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21
Development of Behavioral Response to Auditory Stimuli in Low Birthweight Infants Teiichi Mizuno , MD, Hiroko Suzuki, MA, and Reiko Ohta, MA Department of Child Study, Ochanomizu University, Tokyo (TM); Seibi Educational Research Center of Suginami Ward, Tokyo (HS); Sodegaura Rehabilitation Center, Chiba (RO)
This study was intended to elucidate the behavioral characteristics of auditory stimulation in low-birthweight infants (LBW) in the neonatal period.
Subjects and Methods: The sample was 76 LBW (44 males, 32 females) aged 10 hours to 20 days after birth, 31 to 39 gestational weeks, the one-minute Apgar scores being 3 to 10, and the birth weights 1,320 to 2,460 gm. When the infants were in the supine position at State 3 described by Prechtl et ai, the rattle sound was presented for one minute at a distance of 10 cm from the infant's ear at an intensity of 70 to 80 db. The response was recorded on video tape and analyzed according to the previous study.
Results 1. The response of the head was poor compared with full-term neonates (FT, LBW; 38.2%, FT; 64.8%) up to 5 days of life, and directional movement , i.e. orientating response (OR), did not appear until 20 days of age. The latent time (Lt) of head turning became longer with age, but no significant diffe rence was found between LBW and FT. A gradual increase of Lt of head turning suggested com pletion of the primitive reflex system of LBW such as the appearance of ATNR at 2 weeks of age in FT, and/or hypotonicity of the cervical muscles in LBW.
2. Non-directional movement (NDM) of the eyes decreased from 43 .5 to 18.7%, but OR increased from 47.8 to 81.3% at 14 days of life. Lt became shorter with time and was remarkably reduced at 9 days (NDM; 30.4 to 16.1 sec, OR; 29.5 to 18.2 sec). This implies OR is completed at 10 to 14 days of life, but real OR is known to be elicited at 2 to 3 months of age. This mimic OR of the neonatal period may be different in character from real OR. The average appearance rate and Lt of ocular response were as follows : NDM (FT; 65.9%, 13.3 sec, LBW; 50.0%, 18.8 sec), OR (FT; 25.0%, 16.1 sec, LBW; 35.0%, 23.1 sec) up to 4 days of age, NDM; 19.6 sec, OR; 22.0 sec at 20 days of age. The data indicate that Lt in LBW was longer than that in FT, but the appearance rate of OR steadily increased with time.
3. TIle rate of NDM and OR, and Lt of the eyes or head were not correlated with birth weight.
4. The difference in gestational weeks was not clear from the rate and Lt of response. Gestational weeks and postconceptional weeks also had no significance.
5. These data suggested that the response of the head or eyes depended upon the number of days after birth, and not the postconceptional weeks.
Key words: Low-birth-weight infant, neonatal behavior, auditory response, orientating response.
216 Brain & Development, Vol 4, No 3-4, 1982
22
Ontogenic Development of the Brain Electrical Activity Mapping in Normal Children and Adults Teruyuki Ogawa, MD, and Yoshio Nakashita, MD Department of Pediatrics, Oita Medical College, Oita
Using the method of autoregressive (AR) power spectral analysis, EEGs are decomposed into first and second order elementary processes. The former showed a transient nonoscillatory delta wave, whereas the latter showed oscillatory waves of delta, theta, alpha and beta rhythms in the EEG. Ontogenic development of the brain electrical activity mapping (BEAM) of these component waves was reported.
Materials and Methods EEG-recordings were performed on 24 healthy children and adults, whose ages ranged from 6 months to 20 years. EEG was done with an electroencephalograph with 12-channel monopolar electrodes, and 10 segments (= 100 sec) of 10-second-artifact-free EEG were digitized at 50 samples/sec in each region. Applying AR-power spectral analysis, the average power intensity in each component wave was computed through a minicomputer, PDP 11/40 (DEC). The square roots of the power-intensity of each component wave were as equivalent potentials over each damping frequency . According to Ueno and Matsuoka's method interpolation was performed and interpolated values were quantized into eleven steps. Potential distributions over the surface of the head were printed out on line printers for each damping frequency band classified as follows : delta, theta , alpha-l (slow alpha), alpha-2 (typical alpha), alpha-3 (fast alpha), beta-I, beta-2 and beta-3, respectively.
Results 1) As regards reproducibility of the results, analysis of 100 second EEG data appeared to be almost satisfactory in comparison with analyses of various periods ofEEG data.
2) Delta and theta activities were confined to the frontal and occipital regions during infancy and thereafter showed a high voltage focus around the bilateral frontal regions with increasing age.
3) Alpha-l and alpha-2 activities showed a high voltage focus around the right frontal and left occipital regions during infancy, and then tended to be maximal in the right occipital region with increasing age.
4) The alpha-3 wave was prominent in the parietal regions from 6 months to 3 years old and then it was relatively lateralized to the right side with increasing age .
5) Beta waves showed the same pattern as alpha-3 activity.
Conclusion These results suggest that topographic display of EEG yields compact and easily visualized information on the functional development of the brain in children.
Key words: Brain electrical activity mapping (BEAM), ontogenic development.
