Kuniyasu Takada

Cortical dysplasia in congenital muscular dystrophy with central nervous system involvement (Fukuyama type)

We report five cases of congenital muscular dystrophy with central nervous system involvement of the Fukuyama type (FCMD) in which cerebral cortical dysplasia was not uniform even in the same brain. We have categorized the dysplasia into three major patterns, each with a predictable topography despite individual variations. Cerebellar micropolygyria was localized to the dorsal halves of each hemisphere. Aberrant fascicles of myelinated nerve fibers, closely associated with micropolygyria, were found in the subarachnoid space of the dorsal cerebellar surface in all but one case. We discuss the characteristics of the cortical dysplasia of FCMD, particularly in relation to that of Walkers lissencephaly, pathogenesis, and the relationship between lesions of the central nervous system and skeletal muscle.

Cerebellar micropolygyria in fukuyama congenital muscular dystrophy: Observations in fetal and pediatric cases

Cerebeller micropolygyria in Fukuyama congenital muscular dystrophy (FCMD) was examined neuropathologically by three-dimensional reconstruction and immunohistochemistry in one fetal and two childrens cases. In the childrens cases, a complex columnar network of the molecular layer was mixed with clusters of the granular cell layers, often associated with central blood vessels. Although primitive, cortical dysplasia was also obvious in the fetal cerebellum at 23 weeks of gestation. Ectopic glial proliferation was less extensive than that in the cerebral cortex. It is suggested that leptomeningeal disruption, superficial proliferation of mesenchymal tissue and subsequent mixture of neuroglial and mesenchymal tissues, which may occur transiently during the fetal period in the developing FCMD cerebellum as well as in the cerebrum, play substantial roles in the development of cerebellar cortical dysplasia.

Neuropathological study on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine of the crab-eating monkey

SummaryExperimental parkinsonism was induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the crab-eating monkey (Macaca fascicularis). In the acute stage, the substantia nigra showed necrotic nerve cells, extracellular release of pigment granules and histiocytic infiltration. The nerve cells underwent vacuolation of the cytoplasm with chromatin clumping of the nucleus and disintegration of the nucleolus. The striking feature was the presence of variously-shaped inclusion bodies within abnormal mitochondria which sometimes disclosed a distortion of the cristae. Golgi apparatus and endoplasmic reticulum were also dilated. In the locus ceruleus swollen nerve cells were observed with vacuolated cytoplasm and pyknotic nucleus where expanded mitochondria also contained the inclusions. Some of the inclusion bodies are probably insoluble precipitations due to inhibition of mitochondrial oxidation by a certain metabolite of MPTP. In the protracted stage the substantia nigra revealed a considerable loss of the nerve cells associated with melanophagia and astrocytic proliferation. A few surviving nerve cells showed an increased number of Golgi apparatus and rough endoplasmic reticula, and the presence of autophagosomes, dense bodies and intra-mitochondrial inclusions. These changes are interpreted as being a part of the reparative process from the cellular damage.

A golgi study of the cerebral cortex in Fukuyama-type congenital muscular dystrophy, walker-type “lissencephaly,” and classical lissencephaly

The cortical neuronal organization of the brain was studied and compared in three conditions. The neurons in the polymicrogyric cortex from a subject with Fukuyama-type congenital muscular dystrophy and from a child with ocular dysplasia (Walker-type lissencephaly) were large, irregularly aligned, and not completely mature. In the former condition, the abnormal neuronal arrangement was predominantly in the superficial cortex; in the latter both the superficial and deep cortex were involved. These two diseases may have a similar pathogenetic mechanism. In classical lissencephaly without evidence of other disease manifestations, the neurons were arranged in a radial pattern with heterotopia but no large neurons. The pathogenesis of these conditions is discussed.

Porencephaly and Hydranencephaly: A neuropathological study of four autopsy cases

Four autopsy cases of porencephaly and hydranencephaly were evaluated clinico-pathologically. The patients showed profound mental retardation, convulsive seizures and spastic quadriplegia. The life spans were much shorter in the hydranencephalic cases. Pathologically, the cerebral cortex in the vicinity of the parenchymal defects often showed an abnormal cytoarchitecture, which appeared to be closely correlated with superficial glial proliferation. Several neurofibrillary tangles were found in the nucleus basalis of Meynert and the locus ceruleus in a 23-year-old porencephalic patient, and so-called grumose degeneration of the dentate nucleus in three patients, including a 2-month-old hydranencephalic boy. It is suggested that extensive cerebral defects may cause neuronal degeneration of the subcortical nuclei.

A pathological study of a peripheral nerve in a case of neonatal adrenoleukodystrophy.

SummaryThe pathological findings for a sural nerve biopsy specimen in a case of neonatal adrenoleukodystrophy are described. The density and total number of myelinated fibers in the patient showed no significant changes compared with controls. On electric microscopy, however, thickness of the myelin was smaller in the patient than in controls. Some linear or trilamellar inclusion bodies were found in Schwann cells and fibroblasts, similar to those found in X-linked adrenoleukodystrophy. Büngners bands were also seen on electron microscopy, and myelin ovoids and balls were seen in teased fibers. These results show that a sural nerve biopsy is useful for the diagnosis of neonatal adrenoleukodystrophy. We suspect that axonal or neuronal degeneration occurs with changes in myelin in neonatal adrenoleukodystrophy.

Clinicopathological study in a female infant with 46,XX,i(18q) showing mixed features of both trisomy 18 and monosomy 18p

SummaryClinicopathological and cytogenetic findings in a female infant with 46,XX,i(18q) were reported. She had mixed stigmata of both trisomy 18 and monosomy 18p. Most clinical and pathological findings in this case were compatible with trisomy 18, but several findings such as round flat face, flat nasal bridge, large ears, short webbed neck, low posterior hair line and costovertebral anomalies were compatible with monosomy 18p. Neuropathological study including Golgi study showed minimal dysmorphic abnormalities as seen in trisomy 18.

Progressive encephalopathy associated with cytomegalovirus infection without immune deficiency.

Slowly progressive encephalopathy caused by cytomegalovirus is an unusual disorder, and its pathogenesis remains unknown except for cases associated with the acquired immune deficiency syndrome and organ transplantation. We report a case who showed clinical features of progressive encephalopathy. Cytomegalovirus was repeatedly isolated from urine, and cytomegalovirus-infected cells were detected in bone marrow. Serial computed tomographic head scan revealed periventricular calcification and its progression to the thalamus, cerebellum, and brain stem. On autopsy, there were multiple calcifications and diffuse glial proliferation in the gray and white matter. Perivascular inflammation was only minimal. There was no evidence of immune deficiency. This case suggests that progressive encephalopathy can be caused by cytomegalovirus infection without immune deficiency. This type of cytomegalovirus infection may be unusual, but its serious outcome should remind us to detect it accurately. (J Child Neurol 1993;8:373-377).