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E Sander Connolly

Publications and source records attributed to E Sander Connolly.

At least 73 records · Page 4Linked to original sources
PubMed2004

Combined surgical and endovascular management of a complex posttraumatic dural arteriovenous fistula of the tentorium and straight sinus.

Diagnosis and management of a complex tentorial dural arteriovenous fistula (DAVF) of the straight sinus with vein of Galen aneurysmal dilatation is presented. A 65-year-old woman with remote history of cranial gunshot lapsed into coma after months of progressive neurological decline. Computed tomography brain scan showed cerebellar hemorrhage while arteriography demonstrated a complex arteriovenous fistula of an isolated straight sinus and tentorium with extensive arterial supply. First extracranial then intracranial arterial feeders to the fistula were occluded in separate procedures following initial presentation. Eleven days after presentation, an occipital burr-hole craniotomy was performed, the isolated straight sinus was cannulated under fluoroscopic guidance, and the fistula eradicated with multiple thrombogenic fibered platinum and Gugliemi detachable coils. Staged embolization now represents the standard of care for many complex DAVFs. A multi-disciplinary surgical and endovascular approach is a valuable combination to cure deep lesions with limited surgical or transvascular access.

Aged↗
PubMed2004

Microsurgical treatment of basilar apex aneurysms: perioperative and long-term clinical outcome.

OBJECTIVE: We sought to analyze the perioperative and long-term clinical outcome data for patients with microsurgically treated basilar apex aneurysms. METHODS: We identified 98 consecutively treated basilar apex aneurysms in patients prospectively enrolled in a cerebral aneurysm database. RESULTS: Fifty patients presented with subarachnoid hemorrhage, and 19 aneurysms were giant. Eighty-four of 98 aneurysms were directly clipped. Surgical morbidity was 19.4% for the entire cohort and 8.8% for the unruptured, nongiant subgroup. The most common complication resulting in long-term morbidity was perforator injury. Sixty-seven percent of patients with clipped aneurysms were independent at discharge; this fraction increased to 79.0% at the 3-month follow-up examination. Good long-term outcomes (modified Rankin Scale score < or =2) were achieved in 56 (70%) of 80 cases. The mean Barthel Index of surviving patients was 95.8 +/- 15.0 (median = 100, n = 66). Patients with unruptured, nongiant lesions fared considerably better than patients in other cohorts. Ninety-three percent of this subgroup was independent at discharge; this fraction increased to 100% at the 3-month follow-up examination (n = 27). In univariate analyses, poor clinical grade, giant aneurysm size, major operative complications, and operations performed early in the series were associated with worse outcomes. In the multivariate analysis, unruptured giant aneurysm status was found to confer a tremendous risk for poor outcome (risk ratio, 80.0; 95% confidence interval, 8.0-800.7; P < 0.01). Surviving patients were observed for a mean clinical follow-up period of 7.4 +/- 3.7 years. The annual rate of postoperative subarachnoid hemorrhage was 0.18% for all clipped aneurysms and 0% for completely clipped lesions. CONCLUSION: In comparison to data from the existing literature regarding Guglielmi detachable coil embolization of basilar apex aneurysms, the data presented suggest that surgical clipping should be an important component of a multimodality approach to the treatment of patients with basilar apex aneurysms.

Adult↗
PubMed2004

Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair.

