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We herein present a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), who developed serious acute renal failure with lactic acidosis, followed by rhabdomyolysis. Despite receiving intensive care, he suffered multiple cardiopulmonary arrests and died 10 days after presentation due to a sudden deterioration of his symptoms. Renal pathology revealed diffuse tubular necrosis with interstitial edema and tubular dilatation on light microscopy, and a severe degeneration of intracellular organelles on electron microscopy. These pathological findings could have resulted from multiple cardiopulmonary arrests; however, we must be aware of the extremely rare but sudden occurrence of these fatal conditions in MELAS patients.

Respiratory insufficiency is a critical problem in amyotrophic lateral sclerosis (ALS) patients. We herein present the case of an autopsied patient with sporadic ALS who underwent diaphragm pacing (DP). The pathology showed several localized adhesions with a markedly atrophied diaphragm. A marked loss of motor neurons with Bunina bodies and phosphorylated TDP-43 positive inclusions was found in the spinal cord and primary motor cortex. Mild hyalinization and a few multinucleated giant cells were present around the electrode tracks in the diaphragm. However, no infiltration of inflammatory cells was detected. Our findings suggest that full-time DP might not cause severe damage to adjacent diaphragm tissue.

●Abstract● Purpose: A case of multiple brain infarction caused by embolism of a chondroma in the left vertebral artery is reported. Case presentation: A 38-year-old woman was admitted for cerebral infarction. On angiography, a round filling defect was observed in the V2 segment of the patent left vertebral artery, thought to be a floating embolus. The patient was successfully treated with embolectomy by means of endovascular procedures immediately after angiography. Histopathologic evaluation indicated the embolus to be a piece of chondroma. Conclusion: Cerebral embolism from tumor, especially chondroma, is extraordinarily rare. The source of the embolism in this patient is thought to most likely be the heart.

Heavy-ion irradiation/Delayed encephalopathy/Delayed myelopathy/Brain edema/Hyperpermeability. Aim: The pathogenesis of delayed encephalopathy induced by heavy-ion irradiation was investigated experimentally in cats. The left cerebral hemispheres were irradiated with 15-40 Gy of heavy ions (carbon), and histologically and morphometrically examined 12 months later. Results: In the irradiated cerebral white matter the following occurred as the dose increased: astrocytic swelling, then the dilatation of small blood vessels with a fibrous thickening of the wall, and then loosening of the white matter with cavity formation and diffuse albumin deposition. Pathological features of these cavities suggested that they are induced by long-standing edema. Although the dilated vessels were arteries, veins, and capillaries, arteriovenous shunt and damage of the smooth muscle cells of the arterial media were absent. Changes of the cerebral cortex were scarce. Morphometrically, the irradiated cerebral white matter was swollen, and the capillary density tended to be reduced in the deep cortex and subcortical white matter, but this effect was not dose dependent. Conclusion: Heavy-ion irradiation induces delayed encephalopathy in cats, preferentially involving the white matter. The cardinal pathogenesis was long-standing edema of the white matter due to vascular hyperpermeability, and the vascular dilatation seemed to be caused by a reduction in the vascular bed and/or hemoconcentration due to hyperpermeability.

Background and Purpose— There is little information regarding the pathogenesis underlying diffuse myelin loss in the cerebral white matter and sparing of the U fibers in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in which the medial smooth muscle cells of systemic arteries are characteristically involved. We sought to examine the precise extent and severity of changes in the cerebral arteries in an autopsy case of CADASIL in relation to pathogenesis of the diffuse myelin loss. Methods— We reconstructed 1000 serial sections of the frontal cerebral medullary arteries of an autopsy subject, which was the first identified Japanese case of CADASIL, as confirmed by the presence of ultrastructural deposits of granular osmiophilic material in the media of some visceral arteries and by genetic analysis. Results— We reconstructed 11 medullary arteries of the frontal lobe showing diffuse myelin loss and atrophy of the white matter with sparing of the U fibers. All of these showed complete loss of medial smooth muscle cells over their entire length and severe adventitial fibrosis. Although intimal fibrosis or hyalinosis was present, luminal occlusion was scarce. These changes were also observed in the small and large arachnoidal arteries but were relatively mild in the latter and in the cortical and subcortical medullary arteries. Conclusions— These arterial changes resulted in transformation of the cerebral arteries, in particular almost all the medullary arteries, to a so-called earthen pipe state. This supports the reported findings of a reduction in vascular reactivity to fluctuations in CO 2 levels and systemic blood pressure in CADASIL.

