Lonni Schultz

Background/Objectives: Cognitive impairment and neurological dysfunction in Multiple Sclerosis are increasingly understood as consequences of altered brain network connectivity. Magnetoencephalography offers high temporal resolution for investigating functional connectivity patterns, which may underlie various clinical symptoms. This exploratory pilot study aims to characterize preliminary FC patterns at rest and during cognitive processing in MS patients with a high fatigue burden compared with healthy controls using MEG, complemented by a systematic review of existing MEG literature in MS. Methods: In this pilot study, MEG was utilized to investigate connectivity in MS patients and HCs. Data were acquired during resting-state and a digitized version of the Symbol Digit Modalities Test. A systematic review was also conducted following PRISMA guidelines to synthesize the current evidence on frequency-specific MEG connectivity in MS. Results: MS patients exhibited a connectivity pattern paralleling the directionality of neuronal slowing, described in the spectral power MS literature, during resting-state, characterized by reduced interhemispheric coherence in alpha and beta bands alongside region-specific increases in frontal–parietal and parietal–occipital alpha coherence, reflecting a bidirectional spatial reorganization. Conversely, during the SDMT task, the MS group demonstrated significant compensatory recruitment with increased coherence in theta and gamma bands (specifically in frontal and striatal circuits). The systematic review of 44 MEG studies corroborated these findings, highlighting a consistent trend of frequency-dependent dysconnectivity that aligns with clinical load and disease pathology. Conclusions: We found that in MS, network alterations are state-dependent, shifting from reduced connectivity at rest to increased coherence during cognitive effort. These preliminary findings suggest that MEG-based connectivity may serve as a functional neuroimaging biomarker of underlying network reorganization, for monitoring early cognitive disease progression in MS.

Background/Objective: To describe the clinical features and radiological outcomes of patients with spinal cord neurosarcoidosis, treatments, and long-term follow-up for this rare disorder. Methods: A cross-sectional, retrospective medical chart review was performed for all patients with spinal cord neurosarcoidosis treated at a single center between 01/1995 and 12/2020. Radiological imaging, laboratory test results, the type of immunosuppressive therapy, and function test scores were reviewed. Results: We assessed 39 patients with spinal cord neurosarcoidosis (23 men, 16 women, mean age at presentation 46.4 years, SD 10.2 years). The mean (SD) duration of spinal cord neurosarcoidosis at data abstraction was 9.8 (6.3) years. There were 24 patients (62%) with extensive intramedullary lesions, 8 (21%) with multiple patchy intramedullary lesions, 12 (31%) with leptomeningeal involvement, and 7 (18%) with nerve root enhancement. The cervical spine was the most commonly affected region in 33 patients (85%). The most common presenting symptoms were paresthesia/neuropathic pain in 20 (51%) and weakness of extremities in 15 (38%) patients. Most patients (n = 37; 95%) had been treated with corticosteroids at symptom onset, and methotrexate was the most used immunosuppressive therapy (n = 19; 49%). Of 34 patients with follow-up magnetic resonance imaging (MRI) available, the median time to improvement per MRI was 10.8 months (95% CI, 6.1–17.0 months). Of 31 patients with MRI enhancement at presentation, 18 (58%) had complete enhancement resolution at follow-up, with a median time to resolution of 51.8 months (95% CI, 24.9–83.4 months). Patients had significantly lower pyramidal (p = 0.004) and sensory functional (p = 0.031) systems scores from presentation to the last clinic visit. Conclusions: Because spinal cord neurosarcoidosis is challenging to diagnose and no set treatment guidelines exist, clarifying patients’ clinical parameters and responses to various treatments is needed to improve timely and efficient care. The incidence of spinal cord involvement in sarcoidosis in our cohort was higher than intracranial involvement and most patients had a long extensive intramedullary lesion. We also observed that most patients with spinal cord neurosarcoidosis improved clinically and radiologically after treatment; however, the resolution of MRI enhancement after immunosuppressive therapy may take years. Prospective studies of neurosarcoidosis will be crucial to address questions about effective treatment and long-term prognosis.

Postoperative urinary retention (POUR) is common in neurosurgical patients. The use of alpha-blockade therapy, such as tamsulosin, has benefited many patients with a history of obstructive uropathy by decreasing lower urinary tract symptoms such as distension, infections, and stricture formation, as well as the incidence of POUR. For this study, we targeted patients who had undergone spinal surgery to examine the prophylactic effects of tamsulosin. Increased understanding of this therapy will assist in minimizing the morbidity of spinal surgery. We enrolled 95 male patients undergoing spine surgery in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to receive either preoperative tamsulosin (N = 49) or a placebo (N = 46) and then followed-up prospectively for the development of POUR after removal of an indwelling urinary catheter (IUC). They were also followed-up for the incidence of IUC reinsertions. The rate of developing POUR was similar in both the groups. Of the 49 patients given tamsulosin, 16 (36%) developed POUR compared to 13 (28%) from the control group (P = 0.455). In the control group, 5 (11%) patients had IUC re-inserted postoperatively, whereas 7 (14%) patients in the tamsulosin group had IUC re-inserted postoperatively (P = 0.616). In patients suffering from axial-type symptoms (i.e., mechanical back pain), 63% who received tamsulosin and 18% from the control group (P = 0.048) developed POUR. Overall, there was no statistically significant difference in the rates of developing POUR among patients in either group. POUR is caused by a variety of factors, and further studies are needed to shed light on its etiology.

Magnetic resonance imaging (MRI) has been incorporated as an adjunct to CT to take advantage of its excellent soft tissue contrast for contouring. MR-only treatment planning approaches have been developed to avoid errors introduced during the MR-CT registration process. The purpose of this study is to evaluate calculated dose distributions after incorporating a novel synthetic CT (synCT) derived from magnetic resonance simulation images into prostate cancer treatment planning and to compare dose distributions calculated using three previously published MR-only treatment planning methodologies. An IRB-approved retrospective study evaluated 15 prostate cancer patients that underwent IMRT (n = 11) or arc therapy (n = 4) to a total dose of 70.2-79.2 Gy. Original treatment plans were derived from CT simulation images (CT-SIM). T1-weighted, T2-weighted, and balanced turbo field echo images were acquired on a 1.0 T high field open MR simulator with patients immobilized in treatment position. Four MR-derived images were studied: bulk density assignment (10 HU) to water (MRW), bulk density assignments to water and bone with pelvic bone values derived either from literature (491 HU, MRW+B491) or from CT-SIM population average bone values (300 HU, MRW+B300), and synCTs. Plans were recalculated using fixed monitor units, plan dosimetry was evaluated, and local dose differences were characterized using gamma analysis (1 %/1 mm dose difference/distance to agreement). While synCT provided closest agreement to CT-SIM for D95, D99, and mean dose (<0.7 Gy (1 %)) compared to MRW, MRW+B491, and MRW+B300, pairwise comparisons showed differences were not significant (p < 0.05). Significant improvements were observed for synCT in the bladder, but not for rectum or penile bulb. SynCT gamma analysis pass rates (97.2 %) evaluated at 1 %/1 mm exceeded those from MRW (94.7 %), MRW+B300 (94.0 %), or MRW+B491 (90.4 %). One subject’s synCT gamma (1 %/1 mm) results (89.9 %) were lower than MRW (98.7 %) and MRW+B300 (96.7 %) due to increased rectal gas during MR-simulation that did not affect bulk density assignment-based calculations but was reflected in higher rectal doses for synCT. SynCT values provided closest dosimetric and gamma analysis agreement to CT-SIM compared to bulk density assignment-based CT surrogates. SynCTs may provide additional clinical value in treatment sites with greater air-to-soft tissue ratio.

Our study objective was to identify real-world rates of complications, mortality, and outcomes in patients with neuroleptic malignant syndrome (NMS) over the last decade in the United States. A total of 1346 patients were obtained from the nationwide inpatient sample for the years 2002–2011. Common complications known to be associated with NMS were identified. Multivariable regression analyses were used to identify predictors of mortality. The most prevalent complication was rhabdomyolysis (30.1 %). Other common complications were acute respiratory failure (16.1 %), acute kidney injury (17.7 %), sepsis (6.2 %), and other systemic infections. Unadjusted mortality rate was 5.6 %. Older age, acute respiratory failure, acute kidney injury, sepsis, and comorbid congestive heart failure were significant predictors of mortality. Acute respiratory failure was the strongest independent mortality predictor (p < 0.001). In our large sample population-based study on NMS, we were able to identify the rates of several preselected complications and the mortality. The identification of independent mortality predictors in this study can guide physicians in the management and prognostication of this rare syndrome.

