Diffusion-weighted magnetic resonance imaging in a case of cerebral venous thrombosis

BACKGROUND: Diffusion-weighted imaging (DWI) is the most sensitive MR sequence in acute arterial ischemic stroke but has not yet been evaluated in venous cerebral ischemia. We describe a patient with DWI performed at the acute phase of a venous ischemic stroke. CASE DESCRIPTION: A rapid cerebral MRI including DWI and fast fluid-attenuated inversion recovery (FLAIR) sequences was performed at the acute phase of a venous stroke confirmed by conventional angiography. DWI showed a slight decrease in apparent diffusion coefficient values 3 hours after onset (0.53+/-0.07x10(-3) mm2/s) and was normal 48 hours later (0.064+/-0.15x10(-3) mm2/s). Fast FLAIR sequences showed large left frontoparietal hyperintensities. The lack of a clear decrease in apparent diffusion coefficient values associated with marked FLAIR abnormalities may suggest prominent or early associated vasogenic edema. Physiopathological differences between arterial and venous ischemia may explain the different type of DWI FLAIR abnormalities during the acute phase as well as the better recovery of neurological deficit in venous stroke than in arterial ischemic stroke. CONCLUSIONS: In the context of an acute stroke, the contrast between marked FLAIR and subtle DWI abnormalities on MRI may reflect the venous mechanism of cerebral ischemia.     

Diffusion-weighted imaging in hyperacute stroke--gold standard?

Diffusion-weighted imaging (DWI) is more sensitive than CT and conventional T2-weighted MR imaging in the detection of early cerebral ischemia and infarction. In this case report, we present a case of a 79-year-old woman with symptoms of acute stroke, clinically and radiologically documented progression to complete stroke with an initial negative diffusion-weighted scan.     

Cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia

We describe two women (ages 35 and 36 years) with cerebral ischemia, hepatitis C virus, and mixed cryoglobulinemia. One patient (case 1) was in otherwise good health when left parietal cerebral infarction developed, and she was found to have narrowing of the supraclinoid internal carotid artery siphon, anterior cerebral artery A1, and middle cerebral artery M1 segments bilaterally. Subsequent evaluation revealed abnormal liver enzymes, mixed cryoglobulinemia (type III), hypocomplementemia, and a high positive test result for rheumatoid factor. In the other patient (case 2), cerebral ischemia and seizures developed in the setting of previously documented mixed cryoglobulinemia (type II), membranoproliferative glomerulonephritis, and hypocomplementemia. In this patient, a brain biopsy demonstrated cerebral infarction. Hepatitis C virus infection was confirmed in both patients by polymerase chain reaction detection of hepatitis C virus RNA. These two cases document the occurrence of cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia. Testing for hepatitis C virus and cryoglobulins should be considered in selected patients with cerebral ischemia of inobvious cause.     

Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI

OBJECTIVE: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, T2-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. METHODS: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. RESULTS: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. CONCLUSIONS: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury.     

The role of activators in assembly of RNA polymerase II transcription complexes

Since the negative results of the international Bypass Study, extracranial-intracranial (EC-IC) bypass surgery is infrequently employed in the treatment of patients with cerebral ischemia. Newly acquired evidence concerning the pathophysiology of cerebral ischemia, however, has facilitated the identification of a small subgroup of patients with "hemodynamic" cerebral ischemia. Characteristically, these patients demonstrate severely impaired cerebrovascular reserve capacity due to occlusive disease and insufficient collateral blood supply. Over an 8-year period, 28 patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had recurring episodes of focal cerebral ischemia due to unilateral internal carotid artery occlusion. Computerized tomography (CT) scans either were normal or showed evidence of border zone infarction. The cerebrovascular reserve capacity was studied using 133Xe single-photon emission CT and acetazolamide challenge and was found to be significantly impaired in all patients. Based on these criteria, superficial temporal artery-middle cerebral artery anastomosis was performed to augment collateral flow to the ischemic hemispheres. Two patients died from myocardial infarction, one 4 days and the other 2 months postoperatively. One patient died from massive brain infarction and another suffered a postoperative stroke with incomplete recovery, resulting in a major morbidity and mortality rate of 14%. Minor morbidity included one patient with a subdural hematoma who subsequently recovered completely. The postoperative course was uneventful in 23 patients (82%). Over a mean follow-up period of almost 3 years, no patient had another episode of brain ischemia. Bypass patency was confirmed by postoperative angiography in 26 patients. Follow-up studies of cerebral blood flow (CBF) and cerebrovascular reserve capacity showed significant improvement of the latter while the resting CBF was essentially unchanged. In view of these findings, the authors conclude that EC-IC bypass surgery constitutes appropriate therapy for a subgroup of patients with recurrent focal cerebral ischemia, defined using the strict selection criteria employed in this study.     

Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia

BACKGROUND and PURPOSE: We have recently shown high-dose human serum albumin therapy to confer marked histological protection in experimental middle cerebral artery occlusion (MCAo). We have now used diffusion-weighted magnetic resonance imaging (DWI) in conjunction with morphological methods to expand our understanding of this therapeutic approach. METHODS: Physiologically controlled Sprague-Dawley rats received 2-hour MCAo by the modified intraluminal suture method. Treated rats received 25% human serum albumin solution (1% by body weight) immediately after the MCA was reopened. Vehicle-treated rats received saline. Computer-based image averaging was used to analyze DWI data obtained 24 hours after MCAo and light-microscopic histopathology obtained at 3 days. In a matched series, plasma osmolality and colloid oncotic pressure, as well as brain water content, were determined. RESULTS: Albumin therapy, which lowered the hematocrit on average by 37% and raised plasma colloid oncotic pressure by 56%, improved the neurological score throughout the 3-day survival period. Within the ischemic focus, the apparent diffusion coefficient (ADC) computed from DWI data declined by 40% in vehicle-treated rats but was preserved at near-normal levels (8% decline) in albumin-treated rats (P<0.001). Albumin also led to higher ADC values within unlesioned brain regions. Histology revealed large consistent cortical and subcortical infarcts in vehicle-treated rats, while albumin therapy reduced infarct volume at these sites, on average, by 84% and 33%, respectively. Total infarct volume was reduced by 66% and brain swelling was virtually eliminated by albumin treatment. Microscopically, while infarcted regions of vehicle-treated rats had the typical changes of pannecrosis, infarcted zones of albumin-treated brains showed persistence of vascular endothelium and prominent microglial activation, suggesting that albumin therapy may help to preserve the neuropil within zones of residual infarction. CONCLUSIONS: These findings confirm the striking neuroprotective efficacy of albumin therapy in focal cerebral ischemia and reveal that this effect is associated with DWI normalization and a mitigation of pannecrotic changes within zones of residual injury.     

Deficiency of intercellular adhesion molecule 1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia

Recent evidence has shown crucial roles for cell-adhesion molecules in inflammation-induced rolling, adhesion, and accumulation of neutrophils in tissue. Intercellular adhesion molecule-1 (ICAM-1) is one of these adhesion molecules. Previous studies have shown marked reduction in the size of infarction after focal cerebral ischemia by depletion of granulocytes and administration of the antibody against ICAM-1. In the present study we investigated the role of ICAM-1 in the size of ischemic lesions, accumulation of granulocytes, and microcirculatory compromise in focal cerebral ischemia by using ICAM-1-knockout mice. Ischemic lesions were significantly mitigated in knockout mice after permanent and transient focal ischemia, even though the number of granulocytes in the infarcted tissue was almost the same between knockout and wild-type mice. Depletion of granulocytes further decreased the size of ischemic lesions after transient focal ischemia in ICAM-1-knockout mice. Microcirculation was reduced after focal ischemia, but it was better preserved in the cerebral cortex of knockout mice than that of wild-type mice. The present study demonstrated that ICAM-1 played a role in microcirculatory failure and subsequent development and expansion of infarction after focal cerebral ischemia. However, it is highly unlikely that ICAM-1 played a key role in accumulation of granulocytes after focal cerebral ischemia.     

