Kenzo Takeshita

Plasticity of central motor and sensory pathways in a case of unilateral extensive cortical dysplasia Investigation of magnetic resonance imaging, transcranial magnetic stimulation, and short-latency somatosensory evoked potentials

We studied a 13-year-old girl with unilateral extensive cortical dysplasia who had mild hemiparesis with mirror movement and no sensory deficit. Transcranial focal magnetic stimulation (TMS) to the unaffected hemisphere elicited bilateral motor evoked potentials (MEPs) of the abductor pollicis brevis muscle (APB) with similar latency and amplitude. The scalp positions where the MEP amplitudes were highest were at the same site in the unaffected hemisphere for both APBs. TMS to the affected hemisphere showed no MEP for either APB. These data indicated that the APB response of the paretic side originated from the same motor cortex as for the contralateral APB, probably due to axonal sprouting. In the study of short-latency somatosensory evoked potentials, the cortical representation point of the paretic hand sensation was in the ipsilateral unaffected hemisphere; this point was located anterior to the cortical representation point of the contralateral hand sensation. We conclude that reorganization of primary motor and sensory cortex occurs when there is unilateral extensive brain damage in early gestation. NEUROLOGY 1995;45: 2255-2261

Visuo-perceptual impairment and cerebral lesions in spastic diplegia with preterm birth

Eighteen cases of spastic diplegia (SD) ranging in age from 5 year 4 month to 9 year 5 month with preterm birth were studied to clarify the relationship between visuo-perceptual impairment and their cerebral lesions. All underwent neuropsychological examinations including the Frostig developmental test of visual perception, Tanaka-Binet or Suzuki-Binet intelligence test, and MRI examination. Cerebral lesions were detected in all subjects, and the volume of the peritrigonal white matter of the parietal and occipital lobes was significantly correlated with the visuo-perceptual impairment (r = 0.74, in the axial plane; r = 0.64, in the coronal plane). We propose that visuo-perceptual impairment is caused by cerebral lesions and that the measurement of peritrigonal white matter by MRI is useful for detecting potential visuo-perceptual impairment at an early age.

MR imaging of spastic diplegia

SummaryEighteen children (eleven preterm birth and seven term birth) with clinical evidence of spastic diplegia (SD) were studied to clarify the differences of the lesions between preterm and term SD on MR imaging. All with preterm birth showed similar abnormalities of the periventricular white matter represented by high intensity in T2-weighted imaging and low intensity in T1 imaging. It seemed that the lesions were periventricular leukomalacia (PVL) and dysmyelination pathologically and correlated well clinically with spastic diplegia. SD with term birth group showed various lesions, two brain anomalies (schizencephaly and corpocephaly), one PVL, four showed no lesions. We suggested that SD with preterm birth is not only a clinical but also a pathological entity.

Central Motor Reorganization in Cerebral Palsy Patients with Bilateral Cerebral Lesions

Transcranial magnetic stimulation (TMS) has been used to describe cortical plasticity after unilateral cerebral lesions. The objective of this study was to find out whether cortical plasticity occurs after bilateral cerebral lesions. We investigated central motor reorganization for the arm and leg muscles in cerebral palsy (CP) patients with bilateral cerebral lesions using TMS. Seventeen patients (12 with spastic diplegia, 1 with spastic hemiplegia, and 4 with athetoid CP) and 10 normal subjects, were studied. On CT/MRI, bilateral periventricular leukomalacia was observed in all spastic patients with preterm birth. In two normal subjects, motor responses were induced in the ipsilateral tibialis anterior, but no responses were induced in any normal subject in the ipsilateral abductor pollicis brevis (APB) or biceps brachii (BB). Ipsilateral responses were more common among CP patients, especially in TMS of the less damaged hemisphere in patients with marked asymmetries in brain damage: in 3 abductor pollicis brevis, in 6 BBs, and in 15 tibialis anteriors. The cortical mapping of the sites of highest excitability demonstrated that the abductor pollicis brevis and BB sites in CP patients were nearly identical to those of the normal subjects. In patients with spastic CP born prematurely, a significant lateral shift was found for the excitability sites for the tibialis anterior. No similar lateral shift was observed in the other CP patients. These findings suggest that ipsilateral motor pathways are reinforced in both spastic and athetoid CP patients, and that a lateral shift of the motor cortical area for the leg muscle may occur in spastic CP patients with preterm birth.

A morphometric CT study of Down's syndrome showing small posterior fossa and calcification of basal ganglia.

SummaryWe report characteristic and morphometric changes of cranial computed tomography (CT) with increasing age in 56 patients with Downs syndrome aged from 0 month to 37 years. Patients were compared with 142 normal controls aged 0 to 59 years. Width of ventricles, Sylvian fissures, posterior fossa, pons and cisterna magna were measured on CT. The incidences of the cavum septi pellucidi, cavum vergae and cavum veli interpositi and high density in the basal ganglia were examined. There was high incidence (10.7%) of bilateral calcification of basal ganglia in Downs syndrome, although that of pineal body and choroid plexus calcification was similar in Downs syndrome and controls. Basal ganglia calcification is more frequently seen in young Downs syndrome and may be related to the premature aging characteristic of Downs syndrome. The CT in Downs syndrome showed relatively small posterior fossa, small cerebellum, small brain stem and relatively large Sylvian fissures in those under one year of age. There was a high frequency of midline cava and large cisterna magna. There were no significant atrophic changes on CT except after the fifth decade comparing with controls.

