Recent clinical trials and experimental studies have demonstrated that oxygen free radicals and reactive oxygen species (ROS) have important roles of various neuronal conditions. Neurotrauma is also related to oxidative stress strongly. There are some biomarkers to evaluate ROS generation. On the other hand, the kinetics of free radical in itself has not been evaluated in clinical setting because of difficulty in measurement. Recently, we developed novel free radical (alkoxyl radical: RO･) monitoring using electron spin resonance (ESR) method. We evaluated blood RO･ levels in patients with neurotrauma and other conditions. RO･ levels in patients with neurotrauma were higher than that of healthy volunteers. We also proved that edaravone administration (30 mg i.v) and brain hypothermia therapy suppressed RO･ levels in patients with neurotrauma.

In conclusion, direct free radical monitoring by ESR method is useful to evaluate oxidative stress in patients with neurotrauma in clinical setting.

We described pathophysiology and treatment of experimental acute subdural hematoma (simple type). The hematoma was induced by injecting nonheparinized autologous venous blood into the subdural space over a period of 7 minutes (Miller model). Glucose hepermetabolism was observed in bilateral hippocampus two hours after induction of hematoma. This model produced ischemic cortical damage under hematoma and peri-ischemic hypermetabolism for glucose two hours after induction of hematoma. These hypermetabolism for glucose seen in peri-ischemic cortex and bilateral hippocampus was disappeared four hours after induction of hematoma. Inert silicone mass (same volume to blood) injecting into subdural space produced smaller ischemic cortical volume and no hypermetabolism areas. These results suggest that diffusible substance from the clotted blood may be responsible for these changes. Changes of intracellular second messenger system were also observed in peri-ischmeic area. Transient hypermetabolism accords with an excitotoxic process, which may amplify brain damage after acute subdural hematoma.

Intensive care (hypothermia, increased inspired oxygen fraction) and drugs (glutamate antagonist, free radical scavenger, et al.) were tested to evaluate neuroprotective effect by measuring the degree of ischemic brain damage, brain edema, brain extracellular fluid parameters (glucose, lactate, et al.).

Introduction: Cognitive dysfunction due to cerebral trauma is a serious problem for patients and also society, since young people often suffer head injuries and the dysfunction lingers for the rest of their lives. Recently, this dysfunction has been gradually recognized, and methodologies for rehabilitation have been studied. To cope with this dysfunction, organic interdisciplinary cooperation is necessary —brain surgeons for acute cognitive dysfunction; rehabilitation departments, neurological medicine departments, and clinical psychotherapists for rehabilitation and counseling; and local governments for social rehabilitation. However, such cooperation in each local region is woefully insufficient in Japan. In this circumstance, the Tama District municipality established Tama Society for Research into Cognitive dysfunction in January 2006, with the purpose of developing a local system for enabling patients with cognitive dysfunction to receive better treatment and care, by preparing networks and intra-government cooperation for diagnosis, treatment, physical and social rehabilitation.

Society members: Hospitals that treat acute head injuries, rehabilitation support centers, rehabilitation facilities, and government officials in charge of public welfare inside the medical care zones in Tama District

Activities: A lecture meeting was held twice, to educate medical care and public welfare personnel about cognitive dysfunction. Furthermore, the society members investigated medical care and public welfare facilities related to cognitive dysfunction in Tama District, produced a local map indicating the functions of each facility, and reported them at the third lecture meeting. Based on this information, each municipality is promoting the development of systems for coordinating diagnosis, treatment, and social rehabilitation. Such an integrated cooperative system is expected to accelerate the functional recovery of patients with cognitive dysfunction, whose disorder is often missed at the acute phase and who cannot have a chance to receive rehabilitation and tend to be isolated, and to be diffused as a model system throughout Japan.

The present study used short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI) to evaluate motor cortex excitability in 16 diffuse axonal injury (DAI) patients with memory impairment and compared the data with those of 16 healthy controls. SAI was reduced in patients compared with controls (92±12 vs. 39±11% of the test size; p<0.0001, unpaired t-test). DAI patients tended to have a high resting motor threshold and less pronounced SICI and ICF than controls, but these differences were not significant. A single oral dose (3 mg) of donepezil, an acetylcholinesterase inhibitor that is commonly used to treat Alzheimer's disease, improved SAI in DAI patients with wide individual variations that ranged from an increase of 77% to 18% of test size. These findings suggest that measuring SAI may provide a means of probing the integrity of cholinergic networks in an injured human brain.

Object. Brain injury is known to result in disordered haemostasis. The significant prolongation of coagulapathy was taken to support activation of the extrinsic pathway of the coagulation cascade by tissue thromboplastin, as a result of brain parenchymal injury. We experienced to difficult of treatment of brain parenchymal hemorrhage in decompression craniotomy, and poor outcome.

Methods. The objective of this study was to determine the clinical significance of coagulation and fibrinogenolysis in 178 patients with head injury.

