The Toronto Concussion Study: a prospective investigation of characteristics in a cohort of adults from the general population seeking care following acute concussion, 2016-2020.

Purpose: There is limited research regarding the characteristics of those from the general population who seek care following acute concussion. Methods: To address this gap, a large cohort of 473 adults diagnosed with an acute concussion (female participants = 287; male participants = 186) was followed using objective measures prospectively over 16 weeks beginning at a mean of 5.1 days post-injury. Results: Falls were the most common mechanism of injury (MOI) (n = 137, 29.0%), followed by sports-related recreation (n = 119, 25.2%). Male participants were more likely to be injured playing recreational sports or in a violence-related incident; female participants were more likely to be injured by falling. Post-traumatic amnesia (PTA) was reported by 80 participants (16.9 %), and loss of consciousness (LOC) was reported by 110 (23.3%). In total, 54 participants (11.4%) reported both PTA and LOC. Male participants had significantly higher rates of PTA and LOC after their injury compared to their female counterparts. Higher initial symptom burden was associated with a longer duration of recovery for both male and female participants. Female participants had more symptoms and higher severity of symptoms at presentation compared to male participants. Female participants were identified to have a longer recovery duration, with a mean survival time of 6.50 weeks compared to 5.45 weeks in male participants (p < 0.0001). A relatively high proportion of female and male participants in this study reported premorbid diagnoses of depression and anxiety compared to general population characteristics. Conclusion: Although premorbid diagnoses of depression and/or anxiety were associated with higher symptom burden at the initial visit, the duration of symptoms was not directly associated with a pre-injury history of psychological/psychiatric disturbance. This cohort of adults, from the general population, seeking care for their acute concussion attained clinical and functional recovery over a period of 4-12 weeks.

Prevention and treatment of traumatic brain injury-related delirium: a systematic review.

BACKGROUND: Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care. METHODS: We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies-of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting. RESULTS: We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome. CONCLUSIONS: We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.

Psychosocial Factors Associated with Prolonged Length of Stay in Acquired Brain Injury Rehabilitation: A Retrospective Cohort Study.

OBJECTIVE: In a climate of rising healthcare costs and increasing pressure to reduce inpatient length of stay, hospitals must balance their role as care providers with that as resource stewards. There is a need to understand what factors are associated with patients staying beyond rehabilitation length of stay targets. The aim of this study was to determine psychosocial patient factors that are identifiable on admission that influence length of stay targets in acquired brain injury rehabilitation. METHODS: A retrospective case series of 167 inpatients with acquired brain injury was conducted at an urban, academic rehabilitation hospital. A total of 29 factors were used for data analysis. Logistic and multiple linear regression analysis was utilized to determine if any patient factors were associated with patients exceeding their length of stay targets. RESULTS: Premorbid communal living status (e.g. group home) was associated with an odds ratio of 14.67 of exceeding length of stay target. Patients who did not drive prior to their admission had an odds ratio of 2.63 of exceeding their length of stay target. CONCLUSION: Premorbid communal living and premorbid non-driving status are predictors of patients with acquired brain injuries exceeding target rehabilitation length of stay. These findings may help acquired brain injury rehabilitation programmes plan for the needs of and advocate for patients.

Medical Care Among Individuals with a Concussion in Ontario: A Population-based Study.

BACKGROUND: Concussion affects 1.2% of the population annually; rural regions and children have higher rates of concussion. METHODS: Using administrative health care linked databases, all residents of Ontario with a physician diagnosed concussion were identified using ICD-9 code 850 or ICD-10 code S06. Cases were tracked for 2 years for concussion-related health care utilization with relevant specialist physicians (i.e., neurology, otolaryngology, physiatry, psychiatry, ophthalmology). Billing codes, specialist codes, and time from index to visit were analyzed. Factors associated with increased specialist visits were also examined. RESULTS: In total, 1,022,588 cases were identified between 2008 and 2014 with 2 years of post-concussion health care utilization available. Follow-up by physician within 3 days of injury occurred in only 14% of cases. Mean time between ED diagnosis and follow-up by a physician was 83.9 days, whereas for rural regions it was >100 days. About half of adults (51.9%) and children (50.3%) had at least 1 specialist visit following concussion. Mean time between injury and first specialist visit was 203.8 (SD 192.9) days for adults, 213.5 (SD 201.0) days for rural adults, and 276.0 (SD 202.6) days for children. There were 67,420 neurology visits, 70,404 psychiatry visits, 13,571 neurosurgery visits, 19,780 physiatry visits, 101,788 ENT visits, and 103,417 ophthalmology visits in the 2 years tracking period. Factors associated with more specialist use included age > 18 years, urban residence, and pre-injury psychiatric history. CONCLUSIONS: There are discrepancies in post-concussion health care utilization based on age group and rural/urban residence. Addressing these risk factors could improve concussion care access.

