Michiya Ohta

Glial fibrillary acidic protein in medulloblastoma

SummaryTwenty-four cases of classical medulloblastoma and one case of desmoplastic medulloblastoma were examined for glial fibrillary acidic protein (GFAP) using the immunoperoxidase method to assess astrocytic differentiation. In 16 cases of classical medullablastoma GFAP-positive cells were present in variable numbers.These cells were classified as three different types according to size and shape. The type 1 cell was morphologically identical to the ordinary tumor cell, with a hyperchromatic nucleus and a scanty cytoplasm. The type 2 cell had a fairly rich cytoplasm with short cytoplasmic processes. The type 3 cell was characterized by a relatively large nucleus with sparse chromatin and well-developed cytoplasmic processes, and was considered a reactive astrocyte. The type 1 and some of the type 2 cells seemed to be neoplastic, displaying astrocytic differentiation. The remaining type 2 cells may have been reactive astrocytes.In one case of desmoplastic medulloblastoma, the majority of GFAP-positive cells were arranged in “islands”, and had delicate fibrillated processes. GFAP-positive cells were also observed outside these “islands”, though they were less numerous. Most of them were regarded as type 3 cells, but some were type 2. This may be interpreted as meaning that the glial character of the tumor was expressed more within than outside these “islands”.

Joseph disease in a non‐Portuguese family

We studied four patients with Joseph disease in a Japanese family. There were two clinical types in the family. One was characterized by pyramidal and cerebellar signs with or without extrapyramidal signs; the other, by cerebellar signs, loss of tendon reflexes, and peripheral sensory loss. The family tree indicated autosomal-dominant inheritance. Neuropathologic examination revealed marked degeneration of the substantia nigra, dentate nuclei, Clarke column, and anterior horn cells of the spinal cord. This is the first report of pathologically proven Joseph disease in a non-Portuguese family.

Giant axonal neuropathy: A clinical entity affecting the central as well as the peripheral nervous system

An 8-year-old girl had progressive muscle weakness and a unique posture of the lower limbs, areflexia, distal sensory impairment, and remarkably kinky hair. Histologic examination of the sural nerve showed giant axons filled with neurofilamentous masses. The clinical and histologic findings resembled those of recent cases reported as “giant axonal neuropathy.” Our patients precocious puberty, Babinskis sign, and electroencephalographic abnormalities suggested central nervous system involvement. Two cases previously reported and the present one appear to represent a new clinical entity that affects the central and the peripheral nervous system.

Microvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors: structural basis for altered blood-brain barrier function.

SummaryThe fine structure, histometric characteristics, and permeability of microvessels were studied by electron microscopy in normal and in ethylnitrosourea (ENU)-induced glioma tissue from rats, using horseradish peroxidase (HRP) as a tracer. The tumor vessels were classified into (1) capillary buds (Type I); (2) round small to large capillaries (Type II); (3) sinusoidal or venule-like microvessels (Type III), and (4) abnormal arteriole-like microvessels (Type IV). All endothelial cells, basement membranes and periendothelial cells in the tumor tissue demonstrated changes in structure. The most striking alterations occurred in the endothelial cells; there were abnormal endothelial tight junctions, altered pinocytotic activity, and thickening. In the tracer study, the reaction product of HRP was present around some sinusoidal or venule-like microvessels (Type III) and extended to the widened extracellular spaces around the microvessels. The endothelial cells of Type III microvessels showed decreased nuclear and mitochondrial fractions, and increased euchromatin content and a rough endoplasmic reticulum fraction. The pinocytotic vesicles with the HRP reaction product in the endothelial cells were not increased in number. Fenestrations and gaps of the endothelial cells were observed. These alterations of the endothelial cells of sinusoidal or venule-like microvessels (Type III) are considered to be the main cause of breakdown of the blood-brain barrier in this tumor.

A Case of Hereditary Ceruloplasmin Deficiency with Iron Deposition in the Brain Associated with Chorea, Dementia, Diabetes mellitus and Retinal Pigmentation: Administration of Fresh-Frozen Human Plasma

We report a familial case of hereditary ceruloplasmin deficiency (HCD) showing an A-G transition in intron 6 of the ceruloplasmin gene. Clinical features consisted of chorea, cerebellar ataxia, dementia, diabetes mellitus, retinal pigmentation and iron deposition in the liver and brain without copper overload in those organs. The patient’s children and siblings had similar laboratory results, but did not show any neurological abnormalities. She was medicated for diabetes mellitus at 43 years of age, and neurological signs appeared when she was 52 years old. The laboratory findings were anemia, low concentrations of iron and copper in serum and of copper in urine. Ceruloplasmin was not detected in the serum. The iron and copper contents in the liver were 3,580 and 10 μg/g wet tissue, respectively. MRI of the brain showed iron deposition in the basal ganglia, dentate nucleus and thalamus. This case did not show any abnormal increase in copper in the blood and urine following CuSO45H2O oral overloading test. Following the intravenous administration of commercially available fresh-frozen human plasma (FFP) containing ceruloplasmin, the serum iron content increased for several hours due to ferroxidase activity of ceruloplasmin. In the liver, the iron content decreased more with the combined intravenous administration of FFP and deferoxamine than with FFP administration alone. Her neurological symptoms improved following repetitive FFP treatment.

