The examination of cerebrospinal fluid has provided useful information for diagnosis of CNS infections. The progress of analytical technology has brought the possibility to detect very small amounts of chemical substances. I thought that new information from brain should be obtained by using modern analytical technology for several substances in CSF.
Free amino acid pattern, glutamine, homocarnosine, glutamic acid decarboxylase (GAD), neuron specific enolase (NSE) and 2', 5'-oligoadenylic acid synthetase (2-5 A) in CSF have been examined for information of brain injury and dysfunctions. The results are as follows.
1) The individual difference and constancy of free amino acid pattern in CSF were found in children without any neurological diseases.
2) The levels of free amino acids in CSF increased in the acute phase of bacterial meningitis.
3) High levels of glutamine in CSF of children with acute bacterial meningitis were normalized during the recovery phase.
4) A marked imbalance of free amino acids in CSF was found in children with Lennox-Gastaut syndrome.
5) A decrease of homocarnosine levels in CSF was related with the degree of unconsciousness in children suffering from neurological diseases.
6) High GAD activities in CSF were observed in the acute phase of aseptic meningitis and after intrathecal injection of methotrexate for the therapy against meningeal leukemia.
7) High NSE activities in CSF were found in the acute phase of bacterial meningitis, intracranial hemorrhage, encephalopathy and encephalitis.
8) High 2-5A activities CSF were measured in the acute phase of mumps meningitis with subsequent decreases during the recovery phase.
These results suggest that several substances in CSF are useful as markers of brain injury and dysfunction.

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Gonadal steroids play an important role in exerting functional sexual differentiation of the brain. Recently there has been accumulating evidence that gonadal steroids regulate neuron number, axonal and dendritic growth and synapse formation in the neuronal system containing sex steroid receptors. These provide morphological bases for sexually dimorphic function of the brain. Other than in the developmental process, gonadal steroids are found to take care of neuronal plasticity in certain brain areas.

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Current status of molecular analysis in child neurology was briefly reviewed. Two different methods are available for gene diagnosis of inherited neurological diseases; molecular analysis of the mutant gene itself, which detects single base substitutions, deletions and insertions; and linkage analysis using restriction fragment length polymorphism, which can be applied also to various neurogenetic diseases without information about mutant genes. The PCR amplification method is particularly important and useful for molecular analysis of clinical specimens. A few analytical results were presented in cases with Fabry disease, galactosialidosis and Duchenne muscular dystrophy.

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Actual phenomena of various types of involuntary movements listed below were demonstrated by moving pictures, which were followed by comments on symptomatology, in particular the fundamental characteristics of an indivisual involuntary movement. These characteristicsare, the essence of each involuntary movement, and it is necessary to recognize both its phenomenon itself and its accumulated knowledge in order to realize and interpret the involuntary movement. The following involuntary movements are treated:(1) typical tremor-at-rest in paralysis agitans, (2) atypical parkinsonian tremor, (3) essential tremor, (4) chorea, (5) ballism, (6) athetosis, (7) choreoathetosis, (8) dystonia, (9) spontaneous myoclonus at rest, (10) intention or action myoclonus, (11) intention tremor and (12) hyperkinesies.

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Main diagnostic points on the clinical signs and symptoms of various neurological disorders during the neonatal period and early infancy are briefly mentioned. Application, diagnostic values and limitation of various diagnostic measures including US, CT and MRI are then discussed.

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The type of hypoxic-ischemic brain damage is determined by the distribution of lesions, which has different mechanism in each. Neuroimaging is important for detection of the lesions, but morphological changes appear 12 hours after hypoxic episodes even in neuropathology. Hemodynamic, biochemical and neurophysiological changes during the acute stage are also valuable for earlier diagnosis of the lesions. Doppler sonography and near-infrared spectroscopy, reflected intracranial hemodynamics and metabolism. In our clinicopathological studies, the infants with pontosubicular necrosis showed significantly high incidence in severe hypocarbia, which may be associated with hypoperfusion. Thus, the monitoring of brain hemodynamicsand metabolism may be important for early treatment as well as prevention of the brain damage.

