Minoru Okabe

Rett syndrome: findings suggesting axonopathy and mitochondrial abnormalities

We report the histopathologic findings of 3 sural nerve biopsies and 1 muscle biopsy from 3 patients with Rett syndrome. The 3 sural nerve biopsies demonstrated a few ultrastructural abnormalities, including the presence of many Pi-granules and mitochondrial changes in the cytoplasm of Schwann cells, occasional bands of Büngner and onion-bulb formations, and mitochondrial alterations in myelinated axons. Morphometric analysis disclosed reduction in the number of large myelinated fibers with normal densities in comparison to those of an age-matched normal control. Light microscopic examination of the biopsied muscle from a 6-year-old patient with Rett syndrome revealed the existence of many small, dark, angulated fibers with NADH-TR staining. Ultrastructural investigation of the muscle confirmed the presence of the dumbbell-shaped mitochondria. Peripheral nerve involvement and the possibility of mitochondrial abnormalities in Rett syndrome were suggested by the results.

Electron microscopic study of the biopsied cardiac muscle in Duchenne muscular dystrophy

Cardiac muscular biopsies were performed on 4 patients with Duchenne muscular dystrophy (DMD). None of the patients had cardiac symptoms and all of them exhibited normal electro- and echocardiographic findings. Electron microscopic examination of cardiac muscles from 4 patients with DMD disclosed proliferation of the mitochondria, changes in the cristae, abnormalities of the Z-bands, dilatation of the sarcoplasmic reticulum, deposition of glycogen, and changes in the nuclei. The most striking finding in these patients was that the residual bodies were increased and were observed mainly in the perinuclear region. These ultrastructural features suggest that an extreme exhaustion had already been present in myocardial tissue of the patients prior to the onset of cardiac symptoms.

Proximal and distal motor nerve conduction velocities in Werdnig-Hoffmann disease

Using the latencies of M and F responses, we assessed motor nerve conduction velocity along the entire course of the median and ulnar nerves from the spinal cord to the muscle in 14 patients with the less severe forms of Werdnig-Hoffmann disease. In these forms, the motor nerve conduction velocities were decreased significantly over both proximal (cord-to-elbow) and distal (elbow-to-wrist) segments in both the nerves as compared with normal values; however, the mean motor nerve conduction velocities in the proximal segments were faster than those in the distal segments by about the same amount as the normal controls. These findings indicate that motor conduction abnormalities in Werdnig-Hoffmann disease are diffuse over the entire course of the nerve and appear to eliminate a dying-back process in which the affected axons are severely damaged, beginning with the more distal sites.

Benign familial neonatal convulsions: clinical features of the propositus and comparison with the previously reported cases.

A family with benign familial neonatal convulsions (BFNC) was presented. The propositus had his first episodes of cyanosis on the second day after birth. Thereafter, he also experienced multifocal clonic and/or focal clonic seizures. Between the seizures he appeared well and was essentially normal upon physical examination. Treatment with phenobarbital (4 mg/kg/day, p.o.) was started, and subsequently, he had no further seizures until 3 months of age. At the age of 4 months, he was again admitted to the hospital because of generalized tonic‐clonk seizures. The findings of ictal EEG at that time were characterized by fast spiking with increasing amplitude during the tonic phase. During the clonic phase, there were repetitive bursts of spikes or sharp waves mixed with persisting muscle potentials. The termination of the convulsion was characterized by general voltage depression. Reference to previously reported cases of BFNC revealed that 10–15% of patients with this disorder had epilepsies later in life.

Congenital and Perinatal Cytomegalovirus Infection

Congenital cytomegalovirus infection was found in 0.5% omit of 2,070 newborn infants. None of the congenitally infected infants revealed abnormal clinical and laboratory findings during the period of observation from 2 to 24 months except one case. Impaired specific cell‐mediated immunity was found in congenitally infected infants and this fact seemed to be not a defect but a delay in lymphocytic reactivity.

Skeletal muscle involvement in mucopolysaccharidosis type IIA: Severe type of hunter syndrome

A patient with mucopolysaccharidosis type IIA (MPS IIA) and progressive gait disturbance is described. The histopathology of biopsied muscle was studied; Dorlings method revealed muscle fibers and interstitial cells containing metachromatic granules which suggested the storage of sulfated acidic glycosaminoglycans. Electron microscopy demonstrated that the membrane-bound vacuoles were present in muscle fibers, subsarcolemmal area, vascular endothelial cells, satellite cells, and endomysial fibroblasts. Besides clinical features, this ultrastructural pathology in MPS IIA muscles of MPS IIA was more severe than MPS IIB muscles. The accumulation of glycosaminoglycans in muscle tissue may be an additional factor contributing to gradual motor impairment of patients with MPS IIA.

Histopathological Study of the Biopsied Muscles from Juvenile Patients with Congenital Myotonic Dystrophy

Histopathology and histochemistry were studied in biopsied muscles from eight patients with the congenital form of myotonic dystrophy (congenital MyD) and one patient with the adult form (adult MyD). In the muscle pathology of the four patients aged between 5 and 11 years with congenital MyD, there was no immaturity of the fibers and the histological alterations were minimal. The pathological findings of the adult patient with congenital MyD resembled those of adult MyD. The immature condition of the musculature observed during the early infantile period, therefore, may once improve with motor development during childhood and, after that, the muscle fibers may degenerate in a similar manner to that seen in adult MyD.

Congenital Cytomegalovirus Infection with Unusual Ocular Anomalies

A case of congenital cytomegalovirus infection associated with unusual ocular anomalies is presented. The patient was born at term after an uneventful pregnancy, and generalized petechiae, hepatosplenomegaly, staphyloma of the right eye and anophthalmia of the left eye were observed at birth. Cytomegalovirus was isolated from urine samples of the patient and his mother. Cytomegaiovirus specific cell-mediated immune responses were not significant until one year of age.