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BACKGROUND Growing evidence associates traumatic brain injury (TBI) with increased risk of dementia, but few studies have evaluated associations in patients younger than 55 yr using non-TBI orthopedic trauma (NTOT) patients as controls to investigate the influence of age and TBI severity, and to identify predictors of dementia after trauma. OBJECTIVE To investigate the relationship between TBI and dementia in an institutional group. METHODS Retrospective cohort study (2000-2018) of TBI patients aged 45 to 100 yr vs NTOT controls. Primary outcome was dementia after TBI (followed ≤10 yr). Cox proportional hazards models were used to assess risk of dementia; logistic regression models assessed predictors of dementia. RESULTS Among 24 846 patients, TBI patients developed dementia (7.5% vs 4.6%) at a younger age (78.6 vs 82.7 yr) and demonstrated higher 10-yr mortality than controls (27% vs 14%; P

BackgroundIn patients with severe traumatic brain injury (TBI), coma is associated with impaired subcortical arousal mechanisms. However, it is unknown which nuclei involved in arousal (arousal nuclei) are implicated in coma pathogenesis and are compatible with coma recovery.MethodsWe mapped an atlas of arousal nuclei in the brainstem, thalamus, hypothalamus, and basal forebrain onto 3 tesla susceptibility-weighted images (SWI) in 12 patients with acute severe TBI who presented in coma and recovered consciousness within 6 months. We assessed the spatial distribution and volume of SWI microbleeds and evaluated the association of microbleed volume with the duration of unresponsiveness and functional recovery at 6 months.ResultsThere was no single arousal nucleus affected by microbleeds in all patients. Rather, multiple combinations of microbleeds in brainstem, thalamic, and hypothalamic arousal nuclei were associated with coma and were compatible with recovery of consciousness. Microbleeds were frequently detected in the midbrain (100%), thalamus (83%), and pons (75%). Within the brainstem, the microbleed incidence was largest within the mesopontine tegmentum (e.g., pedunculotegmental nucleus, mesencephalic reticular formation) and ventral midbrain (e.g., substantia nigra, ventral tegmental area). Brainstem arousal nuclei were partially affected by microbleeds, with microbleed volume not exceeding 35% of brainstem nucleus volume on average. Compared to microbleed volume within nonarousal brainstem regions, the microbleed volume within arousal brainstem nuclei accounted for a larger proportion of variance in the duration of unresponsiveness and 6-month Glasgow Outcome Scale–Extended scores.ConclusionThese results suggest resilience of arousal mechanisms in the human brain after severe TBI.

Receptor-interacting protein kinase-1 (RIPK1) is a master regulator of cell death and inflammation, and mediates programmed necrosis (necroptosis) via mixed-lineage kinase like (MLKL) protein. Prior studies in experimental intracerebral hemorrhage (ICH) implicated RIPK1 in the pathogenesis of neuronal death and cognitive outcome, but the relevant cell types involved and potential role of necroptosis remain unexplored. In mice subjected to autologous blood ICH, early RIPK1 activation was observed in neurons, endothelium and pericytes, but not in astrocytes. MLKL activation was detected in astrocytes and neurons but not endothelium or pericytes. Compared with WT controls, RIPK1 kinase-dead ( RIPK1D138N/D138N) mice had reduced brain edema (24 h) and blood-brain barrier (BBB) permeability (24 h, 30 d), and improved postinjury rotarod performance. Mice deficient in MLKL ( Mlkl-/-) had reduced neuronal death (24 h) and BBB permeability at 24 h but not 30d, and improved post-injury rotarod performance vs. WT. The data support a central role for RIPK1 in the pathogenesis of ICH, including cell death, edema, BBB permeability, and motor deficits. These effects may be mediated in part through the activation of MLKL-dependent necroptosis in neurons. The data support development of RIPK1 kinase inhibitors as therapeutic agents for human ICH.

OBJECTIVETraumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US, but the true incidence of TBI is unknown.METHODSThe National Trauma Data Bank National Sample Program (NTDB NSP) was queried for 2007 and 2013, and population-based weighted estimates of TBI-related emergency department (ED) visits, hospitalizations, and deaths were calculated. These data were compared to the 2017 Centers for Disease Control and Prevention (CDC) report on TBI, which used the Healthcare Cost and Utilization Project’s National (“Nationwide” before 2012) Inpatient Sample and National Emergency Department Sample.RESULTSIn the NTDB NSP the incidence of TBI-related ED visits was 59/100,000 in 2007 and 62/100,000 in 2013. However, in the CDC report there were 534/100,000 in 2007 and 787/100,000 in 2013. The CDC estimate for ED visits was 805% higher in 2007 and 1169% higher in 2013. In the NTDB NSP, the incidence of TBI-related deaths was 5/100,000 in 2007 and 4/100,000 in 2013. In the CDC report, the incidence was 18/100,000 in both years. The CDC estimate for deaths was 260% higher in 2007 and 325% higher in 2013.CONCLUSIONSThe databases disagreed widely in their weighted estimates of TBI incidence: CDC estimates were consistently higher than NTDB NSP estimates, by an average of 448%. Although such a discrepancy may be intuitive, this is the first study to quantify the magnitude of disagreement between these databases. Given that research, funding, and policy decisions are made based on these estimates, there is a need for a more accurate estimate of the true national incidence of TBI.

