The basis of treatment for brain injury focuses on the prevention of progressive secondary damage. Protein kinase C–delta (PKC–δ) is activated during ischemia and reperfusion and has been reported to be closely associated with inflammation and apoptosis. Astrocytes release matrix metalloproteinase–9 (MMP–9), which excites exces­sive inflammation by activating PKC–δ. Through this pathway, activa­tion of PKC–δ may excite inflammation in astrocytes and ultimately induce apoptosis. On the other hand, Rottlerin (C30H28O8), an inhibitor of PKC–δ, protects normal brain cells from damage and inflammation and promotes astrocyte proliferation. In this study, we tested whether secondary brain injury can be prevented by suppress­ing PKC–δ and excessive inflammation using Rottlerin.

A rat controlled cortical impact (CCI) model was used as the brain contusion model. Immediately after the injury, an intraperitoneal os­mot­ic pump was placed, and systemic administration of the drug was performed. Rats were divided into three groups: Rottlerin dissolved in dimethyl sulfoxide (DMSO) (Rottlerin–treated group), saline and DMSO as a control (CCI group), and no treatment as a normal control group (Sham group). General tissue staining and immunostaining for PKC–δ were performed, and Tunel staining was performed to as­sess apoptosis. Western blotting was performed to quantify PKC–δ ex­pres­sion, and real–time quantitative reverse transcriptional polymerase chain reaction (Real–time qRT–PCR) was performed to evaluate PKC–δ and MMP–9 expression. While Tunel staining showed many Tunel–positive cells in the CCI group, but not in the Sham group, Tunel–positive cells were observed in the Rottlerin group, but in smaller amounts than in the CCI group. Similarly, in immunostaining with anti–PKC–δ antibody, PKC–δ expression was observed around the brain contusion in the CCI group, whereas PKC–δ expression was only observed under the contusion in the Rottlerin group. Western blotting with PKC–δ antibody showed a significant increase in PKC–δ expression in the CCI group, while PKC–δ expression was sup­pressed in the Rottlerin group and was significantly lower than in the Sham group. Real time qRT–PCR showed a trend toward suppression of PKC–δ expression, although the difference was not significant. However, there was no significant difference in MMP–9 expression, although there was a trend toward suppression.

This study showed that systemic administration of the PKC–δ inhibi­tor rottlerin suppresses PKC–δ. However, it did not suppress MMP–9 activity, possibly due to the existence of a multifactorial pathway of activity for MMP–9. These suggest that Rottlerin may be effective against PKC–δ–related secondary brain injury.

Many elderly patients take oral anti–thrombotic medications for sec­ondary prevention of thromboembolic events; however, oral anti–thrombotics may worsen intracranial hemorrhage due to head trauma. Bleeding that occurs in patients taking anticoagulants can be neutral­ized with a prothrombin complex concentrate (PCC) in the case of warfarin or with idarucizumab in the case of dabigatran, a direct–acting oral anticoagulant. In addition, andexanet alfa has recently be­come available to neutralize factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). We reviewed a case of traumatic intra­cranial hemorrhage in a patient taking Xa inhibitors and discuss the efficacy of this drug.

Purpose: Traumatic brain injury (TBI) is one of a leading cause of death and disability worldwide. It has been known that the survival and functional outcomes are significantly poor in the elderly population. Several criteria have been described to predict the mortality of patients with severe head injury, but only few have been studied on mild injury. We encounter high–functioning elderly patients with mild head injuries, whose functional outcomes gradually worsen over time during hospitalization. There is a need to develop a geriatric specific prognostic models of mild head injury for better treatment, rehabilitation and prevention. We aim to develop a simple scoring system to predict the functional outcomes of elderly with mild head injury.

Subjects and Methods: Retrospective study of patients 65 years or older with mild head injury for 2 consecutive years from September 2019 to September 2021. We evaluated age, sex, past histories (DM, HLP, heart diseases and CKD), GCS on admission, CT findings (contusion, SAH, ASDH and AEDH) and use of antithrombotic drugs. We generated a novel score to predict the functional outcomes of these patients using the beta coefficient. The score was validated in an internal Cohort.

Results: There were 72 patients in the development cohort and 21 patients in the validation cohort. GCS, ASDH, contusion and DM were identified as predictors of functional outcomes and were in­cluded for generating the GACD score. A patient with GACD score > 3 may have high risk of talk–and–deteriorate during hospitaliza­tion. The positive and negative predictive value for our score was 67% and 87%, respectively.

Conclusion: We propose a new and easy–to–use scoring system to predict the functional outcomes of elderly with mild head injury.

Introduction: Chronic subdural hematoma (CSDH) is commonly seen in elderly individuals. In this report, we present a case of a 25–year–old soccer player with arachnoid cyst who developed CSDH and provide a literature review.

