Correlation between disability and transcranial magnetic stimulation abnormalities in patients with multiple sclerosis

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating disorder of the central nervous system. Clinical evaluation, MRI, cerebrospinal fluid testing and evoked potentials (EP) are among the available methods utilized for disease diagnosis and monitoring. To date, no surrogate markers have been established to assess disease evolution and progression. The aim of this study is to assess motor evoked potentials (MEP) of MS patients by transcranial magnetic stimulation (TMS) and investigate the possible correlations between TMS abnormalities and disability in the patient group, which includes a subgroup with no apparent pyramidal tract dysfunction. A total of 131 clinically definite MS patients were included in the study. Motor responses to TMS stimulation were recorded. Absent values, decreases in amplitude, prolongation of latency and central motor conduction time (CMCT) were considered as abnormal. A total of 109 (83%) patients displayed abnormal MEP amplitude, 68 (52%) displayed MEP latency, and 64 (49%) displayed CMCT abnormalities. Abnormal CMCT, latency and amplitude results were correlated with Expanded Disability Status Scale scores (p < 0.001). Our results indicate that TMS-EP in MS patients is correlated with disability, and that these findings may support the role of EPs in predicting disability even in subclinical presentations.     

A transcranial magnetic stimulation study evaluating methylprednisolone treatment in multiple sclerosis

OBJECTIVE: To investigate the efficacy of two different high doses of intravenous methylprednisolone (IVMP) during Multiple Sclerosis (MS) relapses. BACKGROUND: Transcranial Magnetic Stimulation (TMS) is the most sensitive neurophysiological ascertainment to quantify motor disability, to follow the recovery from an MS relapse, and to detect the response to treatment. DESIGN AND METHOD: Twenty-four clinically definite relapsing - remitting MS patients presenting a relapse were randomly assigned to a treatment for 5 days with IVMP 1 or 2 g/day. The response to treatment of each patient was evaluated through Expanded Disability Status Scale (EDSS), Medical Research Council (MRC) score, and TMS by means of motor evoked potential (MEP) parameters. RESULTS: Motor threshold (MT), central motor conduction time (CMCT) and MRC showed a higher improvement with the highest dose of IVMP. Silent period and EDSS improved with both treatments. CONCLUSION: The dose of 2 g/day of IVMP is more effective in MS relapse.     

Transcranial magnetic stimulation: role in the evaluation of disability in multiple sclerosis

BACKGROUND: In patients with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) has shown significant prolongation of central motor conduction time (CMCT). Abnormal CMCT may reflect sub-clinical involvement of motor pathways and correlate with clinical motor disability. OBJECTIVE: To determine the diagnostic yield of TMS in MS and the possible correlation of TMS abnormalities with clinical disability. MATERIALS AND METHODS: Thirty patients with clinically definite MS presenting in acute relapse or with progressive disease course and 30 healthy controls were evaluated. TMS parameters evaluated included threshold intensity, motor evoked potentials (MEP) amplitudes and latencies and CMCT. Reassessment studies were done after three months. STATISTICAL ANALYSIS: Student t-test, Mann-Whitney U test and Spearman's rank correlation test were used to assess the relationships. RESULTS: Patients with MS had significantly higher threshold intensities, prolonged CMCT and reduced MEP amplitudes as compared to controls. Abnormalities in at least one parameter were observed in 86.7% of patients. When inter-side asymmetries in MEP latency and/or in CMCT were considered, the diagnostic yield increased to 96.7%. The diagnostic yield was 74.7% for visual evoked potentials, 13.3% for brainstem auditory evoked response and 10% for cerebrospinal fluid oligoclonal band. One MS patient without pyramidal or cerebellar dysfunction had prolonged CMCT. CMCT abnormalities correlated significantly with the degree of pyramidal signs, limb ataxia, intention tremor, dysdiadokokinesia and overall cerebellar score. In patients who had clinical improvement, follow-up studies showed improvement in CMCT parameters. CONCLUSION: TMS is a highly sensitive technique to evaluate cortico-spinal conduction abnormalities in MS that may have no clinical correlate and in monitoring the course of the disease. The effects of cerebellar dysfunction on TMS results need further evaluation.     

Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a set of disorders associated with preferential degeneration of both upper and lower motor neurons. Navigated transcranial magnetic stimulation (nTMS) is a tool used to perform noninvasive functional brain mapping. We aimed to assess function of upper motor neurons in ALS. Methods: nTMS was performed on 30 patients with ALS (mean age 54.4 ± 12.1 years) and 24 healthy volunteers (mean age 32.7 ± 13.3 years). Results: The resting motor threshold (MT) was significantly higher in ALS patients compared with controls (P < 0.001). The mean map areas were smaller in patients with ALS than in healthy individuals, although some patients with short disease duration had extended maps. Conclusions: Motor area maps serve as markers of upper motor neuron damage in ALS. Further research may elucidate the pathogenic mechanisms of the neurodegenerative process and aid in development of diagnostic and prognostic markers. Muscle Nerve 51 : 125–131, 2015     

Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study

We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the motor task, MS-F patients had less inhibition in the primary motor cortex compared to both other groups. Postexercise, intracortical inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the motor threshold was correlated with the fatigue severity. We conclude that MS patients with fatigue have an impairment of inhibitory circuits in their primary motor cortex. The results also indicate that fatigue severity is associated with an exercise-induced reduction of membrane excitability.     

The sensitivity of transcranial cortical magnetic stimulation in detecting pyramidal tract lesions in clinically definite multiple sclerosis

We determined central motor conduction time (CMCT) (motor cortex to root C-8 and motor cortex to root S-1) as well as the amplitude of the compound muscle action potentials in the hypothenar and the abductor hallucis muscles on both sides in 44 patients with definite MS. We compared the values with standards obtained from 86 healthy controls and correlated them with the degree of clinical deficit of the limbs examined. Thirty-nine patients (88.6%) showed a prolonged CMCT. By comparison, only 74.4% of patients had abnormal visual evoked potentials.     

Neurophysiological features of fasciculation potentials evoked by transcranial magnetic stimulation in amyotrophic lateral sclerosis

We report 13 patients with amyotrophic lateral sclerosis in whom fasciculation potentials (FPs) driven by transcranial magnetic stimulation (TMS) were recorded. A total of 18 different FPs were analyzed. TMS-driven fasciculations had a simple morphology and were stable. Complex potentials were never cortically driven. Recruitment by a slight voluntary contraction was verified in 7 of 13 tested FPs. FPs were driven by threshold stimuli in 7 of 10 patients and by stimuli 5% below threshold in 3 of 6. Mapping demonstrated that FPs were driven in an area close to the center of gravity of the muscle cortical area. In one case FPs were evoked from most of the cortical representation area of a very weak muscle. Three other patients with profuse fasciculations associated with other clinical conditions were also studied. No TMS evoked fasciculation was observed in this group. The results of this systematic study suggest that cortically evoked FPs arise centrally, at spinal cord or even more proximally, and can represent a marker of increased corticomotor excitability, which is predominant at an earlier phase but can persist as the disease progresses. Received: 15 April 1999/Received in revised form: 28 July 1999/Accepted: 2 November 1999     

Investigation of paroxysmal dystonia in a patient with multiple sclerosis: a transcranial magnetic stimulation study.

OBJECTIVE: To study the pathogenesis of paroxysmal dystonia affecting the right body side in a patient with a demyelinating lesion in the descending motor pathways, also involving the basal ganglia. METHODS: Single-pulse transcranial magnetic stimulation (TMS) was applied to study motor evoked potentials (MEPs) and the following silent periods (SPs) in the first dorsal interosseous muscle (FDI) of both sides and in the right extensor carpi radialis muscle (ECR) during voluntary contractions performed outside the dystonic attacks. During the dystonic paroxysms, single-pulse TMS was used to investigate the time course of MEPs and SPs in both FDI and ECR of the right side. Furthermore, paired-pulse TMS was applied at rest to investigate short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in both FDI muscles. RESULTS: At rest SICI and ICF were normal in both motor cortices. During voluntary contraction the MEP was smaller and the SP was longer in the affected FDI than in the contralateral. During the paroxysms, the MEPs and SPs were suppressed in comparison with the responses elicited during voluntary contraction. CONCLUSIONS: These results fit well with the theory of ephaptic excitement of corticospinal axons for the pathogenesis of paroxysmal dystonia due to a demyelinating lesion. SIGNIFICANCE: Identification of the mechanisms underlying paroxysmal dystonia in demyelinating disorders extends our knowledge on the pathophysiology of dystonia.     

