VEP and PERG in patients with multiple sclerosis, with and without a history of optic neuritis.

PURPOSE: Visual electrophysiology is routinely used to detect the visual complications of multiple sclerosis, but the analysis mostly focuses on visual evoked potential (VEP) and especially the P100 component. Our goal was to analyze the components and waveform alterations of VEPs and pattern electroretinograms (PERGs) in patients with multiple sclerosis (MS) with good vision. METHODS: The main VEP and PERG components of 85 patients with MS were analyzed in two groups: 38 patients who had optic neuritis in their history (ON group) and 47 patients who had never had optic neuritis (MS group). The results were compared against a control group of 47 healthy subjects. RESULTS: Both VEP and PERG alterations occurred in a greater number of patients than expected, and these alterations were not necessarily linked to ON in the history or a deterioration of visual acuity. CONCLUSIONS: Both VEP and PERG can detect dysfunction in the visual system in MS, even if the patient has no subjective symptoms. Even if PERG is not routinely used in neuro-ophthalmology, the results suggest that PERG assessment may provide useful information describing the retinal defect in MS.

Interocular amplitude differences of multifocal electroretinograms obtained under monocular and binocular stimulation conditions.

PURPOSE: To compare the interocular amplitude differences of the multifocal electroretinograms (mfERGs) evoked by either monocular or binocular stimulation in healthy subjects with good vision. METHODS: Thirty-five subjects were included in the study. A Roland Consult RETIscan system was used. DTL electrodes were employed. First, the right and left eyes were stimulated separately, then, binocular stimulation was applied. The amplitudes of the scalar products were averaged over five concentric retinal regions (rings). RESULTS: The interocular amplitude differences were 21.55% (SD: ±12.72) under monocular conditions and 18.69% (SD: ±11.64) under binocular conditions. No significant differences were found between the amplitudes and variability values obtained under either monocular or binocular stimulation. CONCLUSIONS: Our results provided no evidence for the advantage of either binocular or monocular stimulating conditions in obtaining mfERGs. A considerable side difference was found between the mfERGs of the two eyes in almost all individual cases.

Clinical and genetic findings in Hungarian patients with X-linked juvenile retinoschisis.

PURPOSE: To determine clinical phenotypes, examine the age dependency of X-linked juvenile retinoschisis (XLRS), and identify mutations in the retinoschisis1 gene (RS1) in 13 Hungarian (Caucasian) families with this disease. METHODS: This study included 72 members in 13 families. Complete ophthalmological examinations, including optical coherence tomography (OCT) and full-field and multifocal electroretinography (ERG), were performed on 20 affected males, 13 female carriers, and 27 healthy controls. The patients were divided into two age groups (Group I <25 years and Group II >25 years), retrospectively, to assess the possible effects of age. Correlations among genotype, age, best corrected visual acuity (BCVA), OCT, and ERG results were analyzed. A modified classification scheme was done to identify the different phenotypes of the disease. In each of the 72 family members and 100 age-matched male controls, all exons and introns of RS1 were amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: Foveal retinoschisis was detected in 25 eyes (62.5%) of patients by funduscopy, and in 29 eyes (72.5%) by OCT, while macular lamellar schisis was recognizable only by OCT in 30 eyes (75%) of patients. Foveal thickness (FT) and total macular volume were significantly increased in younger (Group I) patients only. For patients younger than 26 years, large inner nuclear central cysts were observable by OCT, while after 26 years, foveas were atrophic. White flecks and dots, which were like that seen in fundus albipunctatus, were detected in both eyes of one patient. In both patient groups, characteristically decreased b-waves of standard combined ERG were recorded without any significant difference between the patient groups. The BCVA and ERG parameters of all patients and the OCT of younger patients were significantly worse (p<0.05) than those of age-matched controls. A significant difference between the two age groups was found in case FT, total macular volume, and amplitudes of rod b-wave only. Moderate negative correlation (r=-0.54, p<0.001) was detected between age and FT, while only low negative correlation (r=-0.33, p<0.05) was detected between age and standard combined b-wave amplitudes of full-field ERG. BCVA LogMAR did not show any obvious correlation with age (r=-0.14, p=0.39) or with the type of mutation. Nine different mutations were identified in 25 male patients and 31 female carriers of 13 families: six known and one novel missense mutation (c.575C>T, p.Pro192Leu), one insertion mutation (c.579dupC, p.Ile194Hisfs29ext43), and one frameshift, causing splice site mutation (c.78+1G>C) were detected. These mutations were absent in the 100 age-matched male control samples. CONCLUSIONS: Foveal cystic schisis was found more often by OCT than by funduscopy (+10%), while flat macular lamellar schisis was recognizable only by OCT. Advancing age inversely influenced the size of cavities (FT), and standard combined b-wave amplitudes of full-field ERG, while BCVA, response density, and implicit times of multifocal electroretinography did not show any obvious correlation with age. The atrophic stage of the disease was observable after 26 years of age. The lesions that appeared to be indicative of fundus albipunctatus were proven to be palisades between the splitted retinal layers. Our modified classification scheme was helpful in assessing the prevalence of disease types. In these Hungarian patients, one novel and eight known mutations were detected. The distribution of mutations in RS1 was different to that reported in the literature, because the greatest number of different mutations was in exon 6 instead of exon 4. Two mutation hot spots were found: between c.418-422 in exon 5 and between c.574-579 in exon 6. Genotype-phenotype correlation was not demonstrable.