BackgroundImmune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease.MethodsThirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication.ResultsWe observed reduction of serum IL-6 and C-reactive protein in Foralumab alonevs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjectsvs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events.ConclusionsThis pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage continues to be associated with high levels of morbidity and mortality. This complication had long been thought to occur secondary to severe cerebral vasospasm, but expert opinion now favors a multi-factorial etiology, opening the possibility of new therapies. To date, no definitive treatment option for DCI has been recommended as standard of care, highlighting a need for further research into potential therapies. Milrinone has been identified as a promising therapeutic agent for DCI, possessing a mechanism of action for the reversal of cerebral vasospasm as well as potentially anti-inflammatory effects to treat the underlying etiology of DCI. Intra-arterial and intravenous administration of milrinone has been evaluated for the treatment of DCI in single center case series and cohorts and appears safe and associated with improved clinical outcomes. Recent results have also brought attention to the potential outcome benefits of early, more aggressive dosing and titration of milrinone. Limitations exist within the available data, however, and questions remain about the generalizability of results across a broader spectrum of patients suffering from DCI. The development of a standardized protocol for milrinone use in DCI, specifically addressing areas requiring further clarification, is needed. Data generated from a standardized protocol may provide the impetus for a multi-center, randomized control trial. We review the current literature on milrinone for the treatment of DCI and propose a preliminary standardized protocol for further evaluation of both safety and efficacy of milrinone.

Important differences in the biology of focal and diffuse traumatic brain injury (TBI) subtypes may result in unique pathophysiological responses to shared molecular mechanisms. Interleukin-1 (IL-1) signaling has been tested as a potential therapeutic target in preclinical models of cerebral contusion and diffuse TBI, and in a phase II clinical trial, but no published studies have examined IL-1 signaling in an impact/acceleration closed head injury (CHI) model. We hypothesized that genetic deletion of IL-1 receptor-1 (IL-1R1 KO) would be beneficial in focal (contusion) and CHI in mice. Wild type and IL-1R1 KO mice were subjected to controlled cortical impact (CCI), or to CHI. CCI produced brain leukocyte infiltration, HMGB1 translocation and release, edema, cell death, and cognitive deficits. CHI induced peak rotational acceleration of 9.7 × 10(5) ± 8.1 × 10(4) rad/s(2), delayed time to righting reflex, and robust Morris water maze deficits without deficits in tests of anxiety, locomotion, sensorimotor function, or depression. CHI produced no discernable acute plasmalemma damage or cell death, blood-brain barrier permeability to IgG, or brain edema and only a modest increase in brain leukocyte infiltration at 72 h. In both models, mature (17 kDa) interleukin-1 beta (IL-1β) was induced by 24 h in CD31+ endothelial cells isolated from injured brain but was not induced in CD11b(+) cells in either model. High mobility group box protein-1 was released from injured brain cells in CCI but not CHI. Surprisingly, cognitive outcome in mice with global deletion of IL-1R1 was improved in CHI, but worse after CCI without affecting lesion size, edema, or infiltration of CD11b(+)/CD45(+) leukocytes in CCI. IL-1R1 may induce unique biological responses, beneficial or detrimental to cognitive outcome, after TBI depending on the pathoanatomical subtype. Brain endothelium is a hitherto unrecognized source of mature IL-1β in both models.

While chronic neurological effects from concussion have been studied widely, little is known about possible links between concussion and long-term medical and behavioral comorbidities. We performed a retrospective cohort study of 9205 adult patients with concussion, matched to non-concussion controls from a hospital-based electronic medical registry. Patients with comorbidities before the index visit were excluded. Behavioral and medical comorbidities were defined by International Classification of Diseases, Ninth and Tenth Revision codes. Groups were followed for up to 10 years to identify comorbidity incidence after a concussion. Cox proportional hazards models were used to calculate associations between concussion and comorbidities after multi-variable adjustment. Patients with concussion were 57% male (median age: 31; interquartile range [IQR] = 23–48 years) at enrollment with a median follow-up time of 6.1 years (IQR = 4.2–9.1) and well-matched to healthy controls. Most (83%) concussions were evaluated in outpatient settings (5% inpatient). During follow-up, we found significantly higher risks of cardiovascular risks developing including hypertension (hazard ratio [HR] = 1.7, 95% confidence interval [CI]: 1.5–1.9), obesity (HR = 1.7, 95% CI: 1.3–2.0), and diabetes mellitus (HR = 1.8, 95% CI: 1.4–2.3) in the concussion group compared with controls. Similarly, psychiatric and neurological disorders such as depression (HR = 3.0, 95% CI: 2.6–3.5), psychosis (HR = 6.0, 95% CI: 4.2–8.6), stroke (HR = 2.1 95% CI: 1.5–2.9), and epilepsy (HR = 4.4, 95% CI: 3.2–5.9) were higher in the concussion group. Most comorbidities developed less than five years post-concussion. The risks for post-concussion comorbidities were also higher in patients under 40 years old compared with controls. Patients with concussion demonstrated an increased risk of development of medical and behavioral health comorbidities. Prospective studies are warranted to better describe the burden of long-term comorbidities in patients with concussion.

