RESUMO
Introduction: Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a large multiinstitutional series of patients with NELL1 MN with a focus on secondary associations, pathology findings, and their impact on outcome. Methods: We retrospectively reviewed clinicopathologic features of NELL1 MN from 3 institutions and analyzed clinical and histologic associations with outcome. Results: Of 70 patients, 53% were male with a median age of 66 years; median proteinuria was 5.9 g/d. NELL1 MN was associated with lipoic acid (36%), heavy nonsteroidal antiinflammatory drug (NSAID) use (27%), autoimmune disease (23%), malignancy (10% recent, 23% any), mercury exposure (1%), and 11% had no known secondary association. At median follow-up of 11 months, 72% achieved complete or partial remission. Remission rate was 91% in patients with lipoic acid-associated NELL1 MN and ≥6 months of follow-up. On multivariable analyses, patients with primary NELL1 MN (adjusted odds ratio [OR]: 19.7, P = 0.01) and increasing degree of tubular atrophy and interstitial fibrosis (IFTA) (adjusted OR 1.1, P = 0.01) were less likely to achieve any remission, whereas complete remission (CR) was associated with lipoic acid use (adjusted OR: 10.9, P = 0.04, 95% confidence interval [CI]: 1.2-100) and lesser degrees of IFTA (adjusted OR: 0.79, P = 0.16, 95% CI: 0.66-0.96). Conclusion: Our findings strengthen the association between lipoic acid and NELL1 MN. Furthermore, our findings suggest that discontinuation of lipoic acid without immunosuppression should be considered as the first-line treatment.
RESUMO
Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.
RESUMO
BACKGROUND: Vascular comorbidity (VC) is associated with multiple sclerosis (MS) disease progression and visual dysfunction. The longitudinal effect of VC in people with secondary progressive MS (SPMS) is unclear. This study explored the impact of VC on standard clinical, MRI, and visual outcomes in people with SPMS enrolled in a clinical trial. METHODS: Data were extracted from a 2-year randomized controlled trial (N = 51) testing the supplement lipoic acid in people with SPMS who underwent annual Expanded Disability Status Scales, Timed 25-Foot Walk tests, MRIs, visual acuity testing, and retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) thicknesses per optical coherence tomography (OCT). Post hoc linear mixed-effects regression analysis compared baseline and annualized outcomes between participants without VC (VC-) and with 1 or more VCs (VC+) (hypertension, dyslipidemia, obesity, diabetes, peripheral or cardiovascular disease, tobacco use). RESULTS: The VC- (n = 19) and VC+ (n = 28) participants were similar in age, sex, and MS disease duration and had comparable MS disability, mobility, and brain atrophy at baseline and throughout the 2-year parent study. The VC+ participants had worse baseline visual acuity than those in the VC- group by 0.13 logMAR (P = .041). No significant differences were detected in RNFL or GCIPL baseline thickness or atrophy between groups. CONCLUSIONS: In an SPMS cohort, VC had an inconsistent effect on standard clinical, MRI, and exploratory OCT outcomes, suggesting that the effect of VC may not be evident in smaller cohort studies. Using a more refined definition of VC in future, adequately powered investigations may help effectively elucidate and account for the interaction between vascular risk burden and MS disability.
RESUMO
While conventional magnetic resonance imaging (MRI) is central to the evaluation of patients with multiple sclerosis, its role in detecting the pathophysiology underlying neurodegeneration is more limited. One of the common outcome measures for progressive multiple sclerosis trials, atrophy on brain MRI, is non-specific and reflects end-stage changes after considerable neurodegeneration has occurred. Identifying biomarkers that identify processes underlying neurodegeneration before it is irreversible and that reflect relevant neurodegenerative pathophysiology is an area of significant need. Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple neurodegenerative diseases, including multiple sclerosis. Imaging markers related to inflammation, myelination, and neuronal integrity have been areas of advancement in recent years but oxidative stress has remained an area of unrealized potential. In this article we will begin by reviewing the role of oxidative stress in the pathogenesis of multiple sclerosis. Chronic inflammation appears to be directly related to the increased production of reactive oxygen species and the effects of subsequent oxidative stress appear to be amplified by aging and accumulating disease. We will then discuss techniques in development used in the assessment of MS as well as other models of neurodegenerative disease in which oxidative stress is implicated. Multiple blood and CSF markers of oxidative stress have been evaluated in subjects with MS, but non-invasive imaging offers major upside in that it provides real-time assessment within the brain.
