Resting-State EEG Signature of Early Consciousness Recovery in Comatose Traumatic Brain Injury Patients.

Background Resting-state electroencephalogram (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI) patients. We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in comatose TBI patients. Methods This is a retrospective study of comatose TBI patients who were admitted to a level-1 trauma center (10/2013-1/2022). Demographics, basic clinical data, imaging characteristics, and EEG data were collected. We calculated using 10-minute rsEEGs: power spectral density (PSD), permutation entropy (PE - complexity measure), weighted symbolic-mutual-information (wSMI - global information sharing measure), Kolmogorov complexity (Kolcom - complexity measure), and heart-evoked potentials (HEP - the averaged EEG signal relative to the corresponding QRS complex on electrocardiogram). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, rsEEG data via Support Vector Machine with a linear kernel (SVM). Results We studied 113 (out of 134, 84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50, p .01). Patients who recovered consciousness had higher Kolcom (U = 1688, p = 0.01,), increased beta power (U = 1652 p = 0.003), with higher variability across channels ( U = 1534, p = 0.034), and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04) and showed higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = .026, U = 1639, p = 0.024) than those who didn't recover. The ROC-AUC improved from 0.66 (using age, motor response, pupils' reactivity, and CT Marshall classification) to 0.69 (p < 0.001) when adding rsEEG measures. Conclusion We describe the rsEEG EEG signature in recovery of consciousness prior to discharge in comatose TBI patients. Resting-state EEG measures improved prediction beyond the clinical and imaging data.

Covert Tracking to Immersive Stimuli in Traumatic Brain Injury Subjects With Disorders of Consciousness.

Eye tracking assessments are clinician dependent and can contribute to misclassification of coma. We investigated responsiveness to videos with and without audio in traumatic brain injury (TBI) subjects using video eye-tracking (VET). We recruited 20 healthy volunteers and 10 unresponsive TBI subjects. Clinicians were surveyed whether the subject was tracking on their bedside assessment. The Coma Recovery Scale-Revised (CRS-R) was also performed. Eye movements in response to three different 30-second videos with and without sound were recorded using VET. The videos consisted of moving characters (a dancer, a person skateboarding, and Spiderman). Tracking on VET was defined as visual fixation on the character and gaze movement in the same direction of the character on two separate occasions. Subjects were classified as "covert tracking" (tracking using VET only), "overt tracking" (VET and clinical exam by clinicians), and "no tracking". A k-nearest-neighbors model was also used to identify tracking computationally. Thalamocortical connectivity and structural integrity were evaluated with EEG and MRI. The ability to obey commands was evaluated at 6- and 12-month follow-up. The average age was 29 (± 17) years old. Three subjects demonstrated "covert tracking" (CRS-R of 6, 8, 7), two "overt tracking" (CRS-R 22, 11), and five subjects "no tracking" (CRS-R 8, 6, 5, 6, 7). Among the 84 tested trials in all subjects, 11 trials (13%) met the criteria for "covert tracking". Using the k-nearest approach, 14 trials (17%) were classified as "covert tracking". Subjects with "tracking" had higher thalamocortical connectivity, and had fewer structures injured in the eye-tracking network than those without tracking. At follow-up, 2 out of 3 "covert" and all "overt" subjects recovered consciousness versus only 2 subjects in the "no tracking" group. Immersive stimuli may serve as important objective tools to differentiate subtle tracking using VET.

Predictors and Temporal Trends of Withdrawal of Life-Sustaining Therapy After Acute Stroke in the Florida Stroke Registry.

Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined. DESIGN: Observational study (2008-2021). SETTING: Florida Stroke Registry (152 hospitals). PATIENTS: Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST. Patients who had WLST were older (77 vs 70 yr), more women (57% vs 49%), White (76% vs 67%), with greater stroke severity on the National Institutes of Health Stroke Scale greater than or equal to 5 (29% vs 19%), more likely hospitalized in comprehensive stroke centers (52% vs 44%), had Medicare insurance (53% vs 44%), and more likely to have impaired level of consciousness (38% vs 12%). Most predictors associated with the decision to WLST in AIS were age, stroke severity, region, insurance status, center type, race, and level of consciousness (RF AUC of 0.93 and LR AUC of 0.85). Predictors in ICH included age, impaired level of consciousness, region, race, insurance status, center type, and prestroke ambulation status (RF AUC of 0.76 and LR AUC of 0.71). Factors in SAH included age, impaired level of consciousness, region, insurance status, race, and stroke center type (RF AUC of 0.82 and LR AUC of 0.72). Despite a decrease in the rates of early WLST (< 2 d) and mortality, the overall rates of WLST remained stable. CONCLUSIONS: In acute hospitalized stroke patients in Florida, factors other than brain injury alone contribute to the decision to WLST. Potential predictors not measured in this study include education, culture, faith and beliefs, and patient/family and physician preferences. The overall rates of WLST have not changed in the last 2 decades.

