Evoked potentials II VEP, BAEP doc. MUDr. Valja Kellerová, DrSc. Department of Neurology

Definition of evoked potentials (EP): EP are the electrical manifestations of the response of the nervous system to certain external stimuli a response is in the appropriate cortical receptive area it is time-locked to the evoking stimulus MEP is the response to magnetic transcranial stimulation, registered from the muscle

History In 1947, Dawson in England first revealed a short electrical response elicited by the patellar reflex or by a short electrical stimulus applied to the ulnar nerve. It was recorded in the routine EEG (on the scalp) prevailing in the contralateral central region in a patient with myoclonic seizures. Dawson then examined a group of 14 healthy persons and he found the same responses, but their amplitude was very low.

Principle of acquisition of EP Stimulation of any sensory receptor evokes a minute, tiny electrical signal (for only a few microvolts) in the cerebral cortex. But this signal is overlapped by EEG or EMG activity (as a noise). The EP is recorded from electrodes placed on the patient´s scalp The same kind of electrodes are employed, as in EEG, and electrode placement may follow the 10-20 International System, but only several electrodes are sufficient (and only two to four channels).

Principle of acquisition of EP What is registered in reality is a mixture of evoked and spontaneous electrical activity. More often, the spontaneous activity is of much greater amplitude than the evoked activity. The evoked activity is the “signal” we desire to record and the background activity is “noise”. It is necessary to subtract evoked responses from the random EEG activity (the „noise“). Methods: superimposition (history) averaging

Photographic superimposition Dawson used a photographic technique of superimposition in 1947 EEG activity after the stimulus was registered by a cathode-ray tube and was recorded on photographic film. Repeated responses were recorded on the same position on the film, making higher exposure, whereas EEG activity of random phase makes low exposure and is suppressed. This method does not permit accurate quantification of the waveform´s features

VEP obtained on a cathode-ray tube using Dawson´s superimposition technique (Cigánek L., 1964)

Signal averaging introduced by Dawson, in 1954 the stimulus and the start of averaging have to be synchronized EP are time-locked to the evoking stimulus Since the brain´s spontaneous electrical activity is essentially random with respect to the stimulus, algebraic summing of the signal causes the spontaneous activity to sum to zero, whereas the evoked activity will sum linearly the number of responses averaged: VEP – 100 - 200 or more EP BAEP – 1000 – 2000 – 4000 EP

Averaging enhances a low-level signal Bickford RG 1979

Procedure of evaluation and interpretation: the identification of the various components of EP measuring of components: absolute peak latencies interpeak intervals amplitude morphology – the shape of EP Comparison of the relevant parameters of the patient´s EPs with a set of norms (according to sex, age): from the literature from the laboratory - the own normative data sets

The clinical utility of EPs EPs are objective and quantitative measures of function disorders of sensory systems EPs help define the lesion localization EPs - often more sensitive than detailed neurological examination, can reveal subclinical involvement of a sensory system (‘‘silent’’ lesions) disadvantage: EPs are rarely disease specific can be confounded by end organ disease (for example, VEPs may be abnormal in ocular disease, SSEPs in peripheral neuropathy, and BAEPs in deafness)

Classification of EPs: according to a sort of stimulus (sensory modality): visual evoked potentials (VEPs) to: flash stimuli pattern reversal stimuli somatosensory evoked potentials (SEPs) brainstem auditory evoked potentials (BAEPs)

Examination of VEP: the stimulation Flashes Cigánek, 1961 in infants, without cooperation, shows rough lesions only wide variability, less sensitive to disease than the pattern-reversal VEPs, less reliable for clinical use

Examination of VEP: the stimulation Structural, patterned stimulus checkerboard stimuli with black and white squares black and white squares reverse their position - pattern reversal the patient is asked to fixate on a dot in the centre of the monitor (= the macular area of the retina is stimulated) stimulation of one eye (monocular) full-field stimulation: evaluating the anterior visual pathways (optic nerves and chiasm) half-field stimulation - the chiasmal and retrochiasmal visual pathways (optic tract, radiation and visual cortices)

Parameters influencing VEP: total stimulation field size (the 20-30 degrees of visual angle) size of the checks luminance, contrast stimulus rate (1-2 Hz) analysis time (300 or 250 ms) number of EP averaged (100, 200, 400) at least two trials (averages) should be done to ensure that EP are replicable patient´s cooperation, vigilance, visual acuity (corrective glasses), pupil size…

Electrode placement

Electrode placement active (recording) electrodes – occipital areas Oz, O1, O2 (10/20 system) or 5 cm above the inion (Halliday) midline 5 cm (and 10 cm) lateral to the midline electrode (right and left) reference electrode Fz or Cz (vertex) or 5 cm in front of Cz the ground electrode - Fpz

Normal VEP Nevšímalová, 2002

Normal VEP The normal VEP often contains 3 peaks: The initial peak is negative and occurs at a mean latency of 75 ms, it is designated N75 The most prominent and consistent wave is a positive peak, a mean latency of 100 ms, called P100 A subsequent negative peak at a mean latency of 145 ms (N145)

