Age-dependent diversity of pediatric head injury was overviewed and significance of early implementation of rehabilitation in head-injured children was emphasized.
Survivors from severe traumatic brain injury (TBI) often sustains chronic physical and cognitive dysfunction. It is important for physicians and therapists to provide them with early rehabilitation treatment in a cordinated way. These children often require a long-term support from medical as well as educational specialists after finishing the hospital phase of rehabilitation.

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The aim of this study is to clarify the specific pathophysiology of increased intracranial pressure in an immature brain in relation to its unique cerebral blood flow dynamics and brain tissue oxygen metabolism.
Thirteen puppies were used for an experimental model of brain herniation due to a massive intracerebral hematoma. Along with increasing size of the hematoma, the intracranial pressure (ICP), carotid blood flow (CBF) and cerebral tissue oxygen (CTPO₂) were measured simultaneously and continuously.
The tolerance capacity for an acutely expanding mass lesion, or intracranial compliance, was studied. The ratio of hematoma volume/body weight was obviously higher by more than 200% in a group of younger puppies with open cranial sutures. Dynamic changes of CTPO₂ were noted to be independent in the cerebral subcortical region and the medulla oblongata, when Doppler detection of arterial pulsations showed no flow in the anterior circulation in association with increased intracranial pressure caused by a supratentorial expanding mass lesion. A case with open cranial sutures (1, 500 g of body weight) clearly demonstrated this and survived over 24 hours. With acutely increasing ICP CTPO₂ was elevated modestly in the cerebral subcortical region (p<0.1) and prominently in the medulla oblongata (p<0.005). In conclusion, the posterior fossa structure (brain stem and cerebellum) in the immature age group is protected from an acutely expandingmass lesion in the supratentorial compartment. The posterior fossa behaves as an independent compartment with more prominent CBF and CTPO₂ reactivity in the dynamic changes. The author proposed to name these fidings as “independent compartment phenomena”.

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We investigated the prognosis of 42 children with traumatic brain injuries. The main etiology was a traffic accident in 46 cases, especially during walking and bicycling, and child abuse in 7 cases. Eighteen cases of acute subdural hematoma 18 cases distributed at all ages, 9 cases of diffuse axonal injury mainly during school age, 4 cases of chronic subdural hematoma under 2 years. These were all caused by child abuse. Fifteen cases showed a good prognosis with independent activities of daily living (ADL). The main type of injury was diffuse axonal injury in this group. Twelve cases showed a bad prognosis with completely dependent ADL. The bad prognostic factors were chronic subdural hematoma caused by child abuse, consciousness loss with Glasgow Coma Scale less than 8 or lasting more than 2 weeks. After rehabilitation in our hospital, 37 cases returned to school: an ordinary class in 20 cases, a special class in an ordinary school in 5 cases and a special class in 12 cases. About half of the cases returned to an ordinary class, although with problems such as learning difficulty, danger and bullying.

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One-hundred and seventy traumatic brain inlured persons were admitted to Kanagawa Rehabilitation Hospital for a rehabilitation program during a five-years period. The average age was 30.7years and the male to female ratio was 5: 1.The most common cause of injury was an traffic accident. They exhibited various physical and cognitive dysfunctions. Patients with severe physical and/or cognitive dysfunction had difficulty in community re-integration after finishing the hospital rehabilitation. At present, social resources for traumatic brain injury patients and family to fulfill their various needs are so few that they tend to be isolated from the community.

