Fig. 5.1
Examples of periodic and rhythmic waveforms. EEG is displayed in a longitudinal bipolar montage. Filter settings and scale are shown in the figure. a Left temporoparietal lateralized periodic discharges occurring at 0.5–1 Hz. Note the regular recurrence of waveforms that appear similar in morphology, and a measurable inter-discharge interval. b Frontally predominant generalized rhythmic delta at approximately 2 Hz in a very brief (<10 s) run. Note again a regular recurrence of similar appearing waveforms. Rhythmic discharges are characterized by a lack of an inter-discharge interval
Table 5.1
Updated terminology for periodic and rhythmic discharges
Commonly Used Terminology |
Standardized ACNS terminology |
---|---|
Periodic lateralized epileptiform discharges (PLEDs) |
Lateralized periodic discharges (LPDs) |
PLEDs+ |
LPDs+, with modifiers +F for superimposed faster frequencies or +R for superimposed rhythmic frequencies |
Generalized periodic epileptiform discharges (GPEDs) |
Generalized periodic discharges (GPDs) |
Triphasic waves |
GPDs with triphasic morphology |
Bilateral independent periodic lateralized epileptiform discharges (BIPLEDs) |
Bilateral independent periodic discharges (BIPDs) |
Frontally predominant intermittent rhythmic delta activity (FIRDA) |
Frontally predominant generalized rhythmic delta activity (GRDA) |
Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) with focal rhythmic delta activity |
Stimulus-induced lateralized rhythmic delta activity (SI-LRDA) |
Periodic Discharges: Pathophysiology
Periodic discharges (PD) are thought to represent synchronized, aberrant firing of dysfunctional populations of cortical neurons with prolonged recovery times, or refractory periods, analogous to that observed after the paroxysmal depolarizing shift that characterizes epileptiform discharges [6–8]. In a model of the hippocampal CA3 region, spontaneous excitatory postsynaptic potentials (EPSPs) trigger neuronal bursting by depolarization of postsynaptic neurons in an excitable post-refractory state or even (if the quantity of EPSPs is great enough) neurons still in a refractory state [9]. Decreased interneuronal inhibition of adjacent neuronal column coupling, resulting in excess excitation, may result from frequent depolarizations [10] and manifest as periodic, phase-locked, super-positioned bursts [11]. By contrast, increased inhibitory tone may make otherwise continuous ictal activity appear periodic [12]. In cortical slice models, a silent interval between discharges has been associated with discharge-induced extracellular alkalization and potassium concentrations with intracellular acidification, inhibiting synchronized neuronal firing by uncoupling gap junctions. Interestingly, when the intracellular acidification was prevented, periodicity was replaced with continuous ictal activity [13]. More recently, the observed spatial dynamics of ictal discharges suggest that small cortical areas of tonic firing (termed the ictal wavefront) generate much larger regions of synchronized, rhythmic discharges distinct from the source of ictal activity [14, 15] and that these lower frequency discharges counterintuitively reflect desynchronized neuronal bursting and eventual seizure termination. For this reason, periodic discharges may be recorded on scalp EEG as a result of either multifocal or aberrantly propagating ictal wavefronts, or as a result of increasing refractoriness to a persistent ictal focus. Evidence exists that smaller foci of ictal activity may underlie surface EEG that demonstrates only interictal, periodic, or rhythmic discharges (Fig. 5.2) [16, 17].
