Daniel B. Michael

A Cohort Study of the Safety and Feasibility of Intraventricular Urokinase for Nonaneurysmal Spontaneous Intraventricular Hemorrhage

BACKGROUND AND PURPOSE Small case series have reported potential benefit from thrombolysis after spontaneous intraventricular hemorrhage (IVH). Our objective was to review our experience using intraventricular urokinase (UK) in treating selected patients with IVH. METHODS Using medical records, we identified all patients who received ventriculostomies for CT-confirmed nonaneurysmal nontraumatic spontaneous IVH from December 1992 through November 1996. We reviewed charts and CT images and examined the data for associations with specific outcomes. RESULTS We identified 40 patients, 18 treated with ventriculostomy alone and 22 receiving adjunctive intraventricular UK. The initial Glasgow Coma Scale (GCS) scores of the two groups were similar (P = 0.5). While there was a trend for patients with any intraparenchymal hemorrhage (IPH) to receive UK (P = 0.07), the mean size of IPH in those who received ventriculostomy alone was larger than in those who received adjunctive UK (P = 0.002). There was lower mortality in the group treated with UK (31.8 versus 66.7%; P = 0.03), but there was only a trend toward an increase in favorable outcome (22.2% versus 36.4%; P = 0.3). Overall, the most significant association with outcome was neurological condition at presentation (GCS >5 versus < or = 5; P = 0.003). Receiving UK did not increase the occurrence of complications or hospital length of stay for survivors (P = 0.5). CONCLUSIONS Intraventricular UK remains a safe and potentially beneficial intervention. While it appeared to lower mortality, a randomized, placebo-controlled trial is needed to explore whether the therapy can increase the incidence of favorable outcomes.

Infection related to intracranial pressure monitors in adults: analysis of risk factors and antibiotic prophylaxis

OBJECTIVE Infection is a complication related to intracranial pressure monitoring devices. The timing, duration, and role of prophylactic antimicrobial agents against intracranial pressure monitor (ICPM) related infection have not previously been well defined. Risk factors and selection, duration, and timing of antibiotic prophylaxis in patients with ICPMs were evaluated. METHODS Records of all consecutive patients who underwent ICPM insertion between 1993 and 1996 were reviewed. Patients included were older than 12 years with an ICPM placed for at least 24 hours. Exclusion criteria consisted of ICPM placed before admission or documented CSF infection before or at the time of insertion. Standard criteria were applied to all patients for diagnosis of CSF infection. RESULTS A total of 215 patients were included, 16 (7.4%) of whom developed CSF infection. Antibiotic prophylaxis for ICPM placement was administered to 63% of infected and 59% of non-infected patients. Vancomycin (60%) and cefazolin (34%) were used most often. Sixty per cent (6/16) of patients who developed infection and 45% (53/199) of those without CSF infection received their first antibiotic dose within the 2 hours before ICPM insertion. Risk factors for CSF infection included duration of monitoring greater than 5 days (RR 4.0 (1.3–11.9)); presence of ventriculostomy (RR 3.4 (1.0–10.7)); CSF leak (RR 6.3 (1.5–27.4)); concurrent systemic infection (RR 3.4 (1.2–9.5)); or serial ICPM (RR 4.9 (1.7–13.8)). CONCLUSIONS Administration of antibiotics to patients before or at the time of ICPM placement did not decrease the incidence of CSF infection. Patients found to be at greater risk for infection at our institution included duration of ICPM greater than 5 days, use of ventricular catheter, CSF leak, concurrent systemic infection, or serial ICPM.

Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury

Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) are recognized as markers of brain damage in animal studies. There is, however, relatively little information regarding FFA concentrations in human CSF in normal and pathological conditions. The present study examined FFA concentrations in CSF from 15 patients with traumatic brain injury (TBI) and compared the data with values obtained from 73 contemporary controls. Concentrations of specific FFAs from TBI patients, obtained within 48 h of the insult were significantly greater than those in the control group (arachidonic, docosahexaenoic and myristic, P<0.001; oleic, palmitic, P<0.01; linoleic, P<0.05). Higher concentrations of total polyunsaturated fatty acids (P<0.001) and of arachidonic, myristic and palmitic acids measured individually in CSF (P<0.01) obtained 1 week after the insult were associated with a worse outcome at the time of hospital discharge using the Glasgow Outcome Scale. This preliminary investigation suggests that CSF FFA concentrations may be useful as a predictive marker of outcome following TBI.

Gene expression following traumatic brain injury in humans : analysis by microarray

Global changes in gene expression were analyzed in pericontusional tissue taken during surgery from 4 patients with traumatic brain injury (TBI), in cerebral infarction tissue from a patient with vasculitis and in normal brain tissue resected during craniotomy for meningioma. Of approximately 1,200 genes showing some level of expression by cDNA microarray hybridization, 104 ( approximately 8%) showed differential expression in traumatized tissue. Genes controlling transcriptional regulation, intermediary and energy metabolism, signal transduction, and intercellular adhesion and recognition were differentially affected most often. Four genes previously shown to be associated with TBI (c-Fos, Jun B, HSP70, and Zif/268) were all found to be up-regulated in at least one TBI patient. Thus, the robust response to TBI of several immediate early genes is confirmed, and a longer list of candidate genes from other functional categories is suggested for further studies aimed at understanding the molecular and cellular consequences of TBI.

Measurement of free fatty acids in cerebrospinal fluid from patients with hemorrhagic and ischemic stroke

Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) from patients with ischemic and hemorrhagic stroke (n=25) and in contemporary controls (n=73) were examined using HPLC. Concentrations of CSF FFAs from ischemic and hemorrhagic stroke patients obtained within 48 h of the insult were significantly greater than in control patients. Higher concentrations of polyunsaturated fatty acids (PUFAs) in CSF obtained within 48 h of insult were associated with significantly lower (P<0.05) admission Glasgow Coma Scale scores and worse outcome at the time of hospital discharge, using the Glasgow Outcome Scale (P<0.01).

Incidence of intracranial bullet fragment migration

Migration of retained bullets or bullet fragments may present as a complication of gunshot wounds to the head. This phenomenon has been reported in cases of abscess formation or retained copper fragments. Management of such migratory fragments is controversial. The purpose of this study is to determine the incidence of fragment migration in a population of neurosurgical patients treated for gunshot wounds to the head. Two-hundred and thirteen cases treated at Detroit Receiving Hospital between 1985 and 1987 were reviewed. Each patient treated had initial and one week follow-up imaging studies. Nine cases of documented migratory intracranial bullet fragments were identified. Thus, the incidence in this population is 4.2%. The fragments in eight cases were composed of copper, and in the remaining case, lead. No case was associated with an abscess. Fragments in the anterior fossa were found to migrate towards the sella turcica, while those of the middle fossa and posterior hemispheres migrate towards the confluence of sinuses (Torcula Herophili). Fragment migration was documented as early as 36 h post-injury. Based on this study, we recommend serial imaging studies to look for migrating bullet fragments and surgical removal aided by intra-operative ultrasound to localize the fragment when possible.

Patterns of immediate early gene mRNA expression following rodent and human traumatic brain injury.