Recent studies have suggested that Evan's Index (EI) is not accurate and instead endorse volumetric measurements. Our aim was to evaluate the reproducibility of linear measurements and their correlation to ventricular volume. Using magnetic resonance (MR) images of 30 patients referred for normal pressure hydrocephalus (NPH), EI, frontal-occipital horn ratio (FOR), third ventricular width and height, frontal horn width (FHW), and callosal angle (CA) at the foramen of Monro and the posterior commissure (PC) were independently measured by residents in neurosurgery and radiology, a neurosurgeon and radiologist, and a medical student. Intraclass correlation coefficients (ICC) were calculated to establish inter-rater agreement among the reviewers. Pearson's correlation coefficients were done to assess the relationship of the linear measurements with total ventricular volume. Kappa analyses were performed to assess the degree of agreement between cutpoints determined by the ROC analysis for the linear measurements and reviewers' gestalt impression about ventricular size with volumetric abnormality. The overall inter-rater agreement among reviewers was almost perfect for EI (ICC = 0.913), FOR (ICC = 0.830), third ventricular width, FHW (ICC = 0.88), and CA at PC (ICC = 0.865), substantial for temporal horn width (ICC = 0.729) and CA at foramen of Monro (ICC = 0.779), and moderate for third ventricular height (ICC = 0.496). EI, FOR, third ventricular width, temporal horn width, and CA at PC measures correlated with total ventricular volume. There was fair-to-almost-perfect agreement of the individual reviewer's gestalt responses of abnormatility with volumetric abnormality. Gestalt responses were better for more senior raters. Linear measurements are reliable and reproducible methods for determining ventricular enlargement.

Postoperative urinary retention (POUR) is a common problem in adult neurosurgical patients. The incidence of POUR is unknown and the etiology has not been well established. POUR can lead to urogenital damage, prolonged hospital stay, higher cost, and infection. This study elucidates several risk factors that contribute to POUR in a variety of neurosurgical patients in one institution. A total of 137 neurosurgical patients were prospectively followed up for the development of POUR, which we defined as initial postvoid residual (PVR1) >250 ml 6 hours after removal of an indwelling urinary catheter (IUC). For patients with PVR >250 ml on the third check, IUCs were reinserted and kept in for 5-7 days. Of the 137 patients, 68 (50%) were male, 41% (56/137) were 60 years or older, 86% (118/137) underwent spinal surgery, and 54% (74/137) had anesthesia over 200 minutes. Overall incidence of clinical POUR was 39.4% (54/137). Significantly higher rates of PVR1 >250 were noted in males, patients older than 60 years, and those who underwent spine surgery. When considering all patient characteristics (except selective alpha blockers), only gender, surgery time, and surgery type remained significant. In addition, PVR1 >250 was positively associated with longer length of stay. Of all patients, 24 (18%) had IUCs reinserted postoperatively or should have had one (5 refused and 2 had a third PVR). The association of IUC reinsertion with male gender was significant. Male gender, time of anesthesia >200 minutes, older age, and spinal surgery are the most significant risk factors associated with POUR in neurosurgical patients.

Popular circulation theory of hydrocephalus assumes that the brain is impermeable to cerebrospinal fluid (CSF), and is therefore incapable of absorbing the CSF accumulating within the ventricles. However, the brain parenchyma is permeable to water due to the presence of specific ion channels as well as aquaporin channels. Thus, the movement of water into and out of the ventricles may be determined by the osmotic load of the CSF. If osmotic load determines the aqueous content of CSF in this manner, it is reasonable to hypothesize that hydrocephalus may be precipitated by pathologies and/or insults that produce sustained elevations of osmotic content within the ventricles.