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Computed tomographic angiography (CTA) was invented more than 20 years ago, but only gained acceptance recently, thanks to advancements in the computer technology. It can demonstrate areas of arterial stenosis or occlusion with accuracy nearly that of digital subtraction angiography (DSA). It is also able to clearly illustrate calcification, which is more difficult to define on magnetic resonance angiography and is not clearly depicted on DSA.Our retrospective study attempted to clarify the rate of occlusion or stenosis in the patients with acute ischemic stroke.Over the period of 7 months, 93 consecutive patients were admitted with acute ischemic stroke. Fifty-six patients underwent CTA and were included in this study. Most of the patients were admitted after 6 hours following onset of symptoms. There were 28 men and 28 women, and 80.4% of the cohort was of African-American origin. The majority of strokes were attributed to small-vessel disease (25/56). The rest of the cases were deemed secondary to atheroembolism (15/56), cardioembolism (9/56) or of unclear etiology (7/56). In 24 (42.9%) patients, CTA failed to reveal any abnormalities of the cerebrovascular tree. CTA demonstrated arterial occlusion in ten (17.9%) patients and stenosis of extracranial or intracranial arteries on the symptomatic side in 22 (39.2%) patients. There was very good correlation between CTA and ultrasound techniques (carotid duplex and transcranial Doppler). CTA was superior in demonstrating distal intracranial stenosis.Overall, CTA is an extremely valuable and fast way to emergently evaluate the cerebrovascular anatomy, making it very useful for pre-thrombolysis evaluation of patients with ischemic stroke.

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare cause of status epilepticus. Review of literature demonstrated only four cases of brief status epilepticus (SE) associated with TTP. We describe a young woman with yet incomplete neurological recovery after prolonged refractory status epilepticus. Management required pentobarbital-induced coma for 60 days. Five months after onset, she was conversant and oriented with continued neuromuscular deficits. This is an unusual presentation of severe refractory SE associated with TTP. With aggressive life support and prolonged pentobarbital infusion, however, survival and the chance of meaningful recovery appear to be possible.

One of the important histological changes in cerebral vasospasm after subarachnoid hemorrhage (SAH) is endothelial cell damage, which involves apoptosis. The current study was undertaken to determine whether anti-apoptosis therapy prevents apoptosis and reverses vasospasm in a dog SAH model. Twenty-three mongrel dogs of either sex, weighing 17–25 kg, were subjected to autologous arterial blood injection into the cisterna magna on day 0 and day 2, and sacrificed on day 7. Angiography was performed on day 0 before blood injection and on day 7 before sacrifice. Caspase-2 (Z-VDVAD-FMK, 10 μM) inhibitor, caspase-3 (Z-DEVD-FMK, 10 μM) inhibitor, or vehicle (DMSO) were injected intrathecally from day 2 to day 6. The effects of caspase inhibitors on apoptosis and vasospasm were evaluated by angiography and transmission electron microscopy. The residual diameter of the basilar artery on day 7 in SAH dogs without treatment was 53.4±5.5% of the day 0 diameter. Marked damage to the endothelial cells, including apoptotic like changes, was observed in these arteries. Both caspase inhibitors prevented apoptosis in the endothelial cells. Only caspase-3 inhibitor, however, had a near- significant effect on reducing 13.3% of angiographic vasospasm. Higher doses and early treatment, as well as other more potent apoptosis inhibitors, are recommended for future studies.

BACKGROUND Morphological presentations of cerebral vasospasm, such as dystrophy and desquamation of endothelial cells, corrugation of the internal elastic layer, and necrotic changes in smooth muscle cells, are well defined in large cerebral arteries. This study was undertaken to examine pathological changes in cerebral penetrating arteries in a canine double hemorrhage model. METHODS Eighteen mongrel dogs were subjected to an autologous arterial blood (0.4 mL/kg) injection into the cisterna magna on day 0 and day 2 after withdrawal of an equivalent amount of cerebrospinal fluid. Angiogram was performed on day 0 before the blood injection and on the day the dogs were sacrificed. The dogs were divided into four groups: control (day 0) (n = 4), hemorrhage and sacrificed on day 3 (n = 4), day 5 (n = 5), and day 7 (n = 5). The penetrating arteries were removed and found to be spastic on days 3, 5, and 7, but not in the control group. RESULTS Endothelial dystrophy and partial desquamation were recorded in all dogs sacrificed on days 5 and 7. Condensation of chromatin, blebbing of the membrane, and condensation of cytoplasm were identified in many endothelial cells, features that are consistent with apoptosis. The morphological changes in the penetrating arteries were more pronounced on days 5 and 7. CONCLUSIONS Vasospasm occurred in cerebral penetrating arteries in a canine double hemorrhage model. The morphological change in penetrating arteries, especially apoptosis in endothelial cells, is consistent with an early phase of vasospasm. Vasospasm in a penetrating artery may contribute to the cerebral ischemia that occurs during vasospasm.

BACKGROUND Vasospasm in the penetrating arteries contributes to ischemic neurological deficit. It may be as important as angiographic vasospasm because it would explain the discrepancies between angiographic vasospasm and clinical symptoms in some patients. It may also underlie the different effects of vasodilators. The present study examined this hypothesis by looking at the effect of the inhibitors of mitogen-activated protein kinase (MAPK) on vasospasm of the penetrating arteries. METHODS Twenty-two adult mongrel dogs of either sex were used for the dog double-hemorrhage model. The dogs were randomly divided into four groups: control-hemorrhage, vehicle-treated, PD98059-treated, and U0126-treated groups. The drug injections were started on Day 3 after the first subarachnoid hemorrhage (SAH). The clinical status of the dogs was studied, based on their activity, appetite, and focal neurological symptoms. On Day 7, all the dogs were sacrificed, and the penetrating arteries from the brain stem were prepared for transmission electron microscopy. RESULTS (1) Severe vasospasm developed in the basilar arteries in the SAH-without-treatment group (control), in the DMSO-treated group (DMSO), and in the U0126 treatment group with mean reduction of the basilar artery diameter of 46.57%, 49.3%, and 39.6%, respectively. In the PD98059-treatment group only a mild vasospasm was observed and the mean reduction of the basilar artery diameter was 18.9%. (2) All the dogs in the control SAH and vehicle-treated groups developed severe angiographic and clinical vasospasm. The penetrating arteries were contracted, and the endothelial and smooth muscle cells were dystrophic. (3) The dogs in the U0126-treated group developed severe angiographic, but not clinical, vasospasm. The penetrating arteries were not contracted, and the endothelial and smooth muscle cells were not dystrophic. (4) The dogs in the PD98059 group developed mild angiographic vasospasm. No dog developed clinical symptoms that could be attributed to vasospasm. In morphological studies, the penetrating arteries were slightly contracted, but the cells were not dystrophic. CONCLUSIONS Vasospasm of the penetrating arteries, but not angiographic vasospasm, is consistent with the clinical symptoms and signs of vasospasm. MAPK may be important in maintaining vasospasm of both major and penetrating cerebral arteries. The correlation of the improvement in the clinical score with the reduction of vasospasm in the penetrating arteries demonstrated an important role of penetrating arteries in the morbidity and mortality caused by SAH.

