A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI.

BACKGROUND: Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI. METHODS: 24 older adults with amnestic MCI (aMCI) due to possible Alzheimer's disease enrolled in a phase I trial of open-label accelerated iTBS to the left dorsolateral prefrontal cortex (8 stimulation sessions of 600 pulses of iTBS/day for 3 days). Participants rated common side effects during and after each session and retrospectively (at post-treatment and 4-week follow-up). They completed brain MRI (for safety assessments and electric field modeling), neuropsychiatric evaluations, and neuropsychological testing before and after treatment; a subset of measures was administered at follow-up. RESULTS: Retention was high (95%) and there were no adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participants reported high acceptability, minimal side effects, and low desire to quit despite some rating the treatment as tiring. Electric field modeling data suggest that all participants received safe and therapeutic cortical stimulation intensities. We observed a significant, large effect size (d=0.98) improvement in fluid cognition using the NIH Toolbox Cognition Battery from pre-treatment to post-treatment. CONCLUSIONS: Our findings support the safety, feasibility, and acceptability of accelerated iTBS in aMCI. In addition, we provide evidence of target engagement in the form of improved cognition following treatment. These promising results directly inform future trials aimed at optimizing treatment parameters. TRIAL REGISTRATION NUMBER: NCT04503096.

Template MRI scans reliably approximate individual and group-level tES and TMS electric fields induced in motor and prefrontal circuits.

Background: Electric field (E-field) modeling is a valuable method of elucidating the cortical target engagement from transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), but it is typically dependent on individual MRI scans. In this study, we systematically tested whether E-field models in template MNI-152 and Ernie scans can reliably approximate group-level E-fields induced in N = 195 individuals across 5 diagnoses (healthy, alcohol use disorder, tobacco use disorder, anxiety, depression). Methods: We computed 788 E-field models using the CHARM-SimNIBS 4.0.0 pipeline with 4 E-field models per participant (motor and prefrontal targets for TMS and tES). We additionally calculated permutation analyses to determine the point of stability of E-fields to assess whether the 152 brains represented in the MNI-152 template is sufficient. Results: Group-level E-fields did not significantly differ between the individual vs. MNI-152 template and Ernie scans for any stimulation modality or location (p > 0.05). However, TMS-induced E-field magnitudes significantly varied by diagnosis; individuals with generalized anxiety had significantly higher prefrontal and motor E-field magnitudes than healthy controls and those with alcohol use disorder and depression (p < 0.001). The point of stability for group-level E-field magnitudes ranged from 42 (motor tES) to 52 participants (prefrontal TMS). Conclusion: MNI-152 and Ernie models reliably estimate group-average TMS and tES-induced E-fields transdiagnostically. The MNI-152 template includes sufficient scans to control for interindividual anatomical differences (i.e., above the point of stability). Taken together, using the MNI-152 and Ernie brains to approximate group-level E-fields is a valid and reliable approach.

Safety of MRI in the localization of implanted intracranial electrodes for refractory epilepsy.

BACKGROUND AND PURPOSE: This is an observational study to evaluate the safety of magnetic resonance imaging (MRI) to localize subdural grids and depth electrodes in patients with refractory epilepsy using a 1.5 Tesla MR scanner. METHODS: We implemented an optimized MRI protocol providing adequate image quality for the assessment of subdural grids and depth electrodes, while minimizing the specific absorption rate (SAR). We reviewed all MRI studies performed in patients with subdural grids and depth electrodes between January 2010 and October 2018. Image quality was graded as acceptable or nonacceptable for the assessment of intracranial device positioning. We reviewed the medical record and any imaging obtained after intracranial implant removal for adverse event or complication occurring during and after the procedure. RESULTS: Ninety-nine patients with refractory epilepsy underwent MRI scans using a magnetization-prepared rapid acquisition of gradient echo sequence and a transmit-receive head coil with depth electrodes and subdural grids in place. Two patients underwent two separate depth electrode implantations for a total of 101 procedures and MRI scans. No clinical adverse events were reported during or immediately after imaging. Image quality was graded as acceptable for 97 MRI scans. Review of follow-up CT and MRI studies after implant removal, available for 70 patients, did not demonstrate unexpected complications in 69 patients. CONCLUSION: In our experience, a low SAR MRI protocol can be used to safely localize intracranial subdural grids and depth electrode in patients with refractory epilepsy.

Altered cerebral perfusion in response to chronic mild hypercapnia and head-down tilt Bed rest as an analog for Spaceflight.

