A Topical Adhesive Containing Anesthetic and Heating Components to Reduce Injection Pain with Subcutaneous Multiple Sclerosis Medications: A Pilot Study.

BACKGROUND: Injection pain and fear of pain are common with subcutaneous medications for treating multiple sclerosis (MS). Synera is a peel-and-stick topical adhesive (S-TA) with a novel heating component to enhance the delivery of an anesthetic mixture of lidocaine and tetracaine. We studied the effect of S-TA on pain and other aspects of comfort after subcutaneous MS drug injection. METHODS: Thirty participants with MS having injection reactions to subcutaneous interferon beta (IFNß) or glatiramer acetate (GA) were enrolled in an open-label prospective study. We captured six to seven injections at baseline and with 60- and 30-minute S-TA application times. The primary outcome was immediate pain on injection. Secondary outcomes included 12- and 24-hour pain ratings, 24-hour local injection-site reaction scale scores, 24-hour tenderness, and fear of injection (FOI). RESULTS: Twenty-nine participants completed the study (interferon beta = 4, GA = 25, mean age = 51 years, females = 86%). There were significant reductions in injection pain, pain at 12 and 24 hours, tenderness at 24 hours, local injection-site reaction scale scores, and FOI for the 30- and 60-minute applications of S-TA (all P < .01). Results were similar in the GA subgroup. Adverse events included muscle spasm and lightheadedness (n = 1) and mild dermatitis (n = 1). CONCLUSIONS: These results suggest that S-TA applied 30 or 60 minutes before MS drug injection may reduce pain, tenderness, and FOI. Randomized controlled studies are needed to confirm the efficacy of ST-A.

A Randomized Crossover Trial of Dalfampridine Extended Release for Effect on Ambulatory Activity in People with Multiple Sclerosis.

BACKGROUND: Dalfampridine extended release (D-ER) is indicated to improve walking in people with multiple sclerosis (MS) as demonstrated by an increase in walking speed. This study assessed the effects of D-ER on accelerometer-based measures in people with MS, including intensity of walking and total amount of walking during daily activities. METHODS: In this double-blind placebo-controlled crossover study, people with MS-related walking difficulty were randomized (1:1) to receive 4 weeks of D-ER 10 mg twice daily and 4 weeks of placebo in either order separated by a 2-week washout. Participants wore accelerometers for 7 days at baseline and week 3 of each on-drug period. The primary outcome was the peak activity index (PAI), defined as the most intense 30 individual minutes of the day (strides per minute). Secondary outcomes included daily step count, 6-Minute Walk Test (6MWT), Timed Up and Go (TUG) test, and patient-reported outcomes. A mixed-effects repeated-measures statistical model was used. RESULTS: Forty-three participants were randomized (mean Expanded Disability Status Scale score, 5.17). Least squares mean (standard error) change from baseline on the PAI was 0.6 (0.54) strides/min on D-ER and 0.3 (0.55) strides/min on placebo and in daily step count was 148.7 (222.4) on D-ER and 128.0 (225.4) on placebo. Other accelerometer-based measures and the 6MWT showed no significant differences between D-ER and placebo. The TUG test (P = .042) favored D-ER. There were no serious adverse events. CONCLUSIONS: Dalfampridine did not show an effect on accelerometer-measured ambulatory activity in people with MS-related walking difficulty. More work is needed to confirm these results.

Increased glucose concentration in the hippocampus in early Alzheimer's disease following oral glucose ingestion.

Glucose is the primary source of energy for brain cells. Because energy storage in the brain is limited, an uninterrupted supply of glucose and its rapid metabolism are essential for normal cognitive function. This study utilized an oral glucose load to examine hippocampal glucose metabolism in early Alzheimer's disease (AD) - a disease characterized by progressive deterioration of cognitive function and glucose hypometabolism. Short echo time 1H MR spectra (20 ms) from the right hippocampus of 8 patients with probable AD, 14 healthy elderly and 14 healthy young adults were compared pre- and post-glucose loading. In contrast to the healthy adults, the AD patients exhibited significantly elevated hippocampal glucose concentrations post-glucose ingestion relative to baseline (P < .01). These results suggest that cerebral glucose hypometabolism in AD leads to an increased steady-state concentration of cerebral glucose. This research demonstrates the feasibility of studying cerebral glucose metabolism in AD with 1H MR spectroscopy.

Shortening of hippocampal spin-spin relaxation time in probable Alzheimer's disease: a 1H magnetic resonance spectroscopy study.

We quantified the differential effects of the spin-spin relaxation times (T2) of tissue water and cerebral spinal fluid in order to examine hippocampal T2 changes as a non-invasive bio-marker of Alzheimer's disease (AD). We measured T2 in the right hippocampus of ten patients fulfilling the NINCDS-ADRDA criteria for AD and 40 healthy adult volunteers using localized proton magnetic resonance spectroscopy. The T2 values of AD patients (73 +/- 8 ms) were significantly shorter (P < 0.01) than those of healthy age-matched controls (81 +/- 5 ms), and there was a reduction in T2 for healthy older vs. healthy younger adults (87 +/- 5 ms, P < 0.05). The reduced T2 values with aging are consistent with age-related decreases in tissue water content. Our results suggest that there may be a severe reduction in tissue water content in AD.

Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo.

Absolute concentrations of cerebral metabolite in in vivo 1H magnetic resonance spectroscopy studies (1H-MRS) are widely reported in molar units as moles per liter of tissue, or in molal units as moles per kilogram of tissue. Such measurements require external referencing or assumptions as to local water content. To reduce the scan time, avoid assumptions that may be invalid under specific pathologies, and provide a universally accessible referencing procedure, we suggest that metabolite concentrations from 1H-MRS measurements in vivo be reported in molal units as moles per kilogram of tissue water. Using internal water referencing, a two-compartment water model, a simulated brain spectrum for peak identification, and a spectroscopic bi-exponential spin-spin relaxation segmentation technique, we measured the absolute concentrations for the four common 1H brain metabolites: choline (Cho), myo-inositol (mIno), phosphocreatine + creatine (Cr), and N-acetyl-aspartate (NAA), in the hippocampal region (n = 26) and along the Sylvian fissure (n = 61) of 35 healthy adults. A stimulated echo localization method (20 ms echo time, 10 ms mixing time, 4 s repetition time) yielded metabolite concentrations, uncorrected for metabolite relaxation or contributions from macromolecule resonances, that were expectantly higher than with molar literature values. Along the Sylvian fissure the average concentrations (coefficient of variation (CV)) in mmoles/kg of tissue water were 17.6 (12%) for NAA, 14.2 (9%) for Cr, 3.6 (13%) for Cho, and 13.2 (15%) for mIno. Respective values for the hippocampal region were 15.7 (20%), 14.7 (16%), 4.6 (19%), and 17.7 (26%). The concentrations of the two regions were significantly different (p

Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo.

The (1)H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T(1)) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T(1) model by using known signal intensity values significantly improves the precision of the T(1) measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21 +/- 2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T(1) and spin-spin relaxation (T(2)) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T(2) experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T(1) experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T(2) measurements provided the signal intensity values used in the bi-exponential T(1) model. The mean T(1) values when the signal intensities were constrained by the T(2) results were 1055.4 ms +/- 7.4% for tissue and 5393.5 ms +/- 59% for CSF. When the signal intensities remained free variables in the model, the mean T(1) values were 1085 ms +/- 19.4% and 5038.8 ms +/- 113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T(1) value to be included in the spectroscopic characterization of brain tissue.