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The neurodevelopmental prognosis of periventricular leukomalacia (PVL) has been predicted effectively by ultrasonography (US).
US is the best imaging modality to identify both the early changes of PVL (echogenic phase) and the late changes (cystic phase). In cases with intraventricular hemorrhage, however, it was difficult to differentiate from periventricular hemorrhage in the echogenic phase by US. The PVL resolved to a discrete cyst separate from the ventricle, but periventricular hemorrhage developed a porencephalic cyst. Computed tomography is useful for distinguishing periventricular hemorrhage from PVL in the early changes. However, it is not particularly useful in the late changes, as only extensive cystic lesions can been seen. Magnetic resonance imaging is useful for following the progress in myelination.

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A routine ultrasonographic (US) examination is essential for monitoring intraventricular hemorrhage (IVH) in very low-birth-weight newborn infants. The incidence of IVH was decreased by risk factor analysis using US. Subarachnoidal hemorrhage (SAH), subdural hemorrhage (SDH) and intraparenchymal hemorrhage (IPH) occurred more in mature infants who had difficult deliveries. Final diagnosis was established by cranial computed tomography (CT) or careful US examinations.
Symptoms and signs of intracranial hemorrhage (ICH) were more non-specific than neurological. The possibility of ICH should always be considered and excluded by CT or US in the infants with nonspecific clinical manifestations.

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The neurological sequelae of CNS viral infections in the neonatal period and early infancy are one of the serious causes of brain dysfunction in children. It is often difficult to diagnose the CNS viral infection because of lack of neuorological symptoms. But clinical manifestations are very important for early diagnosis of herpes simplex virus encephalitis and cytomegaloviral infections. We established early diagnosis of CNS viral infections by screening of serum IgM and determining 2' 5' oligoadenyl (2-5 A) synthetase activity in the cerebrospinal fluid (CSF). The results showed high serum IgM levels in 75% and abnormal high levels of 2-5 A synthetase activity in CSF of all cases of the young babies with viral meningitis.

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A guideline for early diagnosis of metabolic disorders affecting central nervous system during neonatal and early infancy was presented. Clinical manifestations associated with inborn errors of metabolism in the neonatal period are poor feeding, vomiting, diarrhea, abnormalities in muscle tonus, dyspnea, convulsion, coma and so on, and these are not specific to each disorder. However, such symptoms or signs as described below have often intimate relation to metabolic disorders:(1) previous children died of undetermined causes during early infancy;(2) complication of sepsis;(3) onset in the early neonatal period;(4) developmental and growth retardation. When newborns and infants have these symptoms or signs, we should start simple screening studies immediately for metabolic disorders, including CBC, hepatic function tests, blood glucose, lactate, pyruvate, ketone bodies, ammonia, blood gas analysis, urinalysis (including nonglucose reducing substance tests and Fe Cl3 reaction) and so on. As for CBC, we have to make our own effort to find spherocytosis and vacuoles in lymphocytes. Family history, especially the mother's personal history, is indispensable. During physical examinations, we must pay attention to facial appearance, skin color, macroglossia, hair abnormalities, peculiar odor of the urine and expirate, and hepatosplenomegaly. When abnormality is found in these clinical signs or simple laboratory examinations, we should not hesitate to start dietary treatment even if special examinations for differential diagnosis are on the way.

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Congenital anomalies of the central nervous system frequently cause severe emotional, economic, and physical hardship for both the child and the family. Craniofacial and developmental abnormalities may cause social unacceptability.
Congenital hydrocephalus may result in neonatal death or mental and motor disabilities. Frequenthospitalization or prolonged, institutionalization may be necessary for the many surviving patients. With recentadvances in the diagnostic techniques of aminocentesis, fetoscopy, ultrasound, computerized tomography (CT) and magnetic resonance imaging (MRI), an improved accuracy in the diagnosis of fetal abnormalities and in the determination of prognosis' is possible in many instances.
When confronted with the diagnosis of congenital anomalies of the central nervous system during the intra-uterine period, there are five options for management: 1) no intervention; 2) termination of the pregnancy; 3) allowing pregnancy to proceed to term; 4) induction of preterm delivery followed by postnatal intervention; and 5) intrauterine surgical intervention.
However, in practice it may be very difficult to choose the best opinion. In order to help make such decisions, this paper reviewed the current understanding of the main congenital anomalies of the central nervous system.
According to a 17 year survey of major congenital neurologic malformations in the USA, the incidence of major central nervous system anomalies (anencephaly, spina bifida and encephalocele) has been declining. This has also been found in Japan.
In the USA an organization was established-The Medical Task Force on Anencephaly-for the purpose of offering guidelines on the ethical issues relating to anencephaly, especially in regard to the use of fetal organs in transplantation.
It is suggested that the current approach to congenital central nervous system anomalies in the USA could be helpful to the physicians dealing with such anomalies in Japan.