Covert Tracking to Visual Stimuli in Comatose Patients With Traumatic Brain Injury.

OBJECTIVES: This study investigated video eye tracking (VET) in comatose patients with traumatic brain injury (TBI). METHODS: We recruited healthy participants and unresponsive patients with TBI. We surveyed the patients' clinicians on whether the patient was tracking and performed the Coma Recovery Scale-Revised (CRS-R). We recorded eye movements in response to motion of a finger, a face, a mirror, and an optokinetic stimulus using VET glasses. Patients were classified as covert tracking (tracking on VET alone) and overt tracking (VET and clinical examination). The ability to obey commands was evaluated at 6-month follow-up. RESULTS: We recruited 20 healthy participants and 10 patients with TBI. The use of VET was feasible in all participants and patients. Two patients demonstrated covert tracking (CRS-R of 6 and 8), 2 demonstrated overt tracking (CRS-R of 22 and 11), and 6 patients had no tracking (CRS-R of 8, 6, 5, 7, 6, and 7). Five of 56 (9%) tracking assessments were missed on clinical examination. All patients with tracking recovered consciousness at follow-up, whereas only 2 of 6 patients without tracking recovered at follow-up. DISCUSSION: VET is a feasible method to measure covert tracking. Future studies are needed to confirm the prognostic value of covert tracking.

Posttraumatic Stress Symptoms Among COVID-19 Survivors After Hospitalization.

OBJECTIVE: Limited data are available on posttraumatic stress symptoms (PTSS) among COVID-19 survivors. This study aimed to contribute to this knowledge base. METHODS: PTSS among COVID-19 survivors who had been hospitalized were investigated. Patients were identified as COVID-19 positive at hospital admission. COVID-19 survivors were surveyed with the Posttraumatic Stress Disorder Checklist (PCL-5) between March and October 2020 at 5- and 12-month postdischarge follow-up points. RESULTS: Of 411 patients, 331 (81%) survived to hospital discharge. Of these survivors, 83 (25%) completed the PCL-5 at the 5-month follow-up. Of those patients, 12 (14%) screened positive for PTSS. At the 12-month follow-up, four of eight patients remained PTSS positive. Mean age of follow-up participants was 62±15 years; 47% were women, 65% were White, and 63% were Hispanic. PTSS-positive patients were predominantly non-White (67% vs. 30%, p=0.02), and although the differences were not statistically significant, these patients tended to be younger (56 vs. 63 years, p=0.08) and have shorter intensive care unit stays (2.0 vs. 12.5 days, p=0.06). PTSS-positive and PTSS-negative groups did not differ significantly in prehospitalization neurological diagnoses (11% vs. 8%), psychiatric diagnoses (17% vs. 21%), and intensive care admission status (25% vs. 25%). More patients in the PTSS-positive group had returned to the emergency department (50% vs. 14%, p<0.01) and reported fatigue at follow-up (100% vs. 42%, p<0.001). In the multivariate logistic regression model, non-White race (OR=11, 95% CI=2-91) and returning to the emergency department (OR=19, 95% CI=3-252) were associated with PTSS-positive status. CONCLUSION: PTSS were twice as common among hospitalized COVID-19 survivors than among those in the general population.

Association of Acute Alteration of Consciousness in Patients With Acute Ischemic Stroke With Outcomes and Early Withdrawal of Care.

