Measurement of interocular delays with dynamic random-dot stereograms

Summary A psychophysical method of measuring interocular delay based on dynamic random-dot stereograms is presented. The measurement requires only about 2 min. The sensitivity of this method to detect differences in the transmission times of the two optic nerves is demonstrated in patients with multiple sclerosis and in healthy subjects in whom interocular delays were produced by using different luminance levels for each eye. This new method may be a useful and economic method for monitoring the time course of optic neuritis.     

The latency distribution of motor evoked potentials in patients with multiple sclerosis

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 7.3 ms in healthy subjects and 10.7 ms 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.     

Fever and evoked potentials in multiple sclerosis

Summary The somatosensory evoked potentials (SEPs) and visual evoked potentials (VEPs) were studied in 19 patients with multiple sclerosis; 17 controls were studied during fever (38.0°–39.7°C) and 2–3 days following return to normal temperature. The latencies of components N₂₀ and P₁₁₄ were measured and specified as abnormal when their value exceeded the standard deviation of the controls by 2.5 times. The corresponding criterion for the evaluation of the amplitude of components N₂₀ and P₁₁₄ was a reduction in amplitude of more than 50%. In the controls fever did not cause significant changes in evoked potentials. On the other hand, patients with multiple sclerosis showed abnormalities in evoked potentials during fever in a greater number of recordings (26 of SEPs and 33 of VEBs) than after return to normal temperature (19 and 27 respectively). In addition, the average latency of components N₂₀ and P₁₁₄ was clearly greater in the patients during fever (N₂₀=29.5±5.2 ms and P₁₁₄=143±18.1 ms) than after return to normal temperature (N₂₀=6.6±3.5 ms and P₁₁₄=134±16 ms). The amplitude of components N₂₀ and P₁₁₄ in patients during fever was clearly smaller than after return to normal temperature. These differences were statistically significant. Finally, in two patients, a decrease was found, during fever, in the conduction velocity of the peripheral somatosensory pathway from the median nerve to the wrist at Erb's point.

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Zusammenfassung Wir studierten die somatosensorisch evozierten Potentiale (SSEP) sowie die visuell evozierten Potentiale (VEP) bei 19 Patienten mit Multipler Sklerose und 17 Kontrollpersonen. Die somatosensorisch und visuell evozierten Potentiale wurden in beiden Gruppen unter dem Einfluß von Fieber als auch zwei bis drei Tage nach dem Abklingen des Fiebers untersucht.Die Latenzzeit der Komponenten N₂₀ und P₁₁₄ wurde als pathologisch bewertet, wenn ihre Werte 2,5 Standardabweichungen über dem Mittelwert von Normalpersonen lagen.Der entsprechende Maßstab für die Bewertung der Höhe der Komponenten N₂₀ und P₁₁₄ war eine Höheminderung über 50%.Wir fanden, daß Fieber bei den Kontrollpersonen keinen wesentlichen Einfluß auf SSEP und VEP hatte. Bei den MS-Patienten haben wir wesentlich mehr Abnormitäten der SSEP und VEP während des Fiebers (26 SSEP und 33 VEP) als nach dem Abklingen des Fiebers (19 SSEP und 27 VEP).Darüber hinaus war der Mittelwert der Latenzzeit der Komponenten N₂₀ und P₁₁₄ bei den MS-Patienten während des Fiebers höher (N₂₀=29,5±5,2 ms; P₁₁₄=143±18,1 ms) als nach dessen Abklingen (N₂₀=26,6±3,5 ms; P₁₁₄=134±16,8 ms).Abgesehen davon war die Höhe der Komponenten N₂₀ und P₁₁₄ während des Fiebers wesentlich kleiner als nach dem Abklingen des Fiebers.Diese Unterschiede sind statistisch signifikant.Ferner fanden wir während des Fiebers bei zwei Patienten eine Verminderung der Erregungsleitungsgeschwindigkeit im N. medianus zwischen Handgelenk und Erbschen Punkt.

