Subcortical hemorrhage caused by cerebral amyloid angiopathy compared with hypertensive hemorrhage.

OBJECTIVES: Most published reports on lobular hemorrhage in cerebral amyloid angiopathy (CAA) include patients diagnosed only by imaging studies. This study analyzed patients with subcortical hemorrhage histologically diagnosed as CAA or non-CAA (hypertensive). METHODS: This is a retrospective study analyzing data from 100 craniotomy cases. Tissue of hematoma cavity wall was collected for histological investigation in hematoma removal by surgery in patients with subcortical hemorrhage. Statistical analyses of blood pressure, hematoma location and volume, outcome, and mortality was performed in CAA and non-CAA groups. RESULTS: There were 47 CAA and 53 non-CAA cases, and average age was significantly older in the CAA group (p < 0.01). Blood pressure was significantly lower (p < 0.01) but hematoma volume was significantly greater (p < 0.05) in the CAA group. Rebleeding occurred in two CAA cases and one non-CAA case, but no re-operations were required. Average score of modified Rankin Scale, which is used to measure the degree of disability in patients who have had a stroke, at three months after surgery was not significantly different between the two groups (CAA: 3.94 ± 1.28, non-CAA: 3.58 ± 1.50). There were seven deaths in the CAA and six in the non-CAA group, and intraventricular hemorrhage highly complicated in the death cases in both groups. In the CAA group, average age of the fatal cases was significantly older than that of the surviving cases (p < 0.05) and six cases demonstrated dementia before onset of hemorrhage. CONCLUSIONS: Surgical removal of a subcortical hemorrhage caused by CAA is not contraindicated. However, age > 80 years, complication with intraventricular hemorrhage, hematoma volume ≥ 50 ml, and dementia before onset of hemorrhage contribute to high mortality, and craniotomy should be carefully considered for such patients. A limitation of this study is that comparison between CAA and non-CAA groups was performed in the patients with only surgically indicated ICH, and does not evaluate entire ICH cases with CAA. However, this study appropriately compared pathologically diagnosed CAA and non-CAA in patients with moderate to severe lobular ICH with surgical indications.

Midline Shift Induced by the Drainage of Cerebrospinal Fluid in Three Patients With External Decompression.

It is not rare that progressive hydrocephalus worsens clinical conditions in a patient with external decompression and drainage or shunt surgery is required. However, spinal drainage or shunt surgeries potentially carry a risk of causing paradoxical herniation in a patient with decompressive craniectomy, particularly in a comatose case with wide craniectomy. Careful and strict observations are necessary for such patients. In our three comatose cases with craniectomy, paradoxical herniation occurred due to excessive drainage after 5-7 days of shunt surgery and lumbar drainage, although the drainage pressure was set at more than 10 cmH2O. Fortunately, in the three cases, the herniation improved within a few days after the drain was clamped and the bed was flattened. However, the Trendelenburg position and epidural blood patch might be necessary if paradoxical herniation occurs acutely after lumbar puncture or drainage because delayed resolution can be fatal in the herniation.

What is the impact of vasospasm on traumatic subarachnoid hemorrhage: Two cases of report.

It is difficult to predict that vasospasm would occur in traumatic subarachnoid hemorrhage (SAH) patients. Younger age, a lower score of Glasgow coma scale (GCS≦8) on admission, and greater cisternal blood volume are considered to correlate with post-traumatic vasospasm. We present two cases of traumatic SAH with post-traumatic vasospasm; one was a 74-year-old man and the other was a 72-year-old woman. They were alert without any neurological deficits on admission, although the SAH was focally thick as if caused by an aneurysmal rupture. The thick SAH was still identified on follow-up CT performed in a few days. The patients demonstrated cognitive dysfunction at the 4th and 5th day of admission, respectively, and imaging studies revealed vasospasm at the artery in the thick SAH. After treatments, the vasospasm resolved and both patients recovered from the disorientation completely in three weeks. The authors considered that focally thick traumatic SAH with poor clearance is the most influential factor to post-traumatic vasospasm independent of age or a GCS score. A low GCS score in head trauma patients might be mainly associated with existence of brain contusion, intracerebral hemorrhage, epidural, or subdural hemorrhages, which are frequently associated with traumatic SAH. If the traumatic SAH is focally thick with poor clearance, it might be better to initiate prompt treatments for vasospasm within 3 days after trauma. The delay in treatments for vasospasm contributes to poor outcomes.