23
Body Movements during Sleep in Full-Term Newborn Infants Susumu Hakamada, MD, Kazuyoshi Watanabe , MD, Kimiko Hara, MD, Shuji Miyazaki, MD, and Toshiyuki Kumagai, MD Department of Pediatric Neurology , Central Hospital, Aichi Prefectural Colony, Kasugai, Aichi (SH, KH, SM, TK); Department of Pediatrics, Nagoya University, School of Medicine, Nagoya, Aichi (KW)
Body movements during sleep were observed in 14 full-term sick newborn infants such as those with perinatal asphyxia, purulent meningitis, mecomium aspiration syndrome, melena, porencephaly, and hydranencephaly. Five newborn infants who had recovered from transient vomiting were examined as a control. Infants with minimally depressed background EEG showed an increase of generalized movement (GM) and localized tonic movement (LTM) in quiet sleep . Hydranencephalic infants revealed an increase of generalized phasic movement (GPM) in active and quiet sleep. On the other hand, a decrease or absence of body movements was observed in infants with severe EEG abnormalities such as moderate, marked and maximal depression. Hydranencephalic and porencephalic neonates showed a decrease of LTM in active sleep. One infant with purulent meningitis, showing markedly depressed EEG, revealed GPM-like movements of much longer duration.
The follow-up study revealed that the absence of body movements or the increase of GPM might indicate a very poor outcome, whereas the presence of L TM, even in a small amount, suggested the preservation of cortical functions. The increase of body movements was also considered to correlate with sleep disturbance and to serve as an indicator of a brain dysfunction.
Key words: Sleep, body movements, polygrap/zy.
24
Auditory Brain Stem Responses in Children with Neurological Disorders Kimiko Takeda, MD, Ryosuke Murata , MD, Osamu Matsuoka , MD, Toshinobu Yamashita, MD, Masayoshi Kin, MD, and Gen Isshiki, MD Departmen t of Pediatrics, Osaka City University, Medical School, Osaka
We examined the physiological function of the brain stem in patients with neurological disorders.
Materials and Methods The subjects were 11 low-birth-weight infants of up to 1 year of age who were neurologically normal , and 26 patients with neurological disorders whose ages ranged between 2 months and 11 years. The electrical potential was recorded between the vertex and the mastoid ipsilateral to the ear which received a click signal. The stimulus used was a one-cycle sinusoidal wave at a frequency of 4 kHz. The repetition rate was 10/sec. The initial stimulus was at 108 dB; the level of the sound was decreased by 5-10 dB at each repetition to 48 dB. Brain stem responses (BSR) were summed on line with a computer (Nih on Koden ATAC-350). BSR audiometry was performed under induced sleep for all subjects. Determinations were made once for normal subjects, and more than once for patients with neurological disorders.
Results 1) In the normal infants of from 2 to 12 months, wave I and wave V latencies shortened with increasing age and with increasing intensity of the stimulus, but waves VI and VII could not be recognized except in the oldest.
2) In infants with neurological disorders, no waves could be recognized, and the response thresholds were at higher levels.
3) In a case of adrenoleukodystrophy as well as a case of metachromatic leukodystrophy , the latencies of peaks I, III and V were significantly longer and the amplitude of each peak significantly decreased as the disease progressed.
4) In cases of West syndrome and Lennox syndrome, the peak latencies of waves I and V were normal.
5) In severe cerebral palsy, waves I and V had prolonged latencies.
These findings suggest that the peak latency of waves I and V and the interval between waves V and I can be used as an index of the physiological maturation and prognosis of neurological disorders.
Key words: Auditory brain stem responses, cerebral palsy, brain stem function, neurophysiological maturation.
Brain & Development, Vol 4, No 3-4, 1982 217
25
Developmental Changes of Brainstem Auditory Evoked Potentials (BAEPs) in Human Infants and Children Yasuhiro Mochizuki, MD, Toh shin Go, MD, Hideo Ohkubo, MD, Teruyuki Motomura, MT, Syozo Nakano, MD, Kenkichi Kataoka, MD, and Hiroatsu Hojo, MD Department of Pediatrics (YM, TG, HO) and Clinical Laboratory (TM), Shizuoka Central Prefectural Hospital, Shizuoka; Department of Neurology , Shizuoka Children 's Hospital, Shizuoka (SN, KK, HH)
Average values of latency, amplitude and threshold of BAEPs were recorded in 165 normal subjects including premature babies, neonates, infants, children and young adults. They were divided into 15 groups based on the age as follows: premature babies; neonates ; I , 2, 3, 6, 9-month-olds; l-year-old; l-year-3-month-olds; l-year-6-month-olds; 2-year-olds; 3-year-olds; 4-yearolds; 5 to 8-year-olds; and 10 to 20-year-olds; A total 200 BAEPs were obtained from these subjects. The recording technique was the same as that already reported [1] .
Results 1) Peak I latency shortened to adult values at 2 months of age. Y-I latency showed steady shortening up to the group of 5 to 8 years of age.
2) Ill-II, Y-IY inter peak latencies showed definite maturational changes similar to Y-I latency, whereas II-I, IY-III latencies showed little changes in each age group.
