Evoked potential findings in Behçet's disease. Brain-stem auditory,visual, and somatosensory evoked potentials in 44 patients

We studied 54 patients with Behçet's disease, 41 males and 13 females, mean age 28 years. Forty-four patients had auditory brain-stem evoked potential (BAEP) recordings, 39 had pattern reversal visual evoked potentials (VEP), 27 had median nerve somatosensory evoked potential (SEP) recordings, and 25 tibial nerve SEPs. BAEPs were abnormal in 16 patients (52%) with neurological manifestations and in 4 (31%) without, because of decreased amplitude of wave V, prolonged I–III or III–V interpeak latencies, or uncertain/absent waves III and/or V. Eleven patients (40%) with neurological symptoms and 3 patients (25%) without, had abnormal VEPs. Absent potentials, decreased amplitude, with or without prolonged P100 latency, were found in 75% of the cases, the rest had prolonged P100 latency only. Median SEPs were abnormal in 8 patients (38%) with neurological manifestations. Four patients (21%) had abnormal tibial SEPs. Decreased amplitude with or without mild slowing in central conduction was the predominant SEP abnormality. SEPs were normal in all patients without neurological symptoms. In total, 84% of patients with, and 38% of patients without, neurological symptoms had abnormalities of one or more EP modality.When used cautiously, EP studies in Behçet's disease might be helpful to separate neuro-Behçet from other disorders with similar symptomatology, to disclose subclinical CNS involvement, to evaluate and monitor CNS disease activity, and to provide objective measures of treatment response.     

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey''s visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM.     

Normal temporal variability of the P100

Determination of clinically significant temporal changes in P100 latency requires knowledge of the degree of normal intraindividual variability. Checkerboard visual evoked potentials using 3 check sizes (17′, 35′ and 70′) were performed serially on 20 healthy volunteers. Each subject was tested at least twice an average of 6 months apart. The P100 latency was measured at Oz with a forehead reference (Pz, O1 and O2 channels were also recorded). The overall average P100 latency change between studies for all check sizes and both eyes was 2.9 msec. However, the maximum absolute latency change was 11 msec. There was no significant difference between the average latency change for the 3 check sizes. The P100 interocular difference changed a mean of 2.5 msec (maximum 9 msec). Amplitude was more variable, with a mean change of about 1.5 μV or 25% (maximum was a 60% decrease in amplitude). A P100 latency change of up to at least 11 msec needs to be acknowledged as normal when assessing the clinical significance of changes in P100 latencies in patients. Also, P100 latency changes greater than 11 or 12 msec are very suggestive of an abnormality in the visual pathway.     

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.     

Event-related auditory evoked potentials and multiple sclerosis

Long latency event-related auditory evoked potentials, particularly the P300 wave, constitute an objective electrophysiological index of cognitive function. For this reason, these potentials have been studied in a series of 101 patients with multiple sclerosis (MS), classified according to McAlpine's criteria into definite, probable and possible cases. The patients were also classified as depressed or non-depressed according to the DSM-III and Research Diagnostic Criteria. They were also subjected to a battery of psychometric tests.In the patient population the N200 and P300 latencies were increased, as were the P200 latencies, when compared with a control population. This electrophysiological pattern had previously been observed in other conditions characterised by subcortical lesions. Partial correlations (at constant disease duration) between the disability score and the cognitive deficit were found to be significant. Patients with an increased P300 latency had a greater disability and the P300 latency was significantly correlated with the duration of the illness.The N200 and P300 latencies were increased in depressed MS subjects, but this increase did not reach the level of significance. Depression was more frequent in the more severely handicapped patients. This suggests that the origin of the depression seen in multiple sclerosis is only partly organic, and that it is one of the factors contributing to the subcortical cognitive deficit in multiple sclerosis.Progressive forms of the disease exhibited the most profound cognitive deficit, and the most marked increase in P300 latency.     