Background and Purpose —We have previously reported that extracellular ATP activates P 2u receptors and increases intracellular free Ca 2+ ([Ca 2+ ] i ) by G protein/phospholipase C/inositol 1,4,5-triphosphate pathways in cerebral artery smooth muscle cells. However, the possible contribution of other signaling pathways remains unclear. This study was undertaken to investigate the role of protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) in mediating ATP-induced Ca 2+ mobilization in rat basilar artery smooth muscle cells (RBASMCs). Methods —RBASMCs were freshly isolated, and [Ca 2+ ] i was monitored by fura 2 microfluorimetry. MAPK phosphorylation was studied by the Western blot technique. Results —ATP produced a biphasic [Ca 2+ ] i response, which consists of releasing Ca 2+ from internal stores and influx from extracellular space. PTK inhibitors tyrphostin 51 and genistein inhibited [Ca 2+ ] i response to ATP. Tyrphostin A1, an inactive analogue of tyrphostins, failed to reduce the ATP-induced response. MAPK kinase inhibitor PD98059, but not U0126, reduced the ATP-induced [Ca 2+ ] i response. Phosphatidylinositol 3-kinase (PI3-K) tyrosine kinase inhibitor wortmannin, but not janus tyrosine kinase (JAK2) inhibitor AG490, partially inhibited the [Ca 2+ ] i response induced by ATP. In addition, ATP enhanced MAPK phosphorylation in a concentration- and time-dependent manner, and genistein, tyrphostin 51, PD98059, and U0126 inhibited MAPK phosphorylation. Conclusions —Extracellular ATP produced [Ca 2+ ] i elevation and MAPK phosphorylation in RBASMCs, and the effect was regulated by PTK. The role of MAPK in ATP-induced [Ca 2+ ] i elevation is not clear. PI3-K tyrosine kinase and JAK2 tyrosine kinase may not play an important role in the ATP-induced [Ca 2+ ] i response in RBASMCs.

BACKGROUND Cerebral vasospasm after subarachnoid hemorrhage is a prolonged contraction that leads to cerebral ischemia or infarction. Morphological studies of cerebral arteries during vasospasm have shown extensive necrosis of smooth-muscle cells and desquamation and dystrophy of endothelial cells. The mechanism of cellular death is unknown. METHODS We report an observation of apoptotic changes in the cerebral arteries of a patient who died after suffering severe cerebral vasospasm caused by aneurysmal rupture. Subarachnoid hemorrhage and cerebral vasospasm were confirmed by computed tomography scanning and angiogram. Histological and immunohistological examinations for apoptosis were performed in cerebral arteries. For control, the arteries from another patient, who died of trauma without head injury, were used. RESULTS Corrugation of the internal elastic lamina and increased amounts of connective tissue was demonstrated by light microscopy. Apoptotic changes, characterized by condensation of chromatin of the nucleus and detachment from the basal membrane, were found on transmission electron microscopy in endothelial cells. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling reaction revealed positive staining of the nuclei of the endothelial cells. CONCLUSIONS This study demonstrates that apoptosis occurred in the cerebral arteries in a patient who died of cerebral vasospasm. The possible role of apoptosis in cerebral vasospasm is discussed.

The pathogenesis of cerebral vasospasm that follows aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. Multiple methods have been used to clarify the mechanism of spasmogen-induced vasospasm, however, each method has its own limitations. Cultured cells lose their phenotype and inter-cellular interactions, and animal models are expensive and can be used only in some established centers. Isolated cerebral arteries have been used extensively to study the contractility by transient exposure to spasmogens that, however, can hardly represent cerebral vasospasm that occurs 2-4 days after SAH. In this study, we cultured arteries with bloody cerebrospinal fluid (CSF) from patients of cerebral vasospasm and studied the contractility of the arteries 1, 3 and 4 days later. This method preserves artery wall structure, prolongs exposure of artery to bloody CSF, and is simple and inexpensive. Cultured rat aorta showed enhanced contractile response to 5-HT (p < 0.001) but reduced response to KCl (p < 0.05) 4 days after culturing with bloody CSF. We concluded that the contractility of arteries was modified by prolonged incubation with bloody CSF. Our observations in this study could be important and may explain some aspects of pathogenesis of cerebral vasospasm.

