Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome.

OBJECTIVE: To determine whether early seizures that occur frequently after intracerebral hemorrhage (ICH) lead to increased brain edema as manifested by increased midline shift. METHODS: A total of 109 patients with ischemic stroke (n = 46) and intraparenchymal hemorrhage (n = 63) prospectively underwent continuous EEG monitoring after admission. The incidence, timing, and factors associated with seizures were defined. Serial CT brain imaging was conducted at admission, 24 hours, and 48 to 72 hours after hemorrhage and assessed for hemorrhage volume and midline shift. Outcome at time of discharge was assessed using the Glasgow Outcome Scale score. RESULTS: Electrographic seizures occurred in 18 of 63 (28%) patients with ICH, compared with 3 of 46 (6%) patients with ischemic stroke (OR = 5.7, 95% CI 1.4 to 26.5, p < 0.004) during the initial 72 hours after admission. Seizures were most often focal with secondary generalization. Seizures were more common in lobar hemorrhages but occurred in 21% of subcortical hemorrhages. Posthemorrhagic seizures were associated with neurologic worsening on the NIH Stroke Scale (14.8 vs 18.6, p < 0.05) and with an increase in midline shift (+ 2.7 mm vs -2.4 mm, p < 0.03). There was a trend toward increased poor outcome (p < 0.06) in patients with posthemorrhagic seizures. On multivariate analysis, age and initial NIH Stroke Scale score were independent predictors of outcome. CONCLUSION: Seizures occur commonly after ICH and may be nonconvulsive. Seizures are independently associated with increased midline shift after intraparenchymal hemorrhage.

Oral (drinking water) two-generation reproductive toxicity study of dibromoacetic acid (DBA) in rats.

In a two-generation study of dibromoacetic acid (DBA), Crl SD rats (30 rats/sex/group/generation) were provided DBA in drinking water at 0 (reverse osmosis-deionized water), 50, 250, and 650 ppm (0, 4.4 to 11.6, 22.4 to 55.6, and 52.4 to 132.0 mg/kg/day, respectively; human intake approximates 0.1 microg/kg/day [0.0001 mg/kg/day]). Observations included viability, clinical signs, water and feed consumption, body and organ weights, histopathology, and reproductive parameters (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios and viabilities, maternal behaviors, reproductive organ weights, sperm parameters and implantation sites, sexual maturation). Histopathological evaluations were performed on at least 10 P and F1 rats/sex at 0 and 650 ppm (gross lesions, testes, intact epididymis; 10 F1 dams at 0, 250, and 650 ppm for primordial follicles). Developmental observations included implantations, pup numbers, sexes, viabilities, body weights, morphology, and reproductive performance. At 50 ppm and higher, both sexes and generations had increased absolute and relative liver and kidneys weights, and female rats in both generations had reduced absolute and relative adrenal weights; adrenal changes were probably associated with physiological changes in water balance. The livers and kidneys (10/sex/group/generation) had no histopathological changes. Other minimal effects at 50 ppm were reduced water consumption and a transient reduction in body weight. At 250 and 650 ppm, DBA reduced parental water consumption, body weight gains, body weights, feed consumption, and pup body weights. P and F1 generation male rats at 250 and 650 ppm had altered sperm production (retained step 19 spermatids in stages IX and X tubules sometimes associated with residual bodies) and some epididymal tubule changes (increased amounts of exfoliated spermatogenic cells/residual bodies in epididymal tubules, atrophy, and hypospermia), although inconsistently and at much lower incidences. Unilateral abnormalities of the epididymis (small or absent epididymis) at 650 ppm in four F1 generation male rats were considered reproductive tract malformations. The no-observable-adverse-effect level (NOAEL) and reproductive and developmental NOAELs for DBA were at least 50 ppm (4.5 to 11.6 mg/kg/day), 45,000 to 116,000 times the human adult exposure level. Reproductive and developmental effects did not occur in female rats exposed to DBA concentrations as high as 650 ppm. Based on the high multiples of human exposure required to produce effects in male rats, DBA should not be identified as a human reproductive or developmental risk.

Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage.

BACKGROUND: It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. OBJECTIVE: To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. METHOD: Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. RESULTS: Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. CONCLUSIONS: A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.

Surgical and endovascular treatment of spinal dural arteriovenous fistulas: long-term disability assessment and prognostic factors.

