Mieko Yoshioka

Cerebral atrophy following ACTH therapy.

In a study of 15 patients with infantile spasms and Lennox syndrome 4 (26.7%) showed no cerebral atrophy and 11 (73.3%) showed mild ventricular and sulcal enlargement before ACTH therapy. Ventricular and sulcal enlargement increased soon after ACTH therapy in most patients. Cerebral atrophy was reversible at over 1 month after ACTH therapy. However, in three instances, cerebral atrophy was not reversible, and one patient with infantile spasms had chronic subdural effusion, which appeared to be a complication of treatment with ACTH. Patients on ACTH therapy should be carefully monitored.

Skewed X inactivation in manifesting carriers of Duchenne muscular dystrophy

We studied X inactivation patterns in manifesting carriers of familial and sporadic Duchenne muscular dystrophy (DMD) or unaffected carriers of DMD by analysis of the methylation of Hpall sites in the first exon of the human androgen‐receptor gene (HUMARA) from peripheral blood samples. Three of the four manifesting carriers, four of the five asymptomatic carriers, and 31 of the 32 female controls were heterozygous for the CAG repeat of HUMARA. All manifesting carriers showed skewed X inactivation, while all unaffected carriers showed almost symmetrical inactivation. One family studied over three generations is noteworthy because it includes two mother/daughter pairs, one an affected pair with skewed X inactivation, and the other a phenotypically normal carrier pair with random X inactivation. On the other hand, the extent of X inactivation for each X chromosome in 31 female controls was widely distributed. These data suggest that in carriers of DMD, both affected and unaffected, it is valuable to analyze the pattern of skewed X inactivation because it provides important prognostic information. Carriers of DMD with skewed X inactivation might show slowly progressive myopathy with advancing age.

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.

Pituitary Hyperplasia Due to Hypothyroidism.

Two cases of hypothyroidism with computed tomographic evidence of enlargement of the pituitary gland are reported: in both the enlargement disappeared after treatment. These findings are in agreement with the previously reported observation that an increase of TSH production in primary hypothyroidism may lead to pituitary hyperplasia.

Congenital muscular dystrophy (Fukuyama type). Repeated CT studies in 19 children.

Abstract Repeated CT examination was carried out on 19 patients with congenital muscular dystrophy (Fukuyama type) (F-CMD). The intervals of examinations ranged from 5–33 months with an average of 23 months. Low density area in the white matter found in 11 patients at the first CT examination was later decreased in 8 and in 3 was unchanged. Cerebral atrophy was decreased in 6 CT scans (5 cases), unchanged in 9 cases and increased in 5 cases. All these findings suggest that F-CMD is not a degenerative disorder, rather may be due to infection during the fetal period.

Clinically manifesting carriers in Duchenne muscular dystrophy

Three manifesting carriers of Duchenne muscular dystrophy were examined clinically and histologically. All had muscle weakness in the upper and lower limbs without facial muscle involvement, onset being at the ages of 35, 19 and 25 years, respectively. Pseudohypertrophy of calves was evident in all cases. Biochemical, electrocardiographic and histological observations revealed the presence of myopathy in all cases. Sex chromatin patterns were normal. Compared with the manifesting carriers previously reported by others, at least one case showed more severe histological findings which were typical of the advanced stage of Duchenne muscular dystrophy. The cardiac involvement in three cases was moderate. A possible involvement of other factors besides Lyonization influencing the development of myopathy in the carriers is suggested.

Leigh syndrome associated with West syndrome

Leigh syndrome (LS) (sub-acute necrotizing encephalomyelopathy) is characterized by symmetric brain lesions occurring mainly in the basal ganglia and associated with variable clinical manifestations such as hypotonia, psychomotor retardation, and feeding difficulties. Patients with LS may develop seizures. Only three patients with LS have been identified in the literature as having West syndrome (WS). We have seen 12 children with LS in the past 20 years, and noticed that as many as five of them developed WS. This report discusses five LS children with WS, comparing them with seven LS children without WS. In all five patients, infantile spasms developed after LS had become evident, in addition to other type(s) of seizures. The onset of LS in all the patients with WS was before 10 months of age. Although not statistically proven, early onset of LS, spasticity, nystagmus, apnea, poor feeding, and cardiac problems seemed to be associated with the development of WS. We were not able to conclude that certain types of symptoms or examination results of patients with LS indicated the development of WS. The association of LS with WS did not markedly influence the prognoses of the children. WS may not be a rare complication of LS, especially in infants under 12 months of age. This report is the first review of LS associated with WS.

