Hospital mortality in ischemia: influence of two vascular risk factors

INTRODUCTION: Acute cerebrovascular disease is a serious neurological problem. Mortality is between 6% and 30%. Most studies are in agreement that advanced age, type of ictus, size of lesion and clinical deterioration are factors determining mortality. However, its relationship to vascular risk factors is not completely clear. OBJECTIVE: To analyze the repercussion of different vascular risk factors on mortality during the acute phase of ictus. PATIENTS AND METHODS: We studied all patients with ictus admitted to the Servicio de Neurología of the Hospital Xeral de Galicia de Santiago de Compostela over a period of 3 years (n = 915). We recorded vascular risk factors and analyzed the causes of mortality whilst in hospital. RESULTS: Hospital mortality due to ictus was 16.8%. Mortality was 14.5% in cerebral infarct, 23.2% in intracerebral haemorrhage and 19.4% in subarachnoid haemorrhage. A total of 20.8% of the patients died of neurological causes, 24.7% of vascular causes, 26% due to infection and of uncertain causes in the remaining 28.6%. There was a neurological cause of death in 46.1% of the patients with subarachnoid haemorrhage, 25.5% with intracerebral haemorrhage and 14.8% with cerebral infarcts. Vascular risk factors associated with greater mortality were age (p < 0.001) and a history of cardiopathy (p < 0.05). CONCLUSIONS: Vascular risk factors which indicated worse prognosis were: age, type of ictus and a history of cardiopathy.     

Acute prognosis and differentiation of various cerebral infarct groups in comparison with cerebral hemorrhage

For clinical trials classification of stroke should be possible at the bedside by simple methods that are available every where. In this study are 1105 patients with every first ischaemic strokes and 130 patients with intracerebral haemorrhages. The differences between severity of clinical symptoms, outcome and risk factors of intracerebral haemorrhages, ischaemic stroke caused by cerebral microangiopathy, ischaemic stroke combined with extracranial carotid stenosis, cardiogenic brain embolism and atherothrombotic stroke, were analysed. Intracerebral haemorrhages show the poorest outcome of all groups (mortality 23.8%), due to increased intracranial pressure. Cardiogenic brain embolism is more frequent in older women (mean age 77.8 y.). Main risk factor is atrial fibrillation with absolute arrhythmia. The outcome of this group is the worst of all subgroups of ischaemic stroke and survivors most often in need of institutionalization. Patients with ischaemic stroke combined with extracranial carotid stenosis are significantly younger (mean age 67.6 y.), predominantly male, and smokers. Their mortality is low (0.63%), but recovery of paresis is slower than in other subgroups. Ischaemic strokes caused by cerebral microangiopathy with hypertension as main risk factor recover most quickly but acute mortality is higher than in ischaemic stroke combined with extracranial carotid stenosis because of higher age (mean age 74.5 y.). Institutionalization is more frequent too because of higher incidence of dementia in this subgroup. The main prognostic factors of all groups are age and severity of clinical symptoms. A special subgroup are infratentorial ischaemic strokes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Traumatic brain contusions: a clinical role for the kinin antagonist CP-0127

Focal cerebral contusions can be dynamic and expansive, leading to delayed neurological deterioration. Due to the high mortality associated with such cerebral contusions, our standard practice had evolved into evacuating contusions in patients who had a deterioration in level of consciousness, lesions > 30 cc and CT suggestion of raised ICP. Experimental brain edema studies have implicated kinins in causing 2 degrees brain swelling. CP-0127 (Bradycor), a specific bradykinin antagonist, has been found to reduce cerebral edema in a cold lesion model in rats. In a randomized, single blind pilot study, a 7 day infusion of CP-0127 (3.0 micrograms/kg/min) was compared to placebo in patients with focal cerebral contusions presenting within 24-96 hours of closed head injury with an initial GCS 9-14. The ICP, GCS, and vital signs were monitored hourly. The total lesion burden (TLB) was measured on serial CT scans. There were no differences in age, baseline GCS, TLB, initial ICP, or laboratory findings between the two groups (n = 20). The mean (+/- s.d.) rise in peak ICP from baseline was greater in the placebo group than with CP-0127 (21.9 +/- 4.7 vs 9.5 +/- 2.0, P = 0.018). In addition, the mean reduction in GCS in the placebo group was significantly greater than in the CP-0127 group (4 +/- 1.0 vs 0.6 +/- 0.4, P = 0.002). Significantly raised ICP and clinically significant neurological deterioration occurred in 7/9 patients on placebo (77%) and only in 1 patient (9%; n = 11) on CP-0127, mandating surgery (P = 0.005). There were no adverse drug reactions, significant changes in vital signs or variations in the laboratory values. The cerebral perfusion pressure was adequately maintained in all patients irrespective of therapy. These preliminary results with CP-0127 provide supporting evidence that the kinin-kallikrein system could be involved in cerebral edema. In this study, treatment with CP-0127 appeared to alter the natural history of traumatic brain contusions by preventing the 2 degrees brain swelling. In addition, CP-0127 obviated the need for surgery in the majority of treated patients. CP-0127 could act on the cerebral vasculature to limit dys-autoregulation and brain swelling or on the blood brain barrier to reduce cerebral edema.     

