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Somatosensory-evoked potentials were recorded during and after 31 operations for intracranial aneurysms, and the changes in the central conduction times, namely, the interpeak latencies between the N14 and N20 peaks in response to bipolar stimulation of the median nerve, were studied. Neuroleptanalgesia and routine intracranial operative procedures such as opening the dura mater, drainage of the cerebrospinal fluid, gentle retraction of the brain, and microsurgical dissection of the circle of Willis, were found to have no significant adverse effect on the evoked responses, whereas the temporary clipping of the major cerebral artery or premature rupture of the aneurysm associated with hypotension or both, often caused significant prolongation of the central conduction time. Prolongation of the central conduction time exceeding 1.2 ms or disappearance of the N20 peak adversely affected the postoperative conditions in 8 of 13 patients (62%).

With the topographic EEG mapping method, the correlation between the morphologic abnormality of the brain and its functional changes was investigated in 13 patients with porencephaly and arachnoid cyst verified by CT scan. The spatial distribution of the EEG activity was displayed in the delta, theta, alpha-1, alpha-2, beta-1, and beta-2 frequency bands. The abnormality of EEG topographic images (e.g., an increase of the power of delta activity and/or a decrease of the power of alpha activity in the involved side of the brain) was more marked in cases with porencephaly than those with arachnoid cyst, and in cases with mental retardation or paralysis than among those without.

SUMMARY Electroclinical features of neonatal seizures were studied in 215 neonates who developed seizures during the first three weeks of life. In 62 of them, clinical fits occurred during the actual polygraphic recording. The electro-clinical correlations were very variable, although there were some statistically significant associations between certain types of seizures and electrical discharges. The relation between seizures and sleep states was investigated in 40 infants who had more than three fits during the recording. The state in which more than 70% of seizures occurred was active sleep in 28% of the cases, quiet sleep in 13%, indeterminate sleep in 8%, and wakefulness in 8%. In 50%, seizures did not tend to occur in a given state. The authors thank Professor Suzuki for his continued interest and encouragement.

A follow-up study was performed on 40 children with tuberous sclerosis and epilepsy. In 68% of the patients with infantile spasms and 73% of those without them, complex partial seizures were observed. Thus, patients with tuberous sclerosis are subject to not only infantile spasms but also complex partial seizures. Patients with infantile spasms showed mental retardation more often than those without. Seizures which had evolved from infantile spasms were more difficult to control than those which had not. The prognosis of infantile spasms associated with tuberous sclerosis was better than that of prenatal group other than tuberous sclerosis. Forty percent of the 40 cases showed asymmetry on EEG, and the asymmetry tended to disappear as the patients grew up.

The biosynthetic activities of protein and collagen from the patient of kinky hair disease, were reduced to 70 and 50%, respectively, compared with control. In tissue cultures, fast-green FCF staining coarse granules were found in the cytoplasm of skin fibroblasts from the patient. Ultrastructurally, collagen fibrils by iliac cartilage biopsy were irregular in width. Ruthenium red staining granules, presumed to be proteoglycans in the cartilage matrix, were relatively small in size and few in number. Chondrocytes showed poor development of organelles and relatively small glycogen accumulation.

Summary In order to elucidate the significance of perinatal brain damage in the etiology of epilepsy, 139 full-term neonates considered to have suffered a severe degree of perinatal hypoxia were examined neurologically and electroencephalographically for two-nine years. Thirty-eight (27.3%) of them developed epileptic seizures during the follow-up period. Sixteen infants developed infantile spasms at ages two-13 months, while 10 manifested generalized motor seizures mainly at one-four years. They all had neonatal background EEGs suggesting a severe degree of brain damage, although the infants with infantile spasms and myoclonic seizures showed more abnormal neonatal EEGs than those with other types of fits. The combination of multiple factors, mainly exogenous and constitutional, is necessary for the development of epileptic seizures, especially in patients with a lesser degree of brain damage.

MIZUTANI, N., MIYAZU, M., MAEHARA, M., ISOMURA, S., WATANABE, K. and IMANISHI, J. Treatment of Subacute Sclerosing Panencephalitis with Human Leukocyte Interferon. Tohoku J. exp. Med., 1985, 146 (3), 277-284-In five patients with Subacute sclerosing panencephalitis (SSPE), human leukocyte interferon (IFN) therapy was tried. IFN was administered intramuscularly, intravenously, and intrathecally. The total dose of administered IFN ranged from 13×106 to 116.92×106 IU. There were no severe side effects except for temporary high fever and vomiting. Observation of the clinical course were made for 26-60 months. At the beginning of the treatment, one of the patients was at the first stage of Jabbour's classification and the other four at the second stage. No clinical improvement was observed and the clinical course was progressive in all patients. At present, one of the patients was at the second stage and the other four were at the fourth stage. EEGs showed progressive deterioration, and cranial CT scan demonstrated progressive cortical atrophy and ventricular enlargement. Measles antibody titers in the serum and CSF also unchanged. On the other hand, permeability of IFN at blood-brain barrier (BBB) was relatively good.

In neonates and infants, sleep-wake parameters indicate characteristic ontogenetic features. Sleep spindle activity also changes with maturation in terms of frequency, amplitude, and amount. For this reason, spindles are one of the useful indices of cerebral function in infants. The literature on the development of spindles in normal and mentally retarded children is reviewed.

