Effects of traumatic subarachnoid hemorrhage on pathological properties in diffuse brain injury: a comparison with aneurysmal subarachnoid hemorrhage

As a result of recent advances in continuous monitoring equipment, it has been reported that vasospasm (VS) and delayed ischemic neurological deficit (DIND) occur as frequently in traumatic subarachnoid hemorrhage (TSAH) as in subarachnoid hemorrhage due to ruptured intracranial aneurysm (ASAH), and these VS and DIND have been reported to affect the outcome of TSAH adversely in many cases. When we compared TSAH secondary to diffuse brain injury (DBI) with ASAH, however, these two conditions were evidently different from each other in nature. Then we compared laboratory data, clinical course, and outcomes of TSAH associated with DBI with those of ASAH, to determine whether TSAH results in poor outcomes of DBI. On CT scans, patterns of SAH distribution were different from each other, and SAH was detected in 76% of the patients with ASAH on day 4, whereas only 2.0% of the patients with TSAH had detectable SAH on day 3. The incidence rates of detectable SAH in both groups remained significantly different from each other after day 2. The cerebral blood flow (CBF) decreased to around 75% of the normal flow in the acute stage of ASAH, and it decreased further to around 65% in the subacute stage. In TSAH, in contrast, CBF varied widely among the patients. The average CBF decreased to about 70% in the acute stage, and then it increased to around the lower limit of the normal range in the subacute stage. The urinary output and serum concentration of low molecular protein compositions in TSAH were markedly different from those in ASAH. In addition, the contour of a low density area (LDA) in CT scans in the subacute-chronic stage was the same as that of the area supplied by the artery being constricted due to cerebro-vascular spasm in ASAH. In TSAH, in contrast, hardly any LDA had a form that was suggestive of this conjuction, with cerebro-vascular spasm and the incidence rate of LDAs was significantly different from that for ASAH. About 30% of the patients with ASAH had ventricular enlargement, which was diagnosed as normal pressure hydrocephalus by cisternography, in the chronic stage. Surgical shunting was effective for these patients. In TSAH, ventricular enlargement was observed in more than 50% of the patients, but almost none of these patients underwent surgical shunting, because it resulted from cerebral atrophy. Regardless of causes of SAH, the severer SAH was, the more often patients had a poor outcome. The outcome of TSAH was, however, significantly poorer than that of ASAH. When SAH was traumatic, it disappeared by the time VS developed and, in addition, changes in CBF and the form and incidence rate of LDAs were different from those in ASAH. We concluded that, although TSAH is an adverse prognostic factor for DBI, it does not contribute to poor outcomes of DBI by giving rise to DIND caused by VS.     

Pretruncal nonaneurysmal subarachnoid hemorrhage

BACKGROUND: Integrins are cell surface receptors which, in part, mediate the adhesion of cells to the extracellular matrix. In addition to providing a molecular "glue" essential for tissue organization and survival, integrins are dynamic signaling molecules. Integrins allow normal, nontransformed cells to sense that they are adhered to the extracellular matrix, thus providing a cell survival signal. This signal allows cells to proliferate in the presence of growth factors and in some instances prevents apoptosis. Integrins also mediate cell migration as it occurs in normal processes such as angiogenesis, wound healing, immune system function, and development. Aberrances in the expression and function of integrins contribute to many disease states including cancer. RESULTS: Focal adhesion kinase (FAK) becomes phosphorylated and activated during integrin-mediated cell adhesion. Focal adhesion kinase is a signal transducer of integrins (and certain soluble growth factors). Cells derived from FAK -/- mouse embryos exhibit reduced migration relative to wild-type cells. Cells which overexpress FAK show increased migration relative to wild-type cells. Focal adhesion kinase promotes cell survival under certain in vitro conditions. Focal adhesion kinase is overexpressed in invasive and metastatic colon, breast, thyroid, and prostate cancers. Enhanced FAK immunostaining is detected in small populations of preinvasive (carcinoma in situ) oral cancers and in large populations of cells in invasive oral cancers. CONCLUSIONS: Focal adhesion kinase is probably not a classical oncogene but may be involved in the progression of cancer to invasion and metastasis. It is hypothesized that overexpression of FAK in subpopulations of tumor cells leads to populations of cells with a high propensity toward invasion and metastasis. Focal adhesion kinase would have a dual role in this regard: Overexpression of FAK leads to (1) increased cell migration and (2) increased cell survival under anchorage-independent conditions. Further work is needed to test this model and to determine whether FAK represents a viable target for anticancer therapy.     

