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.

The aim of the present study was to determine the sensitivity and the profile of motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We measured the central motor conduction time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients, the triple stimulation technique (TST) was also performed. AR was abnormal in 50% of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the highest sub-clinical sensitivity and the best positive predictive value. In the absence of clinical pyramidal signs, an early AR decrease seems to result from demyelination inducing excessive temporal dispersion of the MEP, while in territories with clinical pyramidal signs, it seems to result from conduction failure, which suggests that clinical pyramidal signs may be attributable to conduction failure. This study demonstrates that MEP, especially the AR, is sensitive to motor pathway dysfunction right from the early stages of MS.

Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation based on the principle of electromagnetic induction, where small intracranial electric currents are generated by a powerful, rapidly changing extracranial magnetic field. Over the past 2 decades TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults, but has been used on a more limited basis in children. We reviewed the literature to identify potential diagnostic and therapeutic applications of TMS in child neurology and also its safety in pediatrics. Although TMS has not been associated with any serious side effects in children and appears to be well tolerated, general safety guidelines should be established. The potential for applications of TMS in child neurology and psychiatry is significant. Given its excellent safety profile and possible therapeutic effect, this technique should develop as an important tool in pediatric neurology over the next decade.

OBJECTIVE: To analyse transcranial magnetic stimulation (TMS) variables in a prospective six-month follow-up pilot study on patients suffering from relapsing-remitting multiple sclerosis (RRMS), satisfying inclusion criteria for interferon (IFN) beta-1a treatment. BACKGROUND: So far, no predictive factors are available as to the course of RRMS treated with IFN beta-1 a. DESIGN/METHODS: Fifteen RRMS patients were studied before (month 0 (M0)) and after IFN beta-1a onset (M3, M6). The parameters analysed were motor functional score (mFS), Expanded Disability Status Scale (EDSS), and TMS variables - central motor conduction time (CMCT) and amplitude ratio (AR). RESULTS: Four of the six patients with no motor signs at inclusion, subsequently showed signs of pyramidal dysfunction. All had abnormal M0_TMS variables. The number of M0_TMS abnormalities per patient was greatest in the group that showed mFS worsening, and was significantly correlated with M6_EDSS. The M0_CMCT was significantly correlated with M6_EDSS. During follow-up, the number of patients with abnormal TMS variables decreased from 12/15 to 4/15, and the total number of abnormalities decreased from 33.3 to 16.7%. CONCLUSIONS: TMS variables might be predictive of disease progression. The improvement observed here in the TMS variables may reflect an improvement in MS patients undergoing IFN beta treatment.

We used Motor Evoked Potentials (MEPs), elicited by transcranial magnetic stimulation, for assessing a motor pathways dysfunction in a selected group of Multiple Sclerosis (MS) patients, without limitation in walking. We selected 32 Relapsing Remitting MS patients, in remission phase, with EDSS < or = 3.5 and 20 healthy individuals with similar height and age distribution. We measured the following MEP parameters: motor thresholds; central motor conduction time (CMCT); amplitude and area, both expressed as MEP/CMAP ratio. Patients were divided into two groups according to the EDSS score: non-disabled group (ND; EDSS 0-1.5) and disabled group (D; EDSS 2-3.5). Mean average MEP values were significantly different in the patients compared with the controls. Even in MS patients with no or minor neurological signs (ND group), MEP parameters showed differences from controls and furthermore all MEP parameters were significantly different in the D group compared with the ND group. The 75% of the patients had an amplitude or area alteration; this percentage was significantly higher than the percentage of patients with a CMCT alteration (56.2%). In addition, CMCT increase was always associated with reduced amplitude and area, but amplitude and area alterations were present also in patients with normal CMCT. In early stages of MS, the higher percentage shown in alteration of MEP amplitudes and areas as opposed to CMCTs has not previously been highlighted in the literature. Independently of its pathogenesis (demyelination or axonal loss), the amplitude or area decrease should be considered in clinical trials and in follow-up studies, as a marker of the motor pathways dysfunction, at least as much as CMCT increase.