Cerebral Palsy in Tottori, Japan

From the changing incidence of cerebral palsy (CP) in the Tottori joint study, the absolute number of saved non-CP babies in the period 1955–1984 in the whole of Japan was calculated as about 33,000. The significant decrease of the incidence in the period 1955–1980 was mainly related to the advances made in perinatal medicine. In contrast, the recent reincrease is attributable to low-birth-weight CP. As for the risk factors for quadriplegia or double hemiplegia of CP, maternal toxemia, low Apgar scores and neonatal abnormal signs were important. Diplegia and paraplegia were significantly correlated with low birth weight. Among the babies weighing below 2,000 g, there was a more than 40-fold increased risk of CP compared with that in the general population. As for the risk for low-birth-weight diplegic CP, the number of abnormal signs in the neonatal period is correlated with the brain damage. The next step in preventing perinatal brain damage might be to give more attention to fetal deprivation and to well-balanced and sensible neonatal care of risk babies.

The carbohydrate deficient glycoprotein syndrome in three Japanese children

We describe 3 children (from two families) with a multisystemic disorder characterized by mental retardation, nonprogressive ataxia, polyneuropathy, hepatopathy during infancy and growth retardation. Due to the clinical similarities to a recently recognized disorder associated with carbohydrate-deficient transferrin, we examined serum transferrin by means of isoelectric focusing, and found increases in disialo transferrin and asialotransferrin. Removal of sialic acid with neuraminidase revealed the same transferrin phenotypes as in their parents. Similarly, carbohydrate-deficient fractions of serum alpha 1-antitrypsin were also detected. Therefore, the diagnosis was made of the recently identified carbohydrate-deficient glycoprotein syndrome. This is a genetic disorder with distinctive clinical features and multiple carbohydrate-deficient glycoproteins. These seem to be the first reported Japanese patients with this syndrome.

Varicella with Delayed Hemiplegia

We report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection. In 2 patients, carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery. Their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus, the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection. We believe that our patients had the same pathogenesis. In a survey of infectious diseases in our region, the frequency of varicella with delayed hemiparesis was roughly 1:6,500 varicella patients.

Measles virus-specific T helper 1/T helper 2-cytokine production in subacute sclerosing panencephalitis.

Live measles virus-specific T helper 1/T helper 2-cytokine productions by peripheral blood mononuclear cells in response to live measles, mumps or varicella virus were measured in 15 patients with subacute sclerosing panencephalitis and 15 controls by enzyme-linked immunosorbent assays. Most patients with subacute sclerosing panencephalitis had a defect in measles virus-specific production of interferon-gamma, one of the T helper 1 type cytokines, despite persistent presence of measles virus, with preserved interleukin-10 (T helper 2 type cytokine) synthesis. Patients with subacute sclerosing panencephalitis were divided into two groups: responders (group A) with significant interferon-gamma production (>20 pg/mL) in response to live measles virus and non-responders (group B) with a little or no interferon-gamma production. Comparison of the clinical courses between groups A and B revealed that all the patients of group A retained receptive function for a long time, while most patients of group B lost the function rapidly (P<0.01). An inverse correlation between interferon-gamma production by peripheral blood mononuclear cells and disease progression suggested that interferon-gamma plays an antiviral role in subacute sclerosing panencephalitis.

Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex

AbstractWe have surveyed the mutations of TSC1 and TSC2 from 38 (25 sporadic, 11 familial, and 2 unknown) Japanese patients with tuberous sclerosis complex. In 23 of 38 subjects, we detected 18 new mutations in addition to 4 mutations that had been previously reported. We also found 3 new polymorphisms. The mutations were not clustered on a particular exon in either of the genes. Seven TSC1 mutations found in 3 familial and 4 sporadic cases were on the exons (3 missense, 2 nonsense point mutations, a 1-base insertion, and a 2-bp deletion). Fifteen TSC2 mutations were found in 5 familial cases, 10 sporadic cases, and 1 unknown case. The 12 mutations were on the exons (8 missense, 1 nonsense point mutations, a 1-bp insertion, a 5-bp deletion, and a 4-bp replacement) and 3 point mutations were on the exon-intron junctions. Although the patients with TSC2 mutations tend to exhibit relatively severe mental retardation in comparison to those with TSC1 mutations, a genotype-phenotype correlation could not yet be established. The widespread distribution of TSC1/TSC2 mutations hinders the development of a simple diagnostic test, and the identification of individual mutations does not provide the prediction of prognosis.