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In the management of severe pediatric brain injury, attention has previously been paid to brain edema, ICP elevation and low cerebral perfusion pressure (CPP). However, in the acute stage within 3-6 hours after trauma, brain hypoxia and hyperglycemia associated with diffuse brain injury are often observed. We have pointed out brain thermo-pooling (elevation of brain tissue temperature) and brain hypoxia caused by defective release of oxygen from hemoglobin (due to decrease in red blood cell enzyme (DPG)) as a new mechanism of brain injury.
To treat these pathologic changes, we have developed a brain hypothermia treatment, the major purpose of which is to prevent brain hypoxia, brain thermo-pooling, neurohormonal changes causing cytokine encephalopathy, and a selective, radical-mediated damage of the dopamine A10 nervous system. The brain tissue temperature is initially adjusted to 35° with adequate cerebral oxygenation, followed by brain hypother-mia at 34° for 1 weeks to prevent brain hypoxia, free radical reactions, brain edema and ICP elevation. What is most difficult in the pediatric brain hypothermia treatment is to maintain metabolic balance in the injured brain t:.ssue and pulmonary infections associated with an immune crisis. When a rapid elevation of serum glucose is noted it is critical to lower the value because glucose quickly penetrates the blood-brain barrier and increases pyruvate and lactate by inhibiting the TCA cycle metabolism. Thus, hyperglycemia during brain hypothermia treatment is one of the major target of management. Another problem is immune crisis associated with secondary pulmonary infections. To prevent them, early enteral nutrition and replacement of L-arginine were most useful, as well as preconditioning for rewarming as follows: serum albumin >3.0g/d/; lymphocyte >1500/mm³; T-H (CD4) lymphocytes >55%; serum glucose, 120-140mg/d/; vitamin A >50 mg/d/; Hb >12g/d/ and 2, 3 DPG, 10-15 iμmol/gHb; O₂ER, 23-25% and AT-III, >100%. The clinical benefit of this therapy is still controversial.

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Trauma victims are directly transferred to a level I trauma center bypassing local hospitals. First, airways and cervical stability are secured. Intracranial hematoma should be promptly evacuated. Endotracheal intubation and mechanical ventilation are initiated for children with a Glasgow Coma Score of 10 or less, anisocoria, apnea, and/or hypercarbia. Isotonic crystalloid is used for intravenous fluid maintenance. The goal of intracranial pressure (ICP) management is to maintain the ICP at less than 15mmHg and to maintain minimum cerebral perfusion pressure at 45-55mmHg. External ventricular drainage provides direct control of the ICP by allowing intermittent drainage of the CSF (5-10m//hour). Mannitol is effective but hyperventilation is not recommended.

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Encephalitis/encephalopathy is a neurological syndrome characterized by acute onset, symptoms of intracranial hypertention accompanying severe sequels or death. Encephalitis is caused by microbial infection of central nervous system, such as neurotrophic or conventional viruses. Infectious encephalopathy shows similar clinical symptoms to acute encephalitis, without any evidence of inflammation and microbial infection in brain tissues. The national epidemiological surveillance of the diseases is carried out to study the frequency and prognosis of patients with both diseases. The principal treatment is quite different in the both, in the former the eradication of microbial from the brain and in the latter the reduction of pressure of brain edema. Furthermore, the improvement of the brain with severe destruction requires such new step to reduce the activities of enzymes or cytokines to destroy brain tissues, as a mild hypothermia to lower body and brain temperature to 33-34°.

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Recent data of the National Epidemiological Surveillance of Infectious Diseases (NESID) showed that neurological complications associated with influenza virus infection, such as acute encephalitis/encephalopathy (excluding Reye's syndrome) have increased in number especially among young children. Further investigation is necessary to find the pathogenesis of these serious complications and clarify whether this phenomenon is due to unclarified factor (s) unique in Japan or it has reminded unrecognized in other countries

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Cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for the pathogenecity and even for the neurovirulence of influenza A viruses. WSN, a neurovirulent virus, adapted to mouse brain, grew in vitro in several types of cells including neuroblastoma cells in the absence of trypsin. When mice were intracerebrally inoculated with WSN, the viral antigen was found in the substantia nigra zona compacta and hippocampus. The mice inoculated with viruses isolated from children with acute encephalopathy associated with an influenza virus infection, on the other hand, showed no neurological symptoms. Furthermore, these viruses did not grow in the human neuroblastoma and glioblastoma cells. Since 1991, most of the human influenza A viruses have not agglutinated chicken erythrocytes. Whether this altered receptor binding specificity is related to the occurrence of influenza encephalitis and encephalopathy is now under investigation.