The effect of proteinase inhibitors such as TLCK, TPCK and leupeptin on vascular permeability was investigated in the carrageenin-air-pouch inflammation in rats. When each inhibitor was injected into the air-pouch immediately after carrageenin injection, TLCK, TPCK and leupeptin caused a rapid and significant increase in vascular permeability. The TLCK- and TPCK-induced increase declined gradually, whereas leupeptin inhibited the vascular permeability after the temporary increase. When the inhibitors were injected 5 h after carrageenin injection, TLCK and TPCK increased the vascular permeability, whereas leupeptin was without effect. Cyproheptadine, an anti-histamine and antiserotonin drug, inhibited the leupeptin-induced temporary increase, but failed to inhibit the TLCK- and TPCK-induced increase in vascular permeability. These results suggest that the leupeptin-induced increase in vascular permeability was mediated by histamine and serotonin, while TLCK and TPCK may increase vascular permeability as a result of a direct action on endothelial cells.

✓ Two patients with benign intracerebral cysts are reported and a brief review of the literature is given. Although computerized tomography (CT) scanning is useful in detecting a variety of intracerebral cysts, the CT findings are not specific for any lesion. An exploratory operation with establishment of an adequate route of drainage and a histological examination of the cyst wall are mandatory in the management of patients with a progressive but benign lesion.

Proteinase inhibitors were evaluated for their anti-inflammatory actions on carrageenin-induced inflammation in rats. The development of granulation tissue and the exudate were markedly suppressed by a single injection of l -1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK) into the carrageenin-air-pouch immediately after carrageenin injection, whereas a single injection of TPCK at 12 or 24 hr after carrageenin injection was less effective or slightly effective respectively. These results suggest that proteinase inhibitors exert their anti-inflammatory actions by interfering with the initial inflammatory reactions after carrageenin injection. When the wet weight of granulation tissue and the weight of exudate were measured on day 4 after the simultaneous injection of carrageenin and inhibitors. a single injection of serine- and thiol-proteinase inhibitors including TPCK, leupeptin, antipain, chymostatin and cystamine suppressed the development of granulation tissue, though EDTA and o -phenanthroline, metallo-proteinase inhibitors, were also effective at a high dose. Exudate was reduced by treatment with TPCK in a dose-dependent manner, while EDTA and o -phenanthroline were effective only at a high dose. On the other hand, the migration of polymorphonuclear leukocytes into the carrageenin-air-pouch (the inflammatory lesion) was markedly suppressed by TPCK and leupeptin, while a high dose of cystamine and o -phenanthroline was slightly effective, and antipain, chymostatin. pepstatin, elastatinal, EDTA, trans -1-aminomethylcyclohexane 4-carboxylic acid and aprotinin were without effect.

A 10-year-old girl was reported who showed horizontal nystagmus in association with typical absence and 3-cycles/s generalized, bisynchronous spike-and-wave discharges. In view of the general concept that epileptic nystagmus is a manifestation of partial seizures, the occurrence of such an association deserves documentation.

Prognostic factors for mental and physical development and seizure control were investigated in 194 patients with convulsive disorders in the first year of life, excluding infantile spasms, neonatal convulsions and occasional convulsions. Thirty-three patients with febrile convulsions were included in the study. All patients were followed up to age six or older. The cases were subdivided into five etiologic groups; prenatal, perinatal, postnatal, doubtful and cryptogenic. Those with delayed development before the onset of seizures, or neurological abnormalities at the first visit had significantly less chance of being seizure-free and attaining normal mental and physical development. The prognosis for seizures and mental and physical development was much better in the patients with brief, symmetric, generalized tonic and/or clonic convulsions. This was also true with cryptogenic cases. There was a significant correlation between the initial EEGs and the long-term prognosis for mental and physical development and seizure control. Normal EEG was associated with a good prognosis. From these data, the neurodevelopmental status before the onset, the clinical features of convulsions and EEG findings in the infantile period were demonstrated to be important prognostic factors in addition to etiology.

Hyperargininemia is a rare hereditary disorder of the urea cycle due to a deficiency of arginase, which catalyzes arginine to ornithine and urea. This disorder is the most uncommon among the five inborn errors resulting from enzyme deficiencies of the urea cycle. Patients with this disorder all have similar clinical symptoms, which include vomiting, lethergy, irritability, convulsions and coma. Severe mental deterioration and a marked degree of spasticity of all four extremities are also characteristic.

In two sibling patients with lysinuric protein intolerance (LPI), the therapeutic effect of oral supplement of arginine and citrulline on postprandial hyperammonemia was investigated. Intravenous load of L-alanine (6.6 mmol/kg of body weight), and oral load of L-arginine (0.8 mmol/kg of body weight) or of L-citrulline (1.0 mmol/kg of body weight) during intravenous load of L-alanine were performed to study the preventive effect of arginine or citrulline supplement on hyperammonemia induced by intravenous amino nitrogen load. In the older sibling, the hyperammonemia induced by the intravenous amino nitrogen load was completely prevented by the oral supplement of citrulline, but not completely prevented in the younger sibling. On the other hand, the hyperammonemia was prevented by the oral supplement of arginine only in the younger sibling, but not in the older sibling. In the light of these results, the younger patient received an oral administration of L-arginine and the older patient L-citrulline for the treatment of postprandial hyperammonemia. Two-year observation of each patient revealed that postprandial hyperammonemia and aversion to protein-rich food completely disappeared and that a marked increase of body weight and height was obtained. Furthermore, there was no side effect with these amino acids supplements. The present study suggests that an oral supplement of arginine or citrulline is effective for preventing postprandial hyperammonemia in this disorder.

