NEUROPAIN January’ 18

SUPPLEMENTARY
Evoked potential
• Averaging
• peak and interpeak latency
Clinical interpretation
Visual evoked potential
• abnormal pattern
Brainstem auditory evoked potential
• abnormal pattern
p300
Visual pathway
Auditory Pathway
VEP and Migraine
BAEP and Migraine
EVOKED POTENTIAL
 electricals signals generated by the nervous system in response to sensory stimuli
 a computer averaged electric responses of the nervous system to sensory stimulation
 consist of a sequence of deflections, or waves, each characterized by latency,
amplitude and other features

1. Auditory
2. Visual
3. Somatosensory
  a series of waves that reflect sequential activation of neural structures along somatosensory pathways
EVOKED POTENTIAL
EP are recorded from the surface of the body with electrodes on the scalp or on the
skin over the spinal cord or peripheral nerves
A single response to a stimulus usually has low amplitude and may be partly or
completely obscured by ongoing spontaneous EEG activity  to extract, single
responses are elicited repeatedly and averaged with a computer
EVOKED POTENTIAL
Terminology :
1. Evoked potential : indicate only the average of the individual responses
2. Response : any recording following a single stimulus
3. Peak or wave : denote the upgoing or downgoing deflection that make up
an EP
4. Component : separable contributions in the same peak or wave as in
noise component or low frequency component
4. Event-related potential : Denote both Eps and other kinds of potentials that
are the result of cognitive process following a stimulus or
of pregnancy processes preceding a movement or speech.
EVOKED POTENTIAL
Clinical use  test conduction in the visual, auditory and somatosensory system,
especially in the central part of these system
Helps to localize lesions to certain segments of a central sensory pathway
EVOKED POTENTIAL
EVOKED POTENTIAL
EPs consist of a series of upward and downward deflections called peaks or waves, which
are characterized by polarity, number in sequence, latency, amplitude, waveshape, and
distribution
EPs consist of a series of peaks or waves, each characterized by :
1. positive or negative electric polarity
2. number of wave in a sequence
 Peak was named by number of the peak in the sequence, combinations of polarity and
number of sequence, or polarity and latency
3. latency from the onset of the stimulus or from a preceding peak
4. amplitude with respect to the baseline or to the preceding or subsequent peak of
opposite polarity
5. waveshape
EVOKED POTENTIAL
EVOKED POTENTIAL
For transient EPs, latency is usually expressed either as peak latency or as interpeak latency
A. Peak latency
 the latency to a peak latency is measured from stimulus onset to the point of maximum
amplitude of a negative or positive peak
B. Interpeak latency
 Interpeak latencies (IPLs) are measured between peaks of the same EP and are
commonly used in the evaluation of BAEPs.
 They represent the time of conduction between structures that generate the peaks
Peak latency is increased by lesion in both the peripheral and central parts of the sensory
system
Interpeak latency generally increased only by central lesions but not the peripheral lesions
EVOKED POTENTIAL
EVOKED POTENTIAL
Nomenclature :
1. Polarity-latency
 combination of the letters P or N, standing for positive or negative polarity of the peak
and a number representing peak latency.
 this method is now used for most EP types except BAEPs
 ex: the major occipital positive peak of a VEP to checkerboard reversal which occurs at
about 100msec is labeled P100
2. Number of a peak in sequence
 Peaks may be named by numbering them in the order of their occurrence
 this method is used mainly for BAEPs whose peaks are labeled I-VII
EVOKED POTENTIAL
3. Polarity-number in sequence
 Positive and negative peaks may be named by the letters P and N and by a number
indicating their order of appearance among peaks of the same polarity
 useful in EPs which show more variation in latency than in number of peaks
 ex : major positive peak of the checkboard reversal VEP is named P1 and the negative
peaks preceding and following it are N1 and N2
4. Observed versus characteristic peaks
 each nomenclature may be used to describe either observed or characteristic peak
 ex: For instance, the major positive peak in the VEP to checkerboard reversal,
occurring at a latency of about 100msec in normal adults, is usually P100. The major
positive peak in the VEP of patient may appear at 140msec and is generally presumed to
represent the same peak as that occurring at 100msec in normal subject.
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Lesions in the three major sensory systems can be detected by delays, decrease of
amplitude, or abolition of the characteristic peaks of VEPs, AEPs, and SEPs
EP abnormalities are detected by comparison with control values recorded from
normal subjects
 separate control groups must be established for subjects differing in age and
other variables that cause differences in EP values
Different types of EP abnormalities have different implications. Most important are
increases in peak latency of VEPs and in interpeak latency of BAEPs and SEPs ;
these increases usually indicate a conduction defect in the sensory pathway.
Low amplitude is a less reliable indicator of lesions and is best evaluated by
calculating amplitude ratios.
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Strategy of localization and lateralization uses correlations between EP peaks and
anatomical structures foe BAEPs and SEPs, and combinations of monocular or half-
field stimulation with midline or lateral occipital recording for VEPs
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Abnormally long latency
 increased latency generally indicates decreased conduction velocity and is often
due to lesions which cause slowing of axonal conduction in the central part of the
system.
- VEP : ocular conditions that blur the retinal image
- BAEPs : cochlear lesion
- SEPs : impaired peripheral nerve conduction
 before an increased latency can be interpreted as indicating a lesion in the central
part of sensory pathway, peripheral lesions must be excluded by measure interpeak
latencies.
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Abnormally long latency
1. Abnormally long peak latency
 defect between the point of stimulation and the structure generating the EP peak
 major parameters in VEPs
 ex : stretch from retina to occipital cortex in VEPs
2. Abnormally long interpeak latency
A. acoustic nerve excitation in BAEPs serve as benchmarks that help to distinguish peripheral
lesions, which cause a delay of these peaks and all subsequent ones. Latency of the benchmark
peaks intact but delay the subsequent ones and thereby increase the IPL or central conduction time
B. Latencies between peaks may help to localized lesion to the structure in the central sensory path
C. Interpeak latencies vary less than peak latencies and are more sensitive to pathology  better
indicators of abnormal function
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Abnormal amplitude
A decrease of amplitude often accompanies the increase of latency seen in case of reduced
conduction velocity and is probably due to general slowing of conduction velocities.
Primary axonal defects  reductions of amplitude rather than increases of latency
1. Reduced amplitude :
 suggest conduction defect but usually cannot prove it
2. Abnormal amplitude ratios :
 better indicator of abnormality because is less variable
A. Amplitude ratios of peaks in the same EP are used in evaluation of BAEPs (a commonly
used is the amplitude ratio of waves V/I – indicate brainstem lesion)
B. Amplitude ratios of corresponding peaks of EPs recorded simultaneously from left and right
side of the head – unilateral hemispheric lesion ( retrochiasmal lesions of the visual pathway)
C. Amplitude ratios of peaks EPs recorded successively from midline – evaluate VEPs to
stimulation of either eye (prechiasmal abnormality)
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Abnormal amplitude
3. Complete absence of an entire EP :
 complete interruption of conduction at a point before that generating the first EP
peak.
 complete absence of an EP does not necessarily prove a conduction defect
because it may be due to other factors including peripheral problems such as eye or
ear disorder, technical problems
EVOKED POTENTIAL
CLINICAL INTERPRETATION
Correlation between EP peaks and anatomical structure
abnormality of corresponding peaks, subsequent peaks, representing excitation of
more proximal structures which receive abnormal input from the damage structure
VISUAL
EVOKED
POTENT
IAL
VISUAL EVOKED POTENTIAL
Major criteria distinguishing abnormal from normal VEPs
 the complete absence of a VEP
 an abnormality increased latency of the P100
 abnormally prolonged interocular latency