OBJECTIVE: To compare endovascular versus surface methods for the induction and reversal of hypothermia during neurosurgery in a multicenter, prospective, randomized study. METHODS: Patients undergoing elective open craniotomy for repair of an unruptured cerebral aneurysm (n = 153) were randomly assigned (2:1) to undergo whole-body hypothermia to 33 degrees C, either with an endovascular cooling device placed in the inferior vena cava via the femoral vein (n = 92) or with a surface convective air blanket (n = 61). Active rewarming was accomplished using the same devices. RESULTS: Cooling rates in endovascular and surface blanket groups averaged 4.77 and 0.87 degrees C/h, respectively (P < 0.001). When the first temporary arterial or aneurysm clip was placed, 99% of endovascular patients and 20% of surface blanket patients had reached the target of 33 degrees C (P < 0.001). Obese patients were cooled efficiently with the endovascular approach (3.56 degrees C/h). Rewarming rates averaged 1.88 degrees C/h for endovascular patients and 0.69 degrees C/h for surface blanket patients (P < 0.001). By the end of surgery, 89 and 53% of these patients, respectively, had rewarmed to at least 35 degrees C (P < 0.001). On leaving the operating room, 14% of endovascular patients and 28% of surface blanket patients were still intubated (P = 0.035). The overall safety of the two procedures was comparable. No clinically significant catheter-related thrombotic, bleeding, or infectious complications were reported in the endovascular group. CONCLUSION: Endovascular cooling provided superior induction, maintenance, and reversal of hypothermia compared with the surface blanket, without an increase in complications. Endovascular cooling may have clinical benefit for patients undergoing cerebrovascular surgery, as well as patients with acute stroke, head injury, or acute myocardial infarction.

Adolescent↗
PubMed2004

Chemical meningitis after cerebral aneurysm treatment using two second-generation aneurysm coils: report of two cases.

OBJECTIVE AND IMPORTANCE: In the quest for effective and durable endovascular aneurysm treatment, second-generation aneurysm coils endeavor to increase the biological healing response to the implanted material. We report two cases of large cerebral aneurysms treated concurrently with both available second-generation aneurysm coils and the subsequent development of symptomatic nonbacterial meningitis. CLINICAL PRESENTATION: Two previously healthy patients underwent endovascular treatment for large (>=2 cm) cerebral aneurysms. Both aneurysms were treated using multiple Hydrogel coils (MicroVention, Inc., Aliso Viejo, CA) and Matrix coils (Boston Scientific/Target, Fremont, CA). Careful aseptic technique was observed throughout each procedure, and prophylactic intravenous antibiotics were administered during the perioperative period to both patients. Treatment proceeded uneventfully in both cases with excellent aneurysm occlusion and no immediate postoperative neurological deficits. INTERVENTION: In both cases, the patients were discharged from hospital but quickly were readmitted with stigmata of meningitis. Imaging demonstrated durable occlusion of the aneurysms in both patients and also abnormalities indicative of perianeurysmal and diffuse intracranial inflammatory response. Complete septic workup failed to identify an organism in either patient. Both patients responded to treatment with corticosteroid medication used to modulate the inflammatory response induced by the coil implants. CONCLUSION: Second-generation aneurysm coils were developed to promote more durable occlusion of cerebral aneurysms by promoting more complete volumetric aneurysm occlusion or by eliciting a more prolific inflammatory response. The concurrent use of Hydrogel and Matrix coil systems in large aneurysms may cause an exuberant inflammatory response with both local and systemic manifestations. Although vigilant evaluation and treatment for presumptive bacterial meningitis is required in all such cases, patients respond to immunomodulatory therapy with corticosteroids. More information to understand better the interaction of Hydrogel and Matrix coils is needed.

Embolization, Therapeutic↗
PubMed2004

Far lateral suboccipital approach for the treatment of proximal posteroinferior cerebellar artery aneurysms: surgical results and long-term outcome.

OBJECTIVE: Proximal posteroinferior cerebellar artery (PICA) aneurysms are challenging to treat surgically, with high reported perioperative complication rates. We describe the perioperative course and long-term clinical outcomes obtained via a far lateral suboccipital approach in 20 consecutive proximal PICA aneurysms. METHODS: Data were collected prospectively on the first 20 proximal PICA aneurysms treated surgically by a single surgeon (ESC) between December 1997 and April 2003. All aneurysms were clipped via a far lateral approach. Patients with unruptured aneurysms were assessed at 3 and 12 months after surgery. For all subarachnoid hemorrhage patients, a battery of outcome tests was performed at 3- and 12-month intervals. Outcomes were then compared with those of a contemporaneously managed population of ruptured right-sided posterior communicating artery aneurysms. RESULTS: The far lateral suboccipital approach achieved adequate exposure in all cases. There were no intraoperative complications or intraoperative aneurysm ruptures. All patients with unruptured aneurysms were fully functional at long-term follow-up. At 3 months of follow-up, 93% of the subarachnoid hemorrhage patients achieved a Glasgow Outcome Scale score of 1 to 2. At 12 months of follow-up, 92% achieved a Glasgow Outcome Scale score of 1 to 2. Compared with the patients with a ruptured right-sided posterior communicating artery aneurysm, no difference could be found in quality of life or activities of daily living at either time point. CONCLUSION: The favorable outcomes and low postoperative morbidity in this subset of patients argues that clipping via this approach be considered a first-line therapeutic option. When performed in this manner, PICA aneurysm surgery seems to have no greater morbidity than right-sided posterior communicating artery aneurysm surgery.

