Multimodal monitoring in patients with acute brain injury - A survey from critical care providers.

BACKGROUND: Multimodal neuromonitoring (MMM) aims to improve outcome after acute brain injury, and thus admission in specialized Neurocritical Care Units with potential access to MMM is necessary. Various invasive and noninvasive modalities have been developed, however there is no strong evidence to support monitor combinations nor is there a known standardized approach. The goal of this study is to identify the most used invasive and non-invasive neuromonitoring modalities in daily practice as well as ubiquitousness of MMM standardization. METHODS: In order to investigate current availability and protocolized implementation of MMM among neurocritical care units in US and non-US intensive care units, we designed a cross-sectional survey consisting of a self-administered online questionnaire of 20 closed-ended questions disseminated by the Neurocritical Care Society. RESULTS: Twenty-one critical care practitioners responded to our survey with a 76% completion rate. The most commonly utilized non-invasive neuromonitoring modalities were continuous electroencephalography followed by transcranial doppler. The most common invasive modalities were external ventricular drain followed by parenchymal intracranial pressure (ICP) monitoring. MMM is most utilized in patients with subarachnoid hemorrhage and there were no differences regarding established institutional protocol, 24-h cEEG availability and invasive monitor placement between teaching and non-teaching hospitals. MMM is considered standard of care in 28% of responders' hospitals, whereas in 26.7% it is deemed experimental and only done as part of clinical trials. Only 26.7% hospitals use a computerized data integration system. CONCLUSION: Our survey revealed overall limited use of MMM with no established institutional protocols among institutions. Ongoing research and further standardization of MMM will clarify its benefit to patients suffering from severe brain injury.

Leaving no culture undrawn: Time to revisit the CLABSI and CAUTI metrics.

Central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) are quality metrics for many ICUs, and financial ramifications can be applied to hospitals and providers who perform poorly on these measures. Despite some perceived benefits to tracking these metrics, there are a range of issues associated with this practice: lack of a solid evidence base that documenting them has led to decreased infection rates, moral distress associated with identifying these infections, problems with their definitions, and others. We discuss each of these concerns while also including international perspectives then recommend practical steps to attempt to remediate use of the CLABSI and CAUTI metrics. Specifically, we suggest forming a task force consisting of key stakeholders (e.g., providers, Centers for Medicare & Medicaid Services (CMS), patients/families) to review CLABSI and CAUTI-related issues and then to create a summary statement containing recommendations to improve the use of these metrics.

International Survey of Antiseizure Medication Use in Patients with Complicated Mild Traumatic Brain Injury: A New York Neurotrauma Consortium Study.

BACKGROUND: Seizures and epilepsy after traumatic brain injury (TBI) negatively affect quality of life and longevity. Antiseizure medication (ASM) prophylaxis after severe TBI is associated with improved outcomes; these medications are rarely used in mild TBI. However, a paucity of research is available to inform ASM use in complicated mild TBI (cmTBI) and no empirically based clinical care guidelines for ASM use in cmTBI exist. We aim to identify seizure prevention and management strategies used by clinicians experienced in treating patients with cmTBI to characterize standard care and inform a systematic approach to clinical decision making regarding ASM prophylaxis. METHODS: We recruited a multidisciplinary international cohort through professional organizational listservs and social media platforms. Our questionnaire assessed factors influencing ASM prophylaxis after cmTBI at the individual, institutional, and health system-wide levels. RESULTS: Ninety-two providers with experience managing cmTBI completed the survey. We found a striking diversity of ASM use in cmTBI, with 30% of respondents reporting no/infrequent use and 42% reporting frequent use; these tendencies did not differ by provider or institutional characteristics. Certain conditions universally increased or decreased the likelihood of ASM use and represent consensus. Based on survey results, ASMs are commonly used in patients with cmTBI who experience acute secondary seizure or select positive neuroimaging findings; we advise caution in elderly patients and those with concomitant neuropsychiatric illness. CONCLUSIONS: This study is the first to characterize factors influencing clinical decision making in ASM prophylaxis after cmTBI based on multidisciplinary multicenter provider practices. Prospective controlled studies are necessary to inform standardized guideline development.

Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury.