PURPOSE: Following prolonged stays on the International Space Station (ISS), some astronauts exhibit visual acuity changes, ophthalmological findings, and mildly elevated intracranial pressures as part of a novel process called spaceflight-associated neuro-ocular syndrome (SANS). To determine the pathophysiology of SANS, NASA conducted a multi-investigator study in which 11 healthy participants underwent head-down tilt bed rest, mimicking microgravity-induced cephalad fluid shifts, combined with elevated ambient CO2 levels similar to those on the ISS (HDT+CO2). As part of that study, we examined the effects of HDT+CO2 on cerebral perfusion. METHODS: Using arterial spin labeling, we compared cerebral perfusion before, during, and after HDT+CO2 in participants who developed SANS (n = 5) with those who did not (n = 6). RESULTS: All participants demonstrated a decrease in perfusion during HDT+CO2 (mean decrease of 25.1% at HDT7 and 16.2% at HDT29); however, the timing and degree of change varied between the groups. At day 7 of HDT+CO2, the SANS group experienced a greater reduction in perfusion than the non-SANS group (p =.05, 95% CI:-0.19 to 16.11, d=.94, large effect). Conversely, by day 29 of HDT+CO2, the SANS group had significantly higher perfusion (approaching their baseline) than the non-SANS group (p = .04, 95% CI:0.33 to 13.07, d=1.01, large effect). CONCLUSION: Compared with baseline and recovery, HDT+CO2 resulted in reduced cerebral perfusion which varied based on SANS status. Further studies are needed to unravel the relative role of HDT vs hypercapnia, to determine if these perfusion changes are clinically relevant, and whether perfusion changes contribute to the development of SANS during spaceflight.

Primary Central Nervous System Posttransplant Lymphoproliferative Disorder After Kidney Transplant.

Primary central nervous system posttransplant lymphoproliferative disorder is a rare complication of solid organ transplantation, with increasing incidence in children given a steady rise in pediatric solid organ transplants. Given similar imaging appearance to many opportunistic infections, a high degree of awareness is required for prompt and early diagnosis. We report a case of primary central nervous system posttransplant lymphoproliferative disorder presenting as a single rim enhancing lesion with central restricted diffusion mimicking an intracranial abscess.

Juvenile xanthogranuloma of the subdural spaces mimicking chronic hematoma with positive FDG uptake on PET: case report.

The authors report an unusual presentation of juvenile xanthogranuloma (JXG), a non-Langerhans cell histiocytosis of infancy and early childhood. This entity typically presents as a cutaneous head or neck nodule but can manifest with more systemic involvement including in the central nervous system. However, currently there is limited information regarding specific imaging features differentiating JXG from other neuropathological entities, with diagnosis typically made only after tissue sampling. The authors reviewed the initial images of a young patient with shunt-treated hydrocephalus and enlarging, chronic, extraaxial processes presumed to reflect subdural collections from overshunting, and they examine the operative discovery of a mass lesion that was pathologically proven to be JXG. Their results incorporate the important associated histological and advanced imaging features, including previously unreported metabolic activity on FDG PET. Ultimately, the case underscores the need to consider JXG in differential diagnoses of pediatric intracranial masses and highlights the potential role of PET in the initial diagnosis and response to treatment.

A Helpful Tool in Diagnosing Stroke Mimics: Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

BACKGROUND: Prompt and effective management of acute ischemic stroke in the emergency setting requires a high level of suspicion and accurate diagnosis. Conversely, identifying stroke mimics can be challenging, given the similarity of their clinical symptomatology, the necessary rapid assessment and triage, and the overall frenetic pace inherent in the goal of rapid thrombolysis ("time is brain"). CASE REPORT: We describe a case that involves an elderly patient with acute hemiplegia and dysarthria. Given these concerning symptoms, and multiple preexisting cerebrovascular risk factors (including paroxysmal atrial fibrillation), a "stroke alert" was issued. Imaging was negative for infarct and she was ultimately diagnosed with hemiplegic migraine based on her symptoms and impressive findings on a novel magnetic resonance sequence called arterial spin labeled (ASL) perfusion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Identifying a nonischemic etiology in a presumed stroke patient, while often difficult, can obviate unnecessary treatment, improve patient care, and promote appropriate resource allocation. As imaging and treatment of cerebrovascular disease advances, the optimization of multidisciplinary care should incorporate neuroradiologists informing and availing their clinical colleagues of applications of an ever-expanding imaging armamentarium. This case is an excellent example of both a common challenging stroke mimic and the potential benefits of ASL perfusion imaging in refining and expediting accurate diagnosis. In addition, it serves as a more general introduction to the particular strengths of this noninvasive, noncontrast magnetic resonance technique, which can be employed to assess varied emergent neuropathology.

Spaceflight-Associated Changes in the Opacification of the Paranasal Sinuses and Mastoid Air Cells in Astronauts.

