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M Sean Grady

Publications and source records attributed to M Sean Grady.

At least 19 recordsLinked to original sources
PubMed2006

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response.

Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance. In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at 5 or 27 days post-injury, and tested 48h later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at 7 days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By 1-month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

Animals↗
PubMed2006

Inbred mouse strains as a tool to analyze hippocampal neuronal loss after brain injury: a stereological study.

Traumatic brain injury (TBI) damages the hippocampus both in experimental animal models and in humans. In particular, the mechanical injury in combination with the genetic susceptibility to injury may result in neuronal loss from the hippocampus. This report explores the time-course of neuronal loss in the four primary subregions of the mouse hippocampus after a lateral fluid percussion injury (FPI) to the brain, and how subtle genetic differences between C57BL/6J and C57BL/10J mouse strains influence the extent and time course of neuronal loss. Using design-based stereological procedures, our results indicate negligible neuronal loss ipsilateral to the injury at 2 days postinjury in C57BL/6J mice, whereas a significant number (30-40%) of neurons are lost across all subregions of the hippocampus (dentate, hilus, area CA3, and area CA1) by 1 week, which does not appear to progress at 1 month, compared to sham. Additionally, neuronal counts after lateral FPI in a genetically similar, yet kainic acid-sensitive, mouse strain (C57BL/10J) showed no statistically significant differences in neuron number compared to the C57BL/6J strain in response to brain injury. Hippocampal neuronal loss after lateral FPI and its consequent circuit disruption may depend more on factors related to the mechanics and secondary consequences of the injury, as opposed to subtle genetic variations between inbred mouse strains. The loss of neurons appears to be restricted to the first week post-injury, and the remaining neurons may serve as a substrate for recovery.

Animals↗
PubMed2006

Response of the contralateral hippocampus to lateral fluid percussion brain injury.

Traumatic brain injury is a leading cause of death and disability in the United States. Pathological examinations of humans and animal models after brain injury demonstrate hippocampal neuronal damage, which may contribute to cognitive impairments. Data from our laboratories have shown that, at 1 week after brain injury, mice possess significantly fewer neurons in all ipsilateral hippocampal subregions and a cognitive impairment. Since cognitive function is distributed across both cerebral hemispheres, the present paper explores the morphological and physiological response of the contralateral hippocampus to lateral brain injury. We analyzed the contralateral hippocampus using design-based stereology, Fluoro-Jade (FJ) histochemistry, and extracellular field recordings in mice at 7 and 30 days after lateral fluid percussion injury (FPI). At 7 days, all contralateral hippocampal subregions possess significantly fewer healthy neurons compared to sham-injured animals and demonstrate FJ-positive neuronal damage, but not at 30 days. Both the ipsilateral and contralateral dentate gyri demonstrate significantly increased excitability at 7 days post-injury, but only ipsilateral dentate gyrus hyperexcitability persists at 30 days compared to sham. In the contralateral hippocampus, the transient decrease in the number of healthy neurons, concomitant with FJ damage, and electrophysiological alterations establish a stunned period of cellular and circuit dysfunction. The return of healthy neuron number, absence of FJ damage, and sham level of excitability in the contralateral hippocampus suggest recovery of structure and function by 30 days after injury. The cognitive recovery observed after human traumatic brain injury may stem from a differential injury exposure and time course of recovery between homologous regions of the two hemispheres.

Animals↗
PubMed2006

Impaired fibrinolysis and traumatic brain injury in mice.

