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Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.
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BACKGROUND: Ambulatory spinal surgery is a care delivery model meant to improve patient outcomes and reduce in-hospital length of stay (LOS). We reviewed the experience of implementing an outpatient spine surgery program in Manitoba, Canada and highlight elements that can be used to reduce LOS and re-presentation to hospital. METHODS: This is a retrospective cohort study using data from the Canadian Spine Outcomes and Research Network and independent chart review of adult patients undergoing outpatient spinal surgery between 2015 and 2018. Patient demographics, comorbidities, perioperative course, LOS, and readmissions were analyzed. RESULTS: We included 217 patients in this analysis. The mean LOS was 36.2 hours; 71.98% of patients had a LOS <24 hours. A Kruskal-Wallis test by ranks analysis was conducted and identified 7 elements that correlated with prolonged length of stay (>1 day): age older than 55 (P = 0.027), body mass index >25 (P = 0.045), uncontrolled diabetes (P = 0.015), preoperative use of opioid medication (P = 0.024), American Society of Anesthesiologists classification of 3 (P = 0.023), non-minimally invasive surgical approach, and multilevel procedures. Most (94.1%) of the patients with none of these elements (i.e., age <55, low body mass index, normal/controlled diabetes, minimal preoperative opioid use, American Society of Anesthesiologist classification <3, minimally invasive surgical procedure) had a favorable LOS, <24 hours, compared with 84.8% with 1 risk factor, 80.4% of those with two, 69.8% with three, 53.1% with four, and 31.2% with 5 or more. A small number of patients (14.98%) presented to an emergency department within 90 days of their operation, and there was a 6.28% readmission rate. CONCLUSIONS: We identified several patient and surgical criteria that correlate with prolonged length of stays following planned ambulatory spine surgery. Our work provides some empiric evidence to help guide surgeons on which patients and approaches are ideal for ambulatory surgery.
Subject(s)
Ambulatory Surgical Procedures , Diabetes Mellitus , Adult , Humans , Analgesics, Opioid/therapeutic use , Canada , Diabetes Mellitus/drug therapy , Length of Stay , Patient Readmission , Patient Selection , Postoperative Complications/drug therapy , Retrospective StudiesABSTRACT
OBJECTIVE: Intracerebral abscess is a life-threatening condition for which there are no current, widely accepted neurosurgical management guidelines. The purpose of this study was to investigate Canadian practice patterns for the medical and surgical management of primary, recurrent, and multiple intracerebral abscesses. METHODS: A self-administered, cross-sectional, electronic survey was distributed to active staff and resident members of the Canadian Neurosurgical Society and Canadian Neurosurgery Research Collaborative. Responses between subgroups were analyzed using the Chi-square test. RESULTS: In total, 101 respondents (57.7%) completed the survey. The majority (60.0%) were staff neurosurgeons working in an academic, adult care setting (80%). We identified a consensus that abscesses >2.5 cm in diameter should be considered for surgical intervention. The majority of respondents were in favor of excising an intracerebral abscess over performing aspiration if located superficially in non-eloquent cortex (60.4%), located in the posterior fossa (65.4%), or causing mass effect leading to herniation (75.3%). The majority of respondents were in favor of reoperation for recurrent abscesses if measuring greater than 2.5 cm, associated with progressive neurological deterioration, the index operation was an aspiration and did not include resection of the abscess capsule, and if the recurrence occurred despite prior surgery combined with maximal antibiotic therapy. There was no consensus on the use of topical intraoperative antibiotics. CONCLUSION: This survey demonstrated heterogeneity in the medical and surgical management of primary, recurrent, and multiple brain abscesses among Canadian neurosurgery attending staff and residents.
Subject(s)
Brain Abscess , Neurosurgery , Adult , Humans , Cross-Sectional Studies , Canada , Brain Abscess/surgery , Neurosurgical Procedures , Anti-Bacterial Agents/therapeutic useABSTRACT
BACKGROUND: Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes. METHODS: Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available. RESULTS: Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1-94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poor-performing "Immune-infiltrated" subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing "Cellular" subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versus-other binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52-1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data. CONCLUSIONS: Here, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome-based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.