RESUMO
Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions including multiple sclerosis, diabetes, and schizophrenia. Unfortunately, high-grade proteinuria was an unexpected adverse event specific to the treatment arm of our clinical trial investigating lipoic acid supplementation in patients with multiple sclerosis. This observation led to detection of similar patients in our nephrology practice. Here, we describe four biopsy-proven cases of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation and a fifth suspected case. Discontinuation of lipoic acid and supportive therapy resulted in remission.
Assuntos
Glomerulonefrite Membranosa , Ácido Tióctico , Proteínas de Ligação ao Cálcio , Suplementos Nutricionais , Família de Proteínas EGF , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Proteinúria/induzido quimicamente , Proteinúria/tratamento farmacológico , Ácido Tióctico/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: To compare transcapillary wall water exchange, a putative marker of cerebral metabolic health, in brain T2 white matter (WM) lesions and normal appearing white and gray matter (NAWM and NAGM, respectively) in individuals with progressive multiple sclerosis (PMS) and healthy controls (HC). METHODS: Dynamic-contrast-enhanced 7T MRI data were obtained from 19 HC and 23 PMS participants. High-resolution pharmacokinetic parametric maps representing tissue microvascular and microstructural properties were created by shutter-speed (SS) paradigm modeling to obtain estimates of blood volume fraction (vb ), water molecule capillary efflux rate constant (kpo ), and the water capillary wall permeability surface area product (Pw S ≡ vb *kpo ). Linear regression models were used to investigate differences in (i) kpo and Pw S between groups in NAWM and NAGM, and (ii) between WM lesions and NAWM in PMS. RESULTS: High-resolution parametric maps were produced to visualize tissue classes and resolve individual WM lesions. Normal-appearing gray matter kpo and Pw S were significantly decreased in PMS compared to HC (p ≤ .01). Twenty-one T2 WM lesions were analyzed in 10 participants with PMS. kpo was significantly decreased in WM lesions compared to PMS NAWM (p < .0001). CONCLUSIONS: Transcapillary water exchange is reduced in PMS NAGM compared to HC and is further reduced in PMS WM lesions, suggesting pathologically impaired brain metabolism. kpo provides a sensitive measure of cerebral metabolic activity and/or coupling, and can be mapped at higher spatial resolution than conventional imaging techniques assessing metabolic activity.
Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Substância Branca , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/patologia , Água , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
BACKGROUND: Hesitancy to receive COVID-19 vaccination is a major public health concern. COVID-19 vaccine willingness and the factors contributing to willingness in adults with multiple sclerosis (MS) is unknown. We administered an online survey from 1 December 2020 to 7 January 2021 to adults with MS to estimate COVID-19 vaccine willingness among adults with MS. Bivariate analysis with chi-square testing compared categorical variables associated with vaccine willingness. RESULTS: Of 401 respondents, 70.1% were willing to receive an authorized COVID-19 vaccination if it was available to them, 22.7% were unsure, and 7.2% were unwilling. The most frequent concern for those unsure was vaccine safety. Vaccine willingness was associated with increased perceived personal risk of COVID-19 (χ2 = 45.4; p < 0.0001), prior influenza vaccine acceptance (χ2 = 97.6; p < 0.0001), higher educational level (χ2 = 50.2; p < 0.0001), and if respondents discussed or planned to discuss the COVID-19 vaccine with their neurologists (χ2 = 64.3; p < 0.0001). CONCLUSION: While COVID-19 vaccination willingness is high among people with MS, nearly 30% were either unwilling or unsure about being vaccinated. Neurologists should be aware of patient-centered factors associated with COVID-19 vaccine willingness and address COVID-19 vaccine safety concerns in discussions with their vaccine-unsure MS patients.