Revisiting the ICHD-3 criteria for headache attributed to mild traumatic injury to the head: Insights from the Toronto Concussion Study Analysis of Acute Headaches Following Concussion.

BACKGROUND: There is limited prospective data on the prevalence, timing of onset, and characteristics of acute headache following concussion/mild traumatic brain injury. METHODS: Adults diagnosed with concussion (arising from injuries not related to work or motor vehicle accidents) were recruited from emergency departments and seen within one week post injury wherein they completed questionnaires assessing demographic variables, pre-injury headache history, post-injury headache history, and the Sport Concussion Assessment Tool (SCAT-3) symptom checklist, the Sleep and Concussion Questionnaire (SCQ) and mood/anxiety on the Brief Symptom Inventory (BSI). RESULTS: A total of 302 participants (59% female) were enrolled (mean age 33.6 years) and almost all (92%) endorsed post-traumatic headache (PTH) with 94% endorsing headache onset within 24 hours of injury. Headache location was not correlated with site of injury. Most participants (84%) experienced daily headache. Headache quality was pressure/squeezing in 69% and throbbing/pulsing type in 22%. Associated symptoms included: photophobia (74%), phonophobia (72%) and nausea (55%). SCAT-3 symptom scores, Brief Symptom Inventory and Sleep and Concussion Questionnaire scores were significantly higher in those endorsing acute PTH. No significant differences were found in week 1 acute PTH by sex, history of migraine, pre-injury headache frequency, anxiety, or depression, nor presence/absence of post-traumatic amnesia and self-reported loss of consciousness. CONCLUSIONS: This study highlights the very high incidence of acute PTH following concussion, the timing of onset and characteristics of acute PTH, the associated psychological and sleep disturbances and notes that the current ICHD-3 criteria for headaches attributed to mild traumatic injury to the head are reasonable, the interval between injury and headache onset should not be extended beyond seven days and could, potentially, be shorted to allow for greater diagnostic precision.

The incidence and nature of adverse events in rehabilitation inpatients with acquired brain injuries.

BACKGROUND: Patient safety is important in all healthcare settings. Few studies have examined the state of patient safety in rehabilitation and none have examined patient safety in the setting of acquired brain injury (ABI) rehabilitation. OBJECTIVES: To determine the incidence, most common types, and severities of adverse events among inpatients undergoing ABI rehabilitation. DESIGN: Retrospective case series descriptive study. SETTING: The inpatient ABI rehabilitation program at an academic, tertiary rehabilitation hospital in Canada. PARTICIPANTS: One hundred eight consecutive inpatients with acquired brain injuries. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient charts and incident reports from the hospital's voluntary reporting system were reviewed by three board-certified physiatrists to determine the incidence, type, severity and preventability of adverse events. Adverse events were identified and classified for severity and type using the World Health Organization (WHO) International Classification for Patient Safety. Preventability was rated on a six-point Likert scale. RESULTS: During the study period, the incidence of adverse events was 17.42 ± 3.86 per 1000 patient days. Adverse events affected 52.8% of patients. Most adverse events identified were mild in severity (81.6%) and the rest were of moderate severity. The two most common types of adverse events were (1) patient incidents (50%) such as falls, pressure ulcers and skin tears and (2) patient behaviors such as missing patient, assault, or sexual behaviors (14.5%). Of the 76 adverse events identified in the study, 44.8% were preventable. The hospital's voluntary reporting system did not capture 57.9% of the adverse events identified. CONCLUSIONS: Future efforts to improve patient safety in ABI rehabilitation should focus on reducing falls, skin injuries and behaviors, and removing barriers to voluntary incident reporting. Detection of adverse events through chart reviews provides a more complete understanding of patient safety risks in ABI rehab than relying on incident reporting alone.

Can Sport Concussion Assessment Tool (SCAT) Symptom Scores Be Converted to Rivermead Post-concussion Symptoms Questionnaire (RPQ) Scores and Vice Versa? Findings From the Toronto Concussion Study.

