The efficacy and side effects of oral vitamin K2 therapy were examined in 20 children and adults with probable secondary osteoporosis who had been hospitalized for a long period, due to severe mental and/or physical handicaps. Vitamin K2 was given for 12 months. Bone mineral density significantly increased 4 months after starting oral vitamin K2 therapy (p = 0.0038) and it retained the elevated level after 12 months of treatment. This therapy was particularly effective in patients with severe locomotor dysfunction. Serum total protein levels significantly decreased following the start of this therapy (p = 0.0012). The reasonsof this decrease and its causal relationship to the administration of vitamin K2 are unknown, and should be investigated further.

View full abstract

We report 11 subjects, consisting of sibling cases from 5 unrelated families, with paroxysmal kinesigenic choreoathetosis (PKC). In these subjects the PKC attacks started between the ages of 5 and 17 years and were well controlled with anti-epileptic drugs or subsided spontaneously. In 8 cases from 4 families with PKC, infantile convulsions occurred between the ages of 3 and 8 months and an excellent prognosis was obtained in all but one male. Four of the 8 subjects had complex partial seizures which were characterized by staring, eye deviation, apnea, or loss of consciousness. The nature of these convulsions shared some of the clinical features of benign infantile epilepsies, which have been recently advocated as a new category of epilepsy. There were no differences in the clinical between the cases with and without infantile convulsions

View full abstract

We investigated the incidence of cerebral palsy (CP) in Himeji City with a total population of about 470, 000. In 1983-87 the total number of CP patients and the incidence of CP per 1, 000 live births were 40 and 1.4, respectively. In 1988-92, the figures were 51 and 2.0. Periventricular leukomalacia was indicated in MRI in 11 out of 40 cases (27.5%) in 1983-87, and in 25 out of 51 (49.0%) in 1988-92.
These results suggest that the increase in the incidence of CP mainly depends on changes of medical care for neonates.

View full abstract

We studied seizures that occur during the acute phase of aseptic and bacterial meningitis in childhood. Of the 108 children with aseptic meningitis, five had seizures (4.7%). Four patients developed them within 24 hours of the onset of the initial symptom (fever in 3 cases), and three had repeated seizures on the first day. One case had SIADH complication, but another neurologic abnormalities were not observed. On the 18 children with bacterial meningitis, three cases (16.7%) had seizure, which occurred on the second day of illness. Disturbance of consciousness and cerebral hypertension were observed in 2 cases each, and abnormal cerebral CT findings in all the three. The NSE level in the cerebrospinal fluid was elevated in 2 cases.
Thus, seizures occurring in the acute phase of aseptic meningitis may reflect transient cerebral functional abnormality accompanying fever or SIADH, whereas those in bacterial meningitis may result from neural tissue damage due to encephalopathy or angitis. In aseptic and bacterial meningitis, the presence of seizures in the acute phase was not correlated with the neurological outcome.

View full abstract

Single photon emission computed tomography (SPECT) is a tool to study cerebral blood flow (CBF) kinetics. There are three methods of evaluating SPECT images: visual, semi-quantitative (evaluation of the radioactivity ratio of the cerebral region to the cerebellum [R/CE] or to the thalamus [R/TH]) and quantitative (Matsuda's method by Patlak plot method using ^99mTc-hexamethylpropylene amine oxime radionuclide angiography). We evaluated SPECT images by the quantitative method in 14 patients with neurological disorders and examined the correlation of the results to those obtained by the semi-quantitative method. There was no significant correlation between the R/CE or R/TH ratio and regional CBF except two regions. The evaluation by the semi-quantitative method may have been inappropriate, probably because the cerebellar or thalamic blood flow was not constant in each case.
Evaluation by the quantitative method, on the other hand, seemed to be useful not only for the comparison of CBF among normal subjects, but also in the demonstration of progressive changes of CBF in the same case. The Matsuda's method by the Patlak plot method is suitable for examination of children, since it dose not require aortic blood sampling.

View full abstract

We studied the rehabilitation approach to children with acquired hypoxic encephalopathy. The subjects were 13 children with sequelae of hypoxic encephalopathy. The onset ranged from 1 month to 15 years of age. Recovery was good in no case, moderate in 3, poor in 3, and absent in 7 cases. We evaluated the following factors: condition at the onset, present status, degree of improvement of the functional independence measure (FIM).
In the moderate recovery group, resuscitation was performed within 5 minutes, and consciousness loss disappeared within 3 days. Some patients had no physical disability, whereas others had ataxia. In the no recovery group, consciousness loss was severe and continued more than 5 days. Most of them had spastic quadriplegia. The improvement of FIM was 52.8±23.9 in the moderate recovery group, 12.0±8.2 in the poor recovery group, and 0 in the no recovery group. Pediatricians as well as rehabilitation doctors should use FIM to evaluate the effect of rehabilitation.

