The role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis

doi:10.1016/0022-510X(91)90190-I

Journal of the Neurological Sciences

Volume 106, Issue 1, November 1991, Pages 31-34

https://doi.org/10.1016/0022-510X(91)90190-I Get rights and content

Abstract

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck in a prospective longitudinal study of patients with multiple sclerosis (MS) and normal subjects. MCT measurements showed a high degree of reproducibility in normal subjects and patients with stable MS. In patients with definite MS, there was significant positive correlation between MCT and motor disability. In patients treated with steroids for relapse of MS, there was significant shortening of MCT following treatment in those who clinically improved, but not in those who were clinically unchanged. In a smaller group of patients followed for 3 months, MCT changes tended to mirror the clinical pattern. Magnetic stimulation should prove a useful tool for the quantification of motor disability, and monitoring the response to new treatments in MS.

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Cited by (39)

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee
2023, Clinical Neurophysiology
The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504–32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer’s disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.
The use of transcranial magnetic stimulation in diagnosis, prognostication and treatment evaluation in multiple sclerosis
2015, Multiple Sclerosis and Related Disorders
Citation Excerpt :
A subgroup of 11 clinically stable patients were re-examined over the following 3 months, and a further 27 patients who suffered a clinical relapse were examined during and after steroid treatment. Despite small numbers, there was a statistically significant correlation between clinical findings and CMCT, in that patients who clinically responded to steroid treatment had a robust reduction in CMCT and non-improvers had no change; results from stable patients were unchanged across two readings (Kandler et al., 1991). Similar degrees of improvement in CMCT have also been documented with clinical improvement in response to physiotherapy (Kandler, 1990) and in patients who improve without treatment for a relapse (Sahota et al., 2005), making a specific effect of corticosteroids on neural excitability less likely.
Despite advances in brain imaging which have revolutionised the diagnosis and monitoring of patients with Multiple Sclerosis (MS), current imaging techniques have limitations, including poor correlation with clinical disability and prognosis. There is growing evidence that electrophysiological techniques may provide complementary functional information which can aid in diagnosis, prognostication and perhaps even monitoring of treatment response in patients with MS. Transcranial magnetic stimulation (TMS) is an underutilised technique with potential to assist diagnosis, predict prognosis and provide an objective surrogate marker of clinical progress and treatment response. This review explores the existing body of evidence relating to the use of TMS in patients with MS, outlines the practical aspects and scope of TMS testing and reviews the current evidence relating to the use of TMS in diagnosis, disease classification, prognostication and response to symptomatic and disease-modifying therapies.
Superficial brain stimulation in multiple sclerosis
2013, Handbook of Clinical Neurology
Citation Excerpt :
In longitudinal studies changes in multimodal EP measures correlated with changes in EDSS (O’Connor et al., 1998; Fuhr et al., 2001; Jung et al., 2008; Schlaeger et al., 2012a). Serial measurements of CMCT and TST amplitude ratios thereby allowed for the detection of changes in both directions – not only worsening but also improvement – and also permitted monitoring of treatment responses to corticosteroids given as relapse treatment (Kandler et al., 1991; Salle et al., 1992; Fierro et al., 2002; Humm et al., 2006), and possibly also to interferon-β (Feuillet et al., 2007). The therapeutic response as measured by EP can even precede the clinically detectable response (Nuwer et al., 1987).
Central motor conduction time (CMCT) is the most frequently studied measure derived from transcranial magnetic stimulation (TMS) in multiple sclerosis (MS); it is abnormal in 57–93% of patients. Addition of the triple stimulation technique and combining motor with other evoked potentials (EPs) increases sensitivity. Cross-sectional correlations of TMS measures with clinical assessments of motor dysfunction or global disability are high. Longitudinally, CMCT is sensitive to both worsening and improvement of motor function, showing its potential to detect therapeutic responses. Moreover, combined multimodal EPs are valid quantitative predictors of the clinical course over periods ranging from 2 to 14 years.