Killing of rat adenocarcinoma 13762 in situ by adoptive transfer of CD4+ anti-tumor T cells requires tumor expression of cell surface MHC class II molecules

Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that fetal tissue transplantation may produce neurobehavioral recovery. Accordingly, fetal tissue transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with fetal striatal tissue into the infarcted striatum have produced encouraging results. Transplanted fetal tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although, this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas.     

Monitoring aortic root effluent during retrograde cardioplegia delivery

Early signs of brain infarction can be detected by modern CCT technology even within the first 6 h after stroke. Little is known about the prognostic significance of early infarction signs in CCT. We prospectively evaluated clinical and CCT findings of 95 consecutive patients with an acute ischemia in the territory of the middle cerebral artery. All patients were admitted to our stroke unit within 6 h after stroke. In 55 patients CCT was performed within 3 h, and in 40 cases between 3 and 6 h. In all patients the clinical findings were assessed by the Scandinavian Stroke Scale (SSS). The disability due to stroke was evaluated after 4 weeks by use of the modified Rankin Scale. We could demonstrate the following early signs of cerebral infarction: focal hypodensity (23.2%), obscuration of basal ganglia (12.6%), focal brain swelling (22.1%), hyperdense middle cerebral artery sign (HMCA; 11.5%). In 3 patients early edema led to ventricular compression, in 1 patient to midline shift. The occurrence of early infarction signs did not depend on the etiology of ischemia but was significantly associated with a severe neurological deficit at admission and an unfavourable disability status 4 weeks after stroke. Focal brain swelling and HMCA were often followed by extensive infarction lesions on the follow-up CCT. In conclusion, early signs of hemispheric brain infarction visible on CCT scans performed within 6 h after stroke are correlated with severe stroke and an unfavourable functional outcome. However, a substantial part of our patients had a benign course of the disease in spite of early CCT pathology. Decisions on therapy in individual patients therefore should not depend on early CCT findings exclusively.     

A novel endothelin antagonist, A-127722, attenuates ischemic lesion size in rats with temporary middle cerebral artery occlusion: a diffusion and perfusion MRI study

BACKGROUND AND PURPOSE: Endothelins (ETs) are potent vasoconstrictors. Plasma ET levels increase during acute brain ischemia and may worsen the ischemic damage. Diffusion-weighted MRI (DWI) and perfusion imaging (PI) are powerful tools for evaluation of acute cerebral ischemia. We studied the effects of A-127722, a novel ET(A)-selective ET antagonist, on cerebral ischemic lesion size using 2,3,5-triphenyltetrazolium chloride (TTC) staining postmortem, on acute ischemic lesion development with DWI, and on the cerebral circulation using PI. METHODS: Twenty male Sprague-Dawley rats received either 5 mg/kg of A-127722 or vehicle (n=10 per group) intravenously 30 minutes and subcutaneously 4 hours after middle cerebral artery occlusion (MCAO). Whole-brain DWI and single-slice PI were done before initiation of treatment and repeated frequently thereafter up to 4 hours after MCAO. The animals were reperfused in the MRI scanner 90 minutes after the onset of MCAO. At 24 hours the animals were killed, and the brains were cut into six 2-mm-thick slices and stained with 2% TTC. Percent hemispheric lesion volume (%HLV) was calculated for each animal. RESULTS: Physiological parameters, body weight, neurological scores, and premature mortality (2 versus 2) did not differ between the two groups. No hypotension, abnormal behavior, or other adverse effects were seen. TTC-derived %HLV was 25.3+/-5.6% for controls and 16.2+/-9.6% for treated animals (36% reduction, P<.02). Six animals in each group had successful reperfusion as shown by PI. Among these animals, %HLV was 23.2+/-3.1% for controls and 9.3+/-4.4% for treated animals (60% reduction, P=.0001). The beneficial effect of A-127722 was limited to animals in which successful reperfusion was demonstrated. No difference in PI-detected perfusion deficit size was observed between the groups. DWI did not demonstrate significant in vivo lesion size differences. CONCLUSIONS: A-127722 significantly reduced ischemic lesion size in rats without observable adverse effects. It is not clear whether the effect was due to vasodilatation of collateral arterioles not detectable by PI or whether A-127722 has neuroprotective properties that are independent of vascular effects.     

