What is Ictal-Interictal Continuum?
Uncontrolled seizures are a common medical problem that requires evaluation and management in a hospital environment. These can occur due to failure of multiple organs, severe changes to the body’s internal environment, or diseases that mainly affect the nervous system. Seizures can also be the main cause of associated medical problems.
Seizures that aren’t controlled can rapidly progress into constant seizure states that are either noticeable or not. These situations have increased risks for negative health outcomes and death. Treating seizures can be difficult because of changes in the body that resist treatment and other existing health conditions that can affect how seizure medicines work.
Early recognition and treatment of seizures in patients who are in a critical state is a key part of neurological care. However, it’s not always clear whether the patient’s condition reflects an ongoing seizure process. This is due to the limitations of the diagnostic tools used to identify these abnormalities.
The medical community has started to use the term “ictal-interictal continuum” (IIC) to cover this diagnostic ambiguity. This term was first used by Pohlmann-Eden and colleagues. They suggested that certain patterns in brain activity might indicate a changing state in the body, where a mix of clinical factors and individual patient characteristics might predict whether definitive seizures will occur.
The increase of continuous video EEG (a test that records the electrical signals of the brain) in acute care has shown that certain patterns are extremely common. This has led to a lot of focus on understanding the brain activities that underpin these patterns and its implications for patient treatment and outcomes.
Since its initial description, the IIC term has grown to include other rhythmic patterns that are known to increase the risk of seizures.
The American Clinical Neurophysiology (ACNS) convened a group of experts to set a standard for critical care EEG terminology. In their most recent expert opinion in 2021, the patterns within the IIC are now based on well-established criteria, with the aim of ensuring the same understanding among healthcare providers and researchers.
What Causes Ictal-Interictal Continuum?
When stable, unchanging electrical signals from brain cells create certain patterns in an EEG, which is a brain scan, it can identify that there is some form of disorder or malfunction within the brain. It’s important to point out that the causes for these patterns can be as varied, just like the various diseases or conditions that can affect the brain’s function. The use of these patterns differs, they can be either widespread affecting the entire brain or localized affecting only a certain area. A widespread pattern normally indicates a condition that affects the brain as a whole while localized patterns suggest issues in a specific part of the brain which might be due to some structural damage.
Some common causes for the widespread patterns can be drug side effects, oxygen deprivation to the brain, toxic metabolic encephalopathy which is a type of brain disorder caused by various factors like infections or kidney failure, and sepsis which is a life-threatening response to infection. It’s also observed that certain patterns are often linked with liver or kidney failure, yet it should be stated that the patterns have limited reliability in identifying the exact cause.
Particular care should be given to a broad-spectrum antibiotic used to treat a type of inflammation of the brain, which has been reported as a frequent cause of such patterns, as well as pattern related to withdrawal from medicines used in anesthesia.
When there is some form of damage to the brain that results in synchronized brain cell activity it can produce localized pattern. But it’s worth mentioning that these patterns can emerge even when there’s no clear evidence of damage or swelling on brain scans. Various diseases can cause such patterns, including infections, vascular diseases, autoimmune disorders, cancer, injuries, and inflammation.
The most common cause among these is stroke. Some well-known causes include various types of strokes, brain tumors, traumatic brain injuries, infectious inflammation of the brain, neurodegenerative disorders, autoimmune epilepsy, prion diseases, and sometimes the cause might remain unknown.
As of now, there’s no one-size-fits-all explanation for why these patterns develop in particular groups of patients with brain injuries. It still needs to be figured out.
Risk Factors and Frequency for Ictal-Interictal Continuum
The ictal-interictal continuum (IIC) refers to patterns in brain activity rather than a specific disease. Therefore, we don’t know how common it is, and it’s difficult to say whether it affects one gender more than another because this might depend on the underlying cause of these patterns. Understanding these measures has been made extra tricky because new patterns have been discovered or old ones have been redefined under the IIC umbrella as our understanding of these patterns has evolved.
Even though we’re not sure how common the IIC is, research has investigated the occurrence of seizures associated with these patterns. The results vary quite a bit depending on the type of pattern being investigated. For instance, the occurrence of seizures in severely ill patients can range from 45 to 95% for those with LPD patterns, 43 to 78% for those with BIPD patterns, 11 to 89% for those with GPD patterns, and 35 to 63% for those with LRDA patterns.