Case: A 25–year–old soccer player was diagnosed with asymptomatic arachnoid cyst since childhood. The patient had occasionally hit the ball while playing soccer, but had no restriction on heading the ball. The patient suffered from headache and vomiting after repeated heading practice. He visited to referring hospital two weeks after the onset of symptoms. Head CT showed left middle fossa arachnoid cyst without hemorrhage and CSDH. Although it became a follow–up observation, his symptoms gradually deteriorated, and he revisited the hospital. Brain MRI revealed CSDH characterized by low signal intensity on T1–weighted and FLAIR images, and high signal intensity on T2–weighted images, located at the left subdural and intracranial compartments. The patient was diagnosed with left CSDH and transferred to our hospital. He underwent emergent burr hole drainage surgery, resulting in a favorable outcome.

Discussion: The presence of arachnoid cyst has been reported as a con­tributing factor to CSDH in young individuals. Soccer players have potential risks of chronic head impacts through repeated heading, highlighting the importance of awareness and caution. Treatment options for cases involving arachnoid cysts complicated by chronic subdural hematoma include burr hole surgery or craniotomy, but there are no established treatment guidelines. When the arachnoid cyst wall is ruptured and continuous with the hematoma cavity, less invasive burr hole evacuation under local anesthesia is considered preferable. Once chronic subdural hematoma occurs, it can have im­plications for academic and occupational activities. Arachnoid cysts can contribute to the development of CSDH, emphasizing the need to provide information and raise awareness among soccer players. This case suggests that the occurrence of a chronic subdural hema­toma was triggered by the practice of repeated heading a ball strongly kicked.

Conclusion: Soccer players with arachnoid cysts should be prohibited from repeated heading practice.

The surgical treatment of chronic subdural hematoma (CSDH) is generally performed by irrigation and drainage via burr hole. Recently, endoscopic procedure has also been used for neurosurgery due to its minimally invasiveness and advantages. In this report, we describe the usefulness of neuroendoscopic procedure for CSDH. Of the 309 CSDH cases with 382 sides were operated on between April 2018 and March 2022. Nine sides of these patient underwent neuroendoscpic procedure. The mean age was 84.4 years, 6 cases were male. The left side were 6, and the right side were 3 cases. There were 4 recurrent cases. We discussed the reason for neuro­endoscopic use, intraoperative findings, and postoperative course. Neuroendoscope was introduced because of the preoperative evalua­tion of radiological examinations, which showed initial treatment in 2 cases, and that was considered difficult to irrigate intraoperatively in 1 case. Patients who were assessed as difficult to irrigate pre­operatively based on radiological images continued to show organiz­ing hematoma, septal formation, and other findings intraoperatively. Operation time ranged from 49–115 minutes (median 65 min). The hospital dayranged 9–55 days (median 15 days). No cases of recurrent CSDH were observed after neuroendoscopic procedure during follow up period (30–133 days). The outcome was that 7 patients were discharged home or to their original facility after improving to the state before the onset of the disease, and 2 patients were transferred to a rehabilitation center. Two patients had a decrease in the modified Rankin Scale from the onset, 1 patient had postoperative pneumonia and 1 patient had pleural effusion. Although the number of cases in which neuroendoscopic procedure was introduced in the surgical treatment of CSDH is not large, 9 of 382 (2.4%), all of the cases re­viewed in this study had features that could not be treated by conventional irrigation and drainage, suggesting that neuroendoscopic pro­cedure would be useful.

Traumatic middle meningeal arteriovenous fistula (TMMAVF) is rare, moreover that without skull fracture has been reported in a few cases before. We report a case of TMMAVF without skull fracture at the contralateral side of the head injury. A young woman was transported to our hospital with high–energy trauma. CT image showed skull frac­ture and epidural hematoma on the left side, and subdural hematoma on the right side. Two days after the injury, the MRI showed right tem­poral edema and dilated MMA on the contralateral side of the skull fracture. The CT angiography (3DCTA) showed a poorly developed the Superficial middle cerebral vein (SMCV) and the vein of Trolard, and the TMMAVF. The MRI was performed again 8th days after the injury and the TMMAVF and temporal edema did not dis­appear. The Coil embolization was performed and the TMMAVF was successfully obliterated. After that, symptoms and temporal edema disappeared soon. In the case brain edema was found at the contra­lateral side of head injury, the TMMAVF should be considered using 3DCTA and MRA.

We report a case of delayed basilar artery vasospasm after blunt traumat­ic brain injury. A 40–year–old man presented with dysarthria and right sensory disturbance 34 days after a head injury sustained in a traffic accident while riding a bicycle. No lesion was observed on computed tomo­graphy or magnetic resonance imaging. However magnetic resonance angiography revealed basilar artery stenosis. His symptoms and basilar artery stenosis improved after resting and conservative treatment, although there were slight ischemic changes in the pons and left cerebel­lar hemisphere on diffuse weighted images on magnetic resonance imag­ing. He was discharged 18 days after the admission, as his symptoms had diminished and basilar artery stenosis recovered. No recurrence of symptoms or basilar artery stenosis was noted after the discharge. Cerebral vasospasms are relatively rare after blunt traumatic brain injury, but they may cause cerebral infarction. Therefore, patients who have neurological symptoms after head injury should be carefully examined even if their symptoms are mild.

