Tiffany R. Chang

Iatrogenic Exserohilum infection of the central nervous system: Mycological identification and histopathological findings

An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

Improved aneurysmal subarachnoid hemorrhage outcomes: A comparison of 2 decades at an academic center

OBJECTIVE Management of aneurysmal subarachnoid hemorrhage (aSAH) has evolved over the past 2 decades, including refinement of neurosurgical techniques, availability of endovascular options, and evolution of neurocritical care; their impact on SAH outcomes is unclear. DESIGN/METHODS Prospectively collected data of patients with aSAH admitted to Johns Hopkins Medical Institutions between 1991 and 2009 were analyzed. We compared survival to discharge and functional outcomes at initial clinic appointment postdischarge (30-120 days) in patients admitted between 1991 and 2000 (phase 1 [P1]) and 2000 and 2009 (phase 2 [P2]), respectively, using dichotomized Glasgow Outcome Scale (good outcome: Glasgow Outcome Scale 4-5). RESULTS A total of 1134 consecutive patients with aSAH were included in the analysis (P1 46.4%, P2 53.6%). There were higher rates of poor grade Hunt and Hess (P1 23%, P2 28%; P < .05), admission Glasgow Coma Scale score lower than 8 (P1 14%, P2 21%; P < .005), known medical comorbidites (P1 54%, P2 64%; P = .005), associated intraventricular hemorrhage (P1 47%, P2 55%; P < .05), and older population (P1 51.5%, P2 53.5%; P < .05) in P2. Good outcomes were more common in P2 (71.5%) compared with P1 (65.2%), with 2-fold adjusted odds of good outcomes after correction for various confounding factors (P < .001). CONCLUSIONS Our institutional experience over 2 decades confirms that patients with aSAH have shown significant outcome improvements over time.

Impact of Acute Cocaine Use on Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Acute cocaine use has been temporally associated with aneurysmal subarachnoid hemorrhage (aSAH). This study analyzes the impact of cocaine use on patient presentation, complications, and outcomes. Methods— Data of patients admitted with aSAH between 1991 and 2009 were reviewed to determine impact of acute cocaine use (C). These patients were compared with aSAH patients without recent cocaine exposure (NC) in relation to their presentation, complications such as aneurysmal rerupture and delayed cerebral ischemia, and outcomes including hospital mortality and functional outcome. Results— Data of 1134 aSAH patients were reviewed; 142 patients (12.5%) had associated cocaine use. Cocaine users were more likely to be younger (mean age: C, 49±11; NC, 53±14; P<0.001). There were no differences in rates of poor-grade Hunt and Hess (4–5); (C, 21%; NC, 26%; P>0.05), associated intraventricular hemorrhage (C, 56%; NC, 51%; P>0.05), or hydrocephalus on admission Head CT (C, 49%; NC, 52%; P>0.05). Aneurysm rerupture incidence was higher among cocaine users (C, 7.7%; NC, 2.7%; P<0.05). The association of cocaine use with higher risk of delayed cerebral ischemia (C, 22%; NC, 16%; P<0.05) was not significant after correcting for other factors. Cocaine users were less likely to survive hospitalization compared with nonusers (mortality: C, 26%; NC, 17%; P<0.05); the adjusted odds of hospital mortality were 2.9 times higher among cocaine users (P<0.001). There were no differences in functional outcomes between the 2 groups. Conclusions— Acute cocaine use was associated with a higher risk of aneurysm rerupture and hospital mortality after aSAH.

Fatal exserohilum meningitis and central nervous system vasculitis after cervical epidural methylprednisolone injection.