Adult↗
PubMed2003

Risk factors for continued cigarette use after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cigarette smoking is a risk factor for the formation and rupture of intracranial aneurysms. Few studies have examined predictors of resumption of cigarette smoking after a first episode of subarachnoid hemorrhage (SAH). METHODS: Of 620 SAH patients treated between July 1996 and November 2002, we prospectively evaluated continued cigarette use in 152 smokers alive at 3 months. Univariate and multivariate logistic regression analyses were used to identify potential demographic, social, and clinical predictors of continued cigarette use, defined as smoking > or =1 cigarette per week in the month before follow-up. RESULTS: Thirty-seven percent (56 of 152) resumed smoking after their SAH. Patients who continued smoking were younger, were more often black, had begun smoking at an earlier age, and had a higher frequency of prior alcohol or cocaine use and self-reported depression or anxiety than those who quit (all P<0.05). Smoking at < or =16 years of age (odds ratio [OR], 5.88; 95% confidence interval [CI], 2.33 to 14.29), self-reported depression (OR, 5.29; 95% CI, 2.10 to 13.35), and prior alcohol use (OR, 4.51; 95% CI, 1.45 to 14.05) independently predicted continued cigarette use. Smokers had a functional outcome similar to that of nonsmokers at 3 months but were more likely to resume alcohol consumption (OR, 3.88; 95% CI, 1.91 to 7.88). CONCLUSIONS: More than one third of prior smokers continue to use nicotine after SAH. Young age at smoking onset and a history of depression or alcohol use are risk factors for continued cigarette use. Targeted smoking cessation programs are needed to reduce the high rate of smoking resumption after SAH.

Adult↗
PubMed2003

Ultrarapid, convection-enhanced intravascular hypothermia: a feasibility study in nonhuman primate stroke.

BACKGROUND AND PURPOSE: Hypothermia has been shown to be neuroprotective in a variety of clinical settings. Unfortunately, poor delivery techniques and insufficient data in appropriate preclinical models have hampered its development in human stroke. To address these limitations, we have devised a 10F intravascular catheter capable of rapid systemic cooling of nonhuman primates. METHODS: Placed in the inferior vena cava via a transfemoral approach, the catheter was used to induce mild systemic hypothermia 3 hours after the onset of hemispheric stroke in baboons. RESULTS: Cooling was achieved at a rate of 6.3+/-0.8 degrees C/h. Target brain temperatures (32.2+/-0.2 degrees C) were reached at the same time (47.7+/-6.32 minutes) as target esophageal temperatures (32.0+/-0.0 degrees C). Hypothermia was maintained for 6 hours in all animals. Animals did not experience the infections, coagulopathy, or cerebral edema commonly seen with surface cooling methods in human stroke. CONCLUSIONS: These data suggest that a brief episode of mild core hypothermia instituted at a clinically relevant time point can be achieved in primate stroke and that our intravascular cooling technique provides safe, rapid, and reproducible hypothermia.

Animals↗
PubMed2003

Intracranial pressure following aneurysmal subarachnoid hemorrhage: monitoring practices and outcome data.

