Abstracts from the Third Annual Meeting of Child Neurology in Chugoku and Shikoku District, Okayama, 25 July 1992

Brain & Development, 15 (1993) 321-326 0387-7604/93/$06.00 © 1993 ElsevierSciencePublishers B.V. All rights reserved BRADEV 00063

Proceedings of Meetings

Abstracts from the Third Annual Meeting of Child Neurology in Chugoku and Shikoku District, Okayama, 25 July 1992 (Compiled by) Kenzo Takeshita, MD

Division of Child Neurology, Institute of Neurological Sciences, Tottori University School of Medicine, Yonago, Japan Received 29 March 1993; accepted 15 April 1993 The meeting mentioned above was held at Plaza Hotel, Okayama, Japan, on 25 July 1992, and the abstracts of all papers presented have been compiled by Dr. Kenzo Takeshita, the organizer of the meeting.

Cfinicai efficacy of intravenous cionazepam in status epilepticus Masahiko Kimura, MD, Noriko Suzuki, MD, Yukinori Maeoka, MD and Kunio Yoshino, MD (Clinic of Pediatrics, National Nishi-Tottori Hospital, Tottori, Japan) Seven episodes of status epilepticus (SE) in 4 cases were treated with intravenous clonazepam (CZP). The patients, aged 8-19 years (mean, 13), had epilepsies comprising undetermined ones (2), secondary generalized epilepsy (1) and epilepsy with multifocal independent spikes (1). Fever was the precipitative factor in 5 episodes. All episodes were of convulsive SE. CZP was used when other parenteral anti-epileptic drugs were ineffective. Diazepam (DZP) was used in 6 episodes, phenytoin in 3, phenobarbital in 2, and lidocain, acetazoramide and chloral hydrate in 1 before the CZP administration. The administration of 1 mg CZP resulted in complete control of 6 of the 7 episodes. One episode was partially controlled, in which a generalized seizure became a partial one. Respiratory depression was observed once in a patient who had often shown respiratory depression with DZP. We concluded that intravenous CZP is a useful alternative to DZP in SE. The side effects were less severe than those of DZP.

Fetal hydantoin syndrome Shinichi Yagi, MD, Atsuko Wakunami, MD, Osamu Correspondence address: Dr. K. Takeshita, Division of Child Neurology, Institute of Neurological Sciences, Tottori University School of Medicine, Nishimati 36-1, Yonago, Tottori 683, Japan. Fax: (81) (859) 348 135. Brain & Development, Vol 15, No 4, 1993

Shinohara, MD, Naoki Kataoka, MD, Tetsuro Morita, MD and Shun Mizuta*, MD (Department of Pediatrics, Kawasaki Medical School, Kawasaki, Japan and *Dent of Child Neurology, Okayama University Medical School, Okayama, Japan) It has long been suspected that an association exists between maternal epilepsy, anticonvulsant drugs, and an increased incidence of congenital abnormalities. We report here a case of fetal hydantoin syndrome presenting periventricular leukomalacia. The patient was the product of a 34 week pregnancy, with caesarean sectioning. His mother had suffered from complex partial epilepsy since 9 years of age, and phenytoin, phenobarbital and sodium valproate had been administered. He was admitted to the neonatal intensive case unit of Kawasaki Medical School because of a premature weight of 2,050 g and characteristic dysmorphism. He displayed craniofacial anomalies, including microcepha1-us, hypertelorism, a saddle nose, and low set ears and hair line. Distal digital dysplasia, and a pilonidal sinus, and retention of the testes were also seen. Therefore, a clinical diagnosis of fetal hydantoin syndrome was made at birth. Cranial sonography on admission indicated a periventricular hyperechoic lesion had developed into cystic periventricular leukomalacia over a 2 week period. This was confirmed by both cranial sonography and MRI. A SPECT study with 99mTC HM PAO revealed decreased cerebral blood flow in the frontal, parietal and periventricular subcortical areas at 1 month of age. These findings suggest that the hypoxic event and/or ischemic insult" occurred in utero; however, further detailed studies of these findings are 321

