Cerebral nocardia masquerading as metastatic CNS disease in an endometrial cancer patient.

Nocardia is a bacterial infection primarily originating from organic rich soil, endemic to several international geographic locations. We present the case of a 61-year-old woman previously treated for endometrial carcinoma, who three years later developed metastatic pulmonary disease and received systemic chemotherapy. After five months, she developed a large right posterior lobe lesion, suspicious for metastatic CNS disease. However, following neurosurgical resection of the lesion and infectious disease consultation, a diagnosis of nocardia was made.

Relationship between uterine blood flow and endometrial and subendometrial blood flows during stimulated and natural cycles.

OBJECTIVE: To evaluate the relationship between uterine Doppler flow and endometrial and subendometrial blood flows during stimulated and natural cycles. DESIGN: A prospective observational study. SETTING: A tertiary-assisted reproduction unit. PATIENT(S): Infertile patients undergoing IVF treatment. INTERVENTIONS: A three-dimensional ultrasound examination with power Doppler was performed on the day of egg retrieval in stimulated cycles and the day after the LH surge in natural cycles. MAIN OUTCOME MEASURE(S): Pulsatility and resistance indices of uterine vessels, and the vascularization, flow, and vascularization flow indices of endometrial and subendometrial regions. RESULT(S): Uterine pulsatility and resistance indices were negatively correlated with subendometrial vascularization, flow, and vascularization flow indices in both stimulated and natural cycles, whereas uterine resistance index was negatively correlated with endometrial vascularization and flow indices in natural cycles only. Subendometrial vascularization and vascularization flow indices were significantly lower in patients with an uterine resistance index > or =0.95 than those with an uterine resistance index <0.95. CONCLUSION(S): Uterine blood flow is a poor reflection of subendometrial blood flow during stimulated and natural cycles, and its measurement cannot reflect endometrial blood flow during stimulated cycles.

Fetal arachnoid cyst of the quadrigeminal cistern in MRI and ultrasound.

CASE: The authors report a fetus with an arachnoid cyst of the quadrigeminal cistern without hydrocephalus at 30 gestational weeks. DISCUSSION AND CONCLUSION: We reviewed the literature and could find only 62 reported cases of arachnoid cyst of the quadrigeminal cistern. We present a case without hydrocephalus diagnosed by combining ultrasound (US) and magnetic resonance imaging (MRI). The fetus, born by normal delivery, was followed up and did not show hydrocephalus for 1 year. This combined prenatal study, which uses US and MRI, helps in dispensing proper counseling to parents and assists the gynecologist and the neurosurgeon in the pre- and postnatal management of this condition.

NGF, NT-3 and Trk C mRNAs, but not TrkA mRNA, are upregulated in the paraventricular structures in experimental hydrocephalus.

OBJECTS: This study was designed to detect possible alterations in the expression of neurotrophins and trks in kaolin-induced hydrocephalus by in situ hybridization. METHODS AND RESULTS: Sixteen rats were treated by injection of 25 mg kaolin suspended in 0.1 ml of physiological saline into the cisterna magna. Four rats were injected with saline and served as controls. The kaolin-treated rats were divided into two groups studied 1 and 4 weeks after treatment. Rats were anesthetized and killed, and their brains were rapidly dissected and frozen. DNA oligonucleotide probes for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and trkA, trkB, and C were labeled with [(35)S]dATP using terminal deoxyribonucleotidyl transferase for in situ hybridization. Hydrocephalic brains were also classified according to the degree of ventricular enlargement. The results observed were as follows. (1) The medial septal and striatal NGF mRNA levels increased with severity in animals. (2) Hippocampal trkB and BDNF mRNA levels increased with time in animals with moderate ventricular enlargement. (3) Expression of hippocampal trkB, trkC, and NT-3 mRNA increased in animals with moderate ventricular enlargement, while it apparently decreased in the large ventricular enlargement group reaching normal ranges. (4) In the corpus callosum there was an apparent increase in NGF, NT-3 and trkC mRNA, but not in trkA, in hydrocephalic animals. NT-3 EIA confirmed the presence of NT-3 protein increases in corpus callosum. It is therefore possible that simultaneous NGF, NT-3, and trkC receptor upregulation occurred in glial elements of the white matter. CONCLUSIONS: These results demonstrate that neurotrophins and their receptors are overexpressed in many damaged structures of the severely hydrocephalic brain. There were discrepancies in the distribution of NGF and trkA mRNA, and we hypothesize that NGF mRNA in the damaged white matter structure might be due to the reduced availability of other receptors, such as the low-affinity NGF receptors.