Importance: Head congestion is one of the most common somatic symptoms experienced by astronauts during spaceflight; however, changes in the opacification of the paranasal sinuses or mastoid air cells in astronauts have not been adequately studied. Objectives: To quantify preflight to postflight changes in the opacification of the paranasal sinuses and mastoid air cells in Space Shuttle astronauts and International Space Station (ISS) astronauts and to assess whether there are differences between the 2 groups of astronauts. Design, Setting, and Participants: This cohort study examined preflight and postflight head magnetic resonance images (MRIs) of 35 astronauts who had participated in either a short-duration (≤30 days) Space Shuttle mission or a long-duration (>30 days) ISS mission and had undergone both preflight and postflight MRI. Images were obtained before and after spaceflight. Images were evaluated by 2 neuroradiologists blinded to which mission each astronaut had flown and to which images were preflight or postflight images. Exposure: Spaceflight on the Space Shuttle or the ISS. Main Outcomes and Measures: Measured outcomes included preflight to postflight changes in Lund-Mackay scores for the paranasal sinuses and in scores grading mastoid effusions. Results: Most astronauts in both the Space Shuttle group (n = 17; 15 men; mean [SD] age at launch, 47.7 [3.1] years) and the ISS group (n = 18; 14 men; mean [SD] age at launch, 48.6 [4.7] years) exhibited either no change or a reduction in paranasal sinus opacification as seen on postflight MRI scans (Space Shuttle group: 6 [35.3%] had no sinus opacification before or after spaceflight, 5 [29.4%] had less sinus opacification after spaceflight, 3 [17.6%] had the same amount of sinus opacification before and after spaceflight, and 3 [17.6%] had increased paranasal sinus opacification after spaceflight; ISS group: 8 [44.4%] had no sinus opacification before or after spaceflight, 4 [22.2%] had less sinus opacification after spaceflight, 1 (5.6%) had the same amount of sinus opacification before and after spaceflight, and 5 [27.8%] had scores consistent with increased paranasal sinus opacification after spaceflight). Long-duration spaceflight (ISS group) was associated with an increased risk of mastoid effusion relative to short-duration spaceflight (relative risk, 4.72; 95% CI, 1.2-18.5). Images were obtained a mean (SD) 287.5 (208.6) days (range, 18-627 days) prior to and 6.8 (5.8) days (range, 1-20 days) after spaceflight. Astronauts had undergone either a mean (SD) of 13.6 (1.6) days of spaceflight on the Space Shuttle (17 astronauts) or 164.8 (18.9) days on the ISS (18 astronauts). Conclusions and Relevance: This study found that exposure to spaceflight conditions on the ISS is associated with an increased likelihood for the formation of mastoid effusions. There was no association between exposure to spaceflight conditions and changes in paranasal sinus opacification. The limitations of this study include lack of information concerning medical history and mission-specific operational experience for individual astronauts. Further studies are indicated to determine the cause and composition of the mastoid effusions.

Effects of Spaceflight on Astronaut Brain Structure as Indicated on MRI.

BACKGROUND: There is limited information regarding the effects of spaceflight on the anatomical configuration of the brain and on cerebrospinal fluid (CSF) spaces. METHODS: We used magnetic resonance imaging (MRI) to compare images of 18 astronauts' brains before and after missions of long duration, involving stays on the International Space Station, and of 16 astronauts' brains before and after missions of short duration, involving participation in the Space Shuttle Program. Images were interpreted by readers who were unaware of the flight duration. We also generated paired preflight and postflight MRI cine clips derived from high-resolution, three-dimensional imaging of 12 astronauts after long-duration flights and from 6 astronauts after short-duration flights in order to assess the extent of narrowing of CSF spaces and the displacement of brain structures. We also compared preflight ventricular volumes with postflight ventricular volumes by means of an automated analysis of T1-weighted MRIs. The main prespecified analyses focused on the change in the volume of the central sulcus, the change in the volume of CSF spaces at the vertex, and vertical displacement of the brain. RESULTS: Narrowing of the central sulcus occurred in 17 of 18 astronauts after long-duration flights (mean flight time, 164.8 days) and in 3 of 16 astronauts after short-duration flights (mean flight time, 13.6 days) (P<0.001). Cine clips from a subgroup of astronauts showed an upward shift of the brain after all long-duration flights (12 astronauts) but not after short-duration flights (6 astronauts) and narrowing of CSF spaces at the vertex after all long-duration flights (12 astronauts) and in 1 of 6 astronauts after short-duration flights. Three astronauts in the long-duration group had optic-disk edema, and all 3 had narrowing of the central sulcus. A cine clip was available for 1 of these 3 astronauts, and the cine clip showed upward shift of the brain. CONCLUSIONS: Narrowing of the central sulcus, upward shift of the brain, and narrowing of CSF spaces at the vertex occurred frequently and predominantly in astronauts after long-duration flights. Further investigation, including repeated postflight imaging conducted after some time on Earth, is required to determine the duration and clinical significance of these changes. (Funded by the National Aeronautics and Space Administration.).