necessary to determine whether or not they were due to adverse effects of anticonvulsants. Recently, Buehler proposed that it is possible to identify fetuses at increased risk for phenytoin-induced congenital abnormalities by measuring the activity of epoxide hydrolase in amniocytes. Therefore, further study regarding oxidative metabolism is required to evaluate the adverse effects of anticonvulsant drugs on maternal epilepsy. Dipole tracing method in clinical epilepsy evaluation Harumi Yoshinaga, MD, Katsuhiro Kobayashi, MD and Shunsuke Ohtahara, MD (Department of Child Neurology, Okayama University Medical School, Okayama, Japan) We have reported the clinical applicability of the dipole tracing method for investigating the location and character of epileptic spikes. (i) The dipoles of spikes in benign childhood epilepsy with centro-temporal spikes (BCECS) were strictly localized in the Rolandic area, and showed a difference in location, in comparison to those in other types of childhood epilepsy with centrotemporal spikes. (ii) We examined 2 patients who had both occipital spikes and abnormalities, as indicated by MRI, in the occipital lobe. In 1 case the location of the dipole and the abnormal area on MRI coincided well, while the other showed no agreement. These results suggest that epileptic spikes do not always arise from the abnormal areas indicated on image scanning. (iii) The location of the dipoles and the subdivided area in the frontal lobe, which was suggested by the types of seizures, coincided well. On the basis of these observations, it is evident that dipole tracing would contribute to determination of the precise locations of epileptic spikes in the brain, and would aid subclassification of epileptic syndromes. This non-invasive method is expected to show further advanced clinical applicability. Electro-clinical study of periodic spasms in six cases Masaaki Ogihara, MD, Akinori Hoshika, MD, Tasuku M~vajima, MD, Tetsuhiko Matsuno, MD and Takao Hirata , MD (Department of Pediatrics and *Neonatal Intensive Care Unit, Tokyo Medical College, Tokyo, Japan) We attempted to clarify the precise characterization of detailed seizure types of periodic spasms proposed by Gobbi et al. Subjects. All of the patients had intractable epileptic seizures and different etiological disorders; Kojewnikow syndrome, tuberous sclerosis, partial pachigyria, cryptogenic Lennox-Gastaut syndrome, anoxic encephalopathy, and partial 5q trisomy syndrome. The onset of epileptic seizures ranged from 25 days of life to 7 322

months of age (average, 3 months), the onset of periodic spasms ranging from 6 months to 14 years old (average, 7 years). Brain CT scanning or MRI showed apparent diffuse cerebral lesions in 5 cases• Results. Periodic spasms were preceded by focal seizures in 5 patients, an asymmetric generalized tonicclonic seizure in 1, and an asymmetric tonic seizure in 1. As for the circadian rhythm, in all patients, periodic spasms occurred soon after arousal from sleep, but in 2 patients, periodic spasms occurred in the daytime, as well as soon after arousal• Ictal EEG recordings showed diffuse high voltage slow waves superimposed by low voltage fast waves, and there was asymmetry predominating in 1 cerebral hemisphere in 5 out of the 6 patients. According to detailed observations by means of a video-EEG monitoring system, we classified these into 3 types; unilateral (focal) type, asymmetric generalized type, and symmetric generalized type. The unilateral type was seen in 2 patients, and its repetitive clinical symptoms were localized to one side of the body, resembling focal motor seizures. The asymmetrical generalized type was seen in 4 patients, its manifestations consisting of a combination of massive tonic spasms and focal manifestations such as a fencing posture. The symmetrical generalized type was seen in 1 patient who showed complete symmetric generalized spasms without any focal manifestations. Conclusion. We think that the unilateral periodic spasms are different from the other 2 types, because the clinical manifestations of the unilateral type are the same as those of focal motor seizures. On the other hand, the asymmetric generalized type is classified as generalized seizure, although some degree of focal manifestations exists. It is speculated that the clinical manifestations of the unilateral type are of cortical origin, and the subcortical structure may play a more important role in the generalized type with or without asymmetry. As for the periodic phenomenon, the mechanism can be attributed to both cortical and subcortical brain lesions. An infantile case of hemorrhagic cerebral infarction Takeshi Ueda, MD, Yoko Miyake, MD, Seiichi Fujimoto, MD, Shigenori Hattori, MD, Ryutaro Takahashi, MD and Susumu Miyake, MD (Clinic of Pediatrics, Kagawa Central Hospital, Takamatsu, Japan) We report a rare case of a 10-month-old male infant with hemorrhagic cerebral infarction. The chief complaint was left hemiparesis following generalized convulsions, on the left side dominantly, after he had cried while undergoing a tuberculin'test. The results of blood biochemical examinations, serum lipid levels, blood