Myocardial stunning in hypertrophic cardiomyopathy with normal coronary arteries

Very little has been reported about how patients use home ultraviolet B (UVB) phototherapy. A survey of thirty-one patients who were prescribed a home UVB phototherapy unit to treat psoriasis was performed as a pilot study of home UVB phototherapy usage; twenty-two patients responded. Generally, respondents reported home UVB phototherapy to be very helpful for their psoriasis. We conclude that home UVB is an effective and appropriate treatment for many patients with psoriasis, but screening and education of candidates for home UVB phototherapy is important to ensure compliance with the treatment program.     

Hemodynamics of subarachnoid hemorrhage arrest

Subarachnoid hemorrhage (SAH) causes a spectrum of clinical syndromes from mild discomfort to rapid brain death. The reason for these heterogeneous consequences is poorly understood. A canine autologous shunt model of SAH was used to study this problem. The duration and volume of hemorrhage into the suprasellar cistern at each animal's mean arterial blood pressure were measured at variable hemorrhage flow rates. At high rates of bleeding in seven dogs (18.7 +/- 2.2 ml/min, mean +/- standard deviation), hemorrhage duration was significantly less (191 +/- 116 seconds, p < 0.03) and hemorrhage volume was significantly greater (15.1 +/- 7.0 ml, p < 0.05) than at low flow rates. At low flow rates of bleeding in nine dogs (4.4 +/- 2.2 ml/min), hemorrhage duration was 394 +/- 202 seconds and volume was 10.9 +/- 6.5 ml. Cerebral perfusion pressure (CPP) decreased at all hemorrhage rates but never to 0 mm Hg (perfusion arrest). No correlation between a decrease in CPP and SAH volume or duration was identified. The initial flow rate of SAH had a positive linear correlation with the volume of hemorrhage (23 dogs, r = 0.64, p < 0.01). The data suggest that initial SAH flow rate, and not CPP, has a primary influence on hemorrhage arrest. This finding may influence the clinical rationale for acute management of SAH-induced brain injury.     

Treatment of aneurysmal subarachnoid hemorrhage

Subarachnoid hemorrhage is a formidable and common health care problem. Early diagnosis and management are crucial to reduce the morbidity form this complex and multifaceted disease. Open surgery and endovascular techniques both aim at eliminating the source of hemorrhage. The choice of therapy can be made rationally based on an understanding of the merits, risks, and limitations of each therapy. The care of pregnant patients with subarachnoid hemorrhage and patients who harbor both aneurysms and AVMs can be approached rationally with an understanding of the complex pathophysiology behind these clinical scenarios. Familiarity with the signs of mild SAH, and advances in familial screening, noninvasive imaging, and therapies for vasospasm will continue to lessen the toll of this dramatic illness on the public well-being.     

Cerebral blood flow in subarachnoid hemorrhage

Myelin protein zero (MPZ, P0) is well known as the adhesion molecule responsible for the compaction of the myelin sheath of peripheral nerves. Mutations are linked to Charcot-Marie-Tooth syndrome type 1B (CMT1B) and the more severe Dejerine-Sottas syndrome (DSS). Three mutations leading to phenotypes of increasing severity (Ser34del/CMT1B, Ser34Cys/DSS, INS663GC/DSS) were expressed in S2 insect cells and resulted in a decreased adhesion capability in correlation with their respective phenotypes.     

Cardiopulmonary complications in acute subarachnoid hemorrhage

Pathologic electrocardiogram (ECG) may be present in more than 90% of patients with subarachnoid haemorrhage. The ECG findings are often transient and may mimic acute myocardial ischaemia or infarction. These ECG findings may cause diagnostic problems in patients with subarachnoid haemorrhage who are unconscious or who have atypical symptoms. Life-threatening arrhythmias are also seen and may be responsible for sudden deaths in patients with subarachnoid haemorrhage. Other signs of myocardial injury, such as ventricular wall motion dysfunction, elevated enzymes, and histological evidence of contraction band necrosis are described. The myocardial dysfunction known as neurogenic stunned myocardium is reversible if the patient survives the acute phase, but it may lead to haemodynamic instability and contribute to the origin of neurogenic pulmonary oedema. The myocardial injury in subarachnoid haemorrhage may be due to a massive sympathetic stimulation of the myocardium in response to rapidly increasing intracranial pressure. We illustrate myocardial injury and dysfunction in a case report where a patient had subarachnoid haemorrhage with ventricular fibrillation, pulmonary oedema, left ventricular dysfunction and ST-segment elevation, initially thought to be acute myocardial infarction.     

