1. PLEDs (Periodic Lateralized Epileptiform Discharges) are a pattern seen on EEG characterized by periodic discharges that are lateralized to one hemisphere. 2. They are commonly seen in conditions involving acute brain injury or inflammation such as stroke, encephalitis, tumors, or hypoxic ischemic encephalopathy. 3. PLEDs are associated with a risk of seizures but generally indicate an unstable brain state that will improve over time as the underlying condition resolves. Prognosis depends on the specific cause.

1. Periodic Lateralized
Epileptiform Discharges (PLEDs)
Presenter: Sachin Adukia
Moderator: Dr Gopal Krishna Dash

2. Contents
• History
• nomenclature
• Definition of LPDs
• Classification
• Characteristics
• Evolution
• Etiology
• Pathophysiology
• Relation to seizures and prognosis
• Future direction

3. HISTORY
• Term “periodic” - Cobb & Hill in 1950 who described it
in 5 patients of encephalitis.
• first description of lateralized paroxystic activities -
Alajouanine et al (1955)
• PLEDS -“Chatrian et al” 1964

4. NOMENCLATURE
• Periodic (PDs) (La Roche, 2013)
– Repeating waveforms or discharges with relatively uniform morphology
occurring at nearly regular intervals.
– Applies only to single discharges lasting less than 0.5 second and not
bursts.
– Quantifiable interval between waveforms.
– Intervals have < 50% variation from cycle to cycle
• Generally varies less than 20% within an individual EEG but may vary
significantly from patient to patient; San Juan Orta (2009)
• Lateralized (L)
– unilateral hemispheric or focal patterns
– Can include PDs seen synchronously over both hemispheres but clearly
more prominent on one side
• Epileptiform ???......Controversy
– Hirsch et al (2013)- subcommittee of ACNS- replaced PLEDs with LPDs
(Lateralized Periodic Discharges)

7. PDs are classified as:
• Periodic lateralized epileptiform discharges (PLEDs).
• Bilateral independent PLEDs (BIPLEDs)
• Generalized periodic epileptiform discharges (GPDs)
• Triphasic waves
Brenner RP, Schaul N. Periodic EEG patterns: classification, clinical correlation and
pathophysiology. J Clin Neurophysiol 1990;7:249-267.

10. 4 yr male, arrest with acute diffuse HIE with mild diffuse cerebral edema.

12. 64 yr male, Lt hemisph infarction
EEG- Left hemisph dominant GPDs

15. Reiher et al. (1991) – observed brief and low amplitude focal stereotyped
rhythmic discharges (RDs) closely a/w higher amplitude interictal
epileptiform discharges; subdivided PLEDs as
• PLEDs proper (without RDs)
 Class I - Aperiodic, throughout
 Class II - Metronomic*, intermittent
 Class III – Metronomic*, throughout
• PLEDs plus (with RDs)
 Class IV - brief RDs < 1 sec
 Class V - prolonged RDs
*Metronomic periodicity - recurrence of discharges at constant intervals

16. CHARACTERISTICS
Occurrence
• uncommon , incidence range of 0.1% - 1 %.
• Incidence increases when EEG is performed earlier in the disease course.
• commonly in older patient - stroke
• may also occur in children, infants- infections
Morphology
• Usually surface –ve bi-, tri- & polyphasic spikes and sharp waves,
• maximal ipsilateral to structural involvement
• amplitudes - 100 to 300 µV, may be higher
• Duration- between 100-300 msec
• Recurrence frequency – 1 per 0.5 to 4 sec (usually recur at least every 2 sec)

17. Features
• Persist during both REM and NREM sleep and sometimes recur
during drowsiness after disappearance in wakefulness.
• Reactivity to HV, photic and noxious stimuli is diminished or absent.

18. ETIOLOGY
• Stroke
• Infectious disease
– HSV encephalitis/ Focal Encephalitis
– TBM
– Early stages of CJD
– Abscess
– AIDS,
– Neurosyphilis
• Metabolic Conditions
– Hypoxia,
– Hyponatremia,
– Non-ketotic Hyperosmolar Syndrome
– hypoglycemia,
– alcohol withdrawal,
– Hepatic encephalopathy,
– CO poisoning.

