6 Activation of the EEG

From: The Clinical Neurophysiology Primer

Edited by: A. S. Blum and S. B. Rutkove © Humana Press Inc., Totowa, NJ

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6

Activation of the EEG

Barbara A. Dworetzky, Edward B. Bromfield, and Nanon E. Winslow

Summary

Various procedures are commonly used in the recording of the EEG in an effort to increase the diag- nostic yield of the test. Common methods, such as hyperventilation (HV), photic stimulation, and sleep deprivation, referred to collectively as activation techniques, are traditionally used toward this end. Less common techniques, such as withdrawal of antiepileptic medications, use of specific triggers reported by the patient, and other idiosyncratic methods can be tried as well. This chapter will review methods of activation of the EEG, including HV, photic stimulation, and sleep deprivation. Historical back- ground, physiological mechanisms, standard techniques, and clinical significance will also be reviewed.

Key Words: Hyperventilation; photic stimulation; photic driving; photoparoxysmal response; reflex epilepsy; sleep deprivation.

1. INTRODUCTION

Even in patients with a definite diagnosis of epilepsy, the first EEG will be normal 50% of the time. It is a common and accepted practice to arrange for additional EEGs if the first one is nondiagnostic, because three studies increase the sensitivity of detecting an abnormality to approx 90%. The EEG technologist is trained to use certain techniques to increase the likeli- hood that an abnormality will emerge during the 20- to 30-min sampling of brain activity that is obtained during a routine EEG. Common methods, such as hyperventilation (HV), photic stimulation, and sleep deprivation, referred to collectively as activation techniques, are tradi- tionally used if an EEG would otherwise be interpreted as normal or “nonspecific.” Less com- mon techniques, such as withdrawal of antiepileptic medications, use of specific triggers reported by the patient, and other idiosyncratic methods can be tried as well. This chapter reviews methods of activation of the EEG, including HV, photic stimulation, and sleep dep- rivation. Historical background, physiological mechanisms, standard techniques, and clinical significance will also be reviewed.

2. HYPERVENTILATION 2.1. Background

Activation of seizures by HV was first reported in 1924, even before the discovery of the EEG.

This technique became widely used in the diagnosis of absence seizures. HV responses can vary

widely depending on age of patient and the amount of individual effort put forth. Common HV

responses in adults include no EEG change or mild slowing temporally, frontally, or diffusely. In younger individuals, in contrast, responses can be particularly dramatic, with extremely high voltage synchronous delta waves in bursts or runs. This can be further exaggerated if it has been many hours since the person has eaten a meal (relative hypoglycemia) (Fig. 1). Unless there are definitive spikes embedded within the synchronous delta activity or the record fails to return to baseline within 1 to 2 min of verified completion of over-breathing, the response should be inter- preted as negative, because there is large variation in the normal response. Consistent focal fea- tures, whether epileptiform or not, are interpreted as abnormal.

2.2. Mechanism

With HV, there is a rise in PaO

and a drop in PaCO

. To compensate for the resultant hypocapnia, the cerebral blood vessels constrict. The mechanism of the EEG response to HV is not yet understood, but several theories are reviewed by Takahashi. These include inadequate compensatory vasoconstriction, cerebral hypoperfusion as a result of vasoconstriction, increased neuronal excitability from respiratory alkalosis, synchronous activity of the thalamocortical pro- jections that are enhanced by hypocapnia, and decreased activity of the mesencephalic reticular formation. The more dramatic changes noted in children suggest that immature autoregulation may explain the HV response, or that HV slowing is independent of cerebral blood flow.

Whatever the true mechanism, HV is an accepted, standard technique for activation of the EEG.

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Fig. 1. (A) Start hyperventilation (HV) in an adult. (Continued)

Activation of the EEG 75

Fig. 1. (B) End HV 3 min later with marked bilateral slowing.