Depression is commonly associated with neurologic disorders. Although depression in neurologic conditions often is associated with a negative impact on quality of life, it frequently is poorly managed. Some factors, such as a multidrug regimen, lack of efficacy, and side effects of antidepressants may explain why depression is not adequately treated in patients with neurologic disorders. Therefore, this population needs new approaches for depression treatment, and repetitive transcranial magnetic stimulation (rTMS) may be one of them because it has been shown to be effective for the treatment of depression alone and depression in certain neurologic diseases such as Parkinson's disease and stroke. rTMS is a noninvasive, focal, and painless treatment associated with few, mild side effects. It may be effective in the treatment of neurologic diseases such as Parkinson's disease, stroke, and epilepsy. In this paper, we discuss the potential risks and benefits of rTMS treatment for depression in Parkinson's disease, epilepsy, stroke, multiple sclerosis, and Alzheimer's disease. Lastly, a framework that includes the parameters of stimulation (intensity, frequency, number of pulses, and site of stimulation) for the treatment of depression in neurologic diseases is proposed.

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.

OBJECTIVE: Clinical and electrophysiological evolution after total section of the forearm and nerves resuture. MATERIAL AND METHODS: A young boy aged 14 years with accidental amputation of the right forearm. The forearm was replanted within the first 6 hours after accident. Electromyography, nerve conduction, estimated number of the motor units, single fiber EMG and motor complex reflex responses were studied until 4 years after surgery. RESULTS: Functional recovery was reached in muscles innervated by median and ulnar nerves. After 4 years of evolution EMG showed signs of chronic neuropathy. Nerve conduction did not reach normal values. Single fiber EMG showed increased fiber density and jitter, and intermittent impulse blocking The estimated number of the motor units was severely reduced with high mean amplitude. Motor reflex responses were elicited by cutaneous stimulation consistent with axon reflexes or ephatic responses. CONCLUSIONS: Replanted limbs in selected cases and nerve's resuture may reach a functional recovery for daily activities.

Conventional EMG, nerve conduction studies and SFEMG were performed in 18 patients with various phenotypes of MD. 14 cases showed findings consistent with mild myopathy, 2 patients signs of sensory-motor axonal neuropathy and 2 cases a mixture of myopathy and axonal neuropathy. Motor unit fiber density was mild increased in 8 out of 13 tested cases. Jitter was abnormal in 10 out of 18 tested patients. Jitter abnormalities were not related to myopathic or neurogenic features in the EMG study, and may be observed in muscles without clinical weakness. The results suggest the existence of neuromuscular transmission disturbances in patients with MD.

This study looks at disease diversity, location of lesions, and progression of neuralgic amyotrophy (NA). Forty patients (28 male and 12 female, age range 15 to 70 years) were clinically examined. Muscle atrophy, weakness, and sensory impairment were assessed. Needle EMG and conduction velocities were performed. Careful clinical, electrophysiological, laboratory, and radiological studies excluded other illness. Twenty-two patients were followed for 2 years. Antecedent fever and upper-respiratory tract infection was seen in 22 cases. Pain of sudden onset was always the initial symptom, followed by weakness, mainly in the proximal muscles of shoulder. The affectation was bilateral in 7 cases. Seven cases had a recurrent form of the disease. Clinical and electrophysiological findings suggest axonal lesions of the peripheral nerves, occurring singly (mononeuritis) or in various combinations (mononeuropathy multiplex). Unusual features, such as VII and XI cranial nerves, phrenic nerve, and lateral antebrachial cutaneous nerve affectation, were found. Follow-up showed good function recovery at variable times, even in 1 case with associated myotonic dystrophy (MD). NA is a well-defined entity, with variable clinical expression and data consistent with mononeuropathy or mononeuropathy multiplex, axonal in type. The overall prognosis is good. The progression in a patient with MD suggests that the capability of muscle fiber membrane to accept regenerating nerve sprouts remains in dystrophic muscles.

OBJECTIVE: To analyse the regenerating capability of the peripheral nerve fibers and the capability of the muscle fibers to accept the regenerating and new nerve sprouts in myotonic dystrophy (MD). MATERIAL AND METHODS: One male, aged 58 years, diagnosed of MD at the age of 30 years, suffered neuralgic amyotrophy in the right shoulder girdle 4 weeks before admission. Needle EMG and nerve conduction studies were performed on admission and 6, 12, and 18 months later. RESULTS: On admission there were atrophy and absence of voluntary contraction in deltoids, supra- and infraspinatus muscles. EMG showed abundant fibrillations, positive sharp waves and myotonic bursts in these muscles without voluntary activity, consistent with axonal neuropathy of both axillary and suprascapular nerves. The follow-up showed signs of reinnervation 6 months later and slight loss of long duration and high amplitude MUPs at 18 months of evolution, with good clinical recovery. This is compatible with chronic neurogenic atrophy, presumably as an expression of type grouping. CONCLUSIONS: The reinnervation capability of the nerve fibers and the capability of muscle fibers membrane to accept regenerating and new nerve sprout remain in MD. Myotonic bursts persist after total denervation.

