Motor Evoked Potentials and Disability In Multiple Sclerosis

Objective
This pilot study was designed to determine the effects of Interferon-beta-1a (IFN-ß) therapy (Avonex) on Cortically Evoked Motor Potentials (MEPs) during resting and Fatigued States in individuals with Multiple Sclerosis (MS).

Methods
Eight women with Relapsing/Remitting MS (mean age 36) and mean Expanded Disability Status Scale (EDSS) score of 3.1 were evaluated before and after 3, 6, and 12 months of IFN-ß therapy.

At each test period, MEPs were recorded at rest and following a Fatigue Paradigm (3 min maximal contraction). Effects of IFN-ß on Neurological and functional (7.7 m walk and 10 s finger tapping) status and Fatigue were also examined.

Results
Recovery from post-exercise depression of MEP Amplitudes (PED) was 41, 43, and 43.5% faster at 3, 6, and 12 months, respectively, compared to baseline (P < 0.05).

Percent reduction of MEP amplitude was significantly less at 6 months (P < 0.05) The majority of subjects (5/8 at 3 months; 6/8 at 6 and 12 months) reported decreased physical fatigue.

Functional improvements were observed for walk and finger tapping scores after 3 months of IFN-ß treatment. MEP Latencies were unchanged over the course of the intervention.

Conclusions
Results indicate that IFN-ß therapy may improve the rate of recovery from Central Fatigue.

Background
Pattern Reversal Visual Evoked Potentials (PRVEPs) have a well-documented role in diagnosis of Multiple Sclerosis (MS), but their value as a Visual function surrogate remains controversial.

Methods
We evaluated PRVEP in 37 patients with MS who were participating in a long-term follow-up study following a Phase III trial of Interferon-beta-1a (Avonex).

Patients were examined to determine the Kurtzke Extended Disability Status Score (EDSS), Multiple Sclerosis Functional Composite (MSFC), Contrast Letter Acuity (CLA), and had Cranial MRI scans to determine Whole Brain Atrophy (BPF).

PRVEP was evaluated for P100 Latency, Amplitude, and Waveform morphology.

Two summary scores were created:
1. Score A - Abnormal Latencies, Morphologies, and Amplitudes of each individual eye were added
   
   
2. Score B - Abnormal Latencies, Morphologies, and Amplitude Ratio between eyes was determined

Sixteen patients in this group also had PRVEP at the time they enrolled in the clinical trial, eight years previously.

Results
At the follow-up exam, over 75% of patients had abnormal PVEP parameters while Visual Acuity (VA) was abnormal only in 59%.

Increased PRVEP latency over the eight-year period correlated with deterioration assessed by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041).

Score A was significantly correlated with EDSS, BPF, CLA, Cognitive function, and quality of life assessed with the Sickness Impact profile. No correlation was seen with the MSFC.

Conclusions
The results indicate that PRVEP measures MS-related pathology, and can provide not only diagnostic but also prognostic information during evaluation of MS patients.

While Evoked Potentials are sensitive tools for diagnosing Multiple Sclerosis, little is known about their prognostic value and their role in determining the course of the disease.

To validate the Visual and Motor Evoked Potentials (VEP and MEP) as measures for the course of Multiple Sclerosis, we examined prospectively 30 patients with Relapsing/Remitting or Secondary/Progressive Multiple Sclerosis.

The Expanded Disability Status Scale (EDSS), VEP and MEP were measured at entry and after 6, 12 and 24 months. The Spearman rank correlation was used for statistical analysis.

Applying multiple regression in 15 randomized patients allowed derivation of a formula for predicting changes in EDSS score based on changes in MEP and VEP.

Validation was done by comparing the predicted with the real changes in EDSS in the other 15 patients. The number of pathological VEP and MEP results correlated at all four measurement points with the EDSS (rho > or = 0.6, P < or = 0.01).

When the latencies of VEP and MEP were combined using the sum of their Z scores, correlation with the EDSS was even more significant (rho > or = 0.6, P < 0.001).

Changes over time of ElectroPhysiological data and EDSS were also correlated (rho = 0.43, P < 0.05). Moreover, VEP and MEP at baseline correlated with the EDSS after 2 years (rho = 0.43,P = 0.03).

Reliable prediction of the course of Multiple Sclerosis for individual patients is not possible from VEP and MEP data.

However, we conclude that, for groups of patients with Secondary/Progressive or Relapsing/Remitting Multiple Sclerosis the combined testing of VEP and MEP yields numerical data that allow objective estimation of the course and prognosis of the disease.

Background
To investigate the mechanisms underlying disability in Multiple Sclerosis (MS), 40 patients with the Relapsing/Remitting form of the disease and 13 patients with Secondary/Progressive MS underwent multimodal Evoked Potentials (EP), Motor Evoked Potential (MEP), and Spinal Motor Conduction Time evaluation.

Clinical disability was evaluated by the Expanded Disability Status Scale (EDSS) and Functional System Scales.