Acute vasoconstriction after subarachnoid hemorrhage

OBJECTIVE: Decreased cerebral blood flow (CBF) and cerebral ischemia occurring immediately after subarachnoid hemorrhage (SAH) may be caused by acute microvascular constriction. However, CBF can also be influenced by changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The goal of these experiments was to assess the significance of acute vasoconstriction after SAH and its relationship to changes in CBF, ICP, CPP, and extracellular glutamate concentrations. METHODS: Three experiments were performed using the endovascular filament technique to produce SAH. In the first experiment, CBF, ICP, and CPP were measured for 60 minutes after SAH (n = 21) and were correlated with the 24-hour mortality rate. In the second experiment, rats undergoing SAH (n = 23) or a sham procedure (n = 7) were perfused 60 minutes after SAH for measurement of the circumference and wall thickness of the internal carotid and anterior cerebral arteries and correlation with CBF, ICP, and CPP. In the third experiment (n = 11), extracellular glutamate concentrations determined by hippocampal and cortical microdialysis and high performance liquid chromatography were correlated with physiological changes. RESULTS: CBF reductions to less than 40% of baseline for 60 minutes after SAH predicted 24-hour mortality with 100% accuracy and were used to define "lethal" SAH. In contrast, ICP and CPP 60 minutes after SAH were not correlated with the mortality rate. The vascular circumference was significantly smaller in lethal than in sublethal SAH or sham-operated rats (P < 0.001). Vessel measurements were correlated with both CBF and hemorrhage size (P < 0.01). Extracellular glutamate concentration increased to 600% of baseline after lethal SAH in both hippocampus and cortex and was inversely correlated with CBF (r = 0.9, P < 0.001) but did not increase after sublethal SAH. CONCLUSION: Acute vasoconstriction after SAH occurs independently of changes in ICP and CPP and is associated with decreased CBF, larger hemorrhage size, persistent elevations of extracellular glutamate, and poor outcome. Acute vasoconstriction seems to contribute directly to ischemic brain injury after SAH. Further evaluations of pharmacological agents with the potential to reverse acute vasoconstriction may increase CBF and improve outcome.     

Acute hydrocephalus after subarachnoid hemorrhage

The coracoid process is a part of the scapula and plays an important role in shoulder function. The present case demonstrates bilateral separation of the coracoid processes from the scapular bodies. The cause of this condition was thought to be a failure of fusion of the ossification centers of the coracoid processes with the scapular bodies. Bilateral unfused coracoid processes was identified incidentally in a patient with recurrent dislocation in the left shoulder. However, history of antecedent trauma to the coradoid region was not found. It would be important to distinguish this condition from fracture or nonunion of the coracoid process.     

Risk factors for subarachnoid hemorrhage: a systematic review

BACKGROUND AND PURPOSE: Knowledge of modifiable risk factors for subarachnoid hemorrhage (SAH) is important in terms of prevention. We therefore conducted a systematic review of studies on risk factors for SAH, with emphasis on sufficiently precise criteria for the diagnosis of SAH. METHODS: To identify studies we performed a Medline search from 1966 to 1994 and searched the reference lists of all relevant publications. Studies were included only if they fulfilled predefined methodological criteria. Case-control studies were included if the diagnosis of SAH was proved by CT, angiography, or autopsy in at least 70% of patients. Longitudinal studies were included if the criteria for SAH were based on a review of the medical records. RESULTS: Nine longitudinal studies and 11 case-control studies were included. Significant risk factors were as follows: (1) smoking (relative risk [RR] for longitudinal studies, 1.9; 95% confidence interval [CI], 1.5 to 2.3; odds ratio [OR] for case-control studies, 3.5; 95% CI, 2.9 to 4.3); (2) hypertension (RR, 2.8; 95% CI, 2.1 to 3.6; OR, 2.9; 95% CI, 2.4 to 3.7) and (3) drinking 150 g or more of alcohol per week (RR, 4.7; 95% CI, 2.1 to 10.5; OR, 1.5; 95% CI, 1.1 to 1.9). Use of oral contraceptives, hormone replacement therapy, hypercholesterolemia, and physical activity were not significantly related to the risk of SAH. CONCLUSIONS: We conclude that smoking, hypertension, and alcohol abuse are important risk factors for SAH. Reduction of exposure to these risk factors might result in a decreased incidence of SAH.     