BACKGROUND AND OBJECTIVES: Early consciousness disorder (ECD) after acute ischemic stroke (AIS) is understudied. ECD may influence outcomes and the decision to withhold or withdraw life-sustaining treatment. METHODS: We studied patients with AIS from 2010 to 2019 across 122 hospitals participating in the Florida Stroke Registry. We studied the effect of ECD on in-hospital mortality, withholding or withdrawal of life-sustaining treatment (WLST), ambulation status on discharge, hospital length of stay, and discharge disposition. RESULTS: Of 238,989 patients with AIS, 32,861 (14%) had ECD at stroke presentation. Overall, average age was 72 years (Q1 61, Q3 82), 49% were women, 63% were White, 18% were Black, and 14% were Hispanic. Compared to patients without ECD, patients with ECD were older (77 vs 72 years), were more often female (54% vs 48%), had more comorbidities, had greater stroke severity as assessed by the National Institutes of Health Stroke Scale (score ≥5 49% vs 27%), had higher WLST rates (21% vs 6%), and had greater in-hospital mortality (9% vs 3%). Using adjusted models accounting for basic characteristics, patients with ECD had greater in-hospital mortality (odds ratio [OR] 2.23, 95% CI 1.98-2.51), had longer hospitalization (OR 1.37, 95% CI 1.33-1.44), were less likely to be discharged home or to rehabilitation (OR 0.54, 95% CI 0.52-0.57), and were less likely to ambulate independently (OR 0.61, 95% CI 0.57-0.64). WLST significantly mediated the effect of ECD on mortality (mediation effect 265; 95% CI 217-314). In temporal trend analysis, we found a significant decrease in early WLST (<2 days) (R2 0.7, p = 0.002) and an increase in late WLST (≥2 days) (R2 0.7, p = 0.004). DISCUSSION: In this large prospective multicenter stroke registry, patients with AIS presenting with ECD had greater mortality and worse discharge outcomes. Mortality was largely influenced by the WLST decision.

Withdrawal of Life-Sustaining Treatment Mediates Mortality in Patients With Intracerebral Hemorrhage With Impaired Consciousness.

BACKGROUND AND PURPOSE: Impaired level of consciousness (LOC) on presentation at hospital admission in patients with intracerebral hemorrhage (ICH) may affect outcomes and the decision to withhold or withdraw life-sustaining treatment (WOLST). METHODS: Patients with ICH were included across 121 Florida hospitals participating in the Florida Stroke Registry from 2010 to 2019. We studied the effect of LOC on presentation on in-hospital mortality (primary outcome), WOLST, ambulation status on discharge, hospital length of stay, and discharge disposition. RESULTS: Among 37 613 cases with ICH (mean age 71, 46% women, 61% White, 20% Black, 15% Hispanic), 12 272 (33%) had impaired LOC at onset. Compared with cases with preserved LOC, patients with impaired LOC were older (72 versus 70 years), more women (49% versus 45%), more likely to have aphasia (38% versus 16%), had greater ICH score (3 versus 1), greater risk of WOLST (41% versus 18%), and had an increased in-hospital mortality (32% versus 12%). In the multivariable-logistic regression with generalized estimating equations accounting for basic demographics, comorbidities, ICH severity, hospital size and teaching status, impaired LOC was associated with greater mortality (odds ratio, 3.7 [95% CI, 3.1-4.3], P<0.0001) and less likely discharged home or to rehab (odds ratio, 0.3 [95% CI, 0.3-0.4], P<0.0001). WOLST significantly mediated the effect of impaired LOC on mortality (mediation effect, 190 [95% CI, 152-229], P<0.0001). Early WOLST (<2 days) occurred among 51% of patients. A reduction in early WOLST was observed in patients with impaired LOC after the 2015 American Heart Association/American Stroke Association ICH guidelines recommending aggressive treatment and against early do-not-resuscitate. CONCLUSIONS: In this large multicenter stroke registry, a third of ICH cases presented with impaired LOC. Impaired LOC was associated with greater in-hospital mortality and worse disposition at discharge, largely influenced by early decision to withhold or WOLST.

Multimorbidity and Critical Care Neurosurgery: Minimizing Major Perioperative Cardiopulmonary Complications.

