Main term 1
Main term 2
Plus modifiers
Generalized (G)
Periodic discharges (PDs)
+F
Superimposed fast activity (PDs and RDA only)
Lateralized (L)
+R
Superimposed rhythmic activity (PDs only)
Bilateral independent (BI)
+FR
Both superimposed fast and rhythmic (PDs only)
Multifocal (Mf)
Rhythmic delta activity (RDA)
+F
Superimposed fast activity (PDs and RDA only)
+S
Superimposed sharp waves or spikes or sharply contoured (RDA only)
+FS
Both superimposed fast and sharp waves or spikes or sharply contoured (RDA only)
Spike–and–wave or sharp–and–wave (SW)
No plus modifiers
Additional modifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
Prevalence (% of record) | Rare <1 % | Occasional 1–9 % | Frequent 10–49 % | Abundant 50–89 % | Continuous ≥90 % | ||||
Duration (s) | Very brief <10 s | Brief 10–59 s | Intermediate 1–4.9 min | Long 5–59 min | Very long ≥1 h | ||||
Frequency (cycle/s) | <0.5 | 0.5 | 1 | 1.5 | 2 | 2.5 | 3 | 3.5 | ≥4 |
Sharpness (ms) | Blunt >200 | Sharply contoured >200 with sharp morphology | Sharp 70–200 | Spiky <70 | |||||
Stimulus-induced | Stimulus induced (SI-) | Spontaneous (Sp-) | Unknown | ||||||
The revised 2012 ACNS terminology included changes made based on solicited feedback and studies of inter-rater agreement on the use of the terminology. The first assessment found that inter- and intra-observer agreement for the presence/absence of rhythmic or periodic patterns and for localization of these patterns was moderate and agreement for the modifiers was slight to fair [11]. After initial changes were made to the criteria, an assessment was conducted using the interim version. Inter-rater agreement for the main terms was almost perfect, but agreement on modifiers was more variable [12]. In the most recent assessment, the inter-rater agreement using the revised 2012 ACNS terminology was found to be almost perfect for the two main terms (i.e., pattern location (91 %) and pattern type (85 %)). Modifiers including sharpness, absolute amplitude, frequency and number of phases, and the + S modifier also had an “almost perfect” agreement (greater than 80 %), while the + F and + R modifiers had “substantial agreement.” However, agreement for triphasic morphology and evolution were “moderate” (58 %) and “fair” (21 %), respectively [5]. While further work may need to be done to improve the understanding and reproducibility of some of the modifiers, main terms one and two seem to be easily recognized and reliable. As a result, they have now largely replaced older terminology in both clinical reports and cEEG literature.
An overview of each of the periodic patterns, alternative terminology, characteristics, prevalence, association with seizures, mortality rate, and common etiologies is listed in Table 2.
Table 2
Overview of periodic discharges and rhythmic delta activity patterns
Consortium terminology | Other names | Characteristics | Prevalence | Association with seizures | Mortality rate | Common etiologies |
|---|---|---|---|---|---|---|
LPDs Lateralized periodic discharges | PLEDs | Lateralized repetitive discharges recurring at 0.5–3 Hz; typically with broad field but may be focal | 0.4–1 % (rEEG) | Neoplastic lesions [14] Viral encephalitis, ICH, SAH, and anoxic encephalopathy [18] | ||
BIPDs Bilateral independent lateralized periodic discharges | BIPLEDs | Asynchronous periodic discharges occur independently but simultaneously over both hemispheres | 0.1 % (rEEG) [15] | 70 % [15] | CNS infection, anoxia, chronic epilepsy, stroke, tumor, metabolic abnormalities, bilateral structural lesions2,29 | |
GPDs Generalized periodic discharges | GPEDs | Synchronous discharges that are relatively symmetric in amplitude across homologous regions | 0.01–1 % (rEEG) | 46 % [3] | 36 % in one study [3] | |
GPDs–TW a Generalized periodic discharges Triphasic morphology | Triphasic Waves | Discharges consisting of three phases, each longer than the preceding one with a surface positive high-amplitude wave preceded and followed by negative waves with a smaller amplitude | 20–57 % (rEEG) [1] | Metabolic encephalopathy, steroid responsive encephalopathy, toxic encephalopathy, postictal stupor [28] | ||
LRDA Lateralized rhythmic delta activity | Rhythmic delta pattern as a repetitive waveform with relatively uniform morphology and duration; lateralized to one hemisphere | 4.7 % (cEEG) [4] | 63 % [4] | NR | CNS neoplasm, subarachnoid hemorrhage, subdural hemorrhage, intracerebral hemorrhage, ischemic stroke [1] | |
GRDA Generalized rhythmic delta activity | Rhythmic delta pattern with a generalized distribution | NR | NR | NR | Non-specific, including focal and diffuse processes, limbic encephalitis, toxic-metabolic encephalopathy |
Periodic Discharges
PDs are discharges with both a uniform morphology and duration that repeat with a definable and quantifiable interval between consecutive waveforms [8]. These waveforms recur at nearly regular intervals [7]. The discharges can be generalized, lateralized, bilateral independent, or multifocal [8]. Common etiologies include infectious and toxic-metabolic etiologies.
Lateralized Periodic Discharges
Lateralized periodic discharges (LPDs) are discrete repetitive discharges that are lateralized to one hemisphere and have a consistent morphology that recur at periodic intervals, most frequently, between 0.5 and 3 Hz (Fig. 1). This pattern was first termed “periodic lateralized epileptiform discharges” (PLEDs) by Chatrian et al. in 1964 [18]. The term was then changed to LPDs as part of the new ACNS terminology [9]. Traditionally, the discharges are sharp waves or sharp wave complexes ranging from 50 to 300 μV. The new ACNS terminology proposes that the term applies to all PDs regardless of morphology. The discharges must be lateralized to one hemisphere but can be maximal in any focal area of the brain [18]. Most frequently, the field of discharges is broad, including the parasagittal chains and temporal chains of the ipsilateral hemisphere, though focal PDs are still considered LPDs. LPDs can involve the contralateral hemisphere; this is commonly seen if the discharges are maximal in the frontal or occipital regions; however, the discharges must have higher amplitude over one hemisphere [18]. It is important to exclude periodic artifacts that can mimic LPDs, most commonly electrocardiographic or pulse artifact.
Fig. 1
Lateralized periodic discharges (LPDs) in a 61-year-old man with history of alcohol abuse initially presenting after a witnessed generalized tonic-clonic convulsion. In the emergency department, he was noted to have fever and right hemiparesis. CT of the brain demonstrated multifocal infarcts, including the left MCA territory and bilateral PCA infarcts, thought to be cardioembolic in etiology. LPDs seen here later evolved to discrete seizures
LPDs are typically associated with ipsilateral cerebral dysfunction. As such, there is usually focal slowing or loss of the posterior dominant rhythm in that hemisphere. The contralateral hemisphere may show evidence of an encephalopathy, although it may also be unaffected.
The overall incidence of LPDs was previously estimated to be 0.4–1 % based on routine EEG studies; however, a more recent study evaluating cEEG has reported an incidence as 8.6 % in patients with cEEG monitoring [4, 13, 14]. Classically, this pattern has been considered a transient phenomenon, usually seen within the first days of an acute brain insult and often resolving within days to weeks [13].
In historic literature based on routine EEGs, the most common etiology associated with LPDs is an acute or subacute structural lesion involving the cortex, typically caused by an ischemic stroke [13, 15, 18]. In the authors’ series, neoplastic lesions were the most common cause of LPDs on cEEG, possibly reflecting a difference in monitoring practices [14]. Other etiologies include viral encephalitis (i.e., herpes encephalitis), intracranial hemorrhage, tumors, subarachnoid hemorrhage, and anoxic encephalopathy. LPDs have been described in posterior reversible encephalopathy syndrome, migraine, demyelinating diseases, Creutzfeldt-Jakob disease (CJD), and mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) [29]. While stroke and hypoxic-ischemic encephalopathy are common etiologies for LPDs among neonates, an infectious etiology is more common in the rest of the pediatric population. One study found that 2/3 of pediatric patients with LPDs had central nervous system infections [30].
The majority of patients with LPDs do not have a prior history of epilepsy; however, seizures occur in the majority of patients with LPDs during their hospitalization, seen in 49–100 % of patients with LPDs [4, 15–17]. The most common seizure type associated with LPDs is focal motor seizures [13, 16, 18]. Both clinical and nonconvulsive seizures are associated with LPDs. One study found that of all patients with seizures identified during continuous monitoring, 40 % had LPDs. The majority of the seizures identified were nonconvulsive. Furthermore, approximately 20 % of patients with LPDs had their first seizure after the first 24 h of continuous monitoring, compared to 8 % of patients without LPDs [31].
A subtype of LPDs, namely, LPDs + F (or previously PLEDs+), were first described as LPDs with superimposed rhythmic discharges, typically low-voltage fast activity. This pattern has been reported to be more frequently associated with clinical or electrographic seizures compared to LPDs alone (74 % vs. 6 %, respectively, in one study) [32] (Fig. 2).
Fig. 2
Lateralized periodic discharges with fast activity (LPDs + F) in a 55-year-old woman with history of diabetes presenting with hyperglycemia and altered mental status. Continuous EEG demonstrated 1 Hz left hemispheric LPDs + F as well as frequent electrographic seizures arising from the left parieto-occipital region
LPDs are typically considered ictal if the PDs are time locked to electromyographic recordings demonstrating clonic activity. This pattern is frequently associated with LPDs arising from the hemisphere contralateral to the focal clonic seizures (Fig. 3).
Fig. 3
Ictal lateralized periodic discharges (LPDs) in an 87-year-old woman who presented with altered mental status and rhythmic clonic movements of her left face, arm, and leg after probable convulsion at home. EEG demonstrates lateralized periodic discharges, maximal over the right frontocentral region, time locked with focal movements of the left lower extremity (i.e., EMG lead, “L leg”). MRI of the brain was negative for a focal lesion. Etiology cryptogenic, suspected to be infectious vs. inflammatory
In most studies, LPDs have been associated with a high mortality rate in adults, ranging from 24 to 53 % [13, 15]. LPDs have been found to be an independent predictor of poor outcome (moderate to severe disability or death) in patients with subarachnoid hemorrhage, intracerebral hemorrhage, and patients in the medical intensive care unit [33–35]. Interestingly, in one study of adult patients, the occurrence of seizures in patients with LPDs was associated with a lower likelihood of death as a clinical outcome compared to LPDs that occurred without seizures [15]. In one study of 44 pediatric patients with LPDs, the mortality rate was 23 % and morbidity rate was 50 % [30]. Of the patients with LPDs, a better prognosis is seen among patients with a prior history of epilepsy or children with acute infections.
On account of the strong association with seizures, most experts agree that if LPDs are seen on EEG, the patient should be treated with at least one antiepileptic drug (AED) to prevent further seizures. Whether or not to “treat” LPDs to resolution of the pattern remains highly controversial. A common practice has been to “treat” LPDs when the pattern has a clear clinical correlate. However, the most commonly recognized clinical correlate is clonic motor jerking, which has been shown to be principally a manifestation of the location of LPDs or underlying lesion in or near the motor cortex [36]. LPDs in other locations may have subtle clinical correlates such as aphasia, eye deviation, or cognitive changes, which are subtle and particularly hard to recognize when a patient is in coma [29]. For example, evaluating whether frontopolar or occipital LPDs have a clinical correlate in a patient in iatrogenic coma is not feasible. This does not necessarily mean that all LPDs should be treated aggressively. LPDs can often be seen following clinical seizures or resolution of status epilepticus (SE). They may also be very resistant to escalating medications and can take days to weeks to resolve; thus, it is unclear if aggressive treatment with sedating medications or anesthesia is always warranted [13, 37]. Ultimately, the decision to treat must account for the underlying etiology and overall clinical context including the progression of the patient’s EEG patterns. While there is no agreed-upon prescription for treating LPDs, a common approach in a patient who has had nonconvulsive status that converted to complex LPDs is to watch the LPDs for at least 1–2 days and continue the observation without intervention as long as there is progressive improvement in the complexity and frequency of the LPDs (Fig. 4).
