Pattern-reversal visual evoked potentials in photosensitive epilepsy

VEPs to checkerboard pattern-reversal were recorded from 18 epileptic patients who had EEG photoparoxysmal responses to stroboscopic light. Patients were grouped according to whether seizures were precipitated by environmental light stimuli, or television viewing. Longitudinal studies were conducted on 8 patients treated with valproic acid. We concluded the following: (1) Latency of the major positive peak (P2) of the pattern-reversal VEP was shorter among photosensitive patients than among normal controls. This was especially true of television-sensitive patients. (2) Valproic acid, when effective in controlling seizures, lengthened the P2 latency and decreased VEP amplitude. Studies of drug effects on VEPs may help to elucidate neurochemical mechanisms of the visual cortex. (3) Because of overlap of values with normals, VEP measurements are not at present very sensitive in the diagnosis of photosensitivity. However, longitudinal studies in individuals parallel clinical changes and may be useful as objective measures of improvement.     

Multichannel visual evoked potentials in migraine

Multichannel recordings of visual evoked potentials (VEPs) have proved to be useful in the evaluation of visual field defects. We studied the topographic distribution of transient VEPs in 15 migraine patients (8 with visual aura and 7 without) and 15 age-matched controls during the migraine-free interval. All the subjects included in the study had normal visual fields. VEPs were recorded from 9 electrodes placed on the posterior scalp. Stimuli were full-field and hemifield reversing square wave grating patterns of medium spatial frequency (4 c/deg). The groups did not show significant differences in latencies and amplitudes of the major components (N70, P100) recorded from the midline. However, migraine patients with visual hemianopic aura showed definite asymmetries in the VEP amplitude distribution. Significantly reduced, absent or polarity-invered VEP responses were recorded ipsilateral to the side of the prodromic visual symptoms. Direct comparison of affected and unaffected hemispheres by partial field stimulation confirmed these findings. According to the VEP cortical generator theory, these abnormalities suggest a functional anomaly consistent with the clinical syndrome and detectable also in the migraine-free interval. None of the migraine patients without aura or the controls showed VEP amplitude asymmetries. We conclude that multichannel VEP recordings may discriminate between different subtypes of migraine and contribute important physiopathological information to the study of this disease.     

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.     

Clinical Utility and Limitations of Intraoperative Monitoring of Visual Evoked Potentials

Objectives

During surgeries that put the visual pathway at risk of injury, continuous monitoring of the visual function is desirable. However, the intraoperative monitoring of the visual evoked potential (VEP) is not yet widely used. We evaluate here the clinical utility of intraoperative VEP monitoring.

Methods

We analyzed retrospectively 46 consecutive surgeries in 2011-2013. High luminance stimulating devices delivered flash stimuli on the closed eyelid during intravenous anesthesia. We monitored VEP features N75 and P100 and took patients'' preoperative and postoperative visual function from patient charts. Postoperative ophthalmologic workup was performed in 25 (54%) patients and preoperatively in 28 (61%) patients.

Results

VEP recordings were feasible in 62 of 85 eyes (73%) in 46 patients. All 23 eyes without VEP had impaired vision. During surgery, VEPs remained stable throughout surgery in 50 eyes. In 44 of these, visual function did not deteriorate and three patients (6 eyes) developed hemianopia. VEP decreased transiently in 10 eyes and visual function of all was preserved. VEPs were lost permanently in 2 eyes in two patients without new postoperative visual impairment.

Conclusions

Satisfactory intraoperative VEP monitoring was feasible in all patients except in those with severe visual impairment. Preservation of VEPs predicted preserved visual function. During resection of lesions in the visual cortex, VEP monitoring could not detect new major visual field defects due to injury in the posterior visual pathway. Intraoperative VEPs were sensitive enough to detect vascular damage during aneurysm clipping and mechanical manipulation of the anterior visual pathway in an early reversible stage. Intraoperative VEP monitoring influenced surgical decisions in selected patients and proved to be a useful supplement to the toolbox of intraoperative neurophysiological monitoring.     