脳腫瘍45例における細胞塗抹標本を免疫細胞化学的に検討してみた.GFAPではependymomaを含めたglia系腫瘍に陽性であり, それ以外の腫瘍との鑑別に有用と思われた.またgliomaにおいては悪性度が高くなるにしたがい不均一性となり減少傾向を示した.NFPはglioblastomaの一部の症例とpituitary adenomaに陽性であり, glioblastomaにおいては異分化への発現が示唆された.VimentinはgliomaにおいてGFAPと逆相関する形で陽性となり, glioma細胞の脱分化が示唆された.Cytokeratinはmetastatic carcinomaとpituitary adenomaのみに認められ, 他の脳腫瘍との鑑別に有用と思われた.NSEは特異性を示さず多くの脳腫瘍に陽性であった.S-100はmetastatic carcinomaのみに陰性を示した.また染色性の違いにより細胞像がよく類似するmeningiomaとneurinomaとの鑑別にも有用と思われた.

¶A 17-year-old boy with epileptic seizures due to meningio-angiomatosis without neurofibromatosis type 2 is presented. Low grade astrocytoma in the left temporal lobe was resected when he was 11 years old. A recurrence was suspected on following-up MRI and a positive PET scan with 11C-methionine PET 6 years later around the resected area. The language area was mapped using H2 15O PET activation technique. The lesion was completely resected while preserving the verbal area assisted by three-dimensional imaging protocol of MR-registered PET. The patient was well and seizure-free for 8 years thereafter without antiepileptic drugs. Histologically, there was an increase of dilated arterioles and meningothelial cell-like spindle cells around them, which are characteristic pathological features of meningio-angiomatosis. It is most likely that angiomatous tissue developed perivascular meningiomatous components and formed the meningio-angiomatosis in our presented case. In addition, we presented our protocol of functional neuro-imaging which was useful in terms of the functional neurosurgery.

Background and Purpose— With advances in the therapy of stroke at the postacute phase, the use of animal models for chronological and region-specific evaluation of neurological function has become increasingly important. Our aim was to test long-term behavioral dysfunction in gerbils after focal ischemia and to correlate the results with the regional distribution of infarction in the coordinating cortical regions. Methods— Repetitive unilateral hemispheric ischemia (two 10-minute occlusions, 5-hour interval) was induced in Mongolian gerbils. The elevated body swing test (EBST), bilateral asymmetry test (BAT), and T-maze test were performed to assess asymmetrical motor behavior, somatosensory deficit, and spatial cognitive dysfunction during 4 weeks after ischemia. The results were correlated against the regional infarction volume of the primary motor, somatosensory, and primary visual cortices at 4 weeks after ischemia. Results— In all postischemic gerbils, persistent sensorimotor and cognitive dysfunctions were detectable throughout the postischemic period. Histological examination revealed that a cortical zone of infarction surrounded the selective neuronal death in the ipsilateral cerebral hemisphere. The regional infarction volumes of the primary motor, somatosensory, and visual cortices were significantly correlated with the scores of the EBST, BAT, and T-maze test, respectively. These combinations had the highest regression coefficient of all pairs. Conclusions— Postischemic motor and somatosensory functions were significantly correlated with regional infarction volumes in the corresponding cortical regions. In gerbils, visual abnormality could be independently detected by the T-maze test. Such regional analyses of ischemic lesions would be useful for investigating the functional outcomes of stroke therapy.