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coagulation ability and cerebrospinal fluid were all normal. On the 1st day of illness, CT scans showed a low density area stretching from the anterior portion of the right internal capsule to the right lens nucleus. The lesion was observed as a high density area on the 4th day of illness, so he was tentatively diagnosed as having hemorrhagic cerebral infarction. The EEG findings were slow wave dysrhythmia and a lazy phenomenon in the right hemisphere. Cerebral angiography revealed right internal carotid stenosis in the carotid fork portion. IMP-SPECT showed that the reduction of cerebral blood flow in the right hemisphere was more widespread than had been expected. Phenobarbital, aspirin and flunarizine were administered orally. There was no recurrence of the convulsions or paresis. Reconstructive surgery is planned to prevent a recurrence of the cerebral infarction. Further follow-up studies are recommended to rule out moyamoya disease. A case of influenza A encephalitis with akinetic mutism

Kiriko Tokuda, MD, Nobuyuki Kodani, MD, Hironobu Hata*, MD and Tatsuya Ogino*, MD (Clinics of Pediatrics and *Pediatric Neurology, Matsuyama Red Cross Hospital, Matsuyama, Japan) The term, akinetic mutism (AM), became popular after Cairns et al. proposed it in 1941. AM is a state of silent, immobile wakefulness unresponsive to noxious stimuli. We present a 5-year-old girl with influenza A encephalitis with AM as an early symptom. She was admitted due to unresponsiveness and high fever. On examination, she opened her eyes but no voluntary movement was noted. All extremities were rigidospastic and bilateral 6th nerve palsy was noted. The cerebrospinal fluid showed a raised protein concentration and increased myelin basic protein. The serum complement fixation titer for influenza A virus was less than 1:4 on admission and 1:256 on the 9th hospital day. T2weighted images on MRI revealed hyperintense areas in the subcortical white matter of the bilateral frontal and temporal lobes, and the cortex of the right parietal lobe, thalamus, putamen, external capsule, midbrain, pons and cerebellum. She recovered from AM on the 20th hospital day. On the same day, the hyperintense areas observed previously on T2-weighted MRI imaging of the basal ganglia, and the frontal and temporal lobes had disappeared, but hyperintense areas still remained in the pons and cerebellum. The clinical course suggests disturbance of the pons and basal ganglia, but the cortex and subcortical white matter were also involved, as noted on MRI.