Background: The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Sports Concussion Assessment Tool (SCAT) are widely used self-report tools assessing the type, number, and severity of concussion symptoms. There are overlapping symptoms and domains, though they are scored differently. The SCAT consists of 22 questions with a 7-point Likert scale for a total possible score 132. The RPQ has 16 questions and a 5-point Likert scale for a total of 64 possible points. Being able to convert between the two scores would facilitate comparison of results in the concussion literature. Objectives: To develop equations to convert scores on the SCAT to the RPQ and vice versa. Methods: Adults (17-85 years) diagnosed with a concussion at a referring emergency department were seen in the Hull-Ellis Concussion and Research Clinic, a rapid access concussion clinic at Toronto Rehab-University Health Network (UHN) Toronto Canada, within 7 days of injury. The RPQ and SCAT symptom checklists as well as demographic questionnaires were administered to all participants at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16. Results: 215 participants had 1,168 matched RPQ and SCAT assessments. Total scores of the RPQ and the SCAT had a rho = 0.91 (p < 0.001); correlations were lower for sub-scores of specific symptom domains (range 0.74-0.87, p < 0.001 for all domain comparisons). An equation was derived to calculate SCAT scores using the number and severity of symptoms on the RPQ. Estimated scores were within 3 points of the observed total score on the SCAT. A second equation was derived to calculate the RPQ from the proportion weighted total score of the SCAT. This equation estimated corresponding scores within 3 points of the observed score on the RPQ. Conclusions: The RPQ and SCAT symptom checklists total scores are highly correlated and can be used to estimate the total score on the corresponding assessment. The symptom subdomains are also strongly correlated between the 2 scales however not as strongly correlated as the total score. The equations will enable researchers and clinicians to quickly convert between the scales and to directly compare concussion research findings.

Sleep disturbance and length of stay in the setting of acquired brain injury rehabilitation.

OBJECTIVE: The objective of this study was to investigate the impact and prevalence of sleep-wake disturbances among adult patients admitted for inpatient acquired brain injury rehabilitation. METHOD: This was a retrospective cohort study involving all adults admitted for inpatient ABI neurocognitive rehabilitation at UHN-Toronto Rehabilitation Institute over a 12-month period (n = 165). The primary endpoint of the study was the comparison of functional independent measure efficiency and hospital length of stay between patients reporting sleep disturbance (e.g. increased sleep latency, obstructive sleep apnea [OSA], sleep maintenance insomnia) versus those with normal sleep. RESULTS: We found that more than half (58.2%) of patients experienced sleep disturbance based on a combination of self-report and clinical documentation. The most common sleep disturbance was increased sleep onset latency (28.5%), followed by mixed sleep onset/maintenance insomnia (14.5%) and obstructive sleep apnea (8.5%). Notably, OSA was associated with longer length of hospital stay and reduced functional independence measure (FIM) efficiency in the cognitive domain after accounting for age and number of medical comorbidities. IMPLICATIONS: The results of this investigation underscore the importance of screening patients with brain injury for sleep disturbances due to its high prevalence and impact on rehabilitation efficiency.

Prediction of risk of prolonged post-concussion symptoms: Derivation and validation of the TRICORDRR (Toronto Rehabilitation Institute Concussion Outcome Determination and Rehab Recommendations) score.

BACKGROUND: Approximately 10% to 20% of people with concussion experience prolonged post-concussion symptoms (PPCS). There is limited information identifying risk factors for PPCS in adult populations. This study aimed to derive a risk score for PPCS by determining which demographic factors, premorbid health conditions, and healthcare utilization patterns are associated with need for prolonged concussion care among a large cohort of adults with concussion. METHODS AND FINDINGS: Data from a cohort study (Ontario Concussion Cohort study, 2008 to 2016; n = 1,330,336) including all adults with a concussion diagnosis by either primary care physician (ICD-9 code 850) or in emergency department (ICD-10 code S06) and 2 years of healthcare tracking postinjury (2008 to 2014, n = 587,057) were used in a retrospective analysis. Approximately 42.4% of the cohort was female, and adults between 18 and 30 years was the largest age group (31.0%). PPCS was defined as 2 or more specialist visits for concussion-related symptoms more than 6 months after injury index date. Approximately 13% (73,122) of the cohort had PPCS. Total cohort was divided into Derivation (2009 to 2013, n = 417,335) and Validation cohorts (2009 and 2014, n = 169,722) based upon injury index year. Variables selected a priori such as psychiatric disorders, migraines, sleep disorders, demographic factors, and pre-injury healthcare patterns were entered into multivariable logistic regression and CART modeling in the Derivation Cohort to calculate PPCS estimates and forward selection logistic regression model in the Validation Cohort. Variables with the highest probability of PPCS derived in the Derivation Cohort were: Age >61 years ([Formula: see text] = 0.54), bipolar disorder ([Formula: see text] = 0.52), high pre-injury primary care visits per year ([Formula: see text] = 0.46), personality disorders ([Formula: see text] = 0.45), and anxiety and depression ([Formula: see text] = 0.33). The area under the curve (AUC) was 0.79 for the derivation model, 0.79 for bootstrap internal validation of the Derivation Cohort, and 0.64 for the Validation model. A limitation of this study was ability to track healthcare usage only to healthcare providers that submit to Ontario Health Insurance Plan (OHIP); thus, some patients seeking treatment for prolonged symptoms may not be captured in this analysis. CONCLUSIONS: In this study, we observed that premorbid psychiatric conditions, pre-injury health system usage, and older age were associated with increased risk of a prolonged recovery from concussion. This risk score allows clinicians to calculate an individual's risk of requiring treatment more than 6 months post-concussion.

