Japanese encephalitis - serial CT findings and neuropathology in an autopsy case.

The patient was a 17-year-old man, who developed Japanese encephalitis in the autumn of 1990 in Japan. He was admitted to our hospital 4 days after onset because of consciousness disturbance. On admission, neurological examination demonstrated left hemiparesis, neck stiffness, and Kernig's sign. He developed generalized tonico-clonic seizure, and required a respirator on the next day of admission. Brain CT 10 days after onset demonstrated hypodensities in the right hippocampus, and the CT obtained 39 days after onset showed whole brain atrophy and hypodensities in the anterior portion of the bilateral thalamus. He died 40 days after onset. Postmortem examination demonstrated perivascular and parenchymal infiltration of lymphocytes and macrophages, proliferation of microglia and astrocytes, and necrosis in the gray matter of the brain. Involvement of the hippocampus and thalamus on CT seemed to reflect the severe lesions characterized by cellular infiltration and necrosis. We discussed for the first time the correlation of CT and neuropathological findings in a patient with Japanese encephalitis.

Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

Delayed-onset ataxia in mice lacking alpha -tocopherol transfer protein: model for neuronal degeneration caused by chronic oxidative stress.

alpha-Tocopherol transfer protein (alpha-TTP) maintains the concentration of serum alpha-tocopherol (vitamin E), one of the most potent fat-soluble antioxidants, by facilitating alpha-tocopherol export from the liver. Mutations of the alpha-TTP gene are linked to ataxia with isolated vitamin E deficiency (AVED). We produced a model mouse of AVED by deleting the alpha-TTP gene, which showed ataxia and retinal degeneration after 1 year of age. Because the brain alpha-TTP functions in maintaining alpha-tocopherol levels in the brain, alpha-tocopherol was completely depleted in the alpha-TTP(-/-) mouse brain, and the neurological phenotype of alpha-TTP(-/-) mice is much more severe than that of wild-type mice when maintained on an alpha-tocopherol-deficient diet. Lipid peroxidation in alpha-TTP(-/-) mice brains showed a significant increase, especially in degenerating neurons. alpha-Tocopherol supplementation suppressed lipid peroxidation and almost completely prevented the development of neurological symptoms. This therapy almost completely corrects the abnormalities in a mouse model of human neurodegenerative disease. Moreover, alpha-TTP(-/-) mice may prove to be excellent animal models of delayed onset, slowly progressive neuronal degeneration caused by chronic oxidative stress.

Postmortem study of ataxia with retinitis pigmentosa by mutation of the alpha-tocopherol transfer protein gene.

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.

[A case of progressive systemic sclerosis with Sjögren's syndrome presenting with coma, convulsion and bilateral thalamic hypodensity on computed tomography].

A 35-year-old female with progressive systemic sclerosis (PSS) and Sjögren's syndrome developed consciousness disturbance and generalized seizure after the episode of fever and erythema lasting for 3 weeks. Neurological examination disclosed deep coma and spastic tetraplegia with pathological reflexes. Laboratory data showed mild anemia, severe hypoproteinemia, hypoalbuminemia and increase of protein content in the cerebrospinal fluid. Cranial CT scans obtained after convulsion revealed diffuse brain swelling and bilateral symmetrical hypodensity involving the thalami and posterior limbs of the internal capsule. High-dose corticosteroid therapy and osmotherapy with correction of hypovolemia were started, because severe dehydration, hypoalbuminemia and cerebral vasculitis were suspected to change the vascular permeabilities. Neurological symptoms and CT findings were rapidly improved. Cerebral angiography 4 weeks after convulsion showed definite angitis. The patient was discharged 9 weeks after convulsion. In our case, a possible cause of the characteristic CT findings may be the disturbance of cerebral venous return due to hypovolemia and vasculitis. High-dose corticosteroid therapy may be recommended in patients with collagen disease, who show the bilateral symmetrical thalamic hypodensity on CT scans.

[Effects of Theo-Esberiven on the coronary circulation and myocardial metabolisms in dogs (author's transl)].

In isolated dog heart, Theo-Esberiven 0.1 mg, which contains 12 mg proxyphylline, 2.5 mg rutin and 5 mg Melilotus extract, and proxyphylline (12 mg) increased coronary blood flow (CBF) and was associated with increased heart rate (HR) and myocardial contractile force (MCF). The effect of Theo-Esberiven on CBF was about 1.7 times higher than that of proxyphylline. Theo-Esberiven did not significantly affect myocardial oxygen consumption (QO2) and redox potential (deltaEh), while proxyphylline aggravated myocardial metabolisms, as determined from these parameters. Esberiven 0.1 ml, which contains 2.5 mg rutin and 5 mg Melilotus extract, slightly but signficantly increased CBF and decreased QO2 and deltaEh without changing HR and MCF. In situ, intra-coronary injection of either Theo-Esberiven or proxyphylline resulted in a dose-dependent increase in left circumflex coronary flow (LCCF). The effect of Esberiven on LCCF was much less and was slight at the higher doses. Intravenous injection of Theo-Esberiven (0.1 ml/kg) increased LCCF. Besides this change, marked fall in blood pressure and tachycardia were induced by both Theo-Esberiven and proxyphylline without the change in dP/dtmax. Esberiven by the same route led to the decrease in blood pressure associated with HR and dP/dtmax. These results indicate that Theo-Esberiven may be appropriately prescribed for ischemic heart diseases.