Allison Bethune

Early somatosensory evoked potential grades in comatose traumatic brain injury patients predict cognitive and functional outcome.

Objectives:To relate early somatosensory evoked potential grades from comatose traumatic brain injury patients to neuropsychological and functional outcome 1 yr later; to determine the day (within the first week after traumatic brain injury) that somatosensory evoked potential grade best correlates with outcome; to determine whether somatosensory evoked potential grade improvement in the first week after traumatic brain injury is associated with improved outcome. Design:Prospective cohort study. Setting:Critical care unit at a university hospital. Patients:Median nerve somatosensory evoked potentials were obtained from 81 comatose patients with traumatic brain injury. Somatosensory evoked potential grades were calculated from results obtained on days 1, 3, and 7 after traumatic brain injury. Glasgow Outcome Scale, Barthel Index, Rivermead Head Injury Follow-up Questionnaire, General Health Questionnaire, Stroop Color-Word Test, Paced Auditory Serial Addition Task, and Symbol-Digit Modalities Test scores were obtained 1 yr after injury. Interventions:None. Measurements and Main Results:Somatosensory evoked potential grade on days 1, 3, and 7 related significantly with Glasgow Outcome Scale and Barthel scores (day 3 better than day 1) but did not relate with Rivermead Head Injury Follow-up Questionnaire or General Health Questionnaire scores. Day 3 and day 7 somatosensory evoked potential grades related significantly with Stroop scores. Day 3 somatosensory evoked potential grades related significantly with Symbol-Digit Modalities Test scores. Patients with bilaterally present but abnormal somatosensory evoked potentials, whose somatosensory evoked potential grade improved between days 1 and 3, had marginally better functional outcome than those without somatosensory evoked potential grade improvement. Conclusions:Day 3 somatosensory evoked potential grade related to information-processing speed, working memory, and the ability to attend to tasks 1 yr after traumatic brain injury. Day 3 somatosensory evoked potential grade had the strongest relationship with functional outcome. Somatosensory evoked potential grades were not related to emotional well-being.

Low-frequency connectivity is associated with mild traumatic brain injury

Mild traumatic brain injury (mTBI) occurs from a closed-head impact. Often referred to as concussion, about 20% of cases complain of secondary psychological sequelae, such as disorders of attention and memory. Known as post-concussive symptoms (PCS), these problems can severely disrupt the patients quality of life. Changes in local spectral power, particularly low-frequency amplitude increases and/or peak alpha slowing have been reported in mTBI, but large-scale connectivity metrics based on inter-regional amplitude correlations relevant for integration and segregation in functional brain networks, and their association with disorders in cognition and behaviour, remain relatively unexplored. Here, we used non-invasive neuroimaging with magnetoencephalography to examine functional connectivity in a resting-state protocol in a group with mTBI (n = 20), and a control group (n = 21). We observed a trend for atypical slow-wave power changes in subcortical, temporal and parietal regions in mTBI, as well as significant long-range increases in amplitude envelope correlations among deep-source, temporal, and frontal regions in the delta, theta, and alpha bands. Subsequently, we conducted an exploratory analysis of patterns of connectivity most associated with variability in secondary symptoms of mTBI, including inattention, anxiety, and depression. Differential patterns of altered resting state neurophysiological network connectivity were found across frequency bands. This indicated that multiple network and frequency specific alterations in large scale brain connectivity may contribute to overlapping cognitive sequelae in mTBI. In conclusion, we show that local spectral power content can be supplemented with measures of correlations in amplitude to define general networks that are atypical in mTBI, and suggest that certain cognitive difficulties are mediated by disturbances in a variety of alterations in network interactions which are differentially expressed across canonical neurophysiological frequency ranges.

A novel method in predicting immediate postoperative facial nerve function post acoustic neuroma excision.

