The
postictal state is the
altered state of consciousnessAn altered state of consciousness, , also named altered state of mind is any condition which is significantly different from a normal waking beta wave state. The expression was used as early as 1969 by Charles Tart and describes induced changes in one's mental state, almost always temporary...
that a person enters after experiencing an
epilepticEpilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures...
seizureAn epileptic seizure is a transient symptom of excessive or synchronous neuronal activity in the brain. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms...
, such as those occurring with
frontal lobe epilepsyFrontal lobe epilepsy is the second most common type of epilepsy, after temporal lobe epilepsy. It is similar to temporal lobe epilepsy because it is a type of focal seizure, which means that the seizure starts in a focal area of the brain, commonly referred to as the focus. Frontal lobe epilepsy...
. It usually lasts between 5 and 30 minutes, but sometimes longer in the case of larger or more severe seizures and is characterized by drowsiness,
confusionConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
,
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
,
hypertensionHypertension is a chronic medical condition in which the blood pressure is elevated. It is also referred to as high blood pressure or shortened to HT, HTN or HPN. The word "hypertension", by itself, normally refers to systemic, arterial hypertension.Hypertension can be classified as either...
,
headacheIn medicine a headache or cephalalgia is a symptom of a number of different conditions of the head. Some of the causes are benign while others are medical emergencies.There are a number of different classification systems for headaches...
or
migraineMigraine is a neurological syndrome characterized by altered bodily perceptions, severe headaches, and nausea. Physiologically, the migraine headache is a neurological condition more common to women than to men. The word migraine was borrowed from Old French migraigne...
and other disorienting symptoms. Additionally, emergence from this period is often accompanied by amnesia or other memory defects. It is during this period that the
brainThe brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all...
recovers from the trauma of the seizure.
While the post-ictal period is considered to be the period shortly after a seizure where the brain is still recovering from the seizure, the
ictalIctal refers to a physiologic state or event such as a seizure, stroke or headache. The word originates from the Latin ictus, meaning a blow or a stroke. In electroencephalography , the recording during an actual seizure is said to be "ictal"....
period is considered to be the seizure itself, and the interictal period to be the period between seizures, when brain activity is normal.
Symptoms
Jerome Engel defines the
postictal state as “manifestations of
seizureAn epileptic seizure is a transient symptom of excessive or synchronous neuronal activity in the brain. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms...
-induced reversible alterations in neuronal function but not structure.” Following a seizure it is common to experience feelings of exhaustion, both mental and physical, that can last for a day or two. Patients’ most common complaint after a seizure is an inability to think clearly, specifically “poor
attentionAttention is the cognitive process of selectively concentrating on one aspect of the environment while ignoring other things. Attention has also been referred to as the allocation of processing resources...
and
concentrationIn chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
, poor short term memory, decreased verbal and interactive skills, and a variety of cognitive defects specific to individuals.” This collection of symptoms is known as the postictal state, though the word postictal means nothing more than “after the seizure”.
Postictal migraines are a major complaint among
epilepsyEpilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures...
patients, and can have a variety of etiologies. One possible cause of these migraines is high intracranial pressure resulting from postictal
cerebral edemaCerebral edema is an excess accumulation of water in the intracellular and/or extracellular spaces of the brain.- Vasogenic cerebral edema:...
. At times, patients may be unaware that they had a seizure, and the characteristic migraine is their only clue.
DepressionIn psychology and psychiatry, depression is a state of low mood and aversion to activity. While most often described as a disease or dysfunction, there are also strong arguments for seeing depression as an adaptive defense mechanism....
is also very common after a seizure.
Other symptoms associated with the postictal state are less common.
Todd's paresisTodd's paresis or Todd's paralysis is focal weakness in a part of the body after a seizure. This weakness typically affects appendages and is localized to either the left or right side of the body. It usually subsides completely within 48 hours...
(TP) is a temporary regional loss of function in whatever region just experienced the seizure, and its manifestation depends on where the seizure was located. Loss of motor function is most common, and can range from weakness to full paralysis. About 6% of patients who had tonic-clonic seizures experienced TP afterward, with loss of motor function sometimes accompanied with temporary numbness, blindness, or deafness. TP can also cause
anterograde amnesiaAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
if the seizure included the bilateral hippocampi, and
aphasiaAphasia is an acquired condition in which there is an impairment of any language modality. This may include difficulty in producing or comprehending spoken or written language....
if the seizures began in the language-dominant hemisphere. Symptoms typically lasts about 15 hours, but can last as long as 36 hours, and the clinician must resolve whether the loss of motor function is due to TP or
ischemiaIn medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue...