Delayed full-thickness grafting of lower leg defects following removal of skin malignancies

Cerebral stroke is a serious complication related to carotid endarterectomy (CEA), being most frequently caused by thromboembolic events and less frequently on account of cerebral haemorrhage. The present series comprised five out of 857 (0.6%) patients who had undergone CEA at Oulu University Hospital between the years 1974 and 1993 and suffered a postoperative stroke four to 13 days after surgery due to intracerebral haemorrhage (IH). Preoperatively, all these patients were neurologically intact, with transient ischaemic attacked (TIA) as the main indication for CEA. All five patients had a history of arterial hypertension treated adequately preoperatively, and one patient had high blood pressure levels after surgery. Critical ipsilateral stenosis of the internal carotid artery (> 90%) was detected in the preoperative angiogram in all five cases. The primary outcome after CEA was uneventful in every case, without any signs of neurological deficiency. The symptoms, comprising severe headache, convulsions and/or hemiparesis occurred suddenly four to 13 days (mean seven days) after CEA. The diagnosis of IH was based on computed tomography (CT) findings. All five patients were treated conservatively. Three of them died. We conclude that even normotensive, neurologically intact patients without demonstrable cerebral infarction or postoperative hypertension may suffer cerebral haemorrhage after the relief of high-grade carotid stenosis. The role of possible insufficiency of the autoregulatory mechanisms of the cerebral vasculature on account of long-standing critical stenosis of the internal carotid artery and subsequent uncontrolled hyperperfusion following CEA are discussed.     

MR of cerebral abnormalities concomitant with primary intracerebral hematomas

PURPOSE: To determine whether arteriolar vessel wall degeneration in primary intracerebral hematomas might be associated with ischemic brain lesions and clinically silent (apparently intracerebral) previous hemorrhages. METHODS: The MR images of 120 consecutive patients (mean age, 60 years; age range, 22 to 84 years) with their first stroke caused by a primary intracerebral hematoma were reviewed retrospectively for coexisting ischemic damage and previous bleeds. RESULTS: Early confluent to confluent white matter hyperintensities, lacunes, or infarction were present in 83 (69%) of the patients, and 39 (33%) had had previous hemorrhages consisting of microbleeds or old hematomas. Extensive white matter hyperintensities and lacunes were most frequent in patients with thalamic primary intracerebral hematomas. There was no relationship between the frequency of old hemorrhages and the location of subsequent primary intracerebral hematomas. CONCLUSION: Clinically silent ischemic lesions and previous hemorrhages are a common finding on MR images of patients with primary intracerebral hematoma. They may therefore serve as evidence of diffuse microangiopathy with a possible increased risk for cerebral hemorrhage.     