Abstract: To determine whether the percentage calculated by dividing the amplitude of postexcision direct facial nerve stimulus responses (at pontomedullary junction) by the amplitude of distal ipsilateral transcutaneous (stylomastoid region) maximal stimulus responses and response amplitude progression by increasing stimulus intensities have predictive value for determining normal or near-normal (House-Brackmann Grade 1 or 2) immediate postoperative facial nerve function. Study Design: Intraoperative recordings of three muscle groups: 1) frontalis, 2) orbicularis oculi, and 3) orbicularis oris. Postexcision direct facial nerve stimulation at the pontomedullary junction and transcutaneous maximal facial nerve stimulation at the ipsilateral stylomastoid region and their associated response amplitudes were recorded. Setting: Tertiary referral center. Patients and Methods: Patients who underwent acoustic neuroma surgery from January 2004 to March 2006 with intraoperative facial nerve monitoring and an intact facial nerve after tumor excision were included. Recordings were available for 38 patients. Results: With a stimulus intensity of 0.3 mA at the root exit zone, there was an 81% positive predictive value in patients that exhibited a compound action potential of greater than 20% of maximum (sensitivity, 81%). This increased to 93% when the compound action potential was greater than 50% of maximum. When the amplitude increase was greater than 5 &mgr;V, there was a 77% positive predictive value (sensitivity, 87%). Conclusion: The percentage of the response amplitude of direct facial nerve stimulation at the pontomedullary junction when compared with the maximum response amplitude of ipsilateral transcutaneous stimulation at the stylomastoid foramen is a good predictor of normal to near-normal immediate postoperative facial nerve function. Progression of amplitude response also seems to be a good predictor of normal to near-normal immediate postoperative facial nerve function.

Temporal Profile of Cerebrovascular Reactivity Impairment, Gray Matter Volumes, and Persistent Symptoms after Mild Traumatic Head Injury

Objective Increased awareness around neurocognitive deficits after mild traumatic brain injury (mTBI) has progressed the search for objective, diagnostic, and monitoring tools, yet imaging biomarkers for mTBI and recovery are not established in clinical use. It has been suggested that mTBI impairs cerebrovascular reactivity (CVR) to CO2, which could be related to post-concussive syndrome (PCS). We investigate CVR evolution after mTBI using blood-oxygen-level dependent (BOLD) magnetic resonance imaging (MRI) and possible correlation with PCS. Methods A prospective cohort of 25 mTBI patients and 18 matched controls underwent BOLD MRI CVR measurements. A subset of 19 mTBI patients underwent follow-up testing. Visits took place at a mean of 63 and 180 days after injury. Symptoms were assessed with the Sport Concussion Assessment Tool 2 (SCAT2). Symptoms, CVR and brain volume [gray matter (GM), white matter (WM), and whole brain (WB)], age, and sex, were examined between groups and longitudinally within traumatic brain injury (TBI) patients. Results Traumatic brain injury participants were 72% males, mean age being 42.7 years. Control participants were 61% with mean age of 38.7 years. SCAT2 scores tended to improve among those mTBI patients with follow-up visits (p = 0.07); however, they did not tend to recover to scores of the healthy controls. Brain volumes were not statistically different between groups at the first visit (WM p = 0.71; GM p = 0.36). In mTBI patients, there was a reduction in GM volume between visits 1 and 2 (p = 0.0046). Although mean CVR indexes were similar (WM p = 0.27; GM p = 0.36; and WB p = 0.35), the correlation between SCAT2 and CVR was negative in controls (WM-r = −0.59; p = 0.010; GM-r = −0.56; p = 0.016; brain-r = −0.58; p = 0.012) and weaker and positive in mTBI (brain-r = 0.4; p = 0.046; GM-r = 0.4; p = 0.048). SCAT2 correlated with GM volume (r = 0.5215, p = 0.0075) in mTBI but not in controls (r = 0.2945, p = 0.2355). Conclusion There is a correlation between lower GM CVR indexes and lower performance on SCAT2 in patients with mTBI, which seems to be associated with more symptoms. This correlation seems to persist well beyond 120 days. mTBI may lead to a decrease in GM volume in these patients.

Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound.

Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood–brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer’s disease. Here, we used focused ultrasound to open the blood–brain barrier in five patients with early to moderate Alzheimer’s disease in a phase I safety trial. In all patients, the blood–brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood–brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using [18F]-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer’s disease.Magnetic resonance-guided focused ultrasound with injected microbubbles has been used to temporarily open the blood–brain barrier (BBB) in animal models of Alzheimers disease (AD). Here, the authors use this technology to non-invasively open the BBB in 5 patients with mild-to-moderate AD in a phase I trial, and show that the procedure is safe.

Increased Frontal Lobe Activation After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Neurocognitive deficits are common among survivors of aneurysmal subarachnoid hemorrhage, even among those with good outcomes and no structural lesions. This study aims to probe the neurophysiological underpinnings of cognitive dysfunction among patients with ruptured intracranial aneurysms using magnetoencephalography (MEG). Methods— Thirteen patients who had undergone uncomplicated coiling for aneurysmal subarachnoid hemorrhage and 13 matched controls were enrolled. Neuropsychological tests were done before magnetoencephalography scans. Magnetoencephalography data were acquired in a 151-channel, whole-head magnetoencephalography system for resting state and 2 cognitive tasks (go-no-go and set-shifting). Mean time from treatment to test was 18.8 months. Results— Cognitive tasks of inhibition (go-no-go) indicated greater activation in the right anterior cingulate and inferior frontal gyrus, and cognitive set-shifting tasks (mental flexibility) indicated greater activity in the bilateral anterior cingulate cortex and right medial frontal gyrus among aneurysmal subarachnoid hemorrhage patients, with significantly different timing of activation between groups. Resting-state, beta-band connectivity of the anterior cingulate correlated negatively with Montreal Cognitive Assessment scores (left: r=−0.56; P<0.01 and right: r=−0.55; P<0.01): higher connectivity of this region was linked to poorer cognitive test performance. Conclusions— We have shown increased activation in areas of the anterior cingulate gyrus and frontobasal regions during the execution of more demanding tasks in good grade. The degree of activation in the anterior cingulate gyrus has a negative correlation with cognitive (Montreal Cognitive Assessment) scores. These subtle differences may be related to the common neurocognitive and behavioral complaints seen in this patient population.

Patterns of use of somatosensory-evoked potentials for comatose patients in Canada.

PURPOSE To measure how frequently somatosensory-evoked potentials (SEPs) are used in comatose patients after traumatic brain injury (TBI) and hypoxic ischemic encephalopathy (HIE), how SEPs contribute to outcome prediction and clinical decision making, and how available they are to clinicians. METHODS A novel factual and scenario-based survey instrument to measure patterns of SEPs use in comatose patients due to HIE or TBI was distributed to critical care, neurology, and neurosurgical physicians across Canada. The analysis was based on 86 completed surveys from specialists in neurology (36), neurosurgery (24), and critical care (22). RESULTS Most (73%) of respondents reported that SEPs were available. When provided clinical vignettes, only 36% indicated that they would use them in TBI and 49% would use them in HIE. When respondents ranked the various methods available for establishing prognosis for awakening, SEP was ranked after cerebral blood flow and magnetic resonance imaging. The majority did not accurately estimate chances of awakening when SEP responses were bilaterally absent. CONCLUSIONS There are significant opportunities to optimize the use of SEPs in comatose patients including standardizing SEP testing and reporting, better communicating results to critical care physicians, and improving the understanding regarding the recommended use and interpretation of these tests.