BACKGROUND: Spreading depolarizations (SDs) are associated with worse outcome following subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but gold standard detection requires electrocorticography with a subdural strip electrode. Electroencephalography (EEG) ictal-interictal continuum abnormalities are associated with poor outcomes after TBI and with both delayed cerebral ischemia (DCI) and poor outcomes after SAH. We examined rates of SD detection in patients with SAH and TBI with intraparenchymal and subdural strip electrodes and assessed which continuous EEG (cEEG) measures were associated with intracranially quantified SDs. METHODS: In this single-center cohort, we included patients with SAH and TBI undergoing ≥ 24 h of interpretable intracranial monitoring via eight-contact intraparenchymal or six-contact subdural strip platinum electrodes or both. SDs were rated according to established consensus criteria and compared with cEEG findings rated according to the American Clinical Neurophysiology Society critical care EEG monitoring consensus criteria: lateralized rhythmic delta activity, generalized rhythmic delta activity, lateralized periodic discharges, generalized periodic discharges, any ictal-interictal continuum, or a composite scalp EEG tool for seizure risk estimation: the 2HELPS2B score. Among patients with SAH, cEEG was assessed for validated DCI biomarkers: new or worsening epileptiform abnormalities and new background deterioration. RESULTS: Over 6 years, SDs were recorded in 5 (18%) of 28 patients recorded with intraparenchymal electrodes and 4 (40%) of 10 patients recorded with subdural strip electrodes. There was no significant association between occurrence of SDs and day 1 cEEG findings (American Clinical Neurophysiology Society main terms lateralized periodic discharges, generalized periodic discharges, lateralized rhythmic delta activity, or seizures, individually or in combination). After SAH, established cEEG DCI predictors were not associated with SDs. CONCLUSIONS: Intraparenchymal recordings yielded low rates of SD, and documented SDs were not associated with ictal-interictal continuum abnormalities or other cEEG DCI predictors. Identifying scalp EEG correlates of SD may require training computational EEG analytics and use of gold standard subdural strip electrocorticography recordings.

Pathogenic effect of TP73 Gene Variants in People With Amyotrophic Lateral Sclerosis.

OBJECTIVE: To identify novel disease associated loci for amyotrophic lateral sclerosis (ALS), we utilized sequencing data and performed in vitro and in vivo experiments to demonstrate pathogenicity of mutations identified in TP73. METHODS: We analyzed exome sequences of 87 sporadic ALS patients and 324 controls, with confirmatory sequencing in independent ALS cohorts of >2,800 patients. For the top hit, TP73, a regulator of apoptosis, differentiation, and a binding partner as well as homolog of the tumor suppressor gene TP53, we assayed mutation effects using in vitro and in vivo experiments. C2C12 myoblast differentiation assays, characterization of myotube appearance, and immunoprecipitation of p53-p73 complexes were perform in vitro. In vivo, we used CRISPR/Cas9 targeting of zebrafish tp73 to assay motor neuron number and axon morphology. RESULTS: Five heterozygous rare, nonsynonymous mutations in TP73 were identified in our sporadic ALS cohort. In independent ALS cohorts, we identified an additional 19 rare, deleterious variants in TP73. Patient TP73 mutations caused abnormal differentiation and increased apoptosis in the myoblast differentiation assay, with abnormal myotube appearance. Immunoprecipitation of mutant ΔN-p73 demonstrated that patient mutations hinder ΔN-p73's ability to bind p53. CRISPR/Cas9 knockout of tp73 in zebrafish led to impaired motor neuron development and abnormal axonal morphology, concordant with ALS pathology. CONCLUSION: Together, these results strongly suggest that variants in TP73 correlate with risk for ALS and indicate a novel role for apoptosis in ALS disease pathology.

Dynamic mapping of the corticospinal tract in open cordotomy and myelomeningocele surgery.

