Shigeru Hanaoka

MRI and CT findings in Krabbe disease

The progression and characteristics of magnetic resonance imaging (MRI) and computed tomographic (CT) findings in 3 patients with infantile Krabbe disease (i.e., globoid cell leukodystrophy or galactocerebroside beta-galactosidase deficiency) are reported. We obtained initial CT and MRI studies when patients demonstrated hyperirritability and hypertonicity. The following results facilitated early diagnoses: increased density in the thalami, corona radiata, and cerebellar cortex on CT and plaque-like, high signal intensity in the periventricular region and cerebellar white matter on MRI T2-weighted images. After severe motor and mental deterioration and spasticity had developed, progressive brain atrophy, low density in the white matter, and calcification-like, symmetric, punctate high-density areas in the corona radiata were evident on CT and high signal intensity in T2-weighted images and low signal intensity in T1-weighted images in the white matter were present on MRI. In particular, linear patterns were observed in the centrum semiovale on MRI.

Effect of selenium deficiency on cardiac function of individuals with severe disabilities under long-term tube feeding

Eleven orally fed (group A) and 14 tube‐fed patients (group B) with severe disabilities and neurological disorders were compared to determine whether selenium (Se) deficiency is present in patients undergoing long‐term tube feeding, and to examine if Se supplementation has beneficial effects on their cardiac function. Assessments of Se intake, serum levels of Se, and cardiac‐function analysis including chest X‐ray, electrocardiography (ECG), and M‐mode echocardiography (UCG) were made. For group B, the effect of Se supplementation on cardiac function was assessed. Statistical significance was determined using Mann‐Whitney U test and Wilcoxon signed‐rank test. Deficiencies of Se were found in group B. ECG abnormalities were more common in group B than group A. UCG showed a lower ejection fraction, a lower mean rate of circumferential fiber shortening corrected by heart rate, and a lower diastolic velocity of the left‐ventricular posterior walls in group B than in group A. In group B, Se supplementation resulted in normalized serum Se levels, partial improvement of ECG abnormalities, and an increase of cardiac functions on UCG. It is thought that Se has beneficial effects on the myocardium of chronically tube‐fed patients. Se supplementation is recommended in this population.

Pentobarbital therapy for status epilepticus in children: Timing of tapering

Three children with refractory status epilepticus, unresponsive to intravenous administration of diazepam, phenytoin, and lidocaine, received pentobarbital therapy and were monitored by electroencephalography (EEG). They required mechanical ventilation and vasopressor therapy. Intravenous pentobarbital therapy was successful and without distinct sequelae in all 3 patients, and could be incrementally discontinued without breakthrough seizures after 12-65 hours of a burst-suppression or complete suppression pattern on EEG. Obtaining a suppression pattern was important for controlling status epilepticus in children as well as adults. We suggest that 12 hours after a burst-suppression pattern is obtained, tapering of pentobarbital should be attempted to avoid serious complications of extended pentobarbital anesthesia (e.g., respiratory depression, hypotension, pneumonia).

Diagnosis of Alexander disease in a Japanese patient by molecular genetic analysis

AbstractAlexander disease is a leukodystrophy that is neuropathologically characterized by the presence of numerous Rosenthal fibers in astrocytes. Recently, mutations in the gene encoding glial fibrillary acidic protein (GFAP) were identified in patients with Alexander disease. We sequenced the GFAP gene of a Japanese girl who presented with typical symptoms of Alexander disease but in whom the diagnosis was not proven by histopathology. We identified a missense mutation, R239C, which is identical to the mutation previously reported to be most frequent. As was the case in previously described patients, our patient was also heterozygous for the de novo mutation. Interestingly, despite the fact that this is a de novo mutation, R239C was found to be common in different ethnic groups, implying that the site is a “hot spot” for mutagenesis. Molecular genetic analysis now makes the antemortem diagnosis of Alexander disease possible.

Study of the Maturation of the Child’s Brain Using 31P-MRS

The maturation of human cerebrum and cerebellum in 37 normal children aged 4 months to 13 years 8 months was evaluated by 31P-magnetic resonance spectroscopy using two different conditions of repetition time (TR) (TR = 3 seconds and 15 seconds) in each region. The results were as follows. First, the PME/PDE, PCr/gamma-ATP and Pi/PCr ratios differed between the cerebrum and the cerebellum. The PME/PDE and PCr/gamma-ATP ratios were greater in the cerebellum than in the cerebrum. However, the Pi/PCr ratio was smaller in the cerebellum than in the cerebrum. At TR = 3 seconds, the ratio of (PME/PDE ratio in the cerebellum)/(PME/PDE ratio in the cerebrum) and the ratio of (PCr/gamma-ATP ratio in the cerebellum)/(PCr/gamma-ATP ratio in the cerebrum) manifested a nearly constant value independent of age. Second, the phosphomonoester peak in the cerebrum contained a substance with a longer relaxation time than 3 seconds; this substance was present in large amounts in the early period, then gradually decreased during maturation.