BACKGROUND Percutaneous transluminal angioplasty (PTA) dilates constricted arteries at the circle of Willis to reverse cerebral ischemia caused by cerebral vasospasm. Although 90% of the patients show angiographic improvement after PTA, only 70% show clinical improvement. Why some patients do not improve after PTA is unknown. We report on a 48-year-old woman who failed to improve after PTA and died from aneurysm rerupture. Pathologic studies were performed to determine why PTA failed to reverse the symptoms of cerebral ischemia. METHODS The arteries of the brain were studied by light microscopy using Gomori’s trichrome stain. The arteries were also studied by scanning and transmission electron microscopy. RESULTS The arteries that were dilated with PTA showed compression of the connective tissue, stretching of the internal elastic lamina, and a combination of compression and stretching of the smooth muscle. The small arteries and arterioles that had been treated with an infusion of intra-arterial papaverine were constricted with a thickened intimal layer. CONCLUSION The persistence of cerebral vasospasm in small and perforating arteries may contribute to the failure of cerebral ischemia to reverse after PTA.

In this study, we have reviewed our experience with anticoagulation-associated intraventricular hemorrhage (IVH). Our goal was to determine if IVH is also an independent prognosticator of fatal outcome in patients with anticoagulation-associated intracerebral hemorrhage (ICH).This study is a retrospective analysis of medical records and computed tomographic imaging. Eighty-eight patients with warfarin-associated ICH were analysed, including eight patients with predominant IVH.There was a very low rate of hemorrhage extension in patients with predominant IVH. Despite that, those patients had 50% 30 day mortality. Overall patients with ICH had 45% 30 day mortality. Ventricular extension raised mortality in ICH patients to 75%, while the absence of ventricular extension carried only 23% 30 day mortality. IVH was significantly associated with 30 day mortality (p0.001). Panventricular extension was uniformly fatal in patients with ICH and carried 75% 30 day mortality in patients with predominant IVH. On a multivariate logistic regression model including age, ICH volume and IVH, ICH volume (p0.001) and IVH (p = 0.003) remained independently associated with early mortality.Extension of anticoagulation-associated ICH into ventricular system caused a high mortality, especially in patients with panventricular involvement. IVH is an independent predictor of early death in these patients. In our experience, the majority of IVH do not expand over time and poor outcome appears to be related to the magnitude of the initial insult.

Acute bilateral acute carotid arteries occlusion is a very rare condition. We describe a patient with initial right middle cerebral artery syndrome who developed coma and quadriplegia 1 h after thrombolysis with intravenous tPA and was found to have bilateral cervical internal carotid artery occlusion.

Background and Purpose— Analyze the relationship between the location and extent of sinus thrombosis and presence and severity of brain lesions. Methods— Retrospective chart and neuroimaging review of patients with documented CVST. A CVST score was devised to quantify the extent of cerebral venous sinus thrombosis. Results— Nineteen of 56 (34%) patients had brain lesions. The extent of sinus thrombus was associated with increased risk of brain lesions (CVST score 1.9 among patients without brain lesions versus 3.1 in those with lesions; P =0.006). Age, sex, and acquired or hereditary thrombophilias were not associated with the risk of parenchymal lesions. Functional outcomes were favorable even in patients with extensive CVST and parenchymal lesions at presentation. Conclusions— The extent of the sinus involvement correlates with the risk of brain lesions in patients with CVST, but additional factors might also contribute to their occurrence.

Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage. The delayed occurrence of this complication allows for preventive management and early therapeutic interventions. Yet, accurate and timely diagnosis remains challenging and therapeutic options are rather limited. This review discusses new developments in the diagnosis and medical management of cerebral vasospasm made possible by technological advances and growing understanding of the complex pathophysiology of this disorder. CT protocols including CT perfusion and MRI with diffusion and perfusion sequences are increasingly employed in the evaluation of patients with suspected vasospasm. These radiological studies can add important information to that provided by transcranial Doppler and conventional angiography. Nimodipine for the prevention of delayed functional sequelae and hemodynamic augmentation therapy for the treatment of symptomatic vasospasm remains the mainstay of medical management. Novel strategies under investigation include the use of endothelin receptor antagonists, magnesium sulphate and statins. The value of albumin is being formally studied in an ongoing trial. Interventions to enhance nitric oxide may prove viable in the near future.