     

Subclinical visual field defects in multiple sclerosis

Summary Fourteen patients with definite but inactive multiple sclerosis (MS) and 17 normal controls were examined with the automated perimeter octopus. Most of the patients had subclinical visual field defects, typically consisting of patchy, shallow scotomata located mostly in an area of between 15° and 30° eccentricity. In 8 patients, more than 15% of the tested visual field of at least one eye was abnormal. The severity and extent of the defects was unrelated to a history of optic neuritis. When visually evoked potentials (VEPs) of these subjects were examined using a reversing pattern, no correlation was found in the MS patients between prolonged VEP latencies and the location, depth or extent of visual field defects. Since subclinical visual field defects may be found in MS patients with normal VEP latencies, automated perimetry can be helpful in diagnosing some cases.Supported in part by Geigy Jubilaeumsstiftung, Basel     

Right/left differences of median nerve evoked scalp potentials in multiple sclerosis

Summary Scalp potentials evoked by electrical stimulation of the median nerve at the wrist were examined in multiple sclerosis patients and healthy controls. The latencies of the first negative peak (about 18 ms latency) of the response to right and to left-sided stimulation were compared. Forty-eight of 60 measured latency differences in 15 suspected or certain MS patients were more than 3 standard deviations beyond the average difference in controls (arbitrary norm limit), whereas none of the 56 results of the 14 controls was in that range. Fifteen of 24 latency differences in 6 patients without anamnestic or clinical sensory disturbances in the arms were above the limit. On the other hand, conduction velocity between wrist, neck and scalp did not differentiate controls from patients.We suggest using latency differences of the early components of right and left median nerve-evoked scalp potentials as a mean for the early detection of functional disturbances in multiple sclerosis.Supported in part by Schweiz. Multiple-Sklerose-Gesellschaft (Jubiläumsstiftung der Schweiz. Lebens- und Rentenversicherung), Swiss National Science Foundation, and Stiftung Wiss. Forschung, Zürich     

Central motor conduction as a measure of disease progression in early multiple sclerosis

We monitored disease progression in 27 patients with clinically or laboratory-supported definite multiple sclerosis by means of clinical assessments [expanded disability status scale (EDSS), and the neurologic rating scale (NRS)] repeated at 6 month intervals for 2 years. Each clinical assessment was accompanied by evoked potentials (EP; visual, brain stem auditory, and somatosensory evoked potentials), motor evoked potentials elicited by magnetic stimulation, and magnetic resonance imaging of the brain and brain stem. Central conduction indices were calculated for each central pathway. According to the EDSS 18 patients deteriorated, eight were unchanged and one improved. The central motor conduction index (CMCI) was the only conduction parameter which correlated significantly with both EDSS and NRS at baseline [rho=0.51 (EDSS); -0.65 (NRS)], at final investigation, and when individual changes from baseline to final investigation were addressed (rho=0.38; -0.38). Individual deteriorations or improvements of the CMCI during the 2 years correlated with changes in both EDSS and NRS (rho = 0.51; -0.38). The MRI parameters did not correlate with the clinical scores. The concordance between MRI and CMCI in detection of disease activity was 63%. We conclude that the CMCI stands out as an objective, accurate and easily obtained outcome parameter.     

Motor evoked potentials in multiple sclerosis patients without walking limitation: amplitude vs. conduction time abnormalities

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 ≤ 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. Received in revised form: 3 April 2006     

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.     

视神经炎与多发性硬化的关系研究

目的为了探讨视神经炎与多发性硬化的关系。方法分析２８例视神经炎患者的头颅磁共振（ＭＲＩ）及体感诱发电位（ＳＥＰ）检查情况。结果（１）头颅ＭＲＩ扫描异常率为３２．１％，病灶呈多发性，主要分布在侧脑室旁、半卵圆中心，长Ｔ２信号，少数合并长Ｔ１信号。（２）ＳＥＰ中枢传导异常率为４２．９％，下肢异常多于上肢，单侧异常多于双侧。（３）发病两次及两次以上，脊髓受累机会增加。结论伴有较多的亚临床损害的视神经炎可能是多发性硬化的一个临床类型     

Comparative study of visual evoked potentials in spinocerebellar ataxias and multiple sclerosis

Visual evoked potentials (VEPs) were delayed in 11 out of 18 patients with Friedreich's ataxia, in 1 out of 8 patients with Strumpell's hereditary spastic ataxia, in 2 out of 5 cases with cerebellar atrophy and in 42 out of 50 patients with multiple sclerosis (MS). Responses were normal in 5 cases with Pierre Marie's disease. Amplitude and temporal dispersion were statistically analyzed in the above-mentioned groups of patients with respect to controls. An abnormal temporal dispersion, also considered as interpeak N1P2, was frequently found in MS but only occasionally in spinocerebellar ataxias. Amplitude was statistically reduced in Friedreich's ataxia group, where an inverse relationship between latency and amplitude was found. No relation was found between VEP delay and duration of the disease, in any group considered.     