With increasing prevalence of chronic diseases, multimorbid patients have become commonplace in the neurosurgical intensive care unit (neuro-ICU), offering unique management challenges. By reducing physiological reserve and interacting with one another, chronic comorbidities pose a greatly enhanced risk of major postoperative medical complications, especially cardiopulmonary complications, which ultimately exert a negative impact on neurosurgical outcomes. These premises underscore the importance of perioperative optimization, in turn requiring a thorough preoperative risk stratification, a basic understanding of a multimorbid patient's deranged physiology and a proper appreciation of the potential of surgery, anesthesia and neurocritical care interventions to exacerbate comorbid pathophysiologies. This knowledge enables neurosurgeons, neuroanesthesiologists and neurointensivists to function with a heightened level of vigilance in the care of these high-risk patients and can inform the perioperative neuro-ICU management with individualized strategies able to minimize the risk of untoward outcomes. This review highlights potential pitfalls in the intra- and postoperative neuro-ICU period, describes common preoperative risk stratification tools and discusses tailored perioperative ICU management strategies in multimorbid neurosurgical patients, with a special focus on approaches geared toward the minimization of postoperative cardiopulmonary complications and unplanned reintubation.

What is the Role of Hyperosmolar Therapy in Hemispheric Stroke Patients?

The role of hyperosmolar therapy (HT) in large hemispheric ischemic or hemorrhagic strokes remains a controversial issue. Past and current stroke guidelines state that it represents a reasonable therapeutic measure for patients with either neurological deterioration or intracranial pressure (ICP) elevations documented by ICP monitoring. However, the lack of evidence for a clear effect of this therapy on radiological tissue shifts and clinical outcomes produces uncertainty with respect to the appropriateness of its implementation and duration in the context of radiological mass effect without clinical correlates of neurological decline or documented elevated ICP. In addition, limited data suggest a theoretical potential for harm from the prophylactic and protracted use of HT in the setting of large hemispheric lesions. HT exerts effects on parenchymal volume, cerebral blood volume and cerebral perfusion pressure which may ameliorate global ICP elevation and cerebral blood flow; nevertheless, it also holds theoretical potential for aggravating tissue shifts promoted by significant interhemispheric ICP gradients that may arise in the setting of a large unilateral supratentorial mass lesion. The purpose of this article is to review the literature in order to shed light on the effects of HT on brain tissue shifts and clinical outcome in the context of large hemispheric strokes, as well as elucidate when HT should be initiated and when it should be avoided.

Successful Use of Extracorporeal Membrane Oxygenation for Respiratory Failure After Cranial Surgery.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support is indicated for refractory respiratory failure but carries a high morbidity and mortality in the neurosurgical setting due to associated risks of intracranial hemorrhage. CASE DESCRIPTION: We describe the case of a 62-year-old man who underwent craniotomy for resection of an esthesioneuroblastoma involving the anterior skull base and extending intracranially, through the cribriform plate into the right epidural space. He developed refractory hypoxemic and hypercapnic respiratory failure and circulatory shock in the immediate postoperative period. Our patient was successfully treated with ECMO after other aggressive resuscitative measures proved unsuccessful for several hours. The patient was managed with ECMO for 6 days, after which he was successfully weaned without developing any neurologic complications. CONCLUSION: Our case report is significant because it describes the safe use of ECMO in a controversial setting because our patient had recently undergone craniotomy. We conclude that in dire circumstances the use of ECMO is appropriate and may be safe even in the setting of recent craniotomy.

Therapeutic temperature modulation is associated with pulmonary complications in patients with severe traumatic brain injury.

