Ajith J. Thomas, Christopher S. Ogilvy, Christoph J. Griessenauer and Khalid A. Hanafy
Even though heme-induced cerebral inflammation contributes to many of the adverse sequelae seen in patients with subarachnoid hemorrhage (SAH), little is known about the mechanism; mouse models have shown a critical role for macrophages/microglia. Macrophage CD163 is a hemoglobin scavenger receptor involved in blood clearance after SAH. The authors hypothesized that the modified Fisher score is independently associated with cerebrospinal fluid (CSF) macrophage CD163 expression on postictal day 1, and that CSF macrophage CD163 expression is associated with 1-month neurological outcome.
CSF macrophages from 21 SAH and 28 unruptured aneurysm patients (control) were analyzed for CD163 expression using flow cytometry and confocal microscopy on postictal day 1. Significant associations with modified Fisher scale grades or modified Rankin Scale scores were determined using linear regression and a matched case control analysis.
CSF macrophage CD163 expression was significantly increased in SAH patients compared with controls (p < 0.001). The modified Fisher scale (mF) grades (β = 0.407, p = 0.005) and CSF bilirubin concentrations (β = 0.311, p = 0.015) were positively and independently associated with CSF macrophage CD163 expression when the analysis was controlled for age and sex. CSF macrophages from an SAH patient with a high mF grade had increased co-localization of CD163 and glycophorin A (CD235a, an erythrocyte marker) compared with those from an SAH patient with a low mF grade. The controls had no co-localization. CSF macrophage CD163 expression (p = 0.003) was inversely associated with 1-month neurological outcome, when SAH patients were matched based on mF grade.
This early study suggests that CSF macrophage CD163 expression, as measured by flow cytometry, may have some neuroprotective function given its inverse association with outcome and provides unique insights into the neuroinflammatory process after SAH.
Ajith J. Thomas, Jack P. Rock, Christine C. Johnson, Linda Weiss, Gordon Jacobsen and Mark L. Rosenblum
Object. It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring more than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents.
Methods. Data obtained in 2682 patients with synchronous brain metastases treated between 1973 and 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 population increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median length of survival was 3.2 months. There was no significant difference in the median survival of patients with primary lung/bronchus and those with an unknown primary site (3.3 months and 3.2 months, respectively).
Conclusions. Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in more than 90% of cases, is related to systemic disease; however, despite poor median survival times, certain patients will experience prolonged survival.
Ambuj Kumar and Yad Ram Yadav
Ajith J. Thomas, Jack P. Rock, Christine C. Johnson, Linda Weiss, Gordon Jacobsen and Mark L. Rosenblum
It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring greater than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents.
Data obtained in 2682 patients with synchronous brain metastases treated from 1973 to 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median survival length was 3.3 months. There was no significant difference in the median survival in patients with primary lung/bronchus and those with an unknown primary site (3.2 months and 3.4 months, respectively).
Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in greater than 90% of cases, is related to systemic disease; however, despite poor median survival lengths, certain patients will experience prolonged survival.
Raghav Gupta, Christoph J. Griessenauer, Justin M. Moore, Nimer Adeeb, Apar S. Patel, Christopher S. Ogilvy and Ajith J. Thomas
Given the highly complex and demanding clinical environment in which neurosurgeons operate, the probability of facing a medical malpractice claim is high. Recent emphasis on tort reform within the political sphere has brought this issue to the forefront of medical literature. Despite the widespread fear of litigation in the medical community, few studies have provided an analysis of malpractice litigation in the field. Here, the authors attempt to delineate the medicolegal factors that impel plaintiffs to file medical malpractice claims related to the management of brain aneurysms, and to better characterize the nature of these lawsuits.
The online legal database WestLawNext was searched to find all medical malpractice cases related to brain aneurysms across a 30-year period. All state and federal jury verdicts and settlements relevant to the search criterion were considered.
Sixty-six cases were obtained. The average age of the patient was 46.7 years. Seventy-one percent were female. The cases were distributed across 16 states. The jury found in favor of the plaintiff in 40.9% of cases, with a mean payout of $8,765,405, and in favor of the defendant in 28.8% of the cases. A failure to diagnose and/or a failure to treat in a timely manner were the 2 most commonly alleged causes of malpractice. Settlements, which were reached in 25.8% of the cases, had a mean payout of $1,818,250. Neurosurgeons accounted for 6.7% of all defendants.
Unlike other medical specialties, a majority of the verdicts were not in the defendant's favor. The mean payouts were nearly 5-fold less in cases in which a settlement was reached, as opposed to a summary judgment. Neurosurgeons accounted for a small percentage of all codefendants.