Body movements during sleep were observed in 14 full-term sick newborn infants such as perinatal asphyxia, purulent meningitis, meconium aspiration syndrome, melena, porencephaly, and hydranencephaly. Five newborn infants who had recovered from transient vomiting were examined as 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 an 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 LTM, 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 served to indicate a brain dysfunction.

Body movements during sleep were examined in eight non-eventful preterm babies and two full-term babies using the polygraphic methods including superficial EMG. Typical movements in quiet sleep were startle (St) or generalized phasic movement (GPM) and increased tonic activity in chin muscles. In active sleep, instead of total simultaneous patterns observed in quiet sleep, more un-coordinated and localized movements such as generalized movement (GM), localized tonic movement (LTM), localized phasic movement (LPM) and clonic movement (CM) occurred. Longitudinal study of movements revealed a decrease of St or GPM, GM and LPM. LTM did not decrease with increasing conceptional age. The differences of decreasing tendency among these movements may indicate the differences of maturational changes in the different part of CNS.

The neurotoxin N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found to be taken up into fetal mice through the placenta from a maternal mouse. C57 black mice were mated and MPTP (30 mg/kg) was given intramuscularly at the 18th day of gestation. Definite amounts of MPTP were detected in fetal brains by assay using high-performance liquid chromatography (HPLC) at 1 h after MPTP injection, and much higher contents of MPTP were found in maternal brains, too. An oxidative product of MPTP, the N -methyl-4-phenylpyridinium ion (MPP + ), was also detected in brains of both mother and fetus and its concentrations in their brains were followed at 1, 3, 6, 12, 24h after MPTP injection. The time to reach the maximal MPP + concentration in brains was different between mother and fetus; 1 h and 3 h respectively. In addition to brain, considerable amounts of MPP + were found in fetal liver, maternal liver and kidney, and in the placenta.

Serial changes of cranial CT findings were studied in three siblings with Wilson disease during the course of D-penicillamine therapy. The older two cases with neurological presentation revealed low density areas in the region of the basal ganglia on the CT scans performed before treatment. Mild cortical atrophy and mild enlargement of the lateral and the third ventricles were also observed. The chelating therapy resulted in a considerable improvement of neurological symptoms and disappearance of Kayser-Fleischer rings. The low density areas of the basal ganglia disappeared. However, cortical atrophy and an enlargement of the ventricles were still present. In an asymptomatic girl, the cranial CT scans remained normal after chelating therapy. The cranial CT scan is considered to be of great use both in diagnosis and observation of the clinical course in Wilson disease, and it is also of prognostic value.

The clinical efficacy and safety of Roxithromycin (RU) were compared with those of Midecamycin acetate (MOM) in patients with pneumonia in a double blind study. RU and MOM were administered orally for 14 days with daily doses of 300 mg (150 mg b.i.d.) and 600 mg (200 mg t.i.d.), respectively. The following results were obtained. 1. RU and MOM were administered to a total of 204 patients (RU: 101, MOM: 103). The clinical efficacy was judged in 150 patients (RU: 70, MOM: 80), with 54 of the patients excluded from the total by the committee. 2. The clinical efficacy rates were 81.4% for RU and 70.0% for MOM on the basis of the committee's judgement. There was no significant difference between the two groups. In the evaluation of the clinical efficacy by the doctors in charge, the efficacy rates were 81.4% for RU and 67.5% for MOM, which constitutes a significant difference between the two groups (p less than 0.05). 3. No significant difference was found between the two drugs in bacteriological efficacy. 4. No significant differences were observed in either the incidence of side effects between RU (4.3%) and MOM (4.0%) or in abnormal changes in the laboratory findings. 5. Regarding the clinical usefulness judged by the committee, RU showed a significantly higher rate than MOM (79.2% vs. 67.9%). There was no significant difference in the judgement by the doctors in charge. From the above results, it was concluded that a daily dosage of 300 mg of RU was equal in usefulness to 600 mg daily of MOM in the treatment of mild to moderate pneumonia.

A follow-up study was made on 200 children (115 boys, 85 girls) who had had infantile spasms, in order to compare their present condition over the age of six years with various prognostic factors. 48 of the children (30 males and 18 females) had died, and all the rest were aged six years or older at the time of final follow-up. 139 of the children had received ACTH therapy: at final follow-up, spasms had ceased in 43.5 per cent, and about the same proportion showed normal physical development; 23 per cent had normal mental development and 15.4 per cent were attending ordinary schools. Complete recovery (normal mental and physical development and attending ordinary schools) was achieved in only 19 cases (9.5 per cent). Of the cryptogenic cases, 44.4 per cent had made a full recovery. The poor prognostic factors for continuing seizures were evolution into other types of fits, relapse of seizures after ACTH therapy, seizures concomitant with spasms, and convulsions before the onset of spasms. Poor prognostic factors for physical development were delayed development before the onset of spasms, neurological abnormalities, PEG abnormality, symptomatic aetiology, neonatal convulsions, low birthweight, perinatal asphyxia and being female. Poor prognostic factors for mental development were delayed development before the onset of spasms, neurological abnormalities, PEG abnormality, prenatal and perinatal aetiology, relapse after initial ACTH therapy, laughing attacks, and evolution into other types of fits. Only in the cryptogenic cases was there significant correlation between the delay in treatment and the long-term prognosis for mental development. Poor prognostic factors for educability were very similar to those for mental development. In spite of conflicting views as to the long-term effects of ACTH, prompt treatment seems to be mandatory, at least in cryptogenic cases of infantile spasms.

