A delphi procedure on rehabilitation outcome for patients with moderate to severe traumatic brain injury; first phase of the Neurotraumatology Quality Registry (NET-QURE)

OBJECTIVE: To select a set of rehabilitation outcome instruments for a national Neurotrauma Quality Registry (Net-QuRe) among professionals involved in the care of patients with traumatic brain injury. DESIGN: A 3-round online Delphi procedure. SUBJECTS: Eighty professionals from multiple disciplines working in 1 of the 8 participating rehabilitation centres were invited to participate. The response rate varied from 70% to 76% per round. METHODS: For the Delphi procedure, multiple outcome categories were defined based on the International Classification of Functioning, Disability and Health (ICF) with concomitant measurement instruments. For each category we strived for consensus on one instrument of at least 75%. RESULTS: After the first round, consensus was reached for the category subjective cognitive functioning. After the second round for quality of life, pain, general functioning, anxiety and depression, general psychological functioning, communication (impairment), and personal factors. Finally, after the third round, consensus was reached for activities of daily living, participation, self-awareness, and aphasia. No consensus was reached for the categories motor function, cognitive function, comorbidity, fatigue, and employment status. CONCLUSION: Consensus was reached in 12 out of 17 outcome categories. A Delphi procedure seems to be a feasible method to collectively select measurement instruments for a multicentre study

Anti-Malaria Drug Mefloquine Induces Motor Learning Deficits in Humans

Mefloquine (a marketed anti-malaria drug) prophylaxis has a high risk of causing adverse events. Interestingly, animal studies have shown that mefloquine imposes a major deficit in motor learning skills by affecting the connexin 36 gap junctions of the inferior olive. We were therefore interested in assessing whether mefloquine might induce similar effects in humans. The main aim of this study was to investigate the effect of mefloquine on olivary-related motor performance and motor learning tasks in humans. We subjected nine participants to voluntary motor timing (dart throwing task), perceptual timing (rhythm perceptual task) and reflex timing tasks (eye-blink task) before and 24 h after the intake of mefloquine. The influence of mefloquine on motor learning was assessed by subjecting participants with and without mefloquine intake (controls: n = 11 vs mefloquine: n = 8) to an eye-blink conditioning task. Voluntary motor performance, perceptual timing, and reflex blinking were not affected by mefloquine use. However, the influence of mefloquine on motor learning was substantial; both learning speed as well as learning capacity was impaired by mefloquine use. Our data suggest that mefloquine disturbs motor learning skills. This adverse effect can have clinical as well as social clinical implications for mefloquine users. Therefore, this side-effect of mefloquine should be further investigated and recognized by clinicians

Best practices in data analysis and sharing in neuroimaging using MRI

Given concerns about the reproducibility of scientific findings, neuroimaging must define best practices for data analysis, results reporting, and algorithm and data sharing to promote transparency, reliability and collaboration. We describe insights from developing a set of recommendations on behalf of the Organization for Human Brain Mapping, and identify barriers that impede these practices, including how the discipline must change to fully exploit the potential of the world’s neuroimaging data

A Common Network of Functional Areas for Attention and Eye Movements

AbstractFunctional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level

Variation in neurosurgical management of traumatic brain injury : a survey in 68 centers participating in the CENTER-TBI study

Correction: Volume: 161 Issue: 3 Pages: 451-455 DOI: 10.1007/s00701-019-03815-6 Accession Number: WOS:000460607500003BackgroundNeurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe.MethodsA survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP).ResultsThe survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25mmHg, 18% 30mmHg, and 17% 20mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions.ConclusionDespite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care.Peer reviewe

Statistical Cerebrovascular Reactivity Signal Properties after Secondary Decompressive Craniectomy in Traumatic Brain Injury: A CENTER-TBI Pilot Analysis.

Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI High Resolution Intensive Care Unit (ICU) Sub-Study cohort, we selected those secondary DC patients with high-frequency physiological data for both at least 24 h pre-DC, and more than 48 h post-DC. Data for all physiology measures were separated into the 24 h pre-DC, the first 48 h post-DC, and beyond 48 h post-DC. We produced slow-wave data sheets for intracranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived a Pressure Reactivity Index (PRx) as a continuous cerebrovascular reactivity metric updated every minute. The time-series behavior of the PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these three time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appear not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation

Adjusting for confounding by indication in observational studies: a case study in traumatic brain injury.