.
Postictal psychosis (PP) is a rare but serious complication following seizures, characterized by auditory and visual hallucinations, delusions,
paranoiaParanoia is a thought process heavily influenced by excessive anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs concerning a perceived threat towards oneself. In the original Greek, παράνοια simply means madness...
, affective change, and
aggressionIn psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause pain or harm. Predatory or defensive behavior between members of different species is not normally considered "aggression." Aggression takes a...
. Interestingly, the onset of PP doesn’t begin until hours or days after the seizure has ended. Following the conclusion of the seizure, the patient feels the typical confusion and lethargy of the postictal state, and then gradually recovers to a normal state. This is called the lucid phase. In patients who experience PP, the lucid phase usually lasts between 2 hours and a week (usually more than 6 hours) before psychosis sets in. In about 12-50% of seizure patients, the lucid phase is followed by a period of psychosis that can last for 12 hours to more than 3 months (mean, 9-10 days). This psychosis is treatable with standard antipsychotic drugs, and stops when the patient no longer experiences seizures.
Postictal bliss (PB) is also reported following seizures. This has been described as a highly blissful feeling associated with the emergence from amnesia.
Some of these postictal symptoms are almost always present for a period of a few hours to a day or two. In fact, confusion and lack of responsiveness after a seizure is so common and expected that if a patient doesn’t show these symptoms after a seizure, it can be a signal to clinicians that the event may not be an actual seizure at all. Usually such false seizures are instead related to
syncopeIn phonology, syncope is the loss of one or more sounds from the interior of a word; especially, the loss of an unstressed vowel.-Syncope as a historical sound change:...
or have a psychogenic origin. The postictal state can also be useful for the clinician when determining the focus of the seizure. Decreased verbal memory (short term) tends to result from a seizure in the dominant hemisphere, whereas seizures in the nondominant hemisphere tend to manifest with decreased visual memory. Inability to read suggests seizure foci in the language areas of the speech-dominant hemisphere, and “after a seizure semivoluntary events as mundane as nose wiping tend to be done with the hand
ipsilateral to the seizure focus.”
Causes
While it might seem that the neurons become “exhausted” after the near-constant firing involved in a seizure, the ability of the neuron to carry an
action potentialAn action potential is a transient alteration of the transmembrane voltage across an excitable membrane generated by the activity of voltage-gated ion channels embedded in the membrane. Action potentials play multiple roles in several types of excitable cells such as neurons, myocytes, and...
following a seizure is not decreased. Neurons of the brain fire normally when stimulated, even after long periods of
status epilepticusStatus epilepticus refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes , or recurrent seizures without regaining consciousness between...
. Furthermore, the sodium gradient that allows the axon potential to be propagated is so large in comparison to the tiny number of ions that are let through each channel with each signal that it is highly unlikely that this gradient could be ‘used up’ by high activity during a seizure. Instead, there are four major hypotheses regarding what cellular and molecular mechanisms could cause the observed postictal systems: neurotransmitter depletion, changes in receptor concentration, active inhibition, and cerebral bloodflow changes. It is likely that these may in fact interact or more than one theory may contribute to postictal symptoms.
Neurotransmitter depletion
Neurotransmitters must be present in the
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway from the neuron's cell body or soma....
terminal and then exocytosed into the synaptic cleft in order to propagate the signal to the next neuron. While neurotransmitters are not typically a limiting factor in neuronal signaling rates, it is possible that with extensive firing during seizures neurotransmitters could be used up faster than new ones could be synthesized in the nucleus and transported down the axon. There is currently no direct evidence for neurotransmitter depletion following seizures.
Changes in receptor concentration
In studies that stimulate seizures by subjecting rats to electroshock, seizures are followed by unconsciousness and slow waves on an electroencephalogram (EEG), signs of postictal
catalepsyCatalepsy is also a term used by hypnotists to refer to the state of making a hypnotised subject's arm, leg or back rigid. "Arm catalepsy" is often a pre-hypnotic test performed prior to an induction into a full trance.-Causes:...