2.3. Technique

When there are no epileptiform discharges uncovered during a routine EEG, the HV proce- dure is explained to the patient. Those with severe cardiac or pulmonary disease, uncontrolled hypertension, or a recent vascular event, such as myocardial infarction, stroke, or transient ischemic attack, should not be exposed to this procedure, because hypocapnia and alkalosis may cause vasospasm or decrease cerebral perfusion. To begin the procedure, the technologist instructs the patient to breathe deeply and rapidly for 3 min. Patients are usually lying flat dur- ing a routine EEG, although it has been noted that the effects are enhanced by an upright pos- ture, possibly because of the relative cerebral hypoperfusion. Patients should be told that they might experience symptoms of lightheadedness and tingling, particularly around the mouth and fingertips, although they can be reassured that this is reversible. As mentioned, the time since the last meal should be documented, because low glucose may enhance the response. The EEG is usually recorded on a bipolar montage with the patient’s eyes closed, and should be run on the same montage, at least 1 min before starting the hyperventilating and continued for up to 3 min afterward, documenting the effort that the patient puts forth.

Syncope may lead to prolonged post-HV slowing, and patients with the rare vascular dis-

ease known as Moyamoya can have a delayed “re-buildup” referring to high-voltage diffuse

slowing, which can occur even after HV is completed. Longer duration of HV (up to 6 min)

was shown by Adams and Luders to have a higher yield than 6 h of continuous EEG moni- toring, justifying continuation of this technique when no epileptiform discharges are noted at 3 min, particularly in patients with absence seizures. Occasionally, patients become mildly confused and have difficulty discontinuing the procedure and may require gentle reminders to stop. If this is ineffective, rebreathing CO

with a paper bag or oxygen mask placed over the mouth can be useful. For the pediatric population, it is helpful to have children blow at a pinwheel, although for the very youngest, HV may be captured during the all too common periods of sobbing in the EEG laboratory. HV should be discontinued if repetitive discharges or seizures are elicited.

2.4. Clinical Significance

HV can enhance subtle but significant abnormalities, rendering insignificant ones unchanged or diminished. Additionally, it can be used as an induction technique for nonepileptic seizures. Previous studies have shown that, in patients with partial seizures and a normal baseline EEG, focal interictal discharges were elicited in 6 to 9% of patients using HV, whereas, in children with absence epilepsy, generalized spike and wave activity appeared in 80% of cases. A recent study by Holmes et al. however, suggested that even in known epilepsy patients, seizures were elicited by HV in less than 0.5%.

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Fig. 2. (A) Symmetric photic driving with 12-Hz stimulation frequency. (Continued)

3. PHOTIC STIMULATION 3.1. Background

Photic stimulation is performed in most EEG laboratories for nearly all patients referred for routine EEG. The earliest roots of this activation procedure may be traced back at least to ancient Greece, where descriptions of the potter’s wheel to screen people who might have seizures were documented. Bright lights were noted to cause epileptic seizures at the turn of the 20th century. Intermittent photic stimulation (IPS) with a constant light source was used by 1934, and activation of epileptic discharges by using a strobe technique was soon reported.

Clinical description of young patients’ producing pleasurable feelings by waving their hands in front of a source of light was subsequently reported.

3.2. Mechanism

Physiologically, the photic response is a repetitive visual potential evoked by flash, as the response occurs in a specific time relationship to the light stimulus. Photic driving refers to this time-locked activity generated by visual cortex and seen at the back of the head (Fig. 2A).

Certain stimulus frequencies more readily elicit responses, usually those between 4 and 30 Hz.

Analysis at slower frequencies reveals that the actual response is of positive polarity and

Activation of the EEG 77

Fig. 2. (B) Photic driving “harmonic” response, intermittent photic stimulation at 7-Hz stimulation,

14-Hz driving.

follows the stimulus by approx 100 ms. There is a wide range in amplitude of normal responses.

When they are of particularly high amplitude, one might recognize a “harmonic,” or multiple, of the presented stimulus frequency. For example, a double harmonic response occurs at twice the stimulus frequency (Fig. 2B) and a half harmonic occurs at half the stimulus frequency.

3.3. Technique

Most EEG machines are preprogrammed with the ability to present successive stimulus trains at particular frequencies. Standard techniques for photic stimulation include presenting the strobe light stimuli at a measured distance of 20 to 30 cm with the patient’s eyes closed.

Trains should begin at 1 or 3 Hz, and be presented for 4 to 10 s, with at least 4 s between each train, up to 30 Hz. Subjects may have trouble tolerating these visually presented stimuli directly, and often find it helpful to close their eyes.