Increasing the use of home medication lists in an outpatient neurorehabilitation clinic.

Medication reconciliation in ambulatory care settings helps prevent adverse drug events. Patient involvement in the process is crucial, as clinicians must verify the reported medication history with other sources such as home medication lists or brown-bagged home medications provided by patients. However, only 47.8% of brain injury and stroke adult outpatients at Toronto Rehabilitation Institute, an academic rehabilitation hospital, bring their medications/medication lists to clinic visits. In turn, missing medication information impacts the clinic by causing delays in treatment and interrupted clinic flow. This project aimed to increase the percentage of patients who bring their medications/medication lists to 80% and decrease the impact on clinic visits caused by missing medication information to 10%. This was a controlled before-after study, with the outpatient rehabilitation assessment (OPRA) clinic as the intervention and the spasticity clinic as the control. The model for improvement was used as the project framework. Process mapping, Ishikawa diagrams, driver diagrams and patient surveys generated the change ideas. Verbal reminders during confirmation phone calls, written reminders and medication list templates were implemented. Data were collected on a biweekly basis and analysed using statistical control charts. After six Plan-Do-Study-Act cycles conducted over 49 weeks, both project aims were achieved. The percentage of OPRA clinic patients who brought medications/medication lists was 81.8% and the impact on clinic visits caused by missing medication information was 9.1% of clinic visits. Special cause variation was detected on the statistical control charts. Conversely, there was no special cause variation for the spasticity clinic (the control) for either aim. Lessons learnt include the importance of prolonged data collection when implementing interventions with long lag time, and that verbal reminders may not be effective for patients with cognitive impairments. Future efforts may focus on implementing the bundle of project interventions for the spasticity clinic.

Cost-effectiveness of a high-intensity rapid access outpatient stroke rehabilitation program.

A common strategy to improve cost-effectiveness in healthcare is to offer outpatient care instead of in-hospital care. Toronto Rehabilitation Institute developed an outpatient high-intensity fast-track (FT) stroke rehabilitation program aimed at discharging inpatient stroke rehabilitation patients earlier or bypassing inpatient rehabilitation altogether. This cost-effectiveness analysis compares FT rehabilitation within 1 week of discharge with no FT in a single healthcare payer system. Patient costs and outcomes over a 12-week time horizon were included. Using individual-level FT data from April 2015 to March 2016, incremental cost-effectiveness ratios (ICERs) (with 95% confidence interval) were estimated using regression. Subgroup analysis was completed for patients entering FT directly from inpatient rehabilitation and acute stroke care. Uncertainty was assessed using a cost-effectiveness acceptability curve with a range of willingness-to-pay values ($0-1000 per inpatient day saved). ICER (95% confidence interval) estimate for patients entering FT from inpatient rehabilitation was $404 ($270-620) per inpatient day saved. ICER estimate for direct from acute care admissions was $37 ($20-55) per day saved. At willingness-to-pay of $698 (cost of one alternate level of care day in acute care awaiting rehabilitation), the probability of FT being cost-effective was 99.2 and 100% for patients from inpatient rehabilitation and acute stroke care, respectively. From a single healthcare payer perspective, FT is a cost-effective method of providing appropriate rehabilitation intensity for stroke patients early on, and likely to provide savings to the healthcare system upstream through fewer days awaiting rehabilitation admission.

The Impact of Introducing a Physical Medicine and Rehabilitation Trauma Consultation Service to an Academic Level 1 Trauma Center.