OBJECT: Elevated intracranial pressure (ICP) is an important consequence of aneurysmal subarachnoid hemorrhage (SAH) that often results in decreased cerebral perfusion and secondary clinical decline. No definitive guidelines exist regarding methods and techniques for ICP management following aneurysm rupture. The authors describe monitoring practices and outcome data in 621 patients with aneurysmal SAH admitted to their neurological intensive care unit during an 8-year period (1996-2003). METHODS: A fiberoptic catheter tip probe or external ventricular drain (EVD) was used to record ICP values. The percentage of monitored patients varied, as expected, according to admission Hunt and Hess grade (p < 0.0001). Intracranial pressure monitoring devices were used in 27 (10%) of 264 Grade I to II patients, 72 (38%) of 189 Grade III patients, and 134 (80%) of 168 Grade IV to V patients. There was a strong propensity to favor transduced ventricular drains over parenchymal fiberoptic bolts, with the former used in 221 (95%) of 233 cases. This tendency was particularly strong in the poor-grade cohort, in which EVDs were placed in 99% of monitored individuals. The rates of cerebrospinal fluid infection in patients in whom ICP probes (0%) and ventricular drains (12%) were placed accorded with those in the literature. CONCLUSIONS: Following aneurysmal SAH, ICP monitoring prevalence and techniques differ with respect to admission Hunt and Hess grade and are associated with the patient's functional status at discharge.

Adult↗
PubMed2003

Despite in vitro increase in cyclic guanosine monophosphate concentrations, intracarotid nitroprusside fails to augment cerebral blood flow of healthy baboons.

BACKGROUND: During cerebral angiography, intracarotid infusion of sodium nitroprusside (SNP), an endothelium-independent nitric oxide donor, fails to increase cerebral blood flow (CBF) of human subjects. A confounding effect of intracranial pathology or that of radiocontrast could not be ruled out in these experiments. The authors hypothesized that, if nitric oxide was a significant regulator of CBF of primates, then intracarotid SNP will augment CBF of baboons. METHODS: In studies, CBF (intraarterial (133)Xe technique) was measured in healthy baboons during isoflurane anesthesia at (1) baseline and during (2) induced hypertension with intravenous phenylephrine, (3) concurrent infusions of intravenous phenylephrine and intracarotid SNP, and (4) intracarotid verapamil (positive control drug). In studies, the authors measured tissue cyclic guanosine monophosphate (cGMP) by radioimmunoassay after incubating vascular rings obtained from freshly killed baboons (1) with increasing concentrations of SNP and (2) after SNP exposure following preincubation with the radiocontrast agent, iohexhol. RESULTS: In the studies, coinfusion of intravenous phenylephrine and intracarotid SNP did not increase CBF. However, intracarotid verapamil significantly increased CBF (from 26 +/- 7 to 43 +/- 11 ml x 100 g(-1) x min(-1); P < 0.0001) without a change in mean arterial pressure. In the studies, incubation of intracranial arterial rings in SNP resulted in dose-dependent increases in cGMP concentrations. A similar increase in cGMP content was evident despite iohexhol preincubation. CONCLUSIONS: Collectively, these results suggest that, in healthy baboons, intracarotid SNP does not decrease arteriolar resistance, although SNP could affect proximal arterial tone, as demonstrated by the increase in cGMP content of these vessels.

Animals↗
PubMed2003

Villous hypertrophy versus choroid plexus papilloma: a case report demonstrating a diagnostic role for the proliferation index.

Diffuse bilateral enlargement of the choroid plexus has long been appreciated as a cause of shunt-resistant hydrocephalus in infants, most often secondary to cerebrospinal fluid overproduction. Despite the fact that such lesions have interchangeably been termed 'villous hypertrophy' (VH) or 'bilateral choroid plexus papilloma' (CPP), little attention has been paid to the pathological distinctions that characterize these two entities. We present a case of presumed VH in a 2-week-old female presenting with cerebrospinal fluid production-dependent hydrocephalus that ultimately required bilateral surgical ablation of the choroid plexus. Although the preoperative radiological diagnosis was consistent with VH, postoperative histological analysis suggested bilateral CPP. The neoplastic nature of the lesion was confirmed by specific staining for the proliferation index, showing an MIB-1 labeling index of 4%, characteristic of papilloma. Routine imaging and histological grading of choroid plexus hypertrophy and papilloma have not provided a reliable means of predicting malignant behavior or recurrence after surgical resection. Moreover, none of the previously reported cases of VH in the literature have analyzed pathological specimens for cellular proliferative potential. Therefore, we review the literature on VH and bilateral CPP and discuss the diagnostic and possible prognostic implications of distinguishing these variants by utilizing the MIB-1 marker for the proliferation index.