Morphological measurement of the SEP using a dynamic time warping algorithm

A dynamic time warping technique was created to align the components of digitally high-pass (300 Hz–2500 Hz) filtered somatosensory evoked potentials evoked by median nerve stimulation recorded with a bipolar cephalic montage. A cost function was assigned related to the amount of warping necessary to match a standard wave derived from 24 normal subjects. Its value ranged from 0.525 to 2.456 (mean 1.305±0.501). This contrasted with a mean of 5.089±4.277 (range 0.701–13.972) derived from 25 patients with definite (n = 24) or possible (n = 1) multiple sclerosis chosen on the basis of having few or no clinical abnormalities at the time of testing. Fourteen (56%) of the patients had cost functions that were 3 or more S.D.s above the normal mean as compared to 3 (12%) having prolonged latency of the N19 peak. When used in combination, the cost function and latency yielded 60% abnormalities; 5 times higher than latency measurement alone.     

Clinical and neuroimaging correlates of abnormal short-latency Somatosensory Evoked Potentials in elderly vascular dementia patients: A psychophysiological exploratory study

BACKGROUND: Short Latency Somatosensory Evoked Potentials (SEPs) may serve to the testing of the somatosensory tract function, which is vulnerable and affected in vascular encephalopathy. The aim of the current study was to search for clinical and neuroimaging correlates of abnormal SEPs in vascular dementia (VD) patients. MATERIALS AND METHODS: The study included 14 VD patients, aged 72.93 PlusMinus; 4.73 years, and 10 controls aged 71.20 PlusMinus; 4.44 years. All subjects underwent a detailed clinical examination, blood and biochemical testing, brain MRI and were assessed with the MMSE. SEPs were recorded after stimulation from upper and lower limbs. The statistical Analysis included 1 and 2-way MANCOVAs and Factor analysis RESULTS: The N13 latency was significantly prolonged, the N19 amplitude was lower, the P27 amplitude was lower and the N11-P27 conduction time was prolonged in severely demented patients in comparison to controls. The N19 latency was prolonged in severely demented patients in comparison to both mildly demented and controls. The same was true for the N13-N19 conduction time, and for the P27 latency. Patients with subcortical lesions had all their latencies prolonged and lower P27 amplitude. DISCUSSION: The results of the current study suggest that there are significant differences between patients suffering from VD and healthy controls in SEPs, but these are detectable only when dementia is severe or there are lesions located in the subcortical regions. The results of the current study locate the abnormal SEPs in the white matter, and are in accord with the literature.     

Visual Evoked Response in Diagnosis of Multiple Sclerosis

The diagnostic value of the pattern-evoked response has been assessed in 73 patients referred because of suspected multiple sclerosis. Altogether 52 had delayed responses. Fifty-one patients in the group satisfied McAlpine''s criteria for diagnosing definite, probable, or possible multiple sclerosis. Of these, all but two had delayed responses in one or both eyes, while only three of the remaining 22 patients had delays. In those patients with multiple sclerosis but without any history of optic neuritis the incidence of delayed responses was only slightly less. Of 51 patients with delayed responses 23 had normal discs. Thus subclinical lesions of the visual pathways can be readily detected with this test. The high incidence of abnormal pattern responses, even in patients with no other ocular signs or symptoms, suggests that the test is of value in establishing the diagnosis.     

Pattern visual evoked potentials in the early diagnosis of optic neuropathy in the course of Graves' ophthalmopathy

THE AIM OF THE STUDY: To investigate by means of pattern visual evoked potentials (PVEPs) early neuropathic changes in Graves' ophthalmopathy (GO) patients without any clinical symptoms of optic neuropathy in order to evaluate the prevalence of subclinical optic neuropathy in GO patients and to elucidate whether there is a relationship between PVEP (P100 and N75 latency), intraocular pressure (IOP) and exophthalmometry. MATERIAL AND METHODS: Two groups of patients were examined: 15 patients with GO without clinical signs of dysthyroid optic neuropathy (DON) and 12 healthy controls. The correlations between the N75 and P100 latencies, IOP and Hertel exophthalmometry were investigated. RESULTS: The mean PVEP N75 and P100 latencies were significantly delayed in the GO uncomplicated with DON in comparison with controls (LP100- 106.2 +/- 4.4 ms vs. 102.4 +/- 2.7 ms, p < 0.01 and LN75- 79.0 +/- 3.7 ms vs. 73.9 +/- 2.8 ms, p < 0.001). In GO patients we documented a positive correlation between the LN75 latency and exophthalmometric readings (R = 0.51; p < 0.01). The value of LP100 and LN75 was above the normal limit in 5/30 eyes (17%) and in 3/30 eyes (10%) respectively. CONCLUSIONS: The assessment of PVEPs (especially the P100 latency) in GO patients without clinical signs of DON is a useful tool for the early diagnosis of optic nerve involvement.     

