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E Sander Connolly

Publications and source records attributed to E Sander Connolly.

87 records · Page 5Linked to original sources
PubMed2002

Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal.

Cerebral ischemia stimulates increased activity of polyamine oxidase, a ubiquitous enzyme that catabolizes polyamines to produce 3-aminopropanal. 3-Aminopropanal is a reactive aldehyde that mediates progressive neuronal necrosis and glial apoptosis. Here we report that increased levels of 3-aminopropanal-modified protein levels in humans after aneurysmal subarachnoid hemorrhage correlate with the degree of cerebral injury as measured by admission Hunt/Hess grade. In vitro screening of clinically approved drugs reveals that N-2-mercaptopropionyl glycine (N-2-MPG), an agent clinically approved for prevention of renal stones in patients with cysteinuria, significantly inhibits the cytotoxicity of 3-aminopropanal. N-2-MPG reacts with 3-aminopropanal to yield a nontoxic thioacetal adduct, as confirmed by electrospray ionization mass spectroscopy. Administration of N-2-MPG in clinically relevant doses to rats significantly reduces cerebral 3-aminopropanal-modified protein immunoreactivity and infarct volume in a standardized model of middle cerebral artery occlusion, even when the agent is administered after the onset of ischemia. These results implicate 3-aminopropanal as a therapeutic target for cerebral ischemia.

Aldehydes↗
PubMed2002

A controlled prospective study of neuropsychological dysfunction following carotid endarterectomy.

BACKGROUND: Although subtle cognitive injury as revealed by neuropsychological testing occurs in a substantial number of patients following carotid endarterectomy (CEA), there is controversy about whether this finding is a result of the surgery or the anesthesia. OBJECTIVES: To examine the changes in neuropsychological test performance in patients following CEA vs a control group of patients older than 60 years following spine surgery, so as to determine whether neuropsychological dysfunction after CEA is a result of surgery or anesthesia. METHODS: Patients undergoing CEA (n = 80) and lumbar spine surgery (n = 25) were assessed with a battery of neuropsychological tests preoperatively and on postoperative days 1 and 30. The neuropsychological performance of patients in the control group was used to normalize performance for patients in the CEA group, by calculating z scores using the mean and SD of the change scores in the control group. Significant cognitive dysfunction was defined as performance that exceeded 2 SDs above the mean performance of patients in the control group. RESULTS: Postoperative days 1 and 30 total deficit scores were significantly worse in the CEA group compared with the controls. When individual test results were examined, the CEA group performed significantly worse than the controls on the Rey Complex Figure test and Halstead-Reitan Trails B on day 1, and on the Rey Complex Figure on day 30. Overall, cognitive dysfunction was seen in 22 patients (28%) in the CEA group on day 1 and in 11 (23%) of 48 patients on day 30. CONCLUSIONS: Subtle cognitive decline following CEA occurs and persists for at least several weeks after surgery. This decline was absent in a control group.

Aged↗
PubMed2002

Interhemispheric intracranial pressure gradients in nonhuman primate stroke.

BACKGROUND: Although the development of significant interhemispheric intracranial pressure (ICP) gradients in the setting of unilateral stroke remains controversial, no study to date has investigated the existence of these gradients in a controlled, reproducible, clinically relevant model. Therefore, we used a primate model of reperfused hemispheric stroke to better characterize the development of these gradients. METHODS: Bilateral intraparenchymal ICP was continuously monitored in 7 adult male baboons subjected to left hemisphere reperfused stroke. Interhemispheric ICP gradients were calculated for each baboon and plotted over time. Infarct volume was determined using T2-weighted magnetic resonance imaging (MRI) at sacrifice. RESULTS: A bimodal distribution of interhemispheric ICP gradients was observed in animals with >20% infarct volume (22.1% +/- 0.9; range 21-23%) versus < or = 15% infarct volume (6.6% +/- 2.7; range 1-15%). In animals with >20% infarct volume, interhemispheric gradients developed early and persisted throughout the monitoring period. At 12 hours postreperfusion, animals with large infarcts demonstrated a mean pressure gradient of 13.8 +/- 4.3 mm Hg, compared to a mean gradient of -2.6 +/- 1.1 mm Hg for animals with < or =15% infarct volume. The difference in pressure gradients was statistically significant at all time points from 4 to 12 hours postreperfusion (p < 0.01). CONCLUSIONS: These data suggest that, in nonhuman primates, infarcts of a size approaching 20% of the hemisphere may be associated with significant ICP gradients. With these larger infarcts, ipsilateral monitoring is required if regional cerebral perfusion pressure is to be accurately assessed.