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A case of acute disseminated encephalomyelitis, in which ECHO 30 virus was detected in the cerebrospinal fluid (CSF)

Kouji Nakata, MD, Akio Hirano, MD and Nobuo Ohta, MD (Clinic of Pediatrics, Takamatsu Heiwa Hospital, Takamatsu, Japan) A 4-year-old girl had been diagnosed as having acute disseminated encephalomyelitis (ADEM). She complained of partial seizures following a febrile episode, and transient vision disturbance. These complaints were very mild and there was no fever. Therefore she was not treated with corticosteroids. She recovered rapidly. She had a recurrence. The 1st MRI, performed on the 10th day of this illness, showed no abnormality. The 2nd MRI (64th day) showed high density areas (T2-weighted image) in the right thalamus, and left globus pallidus, putamen and pedunculus cerebri. The 3rd MRI (113th day) showed no abnormality. ECHO virus 30 was detected in a CSF specimen on the 20th day of this illness. This virus was epidemic in Takamatsu city at the time. This virus is well known as the cause of aseptic meningitis but not ADEM. This case is the 1st of A D E M caused by the ECHO 30 virus. A case of progressive familial encephalopathy in infancy with calcification of the basal ganglia and chronic cerebrospinal fluid lymphocytosis (Aicardi)

Hideyuki Shiraishi, MD, Ayame Kobayashi, MD, Hitoshi Sejima, MD, Kazuko Kishi, MD and Masatoshi Ito, MD (Department of Pediatrics, Shimane Medical University, Izumo, Japan) We reported a girl considered to be a case of a 'progressive familial encephalopathy in infancy with calcification of the basal ganglia and chronic cerebrospinal fluid (CSF) lymphocytosis' (Aicardi 1985). At the age of 4 months, she was referred to our clinic for psychomotor delay and hypotonia. There was no abnormality in her intrauterine, perinatal or familial history. She was hypotonic, and had nystagmus and no head control or eye contact. There was no abnormality in routine blood and urine tests, IgG, IgM and IgA levels in serum, or in the chromosomes of lymphocytes. There was no significant change in the T O R C H titer or the lactic acid and pyruvic acid levels in serum and CSF, although a mild increase in protein content and lymphocytosis were found in CSF. On CT scanning, granular calcification in the basal ganglia was found, which had markedly increased at 1 year of age. Endocrinological and electrophysiological examination revealed no abnormality. At 1.5 years of age, she~still has nystagmus, no head control and mild CSF lymphocytosis.

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Although she has acquired eye contact, spasticity is rapidly increasing. MR imaging and proton MR spectroscopy in a case of Hunter syndrome (IIB)

Seishi Shimakawa, AID, Michinori Ito, MD, Etsuo Naito, MD, Hiroshi Akita, MD, Masanobu Tayama, MD, Toshiaki Hashimoto, AID, Yasuhiro Kuroda, MD, Masashi Harada , MD, Ken.lt Matsuzakt , MD, Kouichi Miyoshi*, MD, Eiji Takeda**, MD and Kaoru Nishijyou***, AID (Departments of Pediatrics, *Radiology and **Pathologic Dietetics, Tokushima University School of Medicine, Tokushima, Japan and ***Kagawa Children's Hospital, Zentsuji, Japan) We carried out both magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (IH MRS) in a 15-year-old patient with Hunter syndrome (IIB). We found multi-focal lesions of various sizes that showed prolonged T1 and T2 in the white matter, ventricular enlargement and encephalotrophy. There have been few reports of MRI in mucopolysaccharidosis, so we did not know the relationship between the clinical manifestations and MRI findings in this syndrome. Prolonged TI and T2 in the white matter did not seem to be correlated with the clinical finding of mental retardation. We supposed that NAA was diminished because of the NAA/Cho ratio of 1.79 and the NAA/Cr ratio of 1.42 from the proton spectrum. Lactate was not elevated in the white matter region. We thought it necessary to consider the relationships among clinical manifestations, neuropathologic changes, and findings on MRI and MRS in detail. *

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Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (IH MRS) in a case of the late infantile form of metachromatic leukodystrophy (MLD)