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

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.     

Effects of transcranial direct current stimulation on cognitive dysfunction in multiple sclerosis

BackgroundAround 40%–70% of patients with multiple sclerosis (MS) may experience cognitive impairments during the course of their disease with detrimental effects on social and occupational activities. Transcranial direct current stimulation (tDCS has been investigated in pain, fatigue, and mood disorders related to MS, but to date, few studies have examined effects of tDCS on cognitive performance in MS.ObjectiveThe current study aimed to investigate the effects of a multi-session tDCS protocol on cognitive performance and resting-state brain electrical activities in patients with MS.MethodsTwenty-four eligible MS patients were randomly assigned to real (anodal) or sham tDCS groups. Before and after 8 consecutive daily tDCS sessions over the left dorsolateral prefrontal cortex (DLPFC), patients’ cognitive performance was assessed using the Cambridge Brain Sciences-Cognitive Platform (CBS-CP). Cortical electrical activity was also evaluated using quantitative electroencephalography (QEEG) analysis at baseline and after the intervention.ResultsCompared to the sham condition, significant improvement in reasoning and executive functions of the patients in the real tDCS group was observed. Attention was also improved considerably but not statistically significantly following real tDCS. However, no significant changes in resting-state brain activities were observed after stimulation in either group.ConclusionAnodal tDCS over the left DLPFC appears to be a promising therapeutic option for cognitive dysfunction in patients with MS. Larger studies are required to confirm these findings and to investigate underlying neuronal mechanisms.     

Suppression and long latency excitation of single spinal motoneurons by transcranial magnetic stimulation in health,multiple sclerosis,and stroke

Whether or not suppression at the level of the spinal motoneuron plays a role in motor deficits such as central paresis is unknown. In this study suppression in the firing of tonically active low threshold single motoneurons following low intensity transcranial magnetic stimulation is described in health and disease. Changes in firing probability in the absence of an early excitatory response were studied in a total of 14 motor units from 4 healthy subjects, 5 patients with multiple sclerosis, and 1 patient with stroke. Firing probability began to fall 18–59 ms after the stimulus and remained low for a period of 27–133 ms. There were no obvious differences between the three subject groups. The change in firing probability was not associated with specific physical signs. Late rises in firing probability were seen in 7 of the 14 motor units at latencies that were similar to the secondary peak which is known to occur with higher stimulus intensities. It is argued that the mechanism of partial suppression is not dependent on the full integrity of the pyramidal tract and is likely to involve a transient withdrawal of descending excitatory drive rather than an inhibitory postsynaptic potential at the spinal motoneuron. © 1994 John Wiley & Sons, Inc.     

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis.

OBJECTIVE: To evaluate motor cortex excitability changes by transcranial magnetic stimulation (TMS) following repetitive muscle contractions in patients with multiple sclerosis (MS); to state whether a typical pattern of post-exercise motor evoked potentials (MEPs) is related to clinical fatigue in MS. METHODS: In 41 patients with definite MS (32 with fatigue and 9 without fatigue according to Fatigue Severity Scale) and 13 controls, MEPs were recorded at rest: at baseline condition, following repetitive contractions until fatigue, and after fatigue, to evaluate post-exercise MEP facilitation (PEF) and depression (PED). RESULTS: After exercise, MEP amplitude significantly increased both in patients and controls (PEF). When fatigue set in, MEP amplitude was significantly reduced in normal subjects (PED), but not in patients. Post-exercise MEP findings were similar both in patients with and without fatigue. CONCLUSIONS: Our findings suggest an intracortical motor dysfunction following a voluntary contraction in MS patients, possibly due to failure of depression of facilitatory cortical circuits, or alternatively of inhibitory mechanisms.