The neuropathology of orthotopic liver transplantation: an autopsy series of 16 patients

OBJECTIVE: To examine the neuropathologic findings seen in the setting of orthotopic liver transplantation (OLT) and to asses the role, if any, that the neuropathology had in the patient's death. DESIGN: Retrospective autopsy series of 16 patients. SETTING: Tertiary referral center with a high volume of liver transplantation. PATIENTS: Sixteen OLT patients who died and in whom a complete autopsy, including examination of the brain and spinal cord, was performed. RESULTS: Sixteen patients, including 13 women and 3 men, comprised the study group. Patients ranged in age from 25 to 64 years (mean 44.8 years). Postoperative OLT survival ranged from 1 to 1962 days (mean 236 days). Reasons for the initial OLT included hepatitis (n = 6), fulminant hepatic failure (n = 4), cryptogenic cirrhosis (n = 2), methotrexate toxicity (n = 1), postoperative complication (n = 1), primary biliary cirrhosis (n = 1), and hepatocellular carcinoma (n = 1). Autopsies in 13 (81%) patients showed neuropathology; in only 2 patients, however, was the primary cause of death attributable to these findings. The most common neuropathology was related to anoxia or infarction, specifically, ischemia or focal neuronal necrosis (n = 9), infarction (n = 4), and diffuse anoxic encephalopathy (n = 3). Other central nervous system findings included infection with Aspergillus, Candida, and Toxoplasma (n = 3). The most common cause of death was infection-related in 8 patients. One patient died of pulmonary hypertension, 1 of acute rejection, and 1 of possible hyperacute rejection. Two patients died directly as a consequence of neuropathology findings; one had massive central edema with herniation, and the other had a large intracerebral hemorrhage with herniation. The exact cause of death was unclear in 3 patients. CONCLUSIONS: The most common neuropathology findings in this series were related to ischemia and infarction. Neuropathology findings are a significant cause of morbidity, but were only rarely the main cause of death (n = 2) in the OLT patients in this study.     

Predisposing factors to enlargement of spontaneous intracerebral hematoma

BACKGROUND AND PURPOSE: Enlargement of intracerebral hemorrhage is a major cause of clinical deterioration. Identification of factors that predispose to hematoma enlargement is important in managing patients. METHODS: We selected 186 patients (71 women and 115 men; mean age, 64.8 +/- 12.5 years) with spontaneous intracerebral hemorrhage who had undergone an initial CT within 24 hours and a second scan within 120 hours of symptom onset. We compared patients with (n = 41) and without (n = 145) hematoma enlargement according to clinical characteristics and laboratory data. RESULTS: By multiple logistic regression analysis (n = 139), interaction of long interval (> 6 hours) from onset to first CT and small hematoma (< 25 cm3) strongly reduced risk of enlargement. The analysis also demonstrated that the following factors independently predisposed to enlargement: history of brain infarction; liver disease; interaction of fasting plasma glucose > or = 141 mg/dL and systolic blood pressure on admission > or = 200 mm Hg; and interaction of glycosylated hemoglobin A1c > or = 5.1% and systolic blood pressure on admission > or = 200 mm Hg. CONCLUSIONS: A patient examined > 6 hours after ictus who has a hematoma volume < 25 cm3 is unlikely to experience further hematoma growth. Prevention of brain infarction and premorbid management of liver disease may serve to lower the risk of hematoma enlargement. Although it remains controversial whether antihypertensive drugs should be used in the acute phase of intracerebral hemorrhage, poorly controlled diabetics with high systolic blood pressure (> or = 200 mm Hg) on admission also were at high risk of hematoma enlargement.     

Intracerebral hematoma as an acute manifestation of intracranial tumors

Sixteen patients with spontaneous intracerebral haematoma due to intracranial tumours are discussed. The total number of patients with intracranial tumour treated in the period concerned was 594, so the incidence of tumour haemorrhage was 2.7%. In most of the patients we found metastatic neoplasm (n = 6) and glioblastoma (n = 3). All patients were acute admissions. Seven were comatose, seven were somnolent, and two patients were alert. In ten patients the haemorrhage represented the first reliable clinical sign. In six patients a tumour disease was known. Fourteen patients were operated on. Six patients died. Extensive neuro-radiological examination is very important, particularly since 30% of these acute intracerebral haemorrhages occur in patients with benign intracranial tumours.     