Auditory double click evoked potentials in multiple sclerosis

Brain stem electric responses (BSER), evoked by acoustic stimuli, were investigated in 29 patients with multiple sclerosis and compared with the responses in a control group of 26 young adults without neurological disease or hearing defect. The procedure included monaural and binaural stimulus presentation of single clicks and pairs of clicks. In the evaluations the vertex-positive Jewett I, III and V response components, and the vertex-negative "FFP₇" peak were considered. In the assessment of the BSER components, the FFP₇ (the vertex-negative 7 ms far field potential following the Jewett_v wave) proved to be the best single component with respect to reproducibility in normal subjects. In addition the FFP₇ was the single most consistently abnormal component in the patient group. Determination of the latency of the Jewett components and the interpeak conduction times, however, contributed further to the disclosure of the abnormal cases. Five of the patients whose hearing was impaired were considered separately. Of the remaining 24 patients, 20 (83 %) had BSER abnormalities. Further analysis did not reveal a clear correlation between BSER abnormalities and clinical signs of brain stem dysfunction.     

Erectile impotence in multiple sclerosis: a neurophysiological study

Pudendal evoked potentials, motor evoked potentials of the bulbocavernosus muscle to magnetic stimulation and bulbocavernosus reflex were recorded in 34 patients with multiple sclerosis (MS). Responses were delayed in 26, 20 and 3 cases respectively. No relationship was found between neurophysiological abnormalities and the presence or severity of erectile dysfunction, showing that these tests have little diagnostic usefulness in MS patients with impotence. Nocturnal penile tumescence was assessed in 14 cases: the test result was normal in 10 patients, including 3 severely paraplegic subjects.     

Evaluation of various brain structures in multiple sclerosis with multimodality evoked potentials,blink reflex and nystagmography

Summary Pattern reversal visual evoked potentials (VEP), blink reflexes, auditory brainstem evoked potentials (ABEP), spinal and scalp recorded somatosensory evoked potentials (SSEP), and nystagmographic records were investigated in 55 patients with multiple sclerosis (MS), who were separated in different categories of probability according to the clinical history, symptoms, and signs. The combined use of different electrophysiological methods forms a sensitive battery for investigating clinically uncertain cases of MS. It was stressed that care should be taken in the interpretation of the electrophysiological findings, since a single lesion in the central nervous system, particularly in the brainstem, may affect different functional systems simultaneously and therefore mimic a disseminated disease.

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Zusammenfassung Visuelle musterevozierte Potentiale, der elektrisch ausgelöste Blinkreflex, auditorisch evozierte Hirnstammpotentiale, somatosensorisch evozierte Potentiale mit Ableitung über dem unteren Cervicalmark und dem jeweiligen kontralateralen Handfeld sowie nystagmographische Ableitungen wurden bei 55 Patienten mit einer Multiplen Sklerose untersucht. Die Patienten wurden entsprechend der anamnestischen Daten und der klinischen Symptomatologie in vier Gruppen unterschiedlicher diagnostischer Wahrscheinlichkeit getrennt. Die Resultate zeigten, daß die Kombination verschiedener evozierter Potentiale einen hohen Aussagewert in solchen Fällen haben kann, in denen die Diagnose einer MS klinisch nicht eindeutig ist. Es wird jedoch hervorgehoben, daß die Interpretation der elektrophysiologischen Befunde mit großer Sorgfalt vorgenommen werden soll, da eine einzige Läsion im Zentralnervensystem, besonders im Bereich des Hirnstammes, gleichzeitig verschiedene funktionelle Systeme befallen und dadurch eine disseminierte Erkrankung vortäuschen kann.

     

Short term neurophysiological monitoring in multiple sclerosis bouts. Evaluation of steroid treatment

Visual (VEP) and brainstem auditory (BAEP) evoked potentials (EP) were recorded in 21 multiple sclerosis (MS) patients in acute relapse before and after steroid treatment. VEPs were abnormal in 14/21 patients and BAEPs in 10/21 patients before treatment. In 4 patients with acute optic neuritis (ON), an improvement of VEPs paralleled clinical evolution in 3 cases. Substantial and contrasting changes in VEPs or BAEPs, with no clinical counterpart, were related to a spontaneous fluctuation of EPs in acute relapses of MS. These changes suggest frequent subclinical (multifocal and, possibly, sequential) central nervous system involvement in MS bouts. Group analysis showed nonsignificant changes in EP parameters before and after treatment. Our results indicate that evoked potentials (EPs) are of limited value for monitoring the short-term effect of steroid treatment in MS in bouts.