Traumatic brain injury (TBI) has been associated with intravascular coagulation, which may be a result of thromboplastin released following brain injury. Clots thus formed are lysed by plasmin, which is activated by tissue-type and urokinase-type plasminogen activators (uPA). To evaluate the association between traumatic intravascular coagulation and post-traumatic outcome, uPA knockout (uPA-/-) transgenic mice (n=12) or wild-type littermates (WT; n=12) were anesthetized and subjected to controlled cortical impact (CCI) brain injury. A second group of uPA-/- (n=12) and WT mice (n=12) were subjected to sham injury. Motor function was assessed over 2 weeks using the composite neuroscore test and cognition (learning) was assessed with the Morris Water Maze (MWM) at 2 weeks post-injury, whereupon the animals were sacrificed for cortical lesion volume analysis. Motor function was significantly worse in the brain-injured uPA-/- mice when compared to brain-injured WT mice at 48 h (p<0.05) and one week post-injury (p<0.05). These differences resolved by 2 weeks post-injury. There was no significant difference in post-injury cognitive function between uPA-/- mice and WT mice. However, at 2 weeks post-injury, the brain-injured uPA-/- had a significantly larger volume of cortical tissue loss than their WT counterparts (p<0.05). These results demonstrate that the absence of uPA in mice aggravates acute motor deficit and exacerbates cortical tissue loss following CCI brain injury, and suggests a neuroprotective role of the fibrinolytic process following TBI.

Animals↗
PubMed2006

Spontaneous cerebrospinal fluid leaks: a variant of benign intracranial hypertension.

OBJECTIVES: Previous reports indicate that elevated intracranial pressure (ICP) may cause spontaneous cerebrospinal fluid (CSF) leaks. In this study we examined the clinical diagnosis of benign intracranial hypertension (BIH) in this population using the modified Dandy criteria. METHODS: We performed a retrospective review of clinical data and measurements of ICPs after surgical repair. RESULTS: Sixteen patients with spontaneous CSF leaks were surgically treated from 1996 to 2002. In 11 patients with CSF pressure measurements, strict adherence to the modified Dandy criteria definitively confirmed a diagnosis of BIH in 8 patients (72%) and a likely diagnosis in the 3 remaining patients. The mean ICP was 31.1 cm H20 (range, 17.3 to 52 cm H2O), and 81% of the patients were obese middle-aged women. Clinically, all patients had signs and/or symptoms of elevated ICP, such as headache (91%), pulsatile tinnitus (45%), hypertension (45%), balance problems (27%), and visual complaints (18%). Surgical repair was 100% successful in leak cessation over a mean follow-up of 14.1 months. CONCLUSIONS: Most patients with spontaneous CSF leaks fulfill the modified Dandy criteria; thus, this disorder appears to be a variant of BIH. Further investigation is needed to determine the exact cause of elevated CSF pressures in this group and whether medical or surgical treatments to correct the intracranial hypertension are warranted.

Adult↗
PubMed2005

Endoscopic management of cerebrospinal fluid leak associated with the use of bone wax in skull-base surgery.

OBJECTIVE: To alert otolaryngologists to consider the possibility that bone wax may be associated with cerebrospinal fluid leaks that occur immediately after skull-base craniotomy approaches. STUDY DESIGN AND SETTING: Clinical report from surgical experience in a tertiary care setting. RESULTS: Three patients presented with brisk cerebrospinal fluid leak after craniotomy. Sinus endoscopy revealed bone wax within a small parasphenoid defect in all 3 cases. CONCLUSIONS: Bleeding from areas of the skull base adjacent to the paranasal sinuses during craniotomy can signal a small breach of the skull base. Bone wax may control bleeding from edges of transected bone but also stent the skull-base defect open, preventing fibrin deposition and spontaneous healing and closure. SIGNIFICANCE: Otolaryngologists repairing a cerebrospinal fluid leak after a skull-base craniotomy approach should consider the possibility of encountering bone wax and be able to identify it to better treat their patient.

Adult↗
PubMed2005

Lateral fluid percussion brain injury: a 15-year review and evaluation.