The evolution of EEG, visual and auditory evoked responses (VER and AER) and sleep is described in three cases of semilobar holoprosencephaly. During the neonatal period, the waking EEG was characterized by almost continuous high amplitude rhythmic alpha-theta activity in case 1 and 2, which became discontinuous during quiet sleep. Moderate amplitude rhythmic alpha-theta waves were seen in case 3. This rhythmic alpha-theta activity gradually disappeared with increasing age, being replaced by non-specific slow dysrhythmia. In case 3, the subsequent EEGs were characterized by focal spikes at 4 months, multifocal spikes at 5 and 6 months, hypsarrhythmia at 8 months and bisynchronous diffuse sharp and slow wave discharges at 2 years and 7 months. Ictal EEGs were characterized by desynchronization and/or rapid synchronization, epileptic recruiting rhythm and postical high amplitude slow waves. Definite but mostly abnormal VERs or AERs were obtained in all three cases. In two cases, the evoked responses showed a progressive decrease in amplitude and VERs were abolished finally. No sleep cycle could be identified during the neonatal period probably because of frequent seizures. In two cases no circadian rhythm of sleep developed, although almost normal REM-NREM sleep cycle was present.

Serial poly graphic recordings of two to three hours duration were made in five full-term newborns with trisomy 18 and one full-term newborn with trisomy 13 syndrome. The newborns with 18 trisomy syndrome were poor sleepers with long periods of wakefulness and/or drowsiness. There were no consistent abnormalities in the sleep profile characteristic of 18 or 13 trisomy syndrome. These infants had some difficulty in organizing a stable sleep cycle especially during the immediate neonatal period. There was poor correlation between EEG patterns and states. After one to two weeks, cyclic organization of sleep showed some tendency towards normalization, although there were more trace alternant and fewer high voltage slow patterns in quiet sleep even around and after 44 weeks conceptional age. Other abnormal features of sleep often observed were an increase of indeterminate sleep, a decrease of quiet sleep, and an increase or decrease of active sleep in some records.

A new simple and economical plastic Boyden chamber for in vitro assay of leukocytes chemotaxis was devised by the use of a commercially available immunoassay plate. Zymosan-activated rat serum, formly-methionyl-leucylphenylalanme and leukotriene B4 caused concentration-dependent migration of the leukocytes into the lower chamber. About 50% of the cells loaded in the upper chamber migrated into the lower chamber for 80 min at the optimal concentrations of the three chemoattractants tested.

Electroclinical features of neonatal rhythmic alpha discharges were described on the basis of polygraphic recordings from 37 newborns with seizures. The main presumptive etiological factors were perinatal hypoxia, hypocalcemia, purulent meningitis and intracranial hemorrhage. Apneic seizures were most often associated with temporal alpha discharges, whereas clonic seizures were mainly associated with central ones. Sleep cycles were abolished in half of the infants, but in those with sleep cycles, clinical seizures occurred most frequently during active sleep. Alpha discharges occurring during quiet sleep were not associated with clinical fits. The neonates who suffered from perinatal hypoxia and/or intracranial birth injury all developed abnormally, whereas those with hypocalcemia showed the most favorable outcome. Those with other etiologies demonstrated an intermediate prognosis between the two.

Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9-G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic L-amino acid decarboxylase- and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week-old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice.

Interleukin-1β, tumor necrosis factor-α and lipopolysaccharide stimulated normal rat kidney cell line (NRK-52E) to produce a chemotactic factor for rat neutrophils. This cytokine-induced neutrophil chemoattractant (CINC) was purified to obtain a single band with a M.W. of 63,000 on SDS-PAGE. The purified CINC induced detectable migration and strong chemotaxis of neutrophils at concentrations of 10 −9 M and 10 −7 –10 −8 M, respectively. Checkerboard analysis indicated that CINC was a real chemotactic factor. Amino acid composition of CINC showed that CINC has a resemblance to human monocyte-derived neutrophil chemotactic factor (MDNCF) rather than human complement fragment, C5a.

The time courses of vascular permeability to native bovine serum albumin (BSA). cationized BSA. dextran (mol wt. 40.000) and bovine immunoglobulin G (IgG) in carrageenin-induced inflammation in rats were determined by the fluorometric method. The vascular permeability to BSA increased gradually until about 5 hr after carrageenin injection. The vascular permeabilities to dextran and IgG reached a maximum at 1 hr after carrageenin injection and then decreased. In the early-stage. 0-1 hr after carrageenin injection, dextran was the most permeating of the three. However, in the later-stage. 3-5 hr after carrageenin injection. BSA became the most permeating. Furthermore, cationized BSA was more permeating than native BSA having a negative charge in the early-stage. but the difference between the permeability to cationized BSA and native BSA was decreased at the later-stage. These data suggest that vascular permeability changes qualitatively in carrageenin-induced inflammation in rats, and it is unlikely that the increased vascular permeability is caused by the ultrafiltration through gaps formed between endothelial cells.