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Sommario I potenziali evocati visivi (VEP) ed acustici troncoencefalici (BAEP) sono stati eseguiti in 21 pazienti affentti da sclerosi multipla (SM) in fase di poussée, prima e dopo un ciclo di trattamento con steroidi. Prima del trattamento i VEP edi BAEP sono risultati alterati in 14 e 10 pazienti rispettivamente. 4 pazienti presentavano una neurite ottica (ON) in fase acuta; in 3, dopo il trattamento, è stato rilevato un significativo miglioramento dei VEP e dell'acuità visiva. Significative, ma contrastanti, modificazioni dei VEP e BAEP, riscontrate in altri 5 pazienti, non correlate all'evoluzione clinica, sono suggestive di un interessamento subclinico, multifocale e possibilmente sequenziale, durante una poussée della SM. L'analisi per gruppi non evidenzia differenze statistiche significative tra prima e dopo il trattamento. I nostri risultati indicano che i potenziali evocati sono di limitata utilità ai fini di un monitoraggio a breve termine della SM in poussée.

     

The location by early auditory evoked potentials (EAEP) of acoustic nerve and brainstem demyelination in multiple sclerosis (MS)

Summary Tone pips of suprathreshold intensities elicit an acoustic nerve response (I) and six low amplitude brainstem potentials (II–VII) during the initial 10 ms. Seven waves were studied in 40 control subjects and 5 waves (I–V) in 47 patients with MS. The results suggest involvement of the auditory pathway of 24 of 27 patients in the clinically definite, of 5 of 9 cases in the probable and in none of 5 patients in the possible MS groups. EAEPs were normal in 6 cases with a spinal form with one exception where changes of potential were indicative of a midbrain lesion. Dysfunction within the acoustic pathway was observed at the level of the acoustic nerve and in the medulla oblongata, pons and midbrain. The significance of the bilateral EAEP abnormalities found in some patients at different levels is discussed with regard to a polytopic location of the underlying lesion.This work includes part of a thesis of E. Schäfer (University of Mainz)     

Methodik und Auswertung visuell evozierter EEG-Potentiale bei Verdacht auf multiple Sklerose

Zusammenfassung Durch Schachbrettmusterinversion monoculär evozierte gemittelte EEG-Potentiale haben häufig bei multipler Sklerose verzögerte Latenzen der occipital positiven Welle (über 110 ms) und Latenzdifferenzen über 6–7 ms zwischen rechts-und linksäugiger Reizung.Fixation des Stimulusfeldes am unteren Pol führt zu signifikant längeren Latenzen und geringeren Amplituden als Fixation am oberen Pol. Bei unterer Fixation kann die Verzögerung in extremen Fällen bis zu einer anscheinenden Polaritätsumkehr der gemittelten Potentiale gehen. Zentralfixation führt oft, aber nicht immer zu gemittelten Potentialen, die jenen bei oberer Polfixation ähneln. Fixation des Stimulusfeldes am oberen Pol ist daher der Zentralfixation vorzuziehen, um möglichst geringe Streuung der Ergebnisse zu erreichen.

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Methods and evaluation of visually evoked EEG potentials in cases of suspected multiple sclerosis

Summary In multiple sclerosis, average EEG potentials which are monocularly evoked by checkerboard pattern reversal frequently show increased latencies of the dominant, occipitally positive peak (more than 110 ms), and latency differences of more than 6–7 ms between responses to right and left eye stimulation.Fixation of the stimulus field at the lower border causes significantly longer latencies and smaller amplitudes than fixation at the upper border. With lower border fixation, the increase of response latency may suggest a reversal of response polarity in extreme cases. Central fixation often but not always results in responses similar to upper border fixation. In order to have minimal variability of the results, fixation of the stimulus field at the upper border is preferred over central fixation.

Stipendiat der Roche-Studienstiftung. Adresse: Draskoviceva 4 A, 4100 Zagreb, Jugoslawien.     