TO THE EDITOR: We commend Thompson and colleagues (1) for the development and publication of their recent guidelines for improving entry into and retention in care for persons with HIV. These guidelines are important for consolidating best practices in the approach to this multidimensional and complex issue. However, although we understand the gaps in science that the authors present, we disagree with the III C recommendations for the use of peer navigators and intensive individual outreach. Based on our experiences in Washington, DC, these strategies should be considered vital to engaging clients from impoverished and disadvantaged communities. Both peer navigation and intensive individual outreach have become anchors for successfully engaging and retaining new and lost clients into HIV care, often in minutes rather than weeks or months. Therefore, for us, these guidelines will serve as a minimum effort required to achieve and maintain entry into and retention in care. In 2011, of 210 lost-to-care clients targeted by our outreach efforts, most of whom had detectable viral loads at their last visit, more than 50% required unorthodox approaches that exceeded the measures outlined or not mentioned in these guidelines, such as 17 telephone calls to a single client, an impromptu meeting on a street corner between a physician and client, and twice-weekly telephone calls and monthly written notes for 11 months to a single client. In an era of shrinking health care resources, we do not believe that additional research on entry into care, particularly via randomized trials, should be prioritized over implementation of effective strategies highlighted in federally funded observational studies (2, 3). In addition, a wealth of data exists on barriers to engagement in care (4, 5). Similarly, among our clients, the most common explanations and barriers to care include depression and denial associated with a new diagnosis, noninjection drug use, and delays in securing health insurance. Given this, we believe that the solutions to improving engagement in HIV care largely involve shifting resources to develop targeted policy and implementing structural interventions, such as improving access to integrated mental health and substance use treatment, expanding clinic hours, improving community health literacy, and discussing HIV and alleviating bureaucratic delays in securing health insurance. Finally, the guidelines do not specifically address the integration of pharmacists into health care teams. Inclusion of a doctor of pharmacy on our team for counseling about treatment adherence has been invaluable for client retention. If more research is funded, we agree with the recommendation to conduct operational research to demonstrate the impact of interventions like this, because it will provide evidence to justify funding for this model of service delivery.

Factor VIII in the Setting of Acute Ischemic Stroke Among Patients With Suspected Hypercoagulable State

Background: Elevation of factor VIII is associated with higher risk of large vessel arterial occlusions including stroke. Methods: Factor VIII levels were examined in consecutive patients with acute ischemic stroke (AIS) presenting to a single center between July 2008 and May 2012. Factor VIII levels exceeding the laboratory reference range were considered elevated (>150%). Results: Factor VIII level was elevated in 72.4% (84 of 116) of the patients. Elevated factor VIII level was more frequent in blacks, diabetics, and patients who were anemic. Patients with elevated factor VIII had higher median baseline National Institute of Health Stroke Scale (NIHSS; 5 vs 2, P = .0295) and twice the frequency of neuroworsening (21.4% vs 9.4%), but discharge NIHSS and modified Rankin Scale were similar in the groups. Conclusions: High factor VIII level was found in the majority of tested patients with AIS. Several baseline differences were found between patients with normal and high factor VIII levels, but no differences were identified in outcome.

Impact of pattern of admission on outcomes after aneurysmal subarachnoid hemorrhage

OBJECTIVE Patients with aneurysmal subarachnoid hemorrhage (aSAH) require management in centers with neurosurgical expertise necessitating emergent interhospital transfer (IHT). Our objective was to compare outcomes in aSAH IHTs to our institution with aSAH admissions from our institutional emergency department (ED). METHODS Data for consecutive patients with aSAH admitted to Johns Hopkins Medical Institutions between 1991 and 2009 were analyzed from a prospectively obtained database. We compared in-hospital mortality and functional outcomes at first clinical appointment post-aSAH (30-120 days) using dichotomized Glasgow Outcome Scale (good outcome: Glasgow Outcome Scale 4-5) in ED admissions with IHTs. RESULTS A total of 1134 consecutive patients with aSAH were included in analysis (ED 40.1%, IHT 59.9%). Direct ED admissions had a higher incidence of poor Hunt and Hess grade (4/5) and major medical comorbidities, with no significant differences between the 2 groups in age, intraventricular hemorrhage, and hydrocephalus. In-hospital mortality for ED admissions (14.9%) was significantly lower than that for IHTs (20.5%), with 1.8 times greater adjusted odds of survival after multivariate analysis (P = .001). Emergency department admissions had nearly 2-fold greater odds of good outcomes (odds ratio, 1.89; P < .001) after multivariate analysis. CONCLUSIONS Our institutional ED SAH admissions had significantly better outcomes than did IHTs, suggesting that delays in optimizing care before transfer could deleteriously impact outcomes.