3) The amplitude of peak I increased to adult values at 9 months of age, and showed little changes thereafter. The amplitude of peak III reached adult values at 9 months of age, which gradually increased up to the age group of 5 to 8 years, thereafter showing a decreasing tendency. The amplitude of peak Y reached adult values at 2 to 3 years of age, which increased up to the age group of 4 years, thereafter showing a decreasing tendency.
4) Mean thresholds of BAEPs were 15 dB higher in neonates than adults, but no differences were noted after 1 year and 3 months of age. In groups of more than 5 years of age, mean thresholds of BAEPs were 5 to 10 dB higher than the mean subjectively audible threshold of the same stimuli.
5) TIle Y-I latencies of males were longer than those of females in each age group. Statistically significant differences (p < 0.01) were noted after 5 years of age.
6) The amplitude of peak Y in males was higher than that of females after 2 years of age. However, a statistically significant difference was not confirmed in this study.
Reference 1. Mochizuki Y, Ono Y, Motomura T, et al. Devel
opment of brain stem auditory evoked responses in human infants and young children. Brain Dev (Tokyo) 1979;1:208.
Key words: Brainstem auditory response, auditory development, sex differences.
218 Brain & Development, Vol 4, No 3-4, 1982
26
Short Latency Somatosensory Evoked Potentials in Childhood Masanobu Tayama, MD, Toshiaki Hashimoto, MD, Noboru Kawano, MD, Kyoichi Hiura, MD, Junji Suzue, MD, Tamio Kokawa, MD, Shoichi Endo, MD, Kuniaki Fukuda, MD, Yasunori Tamura, MD, Akio Mori, MD, and Masuhide Miyao, MD Department of Pediatrics, School of Medicine, Tokushima University, Tokushima
The scalp recorded short latency somatosensory evoked potential (SSEP) on median nerve stimulation is a volume conducted potential that has a subcortical origin. SSEP is more useful for the diagnosis of neurological disorders compared with somatosensory evoked potentials. There have been several clinical reports of SSEP in adults, but not yet in children. This report presents SSEP findings in children.
Materials and Methods The subjects were 57 normal children (1 month to 16 years old), 25 neurological patients and 7 normal adults. The median nerve was stimulated transcutaneously at the wrist. Electrical stimuli were applied at a rate of 5-6/sec and were adjusted to produce a small twitch of the thumb. Reference electrodes were placed on the back of the hand or on the ear lobe contralateral to the median nerve stimulated. Recording electrodes were placed at C3 or C4 according to the international 10-20 system, Erb's point and at the seventh cervical spine. 1,200 or 2,400 response were averaged in each recording and the analysis time was 20.48 msec.
Results 1) Four components of SSEP (PI, P2 , P3, Nl) constantly appeared; PI (initial positive potential), P2, P3 (these positive potentials were followed by Nl), and Nl (large negative wave).
2) The latency of each peak was prolonged according to the development , and correlated positively with height and arm length .
3) It was at the age of about 10 years that the adult pattern of SSEP was approached.
4) There was no significant difference between the evoked potentials of right side stimulation and those of left side stimulation, both the awake state and in sleep, but P4 was prolonged during slow wave sleep.
5) In SSEP neurological patients with hemiparesis, the P4 wave was absent on the affected site.
Conclusion 1) In children, SSEP was able to be recorded .
2) The evoked potentials of SSEP changed with development.
3) SSEP will be useful for the diagnosis of neurological disorders.
Key words: Short latency SEP, far field potential, age developmental change.
27
Short Latency Somatosensory Evoked Potentials in Infancy and Early Childhood Shigeto Kasagi, MD, Hiroki Takakura, MD, and Ikuro Suganuma, MD Division of Child Neurology, Brian Research Institute, Tottori University, School of Medicine, Yonago, Tottori
There have been several studies that described short latency somatosensory evoked potentials (short latency SEP) in normal adults and in patients with neurological diseases, but not in childhood. We studied short latency SEP in childhood, especially in infants and young children.
Subjects and Methods Twenty children (Ages; 13 days to 7 years) and 7 adults (Ages; 21-27 years) were healthy, none showed abnormal neurological signs. They were in the supine position and made comfortable (over 5 years), or asleep (under 5 years). Square-wave pulses were delivered via disc electrodes placed over the right median nerve. A series of 1,000 stimuli were presented at a repetition rate of 3/s. Recording electrodes were placed at Cz,
C3 and AI. Reference electrodes were on the back of the left hand (LH). The two channels of Cz-LH and C3-AJ were amplified and averaged.
Results 1) Normal adult control group; We obtained a similar pattern to that reported by Cracco (1976).
2) Childhood group; Short latency SEP showed almost the same pattern as that of normal adults.
3) Peak latencies and interpeak latencies of each component varied according to the age. Twenty subjects were divided into 3 age groups. The following is the mean and standard deviation (SD) of peak latencies and interpeak latencies for each group.
Conclusion 1) In infants and young children, short latency SEP obtained were almost the same as those of adults.
2) Peak latencies and interpeak latencies of each component varied according to the age. Two factors, body growth and maturation of the nervous system, seem to cause the variability.
Key words: Short latency SEP, peak latency, interpeak latency, maturation of the nervous system.
