Akira Tsuru

Developmental assessment-based surgical intervention for intractable epilepsies in infants and young children.

Summary:  Purpose: To define the most appropriate time for surgery for medically intractable epilepsies in infants and young children.

Epidemiological and clinical studies of West syndrome in Nagasaki Prefecture, Japan

Recent advances in diagnostic and therapeutic techniques may have changed incidence and etiologies of West syndrome (WS). We performed a retrospective epidemiological study of WS that occurred in 47 children in Nagasaki Prefecture during a recent 10-year period from 1989 to 1998. The incidence of WS was 3.1/10,000 live births. Thirty-nine patients (83%) had symptomatic WS, in which the prenatal causes were most frequent, followed by low-birth weight (LBW) infants, perinatal and postnatal. Such high frequency of LBW may have been due to a relative increase in survivors of premature babies because of recent advances in perinatal care. The brain computerized tomography/magnetic resonance imaging performed in 41 patients revealed congenital brain malformation (10 patients), destructive brain disorders (13 patients), and no structural abnormalities (18 patients). The seizure outcome was worse in the symptomatic WS than in the cryptogenic WS. The developmental outcome was very poor in both symptomatic and cryptogenic WS. The mean developmental quotient (DQ) in all patients was 25, and only four patients (11%) had a normal DQ (>70). DQ was lower in patients with developmental delay before the onset of WS, symptomatic group, relapse and/or persistence of seizure. Developmental delay seen in WS patients seems to be related to the two major factors, that is, underlying brain abnormalities and the persistent seizures as a result of the former. Therefore, every effort should be made to control seizures, including medical and early surgical treatment, as well as prevention of brain damage through perinatal care.

Immunohistochemical expression of cell adhesion molecule L1 during development of the human brain

We demonstrated the expression of neural cell adhesion molecule, L1, during human brain development by immunostaining with anti-L1 fibronectin domain antibody. In the human cerebellum, the inner half of the external granular and molecular layers, mostly parallel fibres, and the Purkinje cell layer were immunoreactive for L1 from the early foetal period of 13-15 gestational weeks (GW). Immunoreactivity was strongest in the molecular layer in the perinatal period. The subcortical white matter and dentate layer were immunoreactive in foetal life. In the human cerebrum, the outer half of the molecular layer, together with Cajal-Retzius cell bodies, were positively stained until 30-34 GW, when afferent fibres develop over the entire cortex. The fibres in the white matter were strongly immunopositive in the fascicles until early infancy. These results suggest that L1 is temporally and spatially expressed in the developing brain, and may play important roles in neural cell migration, neurite elongation, and axonal fasciculation.

Cystic leukomalacia in the cerebellar folia of premature infants

Cystic necrosis in the cerebellar white matter was found in three premature infants. The necrosis was characteristically localized in the center of the white matter of the superficial cerebellar folia, sparing the overlying cortex. The patients were aged between 28 and 34 gestational weeks, and had a clinical history of severe systemic hypotension. Thus, cystic leukomalacia represents a characteristic brain lesion in premature infants which may be caused by cerebellar hypoperfusion.

Mutation analysis of the ALD gene in seven Japanese families with X-linked adrenoleukodystrophy

AbstractThe childhood cerebral form of X-linked adrenoleukodystrophy (X-ALD) is a severe congenital metabolic disease without a definite effective therapy except for hematopoietic stem cell transplantation in the appropriate disease stage. Seven Japanese families with X-ALD were analyzed for mutations in the ALD gene (ALD). Of the seven families, three were referred to us for prenatal diagnosis, four for carrier detection, and three for confirmation diagnosis of patients. By nucleotide sequencing and/or restriction analysis, all the subjects to be examined were successfully diagnosed. Six different missense mutations in ALD were identified. There was a G→A substitution (G512S) in two unrelated families, and a G→A (R617H), a C→T (R660W), a G→C (R163P), a C→T (S606L), or a G→A (G116E) substitution in each of the other five families. Among the six substitutions, five were those reported previously and the other was a novel mutation. In three families, prenatal diagnosis was carried out after genetic counseling.