Neuroendoscopic anatomy and surgery in pineal region tumors: role of neuroendoscopic procedure in the 'minimally-invasive preferential' management.

The therapeutic modalities for pineal region tumors in Western countries differ from those in far-eastern countries, that is, Japan and Korea, mainly because of the different patient populations. The majority of pineal region tumors in Japan and Korea are radio sensitive and/or chemosensitive, and adjuvant therapy rather than extensive surgery plays the main part in the treatment of these tumors. The authors have applied minimally-invasive preferential management in pineal region tumors in last 8 years. For the therapeutic regimen, if the tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third-ventriculostomy. In the results, our minimally-invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure. Then avoided unnecessary craniotomy and radiotherapy and promised excellent therapeutic outcomes. Neuroendoscopic procedures have a great advantage in the management of chemo- or radiosensitive tumors, such as germinoma, pineoblastoma, or primitive neuroectodermal tumor. The neuroendoscopic anatomy including the lateral and third ventricles with a pineal region tumor with or without tumor dissemination was described in detail, together with the neuroendoscopic surgical technique.

Efficacy of neuroendoscopic procedures in minimally invasive preferential management of pineal region tumors: a prospective study.

OBJECT: This prospective study is based on a consecutive series of 20 patients with pineal region tumors who underwent minimally invasive preferential management. The purpose of this report is to discuss the role of neuroendoscopic procedures in the management of pineal region tumors. METHODS: If the tumor markers alpha-fetoprotein and human chorionic gonadotropin were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third ventriculostomy. Subsequent procedures were determined on the basis of verified individual tumors. For treatment of germinomas and pineoblastomas, if no tumor dissemination was confirmed by pre-, intra-, or postoperative findings, stereotactic radiotherapy or radiosurgery was performed after one course of chemotherapy with the ICE regimen (isofomid, cisplatin, and etoposide) and followed by two additional courses of chemotherapy. For treatment of malignant germ cell tumors, after extensive surgery, adjuvant chemotherapy with the ICE regimen was performed in three courses in all cases. Then radiotherapy was started using various methods, depending on the evidence of tumor dissemination. For treatment of teratomatous and neuroectodermal tumors other than pineoblastomas, extensive surgical removal was performed. As for adjuvant therapy, if the tumor was a low-grade glioma or if the patient was younger than 5 years of age, postoperative treatment did not include radiotherapy. If the tumor was a malignant teratoma or high-grade glioma, conventional focal radiotherapy was performed, followed by chemotherapy with ICE for 1 year. All but two treated patients had ventriculomegaly. Neuroendoscopic procedures were performed in six of 15 treated patients. Neuroendoscopic biopsy with tumor debulking offered enough material for tissue diagnosis, including immunohistochemical analysis and, in one case, revealed evidence of tumor dissemination undetectable on neuroimaging. With one exception, no shunt was required in any patient undergoing endoscopic third ventriculostomy. Stereotactic radiotherapy was performed in indicated cases. Favorable therapeutic outcomes were obtained in all cases of germinoma and pineoblastoma, with follow-up periods ranging from 24 months to 6.5 years. CONCLUSIONS: Our minimally invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure, avoiding unnecessary craniotomy and radiotherapy and promising excellent therapeutic outcomes. The treatment for malignant pineal region tumors remains a subject for further study.

Isolated dilation of the trigono-inferior horn--four case reports.