Fig. 5.2
Example of cortical seizure seen as generalized rhythmic delta on surface EEG. 44-year-old man with respiratory arrest and asystole who presented in coma with myoclonic jerking movements. An invasive cortical electrode was placed for multimodal neuromonitoring. Surface or scalp EEG is displayed in a longitudinal bipolar montage (black waveforms), and depth electrode recordings are displayed in a bipolar montage (blue waveforms), with D1 representing the deepest contact, and D8 representing the most superficial contact. The depth recording demonstrates an evolving ictal theta-alpha pattern with spread into neighboring electrodes, while the scalp EEG reflects 1–1.5 Hz generalized rhythmic delta. Low frequency filter set at 1 Hz; high frequency filter set at 70 Hz; the sensitivity of the scalp recording is set at 7 uV/mm, depth recording at 15 uV/mm
Periodic or rhythmic discharges in some cases may not be ictal, but a manifestation of neuronal death [18, 19] or of an anatomic disconnection between cortical and subcortical regions [5], both of which create conditions for abnormally synchronous cortical oscillations and may contribute to cortical hyperexcitability. Animal studies have demonstrated that while the application of excitatory substances to intact cortex produces irregular rhythmic bursts, much more regular rhythmic bursts occur with thalamectomized cortex [20]. Moreover, nearly regular periodic bursts with interburst suppression are seen upon stimulation of completely undercut perfused cortex. In humans, one case-control study found radiographic evidence of white matter changes and subcortical atrophy (but not cortical atrophy) associated with encephalopathy and generalized periodic discharges with triphasic morphology [21]. Autopsy-based studies, however, have demonstrated that periodic discharges may be recorded distant to a pathologic lesion or from intact cortex [22]. After generalized convulsive status epilepticus (GCSE), periodic discharges are often observed on an attenuated background [23, 24], and others have suggested that periodic discharges particularly represent a “fatigued” state of clonic firing [25]. Periodic discharges have also been recorded in ischemic penumbra of animals undergoing occlusion of the middle cerebral artery [26]; contralateral to the occlusion, rhythmic delta activity was observed, suggesting that periodic and rhythmic discharges reflect broader changes in the balance between inhibition and excitation. Whether periodic discharges reflect aberrant ictal activity or an alteration in inhibitory and excitatory cortical inputs, cortical dysfunction remains the common denominator. Direct cortical injury, such as hypoxia, or widespread metabolic dysfunction, such as acute hepatic failure, may equally result in a similar EEG phenotype, a concept reflected in the term “interictal-ictal continuum,” used to describe periodic or rhythmic patterns that may or not be ictal depending on their complex, underlying contributors [27].
Periodic Discharges: Implications for Seizure Detection
Both periodic and rhythmic discharges are highly associated with the development of clear, unequivocal seizures. In a retrospective analysis of 625 consecutive hospitalized patients undergoing >18 h of C-EEG, periodic discharges were recorded during the first 30 min in 10% (60/625) of patients, 27% (16/60) of whom had a seizure at some point thereafter [28]. Of 570 hospitalized patients undergoing C-EEG, lateralized periodic discharges (LPDs) were associated with seizures only after >24 h of monitoring, with an odds ratio of 3.1 [29], while in a case-control study of generalized periodic discharges (GPDs), only those with GPDs exhibited seizures after >48 h of monitoring compared with controls without GPDs [30]. Currently, guidelines from the Neurocritical Care Society recommend at least 48 h of C-EEG for comatose patients to rule out NCSE [31]. A 2010 survey found that the majority of adult and pediatric neurologists would monitor C-EEG in patients with periodic discharges for >24 h (40% for 24 h, 29% for 48 h, and 15% for 72 h) [32]. We recommend up to 48 h of C-EEG for all hospitalized patients with newly diagnosed periodic or rhythmic discharges where resources are available. Where C-EEG is not available, we recommend repeated EEG evaluation for patients with periodic or rhythmic discharges who exhibit intermittent or persistent changes in neurologic examination.