BACKGROUNDPure arterial malformations (PAMs) are rare vascular anomalies that are commonly mistaken for other vascular malformations. Because of their purported benign natural history, PAMs are often conservatively managed. The authors report the case of a ruptured PAM leading to subarachnoid hemorrhage (SAH) with intraventricular extension that was treated endovascularly.OBSERVATIONSA 38-year-old man presented with a 1-day history of headaches and nausea. A computed tomography scan demonstrated diffuse SAH with intraventricular extension, and angiography revealed a right posterior inferior cerebellar artery–associated PAM. The PAM was treated with endovascular Onyx embolization.LESSONSTo the authors’ knowledge, only 2 other cases of SAH associated with PAM have been reported. In those 2 cases, surgical clipping was pursued for definitive treatment. Here, the authors report the first case of a ruptured PAM treated using an endovascular approach, showing its feasibility as a treatment option particularly in patients in whom open surgery is too high a risk.

Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI.

Moyamoya disease (MMD) is a rare, progressive occlusive disease characterized by bilateral internal carotid artery hypoplasia that often presents with ischemic stroke and intracerebral hemorrhage (ICH). Although MMD-related ICH is generally managed similarly to spontaneous ICH, we present a case in which standard management strategies may have led to an unprecedented devastating outcome. A 37-year-old female without any previous medical history presented with headache and right-sided weakness. A computed tomography (CT) scan revealed a large left basal ganglia ICH. Vessel imaging revealed diffuse narrowing of the entire anterior circulation with prominent leptomeningeal collaterals consistent with MMD. The patient’s systolic blood pressure was kept under 140 mmHg. During the hospitalization, she became hypocarbic while being trialed on pressure support ventilation. Several hours later, she developed fixed and dilated pupils. Repeat CT head showed new diffuse cerebral edema with tonsillar herniation. Despite hyperosmolar therapy, paralytics, pentobarbital, and cerebrospinal fluid diversion, no improvement was noted. Unfortunately, brain MRI revealed multifocal brainstem infarcts with superimposed Duret hemorrhages. Herein, we report diffuse cerebral edema as a complication of MMD-related ICH. We hypothesize that disruptions of delicate cerebral autoregulatory mechanisms led to extensive hypoxic-ischemic injury. In the setting of ICH, aggressive blood pressure management coupled with relative hypocapnia may have likely caused vasoconstriction of poorly compliant arteries leading to worsened cerebral blood flow and ischemia. Therefore, because of its complex pathophysiology, strict adherence to eucapnia should be maintained in MMD-related ICH.

Extra-axial fluid collections (EACs) frequently develop after decompressive craniectomy. Management of EACs remains poorly understood, and information on how to predict their clinical course is inadequate. We aimed to better characterize EACs, understand predictors of their resolution, and delineate the best treatment paradigm for patients.We reviewed patients who developed EACs after undergoing decompressive craniectomy for treatment of refractory intracranial pressure elevations. We excluded patients who had an ischemic stroke, as EACs in these patients have a different clinical course. We performed univariate analysis and multiple linear regression to find variables associated with earlier resolution of EACs and stratified our analyses by EAC phenotype (complicated vs. uncomplicated). We conducted a systematic review to compare our findings with the literature.Of 96 included patients, 73% were male, and median age was 42.5 years. EACs resolved after a median of 60 days. Complicated EACs were common (62.5%) and required multiple drainage methods before cranioplasty. These were not associated with a protracted course or increased risk of death (P0.05). Early bone flap restoration with simultaneous drainage was independently associated with earlier resolution of EACs (β = 0.56, P 0.001). Systematic review confirmed lack of standardized direction with respect to EAC management.Our analyses reveal 2 clinically relevant phenotypes of EAC: complicated and uncomplicated. Our proposed treatment algorithm involves replacing the bone flap as soon as it is safe to do so and draining refractory EACs aggressively. Further studies to assess long-term clinical outcomes of EACs are warranted.

Background COVID‐19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ transplant (SOT) recipients are limited. Methods We examined the electronic medical records of all SOT recipients with COVID‐19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients. Results Of 52 COVID‐19‐positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty‐nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co‐infections occurred in 45% in ICU vs 5% in non‐ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died. Conclusions Our data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID‐19 compared to data in the general population of patients with COVID‐19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.

Background: The primary aim of this study is to describe current trends in racial-, age- and sex-specific incidence, clinical characteristics and burden of cerebral venous thrombosis (CVT) in the United States (US). Methods: Validated International Classification of Disease codes were used to identify all adult new cases of CVT (n=5,567) in the State Inpatients Database of New York and Florida (2006-2016) and all cases of CVT in the entire US from the National Inpatient Sample 2005-2016 (weighted n=57,315). Incident CVT counts were combined with annual US Census data to compute age and sex-specific incidence of CVT. Joinpoint regression was used to evaluate trends in incidence over time. Results: From 2005-2016, 0.47%-0.80% of all strokes in the US were CVTs but this proportion increased by 70.4% over time. Of all CVTs over this period, 66.7% were in females but this proportion declined over time (p Conclusion: The epidemiological characteristics of CVT patients in the US is changing. Incidence increased significantly over the last decade. Further studies are needed to determine whether this increase represents a true increase from changing risk factors or artefactual increase from improved detection.