OBJECTIVES To evaluate the value of different electrophysiological techniques in the diagnosis of neurogenic thoracic outlet syndrome (TOS). MATERIALS AND METHODS Two females, aged 22 and 30 years, with progressive weakness and wasting of the right hand with slight sensory disturbances. Needle EMG, motor and sensory conduction along median and ulnar nerves, sensory conduction of medial (MACN) and lateral (LACN) antebrachial cutaneous nerves. RESULTS Chronic neurogenic atrophy in small hand muscles, more severe in lateral part of thenar eminency, reduced compound muscle action potentials (CMAPs) more severe by median than ulnar stimulation, and reduced amplitude of the SNAPs of ulnar and MACN were the main findings consistent with neurogenic TOS. Both patients had right cervical rib in radiography. CONCLUSIONS Electrophysiological study is useful in the diagnosis of neurogenic TOS. Reduced amplitude of MACN and ulnar nerve SNAPs, predominant denervation in thenar eminency, and reduced amplitude of CMAPs, more by median than by ulnar stimulation, are consistent with the diagnosis.

Automatic analysis of EMG (T/A analysis) and invasive muscle fiber conduction velocity in situ (MFCV) were performed in 15 patients after traumatic lesions of the knee and immobilization with quadriceps atrophy. T/A analysis showed transient reduced number of turns, consistent with inhibition of quadriceps motoneurons, that recovered within the first 2 weeks after the plaster cast had been removed. MFCV was significantly slowed and showed a gradual improvement, reaching normal values after 6 weeks. These results suggest that decrement in activated motor units may be the cause of the disproportionate weakness of the quadriceps muscle on the first days after immobilization by the plaster cast. The recovery of MFCV was related with functional improvement of strength after the first weeks.

OBJECTIVES Muscle fiber conduction velocity (MFCV) was performed in disuse atrophy, in denervated muscle and during reinnervation as a possible index of muscle atrophy, and to clarify the evolution of the fiber size. MATERIAL AND METHODS MFCV was performed in 12 patients with complete denervation of biceps brachii muscle and during various stages of reinnervation. Twenty-one patients with disuse quadriceps atrophy were also tested. Invasive MFCV was performed according to the method reported elsewhere (2). RESULTS MFCV decreased significantly in denervated muscles. Reduction of MFCV was found during the first weeks and was progressive. Peak frequency in histograms decreased and the normal Gaussian distribution was lost. MFCV increased progressively after reinnervation with coexistence of slow and significant increase of faster MFCV. MFCV decreased significantly also during the first weeks after immobilization and improved by rehabilitation therapy. CONCLUSION MFCV is a reliable method to test the muscle fiber size after denervation and immobilization, and its evolution by reinnervation and therapy.

OBJECTIVE: To present the clinical features and DNA analysis of a Spanish SCA6 family. MATERIAL AND METHODS: Four symptomatic members of the family (mean age at onset: 53.75+/-5.21) were examined. SCA6 CAG trinucleotide repeat was analysed in the proband by the polymerase chain reaction (PCR). RESULTS: Early dysphagia, ophthalmoparesis and neck dystonia in the oldest patient, without the loss of vibratory and proprioceptive sensation supporting the theory of phenotypic variability within families with SCA6. Our results are in accordance with the theory that the size of the repeat pattern correlates with the age at onset of the symptoms. Analysis of the SCA6 CAG trinucleotide repeat at the CACNA1A gene in the patient's DNA demonstrated an expanded allele of 22 CAG repeat units. CONCLUSIONS: This study identifies phenotypic differences in the surviving kindred. The diagnosis of SCA6 in family members or single affected patients can be made by direct molecular analysis. This makes predictive testing possible.