Also, the form or shape (morphology) of these activity patterns seems to play a role in the risk of seizures. Patterns with additional features like rhythmicity or fast frequencies superimposed on periodic patterns have been linked to a greater chance of developing discrete seizures and status epilepticus, a serious seizure condition.
Signs and Symptoms of Ictal-Interictal Continuum
If a patient has unusual changes in their mental state or has specific disabilities without any clear reason, non-stop seizures might be the cause. This is especially true for those critically ill patients who need intensive care or patients with a known history of epilepsy. Detection of these seizures at an early stage can lead to immediate diagnosis and treatment. Close observation in the intensive care unit (ICU) can also help in detecting subtle signs of a seizure-like repeated blinking or lip smacking.
Patients showcasing widespread symptoms on the epilepsy spectrum usually show varying levels of cognitive impairments in attention or consciousness. These symptoms could indicate a global problem in brain function. Patients who seem to be at a cognitive starting point may lie within the non-seizure period of the epilepsy spectrum, while patients who progressively become unresponsive move towards the seizure period. It’s essential to rule out and manage any other confusing factors, like metabolic imbalances or sedation, for an accurate understanding of these patterns in critically ill patients.
Localized patterns on the epilepsy spectrum can correlate with cognitive impairments typically seen in the problem region. These impairments can range in severity, depending on the frequency of abnormal electrical discharges, the presence of other diseases, and the patient’s cognitive health before the onset of the disease. However, these changes in mental status or consciousness might be caused by certain disease processes underlying these abnormal discharges. Diseases like cancer, tauopathies (neurodegenerative diseases), autoimmune encephalitis (brain inflammation caused by the body’s immune system), and infectious encephalitis could cause such effects.
Testing for Ictal-Interictal Continuum
An Electroencephalogram (EEG), a test that measures the electrical activity of your brain, is the only test that can identify Irregular Ictal-Ictal Continuum (IIC), essentially abnormal brain waves, in a clinical setting. This test is usually set up following a specific system known as the 10-20 international system. Trained professionals who specialize in brain disorders, namely an epileptologist, clinical neurophysiologist, or general neurologist, are responsible for interpreting the results. Constant video monitoring is essential during this test to make sure there are no physical signs (like twitching or seizures) that could affect the results.
For a pattern on the EEG to be considered an IIC, it needs to not fulfill the criteria for electrographic (based on the EEG readings) or electroclinical seizures (based on both EEG readings and physical signs). Also, it needs to fulfill at least one of the following criteria:
1. Abnormal brain waves, called epileptiform discharges, that average between 1.0 and 2.5 Hz and last at least 10 seconds (results in 10 to 25 discharges in 10 seconds).
2. Abnormal brain waves that average between 0.5 and 1.0 Hz and last at least 10 seconds, but also possess a ‘plus modifier’ or fluctuation.
3. A type of abnormal brain activity, called lateralized rhythmic delta activity, that is greater than 1.0Hz and lasts at least 10 seconds, but also carries a ‘plus modifier’ or fluctuation.
‘Plus modifiers’ are additional features that make the pattern appear more like a seizure. These features can include embedded fast or sharp frequencies, and combinations of fast frequencies and rhythmic or sharp discharges. They are usually superimposed on other types of abnormal brain waves, like periodic discharges or rhythmic delta activity.
Fluctuation is defined as three or more changes that happen no more than one minute apart. These changes could be in frequency (by at least .5/s), shape, or location by at least 1 standard inter-electrode distance, which means the location of the abnormal discharge on the EEG. These changes do not qualify as evolutions of the abnormal discharge.
Treatment Options for Ictal-Interictal Continuum
If a patient displays patterns in their brain activity that might suggest a non-convulsive seizure, doctors will mainly focus on two things. Firstly, they will determine if these patterns truly indicate a seizure, and secondly, they’ll look for any treatable causes behind these unusual patterns. Like with all serious conditions, doctors will first ensure that the patient’s vital signs are stable, and they’ll be prepared to provide breathing assistance or regulate blood pressure if necessary.
If needed, they might perform brain scans, especially if there are specific areas of concern. However, these scans are normally carried out before the continuous video analysis of the patient’s brainwaves, known as EEG. Doctors will also potentially conduct several blood tests, which could include checking the patient’s blood glucose level, complete blood count (CBC), comprehensive metabolic panel (CMP), screenings for toxins, and levels of any existing anti-seizure medications.
Not all patients exhibiting these brainwave patterns will require additional support for their blood pressure or breathing. Some patients, particularly those with severe epilepsy syndromes like static encephalopathy, might have these patterns consistently, even when their condition is stable.
As for treatment, doctors must take into consideration the patient’s overall condition and any other health complications. There isn’t a standard treatment guideline available. Choices for medication include quick-acting drugs like midazolam, lorazepam, or diazepam. Alternatively, they might opt for intravenous administration of non-sedating anti-seizure medications like levetiracetam or valproic acid.
The aim of medication is to conclusively determine whether the brainwave patterns are due to a seizure. Higher doses, as per the American Epilepsy Society guidelines for treating convulsive seizures, may be required. A positive response to drugs would be indicated by an improvement in both the patient’s condition and the brainwave patterns. An improvement in only the brainwave patterns isn’t enough, as some anti-seizure drugs can reduce seizure-like brain activity even if the patient isn’t actually having a seizure.
Simultaneously, doctors will try to identify and stop any medications harmful to the brain and treat the underlying health problem causing the seizure-like activity. For example, if the condition was induced by a medication like the antibiotic cefepime, stopping it would be the priority rather than adding more anti-seizure medications. Once the triggering substance is no longer in the patient’s system, these unusual brainwave patterns may go away on their own.
What else can Ictal-Interictal Continuum be?
The IIC, which stands for “Interictal-Ictal Continuum,” is not a disease in itself. Instead, it’s a set of features seen in an EEG (a test that records the electrical activity of the brain) related to a seizure condition, but it doesn’t meet the formal criteria to be classified as a full-blown seizure. The way these IIC patterns look can differ a lot depending on the underlying cause, but using the rules and guidelines from the American Clinical Neurophysiology Society (ACNS) can help to ensure these patterns are not mistaken for something else.
While one study found GRDA (Generalized Rhythmic Delta Activity), another pattern seen on EEGs, to be associated with seizures in 10% of patients, it’s not considered as a pattern that causes seizures nor does it fit into the group of patterns defined as IIC. There is also a unique type of electrical activity seen in the brain known as Brief potentially ictal rhythmic discharges (BIRDs). BIRDs involve rhythmic activity that is sharply outlined, changes over time, or similar in location and shape like actual seizures in the same recording, and lasts less than 10 seconds. Even though they share clinical implications with IIC patterns, these BIRDs are considered a distinct and separate pattern.
What to expect with Ictal-Interictal Continuum
An EEG (electroencephalogram), a test that records electrical activity in the brain, can’t predict the outcome of a condition all on its own. This holds true for patterns that define something called ‘IIC’. To properly understand the chances of recovery, doctors need to consider your detailed medical history, a neurological exam (brain and nervous system evaluation), and your clinical trajectory (the course of your condition), with the EEG results supporting these other pieces of information. The root cause of brain dysfunction plays the biggest role in predicting what the outcome might be.
Due to the many different reasons these patterns can appear, the prognosis (predicted outcome) can widely vary. For example, in a group of patients who had traumatic brain injury, those with moderate and severe IIC activity didn’t necessarily have a poor outcome. However, in a group of patients with a brain condition called ‘subarachnoid hemorrhage’, those who had periodic discharges were found to have almost 19 times increased risk of poor functional outcome, as per the modified Rankin Scale, a commonly used measure for stroke recovery.
Finally, rhythmic and periodic patterns found in the context of a cardiac arrest (heart stoppage) are generally linked to poor neurological outcomes, but this is not always the case. So, caution must be exercised when interpreting these findings. This is especially important if there’s a worry that the pattern might be showing ongoing seizures that are not being treated actively.
Possible Complications When Diagnosed with Ictal-Interictal Continuum
The complications that come from IIC patterns can be from one of two things. Either a patient is being treated too much for interictal abnormalities, which are patterns that occur in