OBJECT: Spinal cord surgeries carry a high risk for significant neurological impairments. The initial techniques for spinal cord mapping emerged as an aid to identify the dorsal columns and helped select a safe myelotomy site in intramedullary tumor resection. Advancements in motor mapping of the cord have also been made recently, but exclusively with tumor surgery. We hereby present our experiences with dynamic mapping of the corticospinal tract (CST) in other types of spinal cord procedures that carry an increased risk of postoperative motor deficit, and thus could directly benefit from this technique. CASE REPORTS: Two patients with intractable unilateral lower extremity pain due to metastatic disease of the sacrum and a thoraco-lumbar chordoma, respectively underwent thoracic cordotomy to interrupt the nociceptive pathways. A third patient with progressive leg weakness underwent cord untethering and surgical repair of a large thoracic myelomeningocele. In all three cases, multimodality intraoperative neurophysiologic testing included somatosensory and motor evoked potentials monitoring as well as dynamic mapping of the CST. CONCLUSION: CST mapping allowed safe advancement of the cordotomy probe and exploration of the meningocele sac with untethering of the anterior-lateral aspect of the cord respectively, resulting in postoperative preservation or improvement of motor strength from the pre-operative baseline. Stimulus thresholds varied likely with the distance between the stimulating probe and the CST as well as with the baseline motor strength in the mapped myotomes.

Current advances in emergency department care of acute ischemic stroke: part 1: intravenous thrombolysis

This review examines the evidence and indications for the use of intravenous thrombolysis in the treatment of acute ischemic stroke.

Multimodal Outcome Prognostication After Cardiac Arrest and Targeted Temperature Management: Analysis at 36 °C.

BACKGROUND: Targeted temperature management (TTM) represents the standard of care in comatose survivors after cardiac arrest (CA) and may be applied targeting 33° or 36 °C. While multimodal prognostication has been extensively tested for 33 °C, scarce information exists for 36 °C. METHODS: In this cohort study, consecutive comatose adults after CA treated with TTM at 36 °C between July 2014 and October 2016 were included. A combination of neurological examination, electrophysiological features, and serum neuron-specific enolase (NSE) was evaluated for outcome prediction at 3 months (mortality; good outcome defined as cerebral performance categories (CPC) score of 1-2, poor outcome defined as CPC 3-5). RESULTS: We analyzed 61 patients. The presence of two or more predictors out of, unreactive electroencephalogram (EEG) background, epileptiform EEG, absent pupillary and/or corneal reflex, early myoclonus, bilaterally absent cortical somatosensory evoked potentials, and serum NSE >75 µg/l, had a high specificity for predicting mortality (positive predictive value [PPV] = 1.00, 95% CI 0.87-1.00) and poor outcome (PPV = 1.00, 95% CI 0.80-1.00). Reactive EEG background was highly sensitive for predicting good outcome (0.95, 95% CI 0.74-0.99). CONCLUSIONS: Prediction of outcome after CA and TTM targeting 36 °C seems valid in adults using the same features tested at 33 °C. A reactive EEG under TTM appears highly sensitive for good outcome.

The evolving genetic risk for sporadic ALS.

OBJECTIVE: To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. METHODS: Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. RESULTS: Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. CONCLUSIONS: Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates.

Associated Factors and Prognostic Implications of Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges.

IMPORTANCE: The implications of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) sometimes found on prolonged electroencephalographic (EEG) recordings are uncertain. OBJECTIVE: To evaluate the incidence of SIRPIDs and their clinical implications in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, international retrospective study was performed from October 1, 2012, through September 30, 2014, of consecutive adult patients hospitalized in intensive care units with alteration of consciousness who underwent EEG recordings at 3 separate centers. Demographic data, including admission diagnosis, age, sex, history of epilepsy, and EEG findings, were noted. Characteristics of SIRPIDs were documented. Data were evaluated for predictors of SIRPIDs and in-hospital mortality. Data analysis was performed from January 16, 2015, to June 15, 2015. MAIN OUTCOMES AND MEASURES: Incidence of SIRPIDs, association of SIRPIDs with mortality and other EEG characteristics, and EEG and clinical predictors of mortality. RESULTS: A total of 416 patients were studied. The median age of patients was 60 years (interquartile range, 46-71 years), and 252 (60.6%) were male. A total of 104 patients (25.0%) did not survive to hospital discharge. SIRPIDs were identified in 43 patients (10.3%). The proportion of patients with SIRPIDs was not significantly different across the 3 sites (P = .34). Anoxic brain injury (odds ratio [OR], 3.80; 95% CI, 1.73-8.33; P < .001), the use of antiepileptic medications (OR, 3.24; 95% CI, 1.31-8.00; P = .01), electrographic seizures (OR, 2.85; 95% CI, 1.13-7.19; P = .03), generalized periodic discharges with triphasic morphologic features (OR, 3.66; 95% CI, 1.67-8.02; P = .001), and sporadic sharp waves and periodic discharges (OR, 2.59; 95% CI, 1.13-5.92; P = .02) were independently associated with the presence of SIRPIDs. Older age (OR, 1.02; 95% CI, 1.01-1.04; P = .005), anoxic brain injury (OR, 3.49; 95% CI, 1.96-6.21; P ≤ .001), and absence of EEG reactivity (OR, 8.14; 95% CI, 4.20-15.79; P < .001) but not SIRPIDs (OR, 1.73; 95% CI, 0.79-3.78; P = .17) were independently associated with in-hospital mortality. CONCLUSIONS AND RELEVANCE: In critically ill patients undergoing EEG recordings, SIRPIDs occurred in 43 (10.3%) and were associated with other electrographic abnormalities previously reported to indicate poor prognosis. However, SIRPIDs were not independently associated with in-hospital mortality.