The clinical efficacy and safety of Cefodizime (CDZM), a new cephem antibiotic, was objectively compared with that of Cefotaxime (CTX) in patients with respiratory infections under a well-controlled comparative study. Patients were administered CDZM or CTX by drip infusion b.i.d. for 14 days in principle at a daily dose of two grams. The parameters assessed were clinical efficacy, safety and clinical usefulness. The following results were obtained: 1. On the basis of committee judgement the clinical efficacy rate was 78.1% (125/160) for the CDZM group, 82.7% (124/150) for the CTX group, and no significant difference was observed between the two drug groups. On the other hand, on the basis of judgement by physicians in charge, the clinical efficacy rate was 83.1% (133/160) for the CDZM group, 83.9% (125/149) for the CTX group, and no significant difference was observed between the two groups. 2. The corresponding figures for patients with pneumonia and pulmonary suppuration were 82.4% (70/85) for the CDZM group, 79.7% (59/74) for the CTX group and no significant difference was observed according to the committee judgement. The judgement by physicians in charge also revealed 83.5% (71/85) for the CDZM group and 82.2% (60/73) for the CTX group. No significant difference was noted between the two groups. While, the committee judgement for the clinical efficacy in patients with chronic respiratory tract infections showed 73.3% (55/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups. The corresponding figures were 82.7% (62/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups on the judgement by physicians in charge. Furthermore, the clinical efficacy of both drugs on chronic respiratory tract infections was assessed according to "Criteria for Evaluation of Clinical Efficacy of Chemotherapeutics on Chronic Respiratory Tract Infection". It was 76.8% (53/69) for the CDZM group, 76.3% (58/76) for the CTX group, and no significant difference was observed between the two groups. 3. The bacteriological eradication rate of causative pathogens was 92.4% out of 66 patients treated with CDZM and 95.5% out of 67 patients treated with CTX in whom judgement was possible. No significant difference was observed between the two drug groups. 4. The adverse reactions occurred in 4 (2.2%) patients for the CDZM group and 8 (4.5%) patients for the CTX group respectively, with no significant inter-group difference in frequency of these reactions for all cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Summary: A follow-up study was made on 304 children (164 boys, 140 girls) with convulsive disorders, excluding occasional convulsions, in the first year of life. All patients except 45 who died were followed until 6 years of age or older. At the final follow-up, the subjects were divided into six groups according to the degree of mental and physical development (groups I-VI). Seizures were regarded as absent if the patient had been seizure free for more than 3 years. At the final follow-up, seizures had ceased in 57.7%, and 43.4% had normal mental and physical development (group I). As to the initial diagnosis, the percentage of group I at the final follow-up was 81.8% with febrile convulsions and 37.6% with epilepsy. In patients without seizures it was 69.7% with febrile convulsions and 55.8% with epilepsy. Some 80.6% of patients with unclassified generalized motor seizures, 11.5% of those with infantile spasms, 2.9% of those with secondary generalized epilepsy other than infantile spasms, 46.4% of those with partial seizures, and 25.0% of those with hemiconvulsive seizures were finally placed in group I. The percentage of patients without seizures was 81.4, 33.0, 34.4, 57.7, and 100%, respectively. As has been suggested, among the first-year epilepsies, a subgroup with a more favorable prognosis may exist. Further studies regarding the etiology, ictal EEGs, and effectiveness of treatment and long-term prognosis of these cryptogenic benign infantile convulsions are needed to provide a firm basis for understanding convulsive disorders in the first year of life.

Heart rate variability was studied in normal and abnormal newborn infants during sleep in relation to the EEG background. The background EEGs of the full-term newborn infants were classified into normal, minimal depression, mild depression, moderate depression, burst-suppression and flat patterns in order of increasing severity. Nonsequential and sequential histograms were produced with the aid of a computer from some 500 consecutive RR intervals of the ECG recorded on a magnetic tape during polygraphic recordings. The sequential curves mainly showed fast oscillation during quiet sleep and slow oscillation during active sleep in normal infants. The infants who had moderately depressed EEGs presented pronounced oscillation. In those whose EEGs displayed burst-suppression and flat patterns, the sequential curves showed very little heart rate variability. They were often flat (fixed heart rate). Thus, heart rate variability was found to be one of the valuable parameters in evaluating abnormality of the CNS in newborn infants.

Evolutionary changes of the EEG up to one year in 81 infants followed from neonatal periods were studied. Trace alternant (TA) disappeared at 1–2 months in infants with normal outcome and those with cerebral palsy (CP) or mental retardation (MR). In patients with CP & MR or those with CP & MR & epilepsy (EP), the time when TA disappeared was delayed. Fresence of TA at or beyond 2 months suggest severe brain damage such as CP & MR, or CP & MR & EP. The spindle appeared within 3 months in normal infants and those with CP, but in some patients with CP & MR, or those with CP & MR & EP, no spindle ever appeared. The delay of its appearance beyond 3 months is considered to be an unfavorable sign. There is a very good correlation between neonatal background EEGs and the time of disappearance of TA and spindle appearance. The abnormal background EEGs after the first month suggested severe damage, and no specificity such as might reflect a certain type of developmental disability was found.