Familial multiple sclerosis: case study of three affected siblings.

We report on three sisters with new-onset multiple sclerosis (MS). The symptoms of the eldest sister began in 1993 with lower-limb weakness and paraesthesia. In 1998, she had limb weakness, nystagmus and ataxia. Magnetic resonance imaging (MRI) of the brain, the cerebrospinal fluid (CSF) examinations, and evoked potentials verified MS. The middle sister exhibited left-side optic neuritis in 1998. All findings pointed to MS. The third sister had subjective complaints such as paraesthesias and vertigo. MRI and CSF results supported the diagnosis. Both parents and all four grandparents are without neurological signs; the brain MRI examinations on the parents were negative. The prevalence of familial MS in first-degree relatives is 5-10%, while that in twins is 20-30%. In this case, environmental factors seem to play the crucial role. Although the anamnesis as concerns MS proved negative in the other family members examined here, further genetic examination of the sisters is needed.

Spatial contrast sensitivity of migraine patients without aura.

Visual disturbances are frequent symptoms in migraine. Since there is a possibility of separate damage in the magno- or parvo-cellular visual pathway in migraine patients, we performed a study including the measurement of static and dynamic spatial contrast sensitivity on 15 patients suffering from migraine without aura under photopic and scotopic conditions. Fifteen healthy volunteers without primary headache served as controls. The results revealed a marked decrease in contrast sensitivity at low spatial frequencies in the migraine patients. Spatial contrast sensitivity demonstrated some lateralization, as the sensitivity to low spatial frequencies obtained through separate eyes showed significantly larger side-differences in migraine patients than in control subjects. These findings suggest that the mechanisms responsible for vision at low spatial frequencies are impaired in migraine patients. This might indicate impaired function of the magnocellular pathways in this condition.

Effect of late surgery for acquired esotropia on visual evoked potential.

PURPOSE: To asses the effect of strabismus surgery on visual evoked potential (VEP) amplitude after age 5 years in children with acquired esotropia. METHODS: Visual evoked potentials to binocular and monocular pattern reversal stimulation were recorded in 10 children aged 5 to 6 years before and 3 months after surgical correction of their esotropia. Visual function (fusion) was tested by synoptophore after strabismus surgery. Electrophysiological and clinical data were correlated following surgical intervention. RESULTS: A significant increase in pattern VEP amplitudes was noted following strabismus surgery. Visual evoked potential changes were most prominent on binocular stimulation. Binocular fusion showed similarly significant improvement after intervention. Postoperative VEP data, however, were not consistently correlated with functional improvement. CONCLUSION: Surgical intervention in esotropia, even if performed years beyond the end of the classical critical period, can have a strong effect on binocular VEPs and a beneficial effect on the development of binocular fusion.

Fluorescein-ERG, a sensitive method for the detection of vascular damage in diabetic patients.

The purpose of this paper was to provide evidence for the reintroduction of simultaneously performed fluorescein angiography and electroretinography in the detection of diabetic retinopathy. ERG observations were made in conjunction with fluorescein angiography of 13 patients suffering from type I diabetes mellitus for five to 13 years. Only patients without any fluorescein leakage during angiography and without any morphologic changes in the fundus were involved in the study. Gold foil electrodes were used for recording. A stroboscopic lamp provided flashing light stimulation through a monochromatic blue filter. Intravenous fluorescein administration caused an immediate reduction in the ERG response. This reduction was seen both in the control subjects and in diabetes patients. In the control group, the reduction was over in 30-45 min, while in the diabetes group a considerable amplitude elevation was seen in all recordings between 15 and 60 min post-fluorescein. In the adaptation control group, where only repeated ERG recordings were employed every 15 min, a slight decrease in the a wave and a slight elevation of the b wave were observed during the whole recording period. No complaints or side-effects were detected during the observations. As all the patients displayed a normal fluorescein angiography besides elevated b wave after fluorescein administration, and this elevation was seen exclusively in the diabetic group, our study raises the possibility that this diagnostic method can be used in the detection of diabetic retinopathy.

Human oscillatory potentials: components of rod origin.

Oscillatory potentials (OPs) evoked by white flashing light after dark or light adaptation (WDA and WLA conditions) and those evoked by blue flashing light stimulation against a dark background (BDA condition) were recorded in 16 healthy volunteers. When blue flashing light was employed over a scotopic background, the two major OPs of this response (OP2 and OP3) appeared with a latency time that sharply coincided with the third (OP3) and fourth (OP4) components of the OPs evoked by white flashes. The results provide evidence in support of the notion that various elements of OPs represent the activities of different retinal mechanisms, of which OP3 and OP4 seem to be of rod origin.

Electrophysiological and 99mTc-HMPAO-SPECT studies in Menkes disease.

A diagnosis of Menkes kinky hair disease was made in two brothers who had typical clinical symptoms and laboratory findings. The older one, 11 months old at the time of diagnosis, showed an EEG pattern of low amplitude and slow waves. Visual evoked potentials (VEPs) were absent, brainstem auditory evoked potentials (BAEPs) were abnormal. Regional cerebral blood flow (rCBF) studied by hexamethylpropyleneamine oxime single photon emission computed tomography (99mTc-HMPAO-SPECT) revealed reduced blood flow in both frontal and the right temporal regions. The younger boy, followed from birth, started seizures at the age of 3 months and had a hypsarrhythmia-like EEG. BAEPs were abnormal with prolongation of the latencies at the age of 12 months, while VEPs were near normal at 6 months, but disappeared by the age of 18 months. 99mTc-HMPAO-SPECT revealed an unexpected left parietal hyperperfusion.

Electrophysiologic alterations in patients with optic nerve hypoplasia.

