Ryuhei Kodaka

Manganese Deposition in the Brain During Long-Term Total Parenteral Nutrition

BACKGROUND Manganese deposition was suspected in a pediatric patient who received long-term total parenteral nutrition. T1-weighted magnetic resonance images revealed high intensity areas in the globus pallidus. This study was designed to clarify if these abnormal findings were related to manganese deposition and clinical neurological manifestations. METHODS Whole-blood manganese concentrations were measured during manganese supplementation to total parenteral nutrition and after 5 months without manganese. Magnetic resonance images were also examined on each occasion and compared with the blood level of manganese. RESULTS The whole-blood manganese level during supplementation was 135 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was 20 micrograms/L after a manganese-free period of 5 months. Accompanied with normalization of manganese level, abnormal high intensity lesions in the globus pallidus on T1-weighted images also disappeared. No neurological manifestation related to the high manganese level was recognized. CONCLUSIONS It is probable that the high manganese level was elicited by manganese supplementation to total parenteral nutrition. This high manganese condition was confirmed by the measurement of whole-blood manganese level, which was associated with the abnormal high intensity lesions on T1-weighted magnetic resonance images.

Evaluation of myelination by means of the T2 value on magnetic resonance imaging

The progress of myelination in the cerebrum was evaluated by visual inspection, and magnetic resonance (MR) imaging and the transverse relaxation time (T2) was calculated from double echo images. Twenty-three pediatric cases, who did not show intracranial organic changes on MR examination, were included. The T2 values in the corpus callosum (CC), frontal deep white matter (FWM), occipital deep white matter (OWM) and centrum semiovale (CS) were calculated, and the changes in these values with age were followed. During the first year of life, a rapid decrease in the T2 value was seen, followed by a more gradual decrease. The T2 value seemed to reach the adult level between 2 and 3 years of life in all areas examined. The T2 values between 2 and 16 years in CC, FWM, OWM and CS were 59.7 +/- 3.6, 64.5 +/- 5.2, 69.8 +/- 4.8 and 66.3 +/- 3.3 ms (mean +/- S.D.), respectively. The T2 values in patients with clinically diagnosed Pelizaeus-Merzbacher disease (PMD) and late onset Krabbe disease were also calculated. In PMD, non-progressive prolongation of the T2 value was observed in all areas. In late onset Krabbe disease, on the other hand, progressive prolongation of the T2 values was mainly demonstrated in OWM and the posterior part of CS. These results suggest that the T2 value in the cerebral white matter allows more objective judgement than visual inspection, and makes it possible to clarify the mechanism underlying abnormal myelination, i.e. progressive or not.

Central nervous system abnormalities in chromosome deletion at 11q23

Two Japanese pediatric patients with terminal deletion of the long arm of chromosome 11 are described. Both had the morphological abnormalities of the 11q deletion syndrome, such as prominent epicanthal folds, broad flat nasal bridge with short, upturned nose, short philtrum with carp‐shaped mouth, cardiac anomalies and nonprogressive moderate psychomotor developmental delay. Patient 1 is the first case to be reported with 11q deletion with serial magnetic resonance (MR) examinations of cerebral white matter. The initial MR imaging studies demonstrated multiple areas of T1 and T2 prolongation in the cerebral white matter in both patients at the ages of 2 5/12 and 2 1/12 years, respectively. A second MR imaging, performed 1 year after the first in Patient 1, demonstrated slight improvement of the lesions. Neither patient showed clinical deterioration. These results suggest that the lesions were caused by delayed myelination, rather than by demyelination. It is suggested that an unknown factor which is important for myelination is located on the long arm of chromosome 11: perhaps the neural cell adhesion molecule (NCAM).

MR diffusion imaging in Pelizaeus-Merzbacher disease

A case of classical type Pelizaeus-Merzbacher disease was reported. This patient exhibited marked motor and mental developmental delay, and nystagmus, with a positive familial history. Electrophysiological studies, such as on brainstem auditory evoked potentials, blink reflex and somatosensory evoked potentials, suggested marked disturbance of nerve conduction in CNS. T2-weighted magnetic resonance (MR) images revealed non-progressive diffuse T2 prolongation of cerebral white matter after a 2-year interval, indicating congenital hypomyelination in CNS. A newly developed magnetic resonance diffusion imaging method demonstrated the existence of diffusional anisotropy in the corpus callosum, internal capsule, and white matter of the frontal lobe. Although the diffusional anisotropy was considered to depend on the well-developed multiple layers of myelin around the axons, the imaging data of this patient demonstrated that the diffusional anisotropy did not necessarily depend on those multiple layers. These results may indicate the potential usefulness of MR diffusion imaging, combined with electrophysiological studies and conventional MR imaging, for analyzing the lesions of the cerebral white matter.

