Cortical dysfunction underlies disability in multiple sclerosis

Vucic, Steve; Burke, Therese; Lenton, Kerry; Ramanathan, Sudarshini; Gomes, Lavier; Yannikas, Con; Kiernan, Matthew C.

doi:10.1177/1352458511424308

Cited by 61 publications

(93 citation statements)

References 35 publications

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“…To summarize, mild passive HS resulted in greater fatigue perception and impairments in force production in MS patients and corresponding evidence for cortical degeneration or dysfunction, including significantly increased RMT, decreased MEP amp , and decreased recruitment curve slope (35). PED of MEP amp was evident in controls and MS patients; however, the combination of HS and sustained exercise magnified these decrements in MS patients.…”

Section: Discussionmentioning

confidence: 99%

Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls

White

VanHaitsma

Vener

et al. 2013

Journal of Applied Physiology

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White AT, VanHaitsma TA, Vener J, Davis SL. Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls. J Appl Physiol 114: 1697-1704, 2013. First published April 18, 2013 doi:10.1152/japplphysiol.01119.2012.-Heat stress is associated with increased fatigue perception and decrements in function for individuals with multiple sclerosis (MS). Similarly, healthy individuals experience decrements in exercise performance during hyperthermia. Alterations in central nervous system (CNS) function during hyperthermia include reduced voluntary activation of muscle and increased effort perception. The purpose of this investigation was to test the hypothesis that passive heat exposure in MS patients will produce increased subjective fatigue and impairments in physiological measures of central conduction and cortical excitability compared with healthy individuals. Eleven healthy individuals and 11 MS patients completed a series of transcranial magnetic stimulation studies to examine central conduction and cortical excitability under thermoneutral and heat-stressed (HS) conditions at rest and after a fatiguing thumb abduction task. Passive heat stress resulted in significantly greater fatigue perception and impairments in force production in MS patients. Central motor conduction time was significantly shorter during HS in controls; however, in MS patients normal increases in conduction velocity with increased temperature were not observed centrally. MS patients also exhibited decreased cortical excitability during HS, evidenced by significant increases in resting motor threshold, decreased MEP amplitude, and decreased recruitment curve slope. Both groups exhibited postexercise depression of MEP amplitude, but the magnitude of these decrements was amplified in MS patients during HS. Taken together, these results suggest that CNS pathology in MS patients played a substantial role in reducing cortical excitability during HS. passive hyperthermia; recruitment curve; transcranial magnetic stimulation HIGH INTERNAL TEMPERATURE, ranging from 38.6 to 40.3°C, is associated with voluntary exhaustion during aerobic exercise, despite variations in baseline core temperature, heat storage rates, and final skin temperature (4, 10). Similarly, hyperthermia has been shown to produce motor fatigue, evidenced by decreased voluntary activation during sustained maximal voluntary contractions (MVC) (16,34). Cardiovascular strain during thermal stress contributes to the development of fatigue; however, evidence also suggests that hyperthermia alters central nervous system (CNS) functions, resulting in alterations in voluntary activation of muscle, as well as changes in perception of effort (18,24,33). Little is known about the effects of moderate core temperature increases, in the range between 0.5 to 1.0°C, on CNS function in healthy individuals, although some evidence suggests that decrements in function may begin to appear when core temperatures exceed normal levels (1...

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Section: Discussionmentioning

confidence: 99%

Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls

White

VanHaitsma

Vener

et al. 2013

Journal of Applied Physiology

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“…37 Moreover, in patients with progressive MS there is an increased excitability of primary motor cortex neurons and therefore a potential increase of their metabolic demand. [38][39][40] Another hypothesis has associated reduced blood flow with obliterating perivascular MS lesions, but this seems unlikely because one would then expect a more patchy pattern of focal CBF decrease, as seen in central nervous system vasculitis, which is not the case in MS. Microvessel thrombosis and other structural abnormalities have only very exceptionally been observed within MS plaques. 41 The increased CBF in active inflammatory lesions also argue against this theory.…”

Section: Possible Causative Mechanismsmentioning

confidence: 96%

Cerebral Hypoperfusion: A New Pathophysiologic Concept in Multiple Sclerosis?

D’haeseleer

Hostenbach

Peeters

et al. 2015

J Cereb Blood Flow Metab

106

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The exact pathogenesis of multiple sclerosis (MS) is incompletely understood. Although auto-immune responses have an important role in the development of hallmark focal demyelinating lesions, the underlying mechanism of axonal degeneration, the other key player in MS pathology and main determinant of long-term disability, remains unclear and corresponds poorly with inflammatory disease activity. Perfusion-weighted imaging studies have demonstrated that there is a widespread cerebral hypoperfusion in patients with MS, which is present from the early beginning to more advanced disease stages. This reduced cerebral blood flow (CBF) does not seems to be secondary to loss of axonal integrity with decreased metabolic demands but appears to be mediated by elevated levels of the potent vasospastic peptide endothelin-1 in the cerebral circulation. Evidence is evolving that cerebral hypoperfusion in MS is associated with chronic hypoxia, focal lesion formation, diffuse axonal degeneration, cognitive dysfunction, and fatigue. Restoring CBF may therefore emerge as a new therapeutic target in MS.

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“…Due to signal leakage from demyelination in the CST, reduced MEP amplitudes have been observed in MS. 27 However, there was a lack of structural evidence for MS pathophysiology in the CST for our cohort supported by no observed differences in the CST MWF compared to controls. Therefore, changes in corticospinal excitability were also not expected.…”

Section: Discussionmentioning

confidence: 82%

Corticospinal tract integrity measured using transcranial magnetic stimulation and magnetic resonance imaging in neuromyelitis optica and multiple sclerosis

et al. 2015

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Cortical dysfunction underlies disability in multiple sclerosis

Abstract: Together, these findings suggest that cortical dysfunction is associated with disability in MS, and documentation of such cortical dysfunction may serve to quantify disease severity in MS.

Cited by 61 publications

References 35 publications

Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls

Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls

Cerebral Hypoperfusion: A New Pathophysiologic Concept in Multiple Sclerosis?

Corticospinal tract integrity measured using transcranial magnetic stimulation and magnetic resonance imaging in neuromyelitis optica and multiple sclerosis

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