In a patient with hyperargininemia, enzyme replacement therapy such as whole blood exchange transfusion or erythrocyte transfusion was performed, and its effect was confirmed in vitro as well as in vivo. The patient has been treated with the restriction of protein intake, oral administration of an essential amino acid mixture, and sodium benzoate or phenylacetic acid. With these treatments, his plasma ammonia levels were controlled. On the other hand, plasma and CSF concentrations of arginine were not so well controlled. With whole blood exchange transfusion and erythrocyte transfusion, plasma arginine concentrations and plasma ammonia levels were controlled. These effects have continued for about 3 months. Furthermore, the effect of exchanged erythrocytes on the blood arginine levels was also confirmed by in vitro experimentation that mixes arginine with erythrocytes in the medium RPMI 1640. Arginine concentration of the medium did not decrease when arginine was mixed with erythrocytes of the patient, but when arginine was mixed with erythrocytes of mother or normal controls, it decreased rapidly. In calculation, 10(7) of erythrocytes of the mother or normal controls was presumed to metabolize 4-5 nmole of arginine per day. From these results, the erythrocyte exchange transfusion is considered to be effective for the control of clinical and biochemical abnormalities in this disorder.

The effects of two stages of sleep (REM and non-REM sleep) and wakefulness on the visual evoked responses (VERs) were studied in a total of 94 polygraphic EEG recordings obtained repeatedly from 15 pre-term infants. The latencies of various peaks of the VERs did not differ significantly during REM sleep and Stage 3 (characterized by “ trace alternant ”) at all conceptional ages from 29 through 45 weeks. The amplitudes of long latency negative waves at 29–34 weeks conceptional age (N 1 ) and at 35–38 weeks (N 2 ) were significantly greater during REM sleep than during Stage 3. This is in contrast to the findings previously obtained on adults. The latencies were found to be shortest and the amplitudes largest during wakefulness.

SUMMARY The developmental course of infantile spasms and hypsarrhythmia is described in a prospective study of 32 infants who had been examined periodically until the onset of the spasms. The infants were divided into three groups according to their possible etiology. In the perinatal and postnatal groups, the initial EEG showed severe abnormalities suggestive of severe brain pathophysiology resulting from the acute phase of the cerebral insult. In the perinatal group, the neonatal EEGS showed flat activity or a burst-suppression pattern. In the postnatal group, the EEG at the time of the initial cerebral lesion showed marked slow wave dysrhythmia. These early EEG changes in both groups were followed by improvement to normal or mildly abnormal recordings. After the stages of focal or multifocal abnormality, hypsarrhythmia or diffuse polyspike and wave discharges developed. In the prenatal group, the initial EEG was normal or mildly abnormal. The evolutionary changes of the EEGS thereafter were similar to those in the other two groups. The development of hypsarrhythmia or diffuse polyspike and slow wave discharges usually coincided with the onset of the spasms, although in some cases the spasms were associated with focal EEG abnormality. RESUME Evolution de l'aspect des electroencephalogrammes au cours des spasmes infantiles: etude prospective L'allure evolutive des spasmes infantiles de l'hypsarythmie est decrite au cours d'une etude prospective de 32 nourrissons examines regulierement depuis le debut des spasmes. Les nourrissons ont ete divises en trois groupes en fonction d'hypotheses etiologiques. Dans les groupes peri-natal et post-natal, les EEG initiaux montraient de graves anomalies evoquant une physiopathologie cerebrale d'atteinte severe, resultant de la phase aigue de l'agression cerebrale. Dans le groupe perinatal les EEG neo-nataux montraient un trace plat ou une distribution de bouffees de suppression. Dans le groupe post-natal, l'EEG au moment de la lesion cerebrale initiale montrait une dysrythmie marquee d'ondes lentes. Dans les deux groupes, ces modifications EEG primitives ont ete suivies d'ameliorations jusqu'a des enregistrements normaux ou legerement anormaux. Apres la periode des anomalies focales ou multifocales, une hypsarythmie ou des polypointes diffuses et des decharges d'ondes lentes sont apparues. Dans le groupe prenatal, le groupe initial etait normal ou legerement anormal, les modifications evolutives de l'EEG observees ulterieurement etaient semblables a celles que l'on relevait dans les deux autres groupes. Le developpement de l'hypsarythmie ou des polypointes diffuses et decharges d'ondes lentes a coincide habituellement avec le debut des spasmes bien que dans certains cas, les spasmes etaient associes a des anomalies focales de l'EEG. ZUSAMMENFASSUNG Die Entwicklung von EEG Charakteristika beim infantilen Spasmus, eine vorausschauende Untersuchung Der Verlauf der Entwicklung von infantilen Spasmen und Hypsarrythmie wurde in einer vorausschauenden Untersuchung bei 32 Kleinkindern beschrieben, die wiederholte Male bis zum Auftreten der Spasmen untersucht wurden. Die Kinder wurden im Hinblick auf eine mogliche Ursache der Erkrankungein drei Gruppen eingeteilt. In der peri- und postnatalen Gruppe zeigte das EEG hochgradige Veranderungen, die auf einen ausgepragten Hirnschaden schliesen liesen und von der akuten Phase eines cerebralen Anfalles herruhrten. Bei der perinatalen Gruppe zeigte das EEG insgesamt eine abgeflachte Aktivitat mit eingestreuten hohen Potentialkomplexen. Bei der postnatalen Gruppe fand sich im EEG zur Zeit der ersten Hirnschadigung eine bemerkenswerte Dysrhythmie langsamer Wellen. Diesen anfanglichen EEG Veranderungen folgten in beiden Gruppen Verbesserungen bis zu normalen ober geringgradig abnormen Hirnstromkurven. Nach einem Stadium fokaler oder multifokaler Abnormalitaten entwickelten sich Hypsarrhythmien oder diffuse Polyspike-Wave-Entladungen. In der praenatalen Gruppe war das erste EEG normal oder leicht abnorm. Wahrend der fortschreitenden Entwicklung waren die EEG Veranderungen identisch mit denen der beiden anderen Gruppen. Die Entwicklung der Hypsarrhythmie oder der diffusen Polyspikes-Waves-Entladungen traten gewohnlich gemeinsam mit den Spasmen auf, obwohl in einigen Fallen die Spasmen mit fokalen EEG Veranderungen einhergingen. RESUMEN La evolucion de las caracteristicas del EEG en los espasmos infantiles: estudio prospectivo Se describe el curso evolutivo de las espasmos infantiles e hipsarritmia en un estudio prospectivo de 32 ninos que habian sido examinados periodicamente hasta el inicio de los espasmos. Los ninos fueron divididos en tres grupos segun su etiologia. En los grupos perinatal y post-natal, el EEG inicial mostraba anomalias graves sugestivas de una grave fisiopatologia cerebral a consecuencia de la fase aguda de un insulto cerebral. En el grupo perinatal los EEG neonatales mostraban una actividad plana o un esquema de accesos inhibitorios. En el grupo post-natal el EEG en el momento de la lesion cerebral inicial mostraba una marcada disrritmia con ondas lentas. Estos cambios EEG precoces en ambos grupos se siguieron de una mejoria hasta la normalidad o trazados solo ligeramente anormales. Despues de los estadios de anormalidad focal o multifocal, se desarrollo hipsarritmia o descargas difusas de polipuntas y ondas. En el grupo prenatal, el EEG inicial era normal o ligeramente anormal. Los cambios evolutivos subsiguientes en el EEG, eran similares a los vistos en los otros dos grupos. El desarrollo de hipsarritmia o de descargas difusas de polipuntas y ondas lentas generalmente coincidieron con el inicio de los espasmos, aunque en algunos casos los espasmos estaban asociados a una anomalia EEG focal.