Yuri Ushiroguchi, MD, Etsuo Naito, MD, Michinori Ito, AID, Masanobu Tayama, MD, Toshiaki Hashimoto, AID, Yasuhiro Kuroda, MD, Masashi Harada*, AID, Kouichi Miyoshi*, MD and **Eiji Takeda, MD (Departments of Pediatrics, *Radiology and **Pathologic Dietetics, Tokushima University School of Medicine, Tokushima, Japan) The case was a 2-year-old female. Although she developed normally until 1 year old, after that she manifested developmental retrogression, so she was admitted for further evaluation. At the time of admission, she had a poor countenance, and could not roll or stand, and was unstable when sitting. Further, in her lower limbs, hypertonicity and drop foot were found. Protein and NSE were increased in CSF. EEG revealed a tendency of slow waves particularly in the 324

bilateral occipital region. Evoked potentials showed a prolonged central conduction time. The peripheral motor nerve conduction velocity was delayed. Her developmental quotient (DQ) was 29 at 2 years old; compared with 108 at 1 year old, there was obvious developmental retrogression. She was diagnosed as having the late infantile form of MLD, because leukocyte arylsulfatase A activity was extremely low. We carried out MRI and 1H MRS on her. MRI showed extensive demyelination in the cerebral white matter, a specific finding of this disease. On 1H MRS, we recognized decreased N-acetyl-aspartate (NAA) and extremely increased choline (Cho). These findings reflected chronic and progressive demyelination. A case of DRPLA (myoclonus epilepsy form)

Seiji Watanabe, AID, Fumihiko Hamada, AID, Kayoko Yoshimura, AID, Hideo Morita, MD and Takanobu Kurashige, AID (Department of Pediatrics, Kochi Medical School, Nankoku, Japan) A 6-year-old boy with dentatorubropallidoluysian atrophy (DRPLA) is reported. His father was diagnosed as having DRPLA, and the paternal grandmother had had fine motor movement and gait disturbance. Their symptoms started in their 3rd decades. The symptoms of this patient began at 2 years old as speech disturbance. At the age of 4, gait disturbance appeared. From his 5th year, myoclonus and seizures began. Although no remarkable findings were obtained on head CT or MRI, an electroencephalogram showed slow wave dysrhythmia and irregular spikes and waves in the bilateral anterior-temporal and parietal areas. His seizures were almost completely controlled with VPA and CBZ, but his gait disturbance, myoclonus and mental deterioration have progressed. Progressive myoclonus epilepsy including DRPLA must be excluded for a patient with developmental retardation, and the origin of the epilepsy must be found. To distinguish them, a detailed pedigree study is necessary. A case of Arnold-Chiari malformation type 1

Shouichi Endo, MD, Kuniaki Fukuda, MD, Yoshinobu Nakagawa*, MD, Fusamitu Hamazaki*, MD and Takanori Pu*, AID (Clinics of Pediatrics and Neurosurgery, National Kagawa Children's Hospital, Zentsuji, Japan) We reported a case of Arnoid-Chiari malformation type 1 who presented bulbar palsy at 10 years of age. She was delivered with severe asphyxia. In the neonatal period, she presented disturbance of consciousness, subtle seizures and muscle tone abnormality. Her developmental milestones as to motor functions were slightly Brain & Development, Pot 15, No 4, 1993

delayed, but not those as to intelligence. Several convulsions have occurred since 2 years of age. She was diagnosed as having cerebral palsy and received treatment comprising physical training. At 10 years of age, she complained of dysphagia, ataxia, dysarthria and respiratory disturbance. Neurological examination revealed dysfunctioning of the cerebellum, cranial nerves (IX-XII) and pyramidal tract. Brain CT showed only mild dilatation of the lateral ventricles, but brain MRI showed a shift of the cerebellar tonsils and medulla oblongata into the spinal canal. We performed occipital craniectomy and C1, C2 laminectomy. After the operation she has gradually recovered. In particular, the disturbances of swallowing and respiration have almost disappeared. MRI is the most useful method in the diagnosis of Arnold-Chiari malformation type 1. We hope that the early diagnosis of Arnold-Chiari malformation by means of MRI will improve the prognosis of this malformation. Two cases of a double midline germinoma with long-term good quality of life: report and review of the literature