Suicidal Ideation After Mild Traumatic Brain Injury: A Consecutive Canadian Sample

This study aims to elucidate psychosocial and injury features contributing to SI following concussion or mild traumatic brain injury (mTBI) and the time course for its development. Between 1998 and 2012, a sample of 871 patients referred to a follow-up clinic after concussion treatment in an urban tertiary care ED were consecutively offered enrollment at 3 months post injury. Data from psychiatric and social-demographic assessments were consecutively collected at 2 visits (3 and 6 months after injury) respectively. Chi-square and t-tests were performed to identify associations between variables related with SI. Logistic regression analysis was performed to identify factors independently associated. During the enrolment period, 2,296 patients with mTBI presented to the ED. 871 adults completed psychiatric and social demographic clinic assessments at 3 months, and 500 returned at 6 months. Suicidal ideation was expressed by 6.3% at 3 months and 8.2% at 6 months. Regression models showed SI independently associated with: speaking English as a second language (ESL) and injury mechanism (MVC passenger) at 3 and 6 months; and history of depression and marital status at 3 months only. SI is common 3 months after mTBI, and appears more at 6 month follow up. These findings suggest earlier screening for predisposing factors and closer monitoring of those at risk for suicidality.

Feasibility of Magnetoencephalography after endovascular Treatment of ruptured intracranial aneurysms

Objective Among good outcome survivors of aneurysmal subarachnoid hemorrhage (aSAH), only 23% have normal neurocognitive performance, despite imaging that is often normal. The aim of this work is to explore the use of magnetoencephalography (MEG) after endovascular treatment of ruptured aneurysms. Methods Good outcome aSAH patients treated with coiling and matched controls were recruited. Clinical assessments and resting-state MEG and anatomical MRI images were obtained. Brain space was normalized to standard Montreal Neurological Institute (MNI) brain. Areas of interest were identified with Automated Anatomical Labeling (AAL) and “electrodes” reconstructed using vector beamformer. Spectral power density estimates for each location was averaged across the brain to derive mean signal power. Virtual-sensor data closest to the coil was assessed for signal quality. Results Thirteen aSAH patients and 13 matched controls were recruited. Mean age was 54.5 years (SD = 9.9) for controls and 56.8 years (SD = 11.8) for aSAH. The majority of aneurysms (62%) were in the midline. Mean time from aSAH to MEG was 18.8 months (2.4–67.5; SD = 19). Data quality was comparable in both groups, including the virtual-sensors close to the coil mass. Mean signal power showed no significant spectral alterations in the aSAH group. Conclusion MEG is feasible in aSAH patients after endovascular treatment. Our results suggest that the signal quality and strength is good, and the presence of coils does not interfere with testing. Considering the common neurocognitive complaints of aSAH survivors MEG could be developed to diagnose, quantify, and monitor neurocognitive problems after aSAH.

Somatosensory evoked potentials after decompressive craniectomy for traumatic brain injury

Somatosensory evoked potentials (SSEPs) are used for neuroprognosis after severe traumatic brain injury (TBI). However decompressive craniectomy (DC), involving removal of a portion of the skull to alleviate elevated intracranial pressure, is associated with an increase in SSEP amplitude. Accordingly, SSEPs are not available for neuroprognosis over the hemisphere with DC. We aim to determine the degree to which SSEP amplitudes are increased in the absence of cranial bone. This will serve as a precursor for translation to clinically prognostic ranges. Intra-operative SSEPs were performed before and after bone flap replacement in 22 patients with severe TBI. SSEP measurements were also performed in a comparison non-traumatic group undergoing craniotomy for tumor resection. N20/P25 amplitudes and central conduction time were measured with the bone flap in (BI) and out (BO). Linear regressions, adjusting for skull thickness and study arm, were performed to evaluate the contribution of bone presence to SSEP amplitudes. Latencies were not different between BO or BI trials in either group. Mean N20/P25 amplitudes recorded with BO were statistically different (p = 0.0001) from BI in both cohorts, showing an approximate doubling in BO amplitudes. For contralateral–ipsilateral montages r2 was 0.28 and for frontal pole montages r2 was 0.62. Cortical SSEP amplitudes are influenced by the presence of cortical bone as is particularly evident in frontal pole montages. Larger, longitudinal trials to assess feasibility of neuroprognosis over the hemisphere with DC in severe TBI patients are warranted.