Background Reinitiating warfarin sodium therapy in a patient with a recent warfarin-related intracerebral hemorrhage (WAICH) is a difficult clinical decision. Therefore, it is important to assess the outcome of resumption or discontinuation of warfarin therapy after WAICH. Objective To compare patients who survived an episode of WAICH and restarted warfarin therapy with a group of WAICH patients who did not resume warfarin therapy. Design, Setting, and Patients We conducted a follow-up study from November 1, 2001, through December 31, 2005, in a cohort from a single center. Long-term outcome was assessed at last clinical follow-up or via questionnaire. Main Outcome Measures Recurrent WAICH and thromboembolic events. Results Fifty-two patients were discharged from the hospital after a diagnosis of WAICH. Four patients were lost to follow-up. Mean follow-up among all patients was 43 (range, 1-108) months. Of the 23 patients who restarted warfarin therapy, 1 had a recurrent nontraumatic WAICH, 2 had traumatic intracerebral hemorrhages, and 2 had major extracranial hemorrhages. Of the 25 patients who did not restart warfarin therapy, 3 had a thromboembolic stroke, 1 had a pulmonary embolus, and 1 had a distal arterial embolus. Conclusions Restarting warfarin therapy in patients with a recent WAICH is associated with a low risk of recurrence, but patients are subjected to known, substantial risks of warfarin use. Withholding warfarin therapy is associated with a risk of thromboembolization.

Background Intracerebral hemorrhage (ICH) associated with warfarin sodium therapy is becoming more common as the use of this medication increases in the aging population. Objective To delineate factors associated with early mortality, determine variables responsible for poor functional outcome, and evaluate possible reasons for expansion of hemorrhage and associated parenchymal edema. Design Retrospective study of clinical and radiologic information for 88 patients with warfarin-associated ICH. Setting A single hospital. Patients Eighty-eight consecutive patients with warfarin-associated ICH. Methods Patients were included if the international normalized ratio (INR) at presentation with ICH was 1.5 or greater. Computed tomographic scans were reviewed for volumetric analysis of hematoma and perihematomal edema volume. Outcome variables included 7-day mortality, hematoma enlargement, and functional outcome based on the modified Rankin Scale score. Results Seven-day mortality (39.8%) was associated with a lower Glasgow Coma Scale sum score and larger ICH volume at presentation. Univariate analysis revealed that a lower Glasgow Coma Score sum score, larger initial ICH volume, higher initial and 48-hour maximum glucose concentrations, and higher percentage of ICH expansion were significantly associated with poor functional outcome at hospital discharge. At multivariate analysis, only Glasgow Coma Score and ICH volume remained significantly associated with functional outcome measured at hospital discharge and at the last follow-up visit. Conversely, INR at presentation, time to INR correction, initial blood pressure, and enlargement of edema were not associated with functional outcome either at hospital discharge or at the last follow-up. Neither serum glucose concentration at admission nor highest level during the first 48 hours had any correlation with ICH or parenchymal edema enlargement. In addition, neither initial INR nor time to INR correction correlated with expansion of ICH or parenchymal edema. Conclusions Lower level of consciousness at presentation and larger initial ICH volume predict poor prognosis in patients with warfarin-associated ICH. In our study population, INR at presentation was not associated with functional outcome.

An 18-year-old man with anaplastic oligoastrocytoma was pronounced brain dead based on absent confounding factors, absent brainstem reflexes, apnea with CO2 challenge, and isoelectric EEG. Plantar flexion, triple flexion response, and …

The potential causes of acquired macroglossia are extensive. The authors report two cases of subacute marked tongue swelling resulting in airway compromise in patients with refractory status epilepticus requiring prolonged pentobarbital coma. The hospitalization histories of the reported patients were retrospectively reviewed. The tongue swelling completely resolved in one case and significantly improved in the other after discontinuation of pentobarbital infusion or switching to phenobarbital. The authors speculate that the causes were multifarious, likely a combination of localized angioedema due to barbiturate vehicle and triggered by an initial tongue bite. Progressive tongue swelling causing airway obstruction can occur well beyond the acute phase of status epilepticus and may potentially cause problems with extubation in nontracheotomized patients.