Prognostic value of visual evoked potentials in occipital blindness following basilar artery occlusion.

Three patients suffering from sudden occipital blindness following basilar artery occlusion underwent electroretinography and visual evoked potential (VEP) examinations. The VEPs performed early in those blind patients and repeated later seem to be of prognostic value. Responses of normal shape and amplitude after monocular and binocular stimulation were followed by complete recovery of vision. Unequal and subnormal VEPs obtained following monocular stimulation, and even smaller responses reached after binocular stimulation, accompanied permanent unilateral occipital damage resulting in homonymous hemianopsia. Lack of VEP was proved to be a preceding sign of permanent blindness.     

Effects of chronic high serum levels of phenobarbital on evoked potentials in epileptic children

We studied VEP and BAEP in 8 epileptic children with chronic high serum levels of phenobarbital. Records were obtained when the drug serum level was more than 40 mg/l and repeated when serum concentrations was within the normal range. During the periods of high levels, P2 latency of the VEP was abnormally increased in all cases but one. The mean P2 latency decreased according to the reduction of the serum level of phenobarbital (139.6 msec vs. 110.1 msec, P = 0.002), and a significant regression coefficient (r = 0.546, P = 0.0271) w also noted between P2 latency and drug serum concentration. BAEPs were normal in all cases but one, who had a coexisting high level of phenytoin.All these findings suggest that the pharmacological effect of phenobarbital may be detected by VEPs and may result in delay of the P2 component.     

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.     

Mapped distribution of pattern reversal VEPs to central field and lateral half-field stimuli of different spatial frequencies

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli of 3 different sizes (1, 2, 4 c/deg) were recorded from 19 scalp derivations in 50 controls. The stimuli were presented on a full-field (FF) screen of 24° visual angle, and on left and right half-fields (HF) of 12° radius. In 15 controls partial HF stimuli were presented on the central 3 and 6° and as hemiannular stimuli of 12° with occlusion of the central 3 and 6°.An antero-posterior polarity reversal of the N1-P1-N2 sequence was observed for FF VEPs. A tangential polarity reversal was observed for HF VEPs. Also with central or hemiannular stimuli polarity reversals of all VEP components were observed within the scalp.Variants of VEP distribution, absence of prominence of some of the ipsi- or contralateral VEP components were observed in 8–40% of controls.The FF and HF VEP distribution, and the variant VEP asymmetries were partly dependent on the pattern spatial frequency.     

Three-dimensional human pattern visual evoked potentials. II. Multiple sclerosis patients

Pattern visual evoked potentials were obtained from 46 patients with definite relapsing/remitting multiple sclerosis, using both a conventional 5-channel occipital array and a 3-D recording technique consisting of three bipolar derivations approximating the three dimensions of space. These three orthogonal wave forms were displayed as a 3-D Lissajous trajectory for each subject. Two of the 15 patients with completely normal conventional pattern VEPs had abnormalities of the orientation of the B-C curvilinear segment of the 3-D pattern VEPs. Delays in the first major occipital positive component (P100) were evident using both techniques; the correlation between P100 latency and the latency of the corresponding trajectory apex was r = 0.99 (P < 0.01). Post-chiasmal MRI abnormalities were associated with 3-D VEP orientation abnormalities. Three-dimensional pattern VEPs are moderately more sensitive than conventional pattern VEPs at detecting dysfunction posterior to the optic chiasm in demyelinating disease and do not require the use of eccentric fixation to do so.     