This article comprehensively reviews the lateral fluid percussion (LFP) model of traumatic brain injury (TBI) in small animal species with particular emphasis on its validity, clinical relevance and reliability. The LFP model, initially described in 1989, has become the most extensively utilized animal model of TBI (to date, 232 PubMed citations), producing both focal and diffuse (mixed) brain injury. Despite subtle variations in injury parameters between laboratories, universal findings are evident across studies, including histological, physiological, metabolic, and behavioral changes that serve to increase the reliability of the model. Moreover, demonstrable histological damage and severity-dependent behavioral deficits, which partially recover over time, validate LFP as a clinically-relevant model of human TBI. The LFP model, also has been used extensively to evaluate potential therapeutic interventions, including resuscitation, pharmacologic therapies, transplantation, and other neuroprotective and neuroregenerative strategies. Although a number of positive studies have identified promising therapies for moderate TBI, the predictive validity of the model may be compromised when findings are translated to severely injured patients. Recently, the clinical relevance of LFP has been enhanced by combining the injury with secondary insults, as well as broadening studies to incorporate issues of gender and age to better approximate the range of human TBI within study design. We conclude that the LFP brain injury model is an appropriate tool to study the cellular and mechanistic aspects of human TBI that cannot be addressed in the clinical setting, as well as for the development and characterization of novel therapeutic interventions. Continued translation of pre-clinical findings to human TBI will enhance the predictive validity of the LFP model, and allow novel neuroprotective and neuroregenerative treatment strategies developed in the laboratory to reach the appropriate TBI patients.

Animals↗
PubMed2005

Brain tissue oxygen practice guidelines using the LICOX CMP monitoring system.

When a new technology is introduced it is important to empower the bedside practitioner with a resource tool that outlines the purpose, placement procedure, technology application guidelines, and interventions associated with that new technology. This promotes product and patient safety and successful implementation of the new technology. Continued evaluation of bedside clinical practice and the technology used in the care and treatment of the severe brain injured patient can lead to improvements in management and in technology design. Future clinical research initiatives exploring the impact of new technology will enable us to discover cost-effective treatments and interventions that will improve the outcome for a person with traumatic brain injury, a condition that devastates hundreds of thousands of Americans each year.

Critical Care↗
PubMed2005

Self-inflicted submental and transoral gunshot wounds that produce nonfatal brain injuries: management and prognosis.

OBJECT: Penetrating brain injuries caused by self-inflicted gunshot wounds are very often fatal and survivors suffer serious disabilities. Recognition of a possibly more favorable prognosis for a specific type of injury, the submental or transoral handgun or low-energy rifle wound, prompted the authors to review their experience with patients who had attempted suicide in this manner. METHODS: The records of 11 consecutive patients seen over a 10-year period (1992-2001) were retrospectively reviewed. Handguns were used by eight patients and .22 caliber rifles by the others. The patients presented with predominantly unilateral frontal brain injuries that required urgent attention. One elderly patient who had made an advance directive concerning care died. All other patients underwent craniotomy and repair of associated ophthalmological and maxillofacial injuries. Follow-up review ranged from 9 months to 3 years, during which time there were no repeated suicide attempts. All but one patient expressed satisfaction with their appearance and returned to a self-sufficient lifestyle. CONCLUSIONS: Self-inflicted submental and transoral handgun and low-energy rifle wounds may produce serious but survivable brain injuries if the path of the bullet is limited to the frontal area. Early aggressive management of brain, dural, and craniomaxillofacial injuries should return the patient to a highly functional neurological status and restore an acceptable outward appearance. Outcomes, therefore, appear to be much better for these patients than for most patients with a penetrating brain injury due to a self-inflicted gunshot wound.

Adult↗
PubMed2005

Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring.

OBJECT: An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome. METHODS: Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 +/- 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 +/- 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05). CONCLUSIONS: The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.

Adult↗
PubMed2004

The misdiagnosis of acute cervical spine injuries and fractures in infants and children: the 12-year experience of a level I pediatric and adult trauma center.