Headache in patients with chronic subdural hematoma: analysis in 1080 patients.

Headache is a major symptom in chronic subdural hematoma (CSDH) patients. However, some CSDH patients do not complain headache although the hematoma is thick with definite midline shift. This clinical study was performed to identify the mechanism of headache in CSDH patients. We compiled clinical data of 1080 surgically treated CSDH patients (711 males and 369 females), and in 54 cases, the pressure of hematoma was measured during burr hole surgery using a glass-stick manometer. Headache was recognized in 22.6% of patients, while nausea or vomit suggesting increased intracranial pressure was detected in only 3.0%. Ophthalmological examination was performed in 238 patients, and papilledema was identified in only one patient (0.4%). The mean age of patients with headache (59.8 ± 16.9 years) was significantly younger than that of those without (75.7 ± 11.2 years) (P < 0.01). In 54 cases, the mean hematoma pressure was not significantly different between patients with (17.1 ± 6.2 mmH2O) and without (18.4 ± 7.2 mmH2O) headache (P > 0.10). Hematoma thickness was significantly greater in patients without headache (P < 0.01), but the ratio of midline shift to hematoma thickness was significantly greater in patients with headache (P < 0.01). In our results, the status of increased intracranial pressure was rare in CSDH patients, and high hematoma pressure was not a cause of headache. Midline shift was the most influenced factor for headache in our study, and based on the results, the authors consider that the potential cause of headache in CSDH might be stretching or twisting of the pain-sensitive meninges and meningeal arteries or veins.

Prehospital triage for endovascular clot removal in acute stroke patients.

Aim: To establish prehospital triage in accordance with the new guidelines for endovascular therapy, we retrospectively analyzed the monitoring data of the city-wide transportation system using the Maria Prehospital Stroke Scale (MPSS), a novel prehospital stroke scale for emergency medical technicians (EMTs) to predict the likelihood of thrombolytic therapy after transportation. Methods: Kawasaki City, Japan, has six comprehensive stroke centers (CSCs) and six primary stroke centers (PSCs). In CSCs, endovascular therapy can be carried out 24 h a day, 7 days a week, but not in PSCs. There is no "drip and ship" protocol for further endovascular therapy from PSCs to CSCs. We determined the predictive value of MPSS scoring by the EMTs for the performance of endovascular therapy after transportation. Results: There were 2031 patients (mean age, 71.1 ± 13.3 years) registered from April 2012 to March 2015. Multivariate logistic regression analysis indicated that the MPSS score and type of stroke center were independent predictors for performance of endovascular therapy. In particular, the odds ratio (OR) for endovascular therapy was significant for MPSS score 3 (OR, 2.914; 95% confidence interval (CI), 1.152-7.372; P = 0.024), MPSS score 4 (OR, 5.474; 95%CI, 2.300-13.029; P = 0.000), and MPSS score 5 (OR, 11.459; 95%CI, 4.334-30.296; P = 0.000) when MPSS score 1 was set as a reference. The diagnostic accuracy of the MPSS score evaluated by EMTs was 0.689 (95%CI, 0.627-0.751). Conclusions: Prehospital triage using MPSS scores evaluated by EMTs can predict the likelihood of performance of endovascular therapy after transportation, and may become a tool offering a flexible solution for designing a new transportation protocol.

Glioblastoma multiforme versus pleomorphic xanthoastrocytoma with anaplastic features in the pathological diagnosis: a case report.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) with anaplastic features should be strictly distinguished from glioblastoma multiforme (GBM). CASE PRESENTATION: A case of PXA that was initially diagnosed as GBM is presented. A 42-year-old man visited our clinic because of right hemiparesis and total aphasia. Head magnetic resonance imaging demonstrated enhanced multiple cystic lesions in the left temporal lobe suggesting an intra-parenchymal brain tumor. The lesion was partially removed and GBM with a Ki-67 index of 20 % was diagnosed by pathological examination of the resected specimen. Despite receiving radiation and chemotherapy, the patient died 6 months after the first admission. At autopsy, the boundary between the tumor and normal brain tissue was clear. Large parts of the tumor demonstrated typical features of PXA, including pleomorphism, clear xanthomatous cells with foamy cytoplasm, positive silver staining, and a Ki-67 index of less than 1 %. DISCUSSION AND CONCLUSIONS: GBM should be diagnosed only when the majority of the tumor cells are undifferentiated. Although the operative specimen appeared typical GBM histologically, the diagnosis of GBM was subsequently excluded by the autopsy finding that much of the tumor had the characteristic features of a benign PXA. Therefore, the final diagnosis in this case was PXA with anaplastic features. PXA with anaplastic features should be carefully distinguished from GBM to facilitate appropriate decisions concerning treatment.

