Hisakazu Uno

Induction of tumor necrosis factor-α in the mouse hippocampus following transient forebrain ischemia

To assess the role of tumor necrosis factor-α (TNF-α) in modulating the process of cerebral ischemic injury, we identified TNF-α-producing cells and studied the time course of TNF-α expression. Immunoreactivity for TNF-α appeared in white matter of the mouse hippocampus as early as 1.5 h following a 30-min global ischemic insult. Double staining for TNF-α and glial fibrillary acidic protein (GFAP) suggested that the TNF-α-positive cells are most likely microglia, not astrocytes. TNF-α immunostaining decreased at 6 and 24 h but increased again at 3 days, when pyramidal neurons showed degeneration. Adjacent-section staining for microglia and double staining with GFAP suggested that TNF-α-positive cells in the pyramidal cell layer were microglia and those in the white matter were astrocytes. By 5 days TNF-α immunostaining disappeared from these glial cells, while a number of microglia were accumulated in the degenerated hippocampal pyramidal layer. Pyramidal neurons never expressed TNF-α immunoreactivity. Western blotting confirmed biphasic TNF-α expression. Our findings suggest that early production of TNF-α by microglia may activate a cytokine network in postischemic brain resulting in TNF-α synthesis by astrocytes.

Localization of Fas antigen mRNA induced in postischemic murine forebrain by in situ hybridization

The expression of mRNA for the Fas antigen, a membrane-associated protein mediating apoptosis, was localized by in situ hybridization histochemistry in murine brains following 30 min of global cerebral ischemia. Six hours following the ischemia, many labeled cells were detected anew throughout the brain. The hybridization was seen in the small neural cells and in the cells along the walls of the ventricles and vessels, and became undetectable 24 h following the ischemia. These results suggest that the Fas antigen is expressed in the neuron, glia and periventricular cells of the post-ischemic brain.

Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia.

The beneficial effects of angiotensin II type 1 (AT1) receptor blockers (ARB) in cerebrovascular disease have been shown in clinical trials. However, the effects of ARBs vary based on their unique pharmacologic properties. In this study, we focused on telmisartan, a fat-soluble ARB with selective peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist activity, and investigated its effects on ischemic injury in cerebral vasculature using murine models of both transient and permanent focal ischemia. Analysis by triphenyltetrazolium-staining revealed that pre-treatment of mice with telmisartan reduced stroke volume 72 h after the transient ischemic insult in a dose-dependent manner, though such treatment did not reduce stroke volume due to permanent ischemia. Transient ischemia induced pro-inflammatory adhesion molecules, such as ICAM-1 and P-selectin in the ischemic region, and treatment with telmisartan diminished the expression of these adhesion molecules with diminished infiltration of inflammatory cells. The beneficial effect of telmisartan was attenuated, in part, by administration of a PPAR gamma antagonist. Treatment with valsartan (an ARB without PPAR gamma agonist activity) also decreased ischemic injury after transient ischemia, though to a lesser extent than telmisartan. Our findings indicate that telmisartan has a beneficial effect in a murine model of ischemia/reperfusion injury through blockade of AT1 receptors, and, in addition, due to a positive effect via its specific anti-inflammatory PPAR gamma agonist activity.

Prostate Cancer-Induced Oncogenic Hypophosphatemic Osteomalacia

A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl, marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25 (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase of relative osteoid volume and fractional formation rate in the undecalcified section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of 1,25 (OH)2D production and phosphaturia was suggested.

Relationship between Detectability of Ischemic Lesions by Diffusion-Weighted Imaging and Embolic Sources in Transient Ischemic Attacks

Background/Aims: The aim of this study is to clarify the relationship between lesion detectability by diffusion-weighted magnetic resonance imaging (DWI) and the etiology of transient ischemic attacks (TIAs). Methods: A retrospective study was performed on 72 patients with carotid TIAs who underwent DWI studies within 2 weeks after the last episode. Results: Lesions were detected in 24 of 72 patients (33%). The detectability of lesions was 12% (3/25) in the large-artery atherosclerosis (LA) group, 57% (8/14) in the cardioembolism (CE) group, 8% (1/13) in the small-artery occlusion (SA) group, and 60% (12/20) in the other etiology or undetermined etiology (UD) group. Detectabilities in the CE group and the UD group were higher than those in the LA and SA groups. Of 24 patients with DWI-positive lesions, 17 (71%) had embolic sources in the heart; 9 were classified in the UD group because they had embolic sources both in the heart and large artery. Conclusion: Ischemic DWI lesions in TIAs are most likely caused by a cardioembolic mechanism. In TIA patients showing lesions on DWI, heart disease should be surveyed as the possible embolic source.