Endovascular treatment with Guglielmi detachable coil has been developed as a less invasive treatment for cerebral aneurysm. The aim of this study is to clarify the mechanism of the preventive effect of coil embolization.Two aneurysm models were employed. One was a T-shaped bifurcation tube with a spherical dome made of glass, which was used for the measurement of pressure and visualization of flow pattern. The other model was a T-shaped glass tube with a spherical elastic silicone dome, which was used for the measurement of aneurismal wall displacement due to pulsation of flow.1, Guglielmi detachable coil caused no change in intra-aneurismal fluid pressure. 2, Coil insertion obstructed and slowed intra-aneurismal flow. This flow stagnation in the aneurysm might promote thrombus formation. 3, With increase in numbers of coils anchored at the intra-aneurismal wall, the displacement of the wall was considerably depressed. This suggests that coil insertion decreases the stress on the aneurismal wall.1, Coil insertion depresses the pulsatile aneurysm wall movement, and diminishes the stress of the aneurysm wall. 2, Coil insertion obstructs intra-aneurismal flow and facilitates thrombus formation in the aneurysm. These two factors may operate synergistically to prevent aneurysm rupture.

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alpha-TTP) gene was recently proposed. After studying the first postmortem case with this mutation pathologically and biochemically, whether the symptoms can be treated by supplementation of vitamin E or not is discussed. The major pathological findings were retinal atrophy; severe dying back-type degeneration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost identical to those in vitamin E deficient animals and patients with fat malabsorption. Also, mild loss of Purkinje cells was noted. Because robust expression of alpha-TTP was detected in the cerebellum as well as in the liver and the tissue concentration of vitamin E in the cerebellum was still low even after oral supplementation, the mild Purkinje cell loss might be related to the mutant alpha-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of alpha-TTP was detected, and the tissue concentration of vitamin E increased to normal after supplementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.

Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.

The late effects of heavy-ion irradiation on the spinal cord of the rat were investigated histologically and morphometrically. After a single exposure of each animal's lower thoracic and lumbar spinal cord to a carbon-ion beam, the animals were observed clinically for up to 69 weeks and their spinal cords were examined histologically after sacrifice. Paralysis of the hind limbs appeared from 16 to 20 weeks after irradiation with 20 Gy or more. The first histological change seen was vacuolization in the marginal white matter, which appeared 19 to 25 weeks after irradiation with more than 10 Gy. After irradiation with more than 15 Gy, bilateral destructive cavities occurred in the white matter, especially in the lateral tract. These histological changes were similar to those reported frequently for X irradiation. The mean cross-sectional area of the blood vessels in the irradiated spinal cord increased in a manner that was dependent on dose and was significantly larger 15 to 17 weeks after irradiation with 30 Gy. Reconstruction of small destructive lesions from serial sections consistently revealed dilated veins in the centers of these lesions. The effective dose that induces 50% incidence of hind-limb paralysis and destructive cavity formation (ED50) as determined using a curve-fitting method was 18.5 and 19.5 Gy, respectively, and the latent period was shorter than that for X irradiation.

脳虚血のモデルとしては現在に至るまで数多くのモデルが用いられているが, 中でも経眼窩的中大脳動脈閉塞モデルは, その病態がヒトの脳梗塞に近いため広く用いられている.我々はその原法を改良して良好な成績を収めている.即ち, 実験2～7日前に中大脳動脈を経眼窩的に露出し, ナイロン糸をその周囲にかけ, その糸を眼窩内にレジンで固定したチューブを介して眼窩皮下に誘導しておく.実験の際はその糸を牽引することにより中大脳動脈を閉塞し, 糸を抜去することにより再疎通をはかる.我々の改良したモデルは脳内の単一血管の閉塞により脳梗塞が生じ, 必要に応じて再開通が可能である.また脳虚血発症時に麻酔剤を使用する必要がなく, 髄液の漏出等によるartifactの可能性が最小限である等の優れた点があり, 今後の脳虚血の研究に有用であると思われる.

Three cases of neoplastic angioendotheliosis (NAE) presenting with central nervous system (CNS) disease but no skin lesions are described. The histogenesis of the neoplastic cells is discussed. Microscopic examination showed accumulation of neoplastic cells in the vascular system throughout the body and their extravascular proliferation in several organs. Electron microscopic and immunohistochemical studies revealed the presence of Weibel-Palade bodies and factor VIII-related antigen in intravascular and extravascular neoplastic cells in two of the three cases. In the first case the neoplastic cells did not have any T-cell markers. However, in one case no specific markers were found in the neoplastic cells by electron microscopic, enzyme histochemical, or immunohistochemical examination. These findings, although supporting the endothelial origin of the neoplastic cells, indicate the need for further consideration of whether NAE is actually a single disease entity or several different diseases.