Many types of neurologic injury are known to affect the cardiovascular system. Both rhythm and pump function can be dramatically affected. In this chapter, we review the cardiovascular changes that can be seen after neurologic injury and the specific neurologic diseases most commonly associated with those changes. This chapter covers hypertension, cardiomyopathy, shock, arrhythmias, and myocardial ischemia. These neurocardiogenic changes are important to diagnose, understand, and manage in order to simultaneously optimize neurologic recovery and cardiovascular function. Recognition of these neurocardiovascular connections can help neurointensivists and cardiologists best understand the underlying driving forces behind hemodynamic instabilities that can be seen in patients after acute neurologic injury.

A 53-year-old Salvadoran woman with hyperlipidemia and no previous neurologic complaints presented to the emergency department with sudden-onset right-sided weakness and dysarthria while speaking with a friend. Two days prior to presentation, she endorsed a mild bifrontal headache but denied any constitutional symptoms.

Background and Purpose— Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality. Methods— Data are collected prospectively on all patients with LVADs implanted at Brigham and Women’s Hospital. We added retrospectively collected clinical data for these analyses. Results— From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93–515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2–3.5) and all received aspirin (81–325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14–7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99–40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34–11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13–8.85). Conclusions— Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke.

Acute subdural hematoma is a devastating neurological injury with significant morbidity and mortality. In patients with large subdural hematoma resulting in compression of the underlying brain and lateral brain shift, severe neurological deficits and coma can occur. Emergent neurosurgical decompression is a life-saving intervention which improves mortality and neurological function. Persistent coma despite subdural hematoma evacuation is often the result of persistent midline shift, cerebral infarctions related to initial elevated intracranial pressure and herniation, nonconvulsive seizures, and other metabolic and infectious causes; however, a subset of patients remains comatose without a discernable etiology. In this report, we describe an elderly patient who remained comatose without a known cause for several weeks after subdural hematoma evacuation and was found to have delayed cerebral hyperperfusion on brain imaging. After several days, there was marked recovery of consciousness which occurred in a timeframe that matched improvement in brain imaging findings. Cerebral hyperperfusion following subdural hematoma evacuation requires further investigation, and should be considered as a cause of persistent but potentially recoverable coma.

Objectives Aneurysms associated with hemorrhagic moyamoya disease (MMD) are reported to stabilize or recede following revascularization. Case report/results A 29 year-old male with no past medical history presented obtunded with diffuse intraventricular hemorrhage and vascular imaging demonstrating bilateral MMD without any associated aneurysms. He underwent a delayed right-sided STA-MCA bypass and pial synangiosis, and was subsequently discharged on hospital day 24 with a modified Rankin Scale score (mRS) of 2. He returned eleven days later from a rehabilitation facility with recurrent IVH. A saccular 5 mm right P4 segment posterior cerebral artery aneurysm was seen on a diagnostic angiogram and embolized with Onyx glue. Conclusions Distal posterior circulation artery aneurysmal rupture is a rare cause of hemorrhagic MMD. This case demonstrates the capacity of these aneurysms to re-rupture following revascularization and underscores the importance of treating the aneurysms directly.

We present the case of a 63-year-old woman with a glioblastoma multiforme on immunosuppressive steroid doses who developed lethargy and fever. We review the differential diagnosis and emphasize the importance of reframing the case when the clinical course differs from expectation. Once the diagnosis is evident, we discuss the incidence and clinical course in different patient populations.

Traumatic brain injury is a leading cause of hospital visits for children. Hyperosmolar therapy is often used to treat severe traumatic brain injury. Hypertonic saline is used predominantly, yet there remains disagreement about whether hypertonic saline or mannitol is more effective.Literature search was conducted using Pubmed, Cochrane, and Embase. Systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Retrospective and prospective studies assessing use of hyperosmolar therapy in pediatric patients with severe traumatic brain injury were included.Two independent authors performed article review. Two-thousand two-hundred thirty unique articles were initially evaluated, 11 were included in the final analysis, with a total of 358 patients. Study quality was assessed using Modified Newcastle-Ottawa Scale and Jadad score.Of the 11 studies, all evaluated hypertonic saline and four evaluated both hypertonic saline and mannitol. Nine reported that hypertonic saline lowered intracranial pressure and two reported that mannitol lowered intracranial pressure. The studies varied significantly in dose, concentration, and administrations schedule for both hypertonic saline and mannitol. Five studies were prospective, but only one directly compared mannitol to hypertonic saline. The prospective comparison study found no difference in physiologic outcomes. Clinical outcomes were reported using different measures across studies. For hypertonic saline-treated patients, mechanical ventilation was required for 6.9-9 days, decompressive craniectomy was required for 6.25-29.3% of patients, ICU length of stay was 8.0-10.6 days, in-hospital mortality was 10-48%, and 6-month mortality was 7-17%. In mannitol-treated patients, ICU length of stay was 9.5 days, in-hospital mortality was 56%, and 6-month mortality was 19%.Both hypertonic saline and mannitol appear to lower intracranial pressure and improve clinical outcomes in pediatric severe traumatic brain injury, but the evidence is extremely fractured both in the method of treatment and in the evaluation of outcomes. Given the paucity of high-quality data, it is difficult to definitively conclude which agent is better or what treatment protocol to follow.