3.4. Clinical Significance

Photic driving is considered normal unless there is dramatic voltage asymmetry or unilateral absence of the response (not just caused by varying harmonics), or if epileptiform discharges are elicited. The presence of a dramatic, high-amplitude driving response may indicate hyper- autonomic responsiveness, such as is seen in alcohol withdrawal, hyperthyroidism, or migrain- ous disorders. Prominent driving, however, is not considered abnormal, even in the absence of such clinical correlates. Repetitive contractions of the frontalis muscle synchronized to the light flash at a delay of 50 to 60 ms, known as photomyoclonus, was first described by Gastaut, and this phenomenon does not clearly correlate with epilepsy or other neurological disease. Such muscle activity can be differentiated from cortical discharges by its suppression with eye open- ing, and anterior rather than posterior or generalized location. These twitches are always exactly time-locked and do not outlast the stimulus.

The phenomenon of photomyoclonus, similar to an exaggerated driving response, is nor- mal, although, again, perhaps more associated with hyperautonomic states. Photoparoxysmal response (PPR), formerly known as photoconvulsive response, occurs when IPS generate bilaterally synchronous and usually generalized epileptiform discharges, which may outlast the stimulus by several seconds, or indeed even cause a seizure (Fig. 3). Photic-induced seizures are most commonly myoclonic although absence or tonic–clonic seizures can occur.

Discharges are often generalized but more pronounced in frontal leads, and are more likely induced at middle stimulus frequencies (15–20 Hz) or with stimuli presented on eye closure while the patient is awake and alert. The presence of PPR is more likely to indicate idiopathic generalized epilepsy rather than partial epilepsy. This response can be a genetic trait, although it is rarely seen in patients without any history of seizures. Photic stimulation should be discontinued in the presence of polyspike and wave discharges.

Artifacts identified during photic stimulation can mimic PPR, particularly the electroreti- nal response (generated by retinal ganglion cells), and photoelectric effect (from photochem- ical response of the silver electrodes). Occipital spikes can be elicited with photic stimulation in progressive myoclonus epilepsy, such as that seen in infantile ceroid lipofuscinosis.

4. SLEEP DEPRIVATION

4.1. Background and Clinical Significance

The association of epileptic seizures and sleep has been recognized since at least the 19th century. Gowers, as cited by Chokroverty, found that 21% of patients had seizures exclusively during the night, especially during transitions into and out of sleep, as well as 1 to 2 h after

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awakening. With the introduction of the EEG, epileptic discharges during sleep were discov- ered. An increase in discharges during sleep has been a longstanding observation among patients with grand mal seizures. Sleep deprivation has been demonstrated to increase the yield of epileptiform findings even in the absence of sleep production, and may be more activating than sedated sleep; a more recent study of Degen et al., however, did not confirm significant differences in activation of epileptiform activity in patients with and without complete sleep deprivation. Even more recent studies of Malow et al. have shown that slow wave sleep is most likely to include spikes, whereas rapid eye movement (REM) sleep is the least likely to include discharges, even less than waking. Klein et al. found that sleep was more activating than HV for patients with definite interictal epileptiform discharges. Glick’s recent review of the effects of sleep deprivation on EEG concluded that there is a prominent activating effect of light sleep on the EEG, but no evidence of an overall increase in discharge rate after sleep deprivation in waking or other sleep states. Regarding specificity of sleep recording, activity that is “sharp appearing” but seen only during wakefulness and not in sleep is less likely to be “epileptiform”

than discharges that continue or increase during sleep.

4.2. Mechanism

Neuronal synchronization is the underlying basis for epileptiform discharges and ictal events.

Non-REM sleep, mediated by thalamocortical input, is a time of increased synchronization

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Fig. 3. Photoconvulsive response in an 11-yr-old girl with spells of unresponsiveness, aggravated

by bright lights.

when seizures occur in susceptible patients, and focal discharges tend to demonstrate a broader field. This lies in contradistinction to REM sleep, in which there is relative desynchronization of the EEG, and epileptiform discharges or seizures are rare.

4.3. Technique

In many laboratories, partial rather than complete sleep deprivation is used because it is less onerous for patients, less likely to precipitate seizures, and probably just as useful.