Amin Kassam, Ajith J. Thomas, Carl Snyderman, Ricardo Carrau, Paul Gardner, Arlan Mintz, Hilal Kanaan, Michael Horowitz and Ian F. Pollack
The authors reviewed their experience with endoscopic approaches to determine their safety and efficacy in the treatment of pediatric patients who harbor skull base lesions. Although they were interested in ascertaining outcomes after surgery as well as validating and defining indications and limitations of these approaches, the authors recognized that the follow-up duration was inadequate to assess long-term outcomes.
The authors conducted a retrospective review of all endoscopic procedures performed at their institution between January 2000 and September 2005. The procedures were categorized into a series of anatomical modular approaches.
Twenty-five patients 18 years of age or younger were identified. The surgical goals were individualized and included gross-total resection, partial resection, biopsy, decompression of neural structures, and repair of a cerebrospinal fluid (CSF) leak. One patient required an open procedure in addition to the expanded endonasal approach for definitive therapy. No patient suffered a neurological deficit, vascular injury, or central nervous system infection. A CSF leak was the most common complication and occurred in two (8%) of the 25 patients.
In well-selected patients, the expanded endonasal approach represents a safe, effective, and minimally invasive technique for the treatment of skull base lesions in children. Incremental experience is needed for acquiring the skills with endoscopic techniques to progress to the more complex modular approaches.
Raghav Gupta, Nimer Adeeb, Christoph J. Griessenauer, Justin M. Moore, Apar S. Patel, Christopher Kim, Ajith J. Thomas and Christopher S. Ogilvy
Health care education resources are increasingly available on the Internet. A majority of people reference these resources at one point or another. A threshold literacy level is needed to comprehend the information presented within these materials. A key component of health literacy is the readability of educational resources. The National Institutes of Health (NIH) and the American Medical Association have recommended that patient education materials be written between a 4th- and a 6th-grade education level. The authors assessed the readability of online patient education materials about brain aneurysms that have been published by several academic institutions across the US.
Online patient education materials about brain aneurysms were downloaded from the websites of 20 academic institutions. The materials were assessed via 8 readability scales using Readability Studio software (Oleander Software Solutions), and then were statistically analyzed.
None of the patient education materials were written at or below the NIH's recommended 6th-grade reading level. The average educational level required to comprehend the texts across all institutions, as assessed by 7 of the readability scales, was 12.4 ± 2.5 (mean ± SD). The Flesch Reading Ease Scale classified the materials as “difficult” to understand, correlating with a college-level education or higher. An ANOVA test found that there were no significant differences in readability among the materials from the institutions (p = 0.215).
Brain aneurysms affect 3.2% of adults 50 years or older across the world and can cause significant patient anxiety and uncertainty. Current patient education materials are not written at or below the NIH's recommended 4th- to 6th-grade education level.
Siyu Shi, Raghav Gupta, Justin M. Moore, Christoph J. Griessenauer, Nimer Adeeb, Rouzbeh Motiei-Langroudi, Ajith J. Thomas and Christopher S. Ogilvy
Brain arteriovenous malformations (AVMs) are traditionally considered congenital lesions, arising from aberrant vascular development during the intrauterine period. Rarely, however, AVMs develop in the postnatal period. Individual case reports of de novo AVM formation in both pediatric and adult patients have challenged the traditional dogma of a congenital origin. Instead, for these cases, a dynamic picture is emerging of AVM growth and development, initially triggered by ischemic and/or traumatic events, coupled with genetic predispositions. A number of pathophysiological descriptions involving aberrant angiogenic responses following trauma, hemorrhage, or inflammation have been proposed, although the exact etiology of these lesions remains to be elucidated. Here, the authors present 2 cases of de novo AVM formation in adult patients. The first case involves the development of an AVM following a venous sinus thrombosis and to the authors' knowledge is the first of its kind to be reported in the literature. They also present a case in which an elderly patient with a previously ruptured AVM developed a second AVM in the contralateral hemisphere 11 years later. In addition to presenting these cases, the authors propose a possible mechanism for de novo AVM development in adult patients following ischemic injury.
Richard S. Veyna, Donald Seyfried, Don G. Burke, Chris Zimmerman, Mark Mlynarek, Victoria Nichols, Anna Marrocco, Ajith J. Thomas, Panayiotis D. Mitsias and Ghaus M. Malik
Object. Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH.
Methods. A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II–IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test.
Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 ± 0.68 in the MgSO4 treatment group and 2.3 ± 0.73 in the control group (mean ± standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 ± 27 cm/second in MgSO4-treated patients and 102 ± 34 cm/second in the control group (mean ± SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 ± 1.6 and 3.6 ± 1.5 (mean ± SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur.
Conclusions. Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further.