Introduction The Centers for Disease Control and Prevention (CDC) reports that there were 2.87 million cases of traumatic brain injury (TBI) in the United States in 2014, 69 million worldwide. Some studies suggest a connection between TBI and increased risk of dementia, but it remains unclear whether the risk increases with age and TBI severity. Given our aging population, it is essential to better characterize the link between TBI and dementia. Methods We conducted a retrospective cohort study of two major academic medical centers for years 2000-2015. We identified all patients with TBI, aged 45 and older. Variables included age, TBI severity, pre-existing dementia, dementia diagnosed after TBI, years to dementia, and follow-up time. TBI severity was determined by head/neck AIS score, using ICD-PIC software. Mild TBI was defined as AIS 0-2, and Moderate/Severe as AIS 3-6. Analysis was done in R.v.3.0.1 software. Results Overall, there were 14,199 patients with TBI, of which 9,938 (70%) were mild and 4,261 (30%) were moderate/severe. Mean age was 70.5 (±14.0). There were 1,422 cases (10%) of pre-existing dementia, and 850 (6%) cases of dementia diagnosed after TBI. The mean follow-up time was 1,129 (±1,474) days. The 75-84 age group had the highest incidence of TBI (28%). When compared by age group and TBI severity, the proportion of moderate/severe TBI increased with increasing age. The proportion of pre-existing dementia increased with age, as expected. Notably, there is increased incidence of dementia after TBI in patients aged 65 and older (7-10%, p < 0.001). There was no observed effect of TBI severity on the risk of dementia after TBI. Conclusions Our results indicate that TBI is a risk factor for the development of dementia, especially in patients aged 65 and older. Given the global public health burden of these two diseases it is critical to develop effective TBI primary prevention strategies. Key messages TBI is a risk factor for the development of dementia. Need for public health measures to mitigate the risk of TBI in the patient population 65 and older.

ObjectiveTo test the hypothesis that race-, age-, and sex-specific incidence of cerebral venous thrombosis (CVT) has increased in the United States over the last decade.MethodsIn this retrospective cohort study, validated ICD codes were used to identify all new cases of CVT (n = 5,567) in the State Inpatients Databases (SIDs) of New York and Florida (2006–2016). A new CVT case was defined as first hospitalization for CVT in the SID without prior CVT hospitalization. CVT counts were combined with annual Census data to compute incidence. Joinpoint regression was used to evaluate trends in incidence over time.ResultsFrom 2006 to 2016, annual age- and sex-standardized incidence of CVT in cases per 1 million population ranged from 13.9 to 20.2, but incidence varied significantly by sex (women 20.3–26.9, men 6.8–16.8) and by age/sex (women 18–44 years of age 24.0–32.6, men 18–44 years of age 5.3–12.8). Incidence also differed by race (Blacks: 18.6–27.2; Whites: 14.3–18.5; Asians: 5.1–13.8). On joinpoint regression, incidence increased across 2006 to 2016, but most of this increase was driven by an increase in all age groups of men (combined annualized percentage change [APC] 9.2%, p < 0.001), women 45 to 64 years of age (APC 7.8%, p < 0.001), and women ≥65 years of age (APC 7.4%, p < 0.001). Incidence in women 18 to 44 years of age remained unchanged over time.ConclusionCVT incidence is disproportionately higher in Blacks compared to other races. New CVT hospitalizations increased significantly over the last decade mainly in men and older women. Further studies are needed to determine whether this increase represents a true increase from changing risk factors or an artifactual increase from improved detection.

The neuroinflammatory response to traumatic brain injury (TBI) is critical to both neurotoxicity and neuroprotection, and has been proposed as a potentially modifiable driver of secondary injury in animal and human studies. Attempts to broadly target immune activation have been unsuccessful in improving outcomes, in part because the precise cellular and molecular mechanisms driving injury and outcome at acute, subacute, and chronic time points after TBI remain poorly defined. Microglia play a critical role in neuroinflammation and their persistent activation may contribute to long-term functional deficits. Activated microglia are characterized by morphological transformation and transcriptomic changes associated with specific inflammatory states. We analyzed the temporal course of changes in inflammatory genes of microglia isolated from injured brains at 2, 14, and 60 days after controlled cortical impact (CCI) in mice, a well-established model of focal cerebral contusion. We identified a time dependent, injury-associated change in the microglial gene expression profile toward a reduced ability to sense tissue damage, perform housekeeping, and maintain homeostasis in the early stages following CCI, with recovery and transition to a specialized inflammatory state over time. This later state starts at 14 days post-injury and is characterized by a biphasic pattern of IFNγ, IL-4, and IL-10 gene expression changes, with concurrent proinflammatory and anti-inflammatory gene changes. Our transcriptomic data sets are an important step to understand microglial role in TBI pathogenesis at the molecular level and identify common pathways that affect outcome. More studies to evaluate gene expression at the single cell level and focusing on subacute and chronic timepoint are warranted.