Cell stimulation which leads to degeneration triggers a prolonged wave of immediate early gene (IEG) transcription that correlates with neuronal demise. In order to determine the relevance of the prolonged IEG response to human traumatic brain injury, we analyzed IEG mRNA levels in brain tissue isolated following a controlled penetrating injury and an injection of the excitotoxin Quinolinic acid (QA), as well as from tissue recovered during routine neurosurgery for trauma. Total RNA was extracted from tissue and subjected to Northern analysis of IEG mRNAs (c-fos and zif/268). Both models produced rapid and prolonged waves of IEG transcription that appeared to correlate with the severity of injury. Increases in zif/268 mRNA were observed within 1 h with levels reaching their peak at 6 h following excitotoxic injury and 3 h following a controlled penetration. In general, human traumatic brain injury resulted in variable increases in IEG mRNA levels following traumatic injury with the largest IEG mRNA increases observed in tissue collected 0-10 h after injury. This post-injury time corresponds to the peak of the prolonged IEG response observed in rodents following excitotoxic injury. Comparisons were made in IEG response between rodent frontal cortex and human cortex, because the majority of the human tissue originated from the cerebral cortex. These results further support the hypothesis that prolonged IEG transcription serves as a marker of traumatic brain injury and may play a role in neurodegeneration and/or glial activation. Moreover, observations of similar IEG patterns of expression reinforces the importance of rodent models of brain injury providing useful information directly applicable to human brain injury.

Stereolithography: Neurosurgical and medical implications

Abstract We present material to define and understand the concept of Stereolithography (STL) and its potential benefits to the field of neurosurgery and other medical specialties. A historical and scientific review of the literature on stereolithography, its evolution and uses in neurosurgery, forensic medicine, and other medical specialties are described. Considerations regarding different techniques used to obtain STL are discussed. The reproduction of cranial and vascular structures using this technique is evaluated. Data acquisition and model fabrication are the two basic steps required for stereolithography to create custom models for multiple applications in cranio-facial surgery, vascular studies, orthopedic surgery, urology and forensic medicine, among others. Stereolithography is a relatively new technique which continues to grow in many medical fields. Pre-operative education of patients, better understanding of patient anatomy, and the creation of custom-made prostheses are proven benefits of this technique.

The relationship of blunt head trauma, subarachnoid hemorrhage, and rupture of pre-existing intracranial saccular aneurysms.

Abstract Patients with a history of closed head trauma and subarachnoid hemorrhage are uncommonly diagnosed with an intracranial saccular aneurysm. This study presents a group of patients in whom a pre-existing aneurysm was discovered during work-up for traumatic subarachnoid hemorrhage. Without an accurate pre-trauma clinical history, it is difficult to define the relationship between trauma and the rupture of a pre-existing intracranial saccular aneurysm. We retrospectively reviewed 130 patients who presented to Detroit Receiving Hospital between 1993 and 1997 with a diagnosis of subarachnoid hemorrhage (SAH). Of these 130 patients, 70 were spontaneous, and 60 had a history of trauma. Mechanisms of trauma include motor vehicle accident, assault, or fall from a height. Of the 60 patients with subarachnoid hemorrhage and a history of trauma, 51 (86%) did not undergo conventional four-vessel angiography, and had no further neurological sequelae. Nine patients (14%) had a suspicious quantity of blood within the basal cisterns or Sylvian fissure and had a four-vessel angiogram. Five patients (8%) were diagnosed with a saccular intracranial aneurysm, and all underwent surgical clipping of the aneurysm. We conclude that the majority of patients (92%), with post-traumatic SAH do not harbor intracranial aneurysms. However, during initial evaluation, a high level of suspicion must be entertained when post-traumatic subarachnoid hemorrhage is encountered in the basal cisterns or Sylvian fissure, as 8% of our population were diagnosed with aneurysms. [Neurol Res 2000; 22: 165-170]

Gene expression in neurotrauma

Abstract It has been established that following injury to the central nervous system two types of damage take place, the initial insult and the secondary response to injury. This review will focus on the secondary molecular aspects of neurotrauma. These responses may be either deleterious or have protective effects upon the injured cell population. Molecular responses include the regulation of genes which change cellular architecture, up-regulate of growth factors, induce reparative stress responses, influence apoptosis and regulate the transcriptional process. The purpose of this study is to provide the reader with a brief overview of some of the molecular mechanisms which are activated following a neurological insult. [Neurol Res 2001; 23: 203-206]