Four patients presented with isolated dilation of the trigono-inferior horn associated with either mass lesion at the trigone of the lateral ventricle or with shunt over-drainage. We investigated clinical symptoms, course, and neuroradiological findings of these cases. The pressure of the isolated ventricle was measured or estimated at surgery in all cases. The common symptoms were recent memory disturbance and contralateral homonymous hemianopia. Contralateral hemiparesis was observed occasionally. Rapid deterioration of the isolation caused uncal herniation in one case. Comma-shaped dilation of the inferior horn was observed in all cases. Midline shift was not conspicuous except in one case. Intraventricular pressure at surgery was 18 cmH2O, 35 cmH2O, 3 cmH2O, and within normal range. These cases had very similar clinical symptoms and neuroradiological findings. The pathophysiology of isolation suggested three types of isolation (high-, normal-, and low-pressure isolation), depending on the pressure of the isolated ventricle. The isolation of trigono-inferior horn is an important clinical entity as it may cause uncal herniation in patients with high-pressure lesions.

Microvascular Doppler ultrasound-assisted neuroendoscopic surgery.

To achieve endoscopic procedures more safely and less invasively, an operative strategy with ultrasound-assisted neuroendoscopic surgery is described. The improvement in the endoscope unit is that endoscopic viewing can be stopped on the display, anytime we choose and simultaneously visualize the ongoing view on the same display. The ultrasound unit, using a miniature Doppler probe, is to able to detect even invisible vessels in real-time, easily and non-invasively. The information from both units can be switched intraoperatively, whenever required.

Prerequisites for fetal neurosurgery: management of central nervous system anomalies toward the 21st century.

With the dramatic technical advances in neuroimaging, it has become possible to diagnose central nervous system (CNS) anomalies in the fetus in utero with more precise morphological analysis. A new technique, high-resolution magnetic resonance (MR) imaging using heavily T2-weighted fast spin echo sequences, has been reported to solve motion artifact of the fetus. However, it has also been recognized that the morphological fetal CNS findings detected in early development are not always the final features: occasionally they may not be determined in diagnosis and may change developmentally or chronologically during the fetal life in utero. Certain factors of the fetal chronology of CNS anomalies can cause irreversible changes during fetal life. These include: (1) significant delay in the neuronal maturation process in fetal hydrocephalus developed in clinicoembryological stage II in the Perspective Classification of Congenital Hydrocephalus (PCCH), (2) secondary neural injury in the intactly developing spinal cord above the neural placode in fetus with spina bifida aperta (myeloschisis), (3) histological "evolution" of tumors or dysgenetic CNS, and (4) deformity of the normally developed intracranial or intraspinal CNS structures. Considering the current status of fetal surgery in general and technical advances promising improved outcomes, fetal neurosurgery can also be applied in the above-mentioned progressive pathology or pathophysiology in the fetal CNS. However, since the failure of the first trial of fetal neurosurgery in the 1980s, the prerequisites have still not been clarified. In order to use advanced neurosurgery techniques in the management of fetal CNS anomalies, these prerequisites have to be established.

[Clinical application and future prospect of neuroendoscopic surgery].

The clinical application and future prospect of neuroendoscopic surgery are described. In the historical trend, it is emphasized that the neuroendoscopic surgery has become one of the major or leading procedures in "minimally-invasive approaches" to the intracranial lesions. The presently-available instrument include procedures using an endoscope of three different types: rigid-rod, steerable/flexible-fiber-rod and semi-rigid-rod. To use a rigid-rod or fiber-rod scope, it is available to apply forceps, laser, a microballoon and other fine instruments. The indication for neuroendoscopic surgery has been expanded to almost all neurosurgical procedures, as "endoscope-assisted" procedures are applied more to micro neurosurgical procedures (endoscope-assisted microsurgery). The realistic indication for "pure neuroendoscopic surgery" includes reconstruction of cerebrospinal fluid (CSF) pathway such as third ventriculostomy, septostomy, foramen reconstruction, fenestration of septation; removal or biopsy of tumor/cystic lesion, mainly in the intraventricular regions; and removal of hematoma involving the cerebral parenchyma (intracerebral hematoma), ventricles/(intraventricular hematoma) or subdural space (subdural hematoma). The intraparenchymal or deep-seated intracisternal lesions can be the realistic indication for "pure neuroendoscopic surgery" when the instrument are further developed in future. Neuroendoscopic surgery will play a promising and major role in the "minimally-invasive neurological procedure" in the 21st century.

Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells.

Angiotensin II activates p21ras, and mediates cardiac hypertrophic growth through the type 1 angiotensin II receptor in cardiac myocytes. An inhibitor of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase has been shown to block the post-translational farnesylation of p21ras and inhibit protein synthesis in several cell types. Primary cultures of neonatal cardiac myocytes were used to determine whether HMG-CoA reductase inhibitors, lovastatin, simvastatin and pravastatin inhibit the angiotensin II-induced hypertrophic growth. Angiotensin II (10(-6) M) significantly increased protein-DNA ratio, RNA-DNA ratio, ratios of protein synthesis and mitogen-activated protein (MAP) kinase activity. Lipid-soluble HMG-CoA reductase inhibitors, lovastatin (10(-6) M) and simvastatin (10(-6) M) partially and significantly inhibited the angiotensin II-induced increases in these parameters, but a water-soluble HMG-CoA reductase inhibitor, pravastatin (10(-6) M) did not. Mevalonate (10(-4) M) overcame the inhibitory effects of lovastatin and simvastatin on angiotensin II-induced increases in these parameters. A selective protein kinase C inhibitor, calphostin C (10(-6) M) partially and significantly prevented angiotensin II-induced increases in these parameters, and treatment with both lovastatin and calphostin C inhibited completely. Angiotensin II increased p21ras activity and membrane association, and lovastatin inhibited them. These studies demonstrate that a lipid-soluble HMG-CoA reductase inhibitor, lovastatin, may prevent angiotensin II-induced cardiac hypertrophy, at least in part, through p21ras/MAP kinase pathway, which is linked to mevalonate metabolism.

Neuroendoscopic surgery for specific forms of hydrocephalus.

Neuroendoscopic surgery was used to treat patients with various forms of hydrocephalus with specific pathophysiology, including long-standing overt ventriculomegaly in adulthood (LOVA), isolated unilateral hydrocephalus (IUH), isolated IV ventricle (IFV), disproportionately large IV ventricle (DLFV), isolated rhombencephalic ventricle (IRV), isolated quarto-ventriculomegaly (IQV), dorsal sac in holoprosencephaly (DS), and loculated ventricle (LV). A total of 26 operative procedures were performed, with neuroendoscopic surgery in 22 patients, 12 with unique forms of noncommunicating hydrocephalus and 10 with various types of postshunt isolated compartment. These procedures included III ventriculostomy, aqueductal plasty by both rostral and caudal approaches, foraminal plasty in the foramen of Monro/foramen of Magendie, septostomy, IV ventriculostomy, fenestration of septation in the loculated ventricle, fenestration of arachnoid cyst or cystic tumor obstructing a ventricle with or without tumor removal, and dorsal sac ventriculostomy. The characteristics of the cerebrospinal fluid (CSF) dynamics in the individual specific pathophysiologies were delineated by cardiac-gated cine-mode magnetic resonance imaging (MRI) before and after the endoscopic procedure. The consequent success rate (success = restoration of communication of the CSF pathway in the individual patients) was 19/22 (86.4%). The progression of ventricular dilatation was stopped in 17 of 19 patients (89.5%) in whom the endoscopic procedure was successful (radiologically arrested hydrocephalus). Improvement in the clinical symptoms and signs (clinically arrested hydrocephalus) was obtained in 15 of the patients (68.2% of all patients: 5 with LOVA, 3 with IQV, 5 with IUH and 2 with LV). Seven patients (2 LOVA, 2 IFV, 1 DS, 1 DFLV and 1 IRV) underwent a shunt procedure after the neuroendoscopic procedure(s). The postoperative changes of ventriculomegaly were complicated, reflecting the differences in the brain parenchymal compliance and postoperatively corrected CSF flow dynamics in the major CSF pathway.