OBJECT: The authors assessed clinical outcomes of patients with treated spinal dural arteriovenous fistulas (DAVFs) and investigated prognostic factors. METHODS: Thirty consecutive patients with spinal DAVFs were treated at the authors' institution during the past 15 years: seven underwent surgery; seven underwent surgery after failed embolization: and 16 underwent embolization alone. The outcomes of gait and micturition disability, were analyzed. Follow up averaged 3.4 years (range 1 month-11.8 years). Age, duration of symptoms, pre- and postintervention magnetic resonance (MR) imaging findings, and preintervention disability were correlated with outcome. Seventeen patients (57%) experienced improved gait, 12 (40%) were unchanged, and one (3%) was worse. In 11 patients (37%) micturition function was improved, in 15 (50%) it was unchanged, and in four (13%) it was worse. Gait disability, as measured by the Aminoff-Logue Scale, was significantly improved after treatment, from 3.4+/-1.4 (average +/- standard deviation) to 2.7+/-1.5 (p = 0.007). Mean micturition disability scores decreased, but not significantly, from 1.9+/-1 to 1.6+/-1.1 (p = 0.20). Preintervention gait disability was not associated with improvement except for patients with Aminoff-Logue Scale Grade 4 disability (eight of nine improved; p = 0.024). For patients treated within 13 months of symptom onset, mean micturition disability decreased (p = 0.035). No association was found between clinical improvement and age, a symptom duration less than 30 months, or pre- and postintervention MR imaging-documented spinal cord edema. CONCLUSIONS: Spinal DAVF treatment significantly improved patients' mean gait disability score by almost one grade at last follow up. The mean micturition disability score was not significantly improved, unless treatment was performed within 13 months of symptom onset. Longer and more uniform follow-up study is needed to determine if improved and stabilized clinical outcomes are sustained.

N-butyl 2-cyanoacrylate embolization of spinal dural arteriovenous fistulae.

BACKGROUND AND PURPOSE: Because they are not well established, we investigated the technical success and recurrence rates of n-butyl 2-cyanoacrylate (NBCA) embolization of spinal dural arteriovenous fistulae (SDAVF), and assessed clinical outcomes. METHODS: We retrospectively studied all patients with SDAVF treated by NBCA embolization at our institution over an 8-year period. Gait and micturition disabilities were analyzed. Follow-up periods averaged 3.1 years (range, 1 month to 8.9 years). RESULTS: NBCA embolization was feasible in 74% (20/27) of patients. Of 20 patients who underwent embolization, initial embolization failure occurred in two (10%) and fistula occurrence in three (15%). All five patients in whom NBCA embolization failed underwent surgery. All patients who underwent embolization had either improved (55%) or unchanged (45%) gait disability at last follow-up. Seventeen (85%) patients had improved (40%) or unchanged (45%) micturition disability, but three (15%) had worsened. Mean Aminoff gait disability grade significantly decreased at last follow-up (2.4 [1.4] average [SD] vs 3.2 [1.4] [P = .0008]). Mean micturition disability grade decreased, but not significantly (1.4 [1.0] vs 1.7 [1.1] [P = .28]). CONCLUSION: NBCA embolization of SDAVF was technically feasible in 75% of patients. Initial apparent successful embolization was achieved in 90%; the fistula recurrence rate (failure to occlude the draining vein) for NBCA was 15%. Comparing favorably to surgical series, NBCA embolization of SDAVF appears efficacious, significantly improving mean gait disability by almost one grade at last follow-up. Close clinical and angiographic surveillance is mandatory. Longer and more uniform follow-up is needed to determine if clinical improvement and stabilization after NBCA embolization are sustained.

Endoscopic management of cysticercal cysts within the lateral and third ventricles.