Background: Amyloidosis is an uncommon disorder that ultimately leads to fatal multiorgan failure. Ischemic strokes have been sporadically described but are not well characterized. The purpose of this study was to review the pathophysiologic relationship between primary systemic amyloidosis and ischemic stroke, and to determine how often stroke is the first defining manifestation. Methods: Retrospective study of 49 patients with confirmed primary amyloidosis and ischemic stroke. All included patients had biopsy proven amyloidosis. Results: Forty patients were included in the study. Ischemic strokes occurred in 13 patients (32.5%) as the initial presentation of amyloidosis. Patients with initial stroke presentation had the worst outcome, with average survival of 6.9 months after established diagnosis with amyloidosis; strokes developed 9.6 months before diagnosis with primary amyloidosis. Thirty-seven percent experienced recurrent ischemic stroke. The majority (70%) of patients had cardioembolic infarctions. Conclusions: Ischemic stroke is an underappreciated complication of primary amyloidosis. In the absence of obvious clinical and cardiogenic manifestations, primary amyloidosis should be considered when echocardiography demonstrates thickening of the valves, restrictive pattern, and increased echogenicity. Ischemic strokes as an initial presentation of primary amyloidosis carries a worse prognosis.

Subarachnoid hemorrhages caused by intracranial dissections are rare. The management of dissections in these cases not clear.Case report.An 82-year-old woman presented with acute drowsiness and vomiting. CT scan demonstrated extensive subarachnoid hemorrhage and hydrocephalus that subsequently required placement of ventriculoperitoneal shunt. Angiography revealed extensive basilar artery dissection and no aneurysms. The dissection did not produce a critical stenosis and, taking into consideration that the patient had a previous occlusion of her distal left vertebral artery, it was decided to manage the patient conservatively. On a 3-month follow-up, the patient was free of recurrent events.Basilar artery dissection can present with subarachnoid hemorrhage. No guidelines are available for management of basilar artery dissections and treatment should be tailored to the individual patient.

We describe a case of the patient with multiple contraindications for thrombolysis who underwent successful mechanical embolectomy for occlusion of the right carotid terminus. Her pre-procedural NIHSS was 16.The patient demonstrated remarkable recovery within an hour of the procedure, and this clinical improvement was sustained at followup.This case illustrates that mechanical embolectomy is a safe and potentially very effective intervention to treat major intracranial vessel occlusions in patients with multiple contraindications for thrombolysis.

Confluent rat aortic smooth muscle cells were treated with OxyHb in a concentration- and time-dependent manner. A high concentration of OxyHb (100 μM) within 24 h decreased cell density. DNA analysis showed a smear pattern characteristic of cell necrosis. Transmission electron microscopy demonstrated disintegration of the cell membrane and destruction of cell organelles. Western blotting using PARP antibody revealed that 116 kDa PARP was not cleaved to 85 kDa, an apoptosis-related fragment. On the contrary, a low concentration of OxyHb (10 μM) produced apoptotic cell death at 72 h that was supported by DNA analysis and TUNEL staining. These results demonstrated that a high level of OxyHb induced necrosis within 24 h and a low concentration of OxyHb produced apoptosis after 72 h in cultured smooth muscle cells. Morphological alterations induced by OxyHb might contribute to the vascular wall changes in the cerebral arteries following subarachnoid hemorrhage (SAH).

