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Background: Fatigue is a common symptom in people with multiple sclerosis (pwMS) that significantly impairs quality of life. Bright light therapy may be a cheap treatment option with little to no adverse events. Objectives: To evaluate the effectiveness of bright light therapy as a treatment option for MS-related fatigue. Methods: This was randomized sham-controlled trial including 26 pwMS with a Fatigue Severity Scale (FSS) Score ≥36. Participants were assigned to receive either bright white light therapy (n = 13) or dim red light (sham-intervention; n = 13). Participants used the respective intervention for 30 min each morning for two weeks, followed by a two-week washout period. The primary endpoint was the difference in FSS scores following light treatment as calculated by analysis of covariance. Results: There was no significant difference in FSS (F(1,23) = 2.39, p = .136, partial â´2 = .094). However, FSS scores generally improved over the course of the study in a clinically relevant manner. Conclusion: Bright light therapy decreased FSS scores over the course of this study. However, this effect was not significant in comparison to a sham intervention.
RESUMEN
PURPOSE: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as â¯Î³-aminobutyric acid (GABA) and glutamineâ¯+â¯glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients. METHODS: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3â¯T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). RESULTS: RRMS patients had higher fatigue scores relative to HC (pâ¯≤⯠0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (pâ¯=⯠0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, pâ¯=⯠0.008) and Glx (r = 0.511, pâ¯=⯠0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, pâ¯≤⯠0.04) and positively with PFC Glx (r = 0.480, pâ¯=⯠0.028). CONCLUSION: The associations between fatigue and GABAâ¯+â¯and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS.
Asunto(s)
Ácido Glutámico , Esclerosis Múltiple , Encéfalo/diagnóstico por imagen , Fatiga , Glutamina , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Ácido gamma-AminobutíricoRESUMEN
BACKGROUND AND PURPOSE: Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing-remitting MS (RRMS) patients using MR two-dimensional localized correlated spectroscopy (2D L-COSY). METHODS: Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L-COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS: Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose-3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N-acetylaspartate (NAA-2), while increased levels for isoleucine and glucose (P ≤ .05). Only GPC showed positive correlation with all fatigue domains (r = .537, P ≤ .05). On the other hand, Glx-upper, NAA-2, GSH+Hca, and fucose-3 showed negative correlations with all fatigue domains (r = -.345 to -.580, P ≤ .05). While tyrosine showed positive correlation with MFIS (r = .499, P ≤ .05), cognitive fatigue was negatively correlated with total GSH (r = -.530, P ≤ .05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS: Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.
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Fatiga/patología , Giro del Cíngulo/patología , Espectroscopía de Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Carnosina/análogos & derivados , Carnosina/metabolismo , Colina/metabolismo , Creatina/metabolismo , Femenino , Glutatión/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To investigate the EEG-derived functional connectivity at rest (FCR) patterns of fatigued Multiple Sclerosis (MS) patients in order to find good parameters for a future EEG-Neurofeedback intervention to reduce their fatigue symptoms. METHODS: We evaluated FCR between hemispheric homologous areas, via spectral coherence between pairs of corresponding left and right bipolar derivations, in the Theta, Alpha and Beta bands. We estimated FCR in 18MS patients with different levels of fatigue and minimal clinical severity and in 11 age and gender matched healthy controls. We used correlation analysis to assess the relationship between the fatigue scores and the FCR values differing between fatigued MS patients and controls. RESULTS: Among FCR values differing between fatigued MS patients and controls, fatigue symptoms increased with higher Beta temporo-parietal FCR (p=0.00004). Also, positive correlations were found between the fatigue levels and the fronto-frontal FCR in Beta and Theta bands (p=0.0002 and p=0.001 respectively). CONCLUSION: We propose that a future EEG-Neurofeedback system against MS fatigue would train patients to decrease voluntarily the beta coherence between the homologous temporo-parietal areas. SIGNIFICANCE: We extracted a feature for building an EEG-Neurofeedback system against fatigue in MS.