Rapid increase of 'brain-type' transferrin in cerebrospinal fluid after shunt surgery for idiopathic normal pressure hydrocephalus: a prognosis marker for cognitive recovery.

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity. The prognosis for cognitive improvement after shunt surgery has been difficult to predict. We therefore investigated various CSF proteins, hoping to find a biomarker predictive of cognitive performance one to two years after shunt surgery. CSF proteins of 34 iNPH and 15 non-iNPH patients were analysed by Western blotting, revealing two glycan isoforms of transferrin (Tf); 'brain-type' Tf with N-acetylglucosaminylated glycans and 'serum-type' Tf with α2, 6-sialylated glycans. Brain-type Tf levels decreased in iNPH but rapidly returned to normal levels within 1-3 months after shunt surgery. This change was positively correlated with recovery from dementia, per Mini-Mental State Examination and Frontal Assessment Battery scores at 11.8 ± 7.7 months post-operation, suggesting that brain-type Tf is a prognostic marker for recovery from dementia after shunt surgery for iNPH. Histochemical staining with anti-Tf antibody and an N-acetylglucosamine-binding lectin suggests that brain-type Tf is secreted from choroid plexus, CSF-producing tissue.

[A case of ticlopidine-associated thrombotic thrombocytopenic purpura: special emphasis on diffusion weighted MRI].

A 69-year-old man of thrombotic thrombocytopenic purpura (TTP) associated with ticlopidine was reported. The patient initially complained of dysarthria and left hemiparesis one month after oral administration of ticlopidine. These motor symptoms were followed by gradual deline in level of consciousness. On admission, he was in apallic state with focal cerebral signs, accompanied by low-grade fever, and purpuric eruptions. Laboratory findings showed remarkable thrombocytopenia, hemolytic anemia, and renal dysfunction. The patient received diagnosis of TTP based on Moschcowitzs criteria. Prompt initiation of plasma exchange dramatically improved the patient's clinical symptoms. In this case, decreased activities of a disintegrin and metallo proteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in plasma and anti-ADAMTS13 IgG antibodies were detected. Serial diffusion weighted MRI with six-day interval starting from the onset showed two interesting findings. First, appearance and disappearance of scattered high intensity areas were observed in the cerebellum, corpus callosum, cerebral white matter, and neocortex. Second, these lesions roughly corresponded to border-zone infarct in distribution. Cranial MRI findings of TTP in the literature could be classified into the following four groups: 1) multiple infarction caused by microthrombi; 2) infarction caused by occulusion of an intracranial main artery; 3) reversible edema involving the cerebral white matter; and 4) unremarkable finding without specific abnormality. This case could be classified into the group 1. Based on the diffusion weighted MRI findings of this case, a previous pathological report and recent elucidations of clinical conditions, it is hypothesized that TTP is a predisposition for resembling the border-zone infarction in group 1. The border-zone distribution of transient high intensity areas in diffusion weighted MRI in this case could be explained by either high resistant vascules zone or impaired clearance of emboli, taking an autopsy case report into consideration.

Sudden infant deaths from undiagnosed ventricular septal defect - Report of two autopsy cases.

Ventricular septal defect (VSD) has a relatively non-aggressive clinical course; either spontaneous closure or causing congestive heart failure treatable with surgical intervention. We present two autopsy cases of sudden infant deaths from clinically undiagnosed VSDs. Case 1 was an 18-day-old boy. As the deceased coughed and became limp after feeding, he was carried to a hospital. Heart murmur was not auscultated there, so he was brought back to home. He presented severe dyspnea and then he was pronounced dead the next day. Case 2 was a 3-week-old boy. Any abnormality was pointed out at physical examination, although his mother felt his wheeze. He developed respiratory arrest at home in the morning and then he was confirmed dead at the hospital. Heart weights of these babies were heavier than mean weights of each normal development. There were perimembranous VSDs in both cases. Histology revealed that the pulmonary arterial walls were thickened. We diagnosed the cause of death in these cases was cardiac collapse with pulmonary hypertension due to VSD. Congenital heart diseases can be diagnosed as early as before birth, because echocardiograph and fetal echography are prevalent in these days. Most VSDs can be noticed by systolic murmur even today. We consider that the failure of initial clinical diagnosis of VSD in primary physical assessment could lead unexpected sudden death. These two cases reminded us to the importance of auscultation which is conventional but as one of the indispensable measure to find a clue for the congenital abnormality.

Oxidative stress may be involved in distant organ failure in tourniquet shock model mice.

Crush syndrome is characterized by prolonged shock resulting from extensive muscle damage and multiple organ failure. However, the pathogenesis of multiple organ failure has not yet been completely elucidated. Therefore, we investigated the molecular biological and histopathological aspects of distant organ injury in crush syndrome by using tourniquet shock model mice. DNA microarray analysis of the soleus muscle showed an increase in the mRNA levels of Cox-2, Hsp70, c-fos, and IL-6, at 3h after ischemia/reperfusion injury at the lower extremity. In vivo staining with hematoxylin and eosin (HE) showed edema and degeneration in the soleus muscle, but no change in the distant organs. Immunohistological staining of the HSP70 protein revealed nuclear translocation in the soleus muscle, kidney, liver, and lung. The c-fos mRNA levels were elevated in the soleus muscle, kidney, and liver, displaying nuclear translocation of c-FOS protein. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis suggested the involvement of apoptosis in ischemia/reperfusion injury in the soleus muscle. Apoptotic cells were not found in greater quantities in the kidney. Oxidative stress, as determined using a free radical elective evaluator (d-ROM test), markedly increased after ischemia/reperfusion injury. Therefore, examination of immunohistological changes and determination of oxidative stress are proposed to be useful in evaluating the extent of tourniquet shock, even before changes are observed by HE staining.