Objective Radiologic predictors of posttraumatic amnesia (PTA) duration are lacking. We hypothesized that the number and distribution of traumatic microbleeds (TMBs) detected by gradient recalled echo (GRE) magnetic resonance imaging (MRI) predicts PTA duration. Setting Academic, tertiary medical center. Participants Adults with traumatic brain injury (TBI). Design We identified 65 TBI patients with acute GRE MRI. PTA duration was determined with the Galveston Orientation and Amnesia Test, Orientation Log, or chart review. TMBs were identified within memory regions (hippocampus, corpus callosum, fornix, thalamus, and temporal lobe) and control regions (internal capsule and global). Regression tree analysis was performed to identify radiologic predictors of PTA duration, controlling for clinical PTA predictors. Main measures TMB distribution, PTA duration. Results Sixteen patients (25%) had complicated mild, 4 (6%) had moderate, and 45 (69%) had severe TBI. Median PTA duration was 43 days (range, 0-240 days). In univariate analysis, PTA duration correlated with TMBs in the corpus callosum (R = 0.29, P = .02) and admission Glasgow Coma Scale (GCS) score (R = -0.34, P = .01). In multivariate regression analysis, admission GCS score was the only significant contributor to PTA duration. However, in regression tree analysis, hippocampal TMBs, callosal TMBs, age, and admission GCS score explained 26% of PTA duration variance and distinguished a subgroup with prolonged PTA. Conclusions Hippocampal and callosal TMBs are potential radiologic predictors of PTA duration.

Background/Objective: Pharmacological stimulant therapies are routinely administered to promote recovery in patients with subacute and chronic disorders of consciousness (DoC). However, utilization rates and adverse drug event (ADE) rates of stimulant therapies in patients with acute DoC are unknown. We aimed to determine the frequency of stimulant use and associated ADEs in intensive care unit (ICU) patients with acute DoC caused by traumatic brain injury (TBI). Methods: We retrospectively identified patients with TBI admitted to the ICU at 2 level 1 trauma centers between 2015 and 2018. Patients were included if they were stimulant naive at baseline and received amantadine, methylphenidate, or modafinil during ICU admission. Stimulant dose reduction or discontinuation during ICU admission was considered a surrogate marker of an ADE. Targeted chart review was performed to identify reasons for dose reduction or discontinuation. Results: Forty-eight of 608 patients with TBI received pharmacological stimulant therapy (7.9%) during the study period. Most patients were diagnosed with severe TBI at presentation (60.4%), although stimulants were also administered to patients with moderate (14.6%) and mild (25.0%) TBI. The median time of stimulant initiation was 11 days post-injury (range: 2-28 days). Median Glasgow Coma Scale score at the time of stimulant initiation was 9 (range: 4-15). Amantadine was the most commonly prescribed stimulant (85.4%) followed by modafinil (14.6%). Seven (14.6%) patients required stimulant dose reduction or discontinuation during ICU admission. The most common ADE resulting in therapy modification was delirium/agitation (n = 2), followed by insomnia (n = 1), anxiety (n = 1), and rash (n = 1); the reason for therapy modification was undocumented in 2 patients. Conclusions: Pharmacological stimulant therapy is infrequently prescribed but well tolerated in ICU patients with acute TBI at level 1 trauma centers. These retrospective observations provide the basis for prospective studies to evaluate the safety, optimal dose range, and efficacy of stimulant therapies in this population.

The American Academy of Neurology (AAN) has established a core curriculum of topics for residency training in neurocritical care. At present there is limited data evaluating neurology residency education within the neurological intensive care unit. This study evaluates learner concerns with the neurological intensive care unit. The Communication Committee and Resident & Fellow Taskforce within the Neurocritical Care Society (NCS) developed an online survey that consisted of 20 selection and free-text based questions. The survey was distributed to NCS members and then to neurology residency program directors. Statistical analysis of neurocritical care exposure were completed with t or Fisher exact test with p-value

Herpes simplex virus (HSV) is a common cause of viral encephalitis that can lead to refractory seizures. The primary treatment of HSV encephalitis is with acyclovir; however, surgery sometimes plays a role in obtaining tissue diagnosis or decompression in cases with severe mass effect. We report a unique case in which anterior temporal lobectomy was successfully used to treat refractory status epilepticus in HSV encephalitis. Case report and review of the literature. We report a case of a 60-year-old man with HSV encephalitis, who presented with seizures originating from the right temporal lobe refractory to maximal medical management. Right anterior temporal lobectomy was performed for the purpose of treatment of refractory status epilepticus and obtaining tissue diagnosis, with ultimate resolution of seizures and excellent functional outcome. We suggest that anterior temporal lobectomy should be considered in cases of HSV encephalitis with refractory status epilepticus with clear unilateral origin.

