Faculty Bibliography

We have studied the relationship between N70 and P100 of the pattern visual evoked potential in 98 patients with multiple sclerosis and in 59 controls. In patients with multiple sclerosis, P100 was either absent or had prolonged latency in 121 eyes (61.7%), while N70 was absent or prolonged in 97 eyes (49.5%). The total number of eyes with either N70 and/or P100 abnormalities was 137 (69.9%). Eighty eyes (40.8%) had abnormal latency of both P100 and N70, while 41 eyes showed P100 delays without corresponding N70 changes. Seventeen eyes had abnormal N70, but normal P100 latency. N70 and P100 appear to be more often absent in the definite rather than in the possible multiple sclerosis group. These data show that N70 and P100 can be independently affected in patients with MS

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities

Median nerve somatosensory evoked potentials (SEP) were recorded in 7 Cynomolgus monkeys, before and after the administration of N-Methyl 1,4 Phenyl 1,2,3,6 tetrahydropiridine (MPTP), a neurotoxin which induces a parkinsonian syndrome in primates. Following MPTP administration, the amplitude of the negative component recorded at 15 ms over the frontal derivations (N15) decreased by 70% or more. This amplitude reduction was not modified by administration of dopamine precursors. These findings shed light on recent findings in human parkinsonian patients

This paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects, patients with Alzheimer's disease (AD), progressive supranuclear palsy, confusional states, and in subjects with homonymous hemianopsia. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, the topographical distribution of all ERP components is described in detail. In 45% of AD patients, ERPs were normal; in 35%, although present, ERP components were delayed, while in the other 20% the N2 and P3 peaks could not be recorded. In patients with progressive supranuclear palsy, the normal ERP sequence was not identified. Our findings in normals and in hemianopic patients suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, SW should have different origins

In previous studies, we showed that in the monkey, systemically administered N-methyl, 4-phenyl, 1-2-3-6 tetrahydropyridine (MPTP) produces a chronic parkinsonian syndrome accompanied by spatial frequency-dependent abnormalities in both the pattern electroretinogram and visual evoked potential. We describe the effect of intravitreally administered 6-hydroxydopamine (6-OH-DA) on the pattern electroretinogram and pattern visual evoked potential of 3 aphakic monkeys. Because of the aphake condition, several complexities of intravitreal injection of 6-OH-DA could be avoided. Nevertheless, following 6-OH-DA treatment, both the phase and the amplitude of pattern electroretinogram and pattern visual evoked potential became abnormal. This abnormality was most pronounced for the higher spatial frequencies (2.5 and 3.5 cycles per degree), whereas lower spatial frequencies (0.5 and 1.2 cycles per degree) were less impaired. The effects of systemically administered MPTP on pattern electroretinogram and pattern visual evoked potential are similar to the effects of intravitreal injections of 6-OH-DA, suggesting that a retinal catecholaminergic system plays an important role in pattern vision of primates

Using an auditory 'oddball' paradigm and classical conditioning, we have studied auditory evoked potentials (AEPs) and P300-like potentials in monkeys pre- and post-MPTP treatment. Free-field acoustic stimuli were 500 Hz and 4000 Hz tones, which were designated as the 'frequent' and 'rare' conditions, respectively. The 4000 Hz stimuli were reinforced with mild somatosensory electrical stimulation. During the first few weeks following 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) administration, all monkeys gradually developed a parkinsonian syndrome, which partially, but not completely improved within 30-40 days in 2 animals. The amplitudes of the AEP were initially significantly decreased, but progressively returned to pretreatment magnitudes in the 2 monkeys which partially recovered. P300-like potentials were initially abolished in all animals; however, 30-40 days later P300 spontaneously re-emerged in the same 2 monkeys. Latencies of both of these signals were unaffected by MPTP. Acute administration of dopamine precursor during the first phase of neurotoxicity partially and temporarily improved depressed AEP amplitudes, but did not restore absent P300-like potentials. The relevance of these results for Parkinson's disease is discussed

The pattern visual evoked potential (PVEP) and pattern electroretinogram (PERG) were studied in 5 cynomolgus monkeys before and during the development of a parkinsonian syndrome induced by MPTP. The stimuli were vertical bars of four spatial frequencies (0.5, 1.2, 2.5 and 3.5 cycles/degree (cpd) modulated at temporal rates of 1, 4, 6, and 8 Hz. Following MPTP administration, all monkeys developed parkinsonian signs accompanied by changes in the amplitude and latency of the PVEP and PERG. Sinemet L-dopat carbi olopa administration produced temporary recovery of both PVEP and PERG. Two of the monkeys were followed for a prolonged period: 30-40 days after MPTP, the parkinsonian signs showed partial recovery; the PVEP latency and amplitude to 2.5 and 3.5 cpd stimuli and the latency to 1.2 cpd showed improvement but remained abnormal. The latencies of PERGs were normal, but the amplitudes were significantly reduced when stimuli of 2.5 and 3.5 cpd were used. Both PVEP and PERG to 0.5 cpd stimuli returned to normal. No further modifications were seen in the recordings performed 6 months and 1 year later. This study demonstrates (1) that spatial frequency-dependent electrophysiological abnormalities occur in the MPTP-treated monkey, a result previously found in human Parkinson's disease, and (2) that dopamine has a specific function in neurotransmission in the visual system of primates