Laparoscopic splenectomy after arterial embolisation

Laparoscopic splenectomy remains a challenging procedure, as haemorrhage causes the most complications. In order to reduce this risk, preoperative selective embolisation of the splicing artery has been performed in a series of six successful laparoscopic splenectomies in one male and five female patients with a mean age of 34.6 years (range 17-53 yrs). Indications for surgery were immune thrombocytopenic purpura (ITP)(n = 3), non-Hodgkin lymphoma with secondary haemolytic anaemia (n = 1), autoimmune haemolytic anaemia (n = 1) and congenital spherocytosis (n = 1). The mean splenic length was 12.3 cm (range 9-16 cm) and no accessory spleens were identified. Mean operative time was 96.7 min (range 90-150 min). There were no deaths nor haemorrhagic or septic complications. Recovery after surgery was excellent with a mean hospital stay of 5.2 days (range 2-10 days). We conclude that selective embolisation of the splenic artery, just prior to laparoscopic splenectomy adds to the safety, and operating time may be shortened.     

Edward N. Brandt, Jr., M.D

We present the profile of risk factors, etiologic and clinical data of 2,000 consecutive patients with first-ever-in-a-lifetime stroke (cerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage), admitted to the Ege University Hospital between January 1, 1991, and September 31, 1995. This hospital-based registry is the first systematic epidemiologic report on the stroke profile of Turkish people The Ege University Stroke Unit is the only tertiary medical care facility which is organized for patients with different stroke subtypes in Izmir, Turkey. A prospective hospital-based registry using systematic computer coding of data of all stroke patients has been used since January 1991. All patients were evaluated by clinical examination, CT and/or MRI, color duplex and specific cardiac investigations. They were followed up for at least 6 months. The mean age was 62.3 +/- 12 years, and 44.4% were females. Ischemic stroke was found in 77%, primary intracerebral hemorrhage in 19% and subarachnoid hemorrhage in 4%. The major risk factor of ischemic stroke was hypertension (63%), followed by hypercholesterolemia (37%), diabetes mellitus (35%), ischemic heart disease (23%), atrial fibrillation (20%) and smoking (17%). The main cause of primary intracerebral hemorrhage was hypertension (88%), and the principal localization was the thalamus (38%), followed by putamen (28%), lobar(16%), pons(6%), cerebellar(4%), primary intraventricular hemorrhage (4%) and multiple hemorrhages (2%). The over- all 30-day case-fatality rate was 19.7% and the higher mortality rate was found in patients with primary intracerebral hemorrhage (29%) than in those with ischemic stroke (17%). The Ege Stroke Registry allows to estimate the stroke-related problems in patients admitted to a stroke unit and to evaluate the risk factors, etiology and clinical manifestations of stroke in Turkey.     

Acquired von Willebrand disease in patients with high platelet counts

Operative indication and risk factors for unruptured cerebral aneurysms were discussed. During the past 11 years, 38 aneurysms in 33 patients with a mean age of 54 years were operated on. All aneurysms were located in the anterior circulation; 16 were of carotid artery, 15 of the middle cerebral artery, 4 of the anterior communicating artery, and 3 of the distal anterior cerebral artery. Six cases (18.2%) developed neurological deficits postoperatively. The deficits were permanent in 3 cases (morbidity 9.1%). There was one operative death (mortality 3.0%). Operative risk factors were analyzed in 4 particular cases. Of these 4 cases, two cases had large aneurysms (14 and 16mm in diameter) located at carotid-ophthalmic and at the inferior wall of the carotid arteries, respectively. One developed unilateral blindness possibly due to operative manipulation, and the other showed hemiparesis with aphasia due to postoperative carotid stenosis caused by clipping. Of the rest 2 cases; one with multiple (carotid and middle cerebral) aneurysms developed hemiparesis because of postoperative stenosis of the atheromatous parent artery caused by clipping, and the other, with a large (17mm) aneurysm at the distal anterior cerebral artery, died of postoperative intracerebral hematoma. Both of these cases were associated with cerebral ischemic disease. All cases that developed postoperative neurological deficits had varying degrees of hypertension. Reviewing our series and other reports, it can be said that age is one of the most important factors that influence operative mortality. However, a lower risk of rupture develops as age increases. For those under 70 years of age, operation is considered safe in healthy individuals, especially among those without hypertension. However, in cases where there are large aneurysms, multiple lesions, less accessible locations and cerebral ischemic disease, operative risks should be kept in mind. Operative morbidity in these cases is relatively high compared to that found among others. Therefore, planning a meticulous surgical strategy and further careful operative manipulation are essentials, when surgical treatment is indicated.     

Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin

In patients with inferior vena cava (IVC) injuries, predictors of survival are investigated. From 1987 to 1995, 27 IVC injuries were identified among 514 patients with vascular trauma. The ability of clinical determinants to predict survival were retrospectively assessed. IVC injuries occurred in 7 females and 20 males (mean age, 27.7 +/- 2.5 years) from both blunt (n = 14) and penetrating (n = 13) trauma. The mean revised trauma score was 10.2 +/- 0.6. Injuries were treated by primary repair (n = 22), ligation (n = 4), or prosthetic grafting (n = 1). Thirteen patients died (48%), 10 within 12 hours of admission. Suprahepatic (n = 2), retrohepatic (n = 12), suprarenal (n = 1), and infrarenal (n = 12) injuries were associated with 100, 67, 100, and 20 per cent mortality, respectively. Blood transfusions (16 +/- 4 vs 23 +/- 4 units), coagulation factor replacement (7 +/- 2 vs 7 +/- 2 units), and electrolyte solution use (8.6 +/- 1.4 vs 9.6 +/- 1.4 L) were similar among survivors and nonsurvivors. Four complications [venous hypertension (n = 2), IVC thrombosis (n = 1), and pulmonary embolus (n = 1)] occurred in the 14 survivors (28.6%). Blunt injury, revised trauma score, free perforation, injury location, intraoperative hypotension, and blood loss were predictive of mortality. IVC injuries remain extremely lethal, and improved survival is associated with infrarenal penetrating injuries and a contained hematoma.     

Autosomal dominant juvenile recurrent parotitis

OBJECTIVE: To find out how physicians would manage thrombotic complications in patients with primary intracerebral haemorrhage. DESIGN: Fifty-six participants at a British Geriatrics Society session on stroke were asked to state on a self-completion question sheet how they would manage two hypothetical cases. RESULTS: There was support for a wide range of treatments but no consensus on how to treat patients with life-threatening thrombosis after cerebral haemorrhage.     

Hereditary persistence of alpha-fetoprotein. Case report and review of the literature

BACKGROUND: The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature. METHODS: Thirteen patients (male ten, female three; mean age 65 years) underwent simultaneous cardiac surgery and pulmonary resection. Lung pathology consisted of primary lung carcinoma (n = 10), benign disease (n = 2) and carcinoid (n = 1). Lung resections included pneumonectomy (n = 3), lobectomy (n = 4), segmentectomy (n = 1) and local excision (n = 5). Cardiac procedures consisted of coronary artery bypass grafting (CABG) in 11, aortic valve replacement in one and mitral valve repair with CABG in one patient. In all but one case the lung resection was performed prior to heparinization and cardiopulmonary bypass (CPB). In two patients, with suitable coronary anatomy, myocardial revascularization without CPB was performed to reduce morbidity. RESULTS: There was no hospital mortality. Postoperative blood loss and ventilation requirements were reduced in the patients who were operated on without CPB. Prolonged ventilatory support was required in two cases. All patients with benign pathology are alive. In the lung cancer group there have been five late deaths: disseminated metastatic disease (n = 3), anticoagulant related haemorrhage (n = 1) and broncho-pleural fistula (n = 1). Of the remaining five patients four are alive and disease free 7-23 months post-operatively; one patient has recurrent disease 40 months post-operatively. CONCLUSIONS: Simultaneous pulmonary resection and cardiac surgery is associated with acceptable operative morbidity and mortality. In patients with lung carcinoma long-term survival was determined by tumour stage. The avoidance of CPB may be advantageous by decreasing blood loss and ventilation requirements.     

Pregnancy induced hypertension complicated with cerebrovascular accidents

Fourteen patients suffering from pregnancy induced hypertension (PIH) complicated with cerebrovascular accidents were admitted for treatment from 1977-1990. These were 8 cases of cerebral hemorrhage, 4 cases of cerebral infarction and 2 cases of cerebral arteriovenous malformation with intracerebral hematomas. These accounted for 0.34% of all hospitalized PIH cases during the same period and three died. The mortality rate was 0.72%. The etiology, pathology, brain CT scan features, clinical manifestations and treatment of these accidents were discussed.     

Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients

OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].     