( I3ds-30ds) (3M-1Y7M) (3Y6M-7Y) Normal adults
PI 5.85 (0.62) 5.96 (0.48) 6.99 (0.31) 9.31 (0.37) P2 7.92 (0.56) 7.04 (0.55) 8.27 (0.52) 11.43 (0.29) P3 11.71 (0.74) 9.63 (0.59) 10.51 (0.42) 14.34 (0.29) N1 24.95 (4.68) 19.40 (3.78) 17.17 (0.78) 19.06 (0.25) PI -P2 2.04 (0.46) 1.09 (0.20) 1.29 (0.30) 2.11 (0.20) P2 -P3 4.05 (0.55) 2.59 (0.20) 2.24 (0.36) 2.91 (0.53) P3 - N1 3.40 (4.63) 9.96 (3.28) 6.67 (0.89) 4.06 (0.86)
28
F-Wave Study on the Ulnar Nerve in.Children. Part 1. Control Subjects Akihisa Mitsudome, MD, Hiroko Ogata, MD, and Tomoko Uchida, MD Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka
Despite extensive studies on the F-waves of adults, few papers have appeared describing the F-waves of children. We have studied F-waves of children, and here we report the F-waves of normal control children.
The control subjects were 20 children without neurological disorders. Their ages ranged from 6 to 17 years. The ulnar nerve was repetitively stimulated (1 Hz, 10 seconds) at the elbow and the wrist, and
each F-wave was recorded with surface electrodes. 40-100% of stimuli evoked F-waves, and in 25% of the normal subjects all stimuli evoked F-waves.
The latency of the F-wave measured from the stimulus artifact to the beginning of the evoked potential varied. The disparity of the shortest latency and the latest varied by 0.5 to 3.0 msec. The shortest latency was 20.2 ± 3.1 msec at the elbow and 23.3 ± 3.1 msec at the wrist. The amplitude of the F-wave was also irregularly variable between 100 to 1,000 }.LV. FMCV was 60.4 ± 8.6 m/sec (wrist-spinal cord) and 59.8 ± 9.1 m/sec (elbow-spinal cord).
Key words: F-waves, evoked potential, peripheral nerve stimulation.
Brain & Development, Vol 4, No 3-4,1982 219
29
Study on Function of Midbrain Reticular Formation by Evoked Eyelid Microvibration Akihiro Yasuhara, MD, Aiko Yamada, MD, Tadaki Matsumura, MD, and Motohiro Yasuhara, MD Departments of Pediatrics (A Y, A Y, TM) and Physiology (MY), Kansai Medical University, Osaka
The palpebral reflex induced by flash stimulation can be recorded in 2 ways, one is by the photopalpebral reflex (PPR), potential changes, and the other is by photo-evoked eyelid microvibration (MY), acceleration changes. Both responses are known to reflect the function of midbrain reticular formation (RF). Analysis of these responses is therefore helpful for determining the function of RF. This paper deals with several results of MV in a study on various neurological diseases of children.
Subjects and Methods The subjects were 16 cases of neurological disorders, such as, intracranial hemorrhage (ICH), anoxicischemic encephalopathy, early infantile epileptic encephalopathy with suppression-bursts (EIEE), meningoencephalitis with a-coma and a pontine tumor, 114 healthy children and 10 healthy adults as a control group. MV induced by flash stimulation (1 time per 5-10 seconds) was recorded with a crystalline barium titanate-lead pick-up (Nihon-Kohden Inc, MT-47111) placed on the upper eyelid. 30 reactions were analyzed as an average wave with a digital computer.
Results 1) In MV of healthy children and the newborn, increased latency and irregularity of waves were observed compared with those of healthy adults.
2) MV did not appear in the cases of meningoencephalitis with a-coma and EIEE.
3) In a case of a pontine tumor, low MV amplitude was found ..
4) Among 8 cases of intracranial hemorrhage [3 intraventricular hemorrhage (IYH) , 3 subdural hemorrhage (SDH) and 2 subarachnoid hemorrhage 1 , in one case of grade III IVH MV was completely lost and MV was markedly suppressed in one case of SDH. In these cases MV began to appear following the clinical improvement. In the other 6 cases of ICH, MV did not show marked abnormal changes.
5) No MV was recorded in the acute phase of 5 cases of anoxic-ischemic encephalopathy. Among these, 3 cases recovered clinically with the appearance of MV. In one of the rest a depressed response persisted even after the appearance of MY. There were no MV in the last case even though the patient was followed to 8 months old, and this case had a poor course with severely retarded neurological development.
Summary MY is very useful for checking the activity and/or function of RF according to our study. MV analysis will be, furthermore, expected to shed light on the level of consciousness of the newborn.
Key words: Photo-evoked eyelid micro vibration, midbrain reticular formation, level of consciousness, newborn and child.
220 Brain & Development, Vol 4, No 3-4, 1982
30
Sleep Spindle Activity in EEG in Childhood Hisaharu Suzuki, MD, Keiichi Morooka, MD, Hiroko Ikota, MD, Hiroyoshi Koide, MD, and Atsushi Yasaka, MD Department of Pediatrics, Saitama Medical School, Saitama
The significance of spindle waves in the sleep record of EEG was evaluated in controls and children with neurological disorders qualitatively and quantitatively. The children were divided into 6 groups as follows.