In Secondary/Progressive MS patients, Magnetic Resonance Imaging (MRI) was used to obtain a SemiQuantitative estimate of the total lesion load of the Brain.

Results
Spinal Motor Conduction Time was significantly longer in:
1. Secondary/Progressive MS patients than controls (p < 0.001) and
2. Relapsing/Remitting MS patients (p < 0.05), but
3. did not differ between Relapsing/Remitting patients and controls.

Spinal Motor Conduction Times also correlated directly with EDSS scores (p < 0.001) and Pyramidal Functional System scores (p < 0.001).

Brain Lesion Load (4960.3 +/- 3719.0 mm2) and the total number of lesions (67.7 +/- 37.0) in Secondary/Progressive MS did not correlate with disability scores.

For the following EPs, the frequencies of abnormalities were significantly higher in Secondary/Progressive MS patients than Relapsing/Remitting patients:

1. Visual Evoked Potential (p < 0.05)

2. SomatoSensory Evoked Potentials and Upper Limb Motor Evoked Potentials (p < 0.01)

3. BrainStem Auditory Evoked Potentials, Lower Limb SomatoSensory Evoked Potentials and Lower Limb Motor Evoked Potentials (p &lt; 0.001).

Conclusions
These findings suggest that Disability in Secondary/Progressive MS patients is mainly due to progressive involvement of CorticoSpinal Tract in the Spinal Cord.

Objective
To quantify Temperature induced changes (Uhthoff's Phenomenon) in Central Motor Conduction and their relation to clinical motor deficits in 20 Multiple Sclerosis (MS) patients.

Methods
Self-assessment of vulnerability to Temperature and clinical examination were performed.

We used Motor Evoked Potentials to measure Central Motor Conduction Time (CMCT) and applied the Triple Stimulation Technique (TST) to assess Conduction Failure.

The TST allows an accurate quantification of the proportion of conducting Central Motor Neurons, expressed by the TST Amplitude Ratio (TST-AR).

Results
Temperature induced changes of TST-AR were significantly more marked in patients with prolonged CMCT (P=0.037). There was a significant linear correlation between changes of TST-AR and Walking Velocity (P=0.0002).

Relationships were found between pronounced subjective vulnerability to temperature and:

1. Abnormal CMCT (P=0.02)
2. Temperature induced changes in TST-AR (P=0.04)
3. Temperature induced changes in walking velocity (P=0.04)
4. CMCT remained virtually unchanged by Temperature modification

Conclusions
Uhthoff Phenomena in the Motor System are due to varying degrees of Conduction Block and associated with prolonged CMCT. In contrast to Conduction Block, CMCT is not importantly affected by Temperature.

Significance
This is the first study quantifying the Uhthoff's Phenomenon in the Pyramidal Tract of MS patients.

The results suggest that patients with Central Conduction slowing are particularly vulnerable to develop Temperature-dependent Central Motor Conduction Blocks.

Background
Long Latency Reflexes (LLR) include Afferent Sensory, Efferent Motor and Central TransCortical Pathways.

It is supposed that the Cortical Relay Time (CRT) reflects the Conduction of Central TransCortical Loop of LLR.

Recently, evidence related to the Cortical involvement in Multiple Sclerosis (MS) has been reported in some studies. Our aim was to investigate the CRT alterations in patients with MS.

Methods
Upper extremity Motor Evoked Potentials (MEP), SomatoSensory Evoked Potentials (SSEP) and LLR were tested in 28 patients with MS and control subjects (n=22).

The patients with MS were classified according to the clinical form (Relapsing/Remitting [R-R] and Progressive groups). The MS patients with Secondary/Progressive and Primary/Progressive forms were considered as the "Progressive" group.

CRT for LLR was calculated by subtracting the peak latency of SomatoSensory Evoked Potentials (SSEP).

And, that of Motor Evoked Potentials (MEP) by TransCranial Magnetic Stimulation, from the onset latency of the second component of LLR (LLR2) (CRT = LLR2 - [MEP latency + N20 latency])

Results
Cortical Relay Time was calculated as 7.4 +/- 0.9 ms in control subjects. Cortical Relay Time was prolonged in patients with MS (11.2 +/- 2.9 ms) (p<0.0001).

The latencies of LLR, MEP and SSEP were also prolonged in patients with MS. Cortical Relay Time was not correlated with disease severity and clinical form in contrast to other tests.

Conclusions
Our findings suggested that CRT can be a valuable ElectroPhysiological tool in patients with MS.

Involvement of ExtraCortical Neural Circuits between Sensory and Motor Cortices or Cortical involvement due to MS may cause these findings.

Objective
Recent functional and imaging studies have substantially contributed to extend the concept of Multiple Sclerosis (MS), classically regarded as a disease limited to the Myelin Axonal Sheath.

Several findings, in fact, point to a parallel involvement of Neuronal components of the Central Nervous System (CNS) in the course of MS.

In the present study, therefore, we explored, in MS patients, some characteristics of Central Motor Pathways related to changes of Neuronal Excitability as measured using TransCranial Magnetic Stimulation (TMS).

