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

2. 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

3. 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.

4. 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 International System, but only several electrodes are sufficient (and only two to four channels).

5. 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

6. 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

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

8. 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 – or more EP
BAEP – 1000 – 2000 – 4000 EP

9. Averaging enhances a low-level signal
Bickford RG 1979

10. 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

11. 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)

12. 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)

13. 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

14. 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)

15. Parameters influencing VEP:
total stimulation field size (the 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…

16. Electrode placement

17. 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

18. Normal VEP
Nevšímalová, 2002

19. 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)

20. Normal VEP nomenclature (Stejskal, 1993)
Halliday
Celesia
Lueders

21. 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)

22. 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

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

24. Development of retrobulbar neuritis
Hopkins 1993

25. 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

26. Brainstem auditory evoked potentials (BAEPs)
middle-latency (8-60 ms)
long–latency ( 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

27. 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)

28. Examination of BAEP: registration on the scalp, electrode placement

29. 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

30. Normal BAEP

31. 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?

32. BAEP components and the auditory pathway

33. BAEP components and the auditory pathway

34. 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…)

35. 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

36. Abnormal BAEP

37. Abnormal BAEP

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

39. 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