A strategy for using tissue water as a concentration standard in 1 H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with The unsuppressed "internal" water signal was introduced as a concentration reference for single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS) of the brain over a decade ago (1-4). However, to our knowledge, a detailed description of how this method could be applied to spectroscopic imaging (SI), or an examination of its potential sources of error has yet to be reported. In the majority of SI studies that reported "absolute" metabolite concentrations, the metabolite signals were converted to moles per liter or kilograms of tissue using either external metabolite solutions (5-7) or ventricle water (8,9), and relatively few groups have reported using internal water (10,11). The principal advantage of using internal water in SI studies is that certain factors and potential sources of error that need to be considered when using external concentration references (e.g., RF homogeneity, coil loading, or the SI point spread function (PSF)) are obviated, since the water and metabolite signals come from the same voxel and are acquired in essentially the same way.The major assumptions when using internal water, on the other hand, are that the water densities and signal relaxation times of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in the region of interest (ROI) can be reliably estimated and, furthermore, do not change significantly among the studied groups. Moreover, it is essential that the volume fractions of these tissues and CSF in each SI voxel are accurately measured. Measuring partial volume effects is also a requirement when using external referencing methods, but the demand on accuracy is greater when using internal water. This is because only the signal from the combined GM-WM fraction of the total water, in which the detectable metabolites are exclusively located, is used as the concentration reference. The observed water signal, however, arises from a combination of the GM, WM, and CS...

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SUMMARYObjective-To compare state and trait anxiety in mild cognitive impairment (MCI) patients and matched control subjects, and to assess the impact of these variables in predicting conversion to Alzheimer's disease.Methods-One hundred and forty-eight patients with MCI, broadly defined, were assessed and followed systematically. Baseline predictors for follow-up conversion to AD (entire sample: 39/148 converted to Alzheimer's disease (AD)) included the Spielberger State-Trait Anxiety Inventory (STAI).Results-At baseline evaluation, MCI patients had higher levels of state and trait anxiety than controls, with no differences between future AD converters (n = 39) and non-converters. In agestratified Cox proportional hazards model analyses, STAI State was not a significant predictor of conversion to AD (STAI State ≤30 vs. > 30 risk ratio, 1.68; 95% CI, 0.75, 3.77; p = 0.21), but higher Trait scores indicated a lower risk of conversion when STAI State, education, the Folstein MiniMental State Examination and HAM-D (depression score) were also included in the model (STAI Trait ≤30 vs. > 30 risk ratio, 0.36; 95% CI, 0.16, 0.82; p = 0.015).Conclusions-In contrast to two other recent studies that showed anxiety predicted cognitive decline or conversion to AD, in this clinic-based sample, state anxiety was not a significant predictor. However, higher Trait anxiety predicted a lower risk of future conversion to AD. Further research with systematic long-term follow-up in larger samples is needed to clarify the role of state and trait anxiety in predicting MCI conversion to AD.

Highlights The most common neurological chief complaint in patients with COVID-19 is Altered Mental Status. A neurological chief complaint at admission is associated with prolonged hospital stays, death, and intubation. Altered Mental Status at admission is associated with significantly prolonged hospital stay. Patients with Altered Mental Status during the hospital stay, as well as those who had seizures, were more likely to require intubation.

Objectives Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. Design PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. Participants Recruitment area (both studies) LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies) 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study. Exclusion criteria (both studies) 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. Interventions PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200 mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. Outcome measures PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months. We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm × 10cm × 1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 16×16 resulting in 1cm3 voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing. Results PhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint. PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (2 G I, 1 G II and 1 G IV). Median time to onset of abnormal LFTs was 20 weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels. PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had simil...

Background: OnabotulinumtoxinA (BoNT-A) can temporarily decrease spasticity following stroke, but whether there is an associated improvement in upper limb function is less clear. This study measured the benefit of adding weekly rehabilitation to a background of BoNT-A treatments for chronic upper limb spasticity following stroke. Methods: This was a multi-center clinical trial. Thirty-one patients with post-stroke upper limb spasticity were treated with BoNT-A. They were then randomly assigned to 24 weeks of weekly upper limb rehabilitation or no rehabilitation. They were injected up to two times, and followed for 24 weeks. The primary outcome was change in the Fugl–Meyer upper extremity score, which measures motor function, sensation, range of motion, coordination, and speed. Results: The ‘rehab’ group significantly improved on the Fugl–Meyer upper extremity score (Visit 1 = 60, Visit 5 = 67) while the ‘no rehab’ group did not improve (Visit 1 = 59, Visit 5 = 59; p = 0.006). This improvement was largely driven by the upper extremity “movement” subscale, which showed that the ‘rehab’ group was improving (Visit 1 = 33, Visit 5 = 37) while the ‘no rehab’ group remained virtually unchanged (Visit 1 = 34, Visit 5 = 33; p = 0.034). Conclusions: Following injection of BoNT-A, adding a program of rehabilitation improved motor recovery compared to an injected group with no rehabilitation.

Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer’s disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e.g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than nonconverters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD.

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