Methods
Seventy-nine patients affected by Relapsing/Remitting (RR) MS were examined using single and paired TMS in order to assess Excitability Changes in the hand Motor Cortex occurring during Relapse and/or Remission of the disease.

The analyzed parameters were: Motor-Evoked Potential (MEP) threshold, Silent Period (SP), IntraCortical Inhibition (ICI) with paired pulses from 1 to 6 ms InterStimulus Intervals (ISIs), and Central Motor Conduction Time (CMCT).

Results
The analysis of variance exhibited a strong correlation (P < 0.001) between the clinical phase and the type of excitability changes:

1. 'Relapsing' patients showed increased Threshold and reduced SP duration
2. 'Relapsing' patients also displayed a significant lack of normal IntraCortical Inhibition (ICI)
3. By contrast, 'Remitting' patients showed a significant SP prolongation with normal Motor Thresholds

Conclusions
The present findings reveal changes in Cortical Excitability that might play a role in the PathoPhysiology of MS symptoms.

In particular, the Relapsing phase of MS has been found to be associated with Cortical HyperExcitability irrespective of the site of clinical manifestation or new plaque formation.

These results might help to explain the puzzling picture of Neurological symptoms observed in MS patients during different phases of the disease.

Significance
Alterations of Neuronal components of the CNS play a role in MS.

In order to determine the importance of Central Motor Conduction Time (CMCT) and Silent Period (SP) in patients with Multiple Sclerosis (MS), we enrolled this clinical and ElectroPhysiological study.

Additionally, we planned to compare the correlation between ElectroPhysiological findings and clinical status.

We examined 58 patients with Definite MS and 31 controls. Patients were classified as Relapsing/Remitting (N: 37), Secondary/Progressive (N: 21) groups.

Eleven out of 58 patients with MS had no Neurological findings (SubClinical patients).

We evaluated CMCT and the duration of SP. Prolonged CMCT latency was shown in 75.2% of patients. We observed SP abnormalities in 69% of patients.

In SubClinical patients, SP abnormalities (six of 11) were observed more common than CMCT (two of 11). The duration of SP was extremely prolonged in MS patients with Cerebellar Dysfunction.

When the both ElectroPhysiological parameters are taken into account, the abnormality ratio was determined as 89.7%.

Our results indicate that CMCT and SP analysis are complementary tests in evaluating Motor Pathways of patients with MS. We observed a relationship between Cerebellar Dysfunction and SP prolongation.

It is suggested that, SP can be applied in patients with pure Cerebellar Dysfunction and it can be a valuable test in SubClinical cases with MS.

We have made a review on the use of Evoked Potentials in Multiple Sclerosis (MS) for the past 30 years, in the diagnosis of MS, to disclose subclinical lesions or to assess atypical symptoms.

Yet the role of Evoked Potentials in evaluation of Multiple Sclerosis has been changed since MRI is now widely and easily used for the diagnosis of MS.

Evoked Potentials are useful when symptoms are atypical without any objective impairment and when symptoms have already recovered at the time of clinical examination.

Visual Evoked Potentials and SomatoSensory Evoked Potentials are widely used thanks to their diagnostic value and their ability to disclose spatial dissemination of Multiple Sclerosis.

Evoked Potentials have to be recorded in validated technical conditions such as to ensure reliability of data.

And, have to be interpreted in reference to a population of healthy people recorded in the same conditions and in the same age range as MS patients.

Objective
To compare the effects of IntraVenous MethylPrednisolone (IVMP) in patients with Relapsing/Remitting (RR-MS), Secondary/Progressive (SP-MS), and primary progressive Multiple Sclerosis (PP-MS).

Methods
Clinical and NeuroPhysiological follow up was undertaken in 24 RR-MS, eight SP-MS, and nine PP-MS patients receiving Solu-Medrol 500 mg/d over five days for exacerbations involving the motor system.

Motor Evoked Potentials (MEPs) were used to measure Central Motor Conduction Time (CMCT) and the Triple Stimulation Technique (TST) was applied to assess Conduction deficits.

The TST allows accurate quantification of the number of conducting Central Motor Neurons, expressed by the TST amplitude ratio.

Results
There was a significant increase in TST amplitude ratio in RR-MS (p < 0.001) and SP-MS patients (p < 0.02) at day 5, paralleling an increase in muscle force.

TST amplitude ratio and muscle force remained stable at two months. In PP-MS, TST amplitude ratio and muscle force did not change. CMCT did not change significantly in any of the three groups.

Conclusions
In RR-MS and SP-MS, IVMP is followed by a prompt increase in conducting Central Motor Neurons paralleled by improvement in muscle force, which most probably reflects partial resolution of Central Conduction Block.

The lack of similar Clinical and NeuroPhysiological changes in PP-MS corroborates previous clinical reports on limited IVMP efficacy in this patient group and points to pathophysiological differences underlying exacerbations in PP-MS.