Group 1: 28 normal children, 28 EEGs. Group 2: 35 children with simple febrile convul
sion, 35 EEGs. Group 3: 39 children with various types of epilep
sy, 51 EEGs. Group 4: 10 children with various types of cerebral
palsy, 11 EEGs. Group 5: 28 children with various degrees of men
tal retardation, 28 EEGs. Group 6: 19 children with various types of epilep
sy and various degrees of mental retardation, 39 EEGs. The quantity of spindle waves was divided by visual analysis into two groups. A: Abundant appearance of spindle waves, B: poor appearance or lack of spindle waves.
The rate of B of each group was respectively 7.1 %, 5.7%, 5.9%, 18%, 43% and 44%. Groups 5 and 6 showed significantly high rates of low or absent spindle waves compared to other groups. No significant differences were found between groups 1, 2, 3 and 4, or between groups 5 and 6.
The mean duration time of spindle waves was 7.6 sec, 6.5 sec, 6.5 sec, 7.3 sec, 4.0 sec and 2.8 sec, respectively.
We found that spindle waves in the sleep record of EEG were poorly seen in mentally retarded children compared to those with other neurological disorders such as simple febrile convulsion, epilepsy and cerebral palsy, and that extreme spindles were seen only in children with epilepsy and mental retardation.
We concluded that spindle waves in the sleep EEG record are valuable in the diagnosis of neurological disorders.
Key words: Sleep record of EEG, spindle waves, mental retardation, epilepsy, cerebral palsy.
31
Copper and Zinc in Cerebrospinal Fluid of Children with Neurological Diseases Junji Suzue, MD, Masanobu Tayama, MD, Kyoichi Hiura, MD, Noboru Kawano, MD, Toshiaki Hashimoto, MD, and Masuhide Miyao, MD Department of Pediatrics, School of Medicine, Tokushima University, Tokushima
There is a substantially published literature on the concentrations of copper and zinc in the blood of patients with various diseases, but little information is available on the concentrations of copper and zinc in cerebrospinal fluid (CSF) of the children with neurological diseases_ The purpose of this study was to examine the concentrations of copper and zinc in CSF of the patients with various diseases.
Subjects and Methods The concentrations of copper and zinc in CSF were measured by atomic absorption spectrophotometry. The levels of ceruloplasmin in CSF were measured by the method of single radial immunodifusion. CSF from the patients with Guillain-Barre syndrome were column chromatographed on Sephadex G-75 in order to know the molecular weight and the nature of copper compound.
Results 1) The concentrations of copper and zinc in CSF of the children with Guillain-Barre syndrome (5 cases), with polyneuritis (3 cases), with bacterial or viral meningitis (3 cases), with central nervous system (CNS) leukemia (3 cases), with Wilson disease (2 cases) and with non-neurological diseases (8 cases) were tested. Marked increase of CSF copper and zinc concentrations was seen in the patients with GuillainBarre syndrome. While CSF copper and zinc concentration in the patients with polyneuritis and with Wilson disease were not increased. Slight changes in the values of CSF copper and zinc concentrations according to the clinical courses were seen in the patients with bacterial and viral meningitis and with CNS leukemia.
2) The ceruloplasmin levels in CSF of the patients with Guillain-Barre syndrome were increased. The CSF were column chromatographed on Sephadex G-75. The peak of CSF was found at the same position as that of control serum.
Conclusion Our study suggested that the increased CSF copper and zinc concentrations in the patients with GuillainBarre syndrome were partly resulted from the penetration of the serum ceruloplasmin into CSF. However, further investigations will be needed for complete explanation of our results.
Key words: Cerebrospinal fluid, copper, zinc, neurological diseases.
32
Studies on Blood-CSF Barrier of Neurological Disorders in Childhood Kazuhiko Goto, MD, Hiroaki Shiihara, MD, Hirohisa Eguchi, MD, Yasufumi Utsumi, MD, Shinji Kuromori, MD, and Motomizu Ariizumi, MD Department of Pediatrics, Nihon University, School of Medicine, Tokyo
The blood-brain barrier is broken by various disorders of the central nervous system (CNS). In this study, the blood-cerebrospinal fluid-barriers (B-CSF-B) in febrile convulsion, epilepsy, meningitis, and acute encephalitis were examined by S/CSF albumin ratio.
Materials and Methods Subjects were 56 cases with simple febrile convulsion, 35 cases with epilepsy, 10 cases with meningitis and 5 cases with acute encepnalitis. Twenty-four controls were infants having headache or suspicion of bniin tumor with spinal fluid cells less than 20/3 mm'. CSF and serum were simultaneously obtained and stored in the freezer at less than -80°C. Spinal fluid and serum albumins were measured by electroimmunophoresis.
Results In control group, the serum/CSF albumin concentration ratio were 491 ± 145 in patients aged from 6 to 11 months, 385 ± 46 in 4 patients aged 1 year, 649 t 139 in 3 patients aged from 2 to 5 years and 530 ±
126 in 8 patients aged 6 to 10 years. Hyperpermeability of B-CSF-B is observed in 9 out of 10 cases (90%) with meningitis, 4 out of 5 cases (80%) with acute encephalitis, 4 out of 56 cases (7.1 %) with febrile convulsion, and 5 out of 35 cases (14.3%) with epilepsy.
