Plasma antioxidant potential measured by total radical trapping antioxidant parameter in a cohort of multiple sclerosis patients.

BACKGROUND: Oxidative injury has been implicated as a mediator of demyelination, axonal damage, and neurodegeneration in multiple sclerosis (MS). There is a high demand for oxidative injury biomarkers. The aim of the study was to evaluate MS patients' plasma antioxidant potential using the total radical trapping parameter (TRAP) assay and examine its usefulness as an MS disease biomarker. METHODS: A total number of 112 MS patients underwent an analysis of TRAP. In addition, plasma uric acid (UA) levels were analyzed. The neurological and radiological data were collected from patient records from Helsinki University Hospital during 2012-2013 when first-line injectables of moderate-efficacy, natalizumab (NTZ), and fingolimod (FTY) of high efficacy disease modifying therapies and in some cases azathioprine (AZT) were used to treat MS. RESULTS: TRAP values were negatively associated with expanded disability status scale (EDSS) score with p-value .052, ß = -28. There was also a negative association in TRAP values between patients with no medication (n = 22, TRAP mean 1255 µmol/L (95% confidence interval [CI] 1136-1374)) and patients who received NTZ, p-value .020 (n = 19, TRAP mean was 991 µmol/L (95% CI 849-1133) or FTY treatment, p-value .030 (n = 5, TRAP mean 982 µmol/L (95% CI 55-1909). Due to a small sample size, these results were not significant after applying a false discovery rate correction at a 0.05 significance level but are worth highlighting. Men in the study had higher TRAP values, p-value = .001 (TRAP mean 1320 ± 293 µmol/L) than women (TRAP mean 1082 ± 288 µmol/L). UA was positively associated with TRAP values, p-value <.001 and UA levels in men (UA mean 334.5 ± 62.6 µmol/L) were higher compared to women (UA mean 240 ± 55.8 µmol/L), t-test p-value <.001. The significant difference in TRAP levels between genders, with men showing higher TRAP values than women, may be attributed to the variation in UA levels. CONCLUSION: Our findings suggest that lower plasma antioxidant potential is linked to more severe disability measured by EDSS scores. Patients treated with NTZ and FTY had reduced antioxidant power, which might be influenced by the active MS disease rather than the treatments themselves. The study reveals a strong positive correlation between UA levels and TRAP, particularly among women. However, men on average had better antioxidant potential than women. Neither the disease type nor the duration influences TRAP levels. While serving as a marker of antioxidant potential, plasma TRAP in MS patients does not reliably reflect overall oxidative stress (OS) and should not be solely used as an indicator of OS.

Magnetic Nanoparticles in Human Cervical Skin.

Magnetic iron oxide nanoparticles, magnetite/maghemite, have been identified in human tissues, including the brain, meninges, heart, liver, and spleen. As these nanoparticles may play a role in the pathogenesis of neurodegenerative diseases, a pilot study explored the occurrence of these particles in the cervical (neck) skin of 10 patients with Parkinson's disease and 10 healthy controls. Magnetometry and transmission electron microscopy analyses revealed magnetite/maghemite nanoparticles in the skin samples of every study participant. Regarding magnetite/maghemite concentrations of the single-domain particles, no significant between-group difference was emerged. In low-temperature magnetic measurement, a magnetic anomaly at ~50 K was evident mainly in the dermal samples of the Parkinson group. This anomaly was larger than the effect related to the magnetic ordering of molecular oxygen. The temperature range of the anomaly, and the size-range of magnetite/maghemite, both refute the idea of magnetic ordering of any iron phase other than magnetite. We propose that the explanation for the finding is interaction between clusters of superparamagnetic and single-domain-sized nanoparticles. The source and significance of these particles remains speculative.

Gut microbiota are related to Parkinson's disease and clinical phenotype.

In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.

Uric acid and cognition in Parkinson's disease: a follow-up study.

Cognitive changes are common in Parkinson's disease (PD). Low plasma uric acid (UA) level is associated with risk of PD and predicts faster progression of motor symptoms in established disease. Whether UA levels predict cognitive changes has not been studied. In a crossectional study, our group has previously shown an association of plasma and urine UA levels with cognition in PD. The aim of the present controlled longitudinal study was to examine the evolution of cognitive changes and the prognostic value of the UA levels on cognition in the previously reported PD-patient cohort. Of the original 40 patients, 31 were available for follow-up after three years. Both plasma and daily urine UA levels were measured, nutrition was evaluated using 4-day dietary recall diary and cognition was assessed by a thorough neuropsychological examination including computerized tasks with Cognispeed©. The plasma and urine UA levels of the patients remained stable during the follow-up. At the same time, the rate of cognitive decline was unexpectedly slow. A statistically significant deterioration was noted in verbal fluency (p=0.04) and in Cognispeed©'s vigilance task (p=0.0001). In forward linear regression analysis only the baseline daily urine UA level contributed to verbal fluency (p=0.01), picture completion (p=0.001), block design (p=0.006), vigilance (p=0.006), subtraction (p=0.01) and statement verification (p=0.04) tasks. The implications of the study results are discussed.