Oxidative stress in the human brain after subarachnoid hemorrhage

OBJECT: The aim of this study was to verify the patterns of antioxidant enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the human brain after subarachnoid hemorrhage (SAH) to verify whether an "oxidative stress situation" characterizes the brain response to subarachnoid bleeding. METHODS: Forty samples of gyrus rectus or temporal operculum that were obtained during a surgical approach to anterior circulation aneurysms were used for this study. The activity of total SOD, GSH-Px, and the SOD/GSH/Px ratio (which expresses the balance between the production of hydrogen peroxides by dismutation of superoxide radicals and the scavenging potential) were calculated in each case. Twelve samples were obtained from patients who underwent surgery for unruptured aneurysms (control group); 13 samples were obtained during surgical procedures performed within 72 hours of SAH; and 15 samples were obtained during delayed surgical procedures (> 10 days post-SAH). Ten patients presented with clinical deterioration caused by arterial vasospasm. In both SAH groups, the mean total SOD activity was significantly higher than in the control group (p=0.029). The mean activity of GSH-Px did not differ significantly between the SAH and control groups (p=0.731). There was a significant increase in the SOD/GSH-Px ratio in both SAH groups, as compared with controls (p < 0.05). There was a significant correlation between the enzymatic activity and the clinical severity of the hemorrhage, with findings of lower values of SOD and, mainly, of the SOD/GSH-Px ratio in the poor-grade patients. The SOD/GSH-Px ratio was 2.14+/-0.44 in patients who presented with clinical vasospasm and 1.24+/-0.2 in cases without vasospasm. CONCLUSIONS: The results of this study show an imbalance of the antioxidant enzymatic activities in the human brain after SAH. which is linked to the severity of the initial bleeding and possibly modified by the development of arterial vasospasm.     

Prevalence of risk factors in spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage

OBJECTIVE: To evaluate whether differences exist in the occurrence of modifiable risk factors between aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage, since these stroke subtypes have frequently been combined in epidemiological studies and labeled hemorrhagic stroke. DESIGN: Cross-sectional survey. SETTING: Helsinki University Central Hospital in Helsinki, Finland. PATIENTS: One hundred fifty-six consecutive patients with spontaneous intracerebral hemorrhage aged 16 to 60 years (96 males and 60 females) and 281 patients with aneurysmal subarachnoid hemorrhage (145 males and 136 females) who were admitted to an emergency department. MAIN OUTCOME MEASURES: Prevalence of several health habits, previous diseases, and medication of patients with spontaneous intracerebral hemorrhage were compared with that of patients with subarachnoid hemorrhage using multiple logistic regression. RESULTS: Hypertension (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.6-4.3), diabetes mellitus (OR, 26.4; 95% CI, 3.1-221.6), alcohol intake within the preceding week (for 1-150 g of alcohol: OR, 2.0; 95% CI, 1.1-3.6; for 151-300 g of alcohol: OR, 1.7; 95% CI, 0.8-3.8; and for > 300 g of alcohol: OR, 4.4; 95% CI, 2.1-9.1), and anticoagulant treatment (OR, 21.8; 95% CI, 2.3-207.3) were all significantly more common, but current cigarette smoking (OR, 0.3; 95% CI, 0.2-0.5) was less common in patients with intracerebral hemorrhage than in those with subarachnoid hemorrhage simultaneously after adjustment for sex, age, and body mass index. In males, hypertension (OR, 2.3; 95% CI, 1.1-4.5) and alcohol intake (for > 300 g/wk: OR, 5.8; 95% CI, 2.2-15.7) were more common, but current smoking (OR, 0.2; 95% CI, 0.1-0.4) was less common in patients with intracerebral hemorrhage than in those with subarachnoid hemorrhage after adjustment for age, body mass index, and diabetes mellitus. In females, hypertension (OR, 2.9; 95% CI, 1.4-5.8) and anticoagulant treatment (OR, 10.0; 95% CI, 1.0-100.2) were more common in patients with intracerebral hemorrhage after adjustment for age and body mass index. In univariate statistics, patients with intracerebral hemorrhage were also older, more often had previous symptoms of cerebral ischemia, and had higher values for body mass index and gamma-glutamyltransferase than did those with subarachnoid hemorrhage. CONCLUSIONS: Hypertension, diabetes mellitus, anticoagulant treatment, and amount of alcohol taken within 1 week seem more commonly to be associated with intracerebral hemorrhage than with subarachnoid hemorrhage, which is, however, associated more frequently with cigarette smoking.     