AIM: To examine complications associated with the use of therapeutic temperature modulation (mild hypothermia and normothermia) in patients with severe traumatic brain injury (TBI). METHODS: One hundred and fourteen charts were reviewed. Inclusion criteria were: severe TBI with Glasgow Coma Scale (GCS) < 9, intensive care unit (ICU) stay > 24 h and non-penetrating TBI. Patients were divided into two cohorts: the treatment group received therapeutic temperature modulation (TTM) with continuous surface cooling and indwelling bladder temperature probes. The control group received standard treatment with intermittent acetaminophen for fever. Information regarding complications during the time in the ICU was collected as follows: Pneumonia was identified using a combination of clinical and laboratory data. Pulmonary embolism, pneumothorax and deep venous thrombosis were identified based on imaging results. Cardiac arrhythmias and renal failure were extracted from the clinical documentation. acute respiratory distress syndrome and acute lung injury were determined based on chest imaging and arterial blood gas results. A logistic regression was conducted to predict hospital mortality and a multiple regression was used to assess number and type of clinical complications. RESULTS: One hundred and fourteen patients were included in the analysis (mean age = 41.4, SD = 19.1, 93 males), admitted to the Jackson Memorial Hospital Neuroscience ICU and Ryder Trauma Center (mean GCS = 4.67, range 3-9), were identified and included in the analysis. Method of injury included motor vehicle accident (n = 29), motor cycle crash (n = 220), blunt head trauma (n = 212), fall (n = 229), pedestrian hit by car (n = 216), and gunshot wound to the head (n = 27). Ethnicity was primarily Caucasian (n = 260), as well as Hispanic (n = 227) and African American (n = 223); four patients had unknown ethnicity. Patients received either TTM (43) or standard therapy (71). Within the TTM group eight patients were treated with normothermia after TBI and 35 patients were treated with hypothermia. A logistic regression predicting in hospital mortality with age, GCS, and TM demonstrated that GCS (Beta = 0.572, P < 0.01) and age (Beta = -0.029) but not temperature modulation (Beta = 0.797, ns) were significant predictors of in-hospital mortality [χ(2) (3) = 22.27, P < 0.01] A multiple regression predicting number of complications demonstrated that receiving TTM was the main contributor and was associated with a higher number of pulmonary complications (t = -3.425, P = 0.001). CONCLUSION: Exposure to TTM is associated with an increase in pulmonary complications. These findings support more attention to these complications in studies of TTM in TBI patients.

Predictors of clinical failure of decompressive hemicraniectomy for malignant hemispheric infarction.

OBJECT: The aim of this study is to identify pre-operative clinical and/or radiological predictors of clinical failure of decompressive hemicraniectomy (DH) in the setting of malignant hemispheric infarction. These predictors could guide the decision for adjunctive internal brain decompression (e.g. strokectomy) at the time of the initial DH. METHODS: Retrospective chart review of all patients with malignant hemispheric infarction who underwent DH at our institution, from November 2008 to January 2013. Demographics, pre- and post-operative clinical characteristics and neuroimaging data were reviewed. The surgical outcome after DH was evaluated and clinical failure was defined as follows: lack of post-operative resolution of basal cistern effacement, and/or failure to achieve a post-operative decrease in midline shift by at least 50%, and/or post-operative neurological deterioration felt to be due to persistent mass effect, with or without a second, salvage operation (strokectomy). RESULTS: Out of 26 patients included in the study, 7 were considered to have clinical failure of their DH. Preoperative clinical and imaging variables were similar in the two groups, except that the presence of a nonreactive pupil immediately before surgery was associated clinical failure of the DH (p=0.0015). Patients in the clinical failure group had a lower postoperative GCS motor score and a strong but not statistically significant trend towards less favorable functional outcome (GOS 1-3). CONCLUSIONS: The presence of a nonreactive pupil before surgery is associated with clinical failure of DH, and should be taken into account when deciding whether to perform strokectomy at the time of DH.

A Case Report of Listeria monocytogenes Abscesses Presenting as Cortically Predominant Ring-Enhancing Lesions.

INTRODUCTION: Listeria monocytogenes, a common cause of bacterial meningitis, rarely involves the central nervous system (CNS) in the form of multiple cerebral ring-enhancing lesions. METHODS: An 81-year-old woman with rapidly progressive decline in her mental status in the setting of multiple cortically predominant ring-enhancing lesions was transferred to our institution. A mild upper respiratory tract infection and diarrhea symptoms preceded the mental status deterioration. Her past medical history is significant for type 2 diabetes mellitus. In light of the patient's age, the presence of hyponatremia and the history of diabetes mellitus, the empiric antimicrobial treatment was modified to include ampicillin, meropenem, vancomycin, voriconazole and pyrimethamine/sulfadiazine to prevent opportunistic infections. Intravenous dexamethasone was added due to significant perilesional vasogenic edema. RESULTS: The patient presented with stupor, but neither fever nor leukocytosis. CSF results were significant only for a mildly elevated protein level. The report of a repeat brain MRI was as follows: large areas of high FLAIR signals and tubular/lobulated/ring enhacement in bifrontal regions with a smaller focus in the left anterior midbrain, indicating for underlying multicentric glioma or multicentric primary CNS lymphoma. A brain biopsy, however, revealed an early abscess formation caused by a L. monocytogenes infection. CONCLUSION: A high index of suspicion in patients with risk factors for this infection is key to ensure the timely initiation of appropriate empirical antibiotic therapy in the setting of cerebral ring-enhancing lesions. Intravenous ampicillin is the treatment of choice, but meropenem represents a valid alternative.

