A case of epileptic negative myoclonus: therapeutic considerations.

This study presents a patient with epileptic negative myoclonus who showed interictal focal epileptic discharges in the centrotemporal region. The patient's seizures were exacerbated by carbamazepine, zonisamide, and valproate, but completely controlled by ethosuximide, and were suggested to have some relation with thalamocortical oscillation mechanisms. Ethosuximide is supposed to be a drug of worth to try to use in epileptic negative myoclonus patients with centrotemporal spike foci.

Regional cerebral blood flow in diagnosis of childhood onset partial epilepsy.

We compared regional cerebral blood flow assessed by [123I]N-isopropyl-p-iodoamphetamine (IMP) single-photon emission tomography (SPECT) with magnetic resonance imaging (MRI), computed tomography (CT) and interictal surface electroencephalography (EEG) to evaluate its diagnostic potential in 24 patients with partial seizures with onset in childhood. Focal low uptake areas were observed on SPECT scans of 18 patients and were presumed to represent epileptogenic areas in 17. MRI revealed an abnormality in 12 and CT in 6 patients, and all organic lesions showed SPECT abnormalities, too. Six patients without focal structural abnormalities showed regional perfusion deficit on SPECT. Routine scalp EEG revealed an epileptic focus in 17 patients and three of them showed discordant results between SPECT and EEG, which suggested more serious brain disorders. In two patients without EEG localization only SPECT showed focal abnormalities in the probable epileptic area. [123I]IMP-SPECT was useful in locating the epileptic focus, particularly during the early period after the onset of partial seizures when the EEG gave inconclusive results.

Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation.

Severe mental retardation is a rare complication of Duchenne muscular dystrophy (DMD). Here we report that two DMD cases showing severe mental retardation exhibit the same exon skipping event induced by different intron mutations. In the two Japanese DMD patients studied, the complete sequence of exon 66 of the dystrophin gene was found to be absent from the dystrophin mRNA, creating a premature stop codon in exon 67. Novel point mutations at the consensus sequence of the splice donor site of intron 66 (T9857(+2) to C in one case and G9857(+5) to T in the other case) were found to be the cause of complete exon skipping. Remarkably, severe mental retardation cosegregated with an exon 66-skipping event in their families. Furthermore, pachygyria was disclosed by magnetic resonance imaging (MRI) examination of the brain of one case. Our results suggested that exon 66 skipping should be examined in DMD cases with a severe form of mental retardation.

Congenital fiber type disproportion: severe form with marked improvement.

A 30-month-old male exhibited marked hypotonia at birth accompanied by respiratory distress necessitating ventilator support. He subsequently demonstrated marked improvement in muscle power. He became independent of the respirator at 21 days of age and was able to sit without support at 11 months and walked alone at 24 months. Histopathologic analysis of the quadriceps femoris muscle confirmed the diagnosis of congenital fiber type of disproportion at 11 months of age. No other studies have described a patient with a severe neonatal form of congenital fiber type of disproportion who demonstrated such clear improvement. Physicians should be aware of this possibility when they interact with such patients and their families.

Phenotypic differences between T-->C and T-->G mutations at nt 8993 of mitochondrial DNA in Leigh syndrome.

This study reports on a patient with Leigh syndrome with a T-to-C mutation at nucleotide 8993 of mitochondrial deoxyribonucleic acid (T8993C). The authors reviewed 10 Leigh syndrome patients, including ours, with T8993C. Compared with 18 reported patients with Leigh syndrome caused by a T-to-G mutation at nucleotide 8993 (T8993G), Leigh syndrome with T8993C was characterized by a significantly higher frequency of ataxia (P < 0.01). None of the reviewed T8993C-associated Leigh syndrome patients had retinitis pigmentosa, which is one of the characteristic findings in Leigh syndrome with T8993G. The milder symptoms of T8993C-Leigh syndrome can be explained by the milder complex V dysfunction; however, the higher frequency of ataxia in T8993C-Leigh syndrome requires more study.

Brain atrophy in congenital neuromuscular disease with uniform type 1 fibers.