OBJECTIVES: To clarify the diagnostic yield of conduction velocity along muscle fibers in situ (MFCV) in hypokalemic periodic paralyses (HOPPs). MATERIAL AND METHODS: MFCV of the short head of biceps brachii was performed in 3 subjects with primary HOPP and in another 3 with secondary HOPP. RESULTS: MFCV was reduced during the recovery period in 2 of the patients with hereditary HOPP and in 3 with secondary hypokalemia due to hyperaldosteronism, diuretics, and renal tubular acidosis. One case with familiar HOPP showed fluctuating muscle weakness, but never had paralytic attacks. MFCV slowing was similar in both hereditary and secondary HOPP. Direct stimulation during a major attack with quadriplegia showed inexcitability of most muscle fibers. CONCLUSIONS: Inexcitability during major attacks and MFCV slowing in interictal or recovery periods evidenced sarcolemmal altered function. MFCV is a sensitive method for the detection of membrane muscle fiber defects in HOPPs and is also an additional diagnostic criterion of these diseases.

Conduction time of the central motor pathways (CMCT) by transcranial magnetic stimulation (TMS) was performed within the first two weeks in 7 patients with isolated hemicerebellar lesions after stroke. Cerebellar infarcts were small (< 2 cm in diameter) in 5 patients and no brainstem structure was involved in CT studies. The threshold (3 cases) and CMCT (4 cases) were abnormal or asymmetric by stimulation of the motor cortex contralateral to the impaired hemicerebellum. The follow-up study in 2 patients revealed electrophysiological improvement closely related to clinical cerebellar recovery rate. CMCT was significantly longer by cortex stimulation contralateral to the impaired hemicerebellum than by ipsilateral stimulation. Prolonged CMCT was significantly correlated with the rated severity of cerebellar signs. Increased threshold may be due to depressed facilitating action of the deep cerebellar nuclei on contralateral motor cortex. Abnormal CMCT might result in reduced size and increased dispersion of the efferent volleys. Recovery of electrophysiological results could represent in part true potentially reversible functional deficit. Whichever the pathophysiological mechanisms involved, our results demonstrate that the cerebellum dysfunction plays a role in the abnormalities of CMCT elicited by TMS.

OBJECTIVE: To compare the individual latency distributions of motor evoked potentials (MEP) in patients with multiple sclerosis (MS) to the previously reported results in healthy subjects (Firmin et al., 2011). METHODS: We applied the previously reported method to measure the distribution of MEP latencies to 16 patients with MS. The method is based on transcranial magnetic stimulation and consists of a combination of the triple stimulation technique with a method originally developed to measure conduction velocity distributions in peripheral nerves. RESULTS: MEP latency distributions in MS typically showed two peaks. The individual MEP latency distributions were significantly wider in patients with MS than in healthy subjects. The mean triple stimulation delay extension at the 75% quantile, a proxy for MEP latency distribution width, was 7.3ms in healthy subjects and 10.7ms in patients with MS. CONCLUSIONS: In patients with MS, slow portions of the central motor pathway contribute more to the MEP than in healthy subjects. The bimodal distribution found in healthy subjects is preserved in MS. SIGNIFICANCE: Our method to measure the distribution of MEP latencies is suitable to detect alterations in the relative contribution of corticospinal tract portions with long MEP latencies to motor conduction.

BACKGROUND Gray matter atrophy has been implicated in the development of secondary progressive multiple sclerosis (SPMS). Cortical function may be assessed by transcranial magnetic stimulation (TMS). Determining whether cortical dysfunction was a feature of SPMS could be of pathophysiological significance. OBJECTIVES Consequently, novel paired-pulse threshold tracking TMS techniques were used to assess whether cortical dysfunction was a feature of SPMS. METHODS Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing-remitting MS patients (RRMS) and 66 controls. RESULTS Short interval intracortical inhibition (SPMS 3.0 ± 2.1%; RRMS 12.8 ± 1.7%, p < 0.01; controls 10.5 ± 0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 ± 2.2%; RRMS 26.3 ± 3.6%, p <0.05; controls 24.7 ± 1.8%, p < 0.01) were reduced in SPMS, while intracortical facilitation (SPMS -5.2 ± 1.9%; RRMS -2.0 ± 1.4, p < 0.05; controls -0.9 ± 0.7, p < 0.01) and resting motor threshold were increased (SPMS 67.5 ± 4.5%; RRMS 56.0 ± 1.5%, p < 0.01; controls 59.0 ± 1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS (9.1 ± 1.2 ms, p < 0.001) and RRMS (7.0 ± 0.9 ms, p < 0.05) patients compared with controls (5.5 ± 0.2 ms). The observed changes in cortical function correlated with the Expanded Disability Status Scale. CONCLUSION 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.