OBJECTIVE: The objective was to determine the frequency of acute cervical spine injuries and fractures that were misdiagnosed in infants and children (< or =14 years) initially evaluated at a pediatric and adult urban level I trauma center. METHODS AND RESULTS: This was a retrospective, single-institution, case series of pediatric cervical spine injuries and fractures that were misdiagnosed during initial emergency room imaging evaluation. "Misdiagnosed" cases were those cases whose imaging studies initially obtained in the emergency room were misinterpreted based on reevaluation by a senior trauma radiologist blinded to the initial results. Nineteen percent (7 out of 37) were misdiagnosed on initial emergency room imaging evaluation. Five percent were true "missed" fractures, and 14% were "normal and/or developmental variants" read as fractures or dislocation. CONCLUSIONS: The error rate for infants and children < or =8 years was 24%, and for children > or =9 years was 15%. The occiput to C2 region was the most common site of diagnostic error. The most common factors predisposing to misdiagnosis were unfamiliarity with pediatric cervical spine anatomy, failure to recognize normal variants seen during growth and development, and suboptimal conventional film techniques.

Adolescent↗
PubMed2004

Hypoxia is important in the biology and aggression of human glial brain tumors.

We investigated whether increasing levels of tissue hypoxia, measured by the binding of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] or by Eppendorf needle electrodes, were associated with tumor aggressiveness in patients with previously untreated glial brain tumors. We hypothesized that more extensive and severe hypoxia would be present in tumor cells from patients bearing more clinically aggressive tumors. Hypoxia was measured with the 2-nitroimidazole imaging agent EF5 in 18 patients with supratentorial glial neoplasms. In 12 patients, needle electrode measurements were made intraoperatively. Time to recurrence was used as an indicator of tumor aggression and was analyzed as a function of EF5 binding, electrode values and recursive partitioning analysis (RPA) classification. On the basis of EF5 binding, WHO grade 2 tumors were characterized by modest cellular hypoxia (pO2s approximately 10%) and grade 3 tumors by modest-to-moderate hypoxia (pO2s approximately 10%- 2.5%). Severe hypoxia (approximately 0.1% oxygen) was present in 5 of 12 grade 4 tumors. A correlation between more rapid tumor recurrence and hypoxia was demonstrated with EF5 binding, but this relationship was not predicted by Eppendorf measurements.

Aged↗
PubMed2004

Cerebrospinal fluid pressure monitoring after repair of cerebrospinal fluid leaks.

OBJECTIVE: To measure intracranial pressures (ICPs) via lumbar drains after surgical repair of cerebrospinal fluid (CSF) leaks. METHODS: We conducted a retrospective review of ICP measurements through lumbar drains during the immediate postoperative period after CSF leak repair. RESULTS: Eight patients with spontaneous CSF leaks underwent surgery and postoperative CSF pressures were measured via lumbar drains. ICP was elevated in 7/8 patients (mean, 32.5 cm H(2)O). Diuretics reduced ICP (mean, 10 cm H(2)O). Three traumatic CSF leaks patients served as controls (mean, ICP 14 cm H(2)O). CONCLUSION: Measurement of ICP through lumbar drains provides important information regarding the pathophysiology of CSF leaks that has an impact on subsequent medical and surgical treatment. Although the precise cause and mechanism of spontaneous CSF leaks are not fully understood, this study indicates that elevated ICP plays a role and that further medical or surgical treatment to correct the intracranial hypertension may be warranted.

Adult↗
PubMed2004

Mechanical failure of the electrode wire in deep brain stimulation.

The feasibility and efficacy of deep brain stimulation (DBS) has offered new possibilities for treatment of movement disorders. Mechanical failure of the DBS system is a potential complication. Here we report five patients who presented with mechanical failure of the DBS system. Radiographs of the skull and cervical spine were analyzed for disruptions. Seven instances of lead breakage near the connection of the DBS electrode with the extension wire were identified. In one patient this was in the paramastoid area over the skull, while in all others were in the supraclavicular location. The patients consisted of three men and two women ranging in age from 24 to 78 (at the time of first operation), one person suffering three breakages. The length of spanned time from implantation to presentation ranged from 8 to 32 months. Palpation of the electrode lead wire in the neck for breakage proved unreliable. Radiography localized the site of breakage in all but one patient who required intraoperative exploration, which revealed that although the lead wire was disrupted, the two ends remained in contact. The fact that all breakages occurred near the connection wire suggests that to-and-fro motion of the DBS electrode with repeated head turning leads to fatigue and eventual disruption.