Background and Purpose —It has been suggested that mitogen-activated protein kinase (MAPK) is involved in cerebral vasospasm after subarachnoid hemorrhage. The present study was undertaken to explore the inhibitory effect of U0126, a novel MAPK inhibitor, in the contraction of the rabbit basilar artery by 3 spasmogens: hemolysate, oxyhemoglobin, and bloody cerebrospinal fluid (CSF) from patients with vasospasm. Methods —The contraction and relaxation of rabbit basilar arteries were measured by isometric tension. MAPK immunoprecipitation was assessed by Western blot analysis. Results —(1) Pretreatment of the rabbit basilar arteries with U0126 reduced contractions to hemolysate, oxyhemoglobin, or bloody CSF applied subsequently. (2) In the absence of endothelial cells, U0126 produced an inhibitory effect similar to the contractions induced by hemolysate, oxyhemoglobin, or bloody CSF. (3) U0126 relaxed the sustained contraction induced by hemolysate, oxyhemoglobin, or bloody CSF. (4) Hemolysate, oxyhemoglobin, and bloody CSF enhanced MAPK immunoprecipitation. (5) U0126 reduced MAPK immunoprecipitation induced by hemolysate, oxyhemoglobin, and bloody CSF. (6) Hemolysate, oxyhemoglobin, and bloody CSF significantly increased MAPK activity in the rabbit basilar artery. (7) U0126 abolished the effect of hemolysate, oxyhemoglobin, or bloody CSF on MAPK activation. Conclusions —This study demonstrated a role of MAPK in the contraction of rabbit basilar arteries by hemolysate, oxyhemoglobin, and bloody CSF. MAPK inhibitor U0126 may be useful in the treatment of cerebral vasospasm.

Endothelin-1 (ET-1), a potent vascular smooth muscle constrictor, is one of the possible spasmogens in cerebral vasospasm. However, the role of ET-1 in non-muscle compaction (another aspect of the pathogenesis of cerebral vasospasm) has not been reported. This study was undertaken to demonstrate the effect of ET-1, as well as erythrocyte lysate and bloody cerebrospinal fluid (CSF), on fibroblast populated collagen lattice (FPCL) compaction. Human dermal fibroblasts were used to form FPCL. The concentration-dependent effect of ET-1 was examined in the absence and presence of an ETA receptor antagonist (BQ-485), or an ETB receptor antagonist (BQ-788), or both. FPCL compaction was determined by measuring reduction of areas over five days following treatment. To compare the effect of ET-1 on lattice compaction, erythrocyte lysate and bloody CSF obtained from a cerebral vasospasm patient were also tested. We found that ET-1 increased FPCL compaction in a concentration-dependent (but not time-dependent) manner. Erythrocyte lysate produced the strongest compaction, however, without time-dependence. Bloody CSF promoted FPCL compaction in a time-dependent fashion. Compaction induced by ET-1 was inhibited by BQ-485 but not by BQ-788. We concluded that ET-1 promotes FPCL compaction by activation of ETA receptors. Other components in bloody CSF or erythrocytes may also contribute to FPCL compaction.

BACKGROUND Post-traumatic vasospasm is a well-recognized sequela of head injury. The risk factors associated with post-traumatic vasospasm have not been well defined. We studied 119 consecutive patients with head injury to determine the risk factors for post-traumatic vasospasm. METHODS Twenty-nine (27.1%) patients were excluded from the study because of poor insonation (n = 12) or a hospital stay of less than 72 hours (n = 17). Seventy (77.8%) of 90 patients suffered severe head injury. Sixteen (17.8%) patients sustained moderate head injury and four (4.4%) patients sustained mild head injury. All patients were monitored with transcranial Doppler (TCD) ultrasonography daily. RESULTS Post-traumatic vasospasm was detected in 32 (35.6%) of 90 patients. Among these patients, 29 (90.6%) had severe head injury, and three (9.4%) had moderate head injury. None of the patients with mild head injury suffered post-traumatic vasospasm. In most cases, the onset of post-traumatic vasospasm began on the fifth day and lasted 1 to 9 days. In 8 (25%) patients, post-traumatic vasospasm began within the first three days of the head injury. Among 32 patients with post-traumatic vasospasm, 10 (31.2%) patients had mild vasospasm, 20 (65.5%) had moderate vasospasm, and 2 (6.3%) had severe post-traumatic vasospasm. Clinical deterioration was documented in two (2.5%) patients. CONCLUSIONS Development of post-traumatic vasospasm correlated only with severe subarachnoid hemorrhage on initial computed tomographic scan. There was an increased incidence of post-traumatic vasospasm in patients with epidural hematomas, subdural hematomas, and intracerebral hemorrhages. The Glasgow Coma Scale (GCS) score on admission was inversely related to the development of post-traumatic vasospasm. In most cases, the period of vasospasm was short and clinical deterioration was rare. Probably, two varieties of post-traumatic vasospasm exist, one that lasts a shorter time and does not correlate with the presence of SAH, and a second that correlates with the presence of SAH, lasts longer, and resembles aneurysmal vasospasm.

