Fig. 1
SI-LRDA+S: A 64-year-old female with subarachnoid hemorrhage, status post clipping and placement of right frontal external ventricular drain. EEG shows stimulus-induced lateralized rhythmic delta with embedded sharps (SI-LRDA+S) after nurse touches patient; there was no visible clinical response. Sensitivity 7 uV/mm, low frequency filter 1 Hz, high frequency filter 70 Hz, notch 60 Hz, 15 mm/s
Fig. 2
SI seizure. A 52-year-old man status post pulseless electrical activity cardiac arrest and history of alcoholism. EEG shows a stimulus-induced seizure with clinically associated jerking of trunk more than limbs. Sensitivity 7 uV/mm, low frequency filter 1 Hz, high frequency filter 70 Hz, notch 60 Hz, 30 mm/s
Stimulus-induced seizures or periodic discharges likely arise from activation of arousal pathways, including thalamocortical projections, in conjunction with hyperexcitable cortex. Stimulation acts upon normal arousal circuitry, initiated in the upper brainstem reticular activating system and projecting through the reticular nucleus of the thalamus and widespread thalamocortical connections. A highly epileptiform or ictal pattern is thought to occur when hyperexcitable cortex is activated through normal arousal circuitry.
Clinical manifestations are rare with SIRPIDs but may be present, partially depending on the location of the area of cortical hyperexcitability. In a case series from 2008, slightly more than half of the patients with clinical seizures induced by alerting stimuli had lesions in the primary motor region, which may explain the stimulus-induced focal motor seizures [2]. Clinical seizures imply a well-organized propagation of ictal discharges through the cerebrum and brainstem generating clinical motor activity. In some cases, patients’ brains are probably too impaired to generate this type of synchronous, organized, and propagating electrical activity, even if motor pathways are involved.
Prevalence and Clinical Context
The prevalence of SIRPIDs in the intensive care unit (ICU) population was found to be approximately 22 % of patients placed on cEEG [1]. Although most commonly seen with intracerebral hemorrhage (ICH), SIRPIDs were seen with a variety of acute brain injuries such as subarachnoid hemorrhage (SAH) and cerebral infarction. Clinical status epilepticus (SE) was more common in patients with focal or “ictal-appearing” SIRPIDs than non-ictal-appearing SIRPIDs. In addition, patients often had more than one type of SIRPID. The type of SIRPID, ictal versus non-ictal, did not correlate with clinical outcome. Most patients were found to be comatose on the days they showed SIRPIDs. Rarely (probably less than 5 %), SIRPIDs are associated with a clinical manifestation as shown in the case series mentioned above [2]. In this series, nine comatose or encephalopathic patients had clear stimulus-induced focal clinical seizures typically involving clonic hand, face, or upper arm movements. These focal clinical motor seizures were consistently seen after a stimulus, removing any doubt about the ictal nature of these events [2].
Treatment and Management
There are no guidelines on treatment of SIRPIDs. At this time the authors advocate treatment of a pattern that is stimulus-induced in the same manner as spontaneous patterns. There is no inherent reason and no experimental data to suggest that seizures or other patterns are more or less harmful or important due to the fact that they are stimulus induced. For example, a photic-induced convulsive seizure has the same pathophysiology and adverse effects as a spontaneous convulsion. Minimizing patient stimulation by bundling clinical care (i.e., nursing, exams, and procedures) and possibly even premedicating bundled clinical care with short-acting benzodiazepines (or other similar agents) remain unstudied but could be helpful. If there was a reliable measure of acute seizure-related neuronal injury, the value of this intervention could be determined.
Stimulus-induced periodic discharges can be treated (as we recommend with most periodic discharges) with the use of a prophylactic antiepileptic drug (AED) in hopes of preventing seizures and monitoring with cEEG to identify and treat electrographic seizures as quickly as possible. The authors do not advocate attempting to eliminate the periodic discharges, especially if 1 Hz or slower, except in rare circumstances.
Imaging studies have been used to look at SIRPIDs to determine if there are metabolic or blood flow effects that may help decide whether or not to treat SIRPIDs. The authors, however, do not find single-photon emission computed tomography (SPECT) to be useful for this purpose. For example, in 2011, SPECT imaging was used to study a patient who had both stimulus-induced periodic discharges and stimulus-induced evolving LRDA [3]. There was no evidence of increased cerebral blood flow (CBF) over the left hemisphere when the patient was injected 5 s after SI-LRDA at 2–3 Hz over the left temporal lobe, which the authors considered a possible ictal pattern. The authors concluded that this finding implied that the pattern was not ictal, and they did not initiate further treatment with AEDs. However, lack of visible increased cerebral blood flow (a subtraction study comparing a time when the pattern was not present may show a relative increase that is not apparent on a single study) does not necessarily imply a pattern is not ictal or that it is not causing harm. In an acutely injured brain, seizures may not generate the necessary increase in CBF needed to match the energy requirement resulting in neuronal injury without any increased CBF. Of note, in the above case study, the patient had a further decline and was treated with additional AEDs. Subsequent to AED treatment, the patient had a stuttering course of recovery.
This case brings to light an ongoing conundrum relating to patterns of uncertain significance. The EEG may demonstrate a pattern that can now be defined; however, it is not clear what to do with this information and further neuroimaging may or may not aid in determining management [3]. SIRPIDs remain poorly understood and require additional research to determine when they cause neuronal damage, when they contribute to the patient’s poor mental status, when they require treatment, and if they have independent prognostic significance.