Delayed ischemic neurological deficit of short duration in patients with subarachnoid hemorrhage.

We retrospectively examined the duration of delayed ischemic neurological deficits (DIND) attributed to vasospasm following subarachnoid hemorrhage (SAH) in order to delineate the nature and involved factors. Among 605 patients with SAH, 201 developed DIND, and 137 of these had undergone early aneurysmal obliteration. In these 137, duration of DIND was clearly determined in 67 cases. Hypervolemic therapy was instituted only after the onset of DIND. In the 67 patients, the mean duration of DIND was 5.2 days (ranging from 2 to 13 days); 22 patients had DIND lasting only 2 to 3 days, 26 patients had DIND lasting 4 to 6 days, and in 19, DIND lasted 7 to 13 days. Clinical factors associated with short DIND duration (2 to 3 days) as determined by multivariate analysis included internal carotid artery or middle cerebral artery aneurysm, age under 60, and a good World Federation of Neurological Surgeons grade on admission. No patients developed pulmonary edema from hypervolemic therapy, and the outcomes of all 67 patients were extremely favorable. In SAH patients developing DIND after early aneurysmal surgery, 16% (22 of 137) had a documented brief duration of DIND. We believe DIND rapidly improved and resolved with hypervolemic therapy because antecedent brain damage from SAH or surgical manipulation had been minimal.

Synthesis of peptide aldehyde derivatives as selective inhibitors of human cathepsin L and their inhibitory effect on bone resorption.

Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N, O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

Pressure-induced expression of heat shock protein 70 mRNA in adult rat heart is coupled both to protein kinase A-dependent and protein kinase C-dependent systems.

BACKGROUND: Production of heat shock protein 70 (HSP70) in the heart is induced by hemodynamic stress, but its intracellular signal transduction system has not been elucidated well. OBJECTIVE: To investigate the hypothesis that protein kinase A (PKA)-dependent and protein kinase C (PKC)dependent systems are involved in the pressure-induced expression of HSP70 mRNA in perfused adult rat heart METHODS: Isolated tetrodotoxin-arrested Sprague-Dawley rat hearts were perfused as Langendorff preparations at a constant aortic pressure of 60 mmHg. Aortic pressure in rats of the pressure-overloaded group was elevated from 60 to 120 mmHg for 2-120 min. cAMP contents and rates of synthesis of protein were measured by radioimmunoassay and the incorporation of [14C]-phenylalanine into total heart protein, respectively. Expression of HSP70 mRNA was determined by Northern blot analysis. RESULTS: Elevation of aortic pressure significantly increased cAMP content after 2 min of perfusion (by 41%), significantly increased rates of synthesis of protein during the second hour of perfusion (by 41%), and induced expression of HSP70 mRNA maximally after 60 min of perfusion (2.7-fold the control value). Exposure to glucagon, forskolin or 1 -methyl-3-isobutylxanthine mimicked increases in these parameters caused by elevation of aortic pressure. Administration of a selective PKA inhibitor, H-89, significantly prevented induction of increases in expression of HSP70 mRNA and rates of synthesis of protein by a high pressure overload and exposure to agents that increase cAMP content. Furthermore, administration of phorbol ester induced expression of HSP70 mRNA. Administration of a PKC inhibitor, calphostin C, significantly prevented induction of increases in expression of HSP70 mRNA by a pressure overload and by exposure to phorbol ester. CONCLUSIONS: These results suggest that the pressure-induced induction of production of HSP70 is regulated both by PKA-dependent and by PKC-dependent systems during periods of active synthesis of protein in adult rat heart.

Recent advances and racial differences in therapeutic strategy to the pineal region tumor.