Adult↗
PubMed2004

What we research: survey of American Association of Neurological Surgeons and Congress of Neurological Surgeons member publications.

OBJECT: The goal of this study was to create a searchable database of research manuscripts authored by members of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS) to describe the nature and character of the research currently being undertaken by neurosurgeons. METHODS: Manuscripts published by all physician members listed in the 2001 AANS/CNS Membership Directory (6921 physicians) were gathered into a database through individual literature searches of the author name for the calendar year 2001. Duplicate publications were purged and the database was reviewed for accuracy. An internal verification of the database revealed a 4% underreporting rate. Statistics from the database were compiled and displayed with information about AANS/CNS members and their clinical activities. The AANS/CNS members published a total of 2748 research the manuscripts in 479 different journals during 2001. Thirty-eight percent of the manuscripts (1042 of 2748) were authored by US members and 62% (1706 of 2748) by non-US members. The focus of the majority of manuscripts included the areas of brain tumor (26%; 707 of 2748), vascular disease (20%; 558 of 2748), spine (10%; 282 of 2748), and trauma (8%; 233 of 2748). Sixty-nine percent of manuscripts (1897 of 2748) were retrospective and technical clinical studies, and of these 39% (744 of 1897) were case reports. Laboratory investigations made up 15% (414 of 2748) of all manuscripts, whereas prospective randomized clinical trials represented 1% (34 of 2748). CONCLUSIONS: The majority of AANS/CNS member manuscripts are authored by non-US members despite their small AANS/CNS representation. Most research is clinical, based on retrospective data, and includes a large number of case reports. A disparity exists between what neurosurgeons do clinically and both the quantity and subject of their research.

Authorship↗
PubMed2004

Cerebral oxygenation following decompressive hemicraniectomy for the treatment of refractory intracranial hypertension.

OBJECT: Medically intractable intracranial hypertension is a major cause of morbidity and mortality after severe brain injury. One potential treatment for intracranial hypertension is decompressive hemicraniectomy (DCH). Whether and when to use DCH, however, remain unclear. The authors therefore studied the effects of DCH on cerebral O2 to develop a better understanding of the effects of this treatment on the recovery from injury and disease. METHODS: The study focused on seven patients (mean age 30.6 +/- 9.7 years) admitted to the hospital after traumatic brain injury (five patients) or subarachnoid hemorrhage (two patients) as part of a prospective observational database at a Level I trauma center. At admission the Glasgow Coma Scale (GCS) score was 6 or less in all patients. Patients received continuous monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), blood pressure, and arterial O2 saturation. Cerebral oxygenation was measured using the commercially available Licox Brain Tissue Oxygen Monitoring System manufactured by Integra NeuroSciences. A DCH was performed when the patient's ICP remained elevated despite maximal medical management. CONCLUSIONS: All patients tolerated DCH without complications. Before the operation, the mean ICP was elevated in all patients (26 +/- 4 mm Hg), despite maximal medical management. After surgery, there was an immediate and sustained decrease in ICP (19 +/- 11 mm Hg) and an increase in CPP (81 +/- 17 mm Hg). Following DCH, cerebral oxygenation improved from a mean of 21.2 +/- 13.8 mm Hg to 45.5 +/- 25.4 mm Hg, a 114.8% increase. The change in brain tissue O2 and the change in ICP after DCH demonstrated only a modest relationship (r2 = 0.3). These results indicate that the use of DCH in the treatment of severe brain injury is associated with a significant improvement in brain O2.

Adult↗