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External ventricular drainage following aneurysmal subarachnoid haemorrhage

Gigante, Paul; Hwang, Brian Y; Appelboom, Geoffrey; Kellner, Christopher P; Kellner, Michael A; Connolly, E Sander
External ventricular drain (EVD) placement is standard of care in the management of aneurysmal subarachnoid haemorrhage-associated hydrocephalus (aSAH). However, there are no guidelines for EVD placement and management after aSAH. Optimal EVD insertion conditions, techniques to reduce the risk of EVD-associated infection and aneurysmal rebleeding, and methods of EVD removal are critical, yet incompletely answered management variables. The present literature consists primarily of small studies with heterogeneous populations and variable outcome measures, and suggests the following: EVDs may increase the risk of rebleeding; EVDs are increasingly placed by non-neurosurgeons with unclear results; intraparenchymal ICP monitors may be safely considered (with or without spinal drainage) in the setting of difficult EVD placement; the optimal timing and manner of EVD removal has yet to be defined; and the efficacy of prophylactic systemic antibiotics and antibiotic-coated EVDs needs further investigation. Nevertheless, there are no definitive practice guidelines for EVD placement and management techniques in aSAH patients. Large prospective randomised trials are needed to definitively address important gaps in our understanding of EVD management principles in the neurocritical care setting.
PMID: 20854058
ISSN: 1360-046x
CID: 4622212

Clinical grading scales in intracerebral hemorrhage

Hwang, Brian Y; Appelboom, Geoffrey; Kellner, Christopher P; Carpenter, Amanda M; Kellner, Michael A; Gigante, Paul R; Sander Connolly, E
Intracerebral hemorrhage (ICH) carries higher risk of long-term disability and mortality than any other form of stroke. Despite greater understanding of ICH pathophysiology, treatment options for this devastating condition remain limited. Moreover, a lack of a standard, universally accepted clinical grading scale for ICH has contributed to variations in management protocols and clinical trial designs. Grading scales are essential for standardized assessment and communication among physicians, selecting optimized treatment regiments, and designing effective clinical trials. There currently exist a number of ICH grading scales and prognostic models that have been developed for mortality and/or functional outcome, particularly 30 days after the ICH onset. Numerous reliable scales have been externally validated in heterogeneous populations. We extensively reviewed the inherent strengths and limitations of all the existing clinical ICH grading scales based on their development and validation methodology. For all ICH grading scales, we carefully observed study design and the definition and timing of outcome assessment to elucidate inconsistencies in grading scale derivation and application. Ultimately, we call for an expansive, prospective, multi-center clinical outcome study to clearly define all aspects of ICH, establish ideal grading scales, and standardized management protocols to enable the identification of novel and effective therapies in ICH.
PMID: 20490715
ISSN: 1556-0961
CID: 4621202

Genetic determinants of cerebral vasospasm, delayed cerebral ischemia, and outcome after aneurysmal subarachnoid hemorrhage

Ducruet, Andrew F; Gigante, Paul R; Hickman, Zachary L; Zacharia, Brad E; Arias, Eric J; Grobelny, Bartosz T; Gorski, Justin W; Mayer, Stephan A; Connolly, E Sander Jr
Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future.
PMCID:2949164
PMID: 20068580
ISSN: 0271-678x
CID: 155746

Side population hematopoietic stem cells promote wound healing in diabetic mice

Chan, Rodney K; Garfein, Evan; Gigante, Paul R; Liu, Perry; Agha, Riaz A; Mulligan, Richard; Orgill, Dennis P
BACKGROUND:Early evidence suggests that stem cells play a role in normal wound healing. Various impaired wound-healing states might be due to a deficiency in the stem cell repertoire. The authors sought to demonstrate that a new subset of lymphoid progenitor murine hematopoietic stem cells will accelerate wound healing in diabetic mice. METHODS:Bone marrow cells were harvested from C57Bl6/J femurs and separated into side and main populations based on their ability to efflux the vital dye Hoechst 33342 and the presence or absence of CD7 and CD34 markers. Side or main population cells and control solution were applied once topically to 1-cm full-thickness dorsal excisional wounds in lepr db/db and wild-type mice on the day after wounding (n = 12 in each group). Wound closure was followed by computer planimetry. Wounds were harvested after 7 and 25 days for histological analysis. RESULTS:Topical side population treatment had a significant effect on wound closure in diabetic animals, with a higher percentage of wound closure (35 +/- 7.2 percent) in this group on postoperative day 7 compared with animals treated with either main population cells (16 +/- 4.9 percent) or a vehicle control using saline (14 +/- 6.7 percent) (p < 0.05). When side population cells were given to wild-type mice that already had a normal stem cell repertoire, there was a trend toward better wound closure, but no significant differences were found. CONCLUSIONS:Side population-treated wounds healed more quickly than main population-or control-treated wounds in diabetic mice, suggesting that one stem cell subpopulation, but not the majority, harbors the potential for improving the healing process. Further studies are needed to investigate the mechanism of healing and to explore its potential as a therapeutic agent.
PMID: 17632341
ISSN: 1529-4242
CID: 4621192