Impact of case volume on aneurysmal subarachnoid hemorrhage outcomes

PURPOSE To compare aneurysmal subarachnoid hemorrhage (aSAH) outcomes between high- and low-volume referral centers with dedicated neurosciences critical care units (NCCUs) and shared neurosurgical, endovascular, and neurocritical care practitioners. MATERIALS AND METHODS Prospectively collected data of aSAH patients admitted to 2 institutional NCCUs were reviewed. NCCU A is a 22-bed unit staffed 24/7 with overnight in-house NCCU fellow and resident coverage. NCCU B is a 14-bed unit with home call by NCCU attending/fellow and in-house residents. RESULTS A total of 161 aSAH patients (27%) were admitted to NCCU B compared with 447 at NCCU A (73%). Among factors that independently impacted hospital mortality, there were no differences in baseline characteristics: mean age (A: 53.5 ± 14.1 years, B: 53.1 ± 13.6 years), poor grade Hunt and Hess (A: 28.2%, B: 26.7%), presence of multiple medical comorbidities (A: 28%, B: 31.1%), and associated cocaine use (A: 11.6%, B: 14.3%). There was no significant difference in hospital mortality (A: 17.9%, B: 18%), poor functional outcome (A: 30%, B: 25.4%), aneurysm rerupture (A: 2.8%, B: 2.4%), or delayed cerebral ischemia (A: 14.1%, B: 16.1%). CONCLUSIONS The noninferior outcomes at the lower SAH volume center suggests that provider expertise, not patient volume, is critical to providing high-quality specialized care.

Nadir hemoglobin is associated with poor outcome from intracerebral hemorrhage

ObjectiveExamine the relationship between anemia and outcomes from intracerebral hemorrhage (ICH).MethodsPatients admitted with spontaneous ICH between July 2008 and December 2010 were identified from our prospective stroke registry. Patients were divided into two groups based on admission hemoglobin (low vs. normal based on laboratory reference range for gender). Baseline characteristics were compared between groups using Chi-square, t-tests and Wilcoxon Rank Sum tests. Primary outcome was functional status at discharge, with modified Rankin Scale (mRS) 5–6 considered a poor outcome. Cumulative logit and logistic regression models were used to assess the relationships between baseline hemoglobin, nadir hemoglobin, and transfusion with outcomes.ResultsOf the 109 patients, 28% (n = 30) were anemic on admission. Baseline anemia did not predict the primary outcome. Nadir hemoglobin was associated with poor functional outcome at discharge (OR = 1.58, 95% CI 1.31-1.90, p < 0.0001) and remained significant after adjusting for age, baseline NIHSS, transfusion, and length of stay (OR = 1.43, 95% CI 1.06-1.94, p = 0.02). Patients who received a transfusion had 9 times greater odds of having a discharge mRS 5–6 (OR 9.37, 95% CI 2.84-30.88, p = 0.0002) compared with patients who did not receive transfusion. This was no longer statistically significant after adjusting for other factors impacting outcome (OR 4.01, 95% CI 0.64-25.32, p = 0.1392). Neither nadir hemoglobin nor transfusion was found to be independent predictors of in-hospital mortality.ConclusionThis study suggests that nadir hemoglobin, not admission hemoglobin, can be used to predict poor functional outcome. Transfusion was not an independent predictor of poor outcome from ICH.

Treatment Strategies to Attenuate Perihematomal Edema in Patients With Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (SICH) continues to be a significant cause of neurologic morbidity and mortality throughout the world. Although recent advances in the treatment of SICH have significantly decreased mortality rates, functional recovery has not been dramatically improved by any intervention to date. There are 2 predominant mechanisms of brain injury from intracerebral hemorrhage: mechanical injury from the primary hematoma (including growth of that hematoma), and secondary injury from perihematomal inflammation. For instance, in the hours to weeks after SICH as the hematoma is being degraded, thrombin and iron are released and can result in neurotoxicity, free radical damage, dysregulated coagulation, and harmful inflammatory cascades; this can clinically and radiologically manifest as perihematomal edema (PHE). PHE can contribute to mass effect, cause acute neurologic deterioration in patients, and has even been associated with poor long-term functional outcomes. PHE therefore lends itself to being a potential therapeutic target. In this article, we will review 1) the pathogenesis and time course of the development of PHE, and 2) the clinical series and trials exploring various methods, with a focus on minimally invasive surgical techniques, to reduce PHE and minimize secondary brain injury. Promising areas of continued research also will be discussed.

Definition of Traumatic Brain Injury, Neurosurgery, Trauma Orthopedics, Neuroimaging, Psychology, and Psychiatry in Mild Traumatic Brain Injury

Traumatic brain injury (TBI) disrupts the normal function of the brain. This condition can adversely affect a persons quality of life with cognitive, behavioral, emotional, and physical symptoms that limit interpersonal, social, and occupational functioning. Although many systems exist, the simplest classification includes mild, moderate, and severe TBI depending on the nature of injury and the impact on the patients clinical status. Patients with TBI require prompt evaluation and multidisciplinary management. Aside from the type and severity of the TBI, recovery is influenced by individual patient characteristics, social and environmental factors, and access to medical and rehabilitation services.