Posterior Reversible Encephalopathy Syndrome (PRES); Diffuse Polymorphic Delta Activity with Posterior Predominance. A 10-year-old girl with microscopic polyangiitis and chronic renal failure developed visual hallucinations, lethargy, and new-onset seizures. She was on cyclophosphamide. After the visual hallucination, she was found to have elevation of her blood pressure. EEG shows continuously diffuse polymorphic delta activity (PDA) with occipital predominance. Head CT and MRI show diffuse white matter involvement, maximally expressed in the watershed areas in the two hemispheres. The patient recovered after cyclophosphamide was stopped, and the blood pressure was well controlled.

Diffuse slowing is the most common finding on the EEGs in posterior reversible leukoencephalopathy syndrome (PRES).¹ The delta coma EEG pattern is usually seen with more advanced states of encephalopathy and coma. With progression to deeper stages of coma, it appears diffuse and is usually unreactive. Polymorphic delta comas are due to structural abnormalities involving subcortical white matter or profound metabolic coma.^2–4

Posterior-predominant delta activity in this case is probably due to the predominant involvement of posterior head region in PRES.

Posterior Reversible Encephalopathy Syndrome (PRES); Occipital Lobe Seizure. (Same patient as in Figure 6-1) The patient developed a new-onset seizure described as head and eyes deviating to the right side, associated with unconsciousness lasting for approximately 3 minutes. EEG shows ictal activity arising from the left occipital lobe during the seizure.

Occipital lobe seizures have been described as a major clinical manifestation of PRES. This suggests that occipital lobe seizures may play a significant role in the anatomical location of the signal changes, offering an alternative explanation for the posterior location of the lesions, instead of the hypothesis that a paucity of sympathetic innervation in that region is the reason for this location.⁴ Status epilepticus (SE) can be the initial presenting symptom of PRES. Ictal EEG was obtained in six patients with SE in one series. Seizure focus was parieto-occipital in four patients and temporal in two. Seizures in PRES are often occipital in origin, which correlates well with imaging findings of predominant occipitoparietal involvement.⁶

Cerebral Herniation Syndrome; Continuous Polymorphic Delta Activity and FIRDA. A 7-year-old comatose girl with severe TBI causing intraparenchymal hemorrhage required brain decompression. Cranial CT shows bilateral intraparenchymal hemorrhage, much greater in the left fronto-temporal region (open arrow and double arrows), with compression of midline structure and probable bilateral cerebellar infarction/edema (arrow), signs of cerebral herniation syndrome. EEG shows asymmetrically and continuously diffuse mono- and polymorphic delta activity (PDA) with superimposed frontal intermittent rhythmic delta activity (FIRDA). Note a persistent focal suppression of the left fronto-temporal region.

Bilateral but lateralized PDA is characteristic of frontal lobe lesions. Functionally or structurally abnormal thalamocortical interactions, especially involving the dorsal medial nucleus of the thalamus, play a major role in IRDA.^7–9 A combination of FIRDA or OIRDA and continuously focal PDA is the classic sign of impending cerebral herniation from a focal structural abnormality. However, the same combination of patterns can also be seen in patients with focal structural lesions and coexistent toxic or metabolic encephalopathies.^10,11 Therefore, clinical correlation is required.

Improvement of Right Hemispheric FIRDA and PDA; After Resection of Necrotic Tissues, Left Hemisphere. (Same patient as in Figure 6-3) The patient developed signs of cerebral herniation. He underwent another cerebral decompression with resection of necrotic tissues in the left fronto-temporal region. EEG performed after the surgery shows continuous high-voltage polymorphic delta activity (PDA) in the left hemisphere, caused by the surgery. In addition, there is improvement of PDA and FIRDA in the frontal central midline and the right hemisphere.

Unfortunately, despite subsequent treatment with pentobarbital coma, the patient deteriorated and died 4 days after the surgery.

Improvement of FIRDA and PDA in the right hemisphere may be due to decreased intracranial pressure after the surgery, which can affect the thalamocortical interactions.

Electrocerebral Inactivity (ECI); Pulse Artifact. (Same patient as in Figure 6-3 and 6-4) The EEG shows electrocerebral inactivity before the cardiorespiratory support was discontinued. Note rhythmic delta activity, mainly at F3, time-locked with ECG indicating pulse artifact.

Electrocerebral inactivity is defined as “no cerebral activity over 2 μV when recording from scalp or referential electrode pairs, 10 or more centimeters apart with interelectrode resistances under 10,000 Ω (or impedances under 6000 Ω) but over 100 Ω.”¹²

Paradoxical Activation. EEG of a 20-month-old girl with nonaccidental trauma (NAT). There is a period of background attenuation more severe delta slowing following stimulation. This EEG reactivity is called “paradoxical activation.”

In severe encephalopathy, the EEG does not show reactivity to any stimulation and is called “invariant EEG.” In milder encephalopathy, the EEG shows spontaneous variability, evidence of EEG reactivity to stimulation, typically attenuation of amplitude, reduction of delta activity, and increase in frequency. Paradoxical activation is a period of more severe delta slowing following painful stimulation. It is seen less commonly than a typical response to stimuli but is associated with a milder degree of encephalopathy compared to the invariant EEG.¹³

EEG Reactivity in Coma; Diffuse Voltage Attenuation. (Same patient as in Figure 6-6) EEG of a 20-month-old girl with nonaccidental trauma (NAT). There is a period of background attenuation without delta slowing following stimulation.

In severe encephalopathy, the EEG does not show reactivity to any stimulation and is called “invariant EEG.” In milder encephalopathy, the EEG shows spontaneous variability, evidence of EEG reactivity to stimulation, typically attenuation of amplitude, reduction of delta activity, and increase in frequency.¹³

PLEDs (Periodic Lateralized Epileptiform Discharges); Ischemic Stroke Due to Cardiac Transplantation. A 2-year-old boy with bilateral parietal strokes, maximal in the right hemisphere (arrow) occurring after cardiac transplantation. He developed frequent seizures described as head and eyes deviating to the left side, followed by generalized tonic-clonic seizures. MRI shows bilateral watershed infarctions in the frontal parietal regions, much greater in the right hemisphere. EEG shows periodic lateralized epileptiform discharges (PLEDs) in the right parietal temporal region and polymorphic delta slowing in parietal temporal regions, greater on the right, corresponding to the strokes. Note pacemaker rhythm in the ECG channel.

PLEDs usually occur at the rate of 1–2/sec and are commonly seen in the posterior head region, especially in the parietal areas.¹⁴ Seizures occurred in 85% of patients with a mortality rate of 27%.¹⁵ Acute stroke, tumor, and central nervous system infection were the most common etiologies of PLEDs.¹⁶

Periodic Lateralized Epileptiform Discharges (PLEDs); Posterior Reversible Encephalopathy Syndrome (PRES). A 14-year-old boy with ALL s/p bone marrow transplantation who developed posterior reversible leukoencephalopathy syndrome (PRES). He developed a new-onset seizure described as left arm and facial clonic jerking with head and eyes deviating to the left side, followed by a generalized tonic clinic seizure. EEG shows periodic lateralized epileptiform discharges in the right centrotemporal region.

PLEDs were first described by Chatrian et al. (1964) to define an EEG pattern consisting of sharp waves, spikes (alone or associated with slow waves), or more complex wave forms occurring at periodic intervals. They usually occur at the rate of 1–2/sec and are commonly seen in the posterior head region, especially in the parietal areas. It is sometimes associated with EPC.¹⁴ This EEG pattern is usually related to an acute or subacute focal brain lesion involving gray matter.¹⁷ Chronic PLEDs were also reported in 9% of patients with intractable epilepsy who had structural abnormalities such as cortical dysplasia or severe remote cerebral injury.^15,16

In a recent review of 96 patients with PLEDs,¹⁹ acute stroke, tumor, and CNS infection were the most common etiologies. Others included acute hemorrhage, TBI, PRES, familial hemiplegic migraine, and cerebral amyloidosis. PLEDs were more periodic when they were associated with acute viral encephalitis than with other etiologies.²⁰ Seizure activity occurred in 85% of patients, with mortality rate of 27%. However, 50% of patients with PLEDs never developed clinical seizures.¹⁵

Periodic Epileptiform Discharges in the Mideline (PEDIM). A 2-month-old boy with anoxic encephalopathy due to SIDS. He had multifocal clonic seizures. MRI shows bilateral watershed infarction (arrows) as typically seen in anoxic encephalopathy. EEG shows quasiperiodic spikes and sharp waves the Cz electrode.

This activity has the same characteristics as periodic lateralized epileptiform discharges (PLEDs) except for its location in midline vertex. All five patients had acute onset of partial motor seizures involving the lower extremity. All patients had sustained a cerebrovascular insult, either old or new. The PEDIM and seizures suggested an origin from the watershed area between the anterior, middle, and posterior cerebral arteries, involving predominantly the parasagittal region of the cerebral hemisphere. The location of the PEDIM corresponded to the seizure type and focal neurologic deficits.²¹

Periodic Epileptiform Discharges in the Midline (PEDIM); Bilateral Mesial Frontal Infarction. A 9-month-old boy with fever, left facial twitching, and then generalized tonic clonic seizure. CSF findings showed 90 WBCs with 30 PMN, 69 lymphocytes, 1 monocyte; 46 glucose; 15 total protein; and 1000 RBCs. PCR for HSV type 2 was positive. MRI showed bilateral watershed infarction in the mesial frontal regions (arrows). EEG shows quasiperiodic spikes at the central vertex electrode consistent with the PEDIM.

The PEDIM has the same characteristics as periodic lateralized epileptiform discharges (PLEDs) except the location. In one series, all five patients had acute onset of partial motor seizures involving the lower extremity. All patients had strokes. The PEDIM and seizures suggested an origin from the watershed area, involving predominantly the parasagittal, midline parietal, or midline central areas. The patients had partial motor seizures involving predominantly the leg, and EPC with continuous clonic jerks of the legs time-locked with the PEDIM in the EEG. The seizures and PEDIM resolved after initiation of treatment with antiepileptic drugs and treatment of the underlying disorder. The EEG characteristics of PEDIM, other than being in the midline, are similar to those of PLEDs. Similar to PLEDs, the PEDIM carries a poor prognosis, three out of five patients died and two were left with significant neurologic deficits.²¹

Bilateral Independent Periodic Lateralized Epileptiform Discharges (BiPLEDs); Acute Herpes Simplex Encephalitis. A previously healthy 4-year-old girl who presented with high fever, lethargy, vomiting, and a new-onset seizure described as head and eyes deviating to the right side, followed by cyanosis. Initial CSF showed 22 WBCs (lymphocyte predominante) and 6 RBCs with normal glucose and protein. The CSF for HSV PCR was negative on three separated occasions. Brain biopsy was performed over the left occipital region. Pathology revealed numerous histocytes and inflammatory cells with early capillary proliferation scattered throughout the molecular layer. Leptomeninges showed histocytes and chronic inflammatory cells but no evidence of vasculitis. Brain tissue for herpes simplex type 1 DNA PCR was positive. (A) MRI with FLAIR sequence demonstrates hyperintense signal in bilateral temporo-occipital regions, greater on the left (arrow and open arrow). (B) Axial T1-weighted image with GAD shows increased enhancement in the left parieto-occipital regions (double arrows). EEG shows bilateral independent spikes and sharp wave complexes in the posterior temporal region with diffuse delta slowing (arrow head and asterisk). At the last follow-up 1 year later, the patient had moderate global developmental delay, visual anogsia, and well-controlled seizures.

BiPLEDs are PLEDs that are bilateral, generally asynchronous, and differ in amplitude, morphology, repetitive rate, and location. They are most commonly caused by multifocal or diffuse cerebral injury, such as anoxic encephalopathy and CNS infection, and have a poorer prognosis with a mortality of 52%, twice that of patients with PLEDs. It may be classified as periodic short-interval diffuse discharges (PLIDDs).

Bilateral Periodic Lateralized Epileptiform Discharges (BiPLEDs); Pneumococcal Meningitis. A 5-month-old boy with pneumococcal meningitis who was in a comatose state and developed seizures. DWI MRIs are compatible with multifocal ischemic infarctions. EEG performed 4 hours after the seizure described as tonic posturing and nystagmus shows bilateral independent pseudoperiodic polymorphic sharp waves and spikes in the left temporal and right parieto-temporal regions. This finding is consistent with BiPLEDs. The patient subsequently developed NCSE. At 7 months of age, he started having infantile spasms. At a 26-month follow-up, he had severe developmental delay, microcephaly, intractable CPS, and left hemiparesis.

BiPLEDs are PLEDs that are bilateral, generally asynchronous, and differ in amplitude, morphology, repetitive rate, and location. They are most commonly caused by multifocal or diffuse cerebral injury seen in patients with coma due to anoxic encephalopathy, strokes, epileptic seizure disorders, especially complex partial status epilepticus, and encephalitis.^22,23 Stroke was the most frequent cause of PLEDs, while anoxic encephalopathy and CNS infection accounted for the majority of BiPLEDs.²² Patients with BiPLEDs have a poorer prognosis with a mortality of 52%, twice that of patients with PLEDs. BiPLEDs and GPEDs after an anoxic insult carried a poor prognosis for survival. Aggressive treatment of patients may not be warranted when these EEG patterns are seen after anoxic brain injury.²⁴ BiPLEDs may be classified as periodic short-interval diffuse discharges (PLIDDs).

Bilateral Independent Periodic Lateralized Epileptiform Discharges (BIPLEDs); Watershed Infarction Associated with Cardiomyopathy. A 9-year-old boy with dilated cardiomyopathy caused by viral myocarditis. He developed rhythmic shaking of his right arm and leg with eyes deviating to the right side as well as staring off with mouth movement. Examination and CXR were compatible with congestive heart failure. Axial FLAIR MR shows bilateral watershed infarction caused by hypoxic encephalopathy from poor cardiac function. EEG shows bilateral independent pseudoperiodic spikes and polymorphic sharp waves, maximum over the posterior head regions, consistent with BiPLEDs. There was no evolving pattern as seen in his electrographic seizures. The BiPLEDs persisted throughout the prolonged recording.

BiPLEDs are PLEDs that are bilateral, generally asynchronous, and differ in amplitude, morphology, repetitive rate, and location. They are most commonly caused by multifocal or diffuse cerebral injury seen in patients with coma due to anoxic encephalopathy, strokes, epileptic seizure disorders, especially complex partial status epilepticus, and encephalitis.^23,25 Stroke was the most frequent cause of PLEDs, while anoxic encephalopathy and CNS infection accounted for the majority of BiPLEDs.²⁵ Patients with BiPLEDs have a poorer prognosis with a mortality of 52%, twice that of patients with PLEDs. BiPLEDs and GPEDs after an anoxic insult carried a poor prognosis for survival. Aggressive treatment of patients may not be warranted when these EEG patterns are seen after anoxic brain injury.²⁴

BIPLEDs; Bilateral Subdural Hematoma (Non-Accidental Trauma). A 4-month-old boy with a prolonged generalized tonic-clonic seizures due to nonaccidental trauma. Cranial CT and MRI show bilateral subdural hematoma and diffuse intracerebral hemorrhage. EEG during the comatose stage shows bilateral independent periodic lateralized epileptiform discharges in the bitemporal regions (BiPLEDS) (arrow and asterisk). This EEG pattern is commonly seen in patients with coma due to anoxic encephalopathy, strokes, epileptic seizure disorders, especially complex partial status epilepticus, and encephalitis.^23,25

Bilateral Independent Periodic Lateralized Epileptiform Discharges (BIPLEDs); Watershed Infarction Associated with Near Drowning. A 6-year-old boy with hypoplastic left ventricle with cardiac transplantation who developed anoxic encephalopathy due to near drowning. MRI shows a bilateral watershed infarction. EEG demonstrates BiPLEDs.

The following EEG findings are associated with poor outcome in hypoxic encephalopathy (HE): (1) suppression; (2) burst-suppression; (3) alpha- and theta-pattern coma; (4) generalized combined periodic complexes; (4) generalized suppression to ≤20 μV; (5) burst-suppression patterns with generalized epileptiform activity; and (6) generalized periodic complexes on a flat background.

BiPLEDs are usually caused by hypoxic encephalopathy or CNS infections and are typically associated with a poorer prognosis than PLEDs with a mortality of 52%, twice that of PLEDs patients. MRI in patients with BiPLEDs showed injury to the hippocampus bilaterally, bilateral infarction in the ACA territory or gray and white matter. Cortical involvement may be necessary in the pathogenesis in both BiPLEDs and GPEDs in patients with HE. Pathophysiology of PLEDs range from abnormal interactions between the “deranged cortex” and deeper “triggering” structures to increased local cortical irritability, possibly with involvement of normal and abnormal intracortical circuits.²⁶ However, the pathophysiological mechanism responsible for periodicity in the EEG is unknown. GPEDs and BiPLEDs after an anoxic insult carried a poor prognosis for survival. Thus aggressive treatment of patients may not be warranted when these EEG patterns are seen after anoxic brain injury.²⁴

Hemiconvulsion Hemiplegia Epilepsy Syndrome (HHE); Refractory Nonconvulsive Status Epilepticus (NCSE). A 3-year-old boy with high fever, prolonged left hemiconvulsion, eye and head deviation to the left, and lethargy. Cranial CT shows diffuse hypodensity in the entire right hemisphere s/p decompression. EEG shows continuous ictal activity in the right hemisphere, maximally expressed in the fronto-central region. At times, the sharp waves are time-locked with the clonic jerks on the left side. He underwent surgical decompression and, subsequently, removal of necrotic tissue over the right hemisphere. A small focal cortical dysplasia was identified. The patient survived but was left with permanent left hemiparesis and intractable epilepsy.

HHE is a rare sequence comprising a sudden and prolonged hemiclonic seizure during febrile illness in an otherwise normal child, followed by permanent ipsilateral hemiplegia and focal epilepsy. It is often due to CNS infection and less commonly seen in TBI or vascular. Ictal EEG shows high-voltage rhythmic slow waves intermingled with spikes, sharp waves, spike-wave complexes, or low-voltage fast activity. Higher-amplitude and more abundant epileptiform activity with posterior predominance is noted in the affected hemisphere.²⁷

Hemiconvulsion-Hemiplegia Epilepsy (HHE) Syndrome. (Same patient as in Figure 6-17) The EEG shows spike/polyspike-wave complexes time-locked with contralateral hemiclonic seizures of arm and face. Note muscle artifact, maximum in the left temporal region during the left facial twitching (open arrow). Axial and coronal T2 WI MRI shows increased signal intensity in the entire right hemisphere.

The ictal EEG is characterized by bilaterally rhythmic slow waves, with higher amplitude on the hemisphere contralateral to the clinical seizure. The spike-wave complexes are periodically interrupted by a 1- to 2-sec background attenuation.²⁸

Generalized Periodic Epileptiform Discharges (GPEDs); Status Post Cardiopulmonary Resuscitation (CPR). A 4-year-old boy with cardiac arrest after rupture of coarctation of the aorta. Head CT shows bilateral massive cerebral edema. CXR shows congestive heart failure. EEG demonstrates generalized symmetric and synchronous periodic complexes consistent with GPEDs.

Generalized periodic epileptiform discharges (GPEDs) are periodic complexes that occur throughout the brain in a symmetric and synchronized manner. They were not consistently associated with a specific etiology. Whether GPEDs represent an EEG pattern of SE is debated.^29,30 Many believe that GPEDs represent brain damage rather than ongoing SE.^31,32 GPEDs with high amplitude (mean, 110 μV) and longer duration (mean, 0.5 sec) with a preserved inter-GPED amplitude (mean, 34 μV) were more likely to be associated with SE, although these differences could not be used clinically to differentiate between SE and non-SE. Patients whose clinical history and EEG are consistent with SE should be managed aggressively with antiepileptic medications, despite GPEDs. Other characteristics that favor a more optimistic outlook include younger age, higher level of alertness at the time of the EEG, history of seizures in the current illness, and higher inter-GPED amplitude.^33,34 Presence of any GPEDs was independently associated with poor outcome in 90% of those with PEDs versus 63% of those without.³⁵ GPEDs and BiPLEDs after an anoxic insult carried a poor prognosis for survival than PLEDs. Aggressive treatment of patients may not be warranted when these EEG patterns are seen after anoxic brain injury.²⁴

Generalized Periodic Epileptiform Discharges (GPEDs); Refractory Status Epilepticus (RSE). A 9-year-old boy with refractory status epilepticus (RSE) of unknown etiology who was treated with pentobarbital coma but developed cardiorespiratory complications. He developed clinical seizures described as facial twitching and nystagmus while his pentobarbital dosage was decreased. EEG shows generalized periodic polyspikes and polyphasic sharp waves consistent with GPEDs superimposed on low-voltage background activity. The patient died after the cardiorespiratory support was withdrawn 3 days after this EEG.

Asymmetrical Generalized Periodic Epileptiform Discharges (GPEDs); Refractory Status Epilepticus (RSE). (Same recording as in Figure 6-20) EEG consistently shows asymmetric GPEDs with no clinical accompaniment. At times, there are only periodic discharges in the right hemisphere, which simulate PLEDs (not shown).