Immunohistochemical expression of cell adhesion molecule L1 in hemimegalencephaly

We demonstrated immunohistochemically an abnormal expression of the neural cell adhesion molecule L1 in 10 developing brains of children with hemimegalencephaly (HM) aged from 36 weeks gestation to 10 years of age, comparing them with 23 controls aged from 13 weeks of gestation to 14 years. There was dense L1 expression in focal regions of the molecular layer beneath leptomeningeal glioneuronal heterotopia, in areas of cerebral cortex with large neurons, and in the disorganized or neuronal heterotopic sites in the white matter in HM. L1 was also heterogeneously enhanced in the abnormal cortex after 1 year of age, suggesting that axonal growth was delayed. These changes persisted into the older age group in the abnormal areas of cortex in HM. The cell bodies of many enlarged neurons in HM were immunopositive for L1, whereas L1 was usually localized to the processes of normal neurons. The delayed L1 immunoreactivity and enlarged L1-immunopositive neurons may be closely related to the pathogenesis of unilateral megalencephaly with cortical dysplasia and heterotopia.

Protein-losing enteropathy complicated with recurrent convulsions and developmental delay in a 4-month-old boy

Although many disorders can cause PLE, they are classified into two groups from the aspect of the mechanism of protein loss. 2,3 They are: (i) an abnormality of the lymph system such as intestinal lymphangiectasia, lymph duct tumor, retroperitoneal fibroplasia, small intestinal volvulus, constrictive pericarditis, and heart failure; 4 and (ii) an abnormality of intestinal mucosal membrane and/or acceleration of vascular permeability such as allergic gastroenteropathy, eosinophilic gastroenteritis, allergic purpura, acute or chronic gastroenteritis, inflammatory bowel deseases and Menetrier desease. 5

Autosomal dominant onychodystrophy and congenital sensorineural deafness

AbstractThe disease “deafness and onychodystrophy” (DOD) is characterized by congenital hearing impairment and dystrophic or absent nails and teeth. The autosomal dominant form of the disorder has been previously reported only in one family. We describe here another family in which three members in three generations (a girl, her mother, and her maternal grandfather) were affected with DOD. Our finding is consistent with an autosomal dominant mode of inheritance and confirms autosomal dominant DOD (DDOD, MIM *124480) as a recognizable clinical entity.

Effect of Continuous LDL Apheresis with Dextran‐Sulfate Cellulose Column System on a Child with Homozygous Familial Hypercholesterolemia

A new system for selective low density lipoprotein apheresis with an automated regenerating column using dextran‐sulfate (DS) as ligand was evaluated for six months in a 13‐year‐old boy homozygous for familial hypercholesterolemia. Two columns each containing 150 ml of DS cellulose were alternately used after rinsing with a regenerating solution. The patient could well tolerate the volume in the system. The values of plasma total cholesterol decreased by 79.4 ± 4.9% of the pretreatment levels after a total of 5ℓ plasma apheresis, while those of high density lipoprotein cholesterol did not change. Although the values of CH50 decreased, no adverse reaction was seen during the period of treatment. It was concluded that the present apheresis system was highly efficacious and safe for children homozygous for the mutant LDL receptor gene.

A case of achondroplasia with severe respiratory failure, profound developmental delay and hypercreatine phosphokinasemia.

osteochondrodysplasias. The main features of ACH include short-limbed dwarfism, craniofacial deformities, such as macrocephaly, frontal bossing, midface hypoplasia and a depressed nasal bridge, a protuberant abdomen, increased pelvic tilt, rhisomelia, and trident hand.1 Although there is mild to moderate hypotonia and motor developmental delay, intelligence is usually normal. Radiological findings of ACH are flared metaphysis, short tubular bones, wide diaphysis, a small foramen magnum and short cranial base, caudal narrowing etc.2 One of the severe complications is cervical medullary junction compression, which may lead to sudden and unexpected death3 and sometimes requires surgical intervention.4 The causative gene of ACH is the fibroblast growth factor receptor 3 (FGFR3) gene.5 Nearly 99% of ACH patients have a G to A transition (most common) or a G to C transversion at nucleotide 1138 of FGFR3 cDNA.6 Thanatopholic dysplasia (TD), which is characterized by short-limbed dwarfism, narrow thorax and early death due to respiratory distress, also has mutations in the FGFR3 gene.7 We report on an ACH patient with severe respiratory failure, severe developmental delay and suspected myopathy.