Animals↗
PubMed2002

Intracarotid nitroprusside does not augment cerebral blood flow in human subjects.

BACKGROUND: The recent resurgence of interest in the cerebrovascular effects of nitroprusside can be attributed to the possibility of using nitric oxide donors in treating cerebrovascular insufficiency. However, limited human data suggest that intracarotid nitroprusside does not directly affect cerebrovascular resistance. In previous studies, physiologic or pharmacologic reactivity of the preparation was not tested at the time of nitroprusside challenge. The authors hypothesized that if nitric oxide is a potent modulator of human cerebral blood flow (CBF), then intracarotid infusion of nitroprusside will augment CBF. METHODS: Cerebral blood flow was measured (intraarterial (133)Xe technique) in sedated human subjects undergoing cerebral angiography during sequential infusions of (1) intracarotid saline, (2) intravenous phenylephrine to induce systemic hypertension, (3) intravenous phenylephrine with intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and (4) intracarotid verapamil (0.013 mg x kg(-1) x min(-1)). Data (mean +/- SD) were analyzed by repeated-measures analysis of variance and post hoc Bonferroni-Dunn test. RESULTS: Intravenous phenylephrine increased systemic mean arterial pressure (from 83 +/- 12 to 98 +/- 6 mmHg; n = 8; P < 0.001), and concurrent infusion of intravenous phenylephrine and intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with intravenous phenylephrine or with concurrent infusions of intravenous phenylephrine and intracarotid nitroprusside. Intracarotid verapamil increased CBF (43 +/- 9 to 65 +/- 11 ml x 100 g(-1) x min(-1); P < 0.05). CONCLUSIONS: The authors conclude that, in humans, intracarotid nitroprusside sufficient to decrease mean arterial pressure during recirculation, does not augment CBF. Failure of intracarotid nitroprusside to augment CBF despite demonstrable autoregulatory vasoconstriction and pharmacologic vasodilation questions the significance of nitric oxide-mediated vasodilation in human cerebral circulation.

Adult↗
PubMed2002

Ventriculostomy-related infections: a critical review of the literature.

OBJECTIVE: To provide a critical evaluation of the published literature describing risk factors for ventriculostomy-related infections (VRIs) and the efficacy of prophylactic catheter exchange. METHODS: A MEDLINE literature search was performed, and data were extracted from studies published from 1941 through 2001. RESULTS: Published criteria for diagnosing VRIs are highly variable. Intraventricular hemorrhage, subarachnoid hemorrhage, cranial fracture with cerebrospinal fluid leak, craniotomy, systemic infections, and catheter irrigation all predispose patients to the development of VRIs. Extended duration of catheterization is correlated with an increasing risk of cerebrospinal fluid infections during the first 10 days of catheterization. Prophylactic catheter exchange does not modify the risk of developing later VRIs in retrospective studies. CONCLUSION: Categorizing suspected cerebrospinal fluid infections as contaminants, colonization, suspected or confirmed VRIs, or ventriculitis more accurately describes the patient's clinical condition and may indicate different management strategies. A prospective, randomized clinical trial is required to further evaluate the efficacy of prophylactic catheter exchange in limiting the incidence of VRIs during prolonged catheterization. Although prophylactic catheter exchange remains a practice option, the available data suggest that this procedure is not currently justified.

Catheters, Indwelling↗
PubMed2002

Nonconvulsive status epilepticus after subarachnoid hemorrhage.

