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Basic physiology of burst‐suppression

2009; Wiley; Volume: 50; Issue: s12 Linguagem: Inglês

10.1111/j.1528-1167.2009.02345.x

1528-1167

Florin Amzica,

Neuroscience and Neuropharmacology Research

Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternative periods of slow waves of high amplitude (the burst) and periods of so-called flat EEG (the suppression) (Swank & Watson, 1949). It is generally associated with comatose states of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). It has been studied extensively at the EEG level (see review by Brenner, 1985, also this issue), but only sparse information is available with respect to the cellular and ionic mechanisms underlying its patterns. Some of the most fascinating questions pertain to the genesis of bursts: Are they truly spontaneous, what triggers them, what mechanism dictates their quasi-periodicity? Moreover, in clinical practice bursting activities during BS are often associated with jerks resembling those present during epileptic fits. Is there any common link to known seizure mechanisms? At the cortical level, EEG bursts are always associated with phasic synaptic depolarizing intracellular potentials, occasionally crowned by action potentials, in virtually all recorded cortical neurons (Steriade et al., 1994; see Fig. 1A, left panel). This study has also shown that suppression episodes are due to absence of synaptic activity among cortical neurons. However, it was also shown that some thalamocortical neurons display a rhythmic activity in the frequency range of delta oscillations (1–4 Hz) during suppressed periods. Recently we have shown further that BS represents a distinct behavioral frame during which the cortical network is in a hyperexcitable state, and that bursting activity may be triggered by subliminal stimuli (Kroeger & Amzica, 2007; Fig. 1). Intraneuronal and electroencephalographic structure of burst-suppression (BS) patterns. (A) Spontaneous (left) and triggered (right) bursts. Arrows indicate the moments where microstimuli were delivered. Below, variation of the heart rate during the recording shows no consistent relationship to the stimuli. Two spontaneous (sp) and two triggered (tr) events within rectangles are expanded in B to show a full burst following a single excitatory event (B1) and a single response (B2). (C) Averaged (first two traces) and superimposed (n = 11; below) responses. Note stereotyped initial excitatory component in all responses, followed by precise onset of the burst. Modified from Kroeger & Amzica, 2007. The cortical hyperexcitability was demonstrated under various anesthetics ranging from those enhancing Cl− inhibition (propofol, barbiturates) to those boosting glutamate uptake (isoflurane). In the latter case, hyperexcitability resulted from the reduction of cortical inhibition (Ferron et al., 2009), which was corroborated with an outburst of extracellular Cl−, probably reflecting the lesser activity of γ-aminobutyric acid (GABA)A inhibitory synapses. It results that the excitatory–inhibitory balance leans toward excitation. The bursting process is limited in time because bursting activity is accompanied by a depletion of extracellular cortical Ca2+ at levels that are incompatible with synaptic transmission. This generates an overall disfacilitation in cortical networks (Kroeger & Amzica, 2007), which ultimately is responsible for the arrest of neocortical neuronal activities and the ensuing flat EEG. During suppression, the synaptic silence allows neuronal pumps to restore interstitial Ca2+ levels at control levels. At this moment, any external (or intrinsic) signal is able to trigger a new burst in the hyperexcitable cortex. Therefore, the pseudo-rhythmicity of the BS pattern is dictated by the degree of extracellular Ca2+ depletion and the ability of neurons to restore this concentration. These phenomena are modulated by the general state of the nervous system and, therefore, the etiology and the seriousness of the condition. As coma deepens, bursting episodes become shorter, whereas the opposite happens to the suppression, leading eventually to continuous isoelectric EEG. The impaired ability of the central nervous system to keep extracellular Ca2+ ions at normal levels might be precipitated by the fact that, at least as demonstrated with isoflurane, the permeability of the blood–brain barrier is compromised during BS (Tétrault et al., 2008). An interesting issue concerns the similarity between symptoms associated either with bursts during BS or with spike–wave seizures. Moreover, both conditions occur on a background of impaired inhibition. Furthermore, in clinical practice there is often unclear delimitation between comatose BS behavior and epileptic manifestations (e.g., in Hirsch et al., 2004). In addition, the antiepileptic medication obtains poor response (Dan & Boyd, 2006). This calls for one of the two possibilities: Either BS is included in the already complex syndrome of epilepsies (with complicating issues regarding mechanisms and curative strategies) or it is regarded as distinct processes with distinct mechanisms. The latter alternative is supported by the fact that volatile anesthetics (isoflurane in particular) are used both to counteract status epilepticus and to induce BS, further suggesting that bursts of BS do not reflect an epileptic pathology. The author confirms that he has read the Journal's position on issues involved in ethical publication and affirms that this paper is consistent with those guidelines. Disclosure: The author has no conflicts of interest to disclose.