19. Other rare associations
– Neurobehcets
– Fat Embolsim
– Porencephalic cysts
– Sickle cell disease
– Mitochondrial disorders
– Tumor
– Anoxic encephalopathy
– Subarachnoid hemorrhage
– Creutzfeld–Jacob disease
– Cranioencephalic trauma, Hematoma
– Multiple sclerosis
– Migraine

20. • PLEDs - a response to acute process.
• Stroke is most common cause.
• - Embolism >> thrombosis
- watershed infarcts >> single vessel stroke
- Post CEA hyperperfusion (Reigel et al. 1987)
• Acute cortical lesions with subcortical white matter involvement are
MC imaging finding in new-onset PLEDs

21. GARCÍA–MORALES ET AL., J Clin Neurophysiol, Vol. 19, No. 2, 2002

22. THEORIES OF PLEDs NEUROPHYSIOLOGY
• Pohlmann et al (1996) PLEDs are EEG signature of a dynamic
patho-physiological state in which unstable neurobiological processes
create an ictal-interictal continuum.
– an unstable brain state related to the combination of one or more of
seizures, structural injury and metabolic derangement
• No single common unifying mechanism

23. • Cobb and Hill (1950)
“Cortical isolation” hypothesis which suggested that PEDs could arise
from cortex that had been severed from subcortical structures usually
caused by a large white matter lesion.
• Lee 1988, Handforth 1994
PET and SPECT show hypermetabolism and hyperperfusion in PLED foci,
respectively but these reflect increased neuronal activity rather than seizure.
• Kalamangalam (2015)
synchronization of pre-existing local field potentials, through
enhancement of excitatory neurotransmission and inactivation of
inhibitory neurotransmission provoked by the PLED-associated disease
process

24. EVOLUTION OF PLEDS
• 90% acute PLEDs disappear within 4 weeks. (Schwartz 1973) or may evolve to
– Seizure
– Isolated high voltage slow waves with delta/theta activity
– Sporadic spikes or sharp waves
– May persist as Chronic PLEDs, some lasting 18 months to 20 years
(Westmoreland 1986)
– May be recurrent eg in TIAs and symptomatic epilepsy.
• With time PLED Plus evolve into periodic PLEDs (class 2 and 3) & then into
aperiodic PLEDs ( class 1).
– accompanied by decreased frequency of clinical seizures.
• Seizures higher in PLED Plus than PLEDs proper.

26. PLEDs Mimics
• EKG artifact:
 ECG artifact max in Temporal or occipital
 PLEDs usually not as regular
• Other mimics:
External device artefact
Electrode artefact

27. PLEDs in HSE
•hallmark of HSE is pseudoperiodic slow complexes or PLEDs in the
setting of symptoms s/o CNS infection
•Seen in ~80% of adults at some point during illness
•Initially diffusely slow background is seen
within the first week periodic pattern manifests .
•characteristically unilateral, may be bilateral and independent
•temporal in predominance.
•recur per 1.0 to 2.5 sec and abate after weeks
•No correlation with mortality/ prognosis

32. PLEDs in CJD
•pseudoperiodic generalized sharp wave with diffuse slow background.
• biphasic or triphasic sharply contoured waveforms of varying durations
•repeat with a period of 0.5 to 2.0 sec and shorten with disease progress
•Rarely unilateral, typically anterior predominant
•appear within 3 months of onset in almost all
•frequently time locked to myoclonic jerks.

36. Relation of PLEDs to seizures
• Seizures occur at a frequency of 58 – 100% in PLEDs
• Focal motor seizures are the commonest
• sometimes appear to be an interictal feature, may or may not presage
clinical or electrographic seizure
• seizures occur traditionally with PLEDs, but can exist in patients who
never develop either clinical or EEG Sz
• no significant association between seizures and etiology.
• No significant difference in degree of functional outcome between
patients with or without PLED-associated seizures

37. 38 patients (84.4%) of 45 with PLEDs experiencing a seizure disorder.
26 had their first seizure during their acute illness, as PLED was encountered.
8 had SE , and 7 had EPC
Sz can be- focal motor, sensorimotor, CPS, GTCS,, SE, EPC

38. • Schraeder et al, Epilepsia1980
 20 of the 24 patients with PLEDs had seizures
 Seizure disorders a/w PLEDs – may be more refractory
 concurrent Sz and PLEDS = signif. mortality and morbidity
 Pts with no seizures in a/w PLEDS have little chance of developing a
seizure disorder
.

39. • San juan Orta et al, Arch Neurol 2009
 Prognosis depends on the underlying etiology
 The worst prognosis noted for acute severe stroke
 In patients with PLEDs, the absence of clinical seizures at the time of
detection were more associated with death,
 those with non-neoplastic etiology - good clinical outcome ???? caveat
• Nei et al Epilepsia 1999
 PLEDs are the only EEG feature related to poor outcome in SE
independent of etiology.

40. Controversy….Are PLEDs ictal?
? No
Interrupted by seizure and slowly return thereafter.
Are common and self limiting part of the EEG evolution of the acute lesions.
A transient postictal pattern in some epilepsy patients.
? Yes
Exceptionally in EPC, PLEDs may be time locked.
PET hypermetabolism and SPECT Hyperperfusuion reported
 ? Seizure ? Increased Neuronal metabolism
? A peri-ictal pattern
Sequential PLEDs.
Association with seizure vulnerability.
Focal hyperexcitability in penumbra zone

41. •Mortality was unchanged with or without treatment of patients with
PLEDs on cEEG
•PLEDs without structural lesion can be ictal, interictal or postictal
finding on EEG
resulted in a higher mortality rate.

42. 1. no standard management for diagnosis, prevention and Rx of
seizures associated to PLEDs
2. Strongly consider treatment if:
 Presence of myoclonic or clonic movements, nystagmus or rhythmic
blinking time locked to appearance of PDs (ie, ictal PDs).
 Decline in clinical state that coincides with onset of PD
 History of any of the following:
 epilepsy or recent clinical seizure/SE.
 Acute structural lesion a/w high risk of seizures (SAH,ICH,TBI)
3. Start or maintain a conventional AED in all PLEDs without
escalating treatment unless clear ictal electrographic or clinical
semiology is observed

43. BIPLEDs
• defined as periodic discharges are independently and simultaneously
present in both hemispheres.
• First described in HSE
• far less common than PLEDs,
• Incidence in ICU: 4 to 22%, Routine EEG – 0.1%, as low as 0.09%
• Bilaterally asynchronous
• Differ in morphology, amplitude, repetition, rate, site of maximum
involvement
• higher risk for seizures, depressed consc., mortality than PLEDs
• greater vigilance for epileptic activity required than in PLEDs,
• approach to AED management is the same.

44. 46 yr male, acute infarct in bilateral occipital
lobes and posterior thalami

46. 2 yr male, Post op, Arrest with CT s/o HIE
EEG- BiPLEDs

48. PLEDS Vs BIPLEDS
• PLEDS
– Stroke – most common
– Focal seizures 
– FND 
– Coma 
– Mortality less
– Imaging focal lesions
BiPLEDs
– Anoxia and CNS inf. MC,
– Generalized seizures
– FND - less
– Coma 
– Mortality more
– Imaging B/L lesions

49. Ipsilateral Independent PLEDs (IpsiIPs)
• Rare subtype
• First described in 1996
• Ipsilateral but independent in temporal & topographical relationship
• Associated with
– Acute cerebral lesions
– Altered consciousness & seizures
– Resolution with time

51. Multifocal PLEDS
• 3 or more independent foci of PLEDs located over both hemispheres.
• 3 foci are also called TriPLEDs.
• Reflect severe brain dysfunction
• significant mortality rate.
Lawn, Westmoreland & Sharbrough. Clin Neurophysiology 2000;111(12): 2125-2129

53. PEDIMS
• Described by Frere et al – 1989
• Periodic epileptiform discharges in the mid line or “PEDIMS”
• Other than its location, this activity has same characteristics as
commonly encountered PLEDs.
• s/i association with underlying stroke and seizures

54. Chronic PLEDs
• Classified separately as they persist in serial recordings for several
weeks to months /years.
• Requires serial EEGs to document PLEDs.
• No definite differentiating characters in chronic vs. acute
• Background in between discharges usually normal
• Found in chronic cerebral lesions or long standing epilepsy.
 old stroke, tuberous sclerosis, chronic abscess, porencephalic cyst.

55. SIRPID
Stimulus-induced rhythmic, periodic, or ictal discharges
•Periodic, rhythmic, or ictal-appearing discharges consistently induced by
alerting stimuli such as auditory stimuli, sternal rub, examination, suctioning,
turning, and other patient-care activities.
•s/i approximately 20% of cEEG monitoring
•fall somewhere along the ictal-interictal continuum.
•Clinical or subclinical/electrographic seizures in about half of the patients
•SE more frequently in focal or ictal appearing SIRPIDs
•treatment with a conventional AED,
•if already on AED, escalation not recommended
•After cardiac arrest, SIRPIDs a/w poor outcome

57. PLEDs plus: fast RDs

58. GPDs with BSP

59. GPDs with D2/S2

60. Future experimental studies
Should focus on role of cellular mechanisms underlying periodicity
Developing an organized approach to the management of common
EEG patterns encountered in ICU

61. References
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64. Thank You