Deep Vein Thrombosis in the Lower Extremities in Comatose Elderly Patients with Acute Neurological Diseases.

PURPOSE: Comatose elderly patients with acute neurological illness have a great risk of deep vein thrombosis (DVT). In this study, the incidence of DVT and the effectiveness of early initiation of treatment were evaluated in those patients. MATERIALS AND METHODS: Total 323 patients were admitted to our ward due to neurological diseases in one year, and 43 patients, whose Glasgow Coma Scale was ≤ 11 and who was older than ≥ 60 years, were included in this study. D-dimer was measured on admission and day 7, and lower-extremity ultrasonography was performed on day 7. When DVT was positive, heparin treatment was initiated, and further evaluation of pulmonary embolism (PE) was conducted. Vena cava filter protection was inserted in PE-positive patients. Incidence of DVT and PE, alteration of D-dimer value, and effect of heparin treatment were analyzed. RESULTS: DVT was positive in 19 (44.2%) patients, and PE was in 4 (9.3%). D-dimer was significantly higher in DVT-positive group on day 7 (p<0.01). No DVT were identified in patients with ischemic disease, while 66.7% of intracerebral hemorrhage and 53.3% of brain contusion patients were DVT positive. Surgery was a definite risk factor for DVT, with an odds ratio of 5.25. DVT and PE disappeared by treatment in all cases, and no patients were succumbed to the thrombosis. CONCLUSION: Patients with hemorrhagic diseases or who undergo operation possess high risk of DVT, and initiation of heparin treatment in 7 days after admission is an effective prophylaxis for DVT in comatose elderly patients without causing bleeding.

Management for traumatic chronic subdural hematoma patients with well-controlled shunt system for hydrocephalus.

Traumatic CSDH enlarged in two cases with VP or LP shunt system although the shunt valve pressure was increased to 200 mmH2O. In surgery, the hematoma cavity pressure was found to be 130 and 140 mmH2O, suggesting that to raise the shunt valve pressure is not effective for decreasing CSDH volume.

Vertebral Artery Dissection Leading to Fornix Infarction: A Case Report.

BACKGROUND: The subcallosal artery is a proximal branch of the anterior communicating artery and has been recognized as the vessel responsible for fornix infarction. Fornix infarction caused by vascular damage to the posterior circulation has not been reported previously. RESULTS: A 26-year-old woman suffered from fornix infarction due to artery-to-artery embolism after vertebral artery dissection. Cerebral infarctions were also found in the left thalamus, body of the left caudate nucleus, and the left occipital lobe other than the fornix. CONCLUSIONS: Occlusion of the subcallosal artery results in cerebral infarction of fornix, anterior cingulate cortex, and genu of the corpus callosum. However, in our case, lesions were restricted to the territory of posterior circulation. In addition to subcallosal artery, lateral posterior choroidal artery, a perforating branch of the posterior cerebral artery, has been described to send branches to the fornix, so we speculated that the left lateral posterior choroidal artery was actually responsible for fornix infarction.

Quality assurance monitoring of a citywide transportation protocol improves clinical indicators of intravenous tissue plasminogen activator therapy: a community-based, longitudinal study.