SUMMARY Visual evoked responses (vers) were studied in a total of 104 polygraphic eeg recordings of 11 small-for-dates and 15 pre-term infants, with the following results. 1 Definite vers were obtained at as early as 25 weeks gestational age. 2 The latency of each component of the ver showed progressive decrease with increasing conceptional age, both in Stage 3 and in rem sleep. 3 The wave form of the ver manifested a definite sequence of development with conceptional age. 4 The vers of small-for-dates infants were proportional to the conceptional age both in their latencies and wave forms, indicating that they are not affected by the intra-uterine growth retardation. 5 The wave form of the ver, rather than the peak latencies, is an additional and valuable tool for distinguishing between true pre-term and small-for-dates infants, especially in those older than 37 weeks conceptional age. RESUME Maturation des reeponses visuelles evoquees chez les enfants de faible poids de naissance Des reponses visuelles evoquees (vers) ont eteetudiees sur un total de 104 enregistre-ments polygraphiques eeg chez 11 enfants de faible poids pour le terme et chez 15 prematuets vrais avec les resultats suivants. 1 Des vers bien definis ont ete obtenus des 25 semaines d'âge de gestation. 2 La latence de chaque composant des ver ont montre une diminution progressive avec l'âge conceptionnel a la fois au stade 3 et dans le sommeil rapide. 3 Une forme en onde des ver traduit un stade precis des developpements par rapport a l'âge conceptionnel. 4 Les vers des enfants de faible poids pour le terme sont proportionnels a l'âge conceptionnel en ce qui concerne la latence et la morphologie en onde indiquant qu'il n'y a pas d'influence liee au retard de croissance intra-uterine. 5 La forme en onde de la ver, plus que le pic des latences, est un element additionel et de valeur pour etablir une difference entre les vrais prematures et les enfants de faible poids pour le terme, specialement chez ceux qui ont plus de 37 semaines d'âge conceptionnel. ZUSAMMENFASSUNG Die Ausreifung der visuell evozierten Potentiale bei Kindern mit niedrigem Geburtsgewicht Anhand von 104 polygraphischen EEc-Ableitungen von 11 hypotrophen Kindern und 15 Fruhgeborenen wurden visuell evozierte Potentiale (vep) untersucht und Folgendes gefunden. 1 Deutliche vep wurden bereits bei einem Konzeptionsalter von 25 Wochen gefunden. 2 Die Latenz jeder Komponente des vep nahm progressiv mit steigendem Konzeptionsalter ab, sowohl im Stadium 3 als auch im rem Schlaf. 3 Der Wellencharakter bei dem vep zeigte eine deutliche Abhangigkeit der Entwicklung vom Konzeptionsalter. 4 Die vep der hypotrophen Kinder entsprachen dem Konzeptionsalter sowohl in ihrer Latenz als auch in ihrem Wellencharakter, was erkennen last, daD sie von der intrauterinen Wachstumsverzogerung nicht beeintrachtigt werden. 5 Weniger die Spitzenlatenzen als vielmehr der Wellencharakter der vep stellt ein weiteres wertvolles Mas fur die Unterscheidung der wirklichen Fruhgeborenen von den hypotrophen Kindern dar, insbesondere bei den Kindern, deren Konzeptionsalter mehr als 37 Wochen betragt. RESUMEN Maduracion de las respuestas visuales evocadas en ninos con bajo peso al nacer Se estudiaron las respuestas visuales evocadas (ver) en un total de 104 trazados eeg poligraficos en 11 lactantes con peso pequeno al nacer y en 15 nacidos antes de termino. Los resultados fueron los siguientes. 1 Se obtuvieron ver definidos a las 25 semanas de edad gestacional. 2 La latencia de cada componente del ver mostro una disminucion progresiva al aumentar la edad concepcional, tanto en el estadio 3 del sueno como en el sueno REM. 3 La forma de la onda en el ver manifesto una definida secuencia de desarrollo de acuerdo con la edad concepcional. 4 Los ver de ninos con bajo peso al nacer fueron proporcionales a la edad concepcional tanto en sus latencias como en las formas de la onda, indicando que no estan afectadas por el retraso de crecimiento intrauterino. 5 La forma de la onda de los ver, mas bien que las latencias de la punta, constituye un dato adicional y valioso para distinguir entre ninos verdaderamente prematuros y ninos de bajo peso al nacer, especialmente en los que sobrepasan las 37 semanas de edad concepcional.