Clinical presentation
Abnormal VEP findings to detect and localize prechiasmal, chiasmal, and
retrochiasmal lesions
VISUAL EVOKED POTENTIAL
ABNORMAL PATTERN
1. Absence of VEP
 complete absence of any peak larger than residual noise
 indicate clinical defect if lack of focusing and technical problem are excluded
2. Abnormally long P100 latency
 latency of P100 is measured between the pattern reversal
 the peak of the first major occipital positive peak
3. Abnormally long N75 latency
 abnormal delay of the negative peak alone merely raise a suspicion of abnormal
conduction
BRAINSTEM AUDITORY
EVOKED POTENTIAL (BAEP)
The potentials recorded from the Ear and scalp in response to brief auditory stimuli
that assess the conduction through the auditory pathway from the auditory nerve up
to Midbrain.
Transduction of acoustic stimulus by the hair cells create an electrical signal that
appear as evoked potential an is carried through the auditory pathway to the
brainstem and from there to the cerebral cortex
BAEPs are recorded within 10ms after the acoustic stimulus  stimulus is delivered
to one ear via headphones, while the contralateral ear is masked with continuous
white noise
BRAINSTEM AUDITORY
EVOKED POTENTIAL (BAEP)
Five waveforms are recorded within 10ms of auditory stimulus
 Wave I : peripheral portion of the eighth cranial nerve
 Wave II : cochlear nucleus
 Wave III : superior olivary nucleus
 Wave IV : lateral lemniscus
 Wave V : inferior colliculi
Interpeak latencies measured are I-III, III-V and I-V  they are measured as the distance
between the peaks of both waves
 I-III : conduction from the eight nerve into the core of the lower pons
 III-V : conduction from the lower pons to the midbrain
 I-V : conduction from the proximal part of 8th cranial nerve up to the midbrain
BRAINSTEM
AUDITORY
EVOKED
POTENTIAL (BAEP)
BRAINSTEM AUDITORY
EVOKED
Abnormal BAEPs
POTENTIAL (BAEP)
1. Absence of all BAEP waves
 technical problem (lack of stimulus)
 severe conductive of sensorineural hearing loss
2. Absence of all waves following wave I or wave II
 retrocochlear lesion involving proximal acoustic nerve or the pontomedullary region of
brain stem
3. Absent wave V
 midbrain lesion
BRAINSTEM AUDITORY
EVOKED
Coma
POTENTIAL (BAEP)
A. structural lesion
 abnormal in majority due to ME but its not accurate for prognostic
 in ICH, BAEP has been found to indicate brain stem damage and predict outcome
 disappearance BAEP – has occasionally been observed to be transient even in cases of
structural damage