BACKGROUND: Stroke-bypass transportation to the stroke center by paramedics is important to maximize the efficiency of intravenous tissue plasminogen activator (iv-tPA) therapy. To improve access to stroke thrombolysis, a citywide protocol was launched on January 2007 in Kawasaki City (population 1.4 million) using the Maria Prehospital Stroke Scale (MPSS), and quality assurance monitoring has been performed every 6 months. The aim was to identify whether the citywide quality assurance monitoring improves the process and outcome of iv-tPA therapy. METHODS: All of the MPSS-based transportation data prospectively recorded by the Kawasaki City Fire Department and the associated clinical data in the 11 hospitals that accept stroke-bypass transfers were merged every 6 months for the quality assurance monitoring. Clinical indicators such as ambulance call-to-door time, onset-to-needle time, door-to-needle time, frequency of thrombolytic use, and outcome of thrombolytic therapy were analyzed. These clinical indicators were also compared between patients transferred on weekdays and on weekends. RESULTS: A total of 2049 patients was registered from April 2009 to March 2013. Their mean age was 70.4 ± 13.2 (range, 24-98) years, and 64.3% were male. Ambulance call-to-door time decreased gradually from 37.5 ± 12.5 minutes to 33.9 ± 11.7 minutes over 4 years (P = .000, analysis of variance with the post hoc Dunnett test). Onset-to-needle time and door-to-needle time were similar over the 4 years. Good outcome (modified Rankin Scale score <2) after iv-tPA therapy increased from 24.1% to 35.3% (P = .045, 2010 vs. 2012). No deleterious effect of weekend admission was observed based on these clinical indicators. CONCLUSIONS: A citywide MPSS-based transportation protocol significantly decreased the delay in the ambulance call-to-door time. The implementation of standardized cross-institutional quality assurance programs for acute stroke therapy may improve the process and outcome of iv-tPA therapy in the community.

Delayed post-traumatic large subgaleal hematoma caused by diastasis of rhomboid skull suture on the transverse sinus.

PURPOSE: This study aimed to consider an appropriate treatment for large subgaleal hematoma with skull fracture and epidural hematoma (EDH). CASE REPORT: A 6-year-old boy presented at our hospital with head trauma, and computed tomography (CT) showed a thin EDH in the right temporo-occipital area and cranial diastasis in the right lambdoidal suture. However, no neurological deficits were identified in the patient. One week after trauma, he visited our hospital again with a massive fluctuant watery mass extending from the forehead to the right temporoparietal areas, and laboratory data revealed that he was anemic. CT showed a massive subgaleal hematoma with extremely high density around the cranial diastasis. Damage of the transverse sinus was suspected, and emergent sinus repair surgery was performed. The surgery disclosed that bleeding from the transverse sinus was flowing out extracranially through the cranial diastasis. The subgaleal and epidural hematomas were removed, and bleeding from the sinus was stopped by dural tacking sutures along the transverse sinus. Postoperative CT demonstrated complete disappearance of epidural and subgaleal hematomas. The patient recovered from general fatigue without blood transfusion and was discharged 9 days after surgery. CONCLUSIONS: The therapeutic strategy for massive subgaleal hematoma is individualized. However, treatment for massive subgaleal hematoma with skull fracture should not be considered the same as for hematoma without skull fracture. Emergent surgery is recommended before neurological deterioration is recognized in the patient if damage to the dural sinus is suspected.

Anti-Chol-1 antigen, GQ1bα, antibodies are associated with Alzheimer's disease.

The interaction of amyloid ß-proteins (Aß) with membrane gangliosides has been reported to be an early event in Aß fibril formation in Alzheimer's disease (AD). Neuronal degeneration in AD has been postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD), and 11 non-demented age-matched pathological controls) were examined in order to detect anti-glycosphingolipid (GSL) antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα) antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides). However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90%, 9 of 10 cases) and VD (100%), respectively. Most surprisingly, anti-GQ1bα antibodies (IgM) were found in 90% (9/10) and 100% (6/6) in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.

A case of subarachnoid hemorrhage with pituitary apoplexy caused by idiopathic hypertrophic pachymeningitis.

Steroid therapy is considered to improve clinical symptoms in hypertrophic pachymeningitis. We present a 70-year-old man with idiopathic hypertrophic pachymeningitis, whose clinical signs progressively worsened despite steroid therapy. He died of subarachnoid hemorrhage (SAH) with pituitary apoplexy 2 months after the admission regardless of improvement of laboratory data and magnetic resonance imaging appearance by one-and-half-month steroid therapy. Autopsy revealed thickened dura mater supporting the diagnosis of hypertrophic pachymeningitis. Brain parenchyma is generally not affected by the disease; however, histological investigation suggested that inflammation of the dura caused damage to superior hypophyseal artery resulting in SAH and apoplexy in the anterior lobe of the pituitary gland. The higher dose and the longer duration of steroid therapy should have achieved in our case although most laboratory data recovered within the normal range. The aggressiveness of hypertrophic pachymeningitis must be evaluated by clinical signs rather than by laboratory data or imaging examinations.

L-PDMP improves glucosylceramide synthesis and behavior in rats with focal ischemia.