OBJECT: In this report the authors review their 3-year experience with the endoscopic management of patients with hydrocephalus who harbored cysticercal cysts within the third and lateral ventricles. The management plan was to utilize an endoscopic approach to remove the cysts and to incorporate techniques useful in treating obstructive hydrocephalus. The ultimate goals were to avoid having to place a complication-prone cerebrospinal fluid shunt and to eliminate the risk of complications related to cyst degeneration. METHODS: A retrospective analysis of 10 patients with hydrocephalus and cysticercal cysts within the third or lateral ventricles who were endoscopically managed was performed. A general description of the instrumentation and technique used for removal of the intraventricular cysts is given. At presentation, neuroimaging revealed findings suggestive of obstructive hydrocephalus in eight patients. Seven of the 10 patients treated endoscopically were spared the necessity of shunt placement. Three successful third ventriculostomies and one therapeutic septum pellucidotomy were performed. Despite frequent rupture of the cyst walls during removal of the cysts, there were no cases of ventriculitis. The endoscopic approach allowed successful removal of a cyst situated in the roof of the anterior third ventricle. One patient suffered from recurrent shunt obstructions secondary to a shunt-induced migration of cysts from the posterior fossa to the lateral ventricles. CONCLUSIONS: The endoscopic removal of third and lateral ventricle cysticercal cysts, combined with a third ventriculostomy or septum pellucidotomy in selected cases, is an effective treatment in patients with hydrocephalus and should be considered the primary treatment for this condition.

Retrograde transvenous perfusion.

Serious consequences of stroke dictate that new approaches to the treatment of stroke be investigated. We have developed a method for perfusing the patient's own arterial blood retrograde through the venous system to ischemic brain tissue. This treatment has proven beneficial in preventing and reversing serious injury in the laboratory and in a small clinical trial. The laboratory investigation has also demonstrated that this therapy, retrograde transvenous neuroperfusion, can be coupled with hypothermia to potentially increase its benefit. History, experimental development, and the clinical trial are reviewed in this article.

Endoscopic resection of colloid cysts: surgical considerations using the rigid endoscope.

OBJECTIVE: Colloid cysts of the third and lateral ventricles have traditionally been treated by transfrontal and transcallosal microsurgical resection or by stereotactic aspiration. Recently, rigid and flexible ventricular endoscopic techniques have been used to treat these lesions. Our study was undertaken to examine the efficacy of rigid endoscopy in the resection of colloid cysts. METHODS: Fifteen patients with a radiological diagnosis of colloid cysts were given the option of undergoing either endoscopic surgery or craniotomy. The average tumor size was 1.43 cm. Fourteen patients underwent planned endoscopic resections, and a craniotomy was performed initially in one patient. RESULTS: Entire tumor resection was achieved with the endoscope in 12 patients (86%). A craniotomy was required for two colloid cysts that could not be resected endoscopically. In total, complete radiographic resections were achieved in 14 patients (93%). There were no permanent complications, although postoperative deficits included short-term memory loss and hemiparesis, each in one patient. CONCLUSION: Rigid endoscopy affords good optical resolution, high magnification, and excellent illumination. Total or near total resection of colloid cysts should be the goal for all patients and can be achieved using the rigid endoscope, with little morbidity, shortened operative time, reduced length of stay, and resolution of symptoms. Although long-term follow-up is needed, we think that endoscopy should be considered as a primary treatment for most patients.

Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils.

OBJECT: The purpose of this paper is to present the authors' experience with Guglielmi detachable coil (GDC) embolization of multiple intracranial aneurysms and to evaluate the results of this therapy in single-stage procedures. METHODS: Clinical and angiographic evaluations were performed in 38 consecutive patients with multiple intracranial aneurysms treated by GDC embolization between March 1990 and October 1997. Twenty-nine patients presented with subarachnoid hemorrhage (SAH), four with mass effect, and five were asymptomatic. These 38 patients harbored 101 aneurysms, 79 of which were treated with GDCs, 14 by surgical clipping, and eight were left untreated. Of the GDC-treated lesions, a complete endovascular occlusion was achieved in 55 aneurysms (70%), and 24 (30%) presented neck remnants. Twenty-five patients (66%) underwent GDC embolization of more than one aneurysm in the first session. Eighteen (86%) of 21 patients with acute SAH underwent treatment for all aneurysms within 3 days after admission (15 of 21 in one session). Follow-up angiographic studies in 30 patients demonstrated an unchanged or improved result in 94% of the aneurysms (59 lesions) and coil compaction in 6% (four lesions). The overall clinical outcome was excellent in 34 patients (89%), good in one (3%), fair in one (3%), and death in two (5%). CONCLUSIONS: Endovascular treatment of multiple intracranial aneurysms, regardless of their location, with GDCs was performed safely in one session, even during the acute phase of SAH. Treatment of all aneurysms in one session protected the patient from rebleeding and eliminated the risk of mistakenly treating only the unruptured aneurysms.