View full abstract

Dentatorubral- pallidoluysian atrophy (DRPLA) is a neurodegenerative disease showing autosomal dominant inheritance, which is associated with a specific trinucleotide repeat expansion in the DRPLA gene. We performed DNA analysis of two affected and one non-affected individuals of a Japanese family with DRPLA. The proband (case 1) developed seizures at age 17, and these gradually evolved to intractable myoclonic epilepsy. His father (case 2) had manifested gait disturbance since the age of 40, which was followed by progressive dementia. DNA analysis disclosed that these patients had an expanded CAG repeat in the DRPLA gene, which confirmed the diagnosis. The brother of case 1, who was asymptomatic, expressed a desire to undergo predictive DNA testing for DRPLA. We discussed the ethical and social issues of this predictive testing, and decided to carry out the testing after obtaining informed consent from him and his wife. The test revealed no expanded allele, thus proving that he would not develop DRPLA, and relieving him of his fears. Our results suggest that predictive testing improves the psychological well-being of non-affected individuals in DRPLA families.

View full abstract

In the treatment of epilepsy, benzodiazepines are often administered in combination with other antiepileptic drug (s) because of the development of tolerance. In this study, the influence of concurrently administered antiepileptic drugs on tolerance to the anticonvulsant action of the nitrazepam (NZP) was studied using an animal tolerance model. Mice were given vehicle, NZP alone or NZP concurrently with one of six antiepileptic drugs (carbamazepine CBZ, phenytoin PHT, zonisamide ZNS, vigabatrin VGB, lamotrigine LTG, or flunarizine FNR) twice daily for 5 days. Tolerance was assessed by the ability of NZP to prevent pentylenetetrazol-induced clonic convulsions. Tolerance developed in mice treated with NZP alone, NZP plus CBZ, PHT, ZNS, VGB or LTG. On the other hand, mice receiving NZP + FNR showed no tolerance; there was no significant difference in seizure frequency between the vehicle group and NZP+FNR group. These data suggest that co-administration of FNR but not CBZ, PHT, ZNS, VGB or LTG may delay if not prevent development of tolerance to the anticonvulsant action of benzodiazepines.

View full abstract

We reported a male patient with X- linked myotubular myopathy in whom MTM 1 gene mutation was first identified in Japan. The patient had 9- nucleotide insertion between exons 11 and 12 due to aberrant splicing.
The patient showed severe hypotonia and generalized muscle weakness at birth. Mechanical ventilation and tube feeding were necessary because of poor spontaneous respiration and sucking. On muscle biopsy, most of the muscle fibers were small and round, and had peripheral halos, showing immaturity. He had a moderate ventricular dilatation and mild brain atrophy on brain CT and MRI.
However, whether these findings are causally related to the splice-site mutation remained obscure.

View full abstract

A sibling of three year old girl and a year old boy, showed delayed post-anoxic encephlopathy after strangulation. After three days of the accident, the girl developed tetraplegia and choreo-athetosis. Her brother also developed choreo-athetosis two weeks after strangulation. T₂ weighted MRI revealed a high signal intensity in the bilateral putamen and caudate nucleus. After hyperbaric oxygen therapy for two months, their symptoms diminished. We hypothesize that the functional damage of the neurons occurred in the bilateral basal ganglia as delayed neuronal death because of their vulnerability and peculiarity of the local circulation. Hyperbaric oxygen therapy may be effective in rescueing the neurons from hypoxia.

View full abstract

We report here a case of vertebral artery dissection, which is rare in childhood. A 12-year-old, previous healthy girl was admitted to our hospital with symptoms of vertigo, tinnitus, hearing loss, nausea and vomiting. Although there was neither higher cortical dysfunction, motor weakness, sensory disturbance nor slurred speech. She could not stand up because of severe vertigo. Cranial magnetic resonance imaging (MRI) revealed a subacute cerebellar infarct. A left vertebral artery angiogram on the hospital day 3 demonstrated a sharp narrowing at the CI-C2 level. After an anticoagulant therapy for about 2 weeks, all the symptoms disappeared except for mild tinnitus. Two months later, a left vertebral artery angiogram showed an abrupt occlusion at the C1 level. MRI T₁-weighted images demonstrated a thrombus within the false lumen of the dissected vessels. A flow void revealed the patency of the residual true lumen. From these findings, we made a diagnosis of vertebral artery dissection, which was considered to have caused cerebellar infarction. The patient was mostly normal at discharge, and 100 mg/day of aspirin has been given until present.

View full abstract

We report here a case of an 11-year-old boy with juvenile type of dentatorubral-pallidoluysian atrophy (DRPLA). His psychomotor development has been delayed since infancy and cerebellar ataxia was noted at the age of 2 years, indicating an early onset. At the age of 6 years, he had progressive myoclonus epilepsy (PME) and underwent a series of neuroradiological, electrophysiological and pathological examinations, which failed to reveal the etiology. Gene analysis performed at the age of 11 years revealed an expanded CAG repeat at the DRPLA locus in both the patient and his asymptomatic father. In the absence of a positive family history, a diagnosis of DRPLA may be difficult due to its clinical variability. We conclude that DRPLA should be taken into account in the differential diagnosis of childhood PME and that gene analysis should be performed to confirm a diagnosis of DRPLA.

View full abstract