BACKGROUND: It has been shown that exogenic administration of glycosphingolipids (GSLs) induces outgrowth of neurites from cultured nerve cells. Furthermore, the activator of glucosylceramide synthase, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (L-PDMP), is thought to exhibit stimulatory effects on both the biosynthesis and neurotrophic actions of GSL in the same culture system. To investigate the effect of GSLs on focal cerebral ischemia in vivo, L-PDMP was injected into the intraperitoneal space of rats during the chronic phase following permanent occlusion of the left middle cerebral artery (MCA) and thereafter, the levels of GSLs and their effects on behavioral changes were examined Methods: The levels of cerebrosides, sphingomyelin (SM) and ceramide in the ischemic cortex were measured by gas-liquid chromatography (GLC) after separation by high-performance thin-layer chromatography, using the internal standards N-heptadecanoyl-D-cerebroside, N-heptadecanoyl-D-sphingomyelin and N-heptadecanoyl-D-sphingosine, respectively. To determine the sugar components of the cerebrosides, the trimethylsilylated derivatives of their methylglycosides after methanolysis were analysed directly by GLC. RESULTS: The L-PDMP treatment induced a 2.4-fold increase in glucosylceramide, the precursor of gangliosides, but no changes were evident in the levels of SM and ceramide in the ischemic cerebral cortex. The ischemic rats treated with L-PDMP showed improved re-acquisition of memory and learning in the Morris water maze task. CONCLUSION: These results suggest that the pharmacological effects of L-PDMP include significant facilitation of glucosylceramide biosynthesis and improvement of neural function.

Glycosphingolipid antigens in neural tumor cell lines and anti-glycosphingolipid antibodies in sera of patients with neural tumors.

To characterize biomarkers in neural tumors, we analyzed the acidic lipid fractions of 13 neural tumor cell lines using enzyme-linked immunoabsorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining. Sulfated glucuronosyl glycosphingolipids (SGGLs) are cell surface molecules that are endowed with the Human Natural Killer-1 (HNK-1) carbohydrate epitope. These glycosphingolipids (GSLs) were expressed in all cell lines with concentrations ranging from 210 to 330 ng per 2 x 10(6) cells. Sulfoglucuronosyl paragloboside (SGPG) was the prominent species with lesser amounts of sulfoglucuronosyl lactosaminyl paragloboside (SGLPG) in these tumor cell lines as assessed by quantitative HPTLC immunostaining. Among the gangliosides surveyed, GD3 and 9-O-acetylated GD3 (OAc-GD3) were expressed in all tumor cell lines. In contrast, fucosyl-GM1 was not found to restrict to small cell lung carcinoma cells. In addition, we have analyzed serum antibody titers against SGPG, GD3, and OAc-GD3 in patients with neural tumors by ELISA and HPTLC immunostaining. All sera had high titers of antibodies of the IgM isotype against SGPG (titers over 1:3,200), especially in tumors such as meningiomas, germinomas, orbital tumors, glioblastomas, medulloblastomas, and subependymomas. Serum in a patient with subependymomas also had a high anti-SGGL antibody titer of the IgG and IgA types (titers over 12,800). The titer of anti-GD3 antibody was also elevated in patients with subependymomas and medulloblastomas; the latter cases also had a high titer of antibody against OAc-GD3. Our data indicate that certain GSL antigens, especially SGGLs, GD3, and OAc-GD3, are expressed in neural tumor cells and may be considered as tumor-associated antigens that represent important biomarkers for neural tumors. Furthermore, antibody titers in sera of patients with these tumors may be of diagnostic value for monitoring the presence of tumor cells and tumor progression.

Experimental ischemic brain edema: morphological and magnetic resonance imaging findings.

Magnetic resonance (MR) imaging is a powerful tool for detecting and characterizing ischemic edema, a serious complication of ischemic cerebrovascular disorders. In this article the authors investigate the relationships between MR imaging findings and structural/ultrastructural changes in ischemic brain edema by using various animal models of experimental cerebral ischemia. The authors observed the following: 1) Ischemic edema was detectable by diffusion weighted MR imaging as early as 15 minutes after the onset of vascular occlusion. A decrease in the apparent diffusion coefficient (ADC) corresponded to the early cellular/cytotoxic type of brain edema and the decrease was proportionate to the degree of intracellular water accumulation. 2) Postischemic transient normalization of the ADC after the initial decrease did not signify histological recovery but rather slowly progressing infarction. 3) Histological degradation of postischemic tissue correlated with the decrease in tissue elasticity and the magnetization transfer ratio. 4) Transient cytotoxic edema localized in the substantia nigra preceding neuronal death was detectable on MR images after ipsilateral striatal infarction. Thus, MR imaging is a powerful tool for detecting and characterizing brain edema associated with ischemic stroke.