RESUMO
Multiple sclerosis (MS) is a disabling neuroinflammatory disease. Its etiology is unknown, but both oxidative stress and inflammation appear to be involved in disease pathology. Macrophages are the predominant cell type in acute inflammatory brain lesions in MS. Macrophages produce proinflammatory and toxic molecules that promote demyelination and are key players in phagocytosis/degradation of myelin sheathes. Lipoic acid (LA) is an inexpensive, endogenously produced small molecule that exhibits antioxidant and anti-inflammatory effects. Treatment with LA is protective in MS and other inflammatory diseases. To examine the mechanism(s) by which LA may attenuate inflammatory lesion activity in MS, we used healthy control and MS cells to evaluate the effects of LA on levels of inflammatory cytokines, phagocytosis and the immunomodulator cyclic adenosine monophosphate (cAMP) in monocytes and monocyte-derived macrophages (MDMs). LA treatment resulted in a generally less inflammatory phenotype of monocytes and MDMs from healthy controls, and (to a lesser degree) MS donors. LA inhibited monocyte secretion of cytokines relevant to MS in monocytes, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß; LA effects on secretion of these cytokines in MDMs were mixed with inhibition of TNF-α and IL-6, but stimulation of IL-1ß, the latter perhaps as a result of altered macrophage polarization. LA inhibited phagocytosis in both monocytes and MDMs, and increased cAMP levels in monocytes. LA may modulate inflammatory cytokine secretion and phagocytosis via a cAMP-mediated mechanism.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Ácido Tióctico , Células Cultivadas , Citocinas , Humanos , Macrófagos , Monócitos , Esclerose Múltipla/tratamento farmacológico , Ácido Tióctico/farmacologia , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: There is currently no consensus about standardized gait bout definitions when passively monitoring walking during normal daily life activities. It is also not known how different definitions of a gait bout in daily life monitoring affects the ability to distinguish pathological gait quality. Specifically, how many seconds of a pause with no walking indicates an end to one gait bout and the start of another bout? In this study, we investigated the effect of 3 gait bout definitions on the discriminative ability to distinguish quality of walking in people with multiple sclerosis (MS) from healthy control subjects (HC) during a week of daily living. METHODS: 15 subjects with MS and 16 HC wore instrumented socks on each foot and one Opal sensor over the lower lumbar area for a week of daily activities for at least 8 h/day. Three gait bout definitions were based on the length of the pause between the end of one gait bout and start of another bout (1.25 s, 2.50 s, and 5.0 s pause). Area under the curve (AUC) was used to compare gait quality measures in MS versus HC. RESULTS: Total number of gait bouts over the week were statistically significantly different across bout definitions, as expected. However, AUCs of gait quality measures (such as gait speed, stride length, stride time) discriminating people with MS from HC were not different despite the 3 bout definitions. SIGNIFICANCE: Quality of gait measures that discriminate MS from HC during daily life are not influenced by the length of a gait bout, despite large differences in quantity of gait across bout definitions. Thus, gait quality measures in people with MS versus controls can be compared across studies using different gait bout definitions with pause lengths ≤5 s.
Assuntos
Marcha/fisiologia , Esclerose Múltipla/fisiopatologia , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND PURPOSE: Recent findings suggest that a gait assessment at a discrete moment in a clinic or laboratory setting may not reflect functional, everyday mobility. As a step towards better understanding gait during daily life in neurological populations, we compared gait measures that best discriminated people with multiple sclerosis (MS) and people with Parkinson's Disease (PD) from their respective, age-matched, healthy control subjects (MS-Ctl, PD-Ctl) in laboratory tests versus a week of daily life monitoring. METHODS: We recruited 15 people with MS (age mean ± SD: 49 ± 10 years), 16 MS-Ctl (45 ± 11 years), 16 people with idiopathic PD (71 ± 5 years), and 15 PD-Ctl (69 ± 7 years). Subjects wore 3 inertial sensors (one each foot and lower back) in the laboratory followed by 7 days during daily life. Mann-Whitney U test and area under the curve (AUC) compared differences between PD and PD-Ctl, and between MS and MS-Ctl in the laboratory and in daily life. RESULTS: Participants wore sensors for 60-68 h in daily life. Measures that best discriminated gait characteristics in people with MS and PD from their respective control groups were different between the laboratory gait test and a week of daily life. Specifically, the toe-off angle best discriminated MS versus MS-Ctl in the laboratory (AUC [95% CI] = 0.80 [0.63-0.96]) whereas gait speed in daily life (AUC = 0.84 [0.69-1.00]). In contrast, the lumbar coronal range of motion best discriminated PD versus PD-Ctl in the laboratory (AUC = 0.78 [0.59-0.96]) whereas foot-strike angle in daily life (AUC = 0.84 [0.70-0.98]). AUCs were larger in daily life compared to the laboratory. CONCLUSIONS: Larger AUC for daily life gait measures compared to the laboratory gait measures suggest that daily life monitoring may be more sensitive to impairments from neurological disease, but each neurological disease may require different gait outcome measures.