In the case of intracranial subarachnoid hemorrhage in traffic trauma, the distinction between ruptured aneurysm and traumatic hemorrhage is problematic. In this case, a woman who was transported to the hospital with traffic trauma died due to multiple traumas. Before cardiopulmonary arrest, CT and CTA showed findings suspicious of diffuse subarachnoid hemorrhage and basilar artery aneurysm, so a forensic autopsy was per­formed. The results were negative for aneurysm or vascular malformation, and the intracranial subarachnoid hemorrhage was diagnosed due to trauma.

Background: Traumatic brain injury (TBI) is known to induce reactive astrocytes in the traumatized brain, which plays con­tra­dictory role in plasticity and reconstruction after TBI. The positron emission tomography (PET) radioligand ¹⁸F–THK5351 is used to evaluate monoamine oxidase B expression in the re­active astrocytes. This is a first report to evaluate the spatial and tem­poral changes in reactive astrocytes with ¹⁸F–THK5351 PET in the traumatized brain for more than 2 years after a severe TBI.

Case presentation: A teenager suffering from a severe TBI with multiple brain contusions underwent ¹⁸F–THK5351 PET ⁄ CT in the recovery (48 days), chronic (286 days), and maintenance (810 days) phases after the injury. The first PET scan showed intense ¹⁸F–THK5351 uptake in and around the brain contusions. The second PET scan showed reduced uptake of ¹⁸F–THK5351 at the original sites of the brain contusions and sig­nificantly increased uptakes in the deep white matter and basal ganglia surrounding the brain contusions and the corpus cal­losum. In the third PET scan, increased ¹⁸F–THK5351 uptakes in the deep white matter and basal ganglia surrounding the brain contusions were reduced but continued, and increased ¹⁸F–THK5351 uptake in the corpus callosum persisted to the same degree. The patient exhibited slowly but sustained im­provement of neuropsychological impairments during the ob­servation period.

Conclusions: There were evident temporal and spatial changes in ¹⁸F–THK5351 uptake in the traumatized brain for more than 2 years after TBI. Sustained expression of reactive astrocytes may be related to neuronal recovery, but not neuronal damage in this patient. The degree and distribution of reactive astro­cytes detected by ¹⁸F–THK5351 PET can be useful in assessing pathophysiology and predicting prognosis in TBI patients.

Background: Cognitive dysfunction associated with mild traumatic brain injury can cause difficulties in working or attend­ing school due to disorders in memory, attention, emotional, and social behavior. However, “traumatic cognitive dysfunc­tion” is difficult to definitively diagnose in mild head trauma patients without obvious intracranial lesions identifiable on CT or MRI. Consequently, such patients may not be able to receive administrative welfare benefits, and find that recogni­tion of the residual disability is extremely difficult to obtain. Therefore, evaluation of the actual situation to establish novel diagnostic and support systems is urgently needed. Here we report a nationwide survey conducted using a questionnaire format intended to assess the actual situations of patients with cognitive dysfunction caused by mild head trauma.

First survey: A questionnaire survey was sent by mail to 102 cog­nitive dysfunction support facilities for return by mail or fax of the first survey form between August 10 and September 30, 2017. A total of 50 questionnaires were returned with a response rate of 49%. A total of 277 patients were reported with definitive diagnoses of cognitive dysfunction caused by head trauma, including 36 patients with negative imaging findings, between April 1, 2016 and March 31, 2017.

Second survey: A second questionnaire survey investigated patient background, clinical data, radiological findings, medical treatment, and neuropsychological data for the 36 patients identified by the first survey.

Results: Thirteen patients (male ⁄ female = 11 ⁄ 2) had negative imaging findings associated with cognitive dysfunction. Cause of injury was traffic accident in 11 and falling in 2. Posttraumatic amnesia occurred in 6 (46.2%), with duration of less than 6 hours in 2, less than 24 hours in 2, from 72 hours to 1 week in 1, and unknown in 1. All 13 patients had no intracranial ab­normal findings on head CT within 3 days. Head MRI was per­formed in 10 of these 13 patients, and also showed no abnormalities. Multiplex neuropsychological tests revealed memory dysfunction and attention disorder.

Conclusions: The present findings suggest that cognitive dys­function may occur with negative head imaging findings, despite the limitations of the questionnaire survey. The study clarifies the necessity to establish a system for promoting the standardi­zation and optimization of diagnostic imaging and neuropsychological examination. We hope that this study will promote methods to establish definitive diagnosis, rehabilitation, and daily lifestyle support for patients suffering from cognitive dysfunction caused by mild head trauma.