A prospective 1 year follow-up study with somatosensory potentials evoked by stimulation of the posterior tibial nerve in patients with supratentorial cerebral infarction

Somatosensory potentials evoked by stimulation of the posterior tibial nerve (tibial nerve SEPs) were studied in 40 patients with supratentorial non-haemorrhagic cerebral infarction and in 25 control subjects. SEPs were recorded twice in 39 patients and thrice in 35 patients. The first examination was carried out 4–19 days after the onset of the symptoms, the second examination 56–100 days after the stroke, and the third examination 348–393 days after the stroke. Increased side-to-side differences in the P57 and N75 peak latencies and absence of the P40 peak were the most frequent abnormal findings. The latency abnormalities were associated with involvement of the subcortical white matter of the rolandic region. The absence of the P40 peak was, in contrast, closely related to the extension of the infarcted area into the cortical gray matter of during the acute stage, 51% of patients had abnormal SEPs in the second examination and 43% of patients in the third examination. A nearly significant decrease was observed in the number of latency abnormalities, but the number of amplitude abnormalities, including absent responses, did not change during the 1 year follow-up period.     

Abnormal Control of Orbicularis Oculi Reflex Excitability in Multiple Sclerosis

Brain lesions in patients with multiple sclerosis may lead to abnormal excitability of brainstem reflex circuits because of impairment of descending control pathways. We hypothesized that such abnormality should show in the analysis of blink reflex responses in the form of asymmetries in response size. The study was done in 20 patients with relapsing-remitting multiple sclerosis and 12 matched healthy subjects. We identified first patients with latency abnormalities (AbLat). Then, we analyzed response size by calculating the R2c/R2 ratio to stimulation of either side and the mean area of the R2 responses obtained in the same side. Patients with significantly larger response size with respect to healthy subjects in at least one side were considered to have abnormal response excitability (AbEx). We also examined the blink reflex excitability recovery (BRER) and prepulse inhibition (BRIP) of either side in search for additional indices of asymmetry in response excitability. Neurophysiological data were correlated with MRI-determined brain lesion-load and volume. Eight patients were identified as AbLat (median Expanded Disability Status Scale–EDSS = 2.75) and 7 of them had ponto-medullary lesions. Nine patients were identified as AbEx (EDSS = 1.5) and only 2 of them, who also were AbLat, had ponto-medullary lesions. In AbEx patients, the abnormalities in response size were confined to one side, with a similar tendency in most variables (significantly asymmetric R1 amplitude, BRER index and BRIP percentage). AbEx patients had asymmetric distribution of hemispheral lesions, in contrast with the symmetric pattern observed in AbLat. The brainstem lesion load was significantly lower in AbEx than in AbLat patients (p = 0.04). Asymmetric abnormalities in blink reflex response excitability in patients with multiple sclerosis are associated with lesser disability and lower tissue loss than abnormalities in response latency. Testing response excitability could provide a reliable neurophysiological index of dysfunction in early stages of multiple sclerosis.     