Conclusion Disturbance of B-CSF-B in epilepsy seems to be related with the duration and frequency of convulsion, while it seems to be not related with convulsion in febrile seizure. In the cases of meningitis, the permeability of B-CSF-B became normal within 8 or 10 days, and in acute encephalitis, it continued for a relatively long period.
Key words: Blood-CSF-barrier, serum/CSF albumin concentration ratio, epilepsy, meningitis.
Brain & Development, Vol 4, No 3-4,1982 221
33
Change of CSF Protein Fractions in Childhood. 1st Report: Full-Term Babies and Premature Infants Hiromi Arai, MD, Akinori Osawa, MD, Motomizu Ariizumi, MD, and Kazuo Baba, MD Department of Pediatrics, Nihon University, School of Medicine, Tokyo.
There exists a considerable literature on the total protein in cerebrospinal fluid (CSF) in the newborns but little work has been done to study a develop~ mental change of its composition . TIle aim of the present study is to determine the change of CSF protein fractions with gestational aging.
Materials and Methods Fifteen newborn infants born from 28 to 43 weeks of gestational age without organic brain injuries were included in this study. The CSF specimens obtained by lumbar puncture were centrifuged for 10 minutes and stored in a deep-freezer. A band separation of
Gestational No of T.P. Prealb age (weeks) patients (mg/dl) ('10)
28 - 31 3 140 2.3 ± 20 ±0.2
32 - 35 4 97 3.0 ± 15 ± 0.8
36 - 39 4 72 4.3 ±4 ± 1.3
40 -43 4 68 4.8 ± 14 ± 0.9
34
Simultaneous Measurement of CSF Monoamine Metabolites by High-Pressure Liquid Chromatography with Electrochemical Detection (LCEC) Hiroyuki Haraguchi, MD, Yukiharu Une, MD, Atsuko Shionaga, MD, and Minoru Hata, PhD Division of Pediatrics, The Center of Developmental Medicine and Education of Kitakyushu City, Fukuoka
Quantitative analysis of CSF monoamine metabolites ~as become a useful method for studying alterations m the CNS metabolism of living patients. In the present study, five monoamine metabolites in CSF were measured simultaneously by LCEC. A small volume (0.5 m!) of CSF was applied onto an ionexchange resin column, followed by extraction with ethyl acetate at pH 3.0. This fraction contained both acidic (homovanillic acid, dihydroxyphenylacetic acid vanillylmandelic acid and 5-hydroxYindole-3-aceti~ acid), and alcoholic (methoxyhydroxyphenylglycol) metabolites.
The extract was analyzed on a reversed-phase
222 Brain & Development, Vol 4, No 3-4, 1982
CSF protein was made by disc electrophoresis using a 7 . 5 ~ . poly~crylamide gel. The electrophoretogram w~s dIVIded mto 6-zones: prealbumin, albumin, A, B, Band G zone.
Results The CSF protein fractions of each gestational age were shown in Table.
Conclusion Among CSF protein fractions albumin-zone was reduced with increasing gestational age as much as CSF protein concentrations does. Prealbumin-zone which maintained the constant levels, appeared to b~ comparatively elevated with gestational age because of a reduction of albumin zone. The change of CSF protein fractions was assume to be representative of a development of the blood-brain-barrier, however a significance of the Blood-CSF transport of prealbumin was obscure.
Key words: Disc electrophoresis, CSF protein fractions in premature and full· term infants.
Alb A B B' G (%) (%) (%) (%) (%)
75.2 5.4 5.2 3.0 8.9 ±0.6 ± 0 .6 ± 0.3 ± 0.7 ± 1.6
72.2 4.8 7.3 3.1 9.7 ±2.4 ± 0.8 ± 1.5 ± 0.9 ± 0.7
69.2 5.6 6.8 4.3 9.9 ± 2.2 ± 0.6 ± 1.2 ± 0.6 ± 1.5
69.1 5.1 7.2 4.0 9.9 ± 3.0 ± 0 .8 ± 1.6 ± 0.5 ± 1.3
column of TSK-GEL ODS with a mobile phase of phosphate buffer (0.05 mol, pH 6.50). Each analysis required 18 min . The method was sufficiently sensi· tive to detect 50 pg of monoamine metabolites. Analytical recoveries ranged from 62.4% to 82.5% for each metabolite except 5-hydroxyindole-3-acetic acid (41.2%), with good precision (coefficients of variation between 2.3% and 10.2%).
We ha~e encountered three children who developed a progressive dystonic condition in the first decade of life. Investigations of these patients revealed reduced concentrations of lumbar CSF homovanillic acid. In all three cases, therapy with L-dopa resulted in elevati.on of CSF homovanillic acid, which was accompamed by marked clinical improvement. This method will ~rovide a sensitive and specific technique for the slmultaneous measurement of CSF monoamine metabolites.
Key words: CSF monoamine metabolites electro· chemical detection, liquid chromatograph;, L·dopa therapy, progressive dystonia.