EDSS correlated analysis of median nerve somatosensory evoked potentials in multiple sclerosis

Median nerve somatosensory evoked potentials (SEP) were recorded in 30 patients with multiple sclerosis. The examined patients had an expanded disability status scale (EDSS) between 0 and 6. The primary cortical potential N20, the subcortical potentials P14, N13b, N13a and the peripheral potential P9 were recorded simultaneously. In 5 patients normal SEP were observed (group 1) and in 6 patients there were consecutive disturbances of the somatosensory pathway (group 3). In 19 patients subcortical potentials were abnormal or absent while the following potentials were normal or identified which pattern corresponds to amplification within CNS structures (group 2). The EDSS of groups 1 and 2 were similar and lower than the EDSS of group 3, which indicates that amplification mechanisms could represent a positive prognostic factor in SEP diagnosis of multiple sclerosis. Received: 15 March 2000 / Accepted in revised form: 4 September 2000     

Brain-stem auditory evoked potentials in multiple sclerosis: the relation to VEP,SEP and CSF immunoglobulins

Summary One hundred patients with multiple sclerosis (MS) were analysed retrospectively with respect to investigations of brain-stem auditory evoked potentials (BAEP), pattern reversal visual evoked potentials (VEP), somatosensory evoked potentials (SEP), and cerebrospinal fluid immunoglobulins (CSF-IG). BAEP were abnormal in 42% of those with normal VEP and SEP examinations, and in 38% of patients with normal CSF-IG. The chance of obtaining at least one abnormal EP was lower in patients with normal CSF-IG than in patients with abnormal CSF. When a dispersion ratio was included in the criteria for BAEP abnormality, the sensitivity increased compared with conventional BAEP criteria. We recommend that BAEP should still be included in the EP test battery for patients with suspected MS.     

Impairment of vestibulo-collic reflex and linear vestibulo-ocular reflex in pediatric-onset multiple sclerosis patients

ObjectivesThis study aimed to examine the vestibulo-collic reflex (VCR) and linear vestibulo-ocular reflex (lVOR) and their correlation with brain lesions in pediatric-onset multiple sclerosis (POMS).MethodsThe study group consisted of 17 patients (34 ears) with POMS (mean age 18.73 ± 2.02, mean age at disease onset 14.64 ± 1.36 years), and the control group included 11 age-matched healthy subjects (22 ears). Ocular and cervical Vestibular Evoked Myogenic Potentials (oVEMP and cVEMP) were performed to assess IVOR and VCR pathways. Magnetic Resonance Imaging was evaluated in the study group.ResultsIn the POMS group, 47.05 % of oVEMPs and 17.64 % of the cVEMPs were abnormal, while all VEMPs were normal in the control group. The oVEMP amplitude was associated with infratentorial lesion volume (r = −0.459, p = 0.01) and total lesion volume of the brainstem and cerebellum (r = −0.450, p = 0.01). The cVEMP asymmetry ratio was correlated with the deep white matter lesion volume (r = 0.683, p < 0.001). The MVEMP scores were found to correlate only with lesion volumes in the cerebellum (r = 0.488, p = 0.04) and infratentorial region (r = 0.573, p = 0.01).ConclusionsOcular and cervical VEMP abnormalities confirm that lVOR and VCR pathways may be affected in early POMS.SignificanceRoutine use of the VEMP test, especially the oVEMP test is recommended as a useful tool in the follow-up of POMS patients.     

Pudendal nerve somatosensory evoked potentials in probable multiple sclerosis

Bladder dysfunctions are often observed in patients with multiple sclerosis (MS). In order to evaluate their sensitivity in detecting abnormalities in bladder central control pathways, pudendal nerve somatosensory evoked potentials (pSEPs) were recorded in 16 patients with clinically probable MS: six were affected by retention or urge incontinence, and ten were asymptomatic. Conventional visual, auditory and somatosensory evoked potentials were also recorded, and all of the patients underwent a urodynamic examination. Prolonged latency or the absence of pSEP cortical responses was found in eight of the ten asymptomatic patients, and in all of the symptomatic cases (87.5%). The urodynamic evaluation revealed abnormalities in 12 patients (75%). Our findings seem to indicate an early and frequent involvement of bladder control pathways in MS patients, as well as a high rate of subclinical disorders.This work was supported by grants from MURST, Italy