Results. The result of univariate analyses for survival and non-survival was determining association between clinical factor (age, GCS, ISS), hemocoagulative factor and mortality. When simultaneously adjusting for all these factor in multivariate analysis, initial GCS and plasma D-dimer values was independent predicting factor of mortality. Mortality was most strongly related to initial GCS and plasma D-dimer values by ROC curve. In Computed Tomography of brain findings, we found plasma D-dimer value measured within 1 hr after head injury were higher in patients with a focal brain injury group than a diffuse brain injury. The peak of plasma D-dimer values peak was between 3 h to 4 h within head injury from changes of plasma D-dimer values after sever head injury by 19 patients data of 1, 3, 6, 12 hr.

Conclusions. Fibrinogenolysis of increased plasma D-dimer value associated a prediction of mortality and a degree of brain parenchymal damage influenced for the systemic haemostasis in early phase within 1 hr after head injury and increasing within 3 hr to 4 hr after head injury, there is an initial hypercoagulable stage followed by 6 hr after head injury. Therefore, it is important for us to recognize haemostatic disorders at treatment of head injury in acute phase.

Several clinical studies and laboratory data have shown that the decrease in intracranial pressure is one of the effects of hypo­thermia for the patients with severe traumatic brain injury (TBI). Despite such evidence, it has not been shown in the clinical that hypothermia brings a significant improved outcome for the patients with TBI. In this study, we investigated the influence of hypothermia on the intracranial pressue of patients with TBI and their outcome. Fifty-three patients treated with intracranial pressure monitoring were employed in this study. Thirty-seven patients were managed with hypothermia (Hypothermia group; brain temperature 32 – 34 degrees Celsius), and 16 patients were managed at normal temperature (Normothermia group) during the treatment period following TBI. The average GCS score was 7.6±3.2 in the normothermia group, and 5.7±1.9 in the hypo­thermia group. The average age was 56.4±28.7 in the normo­thermia group, and 39.6±23.8 in the hypothermia group. Significant differences were shown in the GCS score and age between the groups. The percentages of patients with favorable outcome (GR + MD) were 50% in the normothermia group, and 51.3% in the hypothermia group. Although the difference in the outcome between the normothermia and hypothermia group was not significant statistically, however, the average intracranial pressure of patients with favorable outcome in the hypothermia group (15.9±1.2 mmHg) was higher than that of patients with favorable outcome in the normothermia group (13.9±1.6 mmHg). The outcome of the patients and the intracranial pressure of patients with favorable outcome were not significantly different however, in the hypothermia group, the patients were inclined to progress better under severe conditions in comparison with the normothermia group.

Since 2000, we adopted mild hypothermia of the present cooling protocol for 3 days at 34 – 35 degrees to improve outcomes of patients with severe traumatic brain injury (TBI). In the present study, we evaluated the efficacy and safety of this protocol retrospectively. Between 2000 and 2008, a total of 35 patients with severe TBI, 16 to 69 years of age, were enrolled. The initial Glasgow Coma Scale scores (GCS) of all patients ranged from 3 to 13, but many patients’ GCS fell down immediately to under 5. All patients had intracranial mass lesions and brain swelling with significant midline shift and underwent hematoma removal operations and craniectomies (SDH 22 cases, contusion 6 and bilateral brain swelling 7). Mild hypothermia was induced by surface cooling and continued 3 days at 34 – 35˚C. Then, the patients were rewarmed at a rate 0.5˚C/day. The Glasgow Outcome Scale at discharge indicated that 20 cases had a favorable outcome (57%) and the mortality rate was 20% in all patients. No patient had severe septic complication during the therapy. We found that this protocol did not improve the prognoses of patients aged 51 years and above, those with higher ICP than 30 mmHg immediately after surgery and those with large contusion and DAI findings on CT. Also subdural hematomas thicker than 18 mm and midline shift of greater than 16 mm on CT were predictive of a poor outcome. The GCS on admission, the presence of pupillary abnormalities were not predictable factors of outcome. CBF and CMRO2 values measured immediately after operations by Xenon-CT, predicted accurately unfavorable outcome. Based on these findings, hypothermia therapy of the present protocol are safe and effective and the age, initial ICP, findings of initial damage and thickness of subdural hematomas or midline shift on CT are predictive factors of outcomes.

There were 9076 head injured patients admitted to the 17 neurosurgical institutes in Miyagi Prefecture and registered in Miyagi Neurotrauma Data Bank between July 1995 and December 2006. The analysis of these patients was made from the view points of cause of head injury, pathophysiology and outcome according to age. The results showed 1) two peaks of occurrence of head injury were seen in the young generation aged 15 – 24 and the older patients aged 60 – 79, 2) traffic accidents was the most frequent cause, followed by fall and fall from the height, 3) 4-wheel accidents was most frequently seen in the age of 15 – 24, motor cycle accidents in 15 – 19, pedestrian accidents in 5 – 9, 4) fall was most frequently seen in the age of 60 – 80, whereas fall from the height was in 0 – 4, 5) a peak of acute subdural hematoma was in the age of 60 – 80, acute epidural hematoma was seen more in younger generation, 6) contusion and diffuse brain injury had two peaks of occurrence, the former is more in the older generation of 60 – 80 and the latter is more in the young generations, 7) the poor outcome clearly increased with age. It was concluded that the cause of head injury, the lesion type and the outcome in head injured patients had an age specificity.