Subject(s)
Chordoma , Chordoma/pathology , Cluster Analysis , DNA Methylation , Humans , Multivariate Analysis , PrognosisABSTRACT
Hypertonic saline (HTS) is a commonly administered agent for intracranial pressure (ICP) control in traumatic brain injury (TBI). The literature on its use is mainly in moderate/severe TBI where invasive ICP monitoring is present. The role of HTS in patients with moderate TBI (mTBI) outside of the intensive care unit (ICU) setting remains unclear. The goal of this scoping review was to provide an overview of the available literature on HTS administration in patients with mTBI without ICP monitoring, assessing its impact on outcome and transitions in care. We performed a scoping systematic review of the literature of MEDLINE, Embase, Scopus, BIOSIS, and the Cochrane Databases from inception to July 31, 2020. We searched for those published articles documenting the administration of HTS in patients with mTBI with recorded functional outcome or transitions in hospital care. A two-step review process was conducted in accordance with methodology outlined in the Cochrane Handbook for Systematic Reviews of Interventions. There were many studies with combined moderate/severe TBI populations. However, most failed to document subgroup analysis for patients with mTBI. Our search strategy identified only one study that documented the administration of HTS in mTBI in which subgroup analysis for mTBI and outcomes were provided. This retrospective cohort study assessed patients with mTBI who did/did not receive prophylactic HTS, finding that those not receiving HTS demonstrated a deterioration in Glasgow Coma Scale (GCS) score in the first 48 h. However, the HTS group did demonstrate a trend to longer hospital stay and pneumonia. Our scoping review identified a significant gap in knowledge surrounding the use of HTS for patients with mTBI without invasive ICP monitoring. The limited identified literature suggests prophylactic administration prevents clinical deterioration, although this is based on a single study with data available for mTBI sub-analysis. Further studies on HTS in non-monitored patients with mTBI are required.
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BACKGROUND: Pressure reactivity index (PRx) has emerged as a means to continuously monitor cerebrovascular reactivity in traumatic brain injury (TBI). However, other intracranial pressure (ICP)-based continuous metrics exist, and may have advantages over PRx. The goal of this study was to perform a scoping overview of the literature on non-PRx ICP-based continuous cerebrovascular reactivity metrics in adult TBI. METHODS: We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2019. Using a two-stage filtering of title/abstract, and then full manuscript, we identified pertinent articles. Data was abstracted to tables and each technique summarized, including pulse amplitude index (PAx), correlation between pulse amplitude of ICP and cerebral perfusion pressure (RAC), PRx55-15, and low-resolution metrics LAx and L-PRx. RESULTS: A total of 23 articles met the inclusion criteria, with the vast majority being retrospective in nature and based out of European centers. Sixteen articles focused on high-resolution metrics PAx, RAC, and PRx55-15, with 6 articles focusing on LAx and L-PRx. PAx may have a role in low ICP situations, where it appears to perform superior to PRx. RAC displays similar behavior to PRx, with a trend to stronger associations with favorable/unfavorable outcome at 6 months, and stronger parabolic relationship with CPP. PRx55-15 provides a focused assessment on the vasogenic frequency range associated with cerebral autoregulation, with preliminary data supporting a strong association with outcome in TBI. LAx and L-PRx display varying associations with 6-month outcome in TBI, depending on the window length of calculation, with shorter windows demonstrating stronger correlations with classical PRx. CONCLUSIONS: Non-PRx continuous ICP-based cerebrovascular reactivity metrics can be split into high-resolution and low-resolution measures. High-resolution indices include PAx, RAC, and PRx55-15, while low-resolution indices include L-PRx and LAx. The true role for these metrics beyond classic PRx remains unclear. Each displays situations where it may prove superior over PRx, given limitations with this currently widely accepted measure. Much future investigation into each of these alternative metrics is required prior to adoption into the clinical monitoring armamentarium in adult TBI.