Assuntos
Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Monitorização Ambulatorial , Esclerose Múltipla Recidivante-Remitente/complicações , Doença de Parkinson/complicações , Adulto , Idoso , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Laboratórios , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Doença de Parkinson/fisiopatologia , Dispositivos Eletrônicos VestíveisRESUMO
BACKGROUND: Secondary progressive multiple sclerosis (SPMS) is characterized by worsening of postural control and brain atrophy. However, little is known about postural deficits and their neuroanatomical correlates in this population. We aimed to determine the neuroanatomical correlates of postural deficits in people with SPMS and whether posture control deteriorates concomitantly with the brain and spinal cord atrophy in 2 years in SPMS. METHODS: This study is a post hoc analysis of data from 27 people with SPMS (mean ± SE age, 58.6 ± 1.1 years). Participants had magnetic resonance imaging (MRI) of the brain and cervical spinal cord followed by sway testing using inertial sensors during standing with eyes open (EO) and eyes closed without (EC) and with (ECC) a cognitive task. Partial correlations investigated relationships between postural control and MRI measures at baseline and 2 years. RESULTS: At baseline, sway measures were inversely related to cortical thickness and cord cross-sectional area (CSA) during the EO task but only to cord CSA with EC (P < .05). After 2 years, the percentage change in sway amplitude and dispersion during EO tasks significantly related to the percentage decline in cord CSA (P < .01). CONCLUSIONS: Cortical and spinal cord inputs are essential for regulation of postural control during standing with EO in SPMS. Without visual input, people with SPMS preferentially rely on somatosensory inputs from the spinal cord for maintaining postural control. Postural deficits related to cord atrophy over 2 years, suggesting that postural control may be a surrogate marker of disease progression in people with SPMS.
RESUMO
BACKGROUND AND PURPOSE: Transvascular water exchange plays a key role in the functional integrity of the blood-brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange. METHODS: A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (vb ) and capillary water efflux rate constant (kpo ) were determined by fitting changes in the 1 H2 O longitudinal relaxation rate constant (R1 ) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images. RESULTS: R1 values and WM volume showed similar trajectories of age-related decline. Among all subjects, vb and kpo averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s-1 , respectively. While vb showed minimal changes over the 40-year-age span of participants, kpo declined 0.06 s-1 (ca. 3%) per year (r = -.66; P < .0005), from near 4 s-1 at age 30 to ca. 2 s-1 at age 70. The association remained significant after controlling for WM volume. CONCLUSIONS: Previous studies have shown that kpo tracks Na+ , K+ -ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in kpo observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.
Assuntos
Envelhecimento/metabolismo , Encéfalo/diagnóstico por imagem , Homeostase/fisiologia , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Substância Branca/metabolismoRESUMO
INTRODUCTION: Multiple sclerosis (MS) affects more than a million people in the US. A considerable portion of these patients either begin with primary progressive disease or eventually transition to secondary progressive MS. A progressive disease course is the most critical factor affecting disability accumulation. The relatively recent development of treatments for relapsing multiple sclerosis has had a profound impact on the disease course for many with MS. Unfortunately, therapies for progressive MS have not had the same degree of advancement in general. New insights into the pathophysiology of progressive MS may lead to new treatments. OBSERVATIONS: In this review, we identify some of the significant challenges encountered in the development of therapies for progressive MS, assess the evidence for use of currently approved therapies for patients with progressive MS, identify some of the current therapies in development from progressive MS, and consider the role for discontinuing therapy in certain patients. CONCLUSIONS: Developing effective disease modifying therapies that slow or stop the gradual accumulation of neurologic disability in progressive MS represents a critical unmet need. As the understanding of the inflammatory and neurodegenerative aspects of MS are better elucidated there may be opportunity for advancement in the treatment of progressive MS.