Diffuse hemispheric ischemic changes are often confirmed in cases of infantile acute subdural hematoma in acute phase, and diffuse brain atrophy was also confirmed in chronic phase. This atrophy is often confirmed in cases where abnormal findings were not confirmed on brain CT or MRI in acute phase. ¹²³I-iomazenil SPECT findings in two cases of acute subdural hematoma were compared with CT findings in these cases in chronic phase.

Case 1 (9-month-old boy) required craniotomy for left acute subdural hematoma, showed left hemispheric diffuse low density on CT on the 4th hospital day, and showed left hemispheric high signal and no abnormal findings in the right hemisphere on diffusion-weighted MRI on the 6th hospital day. ¹²³I-iomazenil SPECT on day 31 showed reduced uptake in the whole left hemisphere and right frontal lobe, which was matched to brain atrophy on CT in chronic phase. Case 2 (8-month-old boy) required craniotomy for left acute subdural hematoma, showed left hemispheric diffuse low density on CT on the 4th hospital day, and showed left hemispheric high signal and slightly elevated signal in the right hemisphere on diffusion-weighted MRI on the 3rd hospital day. ¹²³I-iomazenil SPECT on the 4th day showed uptake reduction in the whole left hemisphere and right frontal lobe, which were matched to brain atrophy on CT in chronic phase.

In conclusion, reduction of ¹²³I-iomazenil uptake with SPECT in two cases of infantile acute subdural hematoma was matched to brain atrophy in these cases in chronic phase. ¹²³I-iomazenil SPECT may predict prospective brain atrophy more accurately than conventional CT and MRI.

Objective. A duty of wear of a rear-seat belt was imposed from June 1, 2008. Although it was reported that non-worn seat belt at the rear-seated crew tended to worsen the head injury, there were no clinically studies to head injuries for rear-seated passengers.

Methods. The study was performed in 12 hospitalized patients in our unit with diagnosis of head injuries at rear-seated crew from January, 2004 to May, 2008.

Results. There were nine cases of brain contusion, eight cases of scalp laceration, including 3 cases of skull fracture under the wound. Also there were five cases of skull base fracture, 3 of acute subdural hematoma, one of acute epidural hematoma, two of diffuse axonal injury, respectively. 4 or more head injury Abbreviated injury score were recognized 75%. There were no special breast-abdominal traumatic injuries. Three passengers were wearing the seat belt; on the other hand 9 passengers were considered un-wearing the seat belt. GOS on discharge were 4 in GR, 5 in MD, 2 in SD, and 1 in D, respectively.

Conclusion. The characters for head injuries of rear-seated passengers were examined. Most of them were un-wearing the seat belt, and head serious injury rate was high. It seemed that long scalp laceration with skull fracture directly under the wound were characteristic. It is expected that head injury for rear-seated passengers will decrease and be slightly after the formation of seat belt wear duty.

We describe a case of hypopituitarism due to traumatic brain injury (TBI). An 11-years-old girl was admitted to our hospital, because she sustained a head injury during a road traffic accident. Her initial Glasgow Coma Scale (GCS) score on admission was seven. Cranial computed tomography (CT) revealed sub­arachnoid hemorrhage and fracture of the left temporal and basicranial bones. Intracranial pressure (ICP) monitoring was initiated. On the third hospital day, diabetes insipidus developed, and antidiuretic hormone (ADH) therapy was required to maintain systemic blood pressure. Severe hypotension, which remained unchanged even after administration of adequate doses of vasopressor, improved dramatically after injecting adreno­corticotropic hormone (ACTH). Moreover, glucocorticoid re­placement therapy was effective in maintaining her blood pressure. Prolonged severe hypotension resulted in hemo­dynamic stroke, and cranial CT on the fifth hospital day revealed a low-density bilateral watershed infarction. The ICP increased; therefore, an emergency bilateral craniectomy was performed on the sixth hospital day. Endocrinological examination revealed hypo­pituitarism in the acute phase; however, hypopituitarism par­tially improved 7 months after the injury, as determined from stimulation tests. The patient spent 235 days in the intensive care unit before she was transferred to a rehabilitation hospital. At the time of the transfer, her GCS score was nine.

This case shows that adrenal insufficiency after TBI may lead to hemodynamic instability, which can be life threatening. It is important to be aware of the clinical signs and symptoms of adrenal insufficiency, and serum cortisol levels should be monitored immediately after TBI. With regard to hypopituitarism, endocrine assessment should be repeated in the chronic phase, because this condition is reversible in some cases.