We tell patients to cut down to half of their usual sleep amount, and to stay awake and not drink any caffeine in the morning before the EEG study is performed, to increase the like- lihood of sleep. Technologists become adept at making the room quiet and warm, and coaxing the patient gently to sleep despite being in a laboratory setting. A second EEG ordered with sleep or sleep deprivation can increase the yield. Generally, conscious seda- tion, such as with chloral hydrate administration, is no longer offered, because special cer- tification and staffing are required and make this problematic. However, conscious sedation is still used in some pediatric facilities in which a sleep EEG may be the only way to obtain an artifact-free tracing.

5. DRUG OR DRUG WITHDRAWAL

Drugs, or the withdrawal of drugs, can precipitate seizures. Historically, pentylenetetrazol (Metrazol) was introduced to bring on convulsive seizures for electroconvulsive shock ther- apy in the 1930s and 1940s. It was later abandoned because of many restrictions on its use.

Antiepileptic drug withdrawal is often used during inpatient long-term video EEG monitor- ing for both diagnostic and therapeutic reasons. Contrary to many patients’ understanding, however, drug withdrawal is rarely used in the EEG laboratory outside of the long-term mon- itoring setting, because the likelihood of seeing interictal discharges, especially focal dis- charges, is not greatly affected by most antiepileptic drugs (and the risk of seizure is high).

In the long-term monitoring setting, concerns raised that medication withdrawal would change the nature of the typical seizures and negate the usefulness for localization has dissi- pated with studies indicating that seizures may more likely generalize, but clinical seizure semiology and electrographic onset are not significantly altered.

6. OTHER METHODS

Additional idiosyncratic activation methods may be justified in patients with “reflex epilepsy” associated with specific stimuli or activities, such as reading or listening to specific music. Patients with psychogenic nonepileptic seizures may perceive similar relationships, and appropriate methods may also induce these spells and establish the correct diagnosis.

The importance of making a definitive diagnosis of epilepsy cannot be overstated.

Although extended recording on either an ambulatory or inpatient basis may have the highest yield, this testing is not appropriate for patients with infrequent spells or those whose interictal discharges can be identified using the simpler and less expensive tech- niques outlined here. The more intensive techniques, however, are preferable to a “thera- peutic trial,” which may lead to prolonged, inappropriate use of potentially toxic medications, not to mention the associated stigma and activity restrictions. In some cir- cumstances, it may be useful to proceed directly to ambulatory EEG after an initial study that includes HV, photic stimulation, and sleep and sleep deprivation is negative, rather than repeating the routine EEG.

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SUGGESTED READING

Adams D, Luders H. Hyperventilation and 6-hour EEG recording in evaluation of absence seizures.

Neurology 1981;31:1175–1177.

Ajmone-Marsan C. Pentylenetetrazol: historical notes and comments on its electroencephalographic activation properties. In: Luders H, Noachtar S, ed. Epileptic Seizures: Pathophysiology and Clinical Semiology. Churchill Livingstone, Philadelphia, PA, 2000, pp. 563–569.

Benbadis SR Johnson K, Anthony K, Caines G, et al. Induction of psychogenic nonepileptic seizures without placebo. Neurology 2000;55(12):1904–1905.

Chokroverty S, Quinto C. Sleep and epilepsy. In: Chokroverty S, ed. Sleep Disorders Medicine, 2nd ed.

Butterworth Heinemann, Woburn, MA, 1999, pp. 697–727.

Degen R, Degen HE, Reker M. Sleep EEG with or without sleep deprivation? Does sleep deprivation activate more epileptic activity in patients suffering from different types of epilepsy? Eur Neurol 1987;26(1):51–59.

Doose H, Waltz S. Photosensitivity: genetics and clinical significance. Neuropediatrics 1993;24:249–255.

Drury I. Activation of seizures by hyperventilation. In: Luders H, Noachtar S, ed. Epileptic Seizures:

Pathophysiology and Clinical Semiology. Churchill Livingstone, Philadelphia, PA, 2000, pp. 575–579.

Gastaut H. Effects des stimulations physiques sur l’EEG de l’ homme. Electroencephalogr Clin Neurophysiol Supp. 1949;2:69–82.

Glick T. The sleep-deprived electroencephalogram: evidence and practice. Arch Neurol 2002;

59(8):1235–1239.

Holmes M, Dewaraja A, Vanhatalo S. Does hyperventilation elicit epileptic seizures? Epilepsia 2004;45(6):618–620.