Diffusion, perfusion, and T2 magnetic resonance imaging of anti-intercellular adhesion molecule 1 antibody treatment of transient middle cerebral artery occlusion in rat

The effect of anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody treatment of transient (2 h) middle cerebral artery (MCA) occlusion in the rat was measured using diffusion (DWI)-, T2 (T2I)- and perfusion (PWI)-weighted magnetic resonance imaging. Rats were treated upon reperfusion with an anti-ICAM-1 monoclonal antibody (n=11) or a control antibody (n=7). DWI, T2I and PWI were performed before, during, and after induction of focal cerebral ischemia from 1 h to 7 days. In both groups, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) values in the ischemic region significantly declined from the preischemic ADCw values (p<0. 05). The post ischemic increase in T2 of the control group was significantly higher at 48 h than in the anti-ICAM-1 treated group (p<0.05). CBF was not significantly different between the two groups. The temporal profiles of MRI cluster analysis, which combines ADCw and T2 maps into a single image, was significantly different between groups. These data suggest that the neuroprotective effect of anti-ICAM-1 antibody treatment is reflected in reductions of T2 and lesion growth during reperfusion and may not be associated with increased cerebral perfusion.     

Mohs micrographic surgery

Gene expression studies with in situ hybridization after focal brain ischemia indicate a variety of distinct anatomical patterns. An important question is to what extent such reactive gene expression correlates with neuronal damage or survival. To study these questions, we focused on two stressed-induced genes, heat shock protein 70 (HSP70) and growth-arrest and DNA damage-inducible gene (GADD) 45 mRNA, and we compared reactive changes in mRNA to loss of the constitutive signal for microtubule-associated protein 2 (MAP2) mRNA. A pixel-based image analysis of mRNA signals was carried out using a highly reproducible model of focal brain ischemia. A poly-l-lysine coated filament was used to occlude the origin of the middle cerebral artery (MCA) for 2 h in ventilated, normothermic rats. Brains were collected after 0, 1, 3 and 6 h, and 1, 3 and 7 days. In situ hybridization analysis was carried out for HSP70 mRNA, GADD45 mRNA and MAP2 mRNA. Autoradiographic data sets were averaged and co-mapped into a common template of the rat brain. These data sets were then compared on a pixel-by-pixel basis with previously acquired image data sets derived from quantitative studies of local cerebral blood flow (LCBF) (obtained at the end of 2-h ischemia) of and infarctive histopathology (obtained at 3 days) in the same focal ischemia model. HSP70 mRNA and GADD45 mRNA were grossly elevated in the hemisphere subjected to ischemia during the first day. Pixel-based analysis showed a strong correlation between HSP70 mRNA signals, the degree of early blood-flow reduction and the probability of histological infarction. GADD45 mRNA was expressed in a more variable fashion. Decreases in MAP2 mRNA signals at 1, 3 and 7 days correlated strongly with histological infarction. These co-mapping procedures allow us to conclude that HSP70 mRNA is a robust indicator of ischemic stress and histological outcome after 2 h of focal brain ischemia. The topographic features of GADD45 expression suggest its possible role in conferring resistance to ischemic injury. Finally, our results indicate that local decreases in constitutive MAP2 expression at 1 day and beyond may be used as a robust marker of tissue regions having a high probability of focal infarction.     

The clinical application of diffusion weighted magnetic resonance imaging to acute cerebrovascular disorders]

Diffusion is a measure of motion freedom and is a sensitive parameter to characterize the tissue at the microscopic level. The methods of measuring in vivo diffusion by magnetic resonance imaging (MRI) have been based mainly on the addition of two motion-probing gradients (MPG) to the spin echo sequence to produce signal attenuation for the spins moving at random. The resultant MR images reflect the intravoxel incoherent motions (IVIM), which contain both water molecule diffusion and perfusion in the capillary network, and can be quantified by an apparent diffusion coefficient (ADC). Diffusion weighted MRI, acquired from IVIM MR imaging by the addition of the very strong MPG predicate water diffusion and anisotropy. High signal or reduced ADC can be observed in case of the slower diffusion. The anisotropy depends upon the orientation of the subjects and the gradients. Greater signal attenuation (faster diffusion) can be observed when the relative orientation of white matter tracts to the MPG is parallel as compared to that obtained with a perpendicular alignment. This anisotropy may preclude the detection or delineation of an ischemic lesion. Diffusion tensor trace has been designated to eliminate this anisotropy effect. In ischemic animal models, low signal (fast diffusion) and high signal (slow diffusion) have been noted in the vasogenic edema and cytotoxic edema, respectively. High signal appears only in case of cerebral blood flow below 15-20 ml/100 g per minute, a value identical to the threshold of tissue at high energetic metabolism and ion homeostasis. ADC value decreases following the cerebral vessel occlusion, or remains unchanged when collateral circulation develops. It has been speculated that reduction in ADC reflects the water shift from extracellular space to intracellular space due to the membrane permeability and/or intracellular osmolality increase. These results suggest that diffusion weighted MRI correlates well with the cell metabolism, and cytotoxic edema plays an important role in the acute cerebral stroke. In clinical setting of acute cerebral ischemia, diffusion weighted MRI may detect superacute infarction by showing high signal (slower ADC) over the 6 hours following the insult, whereas conventional MRI generally fails to do so. In chronic liquefied cerebral infarction, increased ADC, or attenuated signal are the most frequent findings, suggestive of an elevated diffusion. Therefore, diffusion weighted MRI improves early diagnosis of stroke and help differentiate acute from chronic stroke. One disadvantage of diffusion weighted MRI is motion artifact, which may be reduced by the introduction of a navigator echo to correct for the phase shift caused by the first imaging echo, or by the utility of ultrafast imaging technique, such as echo planar. Another shortcomings is the susceptibility artifact incorporating the diffusion weighted MRI. The eddy current may also result from the strong gradients, producing shiftlike artifact. Such artifacts can be compensated for by appropriate shaping of the current pulses sent into the gradient coils, or by use of shielded gradients. As with rapid progresses in perfusion imaging of ischemia penumbra, misery perfusion and luxury perfusion, new insight into the diffusion weighted MRI will be significant.     

Impulsive and compulsive self-injurious behavior in bulimia nervosa: prevalence and psychological correlates