Reproducibility of cortex-muscle coherence.

Cortex-muscle coherence is a frequency-analysis technique that has been increasingly applied in the investigation of movement disorders. To study the intra- and inter-session stability of the cortex-muscle coherence, we recorded from 12 healthy subjects magnetoencephalographic (MEG) and surface electromyographic (EMG) signals during unilateral isometric contractions of the left- and right-hand muscles. Two identical measurements were performed during one session, and the session was repeated once after about 1 year. In one experienced subject, the recordings were repeated seven times within 20 months. The MEG-EMG coherence exceeded the noise level in 10 out of 12 subjects. Both the frequency (correlation coefficient r = 0.77-0.93, P < 0.01) and strength (r = 0.78-0.91, P < 0.01) of coherence were well reproducible within each session for both left- and right-sided contractions. The inter-session reproducibility was high for the mean of cumulative coherence frequency (r = 0.90-0.95, P < 0.01), but relatively low for coherence strength (r = 0.43-0.59, P > 0.05). The results for one subject participating in 8 repeated sessions strongly supported the results of the whole group. Thus, intra-session reproducibility of both strength and frequency of the cortex-muscle coherence is good and studies comparing different conditions at the group level within one session are feasible. However, caution is needed when interpreting absolute levels or changes in the strength of coherence in single subjects between the sessions.

Oscillatory motor cortex-muscle coupling during painful laser and nonpainful tactile stimulation.

Noxious stimulation activates-in addition to the brain structures related to sensory, emotional, and cognitive components of pain-also the brain's motor system. Effect of noxious input on the primary motor (MI) cortex remains, however, poorly understood. To characterize this effect in more detail, we quantified the ongoing oscillatory communication between the MI cortex and hand muscles during selectively noxious laser stimulation. The subjects maintained an isometric contraction of finger muscles while receiving the laser stimuli to the dorsum of the hand. Tactile stimuli with well-known effects on the MI cortex reactivity served as control stimuli. Cortex-muscle coherence was computed between magnetoencephalographic (MEG) signals from the contralateral MI and electromyographic (EMG) signals from the hand muscles. Statistically significant coherence at approximately 20 Hz was found in 6 out of 7 subjects. The coherence increased phasically after both types of stimuli but significantly later after laser than tactile stimuli (mean +/- SEM peak latencies 1.05 +/- 0.12 s vs. 0.58 +/- 0.06 s; P < 0.05), and the coherence increase lasted longer after laser than tactile stimuli (0.87 +/- 0.09 s vs. 0.50 +/- 0.06 s, P < 0.05). The observed coherence increase could be related to stabilization of the motor-cortex control after sensory input. Our findings add to the clinically interesting evidence about the cortical pain-motor system interaction.

Modulation of cortex-muscle oscillatory interaction by ischaemia-induced deafferentation.

We studied the effect of sensory feedback on the oscillatory interaction between activity of the motor cortex and the spinal motoneuron pool during isometric contraction. After inducing ischaemic sensory deafferentation in the upper limb in six subjects, we calculated coherences between simultaneously recorded whole-scalp magnetoencephalographic (MEG) signals and electromyographic (EMG) signals from the first dorsal interosseus muscles. We expected that the dominant frequency of coherence would change if there were interaction through a sensory feedback loop. However, the MEG-EMG coherence frequency did not change significantly during ischaemia. The strength of the coherence was reduced during ischaemia, but returned to the pre-ischaemic level after ischaemia had ended. Reduction of sensory feedback may thus indirectly reduce the amount of corticomuscular coherence, but the lack of change in the dominant coherent frequency suggests that a sensory feedback loop is not essential for the generation of this coherence.

Cortico-muscular coupling in a human subject with mirror movements--a magnetoencephalographic study.

We studied cortico-muscular coupling in a 15-year-old male suffering from congenital mirror movements (MMs) of hands. Cortex-muscle coherence was analyzed between magnetoencephalographic signals and the electromyograms (EMGs) recorded from both hands and feet during uni- and bilateral isometric contractions. Regardless of the side of the intended contraction, the motor cortex contralateral to the contraction was coupled to the muscles of both hands at 20-25 Hz. No coupling was found from the other, ipsilateral hemisphere. EMGs of the two hands were coupled during both intended uni- and bilateral contractions, but only during unilateral contractions could the coupling solely be explained by cortical activation. We suggest that our subject's MMs result from activation of an ipsilateral corticospinal projection, with involvement of additional synchronizing mechanisms at the subcortical, brainstem, or spinal level during bilateral contraction.