Brain Diseases↗
PubMed2003

An improved functional neurological examination for use in nonhuman primate studies of focal reperfused cerebral ischemia.

There is renewed interest in primate models of acute stroke for the evaluation of potential therapeutic agents prior to clinical trials. The development of more precise functional outcome measures would improve the pre-clinical assessment of neuroprotective strategies. We have constructed a grading scale that utilizes an increased number of goal-oriented tasks to assess both behavior and motor function. The new scoring system is designed to enhance precision and accuracy when compared to existing scales. Twenty-seven male baboons were subjected to 1 h of middle cerebral artery territory occlusion followed by reperfusion. Outcome was evaluated using both a standard neurological function scale and a new task-oriented scale. Each scoring system was assessed for reproducibility (inter-observer reliability) and for association with radiographic infarct volume. The task-oriented grading system was significantly less variable than the standard outcome measure (p < 0.0001). The task-oriented neurological scale demonstrated stronger correlation with radiographic infarct volume (p < 0.0001) than the standard scale (p < 0.01) and more accurately reflected infarct size in animals with small strokes. Compared to the accepted system for grading neurological function, the task-oriented scale demonstrates improved inter-observer variability and a better association with radiographic outcome measures. Incorporating this refined neurological evaluation into a baboon model of stroke may serve to increase the functional predictive value of pre-clinical studies.

Animals↗
PubMed2003

Serial magnetic resonance imaging in experimental primate stroke: validation of MRI for pre-clinical cerebroprotective trials.

Precise assessment of stroke outcome is critical for pre-clinical testing of cerebroprotective strategies. Differences in stroke volume measured by various magnetic resonance imaging (MRI) techniques are documented in humans, but not well described in experimental primate stroke. This study characterizes changes in stroke volume using serial MRI scans in a baboon model of reperfused cerebral ischemia. The location/area of hyperintensity on MRI corresponded with the TTC-stained infarct region. T2-weighted fast spin echo (T2W FSE), fluid attenuated inversion recovery (FLAIR), and diffusion weighted imaging (DWI) showed a decrease in infarct volume between 72 h and nine days post-ischemia (p = ns, p = 0.029, and p = 0.006). T2W FSE and FLAIR demonstrated an increase in infarct volume from 24 h to nine days post-ischemia, while DWI displayed a decrease over the same period. While early T2W FSE, FLAIR, and DWI all correlated with late infarct volume (p < 0.001), 72 h T2W FSE was the best direct measure (2.39% +/- 1.40% unity deviation). Serial MRI in a nonhuman primate model of focal cerebral ischemia recapitulates findings in clinical stroke. MRI at 72 h accurately predicts late infarct volume.

Animals↗
PubMed2003

Failure of intraoperative jugular bulb S-100B and neuron-specific enolase sampling to predict cognitive injury after carotid endarterectomy.

OBJECTIVE: Cognitive decline occurs in 25% of patients after carotid endarterectomy (CEA). Elevated serum concentrations of S-100B and neuron-specific enolase (NSE) occur after stroke, and serum S-100B levels at 24 hours are associated with clinical outcome after both stroke and CEA. We hypothesized that we could detect acute elevations in serum levels of these markers obtained intraoperatively from the jugular bulb (JB) and that these elevations would predict cognitive dysfunction postoperatively as measured by neuropsychometric test performance. METHODS: Forty-three patients scheduled for elective CEA were assessed with a battery of neuropsychometric tests before and 1 day after surgery. Before the carotid artery was clamped, a 6-French Fogarty catheter was inserted into the facial vein and threaded 6 cm rostrally into the JB. Serum samples were withdrawn from this catheter and simultaneously from a radial arterial catheter (A-line) at three time points: before clamping, 15 minutes into clamping, and after unclamping the carotid artery. Concentrations between groups were compared by analysis of variance and paired t tests. RESULTS: Total deficit scores were significantly worse in 13 (30%) of the 43 patients 1 day after surgery. There was a trend toward elevations in JB concentrations of S-100B relative to A-line levels 15 minutes after cross-clamping (11% elevation, P = 0.079, paired t test). In addition, 15 minutes after clamping of the carotid artery, levels of S-100B from the JB were significantly elevated compared with levels at baseline (P = 0.040, one-way analysis of variance). No significant changes were found between any time point in levels of S-100B from the A-line blood or of NSE from either the JB or the A-line. Subtle cognitive decline after CEA was not correlated with intraoperative levels of S-100B or NSE, but there was a weak, statistically nonsignificant, association between a rise in 15-minute S-100B levels and cognitive injury that was not seen with JB samples. CONCLUSION: Although intraoperative levels of S-100B and NSE from the JB failed to predict cognitive injury, carotid cross-clamping, independent of injury, seems to be associated with early elevations in S-100B.