Iron overload and antioxidative role of perivascular astrocytes in aceruloplasminemia

Aceruloplasminemia (ACP) is an inherited disorder of iron metabolism caused by the lack of ceruloplasmin activity; the neuropathological hallmarks are excessive iron deposition, neuronal loss, bizarrely deformed astrocytes, and numerous ‘grumose or foamy spheroid bodies (GFSBs)’. We histopathologically examined two autopsied ACP brains, and observed for the first time that GFSBs form in clusters at the ends of perivascular astrocytic foot processes. Both the deformed astrocytes and the GFSBs contained ferric iron and were intensely immunolabelled with antibodies against the antioxidant proteins ferritin and manganese superoxide dismutase (Mn SOD). Ceruloplasmin is largely produced by perivascular astrocytes in the central nervous system and exhibits a ferroxidase activity that inhibits iron‐associated lipid peroxidation and hydroxyl radical formation; therefore, the lack of ceruloplasmin causes direct oxidative stress on astrocytes. The intense immunolabelling of ferritin and Mn SOD most likely reflects a defensive response to iron‐mediated oxidative stress. This study suggests that astrocytes play key roles in iron trafficking and the detoxification of iron‐mediated free radicals at the blood–brain barrier and in the parenchyma in ACP brain. The antioxidative ability of astrocytes is one of their essential neuroprotective effects, and the decompensation of this ability may lead to secondary neuronal cell death in ACP.

Ciliated and goblet cells in craniopharyngioma

SummaryA case of a suprasellar epithelial cyst in a 48-year-old man is reported. The cyst was lined with two different types of stratified epithelium: one was two to three or more layers of squamous cells with overlying ciliated columnar cells and goblet cells at the surface and the other was typical stratified squamous epithelial cells. The tumor was neither a pure Rathkes cleft cyst nor a typical craniopharyngioma but was considered essentially to be a craniopharyngioma with ciliated columnar cells and goblet cells. Thus it might be considered a mixed form of these two tumors. This case indicates the close relationship between craniopharyngiomas and Rathkes cleft cysts.

Clinical observations of juvenile nonprogressive muscular atrophy localized in hand and forearm

SummaryTwenty-seven patients with juvenile nonprogressive muscular atrophy localized in the hand and forearm were analyzed. The clinical characteristics were juvenile male occurrence, insidious onset, specific distribution of localized muscular atrophy and a stationary course. On electromyography, denervation voltage (or giant NMU) is found in the atrophied muscles and sometimes in contralateral nonatrophied ones. Sensory disturbance was not remarkable. Although the etiological factor was not known, strenuous exercise of arms in sports was noted frequently in the history.Zusammenfassung27 Patienten mit „juveniler nonprogressiver Muskelatrophie, lokalisiert an der Hand und dem Vorderarm“ wurden analysiert. Klinisch charakteristische Merkmale waren Vorkommen bei jungen Männern, schleichender Beginn, lokalisierter Befall der erwähnten Muskelgruppe und stationärer Verlauf nach einer anfänglichen Progression. Elektromyographisch wurde eine Denervation in den atrophischen Muskeln und manchmal in den Muskeln der kontralateralen Seite bemerkt. Sensible Ausfälle waren nicht eindrücklich. Obgleich die Ätiologie nicht klar war, wurde häufiger Gebrauch der Hand im Sport in der Krankheitsgeschichte bemerkt.

A quantitative study of the muscle satellite cells in various neuromuscular disorders.

The regenerative ability of muscles was studied in various neuromuscular disorders by quantitative electron microscopy using two indices of both the satellite cell population and the euchromatin percentage of satellite cell nucleus. Both the number of satellite cells and the euchromatin percentage were increased in polymyositis. Duchenne muscular dystrophy and myotonic dystrophy showed only an increased number of satellite cells without increased euchromatin percentage, while amyotrophic lateral sclerosis had only an increased euchromatin percentage without increased satellite cell number. These results suggest that some defects of satellite cell function probably exist in progressive muscular dystrophy and amyotrophic lateral sclerosis, while in polymyositis the muscle fiber may have the ability to regenerate completely. The euchromatin percentages of myonuclei were increased in polymyositis and Duchenne muscular dystrophy, but not in amyotrophic lateral sclerosis or myotonic dystrophy compared to those of controls. This suggests the activated function of the remaining muscle fibers in polymyositis and Duchenne muscular dystrophy.

Familial occurrence of migraine with a hemiplegic syndrome and cerebellar manifestations

IT IS UNDERSTOOD that migraine is a syndrome of unknown etiology manifested by periodic and recurrent headache and that it often has a strong familial tendency. In association with the attack of migraine, the development of hemiparesis, facial paresis, retinal arterial occlusion, or ocular nerve palsy has been reported infrequently, but such symptoms are usually transient and disappear after the attacks. If the neurological manifestations persist, the term “complicated migraine” is applied. Several investigators have seriously suspected the presence of an intracranial vascular lesion in such patients. However, although relatively uncommon, there are several cases of patients in whom the persistent neurological defects were observed in the absence of angiographic findings of vascular malformations. This paper will describe a familial occurrence of hemiplegic migraine in which 4 members are affected, 2 of whom were examined by us. These 2 members had persistent cerebellar manifestations which developed during the course of several attacks of migraine. To our knowledge, cerebellar manifestations in migrainous subjects have not been reported earlier.