Endoscopic management of cysticercal cysts within the lateral and third ventricles.

In this report the authors review their 3-year experience with the endoscopic management of patients with hydrocephalus who harbored cysticercal cysts within the third and lateral ventricles. The management plan was to utilize an endoscopic approach to remove the cysts and to incorporate techniques useful in treating obstructive hydrocephalus. The ultimate goals were to avoid having to place a complication-prone cerebrospinal fluid shunt and to eliminate the risk of complications related to cyst degeneration. A retrospective analysis of 10 endoscopically managed patients with hydrocephalus and cysticercal cysts within the third or lateral ventricles was performed. A general description of the instrumentation and the technique used for removal of the intraventricular cysts is given. At presention, neuroimaging revealed findings suggestive of obstructive hydrocephalus in eight patients. Seven of the 10 patients treated endoscopically were spared the necessity of shunt placement. Three successful third ventriculostomies and one therapeutic septum pellucidotomy were performed. Despite frequent rupture of the cyst walls during removal of the cyst, there were no cases of ventriculitis. The endoscopic approach successfully allowed removal of a cyst situated in the roof of the anterior third ventricle. One patient suffered from recurrent shunt obstructions secondary to a shunt-induced migration of cysts from the posterior fossa to the lateral ventricles. The endoscopic removal of third and lateral ventricle cysticercal cysts, combined with a third ventriculostomy or septum pellucidotomy in selected cases, is an effective treatment in patients with hydrocephalus and should be considered the primary treatment for this condition.

Unruptured aneurysms presenting with mass effect symptoms: response to endosaccular treatment with Guglielmi detachable coils. Part I. Symptoms of cranial nerve dysfunction.

OBJECT: Embolization of intracranial aneurysms by using Guglielmi detachable coils (GDCs) is proving to be a safe method of protecting aneurysms from rupture. Occasionally, patients with unruptured intracranial aneurysms present with symptoms related to the aneurysm's mass effect on either the brain parenchyma or cranial nerves. In the present study, the authors conducted a retrospective review to evaluate the response to GDC embolization in a series of 19 patients presenting with cranial nerve dysfunction due to mass effect. METHODS: Aneurysms were classified by size, shape, wall calcification, and amount of intraluminal thrombus. Patients were classified by duration of symptoms prior to GDC treatment (range < 1 month to > 10 years). Clinical assessment was performed within days of the GDC procedure and at later follow-up appointments (range 1-70 months, mean 24 months). In the immediate post-GDC period, four patients experienced worsening of cranial nerve deficits. Two of the four patients had transient worsening of visual acuity, which later improved to better than baseline status. Another patient who had presented with headache and seventh and eighth cranial nerve deficits from a vertebrobasilar junction aneurysm had improvement in these symptoms, but developed a new diplopia. The fourth patient had worsening of her visual acuity, which had not resolved at the 1-month follow-up examination; this patient later underwent surgical decompression. CONCLUSIONS: On late follow-up review, the response was classified as complete resolution of symptoms in six patients (32%), improvement in eight patients (42%), no significant change in four patients (21%), and symptom worsening in one patient (5%). Patients with smaller aneurysms and those with shorter pretreatment duration of symptoms were more likely to experience an improvement in their symptoms following GDC treatment, although statistical significance was not reached in this series (p=0.603 and p=0.111, respectively). The presence of aneurysmal wall calcification (six patients) or intraluminal thrombus (12 patients) showed no correlation with the response of mass effect symptoms in these patients.