Subject(s)
Brain Injuries, Traumatic/pathology , Cerebrovascular Circulation , Intracranial Pressure , Monitoring, Physiologic/methods , Benchmarking , Brain Injuries, Traumatic/physiopathology , Heart Rate , Homeostasis , Humans , Monitoring, Physiologic/standardsSubject(s)
Fluorescein/administration & dosage , Fluorescent Dyes/administration & dosage , Infratentorial Neoplasms/diagnostic imaging , Infratentorial Neoplasms/surgery , Child, Preschool , Female , Fluorescein/metabolism , Fluorescent Dyes/metabolism , Humans , Infratentorial Neoplasms/metabolism , Injections, IntravenousABSTRACT
Current accepted cerebrovascular reactivity indices suffer from the need of high frequency data capture and export for post-acquisition processing. The role for minute-by-minute data in cerebrovascular reactivity monitoring remains uncertain. The goal was to explore the statistical time-series relationships between intra-cranial pressure (ICP), mean arterial pressure (MAP) and pressure reactivity index (PRx) using both 10-s and minute data update frequency in TBI. Prospective data from 31 patients from 3 centers with moderate/severe TBI and high-frequency archived physiology were reviewed. Both 10-s by 10-s and minute-by-minute mean values were derived for ICP and MAP for each patient. Similarly, PRx was derived using 30 consecutive 10-s data points, updated every minute. While long-PRx (L-PRx) was derived via similar methodology using minute-by-minute data, with L-PRx derived using various window lengths (5, 10, 20, 30, 40, and 60 min; denoted L-PRx_5, etc.). Time-series autoregressive integrative moving average (ARIMA) and vector autoregressive integrative moving average (VARIMA) models were created to analyze the relationship of these parameters over time. ARIMA modelling, Granger causality testing and VARIMA impulse response function (IRF) plotting demonstrated that similar information is carried in minute mean ICP and MAP data, compared to 10-s mean slow-wave ICP and MAP data. Shorter window L-PRx variants, such as L-PRx_5, appear to have a similar ARIMA structure, have a linear association with PRx and display moderate-to-strong correlations (r ~ 0.700, p < 0.0001 for each patient). Thus, these particular L-PRx variants appear closest in nature to standard PRx. ICP and MAP derived via 10-s or minute based averaging display similar statistical time-series structure and co-variance patterns. PRx and L-PRx based on shorter windows also behave similarly over time. These results imply certain L-PRx variants may carry similar information to PRx in TBI.
Subject(s)
Brain Injuries, Traumatic , Cerebrovascular Circulation , Humans , Intracranial Pressure , Pilot Projects , Prospective StudiesABSTRACT
The Full Outline of UnResponsiveness (FOUR) score is a neurologic assessment score. Its benefit over pre-existing scores is its evaluation of brainstem reflexes and respiratory pattern. Our goal was to perform a scoping systematic review of the literature on the application of the FOUR score within pediatric patients. Six databases were searched and 2 reviewers independently screened the results. The initial search yielded 1709 citations; ultimately, 6 studies composed of 571 pediatric patients were used. Four studies examined interobserver reliability of the FOUR score and found it to be good to excellent. All 6 studies demonstrated equivalency of the FOUR score and Glasgow Coma Scale (GCS) in predicting outcome. The existing literature suggests the FOUR score is equivalent to GCS in outcome prediction in pediatric patients; its true superiority over the GCS has not yet been established. It displays good to excellent inter-rater reliability among physicians and nurses.