The clinical and electrophysiologic data (electroretinograms and visual evoked potentials) were studied in 45 patients with optic nerve hypoplasia. The patients were divided into three fairly distinct groups on the basis of their electrophysiologic alterations. Group 1 consisted of 13 patients with almost extinguished visual evoked potentials and with mild electroretinographic alterations. These were the cases that are traditionally recognized as optic nerve hypoplasia. The serious visual impairment in these cases was accompanied by various developmental ophthalmologic and nonophthalmologic abnormalities. Group 2 included 26 patients without any significant visual evoked potential or electroretinographic alterations, but with overt funduscopic signs of optic nerve hypoplasia. These patients were consistently suffering from strabismus and/or amblyopia. The visual functions based on visual evoked potential and electroretinographic recordings could be fairly normal apart from a pathologic ophthalmoscopic picture characteristic of optic nerve hypoplasia. Group 3 included six patients with abnormal albeit well-recordable visual evoked potentials and subnormal or negative-type electroretinograms that suggested an accompanying retinal disease. This finding seems to prove that a subset of patients with optic nerve hypoplasia with nystagmus may have a primary retinal abnormality. Our study provides further evidence that optic nerve hypoplasia is not a uniform disease entity.

Vogt-Koyanagi-Harada syndrome.

The case history is presented of a 40-year-old White women with the Vogt-Koyanagi-Harada syndrome, who was successfully treated with a combination of low-dose prednisolone and cyclosporine. A. Cellular and humoral hypersensitivity to uveal and retinal antigens were demonstrated in the patient.

Visual evoked potentials during the early phase of optic nerve compression in the orbital cavity.

We obtained case histories and electrophysiologic recordings from four patients with transient vision impairment due to acute orbital compression. The visual evoked potentials (VEPs) displayed alterations that depended on the size and consistency of the compressing pathology and also on the duration of the compression. This study provides evidence of the utility of the VEP in the assessment of the severity and reversibility of optic nerve lesions. The case histories also emphasized the necessity to elucidate the pathologic process of compressive lesions of the optic nerve.

Ultrastructural investigations in late infantile type of ceroid lipofuscinosis (Jansky-Bielschowsky).

Ultrastructural findings of biopsy materials of four gipsy first cousin infants suffering from late infantile type of ceroid lipofuscinosis (Jansky-Bielschowsky) were investigated. The diagnostic significance of the conjunctival biopsy is emphasized. The pericytes and the vascular smooth muscle cells of the arterioles proved to be the main inclusion storing cells.

[Electrophysiologic signs of macular diseases]. / Elektrophysiologische Zeichen bei Makulakrankheiten.

In the past two years, we have treated 80 patients at our clinic for regional changes in the macula lutea. The results of the electrophysiological investigations carried out on these patients are reported: scotopic and photopic whole-field electroretinography (ERG), pattern ERG, and analysis of the visual flash- and pattern-evoked potentials. These different tests are suitable for assessing various types of pathological retinal function. Electrophysiological methods are appropriate for evaluating the degree and progression of the disease. In certain hereditary diseases of the retina, such as in Stargardt macular degeneration and in a few early cases of sex-related retinoschisis, electrophysiological data can also be valuable in making a differential diagnosis.

ERG electrode in pediatric patients: comparison of DTL fiber, PVA-gel, and non-corneal skin electrodes.

Hard contact lens electrodes have been the type most frequently used in pediatric electroretinography but they are not well-tolerated by patients. The Dawson Trick Litzkow fiber electrode is better tolerated but it is fragile and difficult to sterilize. A new electrode made from anomalous polyvinyl alcohol gel is inexpensive, has stable electrical recording properties, and can be discarded after use. Dermal electrodes have been used for electroretinogram recording for some time; however, there are few reports that directly compare their performance against standard contact lens assemblies. We compared the DTL and the polyvinyl gel electrodes in the same group of subjects and investigated their recording characteristics along with non corneal skin electrodes placed on the infraorbital ridge. Signal-averaged electroretinogram were obtained under both scotopic and photopic stimulation conditions and the implicit time and amplitudes of the a- and b-waves were determined. Overall, dermal recordings generally had shorter implicit times and lower amplitudes than with the fiber or gel electrodes. The dermal electrodes were best tolerated and outlasted the corneal in repeated use. Since amplitude characteristics of the dermal electrodes were generally about 50% of that obtained with corneal electrodes, we feel that under standardized conditions they are acceptable for most clinical recording situations in infants and young children.