EEG reactivity to pain in comatose patients: Importance of the stimulus type.

INTRODUCTION: Electroencephalogram (EEG) background reactivity is a potentially interesting outcome predictor in comatose patients, especially after cardiac arrest, but recent studies report only fair interrater reliability. Furthermore, there are no definite guidelines for its testing. We therefore investigated the EEG effect of standardized noxious stimuli in comatose patients not reactive to auditory stimuli. METHODS: In this prospective study we applied a protocol using three different painful stimuli (bilateral nipple pinching, pinprick at the nose base, finger-nail compression on each side), grouped in three distinct clusters with an alternated sequence, during EEG recordings in comatose patients. We only analyzed recordings showing any reactivity to pain. Fisher and χ2 tests were used as needed to assess contingency tables. RESULTS: Of 42 studies, 12 did not show any background reactivity, 2 presented SIRPIDs, and 2 had massive artefacts; we thus analyzed 26 EEGs recorded in 17 patients (4 women, 24%). Nipple pinching more frequently induced a change in EEG background activity (p<0.001), with a sensitivity of 97.4% for reactivity. Neither the order of the stimuli in the cluster (p=0.723), nor the cluster order (p=0.901) influenced the results. CONCLUSION: In this pilot study, bilateral, synchronous nipple pinching seems to be the most efficient method to test nociceptive EEG reactivity in comatose patients. This approach may enhance interrater reliability, but deserves confirmation in larger cohorts.

[News in neurology 2014]. / Neurologie.

In 2014, breastfeeding during maternal antiepileptic therapy seems to be safe for the children and can be recommended. Intravenous thrombolysis by Alteplase improves the outcome after a stroke if administered within 4.5 hours and it is also recommended in elderly population over 80 years. ProSavin genic therapy for Parkinson disease is under investigation. The Transcranial Magnetic Stimulation (TMS) has an analgesic effect in neuropathic pain as well as an antidepressant effect. Antagonists of calcitonin gene-related peptide can have a beneficial role in migraine prevention. Diagnostic biomarker panels for Alzheimer disease are under investigation. Oral teriflunomide and dimethyl fumarate (BG-12) for relapsing multiple sclerosis treatment are now available in Switzerland.

Recurrence of status epilepticus: prognostic role and outcome predictors.

OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE) have been studied extensively in hospital- and population-based cohorts. However, little attention has been directed toward SE recurrence after an incident episode. We investigated clinical and demographic characteristics of patients presenting SE recurrence and its specific prognostic role. METHODS: In this observational cohort study, we screened our prospective registry of consecutive adults with SE between April 2006 and February 2014. Demographic and clinical data were compared between incident and recurrent SE episodes; risk of SE recurrence was assessed through survival analysis, and the prognostic role of SE recurrence with multivariable logistic regressions. RESULTS: Of the incident cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI 0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and mortality, prognosis was independently related to Status Epilepticus Severity Score (STESS) and potentially fatal etiology, but not to SE recurrence. SIGNIFICANCE: This study provides class III evidence that SE recurrence involves a significant proportion of patients, and that recurrence risk is independently associated with chronic etiology and to a lesser extent with female gender. However, contrary to underlying cause and SE severity, SE recurrence per se does not independently correlate with outcome. Early identification of patients at higher risk of SE recurrence may influence their management during follow-up.

