Tomoyuki Nakazawa

Congenital muscular dystrophy with glycosylation defects of α-dystroglycan in Japan

Abstract Glycosylation defects of α-dystroglycan (α-DG) cause various muscular dystrophies. We performed clinical, pathological and genetic analyses of 62 Japanese patients with congenital muscular dystrophy, whose skeletal muscle showed deficiency of glycosylated form of α-DG. We found, the first Japanese patient with congenital muscular dystrophy 1C with a novel compound heterozygous mutation in the fukutin-related protein gene. Fukuyama-type congenital muscular dystrophy was genetically confirmed in 54 of 62 patients. Two patients with muscle–eye–brain disease and one Walker-Warburg syndrome were also genetically confirmed. Four patients had no mutation in any known genes associated with glycosylation of α-DG. Interestingly, the molecular mass of α-DG in the skeletal muscle was similar and was reduced to ∼90 kDa among these patients, even though the causative gene and the clinico-pathological severity were different. This result suggests that other factors can modify clinical features of the patients with glycosylation defects of α-DG.

Depressive tendency in children with growth hormone deficiency

Aim:  This study assessed changes in depressive tendency of children with growth hormone deficiency.

A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting γ-aminobutyric acid degradation. We describe here a boy with a severe phenotype of SSADH deficiency. He was referred because of a developmental delay at 4 months of age. At the age of 8 months, severe seizures developed. The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. His seizures were successfully treated with high-dose phenobarbital, and the electroencephalogram (EEG) abnormalities were ameliorated. However, the patient showed a degenerative clinical course with severe neurological deficits. A magnetic resonance imaging (MRI) scan revealed abnormal high intensities in the putamina and caudate nuclei on T2-weighted images, followed by marked atrophic changes. The clinical manifestation of our patient indicates the wide variety of SSADH deficiency phenotypes.

Norovirus encephalopathy in a previously healthy child.

Norovirus causes acute gastroenteritis in all age groups. Afebrile convulsion is an occasional neurologic complication in norovirus infection, but encephalitis is rare. We report the case of a previously healthy 15-month-old girl with norovirus encephalopathy who had a poor neurologic outcome. Norovirus (genogroup II) was detected in plasma and stool by real-time reverse transcription polymerase chain reaction, but the cerebrospinal fluid showed negative result for genome. Elevated concentrations of cerebrospinal fluid interleukin-6, interleukin-10, interferon-γ, and tumor necrosis factor-α were observed on the third day of illness. The encephalopathy in our patient may be related to hypercytokinemia rather than to direct viral invasion.

Neonatal meningitis caused byBifidobacterium breve

We are reporting a male neonate with meningitis caused by Bifidobacterium breve. This is only the second case reported so far to our knowledge. The patients clinical course was excellent and inflammatory indications, such as serum C-reactive protein, were weak. Although the antibiotics used for the patient were effective against this bacterium both in vitro and in vivo, two relapses occurred which might have been caused by an incomplete remission due to the low permeability of antibiotics through the blood-brain barrier under the very mild inflammation of the meninges, and also by the discrepancy between minimum bactericidal concentrations (MBC) and minimum inhibitory concentrations (MIC). Anaerobic meningitis is very rare, but it may exist in more than the reported cases. Anaerobic culture should be performed for patients with culture-negative purulent meningitis.

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with hemophagocytic syndrome

We reported a girl with HHV-6 infection associated with both acute encephalopathy with biphasic seizures and late reduced diffusion, and hemophagocytic syndrome. She had a prolonged convulsion after a one-day history of febrile illness. Cerebrospinal fluid or brain CT showed no abnormalities on admission and her consciousness was recovered on the next day. However, a prolonged seizure and deterioration of consciousness appeared on the sixth day of illness. Diffusion-weighted images revealed marked reduction of water diffusion in the bilateral frontal areas. HHV-6 infection was virologically proven by polymerase chain reaction. She was treated with gamma-globulin, steroid pulse therapy, and brain hypothermia. In addition, decrease in white blood cells and platelet counts, and elevation of liver enzymes and ferritin were noted on the fourth day of illness. Hemophagocytic macrophages were revealed by bone marrow aspiration on the sixth day. Her hematological and blood chemistry abnormalities recovered gradually after steroid pulse therapy. An elevation of interleukin-6, -8, and -10, and tumor necrosis factor in the serum and that of interleukin-4, -6, and-8 in the cerebrospinal fluid were observed at the onset of a late seizure. These facts suggested that hypercytokinemia will be related to the pathogenesis of acute encephalopathy of our patient.

Sepsis associated encephalopathy in an infant with biliary atresia

We describe a girl with sepsis-associated encephalopathy complicating biliary atresia. At 4 months of age, decreased consciousness and repetitive seizures of the left upper and lower extremities occurred in association with fever. Pseudomonas aeruginosa was cultured from blood, while bacterial culture was negative and cell counts were normal in cerebrospinal fluid. The interleukin-6 level in the cerebrospinal fluid was markedly elevated. MRI revealed unilateral subcortical white matter lesions in the right hemisphere. She was diagnosed as having sepsis-associated encephalopathy and was treated with dexamethasone and midazolam. She achieved normal psychomotor development until the last follow-up at 19 months of age, whereas mild atrophic changes were observed in the right hemisphere.

Prolonged Intracranial Hypertension after Recombinant Growth Hormone Therapy due to Impaired CSF Absorption.

We experienced a case of a Japanese boy who developed intractable idiopathic intracranial hypertension (IIH) during growth hormone (GH) treatment. At the age of 4 yr, the boy was diagnosed with idiopathic growth hormone deficiency, and recombinant human GH replacement was initiated. Nine months after initiation of the GH therapy, he began to complain of headache, but papilledema was not observed. His headache persisted thereafter, and right esotropia occurred 10 mo after the initiation of GH therapy, at which time papilledema was detected. No other neurological abnormalities were detected, and the findings of computed tomography and magnetic resonance imaging were normal. In a cerebrospinal fluid (CSF) examination, the pressure was markedly elevated to 450 mmH2O, but no other abnormality was recognized. Impaired CSF absorption was detected using the pressure-volume index technique. The CSF levels of GH and insulin-like growth factor I were not increased. GH therapy was withdrawn after it was suggested that the IIH was associated with the GH therapy, but the headache persisted. The intracranial hypertension did not respond to diuretics, and prednisolone was only transiently effective. Although the funduscopic findings were normalized, increased CSF pressure was still observed. For over 2 yr, repeated lumbar puncture was necessary to protect against visual defect. IIH is an uncommon adverse event during GH therapy, but it must be considered carefully.

Amplitude-integrated EEG revealed nonconvulsive status epilepticus in children with non-accidental head injury

OBJECTIVE We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants. METHODS NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring. RESULTS The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one. CONCLUSIONS Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non-accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately.

A Case of Morganella morganii Meningoencephatitis

Morganella morganii (M. morganii) is a Gram-negative bacillus found in the environment and among normal human intestinal flora. It is a well known cause of urinary tract infections, wound infections, sepsis and other extra-intestinal infections. It also is considered to be an opportunistic pathogen and has been known to occur both in community and nosocomial infections. Most reported cases of severe infections with M. morganii were in patients with some immunological defects. In this paper, we present a rare case in a child who had a residual cavernous hemangioma in the right frontal lobe and suffered from M. morganii meningoencephalitis.