35
Alteration of CSF Homocarnosine Levels in Children with Epilepsy, Febrile Convulsion and Meningitis Hiroshi Takahashi. MD. Toshihiro Honda. MD. Kennichiro Kaneko. MD. Hitoshi Iwasaki. MD. Yoshimasa Minowa. MD. Keiichi Takahashi, MD. and Chikaya Ohtsuka. MD Department of Pediatrics. Juntendo University. School of Medicine. Tokyo
The relationship between CSF homo carnosine (a dipeptide of gamma-amino butyric acid and histidine, specific to the central nervous system) levels and the neurological symptoms such as convulsion and the grade of consciousness in cases with epilepsy and meningitis are discussed.
Materials and Methods The subjects were 32 cases with epilepsy (grand mal and hemiconvulsion: 14 days-15 years), 5 cases with febrile convulsion (1-5 years) and 42 cases with meningitis (5 days-14 years), respectively. Epileptic patients were divided into two groups: uncontrolled (n = 26) and controlled (n = 11).
Cerebrospinal fluid was obtained by lumbar puncture and homocarnosine in CSF was identified and determined with an amino acid autoanalyzer (Hitachi Co).
Results 1) The normal homocarnosine level in CSF was 0.75 ±
0.24 /Lmol/dl (n = 49). Mean homocarnosine levels in CSF of controlled and uncontrolled epileptic children were 0.6] ± 0.25 /Lmol/dl and 1.03 ± 0.37 /Lmol/dl, respectively . A significant difference in homocarnosine levels in CSF was found between the controlled and uncontrolled epileptic groups (p < 0.01). In addition, significant differences in homocarnosine levels in CSF were found between normal subjects and the two epileptic groups (p < 0.1, p < 0.001, respectively).
2) The mean homocarnosine level in CSF of the cases with febrile convulsion was 1.09 ± 0.04 /Lmol/dl, which was significantly higher than that of the controlled epileptic group (0.66 ± 0.41 /Lmol/dl, n = 3: 1-5 years).
3) The cases with meningitis were divided into 3 groups on the consciousness state: clear, somnolence and coma. Although there was no significant difference in homocarnosine levels in CSF between normal children (0.89 ± 0.23 /Lmol/dl, n = 23) and meningitic children with clear consciousness (0.91 ± 0.31/Lmol/dl, n = 68), significant differences in homocarnosine levels in CSF were found between the clear and somnolent groups (0.67 ± 0.32/Lmol/dl, n = 16) (p < 0.01), and between the somnolent and comatous groups (0.39 ± 0.31/Lmol/dl, n = 13) (p < 0.01), respectively.
Conclusion Homocarnosine levels in CSF in the cases of uncontrolled epileptic children were significantly high, and in the cases with meningitis accompanied by disturbed consciousness homocarnosine levels in CSF were significantly low.
Key words: Homocarnosine, cerebrospinal fluid, epilepsy, meningitis.
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Clinico-radiological Studies of Midline Posterior Fossa Low Density Zones on Computed Tomography Yoshitaka Nakada, MD. Takao Enomoto, MD, Takashi Yoshizawa. MD, Atsuro Tsukada, MD, Yutaka Maki, MD, and Junko Fujiwara. MD Departments of Neurosurgery (YN, TE, TY, AT, YM) and Pediatrics (JF), The University of Tsukuba School of Medicine, Ibaraki
Since the advent of computed tomography (CT), the posterior fossa midline anomaly is no more a rare lesion, but its pathophysiological significance is still not fully understood. In this study we classified midline posterior fossa low density zones on CT and investigated the correlation with clinical pictures.
Materials and Methods From Feb 1977 to March 1981 we carried out CT in 1,900 cases below the age of 15, of which 27 showed a large low density area in the posterior fossa. The craniogram, RI-cisternography and/or metrizamide CT were taken into consideration in some cases. Tumors, vascular lesions, traumatic hematoma and/or intraaxial low density areas of unknown etiology were excluded.
Results Extra-axial low density areas were classified into 6 types; mega cisterna magna, cerebellar hemispheric dysplasia, vermian dysplasia, combined dysplasia, Dandy-Walker malformation (DWM) and arachnoid cyst. A large cisterna magna extending upward beyond the midpoint between the posterior rim of the foramen magnum and the internal occipital protuberance was called mega cisterna magna grade I and one extending to the protuberance grade II. Only 18 cases (1 % of total cases examined) formed the latter group. In these cases, the width and the depth of the cistern never exceeded 25 mm. The confluence sinuum was normally positioned. The vermis was not defective. A few cases had accompanying supratentorial anomalies. Of the 7 cases with cerebellar dysplasia, two were the hemispheric type and two the vermian type. The remaining three were combined types. A case with DWM had a cephalocele and pachygyria in addition to the typical triad. A case with an arachnoid cyst showed hydrocephalus and pictures of a tight posterior fossa, which somewhat improved after a shunting operation. Contrary to the mega cisterna magna cases, the cases with DWM or cerebellar dysplasia frequently had accompanying supratentorial malformations. Some cases with cerebellar dysplasia showed mild ventricular dilatation and posterior fossa bulging but the CSF bulk flow was quite normal. Of the 7 cases with cerebellar dysplasia, six showed mental retardation and four had convulsive episodes. There were other accompanying anomalies in six cases. Hypotonus was one of the characteristic features of DWM and vermian type cerebellar dysplasia.
