Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

The lived experiences of experienced Vipassana Mahasi meditators: an interpretative phenomenological analysis.

Research into the effects and mechanisms of mindfulness training draws predominantly on quantitative research. There is a lack of understanding about the subjective experiences of experienced mindfulness meditators, which may provide additional insights into the effects, processes and context of mindfulness training. This qualitative study explored the lived experiences of a novel group of experienced mindfulness meditators who practise Vipassana Mahasi (VM) meditation. The study aimed to understand how experienced VM practitioners make sense of the effects of practice and what processes they ascribe to it. Participants attended semistructured interviews, and their responses were analysed using interpretative phenomenological analysis. Results yielded overarching themes including (a) improvements in hedonic and eudaimonic well-being; (b) insights into self, others and perception of reality; (c) attaining equanimity; and (d) physical and interpersonal difficulties. Participants perceived VM as a ‘cleansing’ process whereby maladaptive responses were eliminated through mindfulness, other supportive mental qualities, decentering and nonattachment. The findings revealed a complex and dynamic set of interdependent outcomes and processes, which are reinforced by Buddhist teachings and ethical practices. This study highlights the need for additional interdisciplinary research into topics such as insight generation and supportive mental qualities cultivated during VM, novel states of well-being informed by Buddhist constructs and interpersonal difficulties related to long-term practice. Findings also suggest that incorporating Buddhist teachings and ethics into mindfulness-based interventions may enhance practitioner understanding and implementation of meditation techniques.N/

Multivariate statistical mapping of spectroscopic imaging data

For magnetic resonance spectroscopic imaging studies of the brain, it is important to measure the distribution of metabolites in a regionally unbiased way; that is, without restrictions to a priori defined regions of interest. Since magnetic resonance spectroscopic imaging provides measures of multiple metabolites simultaneously at each voxel, there is furthermore great interest in utilizing the multidimensional nature of magnetic resonance spectroscopic imaging for gains in statistical power. Voxelwise multivariate statistical mapping is expected to address both of these issues, but it has not been previously employed for spectroscopic imaging (SI) studies of brain. The aims of this study were to (1) develop and validate multivariate voxel-based statistical mapping for magnetic resonance spectroscopic imaging and (2) demonstrate that multivariate tests can be more powerful than univariate tests in identifying patterns of altered brain metabolism. Specifically, we compared multivariate to univariate tests in identifying known regional patterns in simulated data and regional patterns of metabolite alterations due to amyotrophic lateral sclerosis, a devastating brain disease of the motor neurons

Peripheral nervous system electrodiagnostic abnormalities in predominantly Hispanic Multiple Sclerosis patients

•The prevalence of electrodiagnostic abnormalities, especially axonal polyneuropathy, in the MS population may be higher than previously considered.•The presence of a peripheral axonal polyneuropathy may be important in the context of central axonopathy and neurodegeneration in MS.•Sympathetic autonomic nervous system dysfunction is common in MS Peripheral nervous system (PNS) abnormalities in Multiple Sclerosis (MS) have been reported in case reports and small case series over the past several decades. Little is known, however, about the prevalence of electrodiagnostic abnormalities in patients with MS, including not only demyelinating neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but also axonal peripheral neuropathy and sympathetic dysfunction. This is an observational, cross-sectional study with the objective of identifying the prevalence of the electrodiagnostic abnormalities in predominantly Hispanic MS patients in Miami, Florida. Electrodiagnostic data including nerve conduction study (NCS), electromyography (EMG) and sympathetic skin response (SSR) information was prospectively collected in 18 patients (16 females; 43.7±15.2 years) with a diagnosis of MS compared to 18 healthy (16 females; 39.9±11 years), age- and height-matched controls. The study was offered to all-comers in the MS Clinic over a period of 3 months, regardless of clinical suspicion for an underlying neuropathic process, in an effort to estimate the prevalence of abnormalities. Demographic data including age, sex, race/ethnicity was evaluated in addition to MS-specific characteristics including MS subtype, duration of disease, duration of therapy, clinical symptoms and laboratory data. There were no significant differences in baseline characteristics of patients and controls for age (p=0.4) and height (164.0±6.4 vs 162.3±4.6 centimeters; p=0.3). The mean disease duration was 106±27 months (median 107 months; range 5-336 months). The mean Expanded Disability Status Scale (EDSS) was 2.4±1.87 (median: 2.5; range 1.0-6.5). The ethnicity of patients (15 Hispanic, 3 non-Hispanic) and controls (13 Hispanic, 5 non-Hispanic; p=0.56) was similar. The frequency of electrophysiological axonal polyneuropathy (PN) was 77.8% (14/18 patients), and 85.6% of these patients had clinical sensory symptoms. Interestingly, 1 patient had previously unrecognized CIDP. All 18 patients displayed prolonged SSR latencies consistent with autonomic dysfunction. Thirteen patients (72.2%) reported autonomic symptoms such as bladder abnormalities and blood pressure fluctuations. The prevalence of electrodiagnostic abnormalities, especially axonal polyneuropathy, in the MS population may be higher than traditionally considered. The relationship between axonal polyneuropathy and central axonopathy in the context of neurodegeneration in MS should be further explored. Analytic studies may identify common symptomatic and pathophysiologic etiologies to further understanding and potentially guide treatment of MS subtypes with PNS involvement