RESUMO
BACKGROUND: In 2001, we conducted a survey on use of complementary and alternative medicine (CAM) in people with multiple sclerosis (pwMS) in Oregon and Southwest Washington to treat their disease. OBJECTIVES, METHODS: In 2018, we administered a revised survey in the same region to describe updated patterns of CAM use in pwMS and to compare changes in use, perceived benefit, and patterns of communication between participants and providers regarding CAM over the past 17 years. RESULTS: 81% of respondents in 2018 (nâ¯=â¯1014) used a CAM supplement (vitamins, minerals, herbs), 39% used mind-body therapies (mindfulness, massage), 41% used specific diet, and 81% used exercise to treat their multiple sclerosis. Since 2001, use of supplements, exercise, and mind-body therapies have increased (65% to 81%, 67 to 81%, and 14% to 39%). Participants were also nine times more likely to speak to their neurologists about CAM use (6.7% to 55.4%). In 2018, factors associated with CAM use included female sex, progressive disease, and longer time since multiple sclerosis diagnosis. CONCLUSION: These findings highlight the high and increasing prevalence of CAM use in pwMS and factors associated with CAM use, and underscore the importance of research to investigate safety and efficacy of these therapies.
Assuntos
Terapias Complementares/estatística & dados numéricos , Dietoterapia/estatística & dados numéricos , Suplementos Nutricionais , Terapia por Exercício/estatística & dados numéricos , Esclerose Múltipla/terapia , Neurologistas/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos Transversais , Pesquisas sobre Atenção à Saúde , Humanos , Pessoa de Meia-Idade , Terapias Mente-Corpo/estatística & dados numéricos , Oregon , Relações Médico-Paciente , Fatores Sexuais , Fatores de Tempo , Washington , Adulto JovemRESUMO
Clinical trials need to specify which specific gait characteristics to monitor as mobility measures for each neurological disorder. As a first step, this study aimed to investigate a set of measures from daily-life monitoring that best discriminate mobility between people with multiple sclerosis (MS) and age-matched healthy control subjects (MS-Ctl) and between people with Parkinson's disease (PD) and age-matched healthy control subjects (PD-Ctl). Further, we investigated how these discriminative measures relate to the disease severity of MS or PD. We recruited 13 people with MS, 21 MS-Ctl, 29 people with idiopathic PD, and 20 PD-Ctl. Subjects wore 3 inertial sensors on their feet and the lumbar back for a week. The Area Under Curves (AUC) from the receiver operator characteristic (ROC) plot was calculated for each measure to determine the objective measures that best separated the MS and PD groups from their respective control cohorts. Adherence wearing the sensors was similar among groups for 58-66 h of recording (p = 0.14). Quantity of mobility (activity measures, such as a median number of strides per gait bout, AUC = 0.93) best discriminated mobility impairments in MS from MS-Ctl. In contrast, quality of mobility (such as turn angle, AUC = 0.90) best discriminated mobility impairments in PD from PD-Ctl. Mobility measures with AUC > 0.80 were correlated with MS and PD clinical scores of disease severity. Thus, measures characterizing mobility impairments differ for MS versus PD during daily life suggesting that mobility measures for clinical trials and clinical practice need to be specific to each neurological disorder.