Electrophysiological exploration of visual function in mitochondrial diseases

In a group of 10 children (ranging from 5 months to 15 years old) affected by diseases with mitochondrial dysfunction, 4 suffered from mitochondrial myopathy, 4 from mitochondrial encephalopathy and 2 from Friedreich's ataxia. The clinically detectable visual impairment consisted of 3 grey ocular fundi (the other 7 were normal) associated, in 2 subjects, with a mild nystagmus. Electrophysiological assessment, consisting of ERGS and flash VEPs, was systematically performed. The normal ERGs in all subjects confirmed the normal functioning of retinal electrogenesis. In contrast, the VEPs of 6 out of 10 subjects were modified: in 2 of the 4 subjects with mitochondrial myopathy, the VEPs had a hyperamplitude; in the 2 subjects with Friedreich's ataxia, the implicit time of the principal VEP peaks was increased, together with a hyperamplitude in 1 case; lastly, in 2 of the 4 subjects with mitochondrial encephalopathy, the VEPs were altered. These modifications reflected visual pathway conduction disorders with no clinical expression. Various underlying pathophysiological mechanisms possibly responsible for these modifications are discussed.     

Delayed visual evoked potentials are independent of pattern orientation in macular disease

Visual evoked potentials (VEPs) and contrast sensitivity (CS) were studied in patients affected by maculopathy. VEP delays and CS reduction were demonstrated in each affected eye. In distinction to patients affected by multiple sclerosis (MS), in maculopathy patients VEP latency is independent of the orientation of the grating stimulus. It is proposed that stimulating with more than one pattern orientation is useful in the differential diagnostic use of VEPs.     

Serial pattern evoked potential recording in a case of toxic optic neuropathy due to ethambutol

Visual evoked potentials (VEPs) were studied in a patient who developed visual impairment during ethambutol treatment. The ERG and the flash VEP were normal at the time of maximal visual loss, whereas pattern reversal VEPs 2 and 5 months after onset revealed evidence of severe bilateral optic nerve involvement, especially affecting macular fibres. Seven months after onset paramacular PNP complexes with a late positivity (scotomatous response) were recorded after pattern reversal and half-field stimulation, suggesting involvement of fibres subserving central vision. At the time when visual acuity was normal there was still electrophysiological evidence of a mild involvement of the anterior visual pathway. The papillomacular bundle seems to be especially involved in ethambutol eye toxicity.     

Developmental wave form analysis of the neonatal flash evoked potential

A multiple regression technique was used to describe the wave form of the flash evoked potential (VEP) in 64 neonates born between 28 and 39 weeks of gestation. The successive appearance of new features in the VEP with increasing gestational age at birth was used to define 5 components, of which specimens were obtained by averaging VEPs of 18 selected infants. The VEPs of the other 46 infants were expressed as linear sums of the components, each multiplied by a weighting coefficient. The method accounted for 74 ± 11% (mean ± 1 S.D.) of the rms power of the observed VEPs and was used to demonstrate significant effects on wave form maturation from fetal growth retardation and maternal smoking in pregnancy.     

Effects of age and sex on pattern electroretinograms and visual evoked potentials

Pattern-electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were simulataneously recorded in 112 normal individuals aged 20–75. Two sized checks subtending 15′ and 31′ were used as stimuli. A weighted regression analysis was used to determine which of the variables, sex or age, was significant. The latency of the a and b wave of the P-ERGs showed a progressive increase with age but no difference between sexes. The effect was statistically significant for both 15′ and 31′ checks. There was no statistically significant aging effects for VEPs elicited by 31′ checks. Aging, however, affected N70, P100, and the interpeak interval between b wave to N70 and b wave to P100 for responses to 15′ checks. Shorter VEP latencies were noted in females for both 15′ and 31′ checks.The simultaneous recording of P-ERGs and VEPs has demonstrated that aging is a major variable at the retinal level. The effects on the a and b waves are mostly due to optic changes with aging and only partially to aging changes in the neuronal retinal circuitry. The effect of aging on VEPs is different for different size stimuli. The cause is a random neuronal cell loss in the visual pathways from the optic nerve to the visual cortex as the individual ages.The difference in VEP data between sexes may be related to anatomical size and hormonal influences.     