Klein K, Knake S, Hamer HM, Ziegler A, Oertel WH, Rosenow F. Sleep but not hyperventilation increases the sensitivity of the EEG in patients with temporal lobe epilepsy. Epilepsy Res 2003;56(1):43–49.

Malow B, Selwa L, Ross D, Aldrich M. Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy. Epilepsia 1999;40(11):1587–1592.

Misulis K. Essentials of Clinical Neurophysiology. Butterworth-Heinemann, Woburn, MA, 1993.

Patel V, Maulsby R. How hyperventilation alters the electroencephalogram: a review of controversial viewpoints emphasizing neurophysiological mechanisms. J Clin Neurophysiol 1987;4:101–120.

Rosenow F, Luders H. Hearing-induced seizures. In: Luders H, Noachtar S, eds. Epileptic Seizures:

Pathophysiology and Clinical Semiology. Churchill Livingstone, Philadelphia, PA, 2000, pp. 580–584.

Rosenow F, Luders H. Startle-induced seizures. In: Luders H, Noachtar S, eds. Epileptic Seizures:

Pathophysiology and Clinical Semiology. Churchill Livingstone, Philadelphia, PA, 2000, pp.

585–592.

Takahashi T. Activation Methods. In: Niedermeyer E, Lopes Da Silva F, eds. Electroencephalography:

Basic Principles, Clinical Applications, and Related Fields, 4th ed. Lippincott Williams &

Wilkins, Philadelphia, PA, 1999, pp. 261–284.

Wolf P. Activation of seizures by reading and praxis. In: Luders H, Noachtar S, eds. Epileptic Seizures: Pathophysiology and Clinical Semiology. Churchill Livingstone, Philadelphia, PA, 2000, pp. 609–614.

REVIEW QUESTIONS

1. What is the value of HV to the EEG?

2. In what way does hypoglycemia influence the effect of HV on the EEG?

3. Who should not undergo HV?

4. What is the physiological basis for photic driving response?

5. When are photic driving responses abnormal?

6. What are PPRs and what do they signify?

Activation of the EEG 81

7. What is photomyoclonus? Is it considered pathological?

8. What is the photoelectric (photocell) effect?

9. What additional activation methods can be used in the inpatient setting to improve the yield of monitoring?

10. Which sleep stage is least apt to activate epileptiform features?

REVIEW ANSWERS

1. HV is helpful in that it may accentuate focal or epileptiform abnormalities in the EEG. It has an especially high yield in the evaluation of patients with 3-Hz spike wave abnormalities associated with absence epilepsy.

2. Hypoglycemia tends to accentuate the effect of HV on the EEG.

3. Patients with recent or unstable CNS or cardiac ischemia, cardiopulmonary compromise, or uncontrolled hypertension should not undergo HV.

4. Photic driving responses are derived from visual evoked potential responses in the visual cortex.

5. Photic driving responses are abnormal if there are dramatic hemispheric voltage asymmetries or frankly unilateral responses. The affected hemisphere does not generate a response. Otherwise, photic driving responses are considered to be normal (epileptiform activities are also abnormal when elicited, but these are termed PPRs). Some investigators think that prominent photic driv- ing responses, including at high stimulus frequencies, may be a marker of hyperautonomic states, but this phenomenon is insufficiently specific to be deemed pathological.

6. PPRs are denoted by epileptiform discharges generated in the context of IPS, sometimes contin- uing after the completion of the photic train. They signify an underlying epileptic process that is photically sensitive. They are usually encountered in association with generalized epilepsies, although they may also be seen in focal occipital epilepsies.

7. Photomyoclonus refers to entrained contraction of the frontalis muscle in the context of IPS.

It is considered a normal phenomenon.

8. The photoelectric effect refers to an electrode-derived artifact caused by a photochemical reac- tion from the silver electrode in response to light stimulation itself. It may be improved (and ver- ified) by shielding the involved lead from the direct illumination of the strobe source.

9. Other methods of EEG activation during inpatient long-term monitoring include sleep depriva- tion, anticonvulsant withdrawal, and occasionally exposure to stimuli in the context of reflex epilepsies (e.g., reading or writing epilepsies).

10. REM sleep is not conducive to epileptiform activity because it is a more desynchronized pattern.

Non-REM stages are much more productive of epileptiform features.

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