In vivo influence of ceramide accumulation induced by treatment with a glucosylceramide synthase inhibitor on ischemic neuronal cell death.

It has been shown that exogenous ceramide induces delayed neuronal death (DND) of cultured hippocampal neurons. To evaluate the role of endogenous ceramide in ischemic DND, the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), was used to generate ceramide in gerbil hippocampi in vivo. The trimethylsilylated derivatives of ceramide were analyzed directly by gas chromatography mass spectrometry, after separation with high-performance thin-layer chromatography. The ceramide compositions in vehicle hippocampus consisted mainly of C18:0 fatty acyl sphingosine (87.9%), with C16:0 and C20:0 ceramides being minor components (7.1% and 5.1%, respectively). Ceramide level in the hippocampi from gerbils subjected to D-PDMP treatment was 1.5-fold higher than those from vehicle-treated gerbils. In spite of the accumulation of ceramide observed in the D-PDMP group, the histological studies did not reveal any ischemic neuronal death in hippocampal CA1 neurons with the gerbils that had been subjected to a sham operation (2-min sublethal ischemia). These results suggest that the ceramide accumulation induced by blocking the de novo synthesis of glucosylceramide with D-PDMP may be independent of the metabolic pathway underlying ischemic DND.

Dissecting aneurysm of the anterior cerebral artery with severe subarachnoid hemorrhage during treatment for cerebral infarction.

Intracranial dissecting aneurysms cause ischemia, but anticoagulation or antiplatelet agents are administered to most ischemic patients without angiographical investigation. A 55-year-old woman succumbed to a subarachnoid hemorrhage (SAH) during antiplatelet therapy for ischemia caused by a dissecting aneurysm at the anterior cerebral artery, which was identified by conventional angiography on day 11 after admission. The authors emphasize that all dissecting aneurysms manifesting ischemic attack can cause hemorrhage. Therefore, emergency angiography is recommended for patients with ischemia complaining of a headache. If dissection is identified, it may be better to regulate the blood pressure of the patient strictly without anticoagulation or antiplatelet therapy.

Ultrastructural and MRI study of the substantia nigra evolving exofocal post-ischemic neuronal death in the rat.

To clarify the morphological characteristics of exofocal post-ischemic neuronal death (EPND) in the substantia nigra (SN), we investigated the course of light- and electron-microscopic changes of the SN of rats subjected to occlusion of the left middle cerebral artery (MCA) for 1, 2, 4, 7 and 12 days. To assess cellular edema, sequential magnetic resonance (MR) mapping of the apparent diffusion coefficient (ADC) and the T2 value test was performed. Histological and electron-microscopic examination on day 1 showed dotted chromatin clumps in the nuclei of some neurons and mild swelling of the perivascular endfeet of astrocytes in the ipsilateral SN. On day 2, a few cells of the ipsilateral SN pars reticulata (SNr) revealed key morphological signs of apoptosis--apoptotic body-like condensation and segregation of the chromatin and DNA fragmentation-like nuclear remnants. On day 4, 38% of neurons became swollen (pale neurons) with cytoplasmic microvacuoles, which appeared to originate from rough endoplasmic reticulum (rER), mitochondria and Golgi apparatus. Twenty percent of neurons showed massive proliferation of the cisternae of the rER, some of which were fragmented or had lost their normal parallel arrangement. In addition, MR mapping revealed a transient ADC decrease with a T2 increase (signifying a phase of cellular edema), which coordinated with the phase of ultrastructural cellular swelling. Further, the total number of neurons started to decrease gradually, the perivascular endfeet of astrocytes were markedly swollen, and the neuropil became loose on day 4. On day 7, reactive astrocytes and dark neurons occurred most frequently. These results suggest that the EPND in the SN after occlusion of the MCA in adult rats is due to both apoptosis and necrosis, although necrosis seems to be the dominant mechanism of the EPND. However, the morphologic resemblances of EPND to delayed neuronal death suggest these processes have a common pathomechanism.