Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls

2012 ◽  
Vol 18 (10) ◽  
pp. 1500-1506 ◽  
Author(s):  
O Scheidegger ◽  
CP Kamm ◽  
SJ Humpert ◽  
KM Rösler

Background: In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role. Objective: The objective of this study was to analyse the central motor conduction changes in relation to muscle contraction force during muscle fatigue and recovery in MS patients compared to healthy controls. Methods: A total of 23 MS patients with fatigue and 13 healthy subjects were assessed during 2 minutes of fatiguing exercise of the abductor digiti minimi muscle of the hand and the subsequent 7 minutes of recovery. Central motor conduction was quantified by transcranial magnetic stimulation using the triple stimulation protocol and calculating a central conduction index (CCI). Results: Force declined to 36% of the pre-exercise level (SD 16%; p < 0.01) in MS patients and to 44% (SD 9%, p < 0.01) in healthy subjects (group differences, not statistically significant). The decline of the CCI was significantly less marked in patients (–20%, SD 26%, p < 0.05) than in healthy subjects (–57%, SD 15%, p < 0.05; group differences, p < 0.05). The decline of force and CCI were not correlated in either group. Conclusions: During a fatiguing exercise, the decline in central motor conduction is significantly less pronounced in MS patients than healthy subjects, although the reduction of force is similar.

2008 ◽  
Vol 14 (7) ◽  
pp. 995-998 ◽  
Author(s):  
G Koch ◽  
S Rossi ◽  
C Prosperetti ◽  
C Codecà ◽  
F Monteleone ◽  
...  

We tested the effects of 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the motor cortex in multiple sclerosis (MS) subjects with cerebellar symptoms. rTMS improved hand dexterity in cerebellar patients ( n = 8) but not in healthy subjects ( n = 7), as detected by a significant transient reduction of the time required to complete the nine-hole pegboard task. rTMS of the motor cortex may be a useful approach to treat cerebellar impairment in MS patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Emiliano Santarnecchi ◽  
Simone Rossi ◽  
Sabina Bartalini ◽  
Massimo Cincotta ◽  
Fabio Giovannelli ◽  
...  

In ten healthy subjects and in ten patients suffering from Multiple Sclerosis (MS), we investigated the cortical functional changes induced by a standard fatiguing repetitive tapping task. The Cortical Silent Period (CSP), an intracortical, mainlyGABAB-mediated inhibitory phenomenon, was recorded by two different hand muscles, one acting as prime mover of the fatiguing index-thumb tapping task (First Dorsal Interosseous, FDI) and the other one not involved in the task but sharing largely overlapping central, spinal, and peripheral innervation (Abductor Digiti Minimi, ADM). At baseline, the CSP was shorter in patients than in controls. As fatigue developed, CSP changes involved both the “fatigued” FDI and the “unfatigued” ADM muscles, suggesting a cortical spread of central fatigue mechanisms. Chronic therapy with amantadine annulled differences in CSP duration between controls and patients, possibly through restoration of more physiological levels of intracortical inhibition in the motor cortex. These inhibitory changes correlated with the improvement of fatigue scales. The CSP may represent a suitable marker of neurophysiological mechanisms accounting for central fatigue generation either in controls or in MS patients, involving corticospinal neural pools supplying not only the fatigued muscle but also adjacent muscles sharing an overlapping cortical representation.


2012 ◽  
Vol 112 (5) ◽  
pp. 832-840 ◽  
Author(s):  
Birgit Andersen ◽  
Ulrik Ascanius Felding ◽  
Christian Krarup

Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The depression in size of the TST response, but no attenuation of the conventional motor-evoked potential, suggested increased probability of repetitive spinal MN activation during exercise, even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST [quadruple stimulation (QuadS) and quintuple stimulation (QuintS)] to examine the influence of fatiguing exercise on second and third MN discharges after a single TMS in healthy subjects. This method allows an estimation of the percentage of double and triple discharging MNs. Following a sustained contraction of the abductor digiti minimi muscle at 50% maximal force maintained to exhaustion, the size of QuadS and QuintS responses increased markedly, reflecting that a greater proportion of spinal MNs was activated two or three times by the transcranial stimulus. The size of QuadS responses did not return to precontraction levels during 10-min observation time, indicating long-lasting increase in excitatory input to spinal MNs. In addition, the postexercise behavior of QuadS responses was related to the duration of the contraction, pointing to a correlation between repeated activation of MNs and the subject's ability to maintain force. In conclusion, the study confirmed that an increased fraction of spinal MNs fire more than once in response to TMS when the muscle is fatigued. Repetitive MN firing may provide an adaptive mechanism to maintain motor unit activation and task performance during sustained voluntary activity.


2008 ◽  
Vol 14 (8) ◽  
pp. 1056-1060 ◽  
Author(s):  
M Hirotani ◽  
C Maita ◽  
M Niino ◽  
SM Iguchi-Ariga ◽  
S Hamada ◽  
...  

Objectives DJ-1 plays a key role in the anti-oxidative stress function. Increasing evidence supports the role of oxidative stress in the pathogenesis of multiple sclerosis (MS). The aim of this study was to investigate whether the DJ-1 levels were increased in patients with MS and to examine its association with the progression of MS. Methods Quantitative immunoblot assays were performed to evaluate the DJ-1 level in serum and cerebrospinal fluid (CSF) collected from relapsing–remitting patients with MS ( n = 29), disease controls subjects ( n = 14), and healthy subjects ( n = 44). Results No significant difference was observed in the serum DJ-1 level among the patients with MS, disease controls, and healthy controls. However, the CSF DJ-1 levels were significantly higher in the patients with MS than in the disease control subjects ( P < 0.0001). A significant positive correlation was also found between the CSF DJ-1 levels and the Multiple Sclerosis Severity Score ( P < 0.005, r = 0.501). Conclusions These results show that the CSF DJ-1 levels are significantly increased in the CSF of patients with MS and that the CSF DJ-1 levels may be associated with the disease progression of MS. Therefore, DJ-1 possibly plays an important role in the pathogenesis of MS.


2015 ◽  
Vol 44 (6) ◽  
pp. 590-601 ◽  
Author(s):  
Mehrdad Farrokhi ◽  
Masoud Etemadifar ◽  
Maryam Sadat Jafary Alavi ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Mohaddeseh Behjati ◽  
...  

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.


2014 ◽  
Vol 275 (1-2) ◽  
pp. 140-141
Author(s):  
Ulrike Bühler ◽  
René Gollan ◽  
Patrick Belikan ◽  
Frauke Zipp ◽  
Volker Siffrin

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.


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