Direct observation during surgery shows preservation of cerebral microcirculation in patients with traumatic brain injury.

OBJECTIVE: To describe the alterations of the cortical microcirculation of the brain (blood flow and vessel density) in TBI patients who and compare them with a control group. METHODS: Prospective and observational study in a third-level university hospital. Cortical microcirculation in the brain was directly observed using sidestream dark-field (SDF) imaging in 14 patients who underwent surgery: 5 subdural hematomas (SDH) and 9 parenchymal lesions (contusions/hematomas). In this last set of patients, images were recorded in the "pericontusional" areas and in the "surrounding" brain (areas that were as far from the lesion as the craniotomy allowed). These patients were compared to five patients who underwent craniotomy for a disease that did not affect the cortex. RESULTS: There were fewer "pericontusional" images that could be analyzed due to the presence of subarachnoid hemorrhage. The proportion or perfused vessels was similar in all groups: control 99.5% ± 1.3%; SDH 98.6% ± 2.4%; "pericontusional" area 98.2% ± 2.4%; "surrounding" area 98.4% ± 2.5% (p = 0.145). The perfused vessel density index was smaller in the "pericontusional" area: control 6.5 ± 1.6 l/mm; SDH 6.5 ± 2.5 l/mm; "pericontusional" area 5.4 ± 2.6 l/mm; "surrounding" 6.6 ± 2.1 l/mm (p = 0.07). CONCLUSIONS: Although the analysis of pericontusional zone was difficult, there were fewer vessels than in the controls and there was no change in the flow. In the surrounding zone and in patients with SDH, we did not document alterations in the microcirculation. Direct imaging of cerebral microcirculation in TBI patients showed that despite serious brain injury the cerebral microcirculation was remarkably well preserved.

A systematic review on the role of adjunctive corticosteroids in herpes simplex virus encephalitis: is timing critical for safety and efficacy?

BACKGROUND: Most herpes simplex virus encephalitis (HSVE) patients become disabled despite antiviral therapy. Adjunctive corticosteroid therapy may improve outcomes. METHODS: This was a systematic review of the literature addressing the use of corticosteroids in HSVE. RESULTS: Data suggesting that steroids decrease the immunological response and enhance viral replication originated from non-neural microenvironments. Early steroid administration might be harmful because initial damage in HSVE is mediated by viral replication. Steroid treatment improves outcomes in animal models by inhibiting the subsequent inflammatory response. Clinical observations support a similar benefit in symptomatic HSVE patients. Cerebrospinal fluid inflammatory markers might guide appropriate timing in future clinical practice. CONCLUSIONS: Experimental and clinical observations suggest a benefit from adjunctive steroid therapy in HSVE. Nevertheless, current evidence is not yet sufficient to endorse this approach as a standard of practice.

Are steroids a beneficial adjunctive therapy in the immunosuppressed patient with herpes simplex virus encephalitis?

Few reports describe the reactivation of latent herpes simplex virus causing encephalitis (HSVE) in patients undergoing brain radiation therapy and a concomitant steroid regimen. The role for steroid use in the treatment of patients with HSVE has not been fully elucidated. We report the case of a female patient immunosuppressed by steroids and brain radiation who developed HSVE and responded to acyclovir and dexamethasone.

Craniectomy for acute ischemic stroke: how to apply the data to the bedside.

PURPOSE OF REVIEW: Malignant hemispheric infarction is associated with a high mortality rate, approximately 80%, as a result of the development of intracranial pressure gradients, brain tissue shift, and herniation. By allowing the brain to swell outwards and equalizing pressure gradients, decompressive craniectomy appears to significantly reduce the mortality to approximately 20%. This review takes a comprehensive look at the evidence highlighting the benefits and limits of decompressive craniectomy in malignant cerebral infarction. RECENT FINDINGS: Three recent European randomized trials have provided compelling evidence that decompressive hemicraniectomy for large hemispheric infarction is not only lifesaving, but also leads to improved functional outcome in patients 60 years of age or less when treated within 48 h of stroke onset. SUMMARY: Early decompressive hemicraniectomy (60 years old) and perhaps, when delayed beyond 48 h.