We report a patient with congenital neuromuscular disease with uniform type 1 fibers. The patient had manifested muscle weakness and running difficulty since early childhood. Ptosis and ophthalmoplegia were evident, in addition to facial and distal weakness. Her serum creatine kinase level was normal, and electromyography revealed low-amplitude and short duration of motor unit potentials. A muscle biopsy specimen demonstrated absolute predominance of type 1 fibers (> 98%) with no diagnostic structures. Her intelligence was borderline (IQ 80), and dilatation of the lateral ventricles was demonstrated by cranial CT. This is the first report of an abnormality in the central nervous system in congenital neuromuscular disease with uniform type 1 fibers.

[Clinical evaluation of ceftriaxone in the treatment of neonatal infections].

Ceftriaxone (CTRX) was administered to the newborn and its clinical effectiveness as well as its blood and cerebrospinal fluid levels were studied. 1. Average blood levels of CTRX 1 hour after single intravenous administration were 39 micrograms/ml in 2 cases receiving about 10 mg/kg, 70 micrograms/ml in 2 other cases receiving 20 mg/kg and 208 micrograms/ml in one receiving 52.6 mg/kg. As is apparent from these cases data, blood levels of CTRX were dose dependent. Blood levels of the drug were between 3.7 to 12.4 micrograms/ml 24 hours later. Half-lives of the drug in blood in the 5 newborns ranged from 7.13 to 10.6 hours. In a 53-day-old patient receiving 43.4 mg/kg of CTRX via intravenous injection, the one-hour blood level of the drug was 140 micrograms/ml and the half-life was 3.68 hours. The blood level of the drug 36 hours after single intravenous administration with 17.3 to 20.0 micrograms/ml to 5 other cases 0 to 5 days of age ranged from 4.6 to 13.7 micrograms/ml. 2. The cerebrospinal fluid level of CTRX 4 hours after intravenous administration with 49.6 mg/kg to cases of Escherichia coli meningitis was 9.7 micrograms/ml on the first day following the start of the treatment. It increased to 23.6, 25.2 and 31.0 micrograms/ml on the third, fourth and fifth days, respectively, and then gradually decreased. Cerebrospinal level was still 5.8 micrograms/ml on the 22nd day during the recovery period. These levels were far more than 1,000 times as much as the MIC for the pathogen at the highest level, and more than 100 times even at the lowest level. 3. CTRX was administered via intravenous injection once or twice a day (11.0-39.5 mg/kg in total) to 13 newborns and 3 infants. The efficacy of CTRX was good to excellent in 10 cases for treatment of 11 diseases (sepsis 1, pneumonia 4, urinary tract infection 4 and fetal infection 2) and all the pathogens (Streptococcus agalactiae 1, E. coli 3, Klebsiella pneumoniae 2, Citrobacter diversus 1) disappeared. In 6 cases where CTRX was used prophylactically, infection did not occur at all. The efficacy was excellent in another newborn with E. coli meningitis intravenously receiving 49.6 mg/kg of CTRX twice daily for 25 days. 4. No adverse reactions were observed. Mild eosinophilia was observed in 4 cases. Follow-up examinations of 3 of the 4 cases showed that these abnormal levels were returned to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

[Utility and intricacy of molecular diagnosis of spinal muscular atrophy].

To diagnose spinal muscular atrophy (SMA), we examined the deletion of exons 7 and 8 of the survival motor neuron (SMN) gene and exon 5 of the neuronal apoptosis inhibitory protein (NAIP) gene in 7 patients from 6 unrelated families, using the polymerase chain reaction method. Two patients with type I and two with type II SMA had the deletion in SMN, whereas 2 of the 3 patients with type III had no deletion in these genes. Thus, the method was not as useful in type III as in type I and II for making a diagnosis of SMA. Together with the data previously reported by others, our data indicated the possibility that the deletion frequency in type III SMA is lower in Japanese patients (< 40%) than in non-Japanese patients (> 80%). Two siblings had SMA of different severity; the older brother having type III and the younger brother type II. Both had the same deletion in the SMN gene. The different phenotypes in these siblings with the same genotype indicated that caution is required when utilizing molecular data for genetic counseling or prenatal diagnosis of SMA.