Neurophysiological effects of recombinant interferon-gamma and -alpha in man

Treatment of malignant tumors with interferon (IFN) is in some patients accompanied by serious neurological side effects. The present study assessed neurophysiological changes in spontaneous EEG activity, visual-evoked cortical potentials (VEPs), and brainstem auditory-evoked potentials (BAEPs) during IFN-gamma or IFN-alpha therapy in 9 patients. In addition, blood pressure, heart rate and body temperature were monitored. In all sessions under IFN, the latency of the P100 component of the VEP was shortened as compared to baseline conditions. IFN also reduced latencies of BAEP components, and diminished amplitudes of the spontaneous EEG activity within the alpha and beta frequency band. These latter effects were somewhat less consistent than those on VEPs. The major neurophysiological changes appeared to be similar for IFN-gamma and IFN-alpha. The results are in accord with an excitatory effect of IFN on central nervous activity. The magnitude of changes excludes a neurotoxicity of IFN-gamma or IFN-alpha at the doses used in this study.     

Synthesis and biological properties of iron chelators based on a bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide or -thiocarboxamide (BHPTC) scaffold

Bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamides and -thiocarboxamides (BHPTCs) form a family of gemini hexacoordinated bis-tridentate chelating scaffolds. Four molecules were synthesized and shown to chelate iron(III) efficiently with a 1:1 stoichiometry. A dithioamide BHPTC displayed promising antiproliferative activity in several cancerous cell lines, making this molecule an interesting lead compound for the design of new iron-chelating anticancer drugs. Conversely, diamide BHPTCs had significant cytoprotective activity against iron overload in HepaRG cells in vitro, and were as efficient as and less toxic than deferoxamine B (DFO).     

Iron chelation study in a normal human hepatocyte cell line suggests that tumor necrosis factor receptor-associated protein 1 (TRAP1) regulates production of reactive oxygen species

Iron is an essential component of many proteins, and has crucial roles in the proper functioning of proteins involved in cellular respiration, proliferation, and differentiation. It has been recently reported that the deferoxamine (DFO), an iron chelator, induces mitochondrial dysfunction, characterized by an attenuation of oxidative phosphorylation, as well as senescence-like cellular morphology. However, the effects of DFO on mitochondrial heat shock proteins (HSPs) remain poorly understood. In this study, we examined the effect of DFO on tumor necrosis factor receptor-associated protein 1 (TRAP1), a representative mitochondrial HSP, in a normal human hepatocyte cell line, Chang cells. DFO specifically decreased TRAP1 levels, increasing reactive oxygen species (ROS) and caveolin-1 (Cav-1), a marker protein of senescence. To examine whether these effects of DFO are reversed, we established TRAP1-overexpressing Chang cells. DFO treatment to TRAP1-overexpressing cells resulted in decreases in levels of ROS, Cav-1, glutathione peroxidase (GPX), and manganese superoxide dismutase (MnSOD) levels as well as senescence-associated beta-galactosidase (SA beta-gal) activity. These results suggest that TRAP1 might play a role in protecting mitochondria against damaging stimuli via decrease of ROS generation.     

Siderophore Production by Pathogenic Mucorales and Uptake of Deferoxamine B

Clinical reports have established that mucormycosis, mainly caused by Rhizopus spp., frequently occurs in patients treated with deferoxamine B (DFO, Desferal^®) which is misappropriated by these fungi. Siderophore production by twenty mucoralean isolates was therefore investigated using a commercial iron-depleted culture medium. Siderophore production was detected for most of the isolates. Our experiments confirmed that feroxamine B (iron chelate of DFO) promoted in vitro growth of Rhizopus arrhizus. Electrophoretic analysis of somatic extracts revealed iron-regulated proteins of 60 and 32 kDa which were lacking in iron-depleted culture conditions. Using a fluorescent derivative of deferoxamine B, we showed by fluorescence microscopy the entry of the siderophore within the fungal cells, thus suggesting a shuttle mechanism encompassing the uptake of the entire siderophore-ion complex into the cell. This useful tool renders possible a better understanding of iron metabolism in Mucorales which could lead to the development of new diagnostic method or new antifungal therapy using siderophores as imaging contrast agents or active drug vectors.     

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis

The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation-induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD-1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post-recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS-detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.     

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.