of 42kg (body mass index, 17.2kg/m(2)) receiving rivaroxaban developed an intracranial subdural hematoma and was treated conservatively. Because he had a reduced creatinine clearance of 44mL/min, his dosage of rivaroxaban was reduced from 15 to 10mg daily according to official Japanese prescribing information. However, he developed bilateral intracranial subdural hematomas 2weeks later. Plasma rivaroxaban concentration on anti-factor Xa chromogenic assay was elevated at 301ng/mL, suggesting excessive accumulation. He underwent burr hole drainage and resumed anticoagulation with warfarin. Subsequently, he developed a lumbosacral hematoma. He was treated conservatively and discharged without neurological sequelae. The main cause of the increased concentration of rivaroxaban was believed to be his older age and low body weight. The etiology of the spinal hematoma was suspected to be the migration of intracranial hematoma to the spinal subdural space.

A calvarial acute subdural hematoma migrating into the spinal canal in a young male.

It is not common for an acute subdural hematoma (SDH) in the supratentorial region to show rapid resolution or migration during the clinical course. In this report, we present a rare case where the SDH in the supratentorial region was observed to rapidly migrate into the lumbar spinal canal, leading to severe radiculopathy. A 20-year-old male patient was admitted to the emergency department with severe headache after head trauma. The patient's overall condition was good, whereas his Glasgow Coma Scale score was 15 and blood pressure was normal. He had vomited 3 times after the onset of pain. No stiff neck was found, and the computed tomography showed an ASDH over the outer layer of the right hemisphere, causing a 7- to 8-mm shift. During the follow-up, the headache regressed and eventually resolved after 12 hours; however, another severe pain occurred in the lumbar region and in both legs. The pain worsened over time, progressing to sciatica in both legs. Acute SDH associated with a minor head trauma may migrate from the supratentorial compartment into the spinal canal by the help of elastic cerebral tissues in young adults and children.

[Photodocumentation during autopsy]. / Fotodokumentation im Obduktionssaal--Untersuchungen zur Hintergrundgestaltung.

Photography during autopsy is an important part of forensic imaging and essential for the documentation of autopsy findings. A forensic photograph mainly serves the purpose of providing evidence and should be authentic. But aesthetic artwork may improve both the attractiveness and acceptance of autopsies and thus help to increase the autopsy rate. Different materials were compared to each other as photographic backdrop, particularly with regard to reflection and contrast, stability of exposure measurement and monitoring of colour fidelity. The photofoil 9010 Dove Grey proved to be a material of outstanding quality. In practical application, the foil was scratch-resistant and easy to clean. Furthermore, backdrop boards with a gap, e.g. for head and neck, allow special perspectives without a distracting background.

Influences of developmental age on the resolution of diffuse traumatic intracranial hemorrhage and axonal injury.

This study investigated the age-dependent injury response of diffuse traumatic axonal injury (TAI) and regional subdural and subarachnoid intracranial hemorrhage (ICH) in two pediatric age groups using a porcine head injury model. Fifty-five 5-day-old and 40 four-week-old piglets-which developmentally correspond to infants and toddlers, respectively-underwent either a sham injury or a single rapid non-impact rotational injury in the sagittal plane and were grouped by post-TBI survival time (sham, 3-8 h, one day, 3-4 days, and 5-6 days). Both age groups exhibited similar initial levels of ICH and a significant reduction of ICH over time (p<0.0001). However, ICH took longer to resolve in the five-day-old age group. At 5-6 days post-injury, ICH in the cerebrum had returned to sham levels in the four-week-old piglets, while the five-day-olds still had significantly elevated cerebral ICH (p=0.012). Both ages also exhibited similar resolution of axonal injury with a peak in TAI at one day post-injury (p<0.03) and significantly elevated levels even at 5-6 days after the injury (p<0.008), which suggests a window of vulnerability to a second insult at one day post-injury that may extend for a prolonged period of time. However, five-day-old piglets had significantly more TAI than four-week-olds overall (p=0.016), which presents some evidence for an increased vulnerability to brain injury in this age group. These results provide insight into an optimal window for clinical intervention, the period of increased susceptibility to a second injury, and an age dependency in brain injury tolerance within the pediatric population.

Prospective assessment of concomitant lumbar and chronic subdural hematoma: is migration from the intracranial space involved in their manifestation?