INTRODUCTION: Observational studies of interventions are at risk for confounding by indication. The objective of the current study was to define the circumstances for the validity of methods to adjust for confounding by indication in observational studies. PATIENTS AND METHODS: We performed post hoc analyses of data prospectively collected from three European and North American traumatic brain injury studies including 1,725 patients. The effects of three interventions (intracranial pressure [ICP] monitoring, intracranial operation and primary referral) were estimated in a proportional odds regression model with the Glasgow Outcome Scale as ordinal outcome variable. Three analytical methods were compared: classical covariate adjustment, propensity score matching and instrumental variable (IV) analysis in which the percentage exposed to an intervention in each hospital was added as an independent variable, together with a random intercept for each hospital. In addition, a simulation study was performed in which the effect of a hypothetical beneficial intervention (OR 1.65) was simulated for scenarios with and without unmeasured confounders. RESULTS: For all three interventions, covariate adjustment and propensity score matching resulted in negative estimates of the treatment effect (OR ranging from 0.80 to 0.92), whereas the IV approach indicated that both ICP monitoring and intracranial operation might be beneficial (OR per 10% change 1.17, 95% CI 1.01-1.42 and 1.42, 95% CI 0.95-1.97). In our simulation study, we found that covariate adjustment and propensity score matching resulted in an invalid estimate of the treatment effect in case of unmeasured confounders (OR ranging from 0.90 to 1.03). The IV approach provided an estimate in the similar direction as the simulated effect (OR per 10% change 1.04-1.05) but was statistically inefficient. CONCLUSION: The effect estimation of interventions in observational studies strongly depends on the analytical method used. When unobserved confounding and practice variation are expected in observational multicenter studies, IV analysis should be considered

Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study.

BACKGROUND: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. METHODS: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). RESULTS: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. CONCLUSION: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Cardiovascular and metabolic health is associated with functional brain connectivity in middle-aged and older adults: Results from the Human Connectome Project-Aging study

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer\u27s disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and superior temporal regions. Additionally, at the network-level, FC between core brain networks, such as default-mode and cingulo-opercular, as well as dorsal attention networks, showed strong effects of cardiometabolic risk. These findings highlight the lifespan impact of cardiovascular and metabolic health on whole-brain functional integrity and how these conditions may disrupt higher-order network integrity

Early surgery versus conservative treatment in patients with traumatic intracerebral hematoma:a CENTER-TBI study

Purpose: Evidence regarding the effect of surgery in traumatic intracerebral hematoma (t-ICH) is limited and relies on the STITCH(Trauma) trial. This study is aimed at comparing the effectiveness of early surgery to conservative treatment in patients with a t-ICH. Methods: In a prospective cohort, we included patients with a large t-ICH (&lt; 48 h of injury). Primary outcome was the Glasgow Outcome Scale Extended (GOSE) at 6 months, analyzed with multivariable proportional odds logistic regression. Subgroups included injury severity and isolated vs. non-isolated t-ICH. Results: A total of 367 patients with a large t-ICH were included, of whom 160 received early surgery and 207 received conservative treatment. Patients receiving early surgery were younger (median age 54 vs. 58 years) and more severely injured (median Glasgow Coma Scale 7 vs. 10) compared to those treated conservatively. In the overall cohort, early surgery was not associated with better functional outcome (adjusted odds ratio (AOR) 1.1, (95% CI, 0.6–1.7)) compared to conservative treatment. Early surgery was associated with better outcome for patients with moderate TBI and isolated t-ICH (AOR 1.5 (95% CI, 1.1–2.0); P value for interaction 0.71, and AOR 1.8 (95% CI, 1.3–2.5); P value for interaction 0.004). Conversely, in mild TBI and those with a smaller t-ICH (&lt; 33 cc), conservative treatment was associated with better outcome (AOR 0.6 (95% CI, 0.4–0.9); P value for interaction 0.71, and AOR 0.8 (95% CI, 0.5–1.0); P value for interaction 0.32). Conclusions: Early surgery in t-ICH might benefit those with moderate TBI and isolated t-ICH, comparable with results of the STITCH(Trauma) trial.</p