The therapeutic modalities for pineal region tumors in Western countries differ from those in Japan, mainly because of the different patient populations. The majority of pineal region tumors in Japan are radio- and/or chemosensitive, and adjuvant therapy rather than extensive surgery plays the main part in the treatment of these tumors. The specific clinical features of and therapeutic modalities for pineal region tumors, together with racial differences, were analyzed at the joint symposium of the Japanese Society for Pediatric Neurosurgery and the Korean Society for Pediatric Neurosurgery. The results of a cooperative study, together with the collective experience in Korea, confirmed that this specific patient population is nearly identical to the Japanese one. The new therapeutic approaches to pineal region tumors recommended included neuroendoscopic or stereotactic biopsy as a "minimally invasive" initial procedure. The adjuvant therapeutic modalities were further analyzed and neoadjuvant chemotherapy, mainly with cisplatin or carboplatin with or without etoposide (VP-16), was recommended for the treatment of germinoma and nongerminomatous malignant germ cell tumors. "Target radiation therapy" with extensive chemotherapy is a hopeful regimen and a future subject of research.

Identical characteristics of the patient populations with pineal region tumors in Japan and in Korea and therapeutic modalities.

The therapeutic modalities used for tumors of the pineal region in Western countries differ from those in Japan, mainly because of the different patient populations. An extensive survey was conducted to delineate the racial differences in Japan and in Korea in the epidemiology and recent therapeutic modalities for this tumor group. Among the members of International Society for Pediatric Neurosurgery (ISPN), 15 from Japan and 5 from Korea reported their recent findings in 118 (1-25 years of age, mean 7.38-year period) and 125 (1-12 years of age, mean 6.69-year period) histologically verified cases, respectively. The patient populations in the two countries were found to be almost identical, with an extremely high incidence of germ cell tumors representing 71.2% (in Japan) and 80.0% (in Korea) of all pineal region tumors and neuroectodermal tumors representing only 15.2% and 16.8%, respectively. The most common type of pineal region tumor was germinoma (46.6% in Japan and 47.2% in Korea). The majority of tumors were radio- and/or chemosensitive, and adjuvant therapy rather than extensive surgery played the major role in the treatment in both countries. Radical resection of the tumor was recommended as the initial procedure by only 22.2% of neurosurgeons in Japan and 16.6% in Korea. Biopsy was recommended by 38.9% and 50.0%, and radiation therapy by 38.9% and 37.5%, respectively. A minimally invasive procedure, by either a neuroendoscopic (33.3% of biopsies in Japan) or a stereotactic approach (33.3% of biopsies in Korea), was considered to be appropriate as the initial procedure. The study disclosed the almost identical epidemiology of this brain tumor in Japan and in Korea and clarified the consequent therapeutic modalities. The authors emphasize that minimally invasive tissue diagnosis with or without tumor debulking should be considered as the initial step for the treatment planning of the pineal region tumor, followed by the most commonly indicated major procedures, including radiation therapy, chemotherapy and/or radical resection with various methodologies.

[Delayed ischemic neurological deficit that developed over 15 days after subarachnoid hemorrhage].

We retrospectively studied subarachnoid hemorrhage (SAH) patients with delayed ischemic neurological deficit (DIND), and analyzed the factors causing extremely late onset of deficits occurring over 15 days after onset of the SAH. Among 605 patients with SAH, 201 (33%) developed DIND. Among DIND patients, 137 had undergone early aneurysm surgery. In these 137 patients, onset date of DIND was definite in 131 patients. Six patients (5%) developed DIND over 15 days after SAH. All 6 had asymptomatic angiographical vasospasm and infections, most often meningitis, before the onset of DIND. Compared with cases in which there was ordinary onset of DIND, other statistically significant factors among these 6 patients were intracerebral hemorrhage, sepsis and meningitis. We suspect that DIND were manifested subclinically in the early period because of the associated hyperdynamic hemodynamics resulting from sepsis in these patients.