Effects of Electrically Stimulated Exercise Training on Muscle Function in Multiple Sclerosis

To investigate whether electrically stimulated exercise training might reduce muscle fatigue in persons with multiple sclerosis (MS), the dorsiflexor muscles of six patients were trained (60 min/d, 6d/wk, 8 wks) with electrically stimulated endurance exercise (50 Hz tetanic contractions, 25% duty cycle). There was evidence of transient mus cle injury at the onset of training (reduced tetanic force, elevated ratio of inorganic phosphate/phosphocreatine in the resting muscle). There was no significant effect of the training on mean muscle fatigability. After training, four of six patients had reduced fatigue (i.e., fall in tetanic force) during nine minutes of intermittent tetanic contractions. Two subjects had increased fatigue following training. Training-induced changes in fatigability were linearly associated with changes in (1) pre-exercise twitch con traction time (r2 = 0.70), and (2) the decrease in intracellular pH during exercise (r2 = 0.88), suggesting that altered fatigability after training may be associated with changes in the intrinsic properties of the muscle. These results indicate that elec trically stimulated exercise training may benefit some patients with MS. Care must be taken in the design of the stimulation parameters, and signs of muscle injury should be monitored. Further studies are needed to elucidate the most efficacious means of improving muscle strength and resistance to fatigue using electrical stim ulation in MS. Key Words: Metabolism—Muscle injury—Magnetic resonance spec troscopy—Fatigue.—Contraction—Rehabilitation

EVIDENCE OF AN ABNORMAL INTRAMUSCULAR COMPONENT OF FATIGUE IN MULTIPLE SCLEROSIS

The goals of this study were to investigate muscle fatigue in patients with multiple sclerosis (MS), and to determine the relationships between muscle fatigue, clinical status, and perceived fatigue. The fatigability of the anterior tibial muscle was quantitated in patients and controls during 9 min of intermittent stimulation (used to eliminate central sources of muscle fatigue). During exercise, the decline in tetanic force, phosphocreatine, and intracellular pH was greater in patients than in controls. The compound muscle action potential amplitude did not decrease during exercise, indicating that there was no failure of neuromuscular transmission during fatigue. Thus, the excessive fatigue in MS developed from sources beyond the muscle memberane. Following exercise, the recovery of tetanic force was delayed in patients (a pattern that suggests abnormal excitation-contraction coupling), whereas the recovery of metabolites was complete in both groups. Muscular fatigue was correlated with clinical disability but not with perceived fatigue. These results suggests that fatigue in MS has both central (perception, upper motor neuron dysfunction) and peripheral (impaired metabolism and excitation-contraction coupling) components

Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg

Immunoglobulin (Ig) therapy is a first-line treatment for CIDP, which can be administered intravenously (IVIg) or subcutaneously (SCIg) and is often required long term. The differences between these modes of administration and how they can affect dosing strategies and treatment optimization need to be understood. In general, the efficacy of IVIg and SCIg appear comparable in CIDP, but SCIg may offer some safety and quality of life advantages to some patients. The differences in pharmacokinetic (PK) profile and infusion regimens account for many of the differences between IVIg and SCIg. IVIg is administered as a large bolus every 3–4 weeks resulting in cyclic fluctuations in Ig concentration that have been linked to systemic adverse events (AEs) (potentially caused by high Ig levels) and end of dose “wear-off” effects (potentially caused by low Ig concentration). SCIg is administered as a smaller weekly, or twice weekly, volume resulting in near steady-state Ig levels that have been linked to continuously maintained function and reduced systemic AEs, but an increase in local reactions at the infusion site. The reduced frequency of systemic AEs observed with SCIg is likely related to the avoidance of high Ig concentrations. Some small studies in immune-mediated neuropathies have focused on serum Ig data to evaluate its potential use as a biomarker to aid clinical decision-making. Analyzing dose data may help understand how establishing and monitoring patients' Ig concentration could aid dose optimization and the transition from IVIg to SCIg therapy

Intracranial corticospinal tract atlas.

<p>The full-range probabilistic atlas is shown in green. We modified this atlas (shown in red) for our use by including only voxels with probability values greater than 0.20 and by excluding voxels inferior to the cerebral peduncle. The axial MRI image is included to provide anatomical context.</p