Spontaneous subarachnoid hemorrhage: risk factors

The precursive factors to SAH are classified into congenital, familial, intrinsic and extrinsic, pointing out the association between cerebral aneurysms and collagenopathies, genetic transmission disease, aneurysm features, habits and systemic disease.     

Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage

A review of pre- and postoperative prone knee flexion (PKF) data after isolated hamstring tenotomy for 52 patients with cerebral palsy (CP) at an average follow-up of 3 years 4 months showed the frequency of diminished knee flexion to be 71%. Twenty-three percent of the knees actually had improved flexion, whereas 6% were unchanged. On the average, patients' flexion decreased 14.4 degrees from a preoperative PKF of 131.5 degrees to 117.1 degrees postoperatively (p < 0.0001). Only 11.5% of patients had PKF < 90 degrees at most recent follow-up, however; only 1.9% had PKF < 60 degrees. Thirteen percent of ambulators eventually required a rectus femoris transfer to correct "stiff-legged gait."     

Transcranial Doppler in vertebrobasilar vasospasm after subarachnoid hemorrhage

OBJECTIVE: The primary objective of this study was to assess the incidence of vertebrobasilar vasospasm after subarachnoid hemorrhage (SAH) by means of transcranial Doppler ultrasonography and to evaluate the clinical significance of this phenomenon. The secondary objective was to analyze the different factors influencing the development, the severity, and the duration of vertebrobasilar vasospasm. METHODS: Fifty-seven patients with traumatic SAH and 44 patients with spontaneous SAH were evaluated and monitored by means of transcranial Doppler ultrasonography. Vasospasm of the anterior and middle cerebral arteries was defined by mean flow velocities (FVs) exceeding 120 cm per second and at least three times the FV of the internal carotid artery. Vasospasm of the basilar and vertebral arteries was defined by a mean FV exceeding 60 cm per second. RESULTS: Vasospasm of the anterior or middle cerebral arteries was found in 27 patients and was associated with vertebrobasilar spasm in 20 patients. FVs in anterior circulation vessels were neither related to the cause of the SAH nor did they correlate with the outcome. Forty-six patients (45.5%) had FVs exceeding 60 cm per second and 25 (24.8%) had FVs exceeding 85 cm per second. In 10 of these patients, direct or computed tomographic angiography showed arterial narrowing involving the vertebrobasilar system, whereas in 21 more patients, computed tomography disclosed a cerebral infarction involving the vertebrobasilar vascular territory. Vertebral artery FVs in this group were twice that of the ipsilateral carotid artery. Vertebrobasilar vasospasm was significantly more frequent after head injury, although it was not related to the type of intracranial lesion or the Glasgow Coma Scale score at admission. It did correlate, however, with outcome (P < 0.0001) and with the intensity of SAH (P < 0.0001). Delayed neurological deterioration occurred in 14 patients and was significantly more frequent in patients with basilar artery FVs above 85 cm per second (P < 0.001). Prognosis, however, could not be reliably predicted by FVs in the basilar artery, even when an FV of 110 cm per second was chosen for prediction criterion. CONCLUSION: These results suggest that vertebrobasilar vasospasm is more common than previously thought, especially in association with head injury, with which it may significantly contribute to brain stem ischemic lesions and therefore justify specific therapeutic measures.