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CT/ MRI findings, laboratory examinations and prognoses of 42 patients with acute encephalopathy (AE) (Japan Coma Scale≥200) were reported.
1. Findings on CT/MRI were divided into the following 7 categories: Group 1 (normal), Group 2 (CT/MRI looked normal in acute phase, but brain atrophy developed and progressed slowly by weeks or months), Group 3 (CT/ MRI looked normal within a few days after the onset of AE, but cortical laminar necrosis developed at 4-5 days after the onset), Group 4 (marked brain edema developed within 2 days after the onset of AE), Group 5 (AE with symmetric thalamic lesions), Group 6 (symmetric pallidum lesions on MRI which appeared after brain edema disappeared), and Group 7 (the brain shrinked during acute phase, which normalized on the follow up CT/MRI).
2. Serum AST elevated in approximately 50% of the patients with AE. Sixty percent of them exhibited DIC, whose prognoses were poor. Cerebrospinal fluids (CSF) neopterin (NP) and/or interleukin (IL)-6 were elevated in all the 8 patients examined. In the two cases whose serum NP and IL-6 were measured at the same time, their values in the CSF were higher than those in the serum in one case, and almost the same in the other. In a patient with a condition mimicking hemorrhagic shock and encephalopathy, serum IL-6 concentration was very high (94, 000pg/ml).
3. Mild hypothermia (around 34°C) combined with methylprednisolone pulse therapy was excellently effective on AE. A 6-year-old boy exhibited tonsillar herniation at admission recovered well to be able to run.
4. Differentiation between Reye syndrome and HSE, and the pathogenesis of AE were also discussed.

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The prognosis of pediatric encephalitides, such as infantile influenza encephalitis, is still poor because of the rapid progression, severe brain edema, selective bilateral basal ganglia necrosis, and a poor immune function, the mechanism of which is still unknown. Especially, little is known about virus es in CSF and brain tissue with influenza encephalitis, which hampers successful treatment of this condition.
Recently, hypothermia treatment has attracted attention as the management of infantile influenza encephalitis to prevent severe brain edema. Recent clinical studies have revealed brain thermo- pooling (elevation of brain tissue temperature) with damage of blood-brain barrier (BBB). We then studied brain injury mechanism after severe brain injuries, cerebral strokes, reperfusion after shock, and high fever with lower cerebral perfusion pressure in our ICU. The brain thermo-pooling phenomenon results from body temperature higher than 38°C, systolic blood temperature lower than 90-100mmHg, and cerebral perfusion pressure (CPP) lower than 70 mmHg that hinders washout of brain tissue temperature by cerebral blood flow. We have recorded of brain tissue temperature of 40-44°C in various brain injured patients. Some pathophysiological changes in infantile influenza encephalitis may be explained on the basis of this brain thermo-pooling phenomenon. In systemic infection, it causes severe brain edema by activation of cytokines and destruction of BBB, bilateral basal ganglia necrosis by acute severe brain hypoxia, resulting in poor prognosis without control of brain temperature. In other words, brain thermo-pooling, is the major targetof treatment for infantile influenza encephalitis. In this paper, new concepts of the brain injury mechanism and methods of brain hypothermia treatment of pediatric influenza encephalitis are presented.

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We reported a male infant with multiple acyl CoA dehydrogenase deficiency, probably due to electron transfer flavoprotein dehydrogenase deficiency. He was noted to have severe muscle weakness, a high serum creatine kinase (CK) level up to 6920 IU/L, lipid storage myopathy and fatty liver at 6 months of age. A GC/ MS analysis of urinary organic acids showed excess excretion of dicarboxylic acids, including glutaric, 2- hydroxyglutaric, adipic, suberic, sebacic, malonic, ethylmalonic and methylsuccinic acids. On a urinary acylglycine analysis, hexanoylglycine and suberylglycine were increased, but not isovalerylglycine, in amount. No ketosis was noted. The muscle pathology showed increased oil-red O positive lipid droplets of various sizes indicative of lipid storage myopathy. There was diffuse decrease in the activity of ctochrome c oxidase. No ragged-red fibers were noted.
His clinical symptoms improved remarkably after the administration of riboflavin (100mg/day) and Lcarnitine (1000mg/day). He was then diagnosed as having probable riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. The glutaryl CoA dehydrogenase activity in lymphocytes was normal, as were the a-and-A-subunits of electron transfer flavoprotein. These findings led us to suspect electron transfer flavoprotein dehydrogenation deficiency. Although he had several episodes of short-term deterioration in clinical and laboratory findings, he developed normally with normal intelligent till 10 years of age.

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[in Japanese]

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[in Japanese]

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