The aim of this study was to assess the diagnostic accuracy (sensitivity and specificity) of clinical, imaging and motor evoked potentials (MEP) for predicting the short-term prognosis of multiple sclerosis (MS). We obtained clinical data, MRI and MEP from a prospective cohort of 51 patients and 20 matched controls followed for two years. Clinical end-points recorded were: 1) expanded disability status scale (EDSS), 2) disability progression, and 3) new relapses. We constructed computational classifiers (Bayesian, random decision-trees, simple logistic-linear regression-and neural networks) and calculated their accuracy by means of a 10-fold cross-validation method. We also validated our findings with a second cohort of 96 MS patients from a second center. We found that disability at baseline, grey matter volume and MEP were the variables that better correlated with clinical end-points, although their diagnostic accuracy was low. However, classifiers combining the most informative variables, namely baseline disability (EDSS), MRI lesion load and central motor conduction time (CMCT), were much more accurate in predicting future disability. Using the most informative variables (especially EDSS and CMCT) we developed a neural network (NNet) that attained a good performance for predicting the EDSS change. The predictive ability of the neural network was validated in an independent cohort obtaining similar accuracy (80%) for predicting the change in the EDSS two years later. The usefulness of clinical variables for predicting the course of MS on an individual basis is limited, despite being associated with the disease course. By training a NNet with the most informative variables we achieved a good accuracy for predicting short-term disability.

Pallix-Guyot M, Guennoc A-M, Blasco H, de Toffol B, Corcia P, Praline J. Predictive value of motor evoked potentials in clinically isolated syndrome. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2011.01498.x. © 2011 John Wiley & Sons A/S. Objectives -  To assess the predictive role of several measures obtained by transcranial magnetic stimulation (TMS) in patients with clinically isolated syndrome (CIS) for the risk of conversion to multiple sclerosis (MS) during the first 2 years. Materials and methods -  We investigated 34 patients with CIS. After 2 years of follow-up and classification into two groups according to MS diagnosis, initial TMS measures were compared to determine their predictive values for conversion to MS. Results -  Sixteen patients developed MS. We observed a significant difference between the two groups for contralateral silent period and no significant difference for the central motor conduction time, amplitude ratio, motor threshold, ipsilateral silent period, and the transcallosal conduction time. Conclusions -  Contralateral silent period (SP) seems to be a valuable parameter to early distinguish patients who will develop MS or not. This result about SP during CIS has never been described until now. An increased contralateral silent period would predict a conversion to MS with a positive predictive value of 75%, but this result needs to be confirmed in larger groups.

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.

The aim of the present study was to determine the sensitivity and the profile of motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We measured the central motor conduction time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients, the triple stimulation technique (TST) was also performed. AR was abnormal in 50% of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the highest sub-clinical sensitivity and the best positive predictive value. In the absence of clinical pyramidal signs, an early AR decrease seems to result from demyelination inducing excessive temporal dispersion of the MEP, while in territories with clinical pyramidal signs, it seems to result from conduction failure, which suggests that clinical pyramidal signs may be attributable to conduction failure. This study demonstrates that MEP, especially the AR, is sensitive to motor pathway dysfunction right from the early stages of MS.

Motor evoked potentials (MEPs) were studied in 63 patients with disorders affecting central motor pathways. These were classified into five subgroups: motor neuron disease (16), multiple sclerosis (13), cerebral infarction (19), spinal cord lesions (10) and hereditary spastic paraplegia (5). Three patients with hysterical paraplegia were also studied. Results were compared to those obtained from 30 normal subjects. In normal subjects the mean central motor conduction time (CMCT) was 6.4 ms (range 3.4-8.1 ms, SD 1.0 ms) for abductor digiti minimi and 13.2 ms (range 9.7-17.0 ms, SD 2.3 ms) for tibialis anterior. Amplitude of the cortical MEPs was defined as a percentage of the size of the peripheral compound muscle action potential (CMAP) and ranged from 14 to 85%. Fifteen of 16 patients with motor neuron disease and all patients with cerebral infarction, multiple sclerosis (MS), spastic paraparesis and non-MS spinal lesions had abnormal studies including low amplitude, dispersed or absent responses and prolonged CMCTs. Patients with MS had markedly prolonged CMCTs. In three cases of hysterical weakness MEPs were within normal limits. MEPs are a useful method to detect pathology in the central motor pathways and may have a significant role in the diagnosis of disorders involving the upper motor neuron.

OBJECTIVE In an attempt to analyze whether MEP can serve as a valid measure for evaluating neurological dysfunction in multiple sclerosis (MS), we related MEP to clinical and MRI measures. METHODS Transcranial magnetic stimulation was applied in 52 MS patients to determine the central motor conduction time (CMCT) to the extremities. We calculated Z-scores for each CMCT (Zcmct) corrected for height. All patients underwent two clinical measurements and a MRI scan, of which T1 and T2 brain lesion volumes, brain volume, spinal cord volume and the number of T2 spinal cord lesions were derived. RESULTS The clinical measurements correlated significantly with various Zcmct (Spearman correlation coefficients ranged from 0.29 to 0.53; p<0.05). The number of spinal cord lesions, brain T1 and T2 lesion volume and spinal cord volume correlated with various Zcmct (r=0.31-0.53; p<0.05). Linear regression analysis revealed that the clinical measurements were explained by Zcmct left leg and T1 lesion volume (adjusted R(2)=0.38). For one clinical measurement the number of spinal cord lesions was also included (adjusted R(2)=0.43). CONCLUSION We found a relation between MEP, brain and spinal cord MRI measures, and two clinical measures. Moreover, a model for explaining disability in MS revealed that MEP measures provide information in addition to MRI measures. SIGNIFICANCE This study suggests that MEP is a measure that might adequately reflect pathology and neurological dysfunction in MS.

We used Motor Evoked Potentials (MEPs), elicited by transcranial magnetic stimulation, for assessing a motor pathways dysfunction in a selected group of Multiple Sclerosis (MS) patients, without limitation in walking. We selected 32 Relapsing Remitting MS patients, in remission phase, with EDSS < or = 3.5 and 20 healthy individuals with similar height and age distribution. We measured the following MEP parameters: motor thresholds; central motor conduction time (CMCT); amplitude and area, both expressed as MEP/CMAP ratio. Patients were divided into two groups according to the EDSS score: non-disabled group (ND; EDSS 0-1.5) and disabled group (D; EDSS 2-3.5). Mean average MEP values were significantly different in the patients compared with the controls. Even in MS patients with no or minor neurological signs (ND group), MEP parameters showed differences from controls and furthermore all MEP parameters were significantly different in the D group compared with the ND group. The 75% of the patients had an amplitude or area alteration; this percentage was significantly higher than the percentage of patients with a CMCT alteration (56.2%). In addition, CMCT increase was always associated with reduced amplitude and area, but amplitude and area alterations were present also in patients with normal CMCT. In early stages of MS, the higher percentage shown in alteration of MEP amplitudes and areas as opposed to CMCTs has not previously been highlighted in the literature. Independently of its pathogenesis (demyelination or axonal loss), the amplitude or area decrease should be considered in clinical trials and in follow-up studies, as a marker of the motor pathways dysfunction, at least as much as CMCT increase.

For a better understanding of the changes affecting the cortically induced silent period (SP) in motoneuron disease, the excitatory and inhibitory effects of transcranial magnetic stimulation were explored repeatedly in 8 patients with amyotrophic lateral sclerosis (ALS), 3 patients with Kennedy's disease (KD), and 10 healthy subjects. In KD, the background electromyogram (EMG) and the motor evoked potential (MEP) area were both enhanced. However, neither the corticospinal efficiency (MEP gain, the ratio between MEP and background EMG) nor the duration of the SP differed from healthy subjects. In ALS patients, the MEP gain and the SP duration decreased conspicuously with time. We conclude that use of the MEP gain improves detection of corticospinal dysfunction in ALS patients. Part of the SP shortening in ALS seems to reflect the reduced activation of cortical or spinal inhibitory networks by the abnormal corticospinal pathway.