Aged↗
PubMed2002

HuEP5C7 as a humanized monoclonal anti-E/P-selectin neurovascular protective strategy in a blinded placebo-controlled trial of nonhuman primate stroke.

Although inhibiting interaction of beta(2) integrins with cognate immunoglobulin class adhesion receptor ligands is an effective neuroprotective strategy in small mammal models of stroke, the strategy has failed in human trials. A completely different antiadhesion receptor strategy was therefore rigorously tested in a model that may more closely approximate human reperfused stroke. Early leukoadhesive events in postischemic cerebral microvessels are mediated by upregulated selectin-class adhesion receptors on endothelial cells. Therefore, a blocking antibody prepared against common P- and E-selectin epitopes was humanized to suppress complement activation and tested in a reperfused hemispheric stroke model in Papio anubis (baboon). Histological examination of postischemic cerebral microvessels revealed a strong upregulation of E-and P-selectin expression. Placebo-blinded administration of the humanized anti-human E- and P-selectin monoclonal antibody (HuEP5C7, 20 mg/kg IV, n=9; placebo, n=9) immediately after the onset of 1 hour of temporary ischemia resulted in trends showing reduced polymorphonuclear leukocyte (PMN) infiltration into ischemic cortex, reduced infarct volumes (by 41%), improved neurological score (by 35%), and improved ability to self-care (by 39%). Importantly, there was no evidence of systemic complement activation, immune suppression, or pathological coagulopathy associated with this therapy. These data suggest that a humanized anti-E/P-selectin antibody approach is safe and may be effective as a clinical treatment for human stroke.

Animals↗
PubMed2002

ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury.

We showed previously in neocortical explants, derived from developing wild-type and estrogen receptor (ER)-alpha gene-disrupted (ERKO) mice, that both 17alpha- and 17beta-estradiol elicit the rapid and sustained phosphorylation and activation of the mitogen-activated protein kinase (MAPK) isoforms, the extracellular signal-regulated kinases ERK1 and ERK2. We proposed that the ER mediating activation of the MAPK cascade, a signaling pathway important for cell division, neuronal differentiation, and neuronal survival in the developing brain, is neither ER-alpha nor ER-beta but a novel, plasma membrane-associated, putative ER with unique properties. The data presented here provide further evidence that points strongly to the existence of a high-affinity, saturable, 3H-estradiol binding site (K(d), approximately 1.6 nm) in the plasma membrane. Unlike neocortical ER-alpha, which is intranuclear and developmentally regulated, and neocortical ER-beta, which is intranuclear and expressed throughout life, this functional, plasma membrane-associated ER, which we have designated "ER-X," is enriched in caveolar-like microdomains (CLMs) of postnatal, but not adult, wild-type and ERKO neocortical and uterine plasma membranes. We show further that ER-X is functionally distinct from ER-alpha and ER-beta, and that, like ER-alpha, it is re-expressed in the adult brain, after ischemic stroke injury. We also confirmed in a cell-free system that ER-alpha is an inhibitory regulator of ERK activation, as we showed previously in neocortical cultures. Association with CLM complexes positions ER-X uniquely to interact rapidly with kinases of the MAPK cascade and other signaling pathways, providing a novel mechanism for mediation of the influences of estrogen on neuronal differentiation, survival, and plasticity.

Animals↗