B. Metabolic and toxic

Normal
Stroke
Brain stem stroke : abnormal
Locked in syndrome : increased IPL III-V
BRAINSTEM AUDITORY
EVOKED POTENTIAL
Migraine can best be explained as a “Brain state”
(BAEP)
 cellular and vascular functional changes occur at the same time due to
dysfunction of subcortical structures, brainstem and diencephalic nuclei that
modulate sensory inputs
These nuclei act as a “Migraine Mediator” whose dysfunction will lead to abnormal
perception and activation of Trigeminal Vascular System (TVS) which then activate
the central structures
Migraine is mainly due to TVS activation generated within the brain without a
peripheral sensory input
Migraine is the central sensory processing disorder, there is dysfunction of
descending brainstem pain modulatory system
P300
P300
 positive peak
 with a maximum at the vertex
 occurs about 300msec after rare or unexpected stimuli that are interspersed within
a sequence of more common stimuli
 depend on cognitive processes rather than physical characteristics of the stimulus
 therefore called an event related potential (ERP) rather than evoked potential
 abnormalities P300 related to conditions of altered cognitive functioning
P300
Method to producing P300
 two different kinds of stimuli are mixed in one sequence, and the subject is asked
to pay attention to one kind, usually the rarer one, and to ignore the other
 Responses to each kind of stimulus are recorded between an electrode over
central or posterior head regions
 P300 appears after the AEP to stimulation with a rare stimulus if the subject pays
attention to this stimulus
 another way, by instructing the subject to guess whether the next stimulus will be
visual or auditory or whether it will be a single or double click
P300
Normal P300
P300 is a positive peak with a latency of 250-600msec
It may be preceded by EP peak if the recording electrodes are located near the
cortical receiving area of the sensory modality of the stimulus used
↑ latency  increases with the time which the subject needs to distinguish the
rare stimulus
↑ amplitude  rarity of stimulus
Distribution a maximum in the parietotemporal area
P300
Changes of P300 amplitude have been described in various conditions, including
frontal lobe lesions, mental retardation, dementia of various causes, chronic renal
failure, and schizoprenia
P300
VISUAL PATHWAY

Vision is generated by photoreceptors in the retina, a

layer of cells at the back of the eye. The information
leaves the eye by way of the optic nerve, and there is a
partial crossing of axons at the optic chiasm. After the
chiasm, the axons are called the optic tract. The optic
tract wraps around the midbrain to get to the lateral
geniculate nucleus (LGN), where all the axons must
synapse. From there, the LGN axons fan out through the
deep white matter of the brain as the optic radiations,
which will ultimately travel to primary visual cortex, at
the back of the brain
VISU
AL
FIEL
D
AUDITORY PATHWAY
AUDITORY
PATHWAY

Ear :
External Ear
Middle Ear
Inner Ear
MIDDLE EAR
•Membran tympani
•Auditory ossicle
•Musculus tensor tympani and
musculus stapedius
•Oval window dan round
window
•Tuba Eustachian
•Chorda tympani nerve
INNER EAR
•Apparatus vestibular
•Cochlea, bagian dalam
cochlea terdiri dari 3
kompartemen ( scala vestibuli,
scala tympani, scala media)
•Dipisahkan oleh 2 membran,
membran vestibular
(Reisnerr’s) dan membran
basilar
NUKLEUS
VESTIBULOCOCHLEARIS
•Nervus vestibulocochlearis melewati meatus akustikus interna ke fossa kranial
posterior
•Nervus vestibular berakhir di nuklei vestibular
•Nervus cochlearis berakhir di nuklei cochlea
MEKANISME NYERI
MEKANISME NYERI
 Transduction
KERUSAKAN JARINGAN