Clinical outcome after a reactive hypothermic EEG following cardiac arrest.

BACKGROUND: Reactive electroencephalography (EEG) background during therapeutic hypothermia (TH) is related to favorable prognosis after cardiac arrest (CA), but its predictive value is not 100 %. The aim of this study was to investigate outcome predictors after a first reactive EEG recorded during TH after CA. METHODS: We studied a cohort of consecutive comatose adults admitted between February 2008 and November 2012, after successful resuscitation from CA, selecting patients with reactive EEG during TH. Outcome was assessed at three months, and categorized as survivors and non-survivors (no patient was in vegetative state). Demographics, clinical variables, EEG features, serum neuron-specific enolase (NSE) and procalcitonin, were compared using uni- and multivariable analyses. RESULTS: A total of 290 patients were treated with TH after cardiac arrest; 146 had an EEG during TH, which proved reactive in 90 of them; 77 (86 %) survived and 13 (14 %) died (without recovery from coma). The group of non-survivors had a higher occurrence of discontinuous EEG (p = 0.006; multivariate analysis p = 0.026), and a higher serum NSE peak (p = 0.021; multivariate analysis p = 0.014); conversely, demographics, and other clinical variables including serum procalcitonin did not differ. CONCLUSIONS: A discontinuous EEG and high serum NSE are associated with mortality after CA in patients with poor outcome despite a reactive hypothermic EEG. This suggests more severe cerebral damage, but not to higher extent of systemic disease.

Female perpetrators of sexual abuse of minors: what are the consequences for the victims?

INTRODUCTION: The definition of sexual abuse changes according to the moral values and culture of each era. In the past the perpetrators of sexual abuse were perceived to be exclusively male. However, contemporary literature is placing increasing emphasis on the role of female sexual abusers. The aim of the current literature review is to focus on the consequences of sexual abuse in minors when the perpetrator is female. METHODS: A literature search of the main databases for studies was conducted. Restriction was placed on European and North American literature due to perceived culture differences. RESULTS: Victims of sexual abuse by female perpetrators are usually friends or relatives of the abuser and find themselves sometimes under persuasion and psychological coercion to participate in sexual acts. The percentage of male victims is growing. There are severe and longstanding psychological consequences for the victims which are further analyzed. CONCLUSION: Contemporary studies offer limited information about this issue and the consequences it has on the victims. The majority of such cases are not reported. Sometimes sexual abuse by female perpetrators is considered more acceptable than sexual abuse by males. Psychological interventions could be a powerful tool in reduction of female sexual abuse and its consequences on the victims.

Review on female sexual offenders: findings about profile and personality.

INTRODUCTION: Although in the past sexual abuse was perceived as an issue connected only with males the contemporary literature is placing increasing emphasis on the role of female sexual perpetrators. There is still disagreement about the definition of sexual abuse, the frequency that it occurs and the characteristics of the women that are sexual abusers. METHODS: Thorough research of the main databases (MEDLINE and PsycInfo), for case reviews and studies along with restriction on European and North American literature, is due to perceived culture differences. Further investigation for relevant studies through web search engines such as Google, locates agencies and organizations that are interested and connected to sexual abuse issues. RESULTS: Distinction between sexual offense and sexual abuse has as a result difference in the characteristics of female sexual perpetrators. They are mainly young (age up to 36 years old), friends or relatives of the victim, using more persuasion and psychological coercion and legally charged in a lesser extent compared with male abusers. However the psychological consequences for the victim can be more severe. CONCLUSION: A unanimous view of what is female sexual abuse is difficult to reach. Often it is under reported, unrecognized or considered ethically more acceptable than male abuse. It is also connected with an increased self-report of history of sexual abuse of the perpetrators. A typology of female sexual abusers should be developed. Treatments focusing on different psychological interventions along with prevention and public awareness can be a powerful tool in reduction of sexual abuse perpetrated by females.