Lateralized Periodic Discharges (LPDs): Incidence and Association with Seizures
Focal or multifocal regions of periodic discharges are termed LPDs, bilateral independent periodic discharges (BIPDs), or multifocal periodic discharges (MfPDs). LPDs were initially described as repetitive, lateralized, spike- or sharp-wave complexes followed by a slow-wave and lasting from 0.3 to 2 s with repetition rates of 0.2 to 3 Hz [22, 25, 27, 33]. LPDs may be focal or spread broadly over one hemisphere, sometimes with extension to the homologous area on the contralateral side (albeit to a lesser extent). Most often, LPDs and BIPDs have maximum voltage in the frontocentral regions [34]. LPDs tend to vary from patient to patient in their periodicity (0.5–4 s) [27], morphology (e.g., biphasic, triphasic, or polyphasic spike- and sharp-waves) [35], voltage (50–300 μV), and duration (60–1000 ms) [36]. LPDs do not always exist continuously over the entirety of a recording, although LPDs have persisted for months and even years [33, 37, 38]. More commonly, LPDs dissipate between 9 and 16 days (range 1–31 days) after clinical symptom onset, even in the face of progressive neurologic disease (e.g., progressive brain tumor) [22, 25, 33, 39]. Their natural progression proceeds with decreasing frequency, prolongation of discharge duration, and evolution to paroxysmal delta and finally theta frequency slowing [33].
LPDs have been described in 0.4–1% of routine EEGs [27] and in 6–22% of C-EEG series [29, 40, 41]. Clinically, LPDs are often accompanied by focal neurologic deficits and alterations in mental status [33]. LPDs may be the electrographic correlate of focal seizures, such as epilepsia partialis continua [42], focal sensory-motor seizures [43], or complex partial seizures [22, 33, 44]. More often, LPDs occur in association with an acute or subacute focal neurologic disease, usually involving the cortex, capable of generating symptoms independent of LPDs [38, 45]. Table 5.2 lists etiologies associated with LPDs [22, 25, 33, 35–38, 45–64]. The most common etiology underlying LPDs is ischemic stroke [22, 33, 35, 65, 66]. In a meta-analysis of 586 patients from several earlier studies of LPDs (1964–1987), 35% had a primary etiology of ischemic stroke [25]. Interestingly, one in ten had a metabolic etiology, suggesting a role for metabolic stressors in lowering the threshold for LPDs to develop in much the same way that the seizure threshold may be lowered in patients with epilepsy. Studies utilizing C-EEG have confirmed that one-quarter have remote or progressive brain disease [67]. Some have focused on specific disease processes: LPDs were seen in 13% of those with intracerebral hemorrhage (ICH), particularly when bleeding was closer to the cortex (<1 mm) and when ICH was greater than 60 cc 24–72 h post-bleed, and less frequently in the presence of midline shift 3–7 days post-bleed [68]. LPDs were also observed in 20% of those with subarachnoid hemorrhage (SAH) [69]. Within 24–48 h of suspected herpes simplex encephalitis, LPDs were observed in 90% with positive HSV PCRs (at symptom onset) and 30% with negative HSV PCRs; the sensitivity of EEG decreased after 48 h [70]. Even cohorts of patients undergoing C-EEG may under-estimate the frequency of periodic discharges in those with critical neurologic illness such as traumatic brain injury or subarachnoid hemorrhage, because scalp EEG recordings can miss some focal periodic discharges seen only on direct cortical recordings [16, 17]. For instance, in a series of patients with traumatic brain injury (TBI), 38.2% (13/34) had periodic discharges recorded during electrocorticography, of whom 8/13 had no periodic discharges on surface EEG [17].