OBJECTIVE: Although in-hospital seizures have been reported for 3 to 24% of patients with aneurysmal subarachnoid hemorrhage (SAH), nonconvulsive status epilepticus (NCSE) has not been previously described. We sought to determine the frequency and clinical features of NCSE among comatose patients with SAH. METHODS: Between November 1997 and February 2000, we performed continuous electroencephalographic (cEEG) monitoring for at least 24 hours for all patients with aneurysmal SAH who were treated in our neurological intensive care unit and exhibited unexplained coma or neurological deterioration. NCSE was diagnosed when cEEG monitoring demonstrated continuous or repetitive electrographic seizures exceeding 1 hour in duration. Refractory NCSE was treated aggressively with intravenous anticonvulsant administration and continuous-infusion midazolam therapy. RESULTS: Of 233 patients with SAH who survived the first 48 hours of hospitalization, 101 were stuporous or comatose at some point during their hospitalization. Twenty-six of those patients underwent cEEG monitoring, and eight were diagnosed as having NCSE, an average of 18 days (range, 5-38 d) after SAH. All eight patients were receiving prophylactic anticonvulsant therapy. Four patients were persistently comatose and four demonstrated deterioration to stupor or coma; only one exhibited overt tonicoclonic activity. A worst Hunt and Hess grade of IV or V, older age, ventricular drainage, and cerebral edema on computed tomographic scans were identified as risk factors for NCSE (all P < 0.01). NCSE was successfully terminated for five patients (63%), but only one experienced clinical improvement, which was transient; all eight patients eventually died after a period of prolonged coma. CONCLUSION: cEEG monitoring detected NCSE for 8% of patients with SAH and otherwise unexplained coma or neurological deterioration. The seizures were highly refractory to therapy, and the prognosis for these patients was extremely poor. Routine postoperative cEEG monitoring of patients with SAH who are at high risk for NCSE, allowing earlier diagnosis and treatment, offers the best chance of improving the outcomes for patients with this disorder.

Aged↗
PubMed2002

Cerebral injury predicted by transcranial Doppler ultrasonography but not electroencephalography during carotid endarterectomy.

When shunts are selectively used during carotid endarterectomy, the adequacy of collateral cerebral blood flow (CBF) after the carotid artery is clamped is determined by monitors based on different physiologic measurements. In this series of three patients, we used electroencephalography (EEG) to measure neuronal electrical activity and transcranial Doppler ultrasonography (TCD) to measure CBF velocity. In each of our cases, the EEG was unchanged from preclamp values, while TCD CBF velocity was dramatically reduced. All three patients had transient neuropsychometric or neurologic changes after surgery, which resolved.

Aged↗
PubMed2002

Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome.

BACKGROUND AND PURPOSE: Cerebral edema visualized by CT is often seen after subarachnoid hemorrhage (SAH). Inflammatory or circulatory mechanisms have been postulated to explain this radiographic observation after SAH. We sought to determine the frequency, causes, and impact on outcome of early and delayed global cerebral edema after SAH. METHODS: We evaluated the presence of global edema on admission and follow-up CT scans in 374 SAH patients admitted within 5 days of onset to our Neurological Intensive Care Unit between July 1996 and February 2001. Using multivariate analysis, we identified predictors of global cerebral edema and evaluated the impact of global edema on outcome 3 months after onset with the modified Rankin Scale. RESULTS: Global edema was present on admission CT scans in 8% (n=29) and developed secondarily in 12% (n=44) of the patients. Global edema on admission was predicted by loss of consciousness at ictus and increasing Hunt-Hess grade. Delayed global edema was predicted by aneurysm size >10 mm, loss of consciousness at ictus, use of vasopressors, and increased SAH sum scores. Thirty-seven percent (n=137) of the patients were dead or severely disabled (modified Rankin Scale 4 to 6) at 3 months. Death or severe disability was predicted by any global edema, aneurysm size >10 mm, loss of consciousness at ictus, increased National Institutes of Health Stroke Scale scores, and older age. CONCLUSIONS: Global edema is an independent risk factor for mortality and poor outcome after SAH. Loss of consciousness, which may reflect ictal cerebral circulatory arrest, is a risk factor for admission global edema, and vasopressor-induced hypertension is associated with the development of delayed global edema. Critical care management strategies that minimize edema formation after SAH may improve outcome.