Background: Alterations in normal coagulation and hemostasis are critical issues that require special attention in the neurosurgical patient. These disorders pose unique challenges in the management of these patients who often have concurrent acute ischemic and hemorrhagic injuries. Although neurosurgical intervention in such cases may be unavoidable and potentially life-saving, these patients should be closely observed after instrumentation. Case Description: A 57-year-old male with liver cirrhosis secondary to amyloid light-chain amyloidosis was admitted to the intensive care unit for the management of delayed hydrocephalus. An external ventricular drain (EVD) was placed for the treatment and monitoring of hydrocephalus. Five days after EVD placement, a head computed tomography scan revealed a tract hemorrhage. However, on repeated imaging, the size of the hemorrhage continued to increase despite aggressive blood pressure control and several doses of phytonadione. Extensive coagulopathy workup was remarkable for low factor VII levels. In that setting, recombinant activated factor VII was administered to normalize factor VII levels, and the tract hemorrhage stabilized. Conclusion: To the best of our knowledge, this is the first case of spontaneous hemorrhage after EVD placement in the setting of liver cirrhosis-associated factor VII deficiency. Our case highlights the importance of identifying coagulation disorders in neurosurgical patients at high risk for coagulopathy and closely monitoring them postoperatively.

Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy; however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population.

ObjectiveTo define expectations for neurocritical care (NCC) core competencies vs competencies considered within the domain of other subspecialists.MethodsAn electronic survey was disseminated nationally to NCC nurses, physicians, fellows, and neurology residents through Accreditation Council for Graduate Medical Education neurology residency program directors, United Council for Neurologic Subspecialties neurocritical care fellowship program directors, and members of the Neurocritical Care Society.ResultsA total of 268 neurocritical care providers and neurology residents from 30 institutions responded. Overall, >90% supported NCC graduates independently interpreting and managing systemic and cerebral hemodynamic data, or performing brain death determination, neurovascular ultrasound, vascular access, and airway management. Over 75% endorsed that NCC graduates should independently interpret EEG and perform bronchoscopies. Fewer but substantial respondents supported graduates being independent performing intracranial bolt (45.8%), ventriculostomy (39.0%), tracheostomy (39.8%), or gastrostomy (19.1%) procedures. Trainees differed from physicians and program directors, respectively, by advocating independence in EEG interpretation (92.8%, 61.8%, and 65.3%) and PEG placement (29.3%, 9.1%, and 8.5%).ConclusionsBroad support exists across NCC role groups for wide-ranging NCC competencies including skills often performed by other neurology and non-neurology subspecialties. Variations highlight natural divergences in expectations among trainee, physician, and nurse role groups. These results establish expectations for core competencies within NCC and initiate dialogue across subspecialties about best practice standards for the spectrum of critically ill patients requiring neurologic care.

Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as "grade 3 diffuse axonal injury," but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome.Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1 year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients.Mean ± SD number of TMBs was: dorsal brainstem = 0.7 ± 1.4, ventral brainstem = 0.2 ± 0.6, corpus callosum = 1.8 ± 2.8, and global = 14.4 ± 12.5. The mean ± SD TMB volume within AAN nuclei was 6.1 ± 18.7 mmThese findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

Background Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH. Methods In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed. Results Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy. Conclusions In this small trial, IV-D after aSAH was feasible, tolerable and safe. Trial registration number http://clinicaltrials.govNCT01024972.

Objective:To identify predictors associated with survival in civilian penetrating traumatic brain injury (pTBI) utilizing a contemporary, large, diverse 2-center cohort, and to develop a parsimonious survival prediction score for pTBI.Methods:Our cohort comprised 413 pTBI patients retrospectively identified from the local trauma registries at 2 US level 1 trauma centers, of which one was predominantly urban and the other predominantly rural. Predictors of in-hospital and 6-month survival identified in univariate and multivariable logistic regression were used to develop the simple Surviving Penetrating Injury to the Brain (SPIN) score.Results:The mean age was 33 ± 16 years and patients were predominantly male (87%). Survival at hospital discharge as well as 6 months post pTBI was 42.4%. Higher motor Glasgow Coma Scale subscore, pupillary reactivity, lack of self-inflicted injury, transfer from other hospital, female sex, lower Injury Severity Score, and lower international normalized ratio were independently associated with survival (all p < 0.001; model area under the curve 0.962). Important radiologic factors associated with survival were also identified but their addition to the full multivariable would have resulted in model overfitting without much gain in the area under the curve.Conclusions:The SPIN score, a logistic regression–based clinical risk stratification scale estimating survival after pTBI, was developed in this large, diverse 2-center cohort. While this preliminary clinical survival prediction tool does not include radiologic factors, it may support clinical decision-making after civilian pTBI if external validation confirms the probability estimates.

Background Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI. Methods From a prospective TBI outcomes database, 11 patients who underwent acute (≤7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation. Results FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 ± 0.02 vs. 0.55 ± 0.11, p

Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome. Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation. Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores. In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance.