A case of hypertensive encephalopathy with extensive spinal lesions on MRI

A 14-year-old female had repeated vomiting, headache, abdominal pain, visual field deficit and lethargy at the onset of hypertensive encephalopathy. Cerebrospinal fluid (CSF) test revealed a high level of IgG and protein. MRI demonstrated no supratentorial cerebral lesions but hyperintense lesions were observed from the lower pons to the Th8 level of spinal cord and cerebellar cortex on T2 weighted and FLAIR images without contrast enhancement. The two antihypertensive drugs stabilized to control her blood pressure and improved her clinical symptoms. Reexamination of MRI and cerebrospinal fluid test also revealed clear improvement of the above abnormalities. The abnormal findings on abdominal CT and renography led us to suspect renal infarction. Abdominal angiography demonstrated multifocal stenoses of renal interlobar arteries, which were supposed to supply the renal infarcted regions. These suggested that the renal infarctions due to fibromuscular dysplasia caused systemic hypertension. There have been only two reports that demonstrated spinal cord lesions in reversible posterior leukoencephalopathy syndrome (RPLES). We report extensive spinal lesions on MRI and a high level of IgG in CSF at the subacute phase in a young female with RPLES associated with hypertensive (brainstem) encephalopathy.

Long-term prognosis of epilepsies and related seizure disorders in fukuyama-type congenital muscular dystrophy

Fukuyama-type congenital muscular dystrophy is an autosomal recessive disorder prevalent in Japan that is characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. We examined 46 patients with Fukuyama-type congenital muscular dystrophy and followed their progress for more than 3 years, with special reference to long-term prognosis of seizure disorders and the relationship between seizures and neuropathologic abnormalities. Seizures were observed in 37 patients (80%). The average age at onset was 3 years, 1 month. Initial seizures usually occurred after a febrile episode, although one third of patients had afebrile seizures from the onset. All patients had generalized tonic-clonic convulsions at febrile disorders, and these were followed by complex partial seizures or secondary generalized seizures. Later these seizures developed into Lennox-Gastaut syndrome in three patients. Electroencephalography (EEG) showed paroxysmal discharges in 22 of 37 patients with seizures (59%). The main focus was in the frontal, temporal, or central region. Lesions with marked cortical dysplasia detected by computed tomography, magnetic resonance imaging, or autopsy showed focal paroxysmal discharges on EEG. (J Child Neurol 2005;20:385—391).

Three patients with ophthalmoplegia associated with Campylobacter jejuni.

Cranial polyneuropathy is idiopathic in most patients. Idiopathic cranial polyneuropathy is an acute postinfectious syndrome, along with Guillain-Barré syndrome and Miller Fisher syndrome, in which the common preceding pathogen is Campylobacter jejuni. Serum anti-GQ1b antibodies are elevated in Miller Fisher syndrome and Guillain-Barré syndrome with ophthalmoplegia. Three patients with idiopathic cranial polyneuropathy with predominant ocular involvement are presented. C. jejuni isolated from stool specimens belonged to Penner serotypes O:4, O:23, and O:33. Serum anti-GQ1b antibodies were elevated in all patients but demonstrated rapid reduction concomitant with clinical recovery. All patients recovered completely. Because both preceding C. jejuni infection and elevated anti-GQ1b antibodies decreasing with time were seen in all patients, the pathogenesis of idiopathic cranial polyneuropathy with ophthalmoplegia may be similar to that of Miller Fisher syndrome.