Lateralized Rhythmic Delta Activity
Description and Definition
LRDA is defined by the ACNS guidelines as unilateral, or bilateral asymmetric, rhythmic delta activity. Per the guidelines for any pattern to be defined as rhythmic, it must recur regularly for at least 6 cycles in duration, e.g., 1/s for 6 s or 2/s for 3 s. Typically, lateralized rhythmic delta activity (LRDA) is 1–3 Hz in frequency and very brief (more than half were less than 10 s in the only study of LRDA, and almost all were less than 1 min in duration). In contrast, lateralized periodic discharges (LPDs) are typically slower (~1 Hz) and longer in duration (several minutes to hours); however, LRDA seems to carry similar clinical implications as LPDs [4]. See Fig. 3a,b for an example of LRDA and seizures arising from LRDA.
Fig. 3
(a) LRDA: A 60-year-old man with epilepsy, hypertension, and traumatic subdural hematoma, presents with epilepsia partialis continua with continuous jerking of his left side, including during this EEG clip. EEG shows lateralized rhythmic delta (in boxes) with superimposed sharp waves (examples highlighted with arrows) (LRDA+S), which suggests a highly epileptogenic focus and high chance of seizures in the near future or past. Sensitivity 7 uV/mm, low frequency filter 1 Hz, high frequency filter 70 Hz, notch off 30 mm/s. (b) Seizure in same patient: Above patient with electroclinical seizure arising from LRDA, now spreading to the left and associated with head and arm jerking seen on video, Sensitivity 7 uV/mm, low frequency filter 1 Hz, high frequency filter 70 Hz, notch off, 30 mm/s. (c) Evolution of seizure. Sensitivity 7 uV/mm, low frequency filter 1 Hz, high frequency filter 70 Hz, notch off, 30 mm/s. (d) Seizure ends (note return of nearly normal EEG activity on the left, in box) and LRDA+S continues over the right (ellipse). Sensitivity 7 uV/mm, low frequency filter 1 Hz, high frequency filter 70 Hz, notch off, 30 mm/s
Prevalence and Clinical Context
There is only one manuscript published on LRDA in the critically ill [4]. LRDA was uncommon, but, when present, was highly associated with seizures: 63 % of patients with LRDA had seizure(s) during the acute illness. Seizures were most often nonconvulsive in nature (90 %), and all but one arose from the same region as the LRDA. LRDA was associated with seizures just as often as LPDs (63 % vs. 57 %). If both LPDs and LRDA were seen, seizures were even more likely (84 %). This is in contrast to clinically matched control patients with only nonrhythmic slowing, in whom only 20 % had seizures. LRDA is commonly seen in conjunction with other patterns such as LPDs.
LRDA developed within the first 24 h in 80 % of cases, but 10 % emerged after 48 h of recording. This was a bit more delayed in appearance than LPDs, which were noted within the first 24 h in 91 % of patients and always within 48 h. There was a trend toward even higher association with seizures if the LRDA had embedded sharp waves (LRDA + S) or lasted greater than 10 s, but sample sizes were small and further confirmation is needed.
Treatment and Management
Based on the above study, the authors treat LRDA as a highly epileptogenic pattern, identical to LPDs in its association with seizures. The goal of treatment is to prevent definite seizures with AED prophylaxis and not to abolish the pattern, as LRDA is likely to persist despite treatment with AEDs. In addition, it is recommended that cEEG (at least 24–48 h) be performed to identify seizures whether AEDs are given or not. LRDA typically involved a lesion of the cortex or juxtacortical white matter and/or deep gray structures; therefore, its presence should warrant neuroimaging, as with any prominent focal EEG finding [4]. There is some evidence from simultaneous intracranial recordings of LRDA seen on scalp EEG that intracranially there are periodic epileptiform discharges or bursts while LRDA is seen on the overlying scalp EEG [5].
Temporal intermittent rhythmic delta activity (TIRDA) has been described previously in ambulatory patients and is highly associated with temporal lobe epilepsy. TIRDA is a temporal lobe subtype of LRDA that is seen in awake and alert patients with temporal lobe epilepsy.
Brief Potentially Ictal Rhythmic Discharges
Description and Definition
In the neonatal literature, brief discharges were described referring to potentially ictal patterns that were shorter than the arbitrary standard of 10 s required to qualify as an electrographic seizure [6, 7]. These patterns have been termed brief rhythmic discharges (BRDs) or brief electroencephalographic rhythmic discharges (BERDs). These rhythmic patterns are controversial as to whether they are seizures themselves or represent an interictal phenomenon in patients with similar seizure patterns. A similar pattern in the adult population has been described and referred to them as B(I)RDs [8]. The term is left intentionally ambiguous (“potentially ictal”) to demonstrate the difficulty in knowing if the pattern is representative of seizure activity or an interictal phenomenon. Although this may seem like semantics, the terminology may have treatment implications for the clinical team.
One study evaluated neonates with brief (less than 10 s) rhythmic discharges (BRDs) and longer rhythmic discharges (LRDs) and compared them to patients without any rhythmic discharges [7]. They found that any rhythmic discharge was more often seen in healthy “preterm” (less than 38 weeks) newborns and “high-risk” newborns. In addition, in long-term follow-up, BRDs and LRDs both conferred a risk for abnormal neurological development; however, this risk was greater with LRDs than BRDs. In this study, “high-risk” newborns were not clearly defined but predominantly had prematurity, hypoxic-ischemic encephalopathy, neonatal infection, intra- and periventricular hemorrhage, respiratory distress syndrome, CNS malformation, hypoglycemia, leukomalacia, congenital infection, or metabolic defects.
B(I)RDs in adults were described as “very brief (<10 s) lateralized runs of rhythmic activity with a frequency greater than 4 Hz with or without evolution” [8]. These discharges were typically within the theta range, sharply contoured, and 1–3 s in duration. See Fig. 4a,b for typical examples of B(I)RDs and seizures arising from B(I)RDs.