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Among fetal anomalies, the rate of the central nervous system (CNS) abnormality is high, and almost all cases are wanted to diagnose prenatally for the improvement of their prognosis. For instance, anencephaly should be detected for its lethal prognosis. Hydrocephalus has a certain possibility for intrauterine treatment. Spina bifida should be found in utero for the immediate operation after birth. At present, most of these major anomalies of CNS can be successfully screened or diagnosed by using ultrasonography. Brain anomalies such as hydrocephalus, Dandy-Walker anomaly and holoprosencephaly show characteristic dilatation of ventricles, which can be easily found in the routine screening ultrasonography from the beginning of the second trimester of gestation. Ultrasonographic detection of neural tube defects such as anencephaly and spina bifida is not difficult in utero. Thus it is possible to diagnose the most of CNS anomalies by using prenatal ultrasound in the early stage of gestation now. Recent advances of ultrasonography, particularly the development of transvaginal technique have contributed to the earlier diagnosis of CNS anomaly even in the first trimester of gestation.

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Mortality patterns of severely retarded children who were cared at their homes in Tokyo were investigated. We identified sixty-seven physically handicapped children who died in 1988 and 1989 at 15 schools for such children. 42 children out of 67 were severely retarded (children who neither walk nor have IQs over 35). Annual case-fatality rate of severely retarded children was 2.5%. Respiratory tract infections accounted for 38% of the causes of severely retarded children and other respiratory tract diseases such as aspiration and complications of tracheotomy accounted for 29%.

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Auditory event-related potentials (ERPs) were recorded from 53 neurologically normal children of 5 to 15 years of age, and 8 healthy adults. To clarify the developmental changes and to obtain a normative value in childhood, the latency and amplitude of ERPs (N100, P200, N200, and P300) were examined. ERPs were elicited with the auditory oddball paradigm.
P300 components were detected in all subjects. A strong positive correlation was demonstrated between latencies of two trials, and a small latency difference between trials was interpreted as being clinically unimportant. A significant negative correlation was observed between P300 latency and age during childhood (latency (msec) =-9.81 ×(Age) + 459: r= 0.75, p<0.01). A mild negative correlation was also observed between N100, P200 and N200 latency and age. P300-topography of amplitude showed various patterns in young childhood, but in adolescence a maximum point was Pz in almost all subjects.
These findings suggest that auditory ERPs can be easily measured in childhood and are useful for objective evaluation of the cognitive function.

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The changes of pulsatility index (PI) were followed for anterior cerebral artery (ACA) and basilar artery (BA) in 8 hydrocephalic infants. PI increased with the progression of hydrocephalus in both ACA and BA, from an average of 0.69. to 0.80 and from 0.73 to 0.81, respectively. The index made a sharp dip in 6 hours 0.65 for ACA and 0.70 for BA after placing a VP shunt. It eventually stabilized within mean ± SE. (ACA: 0.69 ± 0.0042, BA: 0.71 ± 0.0036).
The index enabled us to observe objectively cerebral vascular resistance of the illness in numerical values. It may become a useful tool for setting criteria for placing a shunt (about 0.80) as well as for judging the shunt effectiveness.
Throughout the entire observation, changes in PI of both ACA and BA were well correlated. Anterior fontanel pressure was also correlated with PI in the period, except PI of BA before the shunt operation. However, the pre-shunt correlation of PI to lateral ventricle enlargement was lost after the shunt operation. And the ventricle size reduced only slightly when PI rapidly decreased in 6 hours after the V-P shunt. These facts indicated that the changes in PI was affected directly by the intracranial pressure rather than the enlarged ventricle.
The findings of this study indicated the necessity of evaluating of the intracranial hemodynamics with other diagnostic approaches in managing infantile hydrocephalus.

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[in Japanese]

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