SUMMARY Quantitative analysis made on spindle-like fast rhythms in the eegs of 39 low-birthweight infants (28 pre-term and 11 small-for-dates) resulted in four main findings. 1 Spindle-like fast rhythms occurred least frequently in the frontal area and most frequently in the occipital and/or central areas. 2 They occurred more frequently at 31–32 weeks' post-conceptional age than at 26–30 weeks, in all behavioural states. After 31 to 32 weeks they decreased with increasing age, to disappear completely around term. They disappeared earlier in rem sleep than in non-REM sleep. 3 A greater number of fast rhythms occurred in rem sleep than in deep sleep at 26 to 32 weeks, while at 33 to 34 weeks the situation was reversed, with more fast rhythms in deep sleep than in rem sleep. 4 The same trend was found for both the pre-term and the small-for-dates infants. The study provides further quantitative evidence in favour of previous findings that cns development is more closely related to post-conceptional age than to post-natal age or birthweight. RESUME Rythmes rapides en fuseaux dans les eeg d'enfants defaible poids de naissance L'analyse quantitative des rythmes rapides en fuseau dans les eeg de 39 enfants de faible poids de naissance (28 prematurts et 11 enfants de poids faible pour le terme) a mis en evidence quatre faits principaux. 1 Les rythmes rapides en fuseau surviennent le moins frequemment dans les rtgions occipitales et/ou centrales. 2 Ils sont plus frequents a 31–32 semaines d'âge conceptuel qu'a 26–30 semaines et ceci dans tous les etats de comporte-ments. Apres 31–32 semaines, ils decroissant avec lâge, jusqu'a disparaitre completement vers le terme. Ils disparaissent plus tot dans le sommeil rapide que dans le sommeil lent. 3 Un plus grand nombre de rythmes rapides surviennent dans le sommeil rapide que dans le sommeil lent de 26 a 32 semaines, tandis qu'on note l'inverse de 33 a 34 semaines. 4 Les memes caracteristiques se trouvent chez les prematures que chez les enfants de faible poids pour le terme. L'etude fournit des elements quantitativs en faveur des faits precedents qui indiquaient deja que le developpement du snc est plus etroitement reliea I'âge conceptuel qu'a l'âge de naissance ou au poids de naissance. ZUSAMMENFASSUNG Spindel ahnliche schnelle Rhythmen in EEGs von Kindern mit niedrigem Geburtsgewicht Die quantitative Analyse der Spindel ahnlichen schnellen Rhythmen in eegs von 39 Kindern mit niedrigem Geburtsgewicht (28 Fruhgeborene und 11 ‘small for dates’) ergab vier wichtige Befunde. 1 Spindel ahnliche schnelle Rhythmen treten selten in der Frontal-region und am haufigsten in den Occipital- und/oder Zentral-regionen auf. 2 Sie traten haufiger in der 31–32 igsten Gestationswoche als in der 26–30 igsten auf in allen Verhaltens-stadien. Nach der 31–32 igsten Woche liesen sie mit zunehmendem Alter nach und verschwanden vollstandig etwa zum normalen Geburtstermin. Sie verschwanden eher im aktiven als im ruhigen Schlaf. 3 In der 26–32 igsten Woche fand sich ein groserer Anteil schneller Rhythmen im REM-SChlaf als im tiefen Schlaf, wahrend dies in der 33–34 igsten Woche umgekehrt war mit mehr schnellen Rhythmen im tiefen Schlaf als im REM-½. 4 Bei den Fruhgeborenen und fur die ‘small-for-dates babies’ wurde derselbe Befund erhoben. Die Studie erbringt einen weiteren quantitativen Beweis fur friihere Befunde, die darauf hindeuten, das die Entwicklung des zns enger an das Konzeptionsalter als an das post-natale Alter und das Geburtsgewicht gebunden ist.