OBJECT: Spinal subdural hematomas (SDHs) are rare and some are concomitant with intracranial SDH. Their pathogenesis and etiology remain to be elucidated although their migration from the intracranial space has been suggested. The authors postulated that if migration plays a major role, patients with intracranial SDH may harbor asymptomatic lumbar SDH. The authors performed a prospective study on the incidence of spinal SDH in patients with intracranial SDH to determine whether migration is a key factor in their concomitance. METHODS: The authors evaluated lumbar MR images obtained in 168 patients (125 males, 43 females, mean age 75.6 years) with intracranial chronic SDH to identify cases of concomitant lumbar SDH. In all cases, the lumbar MRI studies were performed within the 1st week after surgical irrigation of the intracranial SDH. RESULTS: Of the 168 patients, 2 (1.2%) harbored a concomitant lumbar SDH; both had a history of trauma to both the head and the hip and/or lumbar area. One was an 83-year-old man with prostate cancer and myelodysplastic syndrome who suffered trauma to his head and lumbar area in a fall from his bed. The other was a 70-year-old man who had hit his head and lumbar area in a fall. Neither patient manifested neurological deficits and their hematomas disappeared under observation. None of the patients with concomitant lumbar SDH had sustained head trauma only, indicating that trauma to the hip or lumbar region is significantly related to the concomitance of SDH (p < 0.05). CONCLUSIONS: As the incidence of concomitant lumbar and intracranial chronic SDH is rare and both patients in this study had sustained a direct impact to the head and hips, the authors suggest that the major mechanism underlying their concomitant SDH was double trauma. Another possible explanation is hemorrhagic diathesis and low CSF syndrome.

Neuropathologic analysis of hematomas evacuated from patients with spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a devastating cause of morbidity and mortality. Intraparenchymal hematomas are often surgically evacuated. This generates fragments of perihematoma brain tissue that may elucidate their etiology. The goal of this study is to analyze the value of these specimens in providing a possible etiology for spontaneous ICH as well as the utility of using immunohistochemical markers to identify amyloid angiopathy. Surgically resected hematomas from 20 individuals with spontaneous ICH were examined with light microscopy. Hemorrhage locations included 11 lobar and nine basal ganglia hemorrhages. Aß immunohistochemistry and Congo red stains were used to confirm the presence of amyloid angiopathy, when this was suspected. Evidence of cerebral amyloid angiopathy (CAA) was observed in eight of the 20 specimens, each of which came from lobar locations. Immunohistochemistry confirmed CAA in the brain fragments from these eight individuals. Patients with immunohistochemically confirmed CAA were older than patients without CAA, and more likely to have lobar hemorrhages (OR 3.0 and 3.7, respectively). Evidence of CAA was not found in any of the basal ganglia specimens. One specimen showed evidence of CAA-associated angiitis, with formation of a microaneurysm in an inflamed segment of a CAA-affected arteriole, surrounded by acute hemorrhage. In another specimen, Aß immunohistochemistry showed the presence of senile plaques suggesting concomitant Alzheimer's disease (AD) changes. Surgically evacuated hematomas from patients with spontaneous ICH should be carefully examined, paying special attention to any fragments of included brain parenchyma. These fragments can provide evidence of the etiology of the hemorrhage. Markers such as Aß 1-40 can help to identify underlying CAA, and should be utilized when microangiopathy is suspected. Given the association of (Aß) CAA with AD, careful examination of entrapped brain fragments may also provide evidence of AD in a given patient.

Traumatic peritentorial subdural hematomas: a study of 32 cases.

AIM: This study aimed to investigate the clinicoradiological features in patients with traumatic peritentorial subdural hematomas (SDHs). MATERIAL AND METHODS: We retrospectively reviewed the clinical and radiological findings, management criteria, and outcomes in 32 patients with peritentorial SDHs. The outcomes were classified as favorable (good recovery or moderate disability) or poor (severe disability, vegetative state, or death). RESULTS: Of the 32 patients, 19 were male and 13 were female. The patients' ages ranged from 10-92 years (mean age, 60.9 years). Coagulopathies were observed in 23 patients. Twenty-four patients presented with associated intracranial lesions. Eighteen patients had favorable outcomes and 14 had poor outcomes. All patients were treated conservatively. The presence of coagulopathy (p = 0.024) and presence of convexity SDH (p = 0.008) correlated with the outcome. CONCLUSION: The patients with traumatic peritentorial SDHs were predominantly male and relatively elderly, and had a high incidence of coagulopathy, associated intracranial lesions (especially falx SDHs), a high rate of impact in the occipital or frontal regions, and a low incidence of skull fractures. The factors that were correlated with outcome in patients receiving conservative therapy were the presence of coagulopathy and the presence of convexity SDH.