Over the years, The Hopkins Neurocritical Care group has carefully studied the effect of hypertonic solutions clinically and experimentally. The recent report by Koenig et al.1 invites the following comments. Hypertonic saline or mannitol could improve neurologic examination in a patient with a new mass. We and others have observed rapid dramatic changes with osmotic agents. For example, we have observed dilated pupils and extensor responses at baseline, but soon after injection, pupils normalize and improvement to localization to noxious stimuli is seen. Koenig et al. and the editorialists suggest the immediacy of such a response is reversal of transtentorial herniation (TTH), but evidence of that is not provided; there are few clinical details except a GCS sumscore and no CT or MR studies. We are not certain that the clinical improvement is due to decompression or dislodging of tissue squeezed through the tentorium. In fact, when the effects are studied in mannitol, change in midline shift is not observed as changes are too minimal or almost too subtle to catch the eye on serial MRI.2 Many consider that osmotic diuresis cannot physiologically explain the rapid improvement (within 30 minutes or less in many patients). Alternatively, sudden hypertonicity may cause vasodilatation of the cerebral resistance vessels and with an …

Head injury is one of the leading causes of morbidity and mortality in the young population. Many factors complicate head injury and worsen an outcome. One of these factors is posttraumatic cerebral vasospasm. We studied 75 patients admitted to the University of Mississippi Medical Center with head injury. Their ages ranged from 14 to 67 years (mean 30 years, SD 11.63). Eighty percent of the patients were men, and 20% were women. Of these patients, 53 (70.6%) suffered severe blunt trauma, and 4 patients suffered gunshot wounds to the head. Four patients had mild head injury, and 14 had moderate head injury. Posttraumatic vasospasm was detected in 24 (32%) patients. Among these patients, 19 (79.2%) had severe closed head injury, 3 patients had moderate head injury, and 2 suffered gunshot wounds. The severity of the patient's respective condition was correlated with the development of posttraumatic cerebral vasospasm: 50% of the patients with Glasgow Coma Scale (GCS) 3-4 developed PTV, and only 30% with GCS 9-11, and none of the patients with GCS12 developed PTV. Overall, posttraumatic vasospasm started earlier and had a shorter course than did aneurysmal vasospasm. Morphologically, posttraumatic vasospasm resembled the features of aneurysmal vasospasm. We found increased corrugation of the internal elastic lamina and increased amounts of connective tissue in the subendothelial layer. These findings show that posttraumatic vasospasm, although clinically more mild, demonstrates the same morphological changes as aneurysmal vasospasm.

BACKGROUND This is the first report on the use of intra-arterial papaverine and percutaneous transluminal angioplasty in two patients with severe, symptomatic cerebral vasospasm who suffered ruptured arteriovenous malformations (AVMs). CASE DESCRIPTIONS The source of hemorrhage was a venous aneurysm in the first case and a pedicular aneurysm of the distal posterior inferior cerebellar artery in the second case. In both cases, the AVMs were located in the superior vermis and there was minimal subarachnoid hemorrhage. The first patient underwent removal of the AVM before the period of cerebral vasospasm and the second patient underwent removal of the AVM after the cerebral vasospasm had resolved. The outcome was excellent in the first patient and poor in the second patient. CONCLUSION Arteriovenous malformation with ruptured aneurysms may be at high risk for cerebral vasospasm even when there is minimal subarachnoid hemorrhage. We recommend early treatment of AVMs with ruptured pedicular, intranidal, or venous aneurysms to avoid rebleeding and to allow for aggressive treatment of cerebral vasospasm. The management of cerebral vasospasm after AVM rupture is discussed.