OBJECTIVE: Previous retrospective studies suggest that early physical medicine and rehabilitation (PM&R) consultation for trauma patients improves outcome and reduces acute care length of stay (LOS). There have not been controlled studies to evaluate this impact. This study assesses the impact of PM&R consultations on acute trauma patients. DESIGN: This study compared measured outcomes before and after the introduction of a PM&R consultation service to the trauma program at a large academic hospital. The primary outcome measure was acute care LOS. RESULTS: The 274 historical controls and 76 patients who received a PM&R consultation were not different in injury severity score, age, or sex. Length of stay was not different between the two groups. However, when early (≤8 days after injury) versus late (>8 days) consults were compared, the early group had a markedly lower LOS (12 vs. 30 days, P < 0.001). When adjusted for injury severity score, an early consult was associated with an 11.8-day lower LOS (P < 0.001). The early consult group also had fewer complications and less usage of benzodiazepines and antipsychotics. CONCLUSIONS: An acute care PM&R consultation of 8 days or less after admission is associated with a shorter acute care LOS, fewer complications, and less use of benzodiazepines and antipsychotics.

A narrative review of the impact of medical comorbidities on stroke rehabilitation outcomes.

PURPOSE: Medical comorbidities in stroke patients influence acute mortality, but may also affect participation of survivors in rehabilitation. There is limited research investigating the impact of comorbidities on stroke rehabilitation outcomes. The review will explore the literature on the impact of comorbidities on stroke rehabilitation outcome. MATERIALS AND METHODS: The literature was searched systematically, including MEDLINE database, EMBASE and PsychINFO, combining variations of the terms stroke, rehabilitation and comorbidities. Results were limited to English language publications. Included studies had a functional outcome. RESULTS: Twenty relevant articles were identified. Fifteen small prospective or large retrospective studies using global comorbidity scales produced conflicting relationships between comorbidities and rehabilitation outcomes. Five publications addressed specific comorbidities, with three studies finding negative correlation between diabetes and rehabilitation outcomes, although effects diminished with age. In general, there were discrepancies in how comorbidities were identified. Few studies specifically focused on comorbidities and/or rehabilitation outcomes. CONCLUSIONS: There is conflicting evidence regarding the impact of comorbidities on stroke rehabilitation outcomes. However, the presence of more severe diabetes may be associated with worse outcomes. The role of comorbidities in stroke rehabilitation would be best clarified with a large cohort study, with precise comorbidity identification measured against rehabilitation specific outcomes. Implications for rehabilitation Benefit of rehabilitation after stroke in improving functional outcome is well-established. Many stroke patients have comorbid conditions which can impact rehabilitation participation, leading to less benefit obtained from rehabilitation. The burden of comorbid conditions may slow rehabilitation progress, which may warrant a longer duration of rehabilitation to obtain required functional gain to be discharged into the community.

Impact of global cerebral atrophy on clinical outcome after subarachnoid hemorrhage.

OBJECT: Atrophy in specific brain areas correlates with poor neuropsychological outcome after subarachnoid hemorrhage (SAH). Few studies have compared global atrophy in SAH with outcome. The authors examined the relationship between global brain atrophy, clinical factors, and outcome after SAH. METHODS: This study was a post hoc exploratory analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial, a randomized, double-blind, placebo-controlled trial of 413 patients with aneurysmal SAH. Patients with infarctions or areas of encephalomalacia on CT, and those with large clip/coil artifacts, were excluded. The 97 remaining patients underwent CT at baseline and 6 weeks, which was analyzed using voxel-based volumetric measurements. The percentage difference in volume between time points was compared against clinical variables. The relationship with clinical outcome was modeled using univariate and multivariate analysis. RESULTS: Older age, male sex, and systemic inflammatory response syndrome (SIRS) during intensive care stay were significantly associated with brain atrophy. Greater brain atrophy was significantly associated with poor outcome on the modified Rankin scale (mRS), severity of deficits on the National Institutes of Health Stroke Scale (NIHSS), worse executive functioning, and lower EuroQol Group-5D (EQ-5D) score. Adjusted for confounders, brain atrophy was not significantly associated with Mini-Mental State Examination and Functional Status Examination scores. Brain atrophy was not associated with angiographic vasospasm or delayed ischemic neurological deficit. CONCLUSIONS: Worse mRS score, NIHSS score, executive functioning, and EQ-5D scores were associated with greater brain atrophy and older age, male sex, and SIRS burden. These data suggest outcome is associated with factors that cause global brain injury independent of focal brain injury.