Utility of visual evoked potentials using hemifield stimulation and several check sizes in the evaluation of suspected multiple sclerosis

One hundred and eleven patients with suspected multiple sclerosis (64 possible, 47 probable) and 16 with a definite diagnosis of MS were evaluated with pattern-reversal visual evoked potentials (VEPs), employing monocular full-field checks subtending 7′, 14′ and 28′ of visual angle, and right and left hemifield 28′ checks. Thirty-seven patients (29%) had a completely normal study. Sixty-six patients (52%) had abnormal responses to full-field 28′ checks, and in 13 (10%) of these, additional abnormalities were found in one or more of the other test conditions, which indicated the presence of an additional site of dysfunction in the visual pathway. Twenty-four patients (19%) with ‘normal’ full-field 28′ response had abnormalities in one or more of the other test conditions; these included prolonged latency to small size (7′ and 14′) full-field checks, abnormal responses in homonymous hemifields, and abnormal responses limited to a hemifield of one eye. Thus, the use of several check sizes and hemifield stimulation not only increases the sensitivity of VEPs in the evaluation of patients with suspected demyelinating disease, but enhances the capability of the VEP to demonstrate more than one area of visual system impairment.     

A VEP study of the visual pathway function in compressive lesions of the optic chiasm. Full-field versus half-field stimulation

Changes of the pattern reversal visual evoked potentials (VEPs) to half-field stimulation in 50 patients with compressive lesions of the optic chiasm are presented. Temporal half-field stimulation yielded abnormal responses in 85% of the eyes, showing non-recordable P100 in 50% of eyes, while in 35% the P100 was significantly attenuated or delayed. With nasal half-field the percentage of all detactable abnormalities was lower (36% of the eyes). Full-field stimulation revealed VEP abnormalities in 74% of eyes and therefore proved less sensitive than the half-field stimulation.This study adds new evidence that half-field stimulation can be an important adjunct for assessing the function of the optic chiasm.     

Latency and amplitude abnormalities of the scalp far-field P14 to median nerve stimulation in multiple sclerosis. A SEP study of 122 patients recorded with a non-cephalic reference montage

The frequency and characteristics of P14 abnormalities were investigated in 122 patients with probable (68), or definite (54) multiple sclerosis by recording SEPs to median nerve stimulation with a non-cephalic reference montage. The most frequent SEP abnormality found in our series (62% of abnormal results) combined latency increase and amplitude reduction of P14. Interindividual variability, inherent in absolute amplitude measurements, was by-passed by calculating the ration between the amplitudes of far-field P9 and P14 components, which proved to be normally distributed in controls. In spite of the strong association (P ⪡ 0.001) between the P9–P14 interpeak interval (IPL) and the P9/P14 amplitude ratio in MS patients, the latter parameter was found to be the only abnormality in 12 patients whose P9–P14 and P14–N20 IPLs were normal. Also IPLs were increased in 12 patients with normal P14 amplitudes. These results suggest that adding the P9/P14 amplitude criterion to standard IPL data might be useful to detect conduction troubles in MS patients.     

神经生长因子多药联合治疗缺血性视神经病变患者的临床疗效

目的:研究神经生长因子(NGF)多药联合治疗缺血性视神经病变(AION)患者的临床疗效。方法:选择2011年5月至2013年5月在我院接受治疗的AION患者100例(100只眼),根据数字表法随机分成观察组(50例,50只眼)及对照组(50例,50只眼)。对照组给予扩血管药和维生素神经营养性药物控制高血压或糖尿病等合并症,视情况给予糖皮质类激素治疗,观察组在此基础上另给予NGF药物治疗。对比两组疗效、对数视力、视野平均缺损值(MD)及视敏度通过图形视觉诱发电位(P-VEP100)P100波的潜伏期,观察两组不良反应。结果:观察组的总有效率为90.00%(45/50),显著高于对照组的74.00%(37/50),差异有统计学意义(P0.05)。两组在治疗后的对数视力、视野MD以及P-VEP100均有改善,但观察组的改善幅度显著大于对照组,差异有统计学意义(P0.05)。两组不良反应发生率差异无统计学意义(P0.05)。结论:NGF多药联合治疗AION患者疗效更佳,可促进患者视觉功能恢复,值得临床上推广使用。     

Eye closure affects flash VEP latency in dementia

In a group of 27 demented patients (21 with DAT and 6 with MID) with normal pattern VEP (PVEP), the latencies of the main flash VEP (FVEP) components (P1, N2, P2 and N3) were assessed both with open and closed eyes. At variance from controls, demented patients showed that both P2 and N3 components are significantly delayed with closed eyes while neither PI nor N2 timings are affected. Control studies ruled out the possibility that such an outcome might depend on a defective pupillary responsiveness and/or an impaired sensitivity to luminance changes. On these grounds it is suggested that the effect of mode of stimulation on FVEP latency in demented patients is more likely to depend on “central” than on “peripheral” mechanisms. The dependence of latency changes on closure of the eyes seems to negate the direct effect of lesions upon visual structures and suggests an impairment of the modulatory action of non-visual afferents upon the activity of the visual cortex.     

Dissociation of frontal N100 from occipital P100 in pattern reversal visual evoked potentials

We studied the relationship between occipital P100 and frontal N100 in visual evoked potentials produced by pattern reversal in normal subjects and two groups of patients. Recording derivation was critical for interpretation since both Fz and Oz electrode sites are active. In 9 patients, but no normal subjects, P100 was absent. In these patients, use of a standard Oz-Fz montage resulted in the erroneous impression of a ‘normal’ P100 since a downward deflection was produced by the inverting effect of the amplifier on an intact N100 at Fz. When both P100 and N100 were present (at Oz and Fz respectively), their latencies were usually similar but not identical which contributed to apparent latency shifts or W-shaped wave forms in the Oz-Fz derivation. We conclude that use of a non-cephalic or relatively inactive scalp position (such as the mastoid) should be used as a reference site in addition to Fz to reduce interpretive errors.     

The electroretinogram in multiple sclerosis and demyelinating optic neuritis

The electroretinogram (ERG) to flashes of white light presented under photopic conditions and the pattern reversal visual evoked potentials (PR-VEPs) from both eyes were recorded from 14 patients with multiple sclerosis (MS) with monocular demyelinating optic neuritis (DON) and from 11 patients soon after presenting with monocular demyelinating optic neuritis alone. Fifteen and 10 normal subjects, matched for age and sex, were used as controls for each group of patients respectively. In the DON group of patients and controls the flicker following ERG (FF-ERG) to white flashes of light at 40 Hz was also recorded. Skin electrodes and averaging procedures were used for all the recordings. The PR-VEP elicited with stimulation of the affected eye was absent or abnormally delayed, and the amplitude of the ‘b’ wave of ERG of the affected eye was diminished in all patients. The ‘b’ wave latency, however, was similar in both affected and non-affected eyes and the controls. There was no difference in ‘a’ wave amplitude and latency between eyes of patients and normal subjects. The FF-ERG in 8 out of 10 patients with satisfactory recordings was diminished in the affected eye. These results provide neurophysiological evidence that retinal damage is not due to loss of myelin but is an early feature of demyelinating optic neuritis. This damage preferentially affects the retinal elements associated with the generation of the ‘b’ wave of the ERG, probably the glial cells of Müller.     

Clinical correlates of brain-stem auditory evoked potential variables in multiple sclerosis. Relation to click polarity

The correlations between clinical signs and BAEP latency, amplitude and dispersion variables were investigated in 98 multiple sclerosis patients. A new dispersion variable, the wave IV–V “shape ratio” (SR IV–V), correlated most strongly with brain-stem signs (i.e., nystagmus). Severely reduced wave IV–V amplitude was frequently found in patients with vertical nystagmus or internuclear ophthalmoplegia, and interpeak latency (IPL) III–V correlated most strongly with cerebellar dysfunction (i.e., ataxia). The results may reflect different localizing ability among the various BAEP variables.The association between ataxia and increased IPL III–V was significantly stronger for BAEP to C clicks than to R clicks. Patients with abnormal BAEPs to one polarity (C or R) but not to the other, had significantly more clinical dysfunction than patients with normal BAEPs to both C and R clicks. Hence, C vs. R discordance may be interpreted to indicate possible brain-stem dysfunction.     

Neural Correlates of Alerting and Orienting Impairment in Multiple Sclerosis Patients

Background

A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test.

Results

After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (p<0.05). ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05) and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01). With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01) and an ERP parameter (CNV amplitude).

Conclusions

Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients.