INVITED REVIEW
Generalized Periodic Discharges: A Topical Review
Krystal E. Sully* and Aatif M. Husain*†‡
*
Department of Neurology, Duke University Medical Center, Durham, North Carolina, U.S.A.; †Neurodiagnostic Center, Veterans Affairs Medical Center,
Durham, North Carolina, U.S.A.; and ‡Neuroscience Medicine, Duke Clinical Research Institute, Durham, North Carolina, U.S.A.
Summary: Generalized periodic discharges (GPDs) are generalized
discharges that recur with a relatively uniform morphology and
duration. They have a quantifiable interdischarge interval. Over
the past decade, our understanding of these waveforms has
improved considerably. The nomenclature has changed, and
etiologic references have been removed. Many disease states can
cause GPDs, such as anoxia, toxic/metabolic encephalopathy,
infections, nonconvulsive status epilepticus, and hypothermia.
Generally, GPDs are morphologically similar regardless of etiology.
Generalized periodic discharges that are associated with
G eneralized periodic discharges (GPDs) are EEG waveforms
seen in the setting of many different types of encephalo-
pathies. They are generalized, morphologically similar wave-
forms that recur at a regular frequency. Some authors have tried to
evaluate GPDs based on their morphologic characteristics, while
others have focused on prognosis and survival statistics.
Exploration of these questions has shed light to new theories
and fostered much discussion. The evolution of the terminology
used to describe GPDs reflects the attempt of neurologists to grasp
a better understanding of these waveforms.
Our knowledge of GPDs is limited and evolving as new
information comes to light. In this article, we will begin with
a review of the history and nomenclature of GPDs, followed by
information on the etiology and pathophysiology of GPDs. Then,
the discussion will turn to the treatment and prognostic value of
these waveforms.
DEFINITION AND NOMENCLATURE
Historically, GPDs were referred to as generalized periodic
epileptiform discharges.1,2 Other periodic discharges were also
referred to as “epileptiform.” An expert panel of the American
Clinical Neurophysiology Society reviewed the literature and
determined that the association of periodic discharges with
epileptiform activity was not a consistent feature of these
discharges.3 Thus, the word “epileptiform” was eliminated from
the terminology so as to not imply an etiology in the nomenclature.
A new terminology was proposed for all types of periodic
discharges, and that terminology is used in this article.3
Generalized periodic discharges are repeated generalized
waveforms with relatively uniform morphology and duration
The authors have no funding or conflicts of interest to disclose.
Address correspondence and reprint requests to Aatif M. Husain, MD, Department
of Neurology, Duke University Medical Center, 299B Hanes House, 315 Trent
Drive, Box 102350, Durham, NC 27710, U.S.A.; e-mail: Aatif.husain@duke.
edu.
Copyright Ó 2018 by the American Clinical Neurophysiology Society
ISSN: 0736-0258/18/3503-0199
DOI 10.1097/WNP.0000000000000460
clinicalneurophys.com
nonconvulsive status epilepticus are treated with antiseizure
drugs, while others are not necessarily aggressively treated.
Prognosis for most patients with GPDs is guarded, although this is
also dependent on the underlying etiology. As our understanding
of GPDs increases, it is also clear that there is much more to be
learned about these waveforms.
Key Words: Generalized periodic discharges, Encephalopathy,
Coma.
(J Clin Neurophysiol 2018;35: 199–207)
with a quantifiable interdischarge interval between consecutive
waveforms and recurrence of the waveform at nearly regular
intervals.3 These discharges are further described as being
frontally predominant, occipitally predominant, midline predom-
inant, or generalized, not otherwise specified. Additionally,
modifiers should be used to describe the following features of
the GPDs:3
1. Prevalencedhow much of the record per epoch contains the
GPDs
2. Durationdhow long does the GPD activity continues during
the recording, in minutes or hours
3. Frequencydthe number of GPDs occurring in 1 second
4. Number of phasesdthe number of baseline crossings in
a typical GPD waveform
5. Sharpnessdthe time in milliseconds for the sharpest and the
most prominent phase of the GPD
6. Amplitudedthe highest amplitude of the GPD waveform in
an anterior–posterior bipolar montage should be measured;
amplitude of the GPD can also be measured relative to the
background activity
7. Polaritydwhether the highest amplitude of the GPD is
negative, positive, or unclear
8. Stimulus induceddwhether the GPDs occur spontaneously
or are induced with a stimulus
9. Evolving or fluctuatingdwhether the GPDs change in
frequency, morphology, or location (evolution) or whether
the changes are present but not enough to be classified as
evolving (fluctuating)
10. Plusdwhether additional features make the GPD pattern
appear more epileptiform.
Other minor modifiers can also be included when describing
GPDs. These include the following terms:3
1. Quasidused to modify the rhythmic or periodic nature of the
GPDs
2. Sudden or gradual onsetdused to describe how GPDs appear,
suddenly (previously called paroxysmal) or over several
seconds
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 K. E. Sully and A. M. Husain
3. Triphasic morphologydused to describe the shape of the
GPDs
4. Lag of waveformsdeither an anterior to posterior or a poste-
rior to anterior lag may be seen in various components of the
GPD.
Not all modifiers need to be used when describing GPDs.
However, whichever ones are most appropriate for the individual
situation should be considered.
Generalized periodic discharges should be distinguished from
other periodic discharges. They are differentiated from lateralized
periodic discharges (LPDs) by the unilateral nature of LPDs.
Bilateral but asymmetric patterns are often also classified as LPDs,
with lateralization toward the side with the more prominent
waveform. These LPDs are thought to be projected to the
contralateral side. Both GPDs and LPDs that are projected to the
contralateral side are synchronous discharges. Bilateral indepen-
dent periodic discharges are bilateral discharges, but they are
asynchronous, that is, they do not occur in both hemispheres
simultaneously. Additionally, bilateral independent periodic dis-
charges may be symmetric or asymmetric. Finally, multifocal
periodic discharges have at least three independent, lateralized
patterns. At least one of these lateralized discharges must be in
each hemisphere.3
As the above discussion implies, triphasic waves are now
also considered a type of GPD.3 Previously, they were not
included in the classic generalized periodic epileptiform dis-
charge literature. However, because of their morphologic simi-
larity and generalized, synchronous, and symmetric nature, they
are now considered GPDs. This is particularly appropriate as the
term GPD does not imply an epileptic etiology. Traditionally,
triphasic waves have been associated with metabolic encephalo-
pathies.4,5 The overlap in the waveform spectrum of triphasic
waves and GPDs is reflected in the new terminology. If triphasic
waves comprise most of the EEG recording, they are described as
“persistent, continuous, two per second GPDs (with triphasic
morphology).”3
Generalized periodic discharges were previously divided
into three types:
1. Periodic, short-interval, diffuse discharges that were seen
most often in Creutzfeldt–Jakob disease (CJD)
2. Periodic, long-interval, diffuse discharges that were seen with
subacute sclerosis panencephalitis and drug toxicity
3. Burst suppression that can be iatrogenically induced or result
from many causes, such as hypoxic–ischemic encephalopa-
thy, coma, or drug use (such as anesthesia administration or
barbiturate overdose).6
These classifications are not widely used in the literature any
more. Rather the various types of GPDs are now described using
the various modifiers noted above.
ETIOLOGY
The occurrence of GPDs alludes to a global encephalopathy.
Many different types of encephalopathies can result in GPDs.
Common etiologies include anoxia, toxic/metabolic derangements,
200 Journal of Clinical Neurophysiology Volume 35, Number 3, May 2018
Generalized Periodic Discharges
infections, acute neurologic injury, nonconvulsive status epilepti-
cus (NCSE), and hypothermia. While GPDs are nonspecific for
etiology, various features can help differentiate between various
types of encephalopathies.
Anoxic Encephalopathy
Generalized periodic discharges have been reported fre-
quently in patients with anoxic encephalopathy (Fig. 1).7 The
morphology of the GPDs does not appear to be remarkably
different in patients with anoxic encephalopathy compared with
other types of encephalopathy.8 They can be seen within 12 to 24
hours after the onset of the anoxic injury.9 Many other EEG
patterns, such as rhythmic discharges, LPDs, burst suppression,
and background suppression, can also be seen with anoxic
encephalopathy, but GPDs suggest a more severe brain injury.10
Generalized periodic discharges can also occur with other
patterns, such as rhythmic discharges in the alpha and theta
frequency.
Toxic/Metabolic Encephalopathy
Historically, the EEG hallmark of toxic/metabolic ence-
phalopathies was thought to be triphasic waves. These wave-
forms are now called GPDs with triphasic morphology in an
attempt to dissociate etiology from the description. As their
name suggests, these waveforms have three distinct phases.
They were classically associated with hepatic encephalopa-
thy, but later they were noted to occur in other types of
metabolic disorder.11–13 However, GPDs with triphasic mor-
phology should not automatically lead to a diagnosis of
a toxic/metabolic encephalopathy. In many cases, these
waveforms occur in patients with brain lesions with a super-
imposed metabolic disorder.5 Up to 31% of patients with
GPDs with triphasic morphology have a metabolic, infec-
tious, and structural etiology, while only 7% have only
a metabolic etiology.4
Generalized periodic discharges with triphasic morphology
at times look very similar to spike and wave discharges seen in
NCSE, making the distinction between toxic/metabolic and
NCSE challenging. The anterior–posterior lag typically seen in
GPDs with triphasic morphology or their response to a trial of
benzodiazepines do not differentiate nonepileptiform from epi-
leptiform GPD patterns.14,15 However, various other features of
GPDs with triphasic morphology can suggest a toxic/metabolic
encephalopathy versus NCSE (Table 1). The duration of the first
phase and the entire complex is shorter in NCSE. The angles
subtended between the various phases of the complex are bigger
(more blunted), and the amplitude of the second phase is greater
in toxic/metabolic encephalopathy. The discharge is seen more
frequently in the frontocentral areas in toxic/metabolic enceph-
alopathy, while it is more often frontopolar in NCSE. Addi-
tionally, patients with NCSE have a discharge frequency greater
than 2.5 cycles per second, extra spike components, and less
background slowing.4,16 A typical GPD with triphasic mor-
phology pattern is presented in Figure 2A. Figures 2B–2D show
source modeling images for the GPDs seen in Figure 2A. Note
their frontocentral prominence.
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 Generalized Periodic Discharges K. E. Sully and A. M. Husain

FIG. 1. Generalized periodic discharges from a 50-year-old woman with asthma and cocaine abuse who presented after cardiac arrest. The
generalized periodic discharges occur at a frequency of 1 to 2 cycles per second on a suppressed background.

Infections
Generalized periodic discharges have been described as
a classic finding in various types of infections.17 Generalized
periodic discharges with short intervals between discharges,
typically 0.5 to 4 seconds (previously called periodic short-
interval diffuse discharges), are classically associated with CJD,
although there is low specificity for this association (Figs. 3A and
3B). In the patient, the GPDs are often accompanied by jerking
artifact from the accompanying myoclonus. Of note, a new
variant CJD does not show these findings.18 Subacute sclerosis
panencephalitis is associated with a characteristic GPD pattern of
high-voltage, polyphasic complexes intervened by long intervals
of 4 to 30 seconds (periodic long-interval diffuse discharges).6,17
In children, GPDs are common with encephalitis of various
types.19 Systemic infections and sepsis can also cause a GPD
pattern, and these are often similar to those seen in toxic/
metabolic encephalopathies.
Acute Neurologic Injury
Patients presenting with acute neurologic injuries often have
GPDs.7 Common etiologies for neurologic injury resulting in
GPDs include stroke, intracerebral hemorrhage, and head injury.8
Unique morphologic features of GPD in patients with acute
neurologic injury have not been described.
Nonconvulsive Status Epilepticus
An important differential diagnosis for any patient with
GPDs is NCSE.7,8,19,20 The Salzburg EEG criteria for definite
NCSE requires the frequency of the GPDs (or LPDs) to be

TABLE 1. Differentiating GPDs With Triphasic Morphology

Feature Toxic/Metabolic Encephalopathy NCSE
Duration of phase I of waveform Longer Shorter
Duration of entire waveform Longer (mean 0.32 second) Shorter (mean 0.12 second)
Angles between phases Larger (blunted) Smaller (sharp)
Amplitude of phase II Higher (mean 110 mV) Lower (mean 87 mV)
Location Frontocentral Frontopolar
Discharge frequency #2.5 cycles/second .2.5 cycles/second
Extra spike components No Yes
Background slowing More Less
Adapted from Boulanger et al. and Kaplan and Sutter.4,16
GPD, generalized periodic discharges; NCSE, nonconvulsive status epilepticus.

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 K. E. Sully and A. M. Husain Generalized Periodic Discharges

FIG. 2. A, Generalized periodic

discharges with triphasic
morphology from a 72-year-old
woman with myelodysplastic
syndrome, renal failure, and altered
mental status. Notice the triphasic
nature and the anterior to posterior
lag of the waveforms. B, Dipole
source modeling shown on a three-
dimensional brain model for the
generalized periodic discharges
shown in (A). Notice the
frontocentral nature of the dipole.
C and D, Source localization using
Swarm optimization for the
generalized periodic discharges
shown in (A) shown on a standard
MRI (C) and a three-dimensional
brain model (D). Most prominent
localization is in the frontocentral
region.

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 Generalized Periodic Discharges K. E. Sully and A. M. Husain

FIG. 3. A, Generalized periodic discharges from a 70-year-old woman with confusion, speech alteration, confusion, and generalized
myoclonus. Cerebrospinal fluid evaluation for 14-3-3 protein was positive. A presumptive diagnosis of CJD was made. Notice the broad
generalized periodic discharges that are frequently interrupted by very sharp myoclonic artifact. The EEG also appears to be suppressed on
the right side. B, Diffuse-weighted MRI scan from the patient shown in (A). Notice the abnormal areas of cortically based diffusion restriction
bilaterally, worse on the right. Such findings can be noted in CJD. CJD, Creutzfeldt–Jakob disease.

greater than 2.5 cycles per second, or if less than 2.5 cycles per
second, the discharge must be associated with subtle clinical
activity or have spatiotemporal evolution of the graphoelements
(Fig. 4). Possible NCSE may still be present even if these criteria
are not met; this occurs with GPDs less than 2.5 cycles per
second with fluctuation of the graphoelements or if the EEG
pattern improves and background activity returns with the use of
intravenous antiseizure drugs (ASDs) (Table 2).21
Attempts have been made to analyze the characteristics of the
GPDs that are slower than 2.5 cycles per second to see which
features are suggestive of NCSE. Features of GPDs with triphasic
morphology that are more consistent with NCSE than toxic/

FIG. 4. Generalized periodic discharges from 57-year-old man who was status post aortic aneurysm surgery and was noted to have altered
mental status and twitching. The generalized periodic discharges occur at a frequency of 2.5 to 3 cycles per second. This generalized periodic
discharge pattern is consistent with nonconvulsive status epilepticus.

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 K. E. Sully and A. M. Husain
TABLE 2. Salzburg EEG Criteria for Diagnosis of Nonconvulsive Status Epilepticus With GPDs
NCSE
Definite
Probable
Adapted from Leitinger et al.21
ASD, antiseizure drugs; GPD, generalized periodic discharges; NCSE, nonconvulsive status epilepticus.
metabolic encephalopathy have already been presented above and
in Table 1. The GPD characteristics (morphology, amplitude, GPD
duration, inter-GPD interval, and inter-GPD amplitude) may
suggest which ones are associated with NCSE. Generalized
periodic discharges with a high amplitude (mean ¼ 110 mV),
longer duration (mean ¼ 0.5 seconds), and preserved inter–
generalized periodic epileptiform discharge amplitude (mean ¼ 34
mV) were more likely to be associated with NCSE in one study.8
Other investigators have noted similar findings. Generalized peri-
odic discharges without triphasic waves (i.e., those with spike,
polyspikes and others), focal findings on EEG, interburst sup-
pression of less than 10 mV, history of epilepsy, or a structural
abnormality on neuroimaging were more likely to be associated
with NCSE.20 Less risk of seizures was associated when the EEG
was reactive to stimulation, a posterior dominant rhythm was
present, and sleep/wake cycles could be seen. Based on these data,
the authors proposed a GPD score based on which treatment de-
cisions can be made. They proposed that GPDs without triphasic
waves ¼ 3 points, focality on EEG ¼ 2 points, and history of
epilepsy ¼ 1. If the score is 6, treatment with ASD should be
considered, while if the score is 1, treatment should be withheld.20
For in between scores, treatment decisions are less clear.
Hypothermia
Induced hypothermia for surgical procedures, such as aortic
surgery, can result in GPDs (Fig. 5). When temperature falls below
308C, periodic discharges often appear.22,23 Although GPDs are
common, LPDs, bilateral independent periodic discharges, and
multifocal periodic discharges can also occur. As the temperature
drops further, burst suppression and finally electrocerebral inac-
tivity occur. As the temperature falls, the inter-GPD interval
increases, and the amplitude of the background activity decreases.
Toward the end of the surgery, GPD and other periodic discharges
reappear when the temperature is between 208C and 308C.22,24
With the return of normothermia, the GPDs disappear and are
replaced by mixed frequency EEG activity. Generalized periodic
discharges seen in this setting are not suggestive of epileptic
activity and do not need to be treated with ASDs.
The temperature needs to approach 308C for GPDs and other
periodic discharges to be seen. Thus, with therapeutic hypother-
mia (temperature reduction to 338C–368C) used in the treatment
204 Journal of Clinical Neurophysiology Volume 35, Number 3, May 2018
Generalized Periodic Discharges
EEG Criteria
GPDs occurring at a frequency higher than 2.5 cycles per second
GPDs occurring at a frequency not exceeding 2.5 cycles per second and at least one additional
criteria:
 Subtle clinical phenomena
 Typical spatiotemporal evolution of graphoelements
GPDs occurring at a frequency not exceeding 2.5 cycles per second and at least one additional
criteria:
 Fluctuation of graphoelement without evolution
 Only EEG improvement with intravenous ASD
of anoxic encephalopathy, these EEG patterns are usually not
seen.
PATHOPHYSIOLOGY
The pathophysiology of GPDs is not well understood. One
report theorizes that selective synaptic failure, either by disturbed
excitation of inhibitory interneurons or by intrinsic failure of the
interneurons, causes disinhibition of excitatory pyramidal cells,
thus causing GPDs.25 The concern for synaptic neurotransmis-
sion dysregulation may arise in a variety of manners.
Ischemia, postanoxic encephalopathy, toxic/metabolic de-
rangements, and infections interrupt or change cerebral synaptic
neurotransmissions in several ways: blood–brain barrier break-
down, inflammation, neurotransmitter imbalances, and apopto-
sis.26 One proposed mechanism is that the excitatory pyramidal
cells to inhibitory interneurons are sensitive to hypoxia because
they are high energy consumers, with fast-spiking interneurons
being severely affected. The inhibitory interneurons would usu-
ally feed forward to inhibit the pyramidal cells (referred to as
a feedforward inhibitory network) in a properly functioning
system. In an interrupted system, this disinhibition of the excit-
atory pyramidal cells in the setting of hypoxia or ischemia
propagates GPDs.25
NEUROIMAGING
The impact of neuroimaging on the understanding GPDs has
been limited thus far. One study evaluated 21 critically ill
pediatric patients with GPDs.19 Findings included abnormalities
in the white matter, gray matter, deep gray matter nuclei,
hemorrhagic lesions, and leptomeningeal enhancement. Another
study noted that subcortical lesions were most common but were
often associated with cortical lesions.6 Generalized periodic
discharges with triphasic morphology are associated with white
matter changes and cortical or subcortical atrophy.27 It seems that
the underlying etiology has more of an influence on the imaging
findings than the presence of GPDs. The lesions do not seem to
have a discriminatory pattern in association with GPDs.
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 Generalized Periodic Discharges K. E. Sully and A. M. Husain

FIG. 5. Generalized periodic discharges for a 61-year-old man undergoing ascending aorta surgery with hypothermic circulatory arrest. At
the time of this EEG, the patient’s nasopharyngeal temperature was 24.58C. Notice the generalized periodic discharges occurring at long
intervals with suppression of the background EEG. With rewarming the generalized periodic discharges resolved and normal background
activity returned.

there are features of the EEG that suggest a favorable prognosis,

TREATMENT
As a general rule, the value for treating GPDs remains
unclear. If the cells are irreparably damaged because of ischemia,
they are unlikely to benefit from the use of ASD. However, if
there are abnormal excitatory pathways occurring in functioning
cells, then ASD may prove beneficial. Differentiating between
these two states is challenging, and the various characteristics of
the GPDs discussed above are used to determine which state the
GPDs represent.
Generalized periodic discharge patterns that are considered
definite NCSE should be treated with ASDs. Additionally, ASDs
should be considered when patterns consistent with possible
NCSE are noted. The GPD score discussed above can assist with
this determination.20 Treatment of other patterns remains much
more controversial. Some have advocated for aggressively
treating all GPD patterns as NCSE.28 Others have suggested
more restraint, noting that GPD likely represent an injured brain
that may not respond to treatment with ASDs.1,29–31 Addition-
ally, drugs used to treat GPDs may themselves cause hepatic and
renal injury, possibly worsening the metabolic encephalopathy
causing the GPDs. There is general agreement that success of
treatment depends more on the underlying etiology than on the
electrographic seizure pattern.32
Generalized periodic discharges in the setting of anoxic
encephalopathy represent a particularly challenging scenario.
Whereas the underlying etiology of the GPDs is suggestive of
a poor prognosis, if the patient is thought to be in NCSE and
treatment should be considered. A higher GPD frequency, higher
background continuity, and lower discharge periodicity are
suggestive of a better outcome.33 A currently ongoing clinical
trial is exploring whether treatment of NCSE after cardiac arrest
(anoxic encephalopathy) is beneficial. Included in the EEG
patterns that qualify as NCSE is GPDs.34 Data from this trial
will shed light on the value of treating GPDs in at least this
patient population.
PROGNOSIS
EEG has long been used to help prognosticate outcomes
in critically ill patients. The patterns that have usually been
associated with poor outcome are an isoelectric EEG, spontane-
ous burst suppression, electrographic seizures, and periodic
complexes (including GPDs).35 In one study, only 36% of
patients with GPDs were alive at the time of discharge.8 In this
study, patients were more likely to survive if they were younger,
had seizures in addition to GPDs, and had a higher inter-GPD
interval amplitude (33 vs. 18 mV). However, a more recent study
noted that after controlling for age, etiology, and the level of
consciousness, GPDs were not an independent marker for poor
prognosis.7
Etiology of the underlying condition is often considered
a more important prognostic marker than the GPDs.32 Etiology-
specific prognosis is discussed below.

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 K. E. Sully and A. M. Husain
Anoxic Encephalopathy
In anoxic encephalopathy, GPDs often lack variability and
complexity and have a very predictable pattern. They are an early
indicator of poor prognosis in patients whose EEGs have little
background variability and a low inter-GPD amplitude.8,35
Several studies have noted that persistent GPDs are a marker
of fatal outcomes.10,25,33,36 Even in the era of therapeutic
hypothermia, the presence of GPDs or other periodic discharges
after rewarming continues to be suggestive of poor prognosis in
patients with anoxic encephalopathy.37,38
Toxic/Metabolic Encephalopathy
Patients with GPDs because of toxic/metabolic encephalop-
athy tend to have a more favorable prognosis than those with
GPDs because of anoxic encephalopathy. Despite this, in one
study, only 33% of patients with toxic/metabolic encephalopathy
were alive at discharge (compared with 11% of those with anoxic
encephalopathy).8 However, outcomes in these patients are
highly dependent on the underlying cause of the toxic/metabolic
encephalopathy.32
As discussed previously, GPDs with triphasic morphology
are often seen in patients with toxic/metabolic encephalopathy.
Mortality in these patients has been reported as high as 20%, and
in one study, the etiology of these GPDs did not appear to be
predictive of outcome.5
Infections
There is little data on the prognostic significance of GPD
when seen in cases of infections. The available literature suggests
that when GPD are seen in patients with infections of the central
nervous systemCNS, prognosis is poor. In one series, GPDs
classified as periodic, short-interval, diffuse discharge (including
patients with CJD) had a mortality of approximately 50%, while
GPDs classified as periodic, long-interval, diffuse discharge, in-
cluding patients with subacute sclerosis panencephalitis, had
a mortality of approximately 20%.6 However, this study evaluated
only routine EEGs, and mortality was evaluated in the first month.
Long-term outcome of patients with CJD and subacute sclerosis
panencephalitis is poor, regardless of the EEG pattern. In children,
GPDs are often associated with central nervous system infections.
In a study of children with GPDs, 43% of children who survived
had central nervous system infections.19
Acute Neurologic Injury
A few studies have specifically reported outcomes of
patients noted to have GPDs caused by acute neurologic injuries,
other than anoxic encephalopathy and NCSE. More patients with
acute neurologic injuries and GPDs (56%) had a favorable
outcome in one study compared with those with toxic/metabolic
encephalopathy (33%) and anoxic encephalopathy (11%) and
GPDs.8
Nonconvulsive Status Epilepticus
Somewhat conflicting results have been reported in patients
with GPDs and NCSE. One study noted that 50% of patients with
GPDs and NCSE died, while 71% of those with GPDs without
206 Journal of Clinical Neurophysiology Volume 35, Number 3, May 2018
Generalized Periodic Discharges
NCSE died.8 A larger study noted that GPDs and NCSE were an
independent predictor of worse outcome.7 More data are needed to
determine the additional risk posed by GPDs in patients in NCSE.
Hypothermia
Generalized periodic discharges reported in hypothermia
induced for surgery are reversible with rewarming. Between
208C and 308C, burst suppression appears, followed by periodic
discharges. These discharges can be GPDs, LPDs, bilateral
independent periodic discharges or multifocal periodic discharges.
As the temperatures approaches 308C, the EEG becomes contin-
uous.22,24 Barring complications from the surgery, patients with
hypothermia-induced GPDs make a full recovery.
There is much evidence yet to be gathered in understanding
GPDs and how to best manage them. The variety of injurious
afflictions to the brain that cause GPDs may originate from
sources such as ischemia and anoxic encephalopathy to toxic/
metabolic derangements and infections. Nonconvulsive status
epilepticus is a common accompaniment of GPDs. Neuroimag-
ing shows that subcortical lesions are often seen with GPDs, but
cortical lesions may also sometimes occur. When and how
aggressively GPDs should be treated remains a topic of great
debate. The underlying condition, state of the patient, and
morbidity of treatment must be considered in all treatment
decisions. Addressing the underlying etiology and any reversible
causes are the chief considerations in treating GPDs.
Studies evaluating the pathophysiology, correlation with neuro-
imaging, and the long-term prognosis of treating GPDs are needed
to help fill the gaps in knowledge. As the terminology and the
definitions have broadened over the years for what we currently call
GPDs, it is telling that clinical neurophysiologists are more willing
to admit the limited understanding we have of these waveforms.
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