Normal VEP nomenclature (Stejskal, 1993) Halliday Celesia Lueders

Measurements of VEPs, normative data Presence and replicability of VEPs identification of the main components N1 – P1 – N2 peak latencies (and interpeak latency N2-N1) amplitude N1/P1, P1/N2 shape of EP (for instance 2 peaks - „W“ shaped configuration) interocular difference in P1 latency comparison of the patient´s EPs with a set of norms each laboratory should establish its own normative data, have its own control group (age, gender, parameters of stimulation and recording…) with normal values and the boundaries of normality (3SD)

Abnormal VEP, clinical correlation absence of a VEP on monocular stimulation – a lesion of the ipsilateral optic nerve prolonged P100 latency demyelination of the anterior visual pathway a lesion of the ipsilateral optic nerve at times abnormalities detected are subclinical, „silent“ (in multiple sclerosis) interocular difference in latency P100 – optic nerve lesion – retrobulbar neuritis amplitude attenuation P100 – axonal lesion, in compressive lesions (tumours) half-field stimulation - retrochiasmal disorders, but not yet sufficiently reliable and sensitive VEP abnormalities are nonspecific

Abnormal VEP (Růžička, 1997) retrobulbar neuritis on the left eye: latency of P1 is 161 ms

Development of retrobulbar neuritis Hopkins 1993

Use of VEP in neurology Diagnosis of multiple sclerosis (MS) optic nerve demyelination optic neuropathy is often the first sign of MS in definite cases of MS, abnormalities in VEP occur in about 85-90% of patients the changes in the P100 response include expressive interocular difference in latency prolonged absolute latency decreased amplitude, and distorted shape compression of the optic nerve and chiasm by tumours – decreased amplitude and prolonged latency of the P100 response

Brainstem auditory evoked potentials (BAEPs) middle-latency (8-60 ms) long–latency (50-250 ms) in the past - used in objective audiometry wide variability BAEP short - latency, an analysis time of 10 ms generated in the auditory nerve and the brainstem auditory pathways in response to auditory stimuli low variability can be recorded from comatose patients, during narcosis or sleep patient´s cooperation is not necessary

Examination of BAEP: stimulation brief acoustic stimulus (click) monoaural (headset) stimulus intensity: patient´s hearing threshold + 60 dB, with contralateral white noise masking stimulus rate 10 Hz or higher change of stimulus parameters (intensity, rate) cause change of BAEP (in latency, amplitude…) reduced intenzity of the auditory stimulus – the latency of peaks increases and the peak amplitude decreases (audiometry)

Examination of BAEP: registration on the scalp, electrode placement

Electrode placement, recording, averaging active (recording) electrode – Cz, vertex reference electrodes – mastoids (or earlobes) the ground electrode - Fz or Fpz analysis time - 10 ms number of EP averaged (1000 – 2000 – 4000) at least two trials (averages), to ensure that EP are replicable

Normal BAEP

Normal BAEP consists of between 5 to 7 vertex positive peaks, the principal peaks (waves) I-V are of clinical interest I, III, V waves are the most stable, constant they arise at the different levels of the auditory pathway the BAEP components are believed to reflect activity in: wave I – in the auditory nerve (distal part) wave II – proximal part of n.VIII and cochlear nucleus wave III – lower pons, superior olivary nucleus waves IV and V – upper pons or lower midbrain (inferior colliculus), lateral lemniscus VI – corpus geniculatum mediale? VII – radiatio acustica?

BAEP components and the auditory pathway

BAEP components and the auditory pathway

Measurements of BAEP components presence and identification of waves,especially I, III, V peak latencies of all waves, especially I, III, V interpeak latencies reflect conduction in: I-III latency – between auditory nerve and the lower pons III-V latency – between the lower pons and midbrain I-V latency – the total conduction time whithin the brain-stem auditory pathway (between auditory nerve and midbrain) amplitudes of waves I and V and the peak amplitude ratio between V and I inter-ear difference (in peak latencies, and I to V interpeak latencies) comparison of the patient´s EPs with a set of norms (age, gender…)

Abnormal BAEP, clinical applications complete loss of all waveforms – hearing loss or lesion of n.VIII prolongation of all peak latencies (with normal interpeak latencies) – lesion of n.VIII prolongation of some interpeak latencies – brainstem lesion loss of a wave and following waves – lesion at the level of the generator of this wave absence of waveforms following wave I (all the subsequent waveforms are absent) – severe lesion or brain death wave III, IV – pons wave V – midbrain prolongation of peak and interpeak latencies - demyelination

Abnormal BAEP

Abnormal BAEP

Abnormal BAEP (compression of the brainstem by a left acoustic neurinoma, only wave I is present)

Use of BAEP in neurology Localization of brainstem lesions involving the auditory pathway Eight-nerve tumour (acoustic neurinoma) wave I may be absent the I to III interpeak latency may be prolonged in compression of the brain stem, the III to V interpeak latency may be prolonged Demyelinating disease – prolonged interpeak latencies Coma – detecting structural lesions of the brain stem Diagnosis of brain death – only wave I shoul be present