Global cerebral atrophy after subarachnoid hemorrhage: a possible marker of acute brain injury and assessment of its impact on outcome.

There is a correlation between poor neuropsychological outcome and focal regions of atrophy in patients with subarachnoid hemorrhage (SAH). No study has investigated the impact of global brain atrophy on outcome after SAH. In other neurological disorders, such as multiple sclerosis, a correlation has been found between global atrophy and outcome. This analysis of patients entered into a randomized clinical trial of clazosentan in patients with SAH (CONSCIOUS-1) investigated the relationship between global cerebral atrophy, clinical factors, and outcome.The 413 patients in the CONSCIOUS-1 study underwent cranial computed tomography (CT) on admission and 6 weeks after SAH. After patients with large clip/coil artefacts and those with infarctions on CT were excluded, 97 patients remained and had voxel-based volumetric measurements of the baseline and 6-week CT scans. The percentage difference in volume between times was taken and analysed against clinical variables. Relationships were modeled using univariate and multivariate analysis.Age, female gender, and higher body temperature during the patient's stay in the intensive care unit were significantly correlated with brain atrophy. Greater brain atrophy significantly correlated with poor outcome (modified Rankin scale), more severe neurological deficits on the National Institute of Health Stroke Scale (NIHSS), and poorer health status (EQ-5D).

Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 database.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) may develop after aneurysmal subarachnoid hemorrhage (SAH). We investigated factors associated with SIRS after SAH, whether SIRS was associated with complications of SAH such as vasospasm, cerebral infarction, and clinical outcome, and whether SIRS could contribute to a difference in outcome between patients treated by endovascular coiling or neurosurgical clipping of the ruptured aneurysm. METHODS: This was exploratory analysis of 413 patients in the CONSCIOUS-1 study. SIRS was diagnosed if the patient had at least 2 of 4 variables (hypothermia/fever, tachycardia, tachypnea, and leukocytosis/leukopenia) within 4 days of admission. Clinical outcome was measured on the Glasgow outcome scale 3 months after SAH. The relationship between clinical and radiologic variables and SIRS, angiographic vasospasm, delayed ischemic neurologic deficit (DIND), cerebral infarction, vasospasm-related infarction, and clinical outcome were modeled with uni- and multivariable analyses. RESULTS: 63% of patients developed SIRS. Many factors were associated with SIRS in univariate analysis, but only poor WFNS grade and pneumonia were independently associated with SIRS in multivariable analysis. SIRS burden (number of SIRS variables per day over the first 4 days) was associated with poor outcome, but not with angiographic vasospasm, DIND, or cerebral infarction. The method of aneurysm treatment was not associated with SIRS. CONCLUSION: SIRS was associated with poor outcome but not angiographic vasospasm, DIND, or cerebral infarction after SAH in the CONSCIOUS-1 data. There was no support for the notion that neurosurgical clipping is associated with a greater risk of SIRS than endovascular coiling.

Persistent Ca2+ current contributes to a prolonged depolarization in Aplysia bag cell neurons.

Neurons may initiate behavior or store information by translating prior activity into a lengthy change in excitability. For example, brief input to the bag cell neurons of Aplysia results in an approximate 30-min afterdischarge that induces reproduction. Similarly, momentary stimulation of cultured bag cells neurons evokes a prolonged depolarization lasting many minutes. Contributing to this is a voltage-independent cation current activated by Ca(2+) entering during the stimulus. However, the cation current is relatively short-lived, and we hypothesized that a second, voltage-dependent persistent current sustains the prolonged depolarization. In bag cell neurons, the inward voltage-dependent current is carried by Ca(2+); thus we tested for persistent Ca(2+) current in primary culture under voltage clamp. The observed current activated between -40 and -50 mV exhibited a very slow decay, presented a similar magnitude regardless of stimulus duration (10-60 s), and, like the rapid Ca(2+) current, was enhanced when Ba(2+) was the permeant ion. The rapid and persistent Ca(2+) current, but not the cation current, were Ni(2+) sensitive. Consistent with the persistent current contributing to the response, Ni(2+) reduced the amplitude of a prolonged depolarization evoked under current clamp. Finally, protein kinase C activation enhanced the rapid and persistent Ca(2+) current as well as increased the prolonged depolarization when elicited by an action potential-independent stimulus. Thus the prolonged depolarization arises from Ca(2+) influx triggering a cation current, followed by voltage-dependent activation of a persistent Ca(2+) current and is subject to modulation. Such synergy between currents may represent a common means of achieving activity-dependent changes to excitability.