Acute ischemia in the complete territory of the carotid or the middle cerebral artery may lead to cerebral edema with raised intracranial pressure and progression to coma and death. Although clinical data suggest benefit for patients undergoing decompressive surgery for massive space occupying hemispheric stroke, little data about the effects of this procedure on morbidity and outcome is available. The experimental data support an early surgical approach. For early and probably most effective treatment of severe, space-occupying cerebral ischemia, the "malignant" character of the brain edema has to be recognized early after onset of vessel occlusion. Hereby magnetic resonance imaging (MRI) may allow to determine the clinical significance of brain edema early after onset, simultaneously allowing to monitor the evolution of ischemia. We performed serial SE-MRI in rats with acute hemispheric infarctions treated by decompressive craniectomy. Focal cerebral ischemia was induced in 36 rats using an endovascular occlusion technique. Decompressive craniectomy was performed 4 and 24 hours after vessel occlusion in groups of 12 animals each. Twelve animals were not treated by decompressive craniectomy (control group). Four, 24, 48, 72 and 168 hours after MCAO all animals were examined with conventional T1- and T2-weighted SE-MRI. Shift of the midline structures and compression of the ventricles were scored. Changes in weight and neurological performance were measured daily. The infarction volume was calculated by triphenyltetrazolium chloride staining 168 hours after MCAO. While mortality in the untreated group was 33.3%, none of the animals treated by a decompressive craniectomy died (mortality 0%). Neurological behaviour, weight loss and infarction volume were significantly better in the animals treated by early decompressive craniectomy (p < 0.05). Four hours after MCAO all untreated animals showed a massive shift of the midline structures and a massive compression of the ventricles; only 7 of 12 animals treated early by craniectomy showed mild mass effects. Correlation of the histological brain damage with T2-weighted MRI 4 hours after MCAO was poor (r = 0.41); later than 24 hours there was a good correlation (r > 0.7). Our results suggest that decompressive craniectomy in malignant cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. In the acute phase of hemispheric infarction conventional SE-MRI is not sensitive in estimation of infarction size. Later than 24 hours, conventinal SE-MRI proved to be useful in monitoring brain edema and infarction size in this rat model of malignant hemispheric stroke.     

Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging

The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 +/- 4.2% (mean +/- SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 +/- 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH3 signal of N-acetylaspartate (NAA) to 67 +/- 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 +/- 40 ms, considering a J-coupling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T2 of the CH3 signal of creatine/phosphocreatine (Cr/PCr) was observed in the lesion, from 163 +/- 22 ms during control to 211 +/- 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.     

Does an early postnatal check-up improve maternal health: results from a randomised trial in Australian general practice

Nitric oxide from neuronal cells plays detrimental roles in glutamate neurotoxicity and in focal brain ischemia. Nitric oxide directly damages DNA, and breaks in the DNA strands activate poly(ADP-ribose) polymerase (PARP), which brings poly(ADP-ribosyl)ation of the nuclear proteins. The excessive activation of PARP is thought to cause depletion of ATP and the energy failure resulting in cell death. To clarify the involvement of poly(ADP-ribosyl)ation in ischemic insult, we examined poly(ADP ribosyl)ation by immunohistochemical methods and the protective effect of 3-aminobenzamide, which is a PARP inhibitor, on focal brain ischemia using an intraluminal permanent middle cerebral artery occlusion model in rats. Poly(ADP ribosyl)ation was widely and markedly detected 2 hours after the ischemic insult in the cerebral cortex and striatum in which infarction developed 24 hours later. The enhanced immunoreactivity of poly(ADP-ribose) gradually decreased, and 16 hours later, no immunoreactivity was detected. Intraventricular administration of 3-aminobenzamide (1 to 30 mg/kg) 30 minutes before the ischemic insult decreased infarction volume in a dose-dependent manner along with the immunohistochemical reduction of poly(ADP-ribosyl)ation. Pretreatment with 7-nitroindazole (25 mg/kg, intraperitoneally), a selective neuronal nitric oxide synthetase inhibitor, partially reduced poly(ADP-ribosyl)ation. These data suggest the involvement of poly(ADP-ribosyl)ation in the development of cerebral infarction.     