Unique monocyte subset in patients with AIDS dementia

BACKGROUND: 15-30% of patients infected with HIV will develop a debilitating dementia. Whilst HIV enters the brain soon after infection, presumably within monocyte-derived macrophages, not all patients with HIV become demented. Blood monocytes probably cross the blood-brain barrier and give rise ultimately to parenchyma macrophages. We looked for a specific monocyte subset in AIDS patients with dementia. METHODS: Peripheral blood monocytes from three groups were compared: AIDS patients with (n = 12) and without (n = 11) dementia, and ten HIV seronegative healthy controls. We used flow cytometry to analyse monocytes, and cell lysis and apoptosis assays to examine monocyte effects on human brain cells in vitro. FINDINGS: We found a unique subset of monocytes in patients with AIDS dementia. These monocytes were more dense and granular and expressed CD14/CD16 and CD14/CD69. Means (SD) for CD14/CD16 in HIV-negative controls and in AIDS non-dementia and AIDS dementia patients were 6.5% (4), 16% (13), and 37% (21), respectively (p = 0.008 between the two groups of patients). The corresponding means for CD14/CD69 were 7% (6), 8% (10), and 69% (18) (p < 0.0001). INTERPRETATION: CD69 is a member of the natural-killer-cell gene complex that is expressed after activation. Supernatants from cultures containing these dense cells can trigger apoptosis of human brain cells in vitro. The monocyte subset we found in patients with AIDS dementia might enter the brain and expose neural cells to toxic factors.     

Use of fluorocitrate and fluoroacetate in the study of brain metabolism

Between 1984 and 1994, of the 375 patients admitted to our department for intracerebral hemorrhage (ICH), 24 (6.4%) had a recurrent ICH. There were 15 women and nine men and the mean age of the patients was 64.7 +/- 9.4 years (range 49-81) at the first bleeding episode and 68.7 +/- 7.5 years (range 57-83) at the second. The mean interval between the two bleeding episodes was 47.5 +/- 30.5 months (range 3 months to 14.8 years). Nine patients presented with more than one recurrence of ICH. Seventy-one percent of the patients were hypertensive. The site of the first hemorrhage was lobar in 17 patients, ganglionic (putamen, thalamus, or caudate nucleus) in six patients, and subdural in one. The recurrent hemorrhage occurred at a different location from the previous ICH. The most common pattern of recurrence was "lobar-lobar" (14 patients) and more rarely "ganglionic-ganglionic" (five patients), which was always observed in hypertensive patients. The outcome after the recurrent hemorrhage was usually poor, with severe cognitive impairment. By comparison with 81 patients followed up to 24 months (47.9 +/- 22.2 months) with isolated ICH without recurrence, only lobar hematoma and a younger age were risk factors for recurrences whereas sex and previous hypertension were not. The mechanisms of recurrence of ICH were multiple (hypertension, cerebral amyloid angiopathy). Control of blood pressure after the first hemorrhage may prevent ICH recurrences.     

Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage

BACKGROUND AND PURPOSE: A common G-to-T point mutation (Val 34 Leu) in exon 2 of the alpha-subunit of the factor XIII is strongly negatively associated with the development of myocardial infarction. This result suggests that factor XIII Val 34 Leu is interfering with the formation of cross-linked fibrin. The role of factor XIII Val 34 Leu in the pathogenesis of cerebral infarction and primary intracerebral hemorrhage is unknown. METHODS: Six hundred twelve patients with acute stroke, defined by World Health Organization criteria and cranial CT, and 436 age-matched control subjects free of cerebrovascular disease were genotyped for the factor XIII Val 34 Leu mutation. Venous blood was drawn for the determination of hemostatic variables and lipids. Factor XIII genotype was determined through a single-stranded conformational polymorphism technique and plasminogen activator inhibitor (PAI)-1 4G/5G promoter genotype by allele-specific polymerase chain reaction. RESULTS: The mutation was more frequent in patients with primary intracerebral hemorrhage (n=62) (54.8%; P=.05) than in control subjects (41.7%) or in patients with cerebral infarction (n=529) (46.5%; P=.22). There was no relationship between PAI-1 levels and the PAI-1 4G/5G genotype. CONCLUSIONS: There was a slightly higher incidence of factor XIII Val 34 Leu in patients with PICH. This may be related to impaired cross-linking of fibrin and/or coagulation proteins.