Adolescent↗
PubMed2002

Guglielmi detachable coil embolization of posterior circulation aneurysms: a systematic review of the literature.

BACKGROUND: Early multicenter trials of Guglielmi detachable coil embolization of posterior circulations aneurysms have been followed by the publication of numerous single-center experiences. Summary of Review- We performed a MEDLINE literature search and extracted data from single-center reports containing at least 10 posterior circulation aneurysms. Twelve reports (495 aneurysms) were specific to the posterior circulation. Eighty-two percent of aneurysms arose near the basilar apex. Eighty-one percent of patients harbored unruptured aneurysms or presented in good clinical condition. Sixty-three percent of lesions were small, and 41% exhibited a narrow neck. Coil deposition was achieved in 97.6% of cases. Procedural complication and morbidity rates were 12.5% and 5.1%, respectively. Procedural and 30-day mortality rates were 1.4% and 6.7%, respectively. Complete aneurysm occlusion was achieved in 47.6%, near-complete occlusion (90% to 99%) in 43.4%, and incomplete occlusion in 9.0% of cases. There were a total of 52 recurrences (22.2%) in a subset of 234 evaluable patients. Ninety-two percent of these aneurysms exhibited wide necks. The annual risk of subarachnoid hemorrhage after embolization was 0.8%. Eighty-five percent of patients achieved functional independence, while only 5.3% lived dependent lifestyles. The overall mortality rate was 9.8%. CONCLUSIONS: The published literature approximates a large series of basilar apex aneurysms. Embolization is moderately effective in completely excluding an aneurysm from the posterior circulation. The incidence of recurrence in wide-neck aneurysms and incompletely coiled aneurysms is substantial. Coil embolization is effective in preventing early rebleeding. Its role in the treatment of unruptured aneurysms remains unclear.

Cerebrovascular Circulation↗
PubMed2002

Predictors of cognitive dysfunction after subarachnoid hemorrhage.

BACKGROUND: Cognitive dysfunction is a common and disabling sequela of subarachnoid hemorrhage (SAH). Although several clinical and radiographic findings have been implicated in the pathogenesis of cognitive dysfunction after SAH, few prospective studies have comprehensively and simultaneously evaluated these risk factors. METHODS: Between July 1996 and March 2000, we prospectively evaluated 113 of 248 consecutively admitted nontraumatic SAH patients alive at 3 months with a comprehensive neuropsychological evaluation. Summary scores for 8 cognitive domains were calculated to express test performance relative to the entire study population. Clinical and radiographic variables associated with domain-specific cognitive dysfunction were identified with forward stepwise multiple regression, with control for the influence of demographic factors. RESULTS: The study participants were younger (P=0.005), less often white (P=0.006), and had better 3-month modified Rankin scores (P=0.001) than those who did not undergo neuropsychological testing. The proportion of subjects who scored in the impaired range (>2 SD below the normative mean) on each neuropsychological test ranged from 10% to 50%. Predictors of cognitive dysfunction in 2 or more domains in the multivariate analysis included global cerebral edema (4 domains), left-sided infarction (3 domains), and lack of a posterior circulation aneurysm (2 domains). Other variables consistently associated with cognitive dysfunction in the univariate analysis included admission Hunt-Hess grade >2 and thick SAH in the anterior interhemispheric and sylvian fissures. CONCLUSIONS: Global cerebral edema and left-sided infarction are important risk factors for cognitive dysfunction after SAH. Treatment strategies aimed at reducing neurological injury related to generalized brain swelling, infarction, and clot-related hemotoxicity hold the best promise for improving cognitive outcomes after SAH.

Acute Disease↗
PubMed2002

Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic brain.