Brain damage after aortic arch repair using selective cerebral perfusion

BACKGROUND: Selective cerebral perfusion is one of the most popular methods for cerebral protection during aortic arch repair. However, causes of postoperative brain damage are not fully understood. We analyzed brain damage after aortic arch repair using selective cerebral perfusion for true aortic arch aneurysm in regard to preoperative cerebral infarction and intracranial and extracranial occlusive arterial disease. METHODS: Over a 9-year period, 60 patients with true aortic arch aneurysm underwent aortic arch repair using selective cerebral perfusion. Postoperative brain damage was evaluated in regard to preoperative cerebral infarction detected by computed tomography, magnetic resonance imaging, or both in 50 patients and intracranial and extracranial occlusive arterial disease detected by digital subtraction angiography, magnetic resonance angiography, or both in 35 patients. RESULTS: Seven (12%) of the 60 patients died within 30 days of operation. Postoperative brain damage occurred in 6 (10.5%) (3, coma, and 3, hemiplegia) of 57 patients; 3 patients who died without awakening were excluded. Preoperatively, old cerebral infarction was detected in 9 patients (18%), and silent cerebral infarction (lacunar infarction and leukoaraiosis) was diagnosed in 26 patients (52%). Postoperative brain damage occurred in 3 (33%) of the 9 patients with preoperative cerebral infarction and in 3 (23%) of 13 patients with negative preoperative brain findings; this excludes 2 patients who died without awakening. No patient with silent cerebral infarction had postoperative brain damage. Occlusive arterial disease was detected in 7 patients (20%). The incidence of brain damage in these patients was 71% (5/7), which was significantly greater than that of 4% (1/28) in patients without occlusive arterial disease (p < 0.001). CONCLUSIONS: Silent cerebral infarction may not be a risk factor for postoperative brain damage. Preoperative evaluation of intracranial and extracranial occlusive arterial disease provides important information as to whether a patient might sustain brain damage after aortic arch repair using selective cerebral perfusion.     

Cytokines and cell adhesion molecules in cerebral ischemia: experimental bases and therapeutic perspectives

The possibility of reopening an occluded cerebral artery by means of thrombolysis has renewed interest in a number of the several mechanisms that are active during acute cerebral ischemia. Over recent years, it has become apparent that leukocytes play a central role not only during the healing stage of brain infarction but also during the early phases of cerebral ischemia, when it is postulated that these cells produce harmful effects, particularly in the presence of reperfusion. This review is based on the critical analysis of more than 150 publications dealing with the role of leukocytes and some inflammatory mediators (cytokines, chemokines, and adhesion molecules) in cerebral ischemia. Animal studies indicate that leukocyte involvement is promoted by a variety of inflammatory molecules produced immediately after the onset of cerebral ischemia. Considerable experimental evidence suggests that these mediators play a key role in the progression from ischemia to irreversible injury (ie, cellular death and necrosis). However, the precise role of each molecule alone remains to be further elucidated as well as in relation to the complex network existing among different mediators. Progress in our understanding of the inflammatory mechanisms operating in cerebral ischemia has enabled the testing of new compounds with promising results in animals; in contrast, one recent controlled trial of an anti-leukocyte molecule in acute stroke patients showed negative results. This discrepancy may derive in part from our incomplete understanding of the complexity of the inflammatory mechanisms involved in cerebral ischemia. Our analysis suggests that until sufficient knowledge of the underlying disease mechanisms is acquired, more care should be taken when testing new and potentially efficacious drugs in stroke patients.     

Experimental models and treatment trials for cerebral infarction

Recent progress in both experimental and clinical studies of cerebral infarction is outlined, and research on delayed neuronal death and ischemic penumbra is described. Development of animal models to study clinical pathophysiology is reviewed, and our focal cerebral ischemia model which has been used for many years is introduced. With elucidation of the pathophysiology of cerebral ischemia, various pharmaceutical agents have appeared recently in the clinical setting and our experimental trials on the treatment of cerebral ischemia are also introduced. From the clinical aspect, practical methods of treatment including antiplatelet therapy are explained. Cerebrovascular dementia and its prevention are also described.     

Intraoperative use of electroencephalography as an assessment of cerebral blood flow

The electroencephalogram (EEG) is exquisitely sensitive to decreases in cerebral blood flow (CBF). The EEG can detect cerebral ischemia in the awake and generally anesthetized patient. EEG monitoring of CBF during carotid endarterectomy alerts the surgeon to the need for a shunt. In the surgery of intracranial aneurysms, it can detect cerebral ischemia secondary to temporary vessel occlusion or determine the optimal anesthetic doses for brain protection.