Subject(s)
Consciousness Disorders/diagnosis , Child , Glasgow Coma Scale , Humans , Neurologic Examination , Prognosis , Reproducibility of ResultsABSTRACT
The quantification and objective documentation of autonomic dysfunction in traumatic brain injury (TBI) is neither well studied nor extensively validated. Most of the descriptions of autonomic dysfunction in the literature are in the form of vague non-specific clinical manifestations. Few studies propose the use of objective measures of assessing the extent of autonomic dysfunction to link them to the outcome of TBI. Our goal was to perform a scoping systematic review of the literature on the objective documentation of autonomic dysfunction in terms of functional and physiological variables to be linked to outcome of TBI. PubMed/MEDLINE®, BIOSIS, Scopus, Embase, Cochrane Libraries, and Global Health databases were searched. Two reviewers independently screened the results. Full texts for citations passing this initial screen were obtained. Inclusion and exclusion criteria were applied to each article to obtain final articles for review. The initial search yielded 2619 citations. Of 69 articles selected for final review, 14 were chosen based on the inclusion and exclusion criteria and are included in the results of this article. 9 of these articles assessed autonomic dysfunction using functional variables and 7 assessed autonomic dysfunction using physiological variables. Some studies included both functional and physiological variables. Of the nine studies linking autonomic dysfunction to functional variables, nine included heart rate variability (HRV), three included baroreflex sensitivity (BRS), and two included blood pressure variability (BPV). A total of 2714 adult patients were studied. Although the nature of association between autonomic dysfunction and outcome is unclear, the objective quantification of autonomic dysfunction seems to be associated with global patient outcome and other neurophysiological measures. Further studies are needed to validate its use and explore the underlying molecular mechanisms of the described associations.
Subject(s)
Autonomic Nervous System Diseases/physiopathology , Brain Injuries, Traumatic/physiopathology , Recovery of Function/physiology , Autonomic Nervous System Diseases/etiology , Brain Injuries, Traumatic/complications , HumansABSTRACT
INTRODUCTION: There have been attempts to alter the prognosis of severe spinal cord injury in different centers, but none of which have reliably altered the outcome. Some trials use stem cells (SCs) that produced widely differing results. We hereby add our experience in our center of a surgical reconstruction of the damaged spinal cord using a mixture of SCs and Platelet-Rich Protein (PRP) with fibrin coated as a biological scaffold. MATERIALS AND METHODS: Four cases of severely damaged spinal cord have been operated for neurolysis and reconstruction of the spinal cord using SCs and platelet-rich protein (PRP) with fibrin coated harvested from the peripheral circulation of the patient. PRP serves to maintain the position of the SCs. One milliliter suspension contains an average of 2.8 × 106 of autologous hematopoietic SCs. Patients were intraoperatively monitored by somatosensory evoked potential, motor evoked potentials, and delta wave. They are clinically followed postoperatively and electromyogram was repeated every 2 weeks. Magnetic resonance imaging (MRI) was repeated regularly. The patients are followed up for a period between 2 and 3 years. RESULTS: One patient demonstrated motor and objective sensory improvement (P = 0.05), two other patients reported subjective sensory improvement, and the fourth one remained without any improvement (P = 0.1). None of these patients demonstrated any sign of deterioration or complication either on the surgery or on implanting of the SCs. MRI clearly proved that the inserted biological scaffold remained in place of reconstruction. CONCLUSION: SCs may play a role in restoring spinal cord functions. However, the unsolved problems of the use of SCs and related ethical issues should be addressed.
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BACKGROUND: The purpose of this study is to investigate the effect of risk factors including International Normalized Ratio (INR) as well as the Partial Thromboplastin Time (PTT) scores on several outcomes, including hospital length of stay (LOS) and The Extended Glasgow Outcome Scale (GOSE) following TBI in the elderly population. METHODS: Data were retrospectively collected on patients (n=982) aged 65 and above who were admitted post TBI to the McGill University Health Centre-Montreal General Hospital from 2000 to 2011. Age, Injury Severity Score (ISS), Glasgow Coma Scale score (GCS), type of trauma (isolated TBI vs polytrauma including TBI), initial CT scan results according to the Marshall Classification and the INR and PTT scores and prescriptions of antiplatelet or anticoagulant agents (AP/AC) were collected. RESULTS: Results also indicated that age, ISS and GSC score have an effect on the GOSE score. We also found that taking AC/AP has an effect on GOSE outcome, but that this effects depends on PTT, with lower odds of a worse outcome for those taking AC/AP agents as the PTT value goes up. However, this effect only becomes significant as the PTT value reaches 60 and above. CONCLUSION: Age and injury severity rather than antithrombotic agent intake are associated with adverse acute outcome such as GOSE in hospitalized elderly TBI patients.