INFLAMASI

SENSITISASI
SSA MI NOS
Si-Na+
Pg AKTIFASI
ECT. DISC. B, 5HT, Adenosin
R-NE

Activation Pengalaman
Kognitif Inhibisi
KORNU DORSALIS

Behaviour desenden
Psikologik OTAK

PAIN – NO PAIN

External Heat VR1

Pain and auto-sensitization
Ca2+ Na+
Mechanical ACTION
ACTION POTENTIAL
mDEG POTENTIAL
Voltage gated sodium channels
P2X3
Stimuli
Chemical
ATP
action potentials
Generator potentials Woolf & Mitchel, 2001
Modifikasi Meliala, 2003
MEDIATOR INFLAMASI DI
PERIFER

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
Sel-sel rusak → berupa Kalium, asetilkolin, dan Prostaglandin (PG).

Ektravasasi plasma atau migrasi limfosit → bradikinin (BK).

Degranulasi trombosit dan mastosit → serotonin dan histamin (H).
Produk-produk kimia tersebut menimbulkan rangsang pada ujung-ujung
saraf (nosiseptor) untuk memproduksi suatu polipeptida yang disebut
sebagai substansi P (SP).
SERABUT AFEREN DARI PERIFER
KE MEDULA SPINALIS
GATE CONTROL THEORY
GATE CONTROL TEORY

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SENSITISASI PERIFER

Cedera & inflamasi jaringan → perubahan lingkungan kimiawi pada akhir nosiseptor.

Sel yang rusak melepaskan komponen intraselulernya (ATP, ion K+, pH menurun), sel
inflamasi menghasilkan sitokin, chemokine, dan faktor pertumbuhan → merangsang
nosiseptor (nociceptor activators), dan noosiseptor menjadi lebih hipersensitif terhadap
rangsang berikutnya (nociceptor sensitizers).

ATP → reseptor purin P2x3 → mengaktifkan nosiseptor

Proton → reseptor V1 → nyeri beberapa waktu setelah cedera

Prostaglandin E2 (sebuah bentuk prostanoid) dan nerve growth factor → reseptor
prostaglandin E dan tirosin kinase A → sensitisasi tanpa langsung menimbulkan nyeri.

Bradikinin → reseptor B2 → mensensitisasi nosiseptor
 Fosfolipid → asam arakidonat → (dengan bantuan COX-2) prostaglandin H →
prostaglandin E2.
Cyclooxygenase-2 (COX-2) dipicu oleh interleukin 1-IL1 dan tumor necrosis factor-α
(TNF-α), yang keduanya terbentuk beberapa jam setelah permulaan inflamasi.

Komponen sensitisasi → mengaktifkan fosforilasi → perubahan aktivitas reseptor & ion
channel → menurunkan ambang rangsang aktivasi nosiseptor dan meningkatkan
kepekaan ujung saraf → meningkatkan sensitivitas di tempat cedera/inflamasi →
hiperalgesia primer
Back
Back
SENSITISASI SENTRAL

Peningkatan aktivitas eksitatorik → NMDA

Peningkatan sinaps eksitatorik → sprouting

Penurunan aktivitas inhibitori
Back
23 VISUAL EVOKED
POTENTIAL AND MIGRAINE
VISUAL EVOKED POTENTIAL
ABNORMALITIES IN MIGRAINE
PATIENTS
VISUAL EVOKED POTENTIAL AND BRAINSTEM
AUDITORY EVOKED POTENTIALS IN ACUTE
ATTACK AND AFTER THE ATTACK OF
MIGRAINE
TRIGGER VS TENDER POINTS
Back
Back
VAS (VISUAL ANALOGUE
SCALE)

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MECHANISM INJECTION
LIDOCAIN
•The appropriate concentrations blocks nerve conduction.
•They exert their effects not only on nerve fibers (axons and dendrites), but also on
the nerve body, myocardium, skeletal muscles, smooth muscles, and on other
excitable cells by reversibly blocking the transmission of depolarization
waves.
•Additionally, they temporarily block painful signal transmission to the central
nervous system.
•Depending on the concentration, local anesthetics decrease Na influx by
blocking Na channels, and decrease the rate of depolarization in nerve fibers
and other excitable cells.
•Finally, local anesthetics inhibit excitable cells’ ability to spontaneously
discharge