. Administering the opiate antagonist
naloxoneNaloxone is a drug used to counter the effects of opioid overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory system. Naloxone is also experimentally used in the treatment for CIPA;...
immediately reverses this state, providing evidence that increased responsiveness or concentration of the opiate receptors may be occurring during seizures and may be partially responsible for the weariness humans experience following a seizure. When humans were given naloxone in-between seizures, researchers observed increased activity on their EEGs, suggesting that opioid receptors may also be upregulated during human seizures. To provide direct evidence for this, Hammers et al. did
positron emission tomographyPositron emission tomography is a nuclear medicine imaging technique which produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) scanning of radiolabelled ligands before, during, and after spontaneous seizures in humans. They found that opioid receptors were upregulated in the regions near the focus of the seizure during the ictal phase, gradually returning to baseline availability during the postictal phase. Hammers notes that cerebral bloodflow after a seizure can not account for the increase in PET activity observed. Regional bloodflow can increase by as much as 70-80% after seizures but normalizes after 30 minutes. The shortest postictal interval in their study was 90 minutes and none of the patients had seizures during the scanning. It has been predicted that a decrease in opioid activity following a seizure could cause withdrawal symptoms, contributing to postictal depression. The opioid receptor connection with mitigating seizures has been disputed, and opioids have been found to have different functions in different regions of the brain, having both proconvulsive and anticonvulsive effects.
Active inhibition
It is possible that seizures cease spontaneously, but it is much more probable that some changes in the brain create inhibitory signals that serve to tamp down the overactive neurons and effectively end the seizure. Opioid peptides have been shown to be involved in the postictal state and are at times anticonvulsive, and
adenosineAdenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule moiety via a β-N
9-glycosidic bond....
has also been implicated as a molecule potentially involved in terminating seizures. Evidence for the theory of active inhibition lies in the postictal
refractory periodIn physiology, a refractory period is a period of time during which an organ or cell is incapable of repeating a particular action, or the amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following an excitation...
, a period of weeks or even months following a series of seizures in which seizures cannot be induced (using animal models and a technique called
kindlingKindling may refer to:* Material for starting a fire, especially small pieces of dry wood* Kindling, a 1915 film directed by Cecil B. DeMille* Kindling, a 1938 novel by Neville Shute* Kindling, a 1973 album by Gene Parsons...
, in which seizures are induced with repeated electrical stimulation).
Leftover inhibitory signals are the most likely explanation for why there would be a period in which the threshold for provoking a second seizure is high, and lowered excitability may also explain some of the postictal symptoms. Inhibitory signals could be through GABA receptors (both fast and slow IPSPs), calcium-activated potassium receptors (which give rise to
afterhyperpolarizationAfterhyperpolarization describes the part of the hyperpolarization phase of an action potential where the membrane falls below the normal resting potential. Both medium and slow afterhyperpolarization currents can be demonstrated in neurons...
), hyperpolarizing pumps, or other changes in ion channels or signal receptors. These changes would likely have a residual effect for a short time after successfully ending the high activity of neurons, perhaps actively inhibiting normal firing during the after the seizure has ended. However, most of these changes would be expected to last for seconds (in the case of IPSP and AHP) or maybe minutes (in the case of hyperpolarized pumps), but cannot account for the fog that lasts for hours after a seizure.
While not an example of active inhibition,
acidosisAcidosis is an increased acidity . If not further qualified, it usually refers to acidity of the blood plasma....
of the blood could aid in ending the seizure and also depress neuron firing following its conclusion. As muscles contract during tonic-clonic seizures they outpace oxygen supplies and go into
anaerobic respirationIn biology, anaerobic respiration is a way for an organism to produce usable energy carriers without the involvement of oxygen; it is respiration without oxygen. Respiration is a redox reaction that processes energy in a form usable by an organism, chiefly the process of producing ATP, the...
. With continued contractions under anaerobic conditions, the cells undergo lactic acidosis, or the production of lactic acid as a metabolic byproduct. This acidifies the blood (higher H+ concentration, lower pH), which has many impacts on the brain. For one, “hydrogen ions compete with other ions at the ion channel associated with N-methyl-d-aspartate (
NMDANMDA is an amino acid derivative acting as a specific agonist at the NMDA receptor, and therefore mimics the action of the neurotransmitter glutamate on that receptor...
). This competition may partially attenuate NMDA receptor and channel mediated hyperexcitability after seizures.” It is unlikely that these effects would be long-lasting, but by decreasing the effectiveness of NMDA-type glutamate receptors , high H+ concentrations could increase the threshold needed to excite the cell, inhibiting the seizure and potentially slowing neuronal signaling after the event.
