Glymphatics Visualization after Focused Ultrasound-Induced Blood-Brain Barrier Opening in Humans.

It is currently unclear whether the glymphatic system, a brain-wide interstitial fluid-cerebrospinal fluid exchange described in rodents, exists in humans. Focal blood-brain barrier disruption using magnetic resonance-guided focused ultrasound allows parenchymal penetration of gadobutrol contrast, creating an opportunity to study glymphatics in vivo noninvasively. We describe patterns of contrast distribution in the perivascular space, subarachnoid space, and space surrounding large veins draining toward the dural sinuses on fluid-attenuated inversion recovery in subjects with Alzheimer disease and amyotrophic lateral sclerosis. This is the first evidence suggesting glymphatic efflux persists in humans. It's relevance to proteinopathies and drug delivery is discussed. ANN NEUROL 2019;86:975-980.

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.

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.

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.

Generalized peripheral nerve failure during thoracic spine surgery: a case report.

OBJECTIVE: Intra-operative systemic changes impairing peripheral nerve function are not commonly detected with electrophysiology. This case presentation illustrates how somatosensory evoked potential (SSEP) monitoring can detect global changes in peripheral nerve excitability during spine surgery. METHODS: A posterior thoracic spine fixation was performed on a young male with multiple traumatic injuries. Bilateral tibial nerve SSEPs were intraoperatively recorded, along with the right median nerve SSEP for control. RESULTS: A rapid, progressive loss of tibial and median nerve potentials (followed by cortical SSEP loss) occurred 90 min after anaesthetic induction. Oxygenation and fluid volume were adequate throughout the case, despite mean airway resistance being elevated (33 cmH(2)0) and blood pressure being low (80/45 mmHg). Corresponding to the decrease in peripheral nerve responses was a drop in end-tidal CO(2) partial pressure (PaCO(2)) from 37 to 25 mmHg. Approximately, 100 min later, the peripheral and cortically generated SSEPs recovered in 2 of 3 limbs monitored. On emergence from anesthesia it was clear that the patient had bitten and kinked the endotracheal tube thus increasing the airway resistance. Ventilation difficulties were magnified with the patient's prone position. Post-operatively there were no sensorimotor deficits. CONCLUSIONS: Somatosensory evoked potential monitoring during spine surgery can detect uncommon generalized nerve conduction block, and further alert surgical teams to a systemic impairment. This was discovered to result from a compromised endotracheal tube. This can apply in various monitoring situations, as the changes affecting the SSEPs were not related to surgical manipulation.

Role of the unperturbed limb and arms in the reactive recovery response to an unexpected slip during locomotion.

Understanding reactive recovery responses to slipping is fundamental in falls research and prevention. The primary purpose of this study was to investigate the role of the unperturbed limb and arms in the reactive recovery response to an unexpected slip. Ten healthy, young adults participated in this experiment in which an unexpected slip was induced by a set of steel free-wheeling rollers. Surface electromyography (EMG) data were collected from the unperturbed limb (i.e., the swing limb) rectus femoris, biceps femoris, tibialis anterior, and the medial head of gastrocnemius, and bilateral gluteus medius, erector spinae, and deltoids. Kinematic data were also collected by an optical imaging system to monitor limb trajectories. The first slip response was significantly different from the subsequent recovery responses to the unexpected slips, with an identifiable reactive recovery response and no proactive changes in EMG patterns. The muscles of the unperturbed limb, upper body, and arms were recruited at the same latency as those previously found for the perturbed limb. The arm elevation strategies assisted in shifting the center of mass forward after it was posteriorly displaced with the slip, while the unperturbed limb musculature demonstrated an extensor strategy supporting the observed lowering of the limb to briefly touch the ground to widen the base of support and to increase stability. Evidently a dynamic multilimb coordinated strategy is employed by the CNS to control and coordinate the upper and lower limbs in reactive recovery responses to unexpected slips during locomotion.