Endothelial CD39 metabolizes ADP released from activated platelets. Recombinant soluble human CD39 (solCD39) potently inhibited ex vivo platelet aggregation in response to ADP and reduced cerebral infarct volumes in mice following transient middle cerebral artery occlusion, even when given 3 hours after stroke. Postischemic platelet and fibrin deposition were decreased and perfusion increased without increasing intracerebral hemorrhage. In contrast, aspirin did not increase postischemic blood flow or reduce infarction volume, but did increase intracerebral hemorrhage. Mice lacking the enzymatically active extracellular portion of the CD39 molecule were generated by replacement of exons 4-6 (apyrase-conserved regions 2-4) with a PGKneo cassette. Although CD39 mRNA 3' of the neomycin cassette insertion site was detected, brains from these mice lacked both apyrase activity and CD39 immunoreactivity. Although their baseline phenotype, hematological profiles, and bleeding times were normal, cd39(-/-) mice exhibited increased cerebral infarct volumes and reduced postischemic perfusion. solCD39 reconstituted these mice, restoring postischemic cerebral perfusion and rescuing them from cerebral injury. These data demonstrate that CD39 exerts a protective thromboregulatory function in stroke.

Adenosine Triphosphatases↗
PubMed2002

Outcome prediction with serum intercellular adhesion molecule-1 levels after aneurysmal subarachnoid hemorrhage.

OBJECT: Although upregulated adhesion molecule expression has been demonstrated in experimental models of subarachnoid hemorrhage (SAH) and in the cerebrospinal fluid of patients with aneurysmal SAH, the clinical significance of these proinflammatory findings remains unclear. The authors hypothesize that 1) serum levels of soluble intercellular adhesion molecule-l (ICAM-1) are increased in all patients with aneurysmal SAH shortly after the hemorrhagic event, and 2) elevated soluble ICAM-1 values are associated with poor patient outcome, even when controlling for the severity of the initial hemorrhagic insult. METHODS: One hundred one patients were prospectively enrolled and stratified according to their admission Hunt and Hess grade and functional status at discharge (modified Rankin Scale [mRS] score). Soluble ICAM-1 levels were determined every other day for 12 days post-SAH by using the enzyme-linked immunosorbent assay. Early soluble ICAM-1 levels (post-SAH Days 2-4) were increased compared with levels in control patients without SAH (p < 0.05). Patients with aneurysmal SAH who had a poor outcome (mRS Grades 4-6) had significantly higher soluble ICAM-1 levels over the first 2 weeks post-SAH compared with patients who had a good outcome (mRS Grades 0-3, p < 0.01). This association with outcome was predicted by late increases (Day 6, p = 0.07; Days 8-12, p < 0.05) rather than early increases (p = not significant) and was best seen in patients with Hunt and Hess Grades I and II. in whom only those with poor outcomes demonstrated delayed ICAM-1 elevations (p < 0.05). CONCLUSIONS: These data demonstrate a correlation between soluble ICAM-1 levels and functional outcome following aneurysmal SAH that appears to be, at least in part, independent of the initial hemorrhage.

Adolescent↗
PubMed2002

Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule-1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1-2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm. METHODS: Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, < 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade-matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade-matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001). CONCLUSIONS: These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.

Adult↗
PubMedDate not supplied

Pseudoaneurysms of the superficial temporal artery secondary to placement of external ventricular drainage catheters.

BACKGROUND: Pseudoaneurysms of the superficial temporal artery have been described following trauma and various surgical procedures. There are no reports in the literature of these lesions following the placement of external ventricular drainage catheters. This article describes two patients and their successful treatment, and reviews diagnostic and treatment strategies. CASE DESCRIPTION: Two patients developed tender, nonpulsatile masses in the scalp along the former subcutaneous tract of an EVD catheter. Both lesions were successfully excised in the operating room and found to be thrombosed pseudoaneurysms of the superficial temporal artery. CONCLUSION: Pseudoaneurysms of the parietal branch of the STA may occur secondary to incision of the skin for twist drill hole placement or the use of a sharp trocar for subcutaneous tunneling of catheters. Use of a blunt-tipped trocar may reduce the risk of developing pseudoaneurysms secondary to EVD placement. Knowledge of the possibility of developing these lesions from catheter placement may aid the neurosurgeon in proper diagnosis and treatment.

Adult↗