Perfluorocarbon emulsions improve cognitive recovery after lateral fluid percussion brain injury in rats.

OBJECTIVE: Perfluorocarbon emulsions have been shown to improve outcomes in stroke models. This study examined the effect of Oxycyte, a third-generation perfluorocarbon emulsion (04RD33; Synthetic Blood International, Inc., Costa Mesa, CA) treatment on cognitive recovery and mitochondrial oxygen consumption after a moderate lateral fluid percussion injury (LFPI). METHODS: Adult male Sprague-Dawley rats (Harlan Bioproducts for Science, Indianapolis, IN) were allocated to 4 groups: 1) LFPI treated with a lower dose of Oxycyte (4.5 mL/kg); 2) LFPI with a higher dose of Oxycyte (9.0 mL/kg); 3) LFPI with saline infusion; and 4) sham animals treated with saline. Fifteen minutes after receiving moderate LFPI or sham surgery, animals were infused intravenously with Oxycyte or saline within 30 minutes while breathing 100% O2. Animals breathed 100% O2 continuously for a total of 4 hours after injury. At 11 to 15 days after LFPI, animals were assessed for cognitive deficits using the Morris water maze test. They were sacrificed at Day 15 after injury for histology to assess hippocampal neuronal cell loss. In a parallel study, mitochondrial oxygen consumption values were measured by the Cartesian diver microrespirometer method. RESULTS: We found that injured animals treated with a lower or higher dose of Oxycyte had significant improvement in cognitive function when compared with injured saline-control animals (P < 0.05). Moreover, injured animals that received either dose of Oxycyte had significantly less neuronal cell loss in the hippocampal CA3 region compared with saline-treated animals (P < 0.05). Furthermore, a lower dose of Oxycyte significantly improved mitochondrial oxygen consumption levels (P < 0.05). CONCLUSION: The current study demonstrates that Oxycyte can improve cognitive recovery and reduce CA3 neuronal cell loss after traumatic brain injury in rats.

Validation of brain extracellular glycerol as an indicator of cellular membrane damage due to free radical activity after traumatic brain injury.

Following severe traumatic brain injury (TBI), increasing oxygen delivery to the brain has been advocated as a useful strategy to reverse mitochondrial dysfunction and improve neurological outcome. However, this might also promote overproduction of free radicals, responsible for lipid peroxidation and hence brain cell damage. Therefore, a method for monitoring this potential adverse effect in humans is desirable. Glycerol, an end product of phospholipid breakdown, easily detectable in the human brain by means of microdialysis, might represent a reliable indicator of free radical-induced cell membrane damage. Brain microdialysates were collected from 24 adult male Sprague-Dawley rats over a 3-hour period following sham operation (n=6), chemical brain injury via administration of Fenton's reagent (n=6), a powerful hydroxyl radical generator, and lateral fluid percussion injury (FPI; n=12). In the FPI animals, post-traumatic i.v. administration of either normal saline or the free radical scavenger Tempol (10 mg/kg, followed by an infusion of 30 mg/kg/h over 3 h) was carried out to evaluate the effect of blockade of free radical generation. Samples were analyzed for the presence of glycerol and the marker of hydroxyl radical (OH.) by generation of 2,3-DHBA (dihydroxybenzoic acid). Brain tissue staining with TTC (2,3,5-triphenyltetrazoium chloride) was performed for lesion size assessment. Rats subjected to either Fenton's reagent administration or FPI exhibited significantly higher levels of glycerol as compared with shams (p=0.05). However, when the FPI was followed by Tempol administration, concentration of both glycerol and 2,3-DHBA decreased significantly (p=0.05). Furthermore, TCC staining revealed a significant reduction of secondary brain tissue damage in Tempol-treated animals (p=0.05). Our data suggest that injury-induced increases in microdialysate glycerol levels are a valid indicator of free radical activity, and their amelioration following Tempol treatment accords with less histological damage in response to FPI.