Category |
Etiology |
---|---|
Neurovascular |
Ischemic infarct (arterial occlusion, watershed infarct, global anoxic ischemic injury, neonatal encephalopathy, sickle cell disease)
Intracerebral hemorrhage (acute or remote)
Cerebral venous occlusion
Subarachnoid hemorrhage (acute or remote)
Periarteritis nodosa
Arterio-venous malformation
Angioma
Carotid endarterectomy, carotid stenting
Posterior reversible encephalopathy syndrome
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) |
Space occupying lesion, malignancy |
Tumor (primary, metastatic)
Abscess
Cystic lesion
Carcinomatous meningitis |
Infection, inflammation, autoimmune |
Viral encephalitis (Epstein–Barr virus, influenza B, cytomegalovirus, Japanese encephalitis)
Necrotizing encephalitis (herpes simplex virus)
Bacterial meningitis
Bacterial cerebritis
Neurocysticercosis
Behçet disease
Paraneoplastic encephalitis
Multiple sclerosis
Neurosyphillis
Rasumussen encephalitis
Tuberculoma, tuberculous meningitis or vasculitis
Post-vaccinal encephalomyelitis
Encephalomalacia
Anti-NMDAR, anti-Hu, VGKC complex/LGI1-antibody encephalitides
Central nervous system toxoplasmosis
Acute disseminated encephalomyelitis |
Trauma |
Head trauma (acute or remote), contusion
Subdural hematoma
Post-craniotomy |
Systemic Illness |
Electrolyte imbalance (hypo/hyperglycemia, hypo/hypercalcemia, hypo/hypernatremia, hyper/hypokalemia, hypomagnesemia)
Alcohol intoxication/alcohol-related seizures
Alcohol/benzodiazepine withdrawal
Hypertensive encephalopathy, eclampsia
Syndrome of inappropriate anti-diuretic hormone
SIRS, sepsis, fever, or acidosis
Deep hypothermia
Hepatic encephalopathy
Hypothyroidism
Hyperosmolar non-ketotic state
Reye syndrome
Iatrogenic (i.e., aminophylline) |
Epilepsy |
Cortical dysplasia
Tuberous sclerosis
Postictal
Post-electroconvulsive therapy
Chronic ipsilateral perinatal hemorrhage with cerebral palsy
Leukodystrophy
Idiopathic epilepsy |
Migraine |
Migraine with aura
Familial hemiplegic migraine |
Degenerative |
Creutzfeldt–Jakob disease |
LPDs are frequently associated with seizures, found in 49–90% of patients with LPDs [25, 27, 46], although in many studies using routine EEG, recordings were not made until a seizure was suspected clinically, likely enriching the cohort of patients with LPDs to include those at highest risk for seizures. In more recent C-EEG series, 27–49% of those with LPDs on C-EEG developed seizures [28, 29, 40]. The addition of “plus” characteristics (superimposed faster frequencies or rhythmic waveforms in conjunction with LPDs) increases the risk for seizures. LPDs+ account for between 17 and 60% of all LPDs, and LPDs+ and BIPDs+ are associated with seizures in 85 and 100% of cases, respectively, [36, 46].
Lateralized Periodic Discharges: Prognosis
LPDs have been associated with increased morbidity and mortality. The overall mortality in adult patients with LPDs of any etiology ranges from 27 to 52% [25, 47, 71]. In two separate studies of patients being treated for status epilepticus (SE), LPDs were significantly associated with death or poor outcome [71, 72] and the presence of LPDs increases the odds that SE will become refractory [73]. After SAH, the presence of LPDs increases the odds for poor outcome by a factor of 18.8 after adjusting for age and disease severity; after ICH, the odds ratio for poor outcome increases to 11.9 [68, 69]. Some have suggested that an acute etiology underlying LPDs serves as a key determinant of outcome [34], but a case-control study of 37 patients with LPDs without acute brain injury compared with age- and etiology-matched controls found LPDs were independently associated with functional decline [67]. Another case-control series of LDPs, BIPDs, and GPDs found an independent association with death or disability, along with age and liver dysfunction, with a dose effect suggestive of increasing morbidity with increasing discharge burden [74]. Nevertheless, the duration of discharges does not appear to predict condition at discharge (following commands, vegetative or deceased) in patients admitted to a neurointensive care unit, even if periodic discharges continue for five or more consecutive days [39].
Lateralized Periodic Discharges: Diagnostic Approaches
Evidence is lacking that LPDs independently create harm sufficient to warrant aggressive management in all cases. Thus, management of LPDs requires an individual approach in order to stratify the effect of LPDs on a given patient. Seizures, both convulsive and nonconvulsive, demonstrate clear adverse effects on both the brain and the body [75, 76] and the first point of distinction rests on whether an LPD pattern represents ictal activity. Proposed definitions of nonconvulsive seizures based on EEG include periodic discharges with a frequency >2.5 Hz [77]. LPDs with clinical seizure activity, e.g., contralateral hand twitching, are unequivocally ictal [12, 37, 41] regardless of the frequency of the LPDs. Interestingly, LPDs with a clear clinical correlate occur more often when the LPDs arise near motor cortex [41] suggesting that LPDs arising more broadly or from less eloquent areas may still be ictal despite a lack of clear clinical correlate. This is supported by studies that have demonstrated LPDs in association with FDG-PET hypermetabolism or SPECT hyperperfusion, physiologic changes expected during an ictal study in patients with epilepsy [43, 78–81]. For instance, in a series of patients undergoing workup for focal SE, three exhibited LPDs with hypermetabolic regions concordant with the region of LPD activity [80]. Other methods of determining regions of hyperperfusion include susceptibility weighted or arterial spin labeling MRI sequences [82, 83]. After traumatic brain injury, periodic discharges recorded in the cortex and on scalp EEG have been shown to create metabolic crises by increasing demand relative to supply, leading to increases in the lactate to pyruvate ratio on cerebral microdialysis [17]. In certain other populations, such as trauma, focal vascular stenosis, or deep barbiturate coma, hypermetabolism or hyperperfusion may be difficult to interpret or unreliable without carefully comparing pre- and post-treatment imaging for a given patient [81].
Both hyperemia and supply–demand mismatch may result in the MRI changes associated with SE. In contrast to arterial ischemia, ictal changes on MRI do not follow vascular territories and may affect network structures such as the hippocampus, dentate gyrus, and pulvinar nucleus of the thalamus [84]. In one study of 69 patients with SE, restricted diffusion was seen across cortical or thalamic regions in 19, all of whom had repetitive seizures and LPDs [85]. When MRI changes occur in a region that is generating LPDs, it is possible that the LPDs represent an ictal pattern (Fig. 5.3), but many seizures do not generate restricted diffusion on MRI [48], and in other cases diffusion restriction may be confined within the thalamus [86, 87]. Others have noted that MRI changes resolve over days to months, and particularly after SE some T2 signal changes remain persistent [88, 89].
Fig. 5.3
Example of lateralized periodic discharges with radiographic ictal correlate. 72-year-old woman with 2 years of progressive Parkinsonism, depression, and hallucinations admitted with psychosis and catatonia. On admission, she developed a secondarily generalized seizure. Continuous EEG monitoring demonstrated: a near-continuous waxing and waning 1–1.5 Hz lateralized periodic discharges (LPDs) with superimposed fast and rhythmic frequencies (black arrowheads); her mental status was described as obtunded, and she was started on multiple anti-seizure drugs (ASDs) over the course of a 48 h period, during which, b the discharges were seen to become higher in voltage and more regular. c MRI diffusion weighted sequences demonstrated cortical restricted diffusion in the left temporal and parietal lobes and d SPECT demonstrated hyperperfusion in the same region. She was intubated and brought to the neurointensive care unit, where continuous infusion midazolam was started. On initiation of midazolam, e the previously seen LPDs suddenly became perfectly regular at 1.5 Hz, with a clear maximum at P3. Midazolam was weaned, and over the next few days, f, g simply configured stimulus-induced rhythmic, periodic, or ictal discharges were seen at 1 Hz in this same region (stimulation at the vertical red line). These lasted 5–10 s, and no additional ASDs were added. Low titers of voltage-gated potassium channel antibodies were discovered, and she gradually woke up after a course of steroids and rituximab. EEG is displayed in a longitudinal bipolar montage; high frequency filter set at 70 Hz and low frequency filter set at 1 Hz; sensitivity is set at 7 uV/mm
Indirect evidence for the ictal nature of LPDs comes from their emergence from anti-seizure drug (ASD) discontinuation [47, 90] and their prevention or resolution with ASDs [37]. We and others advocate for a trial of anti–seizure drug therapy (TOAST) as an important diagnostic step in evaluating patients with LPDs and other periodic or rhythmic patterns [81, 92]. Table 5.3 [91–93] outlines an approach to evaluate LPDs and other periodic or rhythmic patterns when those patterns do not fulfill criteria for nonconvulsive seizures (outlined in previous chapters) when there are no clear ancillary markers of ongoing ictal injury patterns (e.g., MRI, PET, or SPECT changes). We recommend nonsedating ASDs (e.g., levetiracetam) given in doses adequate for treating unequivocal seizures, rather than benzodiazepines where possible, as there are risks for respiratory depression, particularly in the elderly [94]. A TOAST is safe with proper monitoring of cardiopulmonary status.
Step |
|
---|---|
1 |
Recognize a periodic or rhythmic pattern that does not fulfill commonly accepted definitions of seizures or status epilepticus and verify that there has been no convincing evidence of ongoing neuronal injury (e.g., new restricted diffusion on MRI in the region of the abnormal pattern; new hyperperfusion on a radiographic flow study) |
2 |
Verify adequate monitoring of blood pressure, cardiac telemetry, and peripheral oxygenation prior to administering medications |
3 |
During continuous video EEG recording and in the presence of the periodic or rhythmic discharge, perform a neurologic examination, specifically documenting (on the EEG recording):
Level of arousal
Any focal neurologic deficits
Response of the EEG to stimulation during neurologic exam |
4 |
Administer one of the following, and document (on the EEG recording):
Lorazepam 1–2 mg
Midazolam 2–5 mg
Levetiracetam 30 mg/kg
Lacosamide 200 mg |
5 |
After benzodiazepines, monitor for 5–10 min; after ASDs, monitor for 15 min following completion of infusion. |
6 |
Review the EEG and repeat neurologic examination, documenting the same findings as reported previously for comparison |
7 |
If there is no change in the periodic or rhythmic pattern and there is no clinical change, REPEAT step 4–7 |
8 |
Interpretation:
Positive response:
Improvement in the background periodic or rhythmic discharges to <0.5 Hz or <10 second runs
and
Clinical improvement in level of arousal or in focal neurologic deficits, or
Restoration of previous absent normal background EEG features, including:
Posterior dominant rhythm
Sleep transients
Inconclusive response:
Improvement in the background periodic or rhythmic discharges to <0.5 Hz or <10 second runs
and
No clear clinical improvement, or
Decrease in the level of arousal
No response:
No improvement in the background periodic or rhythmic discharges
and
Decrease in level of arousal, or
Signs of respiratory depression or cardiovascular instability (e.g., hypotension or cardiac arrhythmia) |
Lateralized Periodic Discharges: Management
In a survey of 105 neurologists presented with the scenario of LPDs in a lethargic patient the day following termination of NCSE, 15% would add a new ASD, 10% would increase an existing ASD, and 85% would not make any medication changes [95]. Although now 13 years old, this survey highlights persistent equipoise regarding LPDs. Many approaches the management of LPDs by relying on the appearance of the LPDs: for instance, periodic discharges superimposed on a relatively flat background may represent an epileptic encephalopathy as opposed to ongoing ictal activity [96], a reflection of the severity of the underlying brain injury, perhaps warranting less aggressive treatment. On the other hand, periodic discharges with superimposed faster frequencies (LPD+) are highly associated with seizures and may warrant more aggressive treatment [36] (see Fig. 5.3). Although the appearance of LPDs or BIPDs can be informative, the inter-rater agreement for modifier terms and background descriptions is not sufficient to make practice recommendations [5, 97]. Instead, management depends on a proactive diagnostic approach as described above.
When periodic discharges are not clearly ictal and there is no definitive evidence for ongoing neuronal dysfunction, then the management of LPDs depends on the result of a TOAST, described in Table 5.3. If there is clear clinical improvement after an adequate dose of a nonsedating ASD or a benzodiazepine, the ASD should be continued at maintenance dosing and the C-EEG monitored for recurrence of the ictal periodic pattern. If there is evidence suggestive of ongoing neuronal injury and the pattern does not remit with this initial step, additional ASDs may be considered. In a retrospective case-control study, 7/23 (30%) patients with LPDs had clinical and electrographic improvement to ASDs (diazepam or clonazepam, with or without fosphenytoin); interestingly, all seven had LPD+ [74]. Definitive management with “anesthetic” drugs typically used for GCSE, may be warranted in some circumstances.
Often, the background EEG improves despite a lack of clear clinical improvement, and it is not unreasonable to continue maintenance ASD while awaiting a slow improvement in clinical status over the course of 24–48 h [98]. Some consider the restoration of previously absent normal background features (e.g., an alpha frequency posterior dominant rhythm, or sleep transients) an unequivocal trial; but a clinical improvement proximate to the use of ASDs remains the gold standard, defining a pattern as ictal. If a TOAST is inconclusive or negative, the pattern itself may not necessarily require treatment, but rather it may be appropriate to observe the pattern over time while addressing concurrent medical comorbidities. This is particularly true for GPDs, as discussed below.
It should be noted that the use of a TOAST has never been studied for reliability, sensitivity, or specificity. Some ictal discharges, e.g., those associated with refractory SE, may not respond to a single ASD immediately or may require more aggressive therapy in order to achieve seizure freedom. Conversely, ASDs can attenuate waveforms that are potentially non-ictal, such as some GPDs with Triphasic Morphology [99], discussed later in this chapter. Finally, decreasing the discharge frequency of, or complete resolution of, LPDs may reflect the natural history of the discharges rather than a specific response to an ASD, depending on the acuity of the underlying etiology.
We recommend ASD prophylaxis routinely when LPDs are seen during C-EEG recording because of their close association with seizures. Although the choice of ASD is often debated, an ideal agent should cover both focal and generalized seizures, with minimal medication interactions and relatively rapid titration. Phenytoin has been used as prophylaxis for acute seizures after acquired brain injury [100], but others have shown similar efficacy for seizure prevention using levetiracetam [101], which exhibits far fewer side effects. Valproic acid and lacosamide are used in some cases, depending on the patient.
In a series of 24 patients with LPDs, 11 of 15 adults with LPDs developed later epilepsy [49]. In a case-control series, 48.1% of patients with LPDs developed epilepsy compared with 15.7% of controls [74], but in multivariate analysis this was not an independent association. Whereas some have proposed treating patients with LPDs long-term based on these risks [46, 78], others taper ASDs during hospitalization provided no unequivocal seizures are recorded. The majority of patients with LPDs have an acute symptomatic cause, and the prevention of acute seizures after acquired brain injury has not shown a decrease in the incidence of subsequent epilepsy. Therefore, we reason that only a short course (7 days or through the hospitalization) of ASDs is warranted to prevent seizures during the acute illness. On the other hand, those who exhibit clinical seizures or develop unequivocal electrographic seizures may be at increased risk for epilepsy and may warrant a longer term treatment. We recommend a 3–6 month course of ASDs, with consultation with a neurologist or epileptologist prior to weaning medication.
Bilateral Independent Periodic Discharges
BIPDs have been described since the earliest mention of LPDs [22], but there have been few studies of BIPDs, in part because they are less commonly recorded. BIPDs have been reported in approximately 0.1% of patients undergoing routine or outpatient EEG, and in 1–5% of C-EEG [34, 46, 102]. Table 5.4 lists the etiologies associated with BIPDs. Whereas LPDs have a stronger association with focal seizures (albeit coexisting at times with BIPDs), BIPDs have a greater association with generalized seizures [102]. BIPD+ patterns are invariably associated with seizures [46]. Clinically, BIPDs are less often associated with focal neurologic deficits and more with coma, likely as a result of bilateral cortical involvement. While BIPDs have traditionally been associated with substantial mortality (52–61% according to most series [46, 102]), thus far there have been no dedicated case-control series to confirm an independent association. The substantial mortality seen in patients with BIPDs likely reflects the severity of the underlying etiology, but more than 20% of patients with BIPDs in one series were living independently at a mean follow up of 18 months [34], and relatively benign BIPDs have been documented after bilateral strokes [103]. When controlling for disease severity after SAH or ICH, BIPDs have not been found to confer an independent risk for poor outcome, in contrast to LPDs [68, 69].
Category |
Etiology |
---|---|
Neurovascular |
Anoxic encephalopathy
Bihemispheric infarcts
Cerebral vasculitis
Sickle cell disease
Amyloid angiopathy |
Infection, inflammation, neurodegeneration, autoimmune |
Herpes simplex virus encephalitis
Bacterial meningitis (haemophilus influenza, Klebsiella pneumoniae)
Other viral encephalitis (adenoviral encephalitis)
Hashimoto encephalopathy |
Systemic illness |
Hepatic encephalopathy
Alcohol-related seizures |
Degenerative |
Creuzfeldt–Jacob Disease |
Generalized Periodic Discharges (GPDs)
GPDs are described as synchronous, bihemispheric periodic discharges [30]. GPDs may co-occur with LPDs (21.5%, vs. 10% of controls matched for age, etiology, and level of arousal) and BIPDs (10.5% vs. 1.5%) [30]. Clinically, GPDs are associated with lethargy or coma in 92% of cases. Myoclonus is sometimes seen in conjunction with specific disease processes associated with GPDs, such as Creutzfeldt–Jakob disease (CJD) or anoxic ischemic injury. Other causes of GPDs are listed in Table 5.5 [30, 34, 44, 60, 104–112]. GPDs have been variably subclassified. (“triphasic morphology,” the most common subtype of GPDs, will be discussed separately.) Prior reviews have distinguished periodic short-interval diffuse discharges (PSIDDs), which occurs every 0.5–4 s, from periodic long-interval diffuse discharges (PLIDDs), which are polyphasic and occur every 4–30 s [113]. The standardized ACNS terminology regards polyphasic discharges as bursts with >4 phases, and PLIDDs would now be classified as either a burst–suppression pattern or, when background activity is preserved, continuous with high-amplitude bursts [4]. PLIDDs have a close association with subacute sclerosing panencephalitis (SSPE), a now rare form of progressive degenerative post-measles encephalitis, and have been observed with ketamine or PCP toxicity. While anoxia is clearly associated with burst–suppression on EEG, “burst–suppression with identical bursts” is a regular, recurrent polyphasic bursting pattern seen after severe diffuse anoxia and may be considered part of the PLIDD category. A retrospective blinded study of 101 cardiac arrest patients following return of spontaneous circulation found this pattern in 20, all of whom had poor six month neurologic outcome (CPC 3–6), compared with 10 of 28 patients with poor outcome and a more typical suppression–burst pattern [114]. This chapter will focus on short-interval GPDs.
Category |
Etiology of GPDs |
Etiology of GPDs with triphasic morphology |
---|---|---|
Neurovascular |
Hypoxic encephalopathy
Acute ischemic stroke
Subarachnoid hemorrhage
Intraventricular hemorrhage
Intracerebral hemorrhage |
Anoxic encephalopathy
Pontine ischemic stroke
Binswanger encephalopathy
Cerebellar hematoma |
Space occupying lesion, malignancy |
Acute hydrocephalus
Central nervous system tumor |
Hydrocephalus
Midline diencephalic structures (glioma, craniopharyngioma)
Cerebral carcinomatosis
Multifocal cerebral lymphoma |
Infection, inflammation, autoimmune |
Sepsis
Herpes encephalitis
Subacute sclerosing panencephalitis
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