A 68-year-old man with paroxysmal atrial fibrillation on warfarin, left subclavian thrombosis treated with carotid-subclavian bypass, and lung adenocarcinoma treated with pneumonectomy, chemotherapy, and prophylactic cranial irradiation and in remission since 1987 was admitted to our neurocritical care unit with acute onset of right-sided weakness, expressive aphasia, and lethargy. On admission his temperature was 101.7°F, and initial blood pressure was 140/60 mm Hg. There was no nuchal rigidity. He was alert and mute with impaired comprehension. He had left gaze preference. Vision was impaired in the right field. There was weakness of the right lower face. Strength was full on the left side, the right arm was weak with only antigravity movement, and he withdrew the right leg to painful stimuli. Babinski sign was present on the right. The authors thank Dr. Farzaneh Sorond (Neurology Department, Brigham and Women's Hospital) for critical review of the manuscript.

Summary A 52-year-old woman with a 10-year history of relapsing-remitting multiple sclerosis (RRMS) was started on natalizumab after she developed side effects for interferon β-1a and glatiramer acetate. The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura. Laboratory testing revealed progressive worsening thrombocytopenia up to 3 weeks following natalizumab discontinuation. Platelet antibodies to platelet-specific antigen as well as antibodies against natalizumab were positive. Bone marrow biopsy was negative. The patient was diagnosed with drug-induced immune thrombocytopenia (DITP) as a rare case of natalizumab side effect which was treated with intravenous methylprednisolone followed by rituximab with successful resolution of thrombocytopenia. The patient had a stable course of RRMS with no relapses and no brain MRI changes at 2 years after initiation of rituximab.

It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI. We retrospectively analyzed consecutive, prospectively enrolled patients of ≥50 years (n = 136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0–4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12 months, respectively. After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12 months defined as mRS 3–6 and GOS 1–3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3 months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) ≤12; p = 0.001], or had mild TBI (GCS 13–15; p = 0.002), respectively. We provide first evidence that preexisting cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization.

We examined factors associated with withdrawal of care (WOC) in moderate-severe traumatic brain injury (msTBI) patients, and how WOC may affect short-term mortality and receipt of neurosurgery. Variability in msTBI-related outcome prognostication by clinicians from different specialties was also assessed. Rates of WOC, factors associated with WOC, and the relation between WOC and in-hospital case-fatality rate (CFR) and neurosurgery were determined in 232 prospectively enrolled msTBI patients in the ongoing OPTIMISM Study at a level-1 trauma center. In a concomitant web-based survey with clinical vignettes, outcome prognostication comfort, treatment aggressiveness, and WOC recommendations were examined among 106 respondents from neurology, neurocritical care, neurosurgery, trauma and anesthesia/critical care. The average age of the study sample was 53 years, with a median Glasgow Coma Scale of 6. The in-hospital CFR was 36 and 68 % of patients had WOC. Factors independently associated with WOC were advanced age, pupillary reactivity, lower intensive care unit-length-of-stay, pre- and in-hospital cardiac arrest, herniation, intracranial pressure crisis, and pre-existing endocrine disease. Inclusion of WOC in our multivariable regression model predicting in-hospital CFRs negated all other variables. Survey results suggested that in younger patients, some clinicians prognosticated overly pessimistically based upon data available at the time of presentation. In our msTBI cohort, WOC was the most important predictor of in-hospital mortality. We identified several important independent predictors of WOC. Large within-center variability in msTBI outcome prognostication with varying levels of possible clinical nihilism exists, which may form the basis of self-fulfilling prophecies.

Introduction: Ischemic stroke is a major cause of morbidity and mortality. However, the interface of various premorbid medical conditions, vascular risk factors prior, prior antithrombotic or statins medication use, and in-hospital complications in effecting outcomes is not clearly established. We attempt establishing factors associated with improved outcomes after an acute ischemic stroke (AIS). Materials and Methods: Using the prospectively collected database, University Health Consortium from 1999 to 2004, a national USA database, multivariate step-wise backward regression analysis was performed and we were able to define premorbid characteristics, and medications that affect the outcome of AIS. Results: Initial stroke severity and poststroke in-hospital complications were associated with a poor outcome, while prior antiplatelet drug use was associated with an improved outcome. Statin use demonstrated a trend toward an improved outcome.

A 45-year-old man with no significant medical history presented following an electric current injury (380 V). He developed multiple systemic injuries including third degree burns and after 1 week of hospitalisation he reported unilateral visual changes. Examination suggested the presence of optic nerve oedema without evidence of haemorrhage, exudate or vessel abnormality. This was considered to be related to the electric shock. A trial of corticosteroids was considered. He was followed up to 5 months in clinic and was noted to have developed unilateral optic atrophy and no other systemic manifestations. Initial and 5 months follow-up optic nerve colour photograph and optical coherence topography were documented. The present case highlights the fact that electric current injury can present with only a unilateral ischaemic optic neuropathy, the need for early diagnosis for timely treatment and the controversial role of corticosteroids.