Measures of transcallosal connectivity (ipsilateral silent period and interhemispheric inhibition) are altered even in early MS, and yield complementary information on subclinical changes. Pathological brain plasticity in MS has been demonstrated by paired associative stimulation studies revealing a compensatory role of the ipsilateral motor and premotor areas. Central motor fatigue is associated with reduced motor EP amplitudes and increased cortical silent periods in normal controls, whereas patients with MS suffering from subjective fatigue show various abnormalities in cortical modulation of the motor system.
The clinical diagnostic utility of transcranial magnetic stimulation: Report of an IFCN committee
2008, Clinical Neurophysiology
Citation Excerpt :
Most studies indicated a significant correlation between CMCT or TST abnormalities and clinical motor signs or motor disability (Ingram et al., 1988; Van Der Kamp et al., 1991; Britton et al., 1991; Jones et al., 1991; Facchetti et al., 1997; Kidd et al., 1998; Magistris et al., 1999). For example, prolonged CMCTs improve during a relapse treated by high-dose corticosteroids and this correlates with clinical improvement (Kandler et al., 1991a; Salle et al., 1992; La Mantia et al., 1994; Fierro et al., 2002). CMCT measures integrated into a multimodal evoked potential (EP) score revealed close correlations with the Expanded Disability Status Scale (EDSS) (Bednarik and Kadanka, 1992; O’Connor et al., 1998; Fuhr et al., 2001; Comi et al., 2001; Leocani et al., 2006).
The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer’s disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.
Alteration of motor nerve recovery cycle in multiple sclerosis
2007, Clinical Neurophysiology
Citation Excerpt :
Nerve excitability changes did not correlate with EDSS score or disease duration, as previously shown for nerve conduction abnormalities in MS patients (Antonini et al., 1995; Sarova-Pinhas et al., 1995; Zee et al., 1991). In contrast, MEP abnormalities, found in 55% of our patients, correlated with disability scores, as also previously shown (Fuhr et al., 2001; Ingram et al., 1988; Jones et al., 1991; Kandler et al., 1991; Schmierer et al., 2002). Nerve excitability changes, in particular regarding the supernormal period, are likely to impact clinically according to activity-dependent conduction failure rather than to rest alteration.
To study peripheral motor nerve excitability in patients with multiple sclerosis (MS).
Twenty MS patients with normal nerve conduction parameters and no predisposing factors for peripheral neuropathy were included. Compound muscle action potentials were recorded from the abductor digiti minimi muscle to paired-pulse stimulation of the ulnar nerve at the wrist, with various interstimuli intervals (ISIs) ranging from 1 to 7 ms. The motor nerve recovery cycle was studied using a subtraction method. We measured the durations of the absolute and relative refractory periods (ARP, RRP) and the percentages of refractoriness and supernormality at 2.6 and 7 ms ISIs. The results obtained in MS patients were compared to normative values established in 20 age-matched healthy subjects. Correlations were made between excitability parameters and MS type (relapsing-remitting or progressive), EDSS score, disease duration, and motor evoked potential (MEP) abnormalities.
Supernormality was extremely reduced, refractoriness was increased and both ARP and RRP were prolonged in MS patients vs. healthy controls. These alterations did not correlate to clinical features or to the presence of MEP abnormalities.
Changes in motor nerve recovery cycle revealed the existence of subtle impairment in the peripheral nervous system of MS patients, mainly characterized by a reduced supernormality.
Peripheral nerve excitability alterations in MS may be due to axoglial paranodal dysjunction or juxtaparanodal dysfunction.
Use of Neurophysiologic Techniques in Clinical Trials
2005, Electrodiagnosis in Clinical Neurology: Expert Consult - Online and Print

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Research articleThe role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis

Abstract

Lancet

J. Neurol. Sci.

J. Neurol. Sci.

Lancet

Magnetic stimulation of the human brain and peripheral nervous system: an introduction and the results of an initial clinical evaluation

Neurosurgery

Magnetic and electrical stimulation of the brain: safety aspects

Central motor conduction in multiple sclerosis: evaluation of abnormalities revealed by transcutaneous magnetic stimulation of the brain

J. Neurol. Neurosurg. Psychiat.

Research article
The role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis