Ebook Practical guide for clinical neurophysiologic testing EEG (2/E): Part 2

9
ActivationProcedures
THORUYAMADAand
ELIZABETHMENG

Activationproceduresincludevarioussensoryandpharmacologicalstimulations
toalterthephysiologicalstate.Theyareusuallyaimedatelicitingorenhancing
abnormal activity, especially epileptiform activity. The most commonly used
sensory stimulation is photic stimulation. Others include tactile or electrical
stimuli for somatosensory stimulation and music or sounds for auditory
stimulation. Pharmacological activation includes pentylenetetrazol to induce a
seizure or benzodiazepine to attenuate one. The most routine activation
proceduresinanyEEGlaboratoryarehyperventilation(HV),photicstimulation
(PS),andsleep.


Hyperventilation


NORMALHYPERVENTILATIONRESPONSE
Thisprocedureconsistsofdeepandregularbreathingatarateofabout3to4per
10 seconds for a period of 3 to 5 minutes. In young children, HV can be
successfully performed by asking the child to blow on a pinwheel. A
characteristicHVresponseconsistsofbilaterallydiffuseandsynchronousslowwave bursts, initially with theta frequency and then progressing to delta
frequency.Thisiscalled“HVbuildup”(Figs.9-1AandBand9-2AandB).The
amplitudemayreachashighas500μV.Theta–deltabuildupbyHVisusually
anterior dominant in adolescents or adults but may be posterior dominant in
children. These occur in a serial semirhythmic fashion with fluctuating
amplitude (Video 9-1). The effect is most prominent in children between the
ages 8 and 12 years and progressively decreases toward adulthood (compare
Figs.9-1Band9-2B);aclearHVresponseisseeninabout70%ofchildren,but

inadults,itmaybelessthan10%.1HVeffects,however,varyconsiderablyfrom
one individual to another. Physiologically, HV reduces the carbon dioxide
concentration (PCO2), which causes vasoconstriction and reduction of cerebral
blood flow. The reduction of PCO2 (hypocapnia) is likely the major factor in
producingHVbuildup.1HVbuildupisenhancedbyabloodsugarlevelbelow
80 mg/100 mL.2 Therefore, HV buildup may be more prominent when the
patientishungryorhis/herlastmealwassometimeago.Insubjectswhoshowa
low-voltageandpoorlydefinedalpharhythm,HVmaybringoutabetterdefined
alpharhythm.



FIGURE9-1|ComparisonofrestingEEGintheawakestate(A)and
EEGduringhyperventilation(B)ina5-year-oldboy.Notetheincrease
of posterior delta waves (posterior slow waves of youth) and
semirhythmic 3- to 4-Hz generalized delta–theta bursts during
hyperventilation(B).



FIGURE9-2|ComparisonofrestingEEGintheawakestate(A)and
EEG during hyperventilation (B) in a 38-year-old man. Note the
generalized bursts of 4- to 6-Hz theta waves. This is unusually
prominentHVresponseinthisageofpatient.Thefrequencyofbursts
isfasterthanthatseeninchildren(Fig.9-1B).
Some delta bursts induced by HV may include “spiky” or spike-like
discharges (small notched spikes preceding or mixed with theta–delta activity)
especially in children. Unequivocal spikes or clear focal or lateralizing (focal)
changes elicited by HV are considered to be abnormal. After cessation of HV,
the patient may complain of numbness or tingling in the fingers and lips,

transientblurringofvision,orringingintheears.Somemayevenshowchanges
of consciousness or awareness. These symptoms are self-limiting and are not
necessarily associated with EEG changes or related to the degree of buildup.
Likewise,aftercessationofHV,theslowwavesdisappearquicklyandtheEEG
returns to the pre-HV state within 30 seconds. In some subjects, though, the
effect may continue for a minute or longer. One should be cautious in
interpretingalong-lastingpost-HVeffect,sincesomesubjectsmaycontinueto


hyperventilate even after being told to stop. The technologist should observe
carefully to make sure that the patient did indeed stop HV. If the delta bursts
appearlongerthan1minuteinthepost-HVperiod,theyarenotlikelyrelatedto
theHVeffect.(Anexceptiontothisisseeninmoyamoyadisease.)3,4


ABNORMALHYPERVENTILATIONRESPONSE
HV is a well-known activation procedure for inducing absence seizures. HV
activates more than 80% of untreated children with absence seizures.5 It is
important for the technologist to document clinical signs associated with an
absence seizure. With a sudden onset of rhythmic (monomorphic) 3-Hz spike–
wavebursts(Fig.9-3;Video9-2,alsoseeVideo10-6),thepatientusuallystops
HVandoftenstaresintospace,sometimeswitheyelidorfacialmuscletwitches.
If3-Hzspike–waveburstslastlongerthan5seconds,thetechnologistisusually
able to observe a clinical change by examining the patient’s level of
consciousness.Anastutetechnologistwillquicklyaskthepatienttoremember
wordspresentedduringtheeventandaskthepatientaftertheeventifheorshe
canrecallthepresentedwords.Ifthepatient’scommunicationorconsciousness
is impaired, the patient will not be able to recall the word spoken during the
episode.Amoreaccurateassessmentmaybemadebytestingreactiontime;the
patient is instructed to press a button (which makes a mark on the EEG

recording)inresponsetoanauditorysignalgivenbythetechnologistduringthe
eventof3-Hz spike–wave bursts.Withcessationofthespike–wave bursts, the
patientusuallyresumesHVwithoutbeingpromptedbythetechnologist.There
isnopostictalconfusionorimpairedconsciousness.


FIGURE 9-3 | Typical 3-Hz spike–wave bursts, characteristic for
absence seizures, induced by hyperventilation in an 8-year-old girl.
Apparently,aclinicalseizurewasassociatedwiththeeventinvolving
staringandblinkingasnotedbyatechnologist.
HV may also activate focal or other types of generalized seizures, or
precipitate interictal epileptiform activity, though the incidence of such
activationisfarless(~5%)thanthatforabsenceseizures.Muchmorevigorous
andprolongedHVisusuallyrequiredtoelicitpartialseizures.6
HVmayaccentuatefocalslowing,whichissometimesusefulforverifying
uncertainorsubtlefocalfeaturesobservedintherestingEEG.OneuniqueHV
effecthasbeenobservedinmoyamoyadiseaseinwhichthedeltaburstsreappear
3to5minutesaftercessationofHV,calledthe“re-buildup”HVeffect.3,4


CONTRAINDICATIONS
HYPERVENTILATION

OF

The American Clinical Neurophysiology Society (formerly American EEG
Society)7 recommended that HV should not be performed in certain clinical
settings.
Included contraindicationsareacutestroke,recentintracranialhemorrhage,
large-vessel stenosis, recent TIA, moyamoya disease, severe cardiopulmonary

disorders, and sickle cell disease or trait. All these conditions are related to
cerebrovascularproblems.


PhoticStimulation
Photic stimulation is a routine activation procedure performed in most EEG
laboratories.Thisisdoneprimarilytoelicitaphotoparoxysmalresponseforthe
diagnosis of photosensitive epilepsy. Photic stimulation provides other
physiologicalresponsesbutoflessdiagnosticvalue.


PROCEDURE
Photicstimulationcommonlyusesastroboscopetodeliverarepetitive,diffuse,
flashinglightofbriefduration(10to30ms).Therepetitiverateisusually1to
30 Hz. The strobe light is placed directly in front of the patient’s eyes at a
distanceofabout30cm.Thepatient’seyesareusuallyclosedduringdeliveryof
photicstimulation,butsomelaboratoriesprefertohavetheeyesopenatfirstand
closed during the middle of photic stimulation (because this may enhance the
incidenceofthephotoparoxysmalresponse).
Thedurationofeachsetofrepetitivestimuliisusually10seconds,followed
by 10 seconds of resting time before delivering the next set of stimuli. The
stimulus rates vary according to laboratory protocols and technologist
preference. It is typical to deliver a series of six to eight different frequencies.
Somelaboratoriesincludecrescendotypeanddecrescendotypeofstimulusrates
with a progressively increasing stimulus rate from 1 to 30 Hz and then a
progressivelydecreasingstimulusratefrom30to1Hz(seeFig.7-26C).


PHOTICDRIVINGRESPONSE
Thephoticdrivingresponseselicitedby5-to30-Hzstimuliconsistofoccipital

dominant rhythmic waves with a one-to-one frequency relationship with each
flash(Fig.9-4A).Withinonesetofflashes,thedrivingresponsefrequencymay
changefromone-to-onetoaharmonicorsubharmonicpattern(Fig.9-4B).The
responses are usually most prominent at the flash frequency closest to the
frequency of the individual’s alpha rhythm. In a young child, the driving
responsemaybeelicitedatthetafrequencyflashes.Theamplitudeofthephotic
driving response is generally higher in children and better visualized in adults
with low-voltage background activity. The patients who have large lambda
wavesand/orPOSTStendtohavelargephoticdrivingresponses(see“Lambda
Waves,”Chapter7;seealsoFig.7-26A–C).Aphoticdrivingresponseisabsent
in a blind person, but absence of a photic driving response per se is not an
abnormal finding. It should be noted that the photic response with a slow
frequency (<3 Hz) is not a driving response but rather an evoked potential
elicited by each flash (Fig. 9-5). In some subjects, there are diffuse sharp
dischargesattheonsetoroffsetofphoticstimulation,calledtheon-responseand
off-response,respectively(seeFig.9-4B).



FIGURE 9-4 | Typical photic driving response with 14-Hz photic
stimuli. Note the rhythmic activity with photic stimulation. The
drivingresponsesfadetowardtheendofthestimulation(A).Insome
individuals, the frequency of the occipital response becomes half
(subharmonic) of the frequency of photic stimuli (B). In this
individual,thedrivingresponsestartedwiththesamefrequencyasthe
stimulusfrequencyatfirstbutbecamehalfthefrequencyinthemiddle
ofphoticstimulation.Notethe“on-response”bybroadsharptransient
occurring approximately 150 to 200 ms. after the onset of photic
stimulation(indicatedbyverticalline).

FIGURE 9-5 | Photic responses at slow-frequency rates. In some
individuals,theremaybeadistinctresponseatslow-frequency(1-to
3-Hz) stimulation. Note the small sharp and wave complex in the
occipitalelectrodes,timelockedto,butslightlyfollowing,eachflash.
Examples are shown in the rectangular box. This is not a driving
responsebutratheraphotic-inducedevokedpotential.


PHOTOPAROXYSMALRESPONSES
Thiswasformerlyreferredtoasthe“photoconvulsiveresponse,”buttheuseof
this term is now discouraged. Photoparoxysmal responses (PPRs) typically
consist of high-amplitude generalized irregular spike–wave or polyspike–wave
bursts,witheitherbianteriororbiposteriordominance(Figs.9-6AandBand97AandB;Videos9-3;seealsoVideo10-7;Figs.10-6B,10-18B,and 10-21B).
Themosteffectivefrequencyis15to20Hz.8TheincidenceofPPRishighest
betweenages6and15anddecreaseswithage.9,10PPRscorrelatehighlywitha
diagnosis of epilepsy; approximately 70% to 80% of patients with PPRs have
epilepsy.11,12TheseizurecorrelationisespeciallyhighinPPRswithspike–wave
bursts that persist well beyond termination (>200 ms) of the flash stimulus
(sustainedPPR)(seeFigs. 9-6Aand 9-7B),ascomparedtothePPRsinwhich
thespike–waveburstsceaseatorbeforetheterminationoftheflashstimulus13
(self-limitedPPR)(Fig.9-6B).ThefrequencyofPPRsistypicallyindependent
ofthephoticstimulusrates.Someoftheatypicalphoticdrivingresponsesmay
consistofspike–wave-likedischargeswhicharetimelockedandsustainedina
one-to-onerelationshipwiththestimulusrate.Theseshouldnotbeconsidereda
PPR(Fig.9-8).



FIGURE 9-6 | Example of photoparoxysmal responses. In (A),

generalizedirregularpolyspike–waveburstsstartedimmediatelyafter
theonsetof11-Hzphoticstimulation.Spike–wavescontinueddespite
quick cessation of photic stimulation (unlimited photoparoxysmal
response). In (B), generalized irregular spike–wave bursts started in
the middle of photic stimulation and ceased despite continuation of
photic stimulation (self-limited photoparoxysmal response). A
sustained photoparoxysmal response (A) is more epileptogenic and
more likely associated with a history of seizure than the self-limited
photoparoxysmalresponse(B).



FIGURE 9-7 | Photoparoxysmal response with occipital onset in an
11-year-oldgirl.Thephotoparoxysmalresponsestartedintheoccipital
regions with frequency-dependent repetitive sharp discharges and
became frequency-independent assuming spike–wave discharges
toward the end of photic stimulation (A). In crescendo photic
stimulation, spike discharges started in the occipital electrodes at
around 12-Hz photic stimuli and then evolved to generalized spike–
wave bursts, which continued well after the cessation of photic
stimulation(B).


FIGURE 9-8 | Prominent photic responses in a 69-year-old woman.
Note the repetitive spike–wave discharges consistently time locked
witheachflash.Thisisnotaphotoparoxysmalresponse.
TheseizuretypemostoftenassociatedwithPPRisgeneralizedtonic–clonic
(>80%). Juvenile myoclonic epilepsy (JME) has an incidence of PPR greater
than 1/3.14 Absence and myoclonic seizures represent less than 10% of all
PPRs.15Partialseizures,especiallytemporallobeseizures,associatedwithPPRs

are extremely rare, if any, but may occur with occipital lobe seizures (see Fig.
10-6AandB).16IfPPRisobservedinapatientwithcomplexpartialseizure,this
likelysuggeststhatthispatienthasbothtypesofseizures:primarygeneralized
andcomplexseizures.
SomePPRsare morereadilyactivatedbyapatternsuchasdotsorstripes.
Overall, pattern stimulation is more effective for eliciting PPRs than a diffuse
strobe light.17 The color of photic stimulation also affects the degree of
photosensitivity. A red color is more effective for eliciting PPRs than white
flashes, and blue tinted sunglasses have been recommended for preventing
seizureduetophotosensitiveepilepsy.18Technologistsshouldbeabletoquickly


identifytheonsetofaphotoparoxysmalresponse(epileptiformactivity)sothat
thestimulusmaybestoppedbeforeprovokingaclinicalgeneralizedtonic–clonic
seizure. Once the technologist recognizes the PPRs, however, the same
frequency of photic stimulation should be repeated to verify that the evoked
epileptiform activity is indeed induced by photic stimulation and is not an
incidental occurrence during photic stimulation. In this situation, the
technologistmustbeextremelyalertsoastostopphoticstimulationimmediately
upontheonsetofaphotoparoxysmalresponse(seeFig.9-6A).Thetechnologist
should also be able to differentiate a photoparoxysmal response from
physiological variants of photic stimulation (see Fig. 9-8) or from a
photomyogenic response (see “Photomyogenic Response”), which is not
consideredtobeabnormal.
One remarkable incidence occurred in December 1997 in Japan;
approximately 700 children throughout Japan had seizures almost
simultaneously while watching a television cartoon program called pocket
monster, or “Pokemon.”19 This was apparently caused by alternating red/blue
framesflickeringat12HzontheTVscreen.Aphotosensitiveseizuremayalso
betriggeredbyplayingvideogames.20

Theanimalmodelofphotosensitiveepilepsyhasbeenstudiedextensivelyin
thephotosensitivebaboon,Papiopapio.21


PHOTOMYOGENICRESPONSE
The photomyogenic response (PMR) (formerly referred to as the
“photomyoclonic response” [the term is now discouraged]) consists of EMG
artifacts time locked with the flash frequency (Fig. 9-9A). These muscle
potentials most often arise from frontal and orbicularis oculi muscles. Visible
muscle twitches, time locked with the stimulus, may appear in the eyelids or
face.Insomeoccasions,musclecontractionsprogressivelyincrease(Fig.9-9B),
involving larger muscle groups, spreading to the neck or upper body as the
stimuluscontinues.Thismayappearclinicallytobeageneralizedclonicseizure.
In addition to the time-locked characteristics, stopping the stimulus will
immediately stop the response in PMR. It is important for the technologist to
noteifthereareanymuscletwitches(ofteneyelidtwitches)associatedwiththe
PMRs.