Retrograde transvenous neuroperfusion: a back door treatment for stroke.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and the leading cause of adult disability in the United States. The clot-lysis drug tissue plasminogen activator is the only treatment that has been effective for acute stroke patients, yet there are significant limitations to its use and effectiveness. In this study retrograde transvenous neuroperfusion (RTN) was evaluated for its efficacy in reversing acute ischemia, preventing paralysis, and limiting pathological evidence of infarction in baboons. METHODS: Ten adult male baboons underwent 3.5 hours of reversible middle cerebral artery occlusion (MCAO) under isoflurane (0.25% to 1.5%) anesthesia. Five randomly chosen animals received RTN treatment 1 hour after start of MCAO. Somatosensory evoked potentials were recorded during MCAO. Animals were assigned daily neurological scores. Animals were killed 6 days after MCAO, and brains were quantitatively analyzed for infarct volume. RESULTS: Within 1 hour after RTN was started, treated animals showed significantly improved somatosensory evoked potentials (103.3% versus 75% of baseline; P<0.01). Likewise, the combined neurological score for the RTN-treated group was 99.2, while the combined mean score for the untreated group was 66.4 (P<0.015). The mean infarction volume was 8.8+/-3.1% (of contralateral hemisphere) for the control group and 0.3+/-0.2% for the RTN-treated group (P<0.01). No increased mortality was seen in the RTN-treated group. CONCLUSIONS: We conclude that RTN treatment during MCAO effectively reverses the pathophysiological sequelae of ischemia, even when the treatment is initiated 1 hour after the onset of ischemia. Although the infarct volume in the control group was variable when quantitatively assessed 6 days after 3.5 hours of MCAO, virtually no evidence of infarcts was seen in the RTN-treated group.

Endoscopy and stereotaxy for aneurysms.

The combination of the endoscope and frameless stereotaxy improves surgical results by allowing the surgeon to look around structures and into tight spaces, monitor the success of aneurysm clipping, decrease the risk of perforator or cranial nerve injury, plan the surgical approach, and track surgical instruments in the surgical field. This article discusses the use of endoscopy and frameless stereotaxy in aneurysm surgery.

Incidence of cerebral vasospasm after endovascular treatment of acutely ruptured aneurysms: report on 69 cases.

Cerebral vasospasm is the most common cause of morbidity and mortality in patients admitted to the hospital after suffering aneurysmal subarachnoid hemorrhage (SAH). The early surgical removal of subarachnoid clots and irrigation of the basal cisterns have been reported to reduce the incidence of vasospasm. In contrast to surgery, the endovascular treatment of aneurysms does not allow removal of subarachnoid clots. In this study the authors measured the incidence of symptomatic vasospasm after early endovascular treatment of acutely ruptured aneurysms with Guglielmi detachable coils (GDCs). Sixty-nine patients classified as Hunt and Hess Grades I to III underwent occlusion of intracranial aneurysms via GDCs within 72 hours of rupture. The amount of blood on the initial computerized tomography (CT) scan was classified by means of Fisher's scale. Symptomatic vasospasm was defined as the onset of neurological deterioration verified with angiographic or transcranial Doppler studies. Hypertensive, hypervolemic, hemodilution therapy, with or without intracranial angioplasty, was used to treat vasospasm after GDC placement. Symptomatic vasospasm occurred in 16 (23%) of 69 patients. The clinical grade at admission and the amount of blood on the initial CT were both associated with the incidence of subsequent vasospasm. At 6-month clinical follow-up examination, 12 of these 16 patients experienced a good recovery, two were moderately disabled, and two patients had died of vasospasm. In conclusion, the 23% incidence of symptomatic vasospasm in this series compares favorably with that found in conventional surgical series of patients with acute aneurysmal SAH. These results indicate that endovascular therapy does not have an unfavorable impact on cerebral vasospasm.

Intracranial aneurysms treated with the Guglielmi detachable coil: midterm clinical results in a consecutive series of 100 patients.

A prospective study was designed to evaluate clinical outcome in a series of 100 consecutively treated patients who underwent endovascular embolization of 104 intracranial aneurysms using Guglielmi detachable coils (GDCs). Midterm clinical outcome (2-6 years, average 3.5 years) was obtained for 94 patients and was classified according to a modified Glasgow Outcome Scale. Of nine patients treated in the acute phase of severe subarachnoid hemorrhage (Grade IV or V), seven died from the initial hemorrhage, one had a poor outcome, and one had a fair midterm outcome, with no post-GDC embolization hemorrhages. Twenty patients underwent subsequent surgical or endovascular procedures that did not include the use of GDCs. These included aneurysm clipping in nine patients and parent vessel sacrifice in 11 patients. None of these 20 patients experienced post-GDC embolization hemorrhage. The postoperative midterm clinical outcomes of these 20 patients did not significantly differ from the outcomes of patients who underwent GDC embolization as their definitive treatment. Six patients died of unrelated causes prior to reaching the 2-year survival point, with no post-GDC embolization hemorrhage. The midterm outcomes of the remaining 61 patients who underwent GDC embolization as their definitive treatment were classified as excellent (46 patients [75%]), good (seven patients [11%]), fair (three patients [5%]), poor (one patient [2%]), or dead (four patients [7%]). All four patients died from giant lesions. At midterm follow up, the surviving 57 patients' neurological statuses were unchanged or improved in 54 cases and worsened in three cases. The midterm post-GDC embolization hemorrhage rate was 0% for small aneurysms, 4% (one case) for large aneurysms, and 33% (five cases) for giant lesions. The GDC procedure is a safe, effective, and reliable means of preventing aneurysm hemorrhage in patients with small and large intracranial aneurysms. Results, however, are less satisfactory in cases involving giant lesions. Further follow-up review is necessary to establish durability in the longer term. Patients with Grade IV or V subarachnoid hemorrhage in this series generally had poor outcomes even if the GDC procedure was successful in occluding the aneurysm.