Yoshifumi Matsumoto, MD, Syouji Konishi, MD, Mikio Takaya, MD, Toshiki Yamasaki, MD and Kouzo Moritake, MD (Department of Neurosurgery, Shimane Medical University, Izumo, Japan) Two rare childhood cases of a double midline germinoma in the pineal and suprasellar regions are presented with special reference to the good quality of life for 5 years or more. Six pertinent patients reported previously are reviewed, including ours, and the therapeutic problems and prognostic factors associated with multiple midline germinomas are discussed. Case 1. A 14-year-old boy had a 1-month history of diabetes insipidus. Initial computed tomography (CT) showed 2 hyperdense masses in the pineal and suprasellar regions, which became homogenously enhanced after i.v. injection of contrast medium. Cerebrospinal fluid (CSF) cytology revealed a characteristic two-cell pattern. He received irradiation with 50 Gy of the whole brain and local lesions, and with 24 Gy of the spinal neural axis. After the radiotherapy, he showed a complete response, based on the CT appearance. Nine years follow-up CT and magnetic resonance imaging (MRI) showed no tumor evolution. He has undergone replacement therapy with ADH alone. Case 2. A 13-year-old boy had a 1-month history of headache and diabetes insipidus. He became comatose because of acute obstructive hydrocephalus, and underwent a ventriculo-peritoneal shunt operation. After the shunt, he recovered with clear consciousness, and neurological examination revealed Parinaud's sign and diaBrain &Development, Vo115,No 4, 1993

betes insipidus. CSF cytology showed a pathognomonic two-cell pattern, and a tumor marker study revealed a high fl-HCG value in both CSF and serum. Initial CT showed 2 hyperdense mass lesions, with homogeneous contrast enhancement, in the pineal and suprasellar regions. Radiotherapy was carried out with 50 Gy for the whole brain and local lesions, and with 24 Gy for the spinal neural axis. After the radiotherapy, a tumor marker study showed no fl-HCG in either CSF or serum, and serial CT disclosed the disappearance of the tumors. Because of the positive fl-HCG finding on the 1st CSF examination, PVB therapy (Cisplatin, Vinblastin, Bleomycin) was continued for 3 years (3 cycles/ year). Five years follow-up CT and MRI showed no tumor recurrence. He has undergone replacement therapy with ADH and cortisol. A male case of hemimegalencephaly with complex partial seizures and learning disabilities

Harumi Tanaka, MD, Takashi Ichiyama, MD and Takashi Hayashi, MD (Department of Pediatrics, Yamaguchi University School of Medicine, Ube, JApan) The patient, a left-handed 6-year-old boy; has suffered from epileptic seizures, including complex partial and secondary generalized ones, since 5 years old. He is hyperkinetic and has communication disorders. Rightsided hemimegalencephaly, left hemispheric hypoplasia of the occipital region and agenesis of splenium in the corpus callosum were revealed on MRI. EEG disclosed independent spikes in the right parito-centro-temporal and left frontal portions. VEP showed a poor left-sided IVth wave. Neuropsychological examinations revealed an IQ of 82, with an inferior verbal IQ score compared with the performance IQ. His verbal deficit may be due to a disturbance of visual-motor skills. His recent memory is involved. Visual perception is damaged, associated with right-sided unilateral spatial neglect. These facts suggest that the hemimegalencephalic right hemisphere may be provoking epileptic seizures, and the hypoplastic left one and agenesis of the callosal splenium may be disturbing his verbal function and visual perception. A case of Angelman syndrome with albinism