Benzodiazepine receptor binding in the spontaneously epileptic rat and its parent strains.

Central type benzodiazepine (BDZ) receptor binding in spontaneously epileptic rats (SER) and their parent strains, tremor rats and zitter rats, and Kyoto/Wistar rats were investigated. Significantly lower BDZ receptor densities (Bmax) and no differences in affinity (KD) were found in the hippocampus of the two epileptic strains, SER and tremor rats, in comparison with Kyoto/Wistar rats and zitter rats. This abnormality is considered to be due to a tremor gene and to be related to absence-like seizures in SER and tremor rats. A significant decrease of KD and an increase of Bmax in the brain stem were found in SER in comparison with Kyoto/Wistar rats. These changes may be due to a zitter gene, since zitter rats show the same tendency, and they may be related to tonic seizures in SER. Bmax was significantly increased in the cerebellum and hippocampus of the zitter rats, while KD was not changed, in comparison with Kyoto/Wistar rats and tremor rats. These changes may reflect the relatively selective loss of tissue lacking BDZ receptors or an upregulation in response to the loss of GABAergic neurons in zitter rats.

Improved bone mineral status in very low birthweight infants fed human milk mixed with preterm formula.

The bone mineral status of very low birthweight (VLBW) infants fed exclusively their own mother's milk (group I) was compared with that of VLBW infants fed mother's milk in the initial 4 weeks followed by a 1:1 mixture of mother's milk and preterm formula containing high phosphorus (P) and calcium (Ca) (group II). In both groups, most infants showed a biochemical picture characteristic of phosphorus deficiency syndrome by the fourth week. Thereafter, serum alkaline phosphatase activity (ALP) decreased and serum P increased in all group II infants. Conversely, serum ALP rose and hypophosphatemia persisted in most group I infants. Group II had a significantly higher serum P at weeks 8 and 12 and a significantly lower ALP at week 12 than group I. Furthermore, group II had a lower incidence of severe radiographic abnormalities than group I at week 12. We confirmed previous observations that VLBW infants fed exclusively human milk require P and Ca supplementation to prevent metabolic bone disease of prematurity.

Changes of NMDA receptor binding in spontaneously epileptic rat and parent strains.

We measured the binding of [3H]3-[(+/-)2-carboxypiperazin-4-yl] propyl-1-phosphonic acid ([3H]CPP), a competitive ligand for N-methyl-D-aspartate (NMDA) receptors, in double mutant spontaneously epileptic rats (SER: zi/zi, tm/tm) and their parent strains, zitter rats and tremor rats, and WTC rats (control rats from tremor rats derived from Kyoto:Wistar rats) before and after the onset of seizures in tremor rats and SER. Significantly lower [3H]CPP binding receptor density (Bmax) was found in the cortex of SER and zitter rats at 12-15 weeks of age than in that of WTC rats and tremor rats, and at 4 weeks of age the Bmax in zitter rats was lower than that in the other strains. The reduction of Bmax in SER at 12-15 weeks of age may reflect a down regulation of NMDA receptors due to repetitive tonic seizures in SER.

Assessment of tubular function in neonates using urinary beta 2-microglobulin.

Renal proximal tubular function was assessed in neonates by measuring urinary beta 2-microglobulin (beta 2M) concentrations on days 1, 4, 7, 14 and 28. Values were elevated in stable preterm low-birthweight (LBW) neonates but not in stable term LBW neonates, suggesting that proximal tubular maturation is related to gestational age rather than birthweight. The urinary beta 2M was significantly increased on day 1 in neonates with the meconium aspiration syndrome but was not significantly different from normal subsequently. This indicated that although the proximal tubular cells may be susceptible to perinatal hypoxia, they maintain a remarkable capacity to recover in a relatively short period. Neonates with transient tachypnoea of the newborn had normal urinary levels of beta 2M indicating their renal tubular function was not impaired.