Assuntos
Atividades Cotidianas , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Esclerose Múltipla/fisiopatologia , Doença de Parkinson/fisiopatologia , Idoso , Fenômenos Biomecânicos , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Esclerose Múltipla/complicações , Doença de Parkinson/complicações , Índice de Gravidade de Doença , Dispositivos Eletrônicos VestíveisRESUMO
PURPOSE: We determined if a high-intensity aerobic exercise program would be safe, improve expected fitness and clinical outcomes, and alter exploratory phosphorous magnetic resonance spectroscopy (P MRS) outcomes in persons with multiple sclerosis (PwMS). METHODS: This open-label prospective pilot study compared two cohorts of ambulatory PwMS matched for age, sex and VËO2max. Cohorts underwent 8 wk of high-intensity aerobic exercise (MS-Ex, n = 10) or guided stretching (MS-Ctr, n = 7). Aerobic exercise consisted of four 30-min sessions per week while maintaining ≥70% maximal HR. Changes in cardiorespiratory fitness, clinical outcomes, and P MRS of tibialis anterior (TA) muscle and brain were compared. Cross-sectional P MRS comparisons were made between all MS participants and a separate matched healthy control population. RESULTS: The MS-Ex cohort achieved target increases in VËO2max (mean, +12.7%; P = <0.001, between-group improvement, P = 0.03). One participant was withdrawn for exercise-induced syncope. The MS-Ex cohort had within-group improvements in fat mass (-5.8%; P = 0.04), lean muscle mass (+2.6%; P = 0.02), Symbol Digit Modalities Test (+15.1%; P = 0.04), and cognitive subscore of the Modified Fatigue Impact Scale (-26%; P = 0.03), whereas only the physical subscore of the Modified Fatigue Impact Scale improved in MS-Ctr (-16.1%; P = 0.007). P MRS revealed significant within-group increases in MS-Ex participants in TA rate constant of phosphocreatine (PCr) recovery (+31.5%; P = 0.03) and adenosine triphosphate/PCr (+3.2%; P = 0.01), and near significant between-group increases in TA PCr recovery rate constant (P = 0.05) but no significant changes in brain P MRS after exercise. Cross-sectional differences existed between MS and healthy control brain PCr/inorganic phosphate (4.61 ± 0.44, 3.93 ± 0.19; P = 0.0019). CONCLUSIONS: High-intensity aerobic exercise in PwMS improved expected cardiorespiratory and clinical outcomes but provoked one serious adverse event. The P MRS may serve to explore underlying mechanisms by which aerobic exercise exerts cerebral benefits.
Assuntos
Encéfalo/metabolismo , Terapia por Exercício/métodos , Treinamento Intervalado de Alta Intensidade , Esclerose Múltipla/metabolismo , Esclerose Múltipla/reabilitação , Músculo Esquelético/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Composição Corporal , Aptidão Cardiorrespiratória , Cognição/fisiologia , Terapia por Exercício/efeitos adversos , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Treinamento Intervalado de Alta Intensidade/efeitos adversos , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Exercícios de Alongamento Muscular , Fosfatos/metabolismo , Fosfocreatina/metabolismo , Projetos Piloto , Estudos Prospectivos , Síncope/etiologiaRESUMO
BACKGROUND: Limited prospective information exists regarding spectral-domain optical coherence tomography (SD-OCT) in secondary progressive multiple sclerosis (SPMS). OBJECTIVE: Document cross-sectional and longitudinal retinal nerve fiber layer (RNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) features of an SPMS clinical trial cohort. METHODS: Prospective, observational study using a 2-year randomized placebo-controlled SPMS trial cohort with yearly SD-OCT testing. Post hoc analysis determined influences of optic neuritis (ON), disease duration, and baseline SD-OCT on annualized atrophy rates and on correlations between OCT and brain atrophy. RESULTS: Mean RNFL and GCIPL values of patients ( n = 47, mean age = 59 years, mean disease duration = 30 years) were significantly lower among eyes with prior ON than those without (no history of ON (NON)). Annualized RNFL (-0.31 µm/year) and GCIPL (-0.29 µm/year) atrophy rates did not differ between ON and NON eyes. Baseline RNFL thickness >75 µm was associated with greater annualized RNFL atrophy (-0.85 µm/year). Neither RNFL nor GCIPL atrophy correlated with whole-brain atrophy. CONCLUSION: This study suggests that eyes with and without ON history may be pooled for atrophy analysis in SPMS clinical trials using SD-OCT. Low baseline RNFL, small retinal atrophy rates, and lack of correlation with whole-brain atrophy in this population are important trial design considerations.