Regional cortical dysplasia associated with suspected hypomelanosis of ito

A 15-year-old girl with epilepsy, whose skin lesions were reminiscent of hypomelanosis of Ito, is reported. She manifested hypopigmented linear streaks on her upper and lower limbs. Brain magnetic resonance imaging examinations demonstrated poor differentiation of cerebral gray and white matter of her left occipital lobe, with accompanying gliosis. This region also revealed narrowing of sulci, considered to be mass effect. In this region, almost continuous spike discharges were evident on electroencephalograms, and low-perfusion status was observed on single photon emission computed tomography at rest. She also manifested right lower homonymous quadrant anopsia, which may have its origin in the lesion detected, which appeared to be a migration disorder of neuroblasts in our patient, suggesting that the spectrum of hypomelanosis of Ito might be involved.

Decrease of the central type benzodiazepine receptor in cortical tubers in a patient with tuberous sclerosis.

An 18-year-old man with tuberous sclerosis was studied with I-123 lomazenil SPECT and the findings were compared with those of MRI. In all cortical tubers detected with MRI, 1-123 iomazenil binding 180-191 minutes after intravenous administration was decreased significantly. This result indicates that the binding potential of 1-123 lomazenil is decreased in cortical tubers.

The moment of intraventricular hemorrhage.

A continuous monitoring of the germinal layer by linear scanning ultrasound has been proposed for the purpose of ascertaining the moment of intraventricular hemorrhage (IVH). Using a VHS videotape, we performed the 48 hours monitoring in 7 immature infants weighing less than 1,000 g who required respiratory support. Four cases of these developed IVH. In one case, which was 755 g in birth weight and 24 weeks in gestational age, the moment of IVH was successfully demonstrated on the ultrasonic monitor. At that moment, there were no significant changes in heart rate and systemic blood pressure. No direct manipulation or treatment, such as an endotracheal suctioning or a heel puncture which might induce a blood pressure fluctuation, was being given at the moment of IVH. About 15 minutes after the episode, abnormal seizure-like movement periodically developed.

A Transcranial Doppler Ultrasonography Study of Cerebrovascular CO2 Reactivity in Mitochondrial Encephalomyopathy

BACKGROUND AND PURPOSE To elucidate the pathogenic role of vascular involvement such as mitochondrial angiopathy in patients with mitochondrial encephalomyopathy (MEM). we used the transcranial Doppler sonography (TCD) method to detect impairment of cerebrovascular CO2 reactivity. METHODS The cerebral perfusion reserve in 13 MEM patients, including 6 with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) was studied by TCD for different CO2 partial pressures. For the parameter of mean flow velocity, the mean spatial Doppler frequency (fm) was obtained from the right and left middle cerebral arteries and basilar artery under conditions of normocapnia, hypercapnia, and hypocapnia in cases in which hyperventilation was possible. By fitting the obtained fm and the end-tidal CO2 partial pressure (PETCO2) to the exponential formula fm = a x e(K < PETCO2), where a is the theoretical fm at a PETCO2 of 0 mm Hg, the parameter K, an index of CO2 reactivity, was calculated. RESULTS The K value was lower than control values at at least one site of the middle cerebral arteries and basilar artery of all patients with MELAS as well as the other MEM patients except for one patient with myoclonic epilepsy with ragged-red fiber and one with Kearns-Sayer syndrome. CONCLUSIONS Our results suggest that there is a high incidence of impairment of cerebrovascular CO2 reactivity in MEM patients. Moreover, the noninvasive TCD method was found useful for evaluation of cerebral hemodynamics in MEM patients.

Long‐Term Outcome of Functional Hemispherectomy in Two Cases of Diffuse Cortical Dysplasia of One Hemisphere

Purpse: Patients with diffuse cortical dysplasia in one cerebral cortex, such as those with cortical hemihypertrophy, are well known to have intractable epileptic seizures and severe developmental delay of mental state and motor skills. We previously reported that the region of cortical dysplasia shows the histologic characteristics of neuronal hyperactivity with impaired γ‐aminobutyric acid (GABA)‐mediated transmission. Resections of one hemisphere have historically been performed to control such epileptic seizures, although often they also cause severe complications such as massive bleeding and hydrocephalus. To decrease the severity and incidence of such complications, a procedure known as modified hemispherectomy was recently developed. We performed functional hemispherectomies on two cases of intractable epilepsy caused by unilateral cortical dysplasia. The purpose of this study was to evaluate the long‐term clinical effects of this surgery for epileptic seizure, including the effects on mental state and motor skills.

Interaction between valproate formulation and phenytoin concentrations.

Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was replaced by the same dose as a slow-release tablet.The mean plasma phenytoin level rose significantly from 14.4 to 18.7 μg·ml−1. Nine of eleven patients had markedly increased phenytoin levels (by 21 to 72%), and two developed toxic symptoms.The results indicate that changing valproate formulations can cause major alterations in the plasma concentration of co-administered phenytoin.