Otoacoustic emission in patients with neurological disorders who have auditory brainstem response abnormality

Otoacoustic emissions (OAEs) were evaluated in 51 ears of 30 patients with a severe auditory brainstem response (ABR) waveform abnormality. Thirteen ears showed no ABR to click sound of higher intensity than 100 dBSPL (group 1). Fourteen ears exhibited only wave V or a decreased amplitude pattern of ABR (group 2). Twenty-four ears showed a predominant wave I or no wave III pattern (group 3). Almost all the ears with absent ABR showed no OAE, which strongly suggested hearing loss of cochlear origin, although one patient with alternating hemiplegia of childhood exhibited definite OAEs and auditory reactions without ABR. One patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) and her mother in group 2 had OAE abnormalities, which also suggested mild to severe hearing impairment. When OAEs are present, an accompanying ABR abnormality may be produced by brainstem dysfunction of the underlying disorder such as Pelizaeus-Merzbacher disease. There was a significant relationship (chi-square test P<0.001) between the positivity of the distortion product OAE response and the clinical auditory reactions in 24 patients, although their ABR abnormalities did not reflect hearing impairment directly. Careful examination of both audiometry and OAEs might be necessary for further assessment of the hearing function in pediatric patients with neurological disorders and specific auditory nerve disease.

Apneustic breathing in children with brainstem damage due to hypoxic–ischemic encephalopathy

To confirm the presence of apneusis in patients with hypoxic–ischemic encephalopathy and to clarify which factors influence their respiratory patterns, polygraphic studies were performed on two patients. Apneusis was clinically suspected in both patients who had severe brainstem damage. In one subject, inputs of vagal afferents from the gastrointestinal tract and the urinary bladder often resulted in extreme tachypnea instead of apneusis. Lung inflation facilitated expiration during inspiratory arrest. Expiration preceded a periodic inhibition of rigospastic discharge in the right biceps muscle. In the other subject, prolonged inspiratory pauses with cyanosis occurred with or without preceding epileptic seizure. Both phenytoin dose reduction and treatment with tandospirone, a serotonin‐1A agonist, were effective in improving the respiratory distress in this subject.

Neuropathology of early-infantile epileptic encephalopathy with suppression-bursts; comparison with those of early myoclonic encephalopathy and West syndrome

For the critical lesions and pathomechanism of early-infantile epileptic encephalopathy (EIEE) with suppression-bursts, we investigated the brains of EIEE, early myoclonic encephalopathy (EME), and West syndrome (WS) patients using immunohistochemical technique and neuropathological examination. We could compare with the results of these diseases. The EIEE patients had the most severe lesions, which were in the putamen, thalamus, hippocampus as well as the tegmentum of the brainstem. Among the syndromes, EIEE brains showed the most expanded lesions. Tyrosine hydroxylase-immunopositive cells and fibers were not demonstrated in EIEE, but were detected in WS. Reduced tyrosine hydroxylase immunoexpression in the EIEE brains was in the putamen, globus pallidus, and substantia nigra. Tryptophan hydroxylase immunoreactivity was reduced in the three epileptic syndromes, but especially in EIEE. Reduced expression of tyrosine hydroxylase and tryptophan hydroxylase may demonstrate dysfunction of the catecholaminergic and serotonergic neurons. From this study, the lesions in EIEE were widespread, including in the lower brainstem and cerebellum, compared with in EME and WS. Dysfunction of the catecholaminergic and serotonergic systems could be suggested. These characteristic changes may lead to the pathophysiology of EIEE.

Mechanical ventilation care in severe childhood neurological disorders

Forty-five patients underwent long-term life-sustaining mechanical ventilation care in the Child Neurology Ward, National Center Hospital for Mental, Nervous and Muscular Disorders from 1990 to 2000. Twenty patients had chronic respiratory insufficiency due to neuromuscular disorders, nine of whom underwent home mechanical ventilation care. Nineteen of the 45 patients had chronic respiratory insufficiency due to progressive central nervous system disorders, three of whom underwent home mechanical ventilation care. Six patients with chronic respiratory insufficiency due to the sequelae of transient events were on ventilation, two of whom underwent home mechanical ventilation care. In some patients, especially ones with neuromuscular disorders, mechanical ventilation care is very useful for improving their daily activity and quality of life. In other patients, however, mechanical ventilation care is merely a means of prolonging life without visible improvement of their quality of life. As medical resources are limited, home mechanical ventilation care is a recommended method for patients who need life-sustaining mechanical ventilation care. Considering an individual or social consensus, the indication of long-term life-sustaining mechanical ventilation care for chronic respiratory insufficiency due to severe childhood neurological disorders should be further discussed.

A case of Noonan syndrome with cortical dysplasia

We report the case of a 20-year-old woman with Noonan syndrome. She had severe mental retardation and intractable epilepsy. Magnetic resonance imaging revealed dilated perivascular spaces and a dysplastic lesion in the left temporal lobe, which is thought to have caused her neurologic symptoms. These findings suggest that neuronal in addition to somatic migration can be impaired in Noonan syndrome.