Cerebral salt-wasting syndrome due to hemorrhagic brain infarction: a case report

IntroductionCerebral salt-wasting syndrome is a condition featuring hyponatremia and dehydration caused by head injury, operation on the brain, subarachnoid hemorrhage, brain tumor and so on. However, there are a few reports of cerebral salt-wasting syndrome caused by cerebral infarction. We describe a patient with cerebral infarction who developed cerebral salt-wasting syndrome in the course of hemorrhagic transformation.Case presentationA 79-year-old Japanese woman with hypertension and arrhythmia was admitted to our hospital for mild consciousness disturbance, conjugate deviation to right, left unilateral spatial neglect and left hemiparesis. Magnetic resonance imaging revealed a broad ischemic change in right middle cerebral arterial territory. She was diagnosed as cardiogenic cerebral embolism because atrial fibrillation was detected on electrocardiogram on admission. She showed hyponatremia accompanied by polyuria complicated at the same time with the development of hemorrhagic transformation on day 14 after admission. Based on her hypovolemic hyponatremia, she was evaluated as not having syndrome of inappropriate secretion of antidiuretic hormone but cerebral salt-wasting syndrome. She fortunately recovered with proper fluid replacement and electrolyte management.ConclusionsThis is a rare case of cerebral infarction and cerebral salt-wasting syndrome in the course of hemorrhagic transformation. It may be difficult to distinguish cerebral salt-wasting syndrome from syndrome of inappropriate antidiuretic hormone, however, an accurate assessment is needed to reveal the diagnosis of cerebral salt-wasting syndrome because the recommended fluid management is opposite in the two conditions.

Severe and prolonged ictal paresis in an elderly patient

We report an 84-year-old female who showed a rare manifestation of epilepsy, ictal paresis, a type of simple partial seizure presenting with focal motor dysfunction. While the patient exhibited severe left hemiplegia which lasted for a week, cranial diffusion-weighted MRI demonstrated slightly high intensity in the right posterior quadrant, and electroencephalography (EEG) showed continuous epileptiform discharges located mainly in the right parieto-occipital area, strongly suggesting that the patient was in an ictal state. 99mTc-hexamethylpropylene amine oxime-single photon emission computed tomography (HMPAO-SPECT) showed markedly high blood perfusion in the right parieto-temporo-occipital areas. Considering the distribution of EEG epileptiform activities and HMPAO-SPECT hyperperfusion, it is most likely that the ictal paresis of our patient was associated with epileptic activities at the sensorimotor area which caused either direct or indirect activation of an inhibitory system. Careful clinical consideration of the possibility of ictal paresis is needed in elderly patients, especially in those with preexisting dementia, because paresis can be as severe as complete flaccid hemiplegia and can last as long as for a week.

Ipsilateral hemiparesis in lateral medullary infarction: Clinical investigation of the lesion location on magnetic resonance imaging

BACKGROUND In 1946, Opalski reported two cases of Wallenberg syndrome with ipsilateral hemiparesis (IH). His hypothesis seems to be based on the view that IH is caused by post-decussating pyramidal tract damage. Afterwards, other researchers proposed a different hypothesis that ipsilateral sensory symptoms of limbs (ISSL) or ipsilateral limb ataxia (ILA) caused by lateral medullary infarction (LMI) might lead to ipsilateral motor weakness. The present study is aimed to clarify whether IH in LMI patients is attributable mainly to ISSL/ILA or disruption of ipsilateral post-decussating pyramidal tract. METHODS Thirty-two patients with acute LMI admitted during the last 13years were divided to IH Group (n=7) and Non-IH Group (n=25). Lesion location/distribution on MRI and neurological findings were compared between the two groups. RESULTS LMI involved the lower medulla in all seven IH patients and 12 of 25 Non-IH patients. The lower medullary lesion extended to the cervico-medullary junction (CMJ) in four of seven IH patients and one of 12 Non-IH patients. Definitive extension to upper cervical cord (UCC) was confirmed in none of the patients. ISSL was found in two IH and three Non-IH patients all showing only superficial sensory impairments. ILA or hypotonia was observed in 57% of IH and 60% of Non-IH patients. CONCLUSION IH in LMI appears to be due mainly to post-decussating pyramidal tract damage at the lower medulla instead of ILA or ISSL participation.

A case of cortical infarction with isolated sensory disturbance in the c8 nerve root area.

Hisakazu Uno Department of Cerebrovascular Medicine, National Cardiovascular Center 5-7-1 Fujishiro-dai Suita, Osaka 565-8565 (Japan) Tel. +81 6 6833 5012, Fax +81 6 6835 5137, E-Mail hunohino@hsp.ncvc.go.jp Fig. 2. a MRI (diffusion-weighted imaging) the day before admission demonstrated a recent, small cortical infarction in the vicinity of the left central sulcus. Follow-up MRI (fluid-attenuated inversion recovery imaging) at 11 days after admission confirmed the cortical lesion, as shown in horizontal ( b ) and coronary ( c ) sections. Fig. 1. Temperature, pain and tactile sensations were impaired on the right ulnar side of the hand and forearm consistent with the C 8 nerve root region.

Myxedema ascites in an 89-year-old woman with end stage renal disease

Ascites appearing in an end-stage renal disease (ESRD) patient is usually ascribed to volume overload, and other possible etiologies are often overlooked. In this short report, we describe an 89-year-old female patient with ESRD who presented clinical ascites that resolved completely on thyroid replacement therapy.