Takaatsu Eguchi, MD, Takamasa Kishi, MD, Naoto Fujita, MD, Yoshiko Kawashima, MD, Kohtaroh Muraki, MD, Kazuhiro Ueda, MD, Shinji Saitoh*, MD and Norio Niikawa*, MD (Department of Pediatrics, Hiroshima University School of Medicine, Hiroshima, Japan and *Department of Human Genetics, Nagasaki University School of Medicine, Nagasaki, Japan) We reported a 5-year-old boy with Angelman syn325

drome with albinism. His family history was normal. He was noticed to have white skin and bronzed-hair at birth. Mental and motor development was severely delayed, and he cannot walk without help at present. He never developed speech. Unprovoked outbursts of laughter began at 10 months of age. Fever-induced GTCs started at 1 year and 10 months of age, and atonic seizures started at 3 years and 1 month of age. The seizures were fairly well controlled with valproic acid. Southern blot and densitometry analysis revealed a partial deletion at the locus in the Angelman/PraderWilli region (AS/PWS) of chromosome 15. The dinucleotide repeat polymorphism at the D15Sll locus showed that the deficient allele was of maternal origin. In Angelman syndrome, ocular hypopigmentation has often been reported, but the association of albinism has rarely been reported. The gene locus of albinism is supposed to have been mapped near AS/PWS of chromosome 15, and thus we consider that our case possibly has a contiguous gene syndrome.

Diagnostic significance of EEG in Angelman syndrome Satoshi Maniwa, MD, Yoko Ohtsuka, MD, Shunsuke Ohtahara, MD, Norio Niikawa*, MD and Shinji Saitoh*, MD (Department of Child Neurology, Okayama University Medical School, Okayama, Japan and *Department of Human Genetics, Nagasaki University School of Medicine, Nagasaki, Japan We reported a 3-year and 5-month-old boy (Case 1) and a 4-year and 5-month-old girl (Case 2) with Angelman syndrome. Although deletions of the long arm of chromosome 15 were not detected with high-resoluti'on banding techniques, in both cases Southern blot analyses revealed a DNA deletion involving the D15Sll locus and the GABA receptor/~3 subunit gene of chromosome 15, which is specific for Angelman syndrome. In case 1, molecular probe analysis indicated that the chromosome with the deletion of the D15Sll locus was maternally inherited. On the 1st EEG at 1 year and 0 months of age in Case 1, persistent high ampli-

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tude rhythmic 4-6 c/s activities were observed during the waking state, but no epileptic discharge was detected. High amplitude posterior dominant 3-4 c/s spikes and waves appeared in addition to the activities at 1 year and 3 months of age. Waking EEG in Case 2 showed both findings on the 1st EEG at 2 years and 0 months of age. We conclude that the characteristic EEG feature of persistent high amplitude rhythmic 4-6 c/s activities is very helpful for the early diagnosis of Angelman syndrome.

A case with progressive failure to thrive, muscle hypotonia, liver dysfunction and elevated protein in CSF Masayuki ltoh *, MD, Shinjiro Akaboshi, Tatsuya Koeda, MD, Kenzo Takeshita, MD and Eisaku Ohama*, MD (Divisions of Child Neurology and *Neuropatholnstitute of Neurological Science, Faculty of Medicine, Tottori University, Yonago, Japan) We reported an infant, whose diagnosis was not given, with failure to thrive, muscle hypotonia, liver dysfunction and elevated protein in CSF. The early manifestations included failure to thrive and hypotonia at 4 months of age. At 6 months, she was admitted to our clinic because of poor weight gain, recurrent vomiting and lethargy. At that time, examination revealed dehydration, hepatomegaly, poor head control and the absence of deep tendon reflexes, but there were no symptoms of convulsions or abnormal eye movement. Laboratory studies showed obstructive liver dysfunction, metabolic acidosis, an increased ketone ratio (]~ hydroxy butyric acid/acetoacetate) in serum, and elevation of lactate and protein in CSF. A muscle biopsy revealed nothing distinctive, although there were some myopathic findings. Also there was no ABR response. The symptoms progressively worsened after admission. She died of multiple organ failure at 8 months old. Pathological studies disclosed varying degrees of cell dilatation and formy cells in most organs. There were Alzheimet type 2 glias, and dilatation of the pericellular space and perivascular space in the brain.

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