Key words: CT, low density area, cerebellar dysplasia. Dandy-Walker syndrome, mega cisterna magna, arachnoid cyst.
Brain & Development, Vol 4, No 3-4, 1982 223
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Evaluation of Brain CT with Two Dimensional Measurement-Comparison of Juvenile and Senile Changes on CT -Mikio Hiraiwa, MD, Chizuru Nonaka, MD, Toshiaki Abe, MD, Kazuhiko Ohmi, MD, Tomoko Togo, MD, and Yasuko Fujita, MD Department of Pediatrics, Teikyo University, School of Medicine, Tokyo
There are some papers on the changes in CT findings with ageing. Previous authors applied one dimensional measurement Oinear measurement) or visual impression. These methods are not satisfactory for objective evaluation of CT, as we reported last year. With two dimensional measurement we investigated the changes in CT with ageing.
The cases studied were as follows: 59 children, aged from 0 to 5 years old and 35 adults aged from 32 to 78 years old, with neurological disorders for whom brain CT was performed with a General Electrics (USA) Model CT/T-8800. Measurements were taken at the slice through the foramen of Monro. Intracranial area (lC), brain area (BA), ventricular area (V A), and bifrontal fluid collection area (BFC: cerebrospinal fluid-like low density area between skull and frontal lobe) were measured. Methods for two dimensional measurements were previously reported [1] .
For comparison of each age group, we took new indices as follows: 1) brain area index (BAI; BA x 100/ IC), 2) ventricular area index (VAl; VA x 100/IC), 3) bifrontal fluid collection area index (BFCI; BFC xl 00/ IC). Table 1 shows the changes of each indices with ageing.
Table 1
BAI VAl BFc/
0- 3m 91.6 1.5 3.2 4- 6m 92.0 1.6 3.0 7 -11m 94.8 1.1 1.9 1 - 2y 95.7 1.1 1.2 3- 5y 96.5 1.1 0.4
31 - 40y 96.5 1.2 0.5 41 - SOy 96.3 1.9 0.2 51 - 60y 94.1 2.1 1.1 61 - 70y 92.9 2.3 1.5 71 - 78y 87.9 4.3 2.5
BAI increased rapidly in children, especially in infancy, and slowly diminished in the senile group with ageing. V AI showed no obvious changes in the juvenile group, but in the senile group it increased slowly. BFCI decreased rapidly in infancy and increased after the fifties.
CT findings obtained for juvenile and senile patients are often evaluated as brain atrophy. But there were marked differences, as is shown. Therefore, when CT scans for juvenile or senile patients are studied, it should be considered whether there are factors of an age-related changes.
224 Brain & Development, Vol 4, No 3-4,1982
Reference 1. Hiraiwa M, Abe T, Fujii R, et a!. Two dimensional
measurement of ventricular and arachnoidal space on CT. Teikyo Med J 1980;3:39-46.
Key words: CT -objective measurement, CT -age· related changes, CT - two dimensional measurement.
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Change of Brain CT in Children with Two Dimensional Measurement Chizuru Nonaka, MD, Mikio Hiraiwa, MD, Toshiaki Abe, MD, Kazuhiko Ohmi, MD, Tomoko Togo, MD, Yasuko Fujita, MD, and Ryochi Fujii, MD Department of Pediatrics, Teikyo University, School of Medicine, Tokyo
There are some reports that describe changes of CT findings with ageing in children, but these works were done by using one dimensional measurement. But this method is thought to be insufficient for objective evaluation of CT findings. We reported last year a method of two dimensional measurement as a more objective one. Then with an application of our method, we discussed changes of CT findings with ageing in children.
Seventy-four children with neurological disorders, aged from 10 days to 12 years old, on whom CT had been performed with a General Electrics (USA) Model CT/T 8800, were studied.
We measured intracranial area (lCA), brain area (BA), ventricular area (V A) and bifrontal fluid collection area (BFC; cerebrospinal fluid-like low density area between skull and frontal lobe) at the slice through the foramen of Monro.
ICA and BA increased with ageing, but V A showed no obvious changes. The increases of IC and BA were significant in infancy and the toddler period. BFC decreased with ageing on the average and was invisible in many cases over three years old.
Since the skull and brain developed with ageing, we looked for new indices for relative comparison of age groups. Brain area index (BAI: BA x 100/ICA), ventricular area index (VAl: VA x 100/ICA), and bifrontal fluid collection area index (BFCI: BFC x 100/ ICA) were used for comparison. The increase of BAI well matched that of BA, and the decrease of BFCI well matched that of BFC. VAl was slightly higher in early infancy than in the later period.
IC and BA were slightly larger in males than in females, but the difference was not significant.
These results were in line with the data for head circumference and brain weight changes with ageing already known.
We concluded that two dimensional measurement is an objective method for evaluation of CT findings from the viewpoint of development in children.
Reference 1. Nonaka C, Hiraiwa M, Abe T, et a!. Change of
brain and cerebrospinal fluid area on CT with development in childhood. Teikyo Med J (Tokyo) 1980;3:371-7.
Key words: Brain CT, two dimensional measurement, ageing.