Cerebral bloodflow changes
Cerebral
autoregulationAutoregulation is a process within many biological systems, resulting from some internal adaptive mechanism that works to adjust the systems response to stimuli. While most systems of the body show some degree of autoregulation, it is most clearly observed in the kidney, the heart, and the brain...
typically ensures that the correct amount of blood reaches the various regions of the brain to match the activity of the cells in that region. In other words, perfusion typically matches metabolism in all organs, but especially in the brain, which gets the highest priority. However, following a seizure it has been shown that sometimes cerebral blood flow is not proportionate to metabolism. While cerebral blood flow didn’t change in the mouse hippocampus (the foci of seizures in this model) during or after seizures, increases in relative glucose uptake were observed in the region during the ictal and early postictal periods. Animal models are difficult for this type of study because each type of seizure model produces a unique pattern of perfusion and metabolism. Thus, in different models of epilepsy, researchers have had differing results as to whether or not metabolism and perfusion become uncoupled. Hosokawa’s model used EL mice, in which seizures begin in the
hippocampusThe hippocampus is a major component of the brains of humans and other mammals. It belongs to the limbic system and plays important roles in long-term memory and spatial navigation. Like the cerebral cortex, with which it is closely associated, it is a paired structure, with mirror-image halves in...
and present similarly to the behaviors observed in human epileptic patients. If humans show similar uncoupling of perfusion and metabolism, this would result in hypoperfusion in the affected area, a possible explanation for the confusion and ‘fog’ patients experience following a seizure. It is possible that these changes in blood flow could be a result of poor autoregulation following a seizure, or it could in fact be yet another factor involved in stopping seizures.
Treatments
Observing neuropeptide transcription levels during and after seizures provides a window into how the brain responds to seizures. Some neuropeptides (such as
galaninGalanin is a neuropeptide present in humans and other mammals. It is a peptide consisting of a chain of 29 amino acids .Galanin is formed by the cleavage of a prepropeptide encoded by a gene known as GAL...
, thyrotropin releasing hormone (TRH),
neuropeptide YNeuropeptide Y is a 36 amino acid peptide neurotransmitter found in the brain and autonomic nervous system.NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy. The main effect is increased food...
,
somatostatinSomatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
, and
cortistatinCortistatin is a neuropeptide that is expressed in inhibitory neurons of the cerebral cortex, and which has a strong structural similarity to somatostatin. Unlike somatostatin, when infused into the brain, it enhances slow-wave sleep. It binds to sites in the cortex, hippocampus and the amygdala....
) are believed to have anticonvulsant and neuroprotective properties. In accordance with this perceived function, mouse studies using have used microarrays to show that transcription of these genes is increased many-fold following a seizure. The number of transcripts of these molecules typically peaks around 24 hours following the seizure, but can remain statistically significantly above normal levels for up to 72 hours.
Wilson observed a higher magnitude of increase in adult rats compared to immature rats, which is of note particularly because young mice have a much shorter postictal refractory period. Also, administering exogenous TRH, has been shown to improve postictal cognition in humans, as measured with neuropsychological tests. This evidence further suggests a natural role for these molecules in ending and/or recovering from seizures, and may give rise to pharmaceuticals that mitigate postictal symptoms in the future.
In support of the opioid theory of the postictal state, pretreatment of rats with
morphineMorphine is a highly potent opiate analgesic psychoactive drug, is the principal active ingredient in Papaver somniferum , is considered to be the prototypical opioid. Like other opioids, e.g...
increased postictal symptoms and pretreatment with naloxone decreased postictal symptoms (as measured by the presence of EEG slow waves, increase in EEG spike activity, decreased memory, affective pain response, and explosive motor behavior). However, it is believed that opioid peptides serve a very useful purpose in ending the seizures, so pretreating humans with naloxone would put the patient at risk of status epilepticus. Naloxone may, however, prove a useful treatment for improving symptoms after seizures have ended. It is not known if this would also put the patient at risk of another seizure in the near future as a result of shortening the postictal refractory period.
Conclusion
There are few explanations for what could cause the long lasting symptoms of the postictal state, with patients complaining of difficulty thinking clearly and loss of short-term memory function for hours and even days. The cellular and molecular changes hypothesized to take place following a seizure would only have effects lasting for minutes. Todd’s paresis can last for 24 or 48 hours, and reversible neurological defects (typically short term memory) can last for months, suggesting that more permanent changes in neuron structure may take place following seizures. It should be noted that most patients do not display any long term neurological defects following seizures, and seizures are not believed to be damaging to the brain. It is possible in the small fraction of patients that do experience short term memory loss for weeks or months following a seizure, structural changes may take place that are eventually compensated for structurally or functionally, causing symptoms to eventually disappear.