Thalamostriate artery aneurysm within the third ventricle. Case report.

The authors report the case of a 7-mm saccular aneurysm, located within the third ventricle and arising from the distal portion of a thalamostriate artery. The patient presented with an intraventricular hemorrhage and was treated via a frontotemporal craniotomy with translamina-terminalis approach for resection of the aneurysm. The etiology of the aneurysm was presumed to be idiopathic. Previously only one other third ventricular aneurysm has been reported. An intraventricular aneurysm arising from a perforating artery should therefore be considered as a rare cause of an intraventricular hemorrhage. Potential surgical approaches to third ventricular aneurysms are discussed.

SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist.

An extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist, SB 209670, has been synthesized and characterized. SB 209670, which was rationally designed using conformational models of ET-1, selectively inhibits binding of 125I-labeled ET-1 to cloned human ET receptor subtypes ETA and ETB (Ki = 0.2 and 18 nM, respectively). SB 209670 produces concentration-dependent inhibition of ET-1-mediated vasoconstriction in isolated vascular tissues and in vivo following either intravenous or intraduodenal administration. SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty. SB 209670 will be useful in characterizing and classifying the physiological and pathophysiological effects of ET.

Microvasculature in brain biopsy specimens from patients with Alzheimer's disease: an immunohistochemical and ultrastructural study.

Brain biopsy specimens from five patients with Alzheimer's disease obtained in the course of a trial of intracerebroventricular bethanechol were studied by immunohistochemical (antibody to A4 peptide) and ultrastructural techniques, with particular emphasis on the microvessels. In some cases, numbers of A4-immunoreactive lesions (senile plaques) correlated well with numbers of plaques demonstrable by silver stains. Prominent A4-immunoreactive amyloid angiopathy was seen in one patient. The patient with severe cerebral amyloid angiopathy (CAA) showed extensive arteriolar deposition of amyloid filaments with apparent destruction of the media but remarkably intact endothelium. A cell of origin for amyloid filaments was not apparent, although close proximity to smooth muscle cell remnants in the arteriolar media suggested this as one possible cell of origin. Frequent vessels showed medial or adventitial collagen deposition, even when the amount of amyloid was minimal or negligible. Thus relatively severe CAA can exist in the absence of overt endothelial injury, although related studies on this tissue indicate definite abnormalities of the blood-brain barrier. Conversely, destruction of smooth muscle cells and collagen deposition in vessel walls may be the cellular correlates of arteriolar weakening that can lead to CAA-related brain hemorrhage.

Inpatient PTSD treatment: a study of pretreatment measures, treatment dropout, and therapist ratings of response to treatment.

Pretreatment measures including demographic variables, adjustment index variables and psychological testing variables were studied in relationship to treatment dropout and therapist ratings of overall response to treatment among PTSD veterans in an inpatient PTSD program. Analysis comparing a group of fourteen veterans who dropped out of treatment early and a random sample of fourteen who successfully completed treatment showed no significant differences. Analysis comparing a group of 35 veterans who received the highest therapist ratings on response to treatment with a group of 35 veterans receiving the lowest ratings on response to treatment also showed no significant differences. Analysis of subgroups of patients who had completed the Millon Clinical Multiaxial Inventory (MCMI) and received high versus low therapist ratings showed one significant difference on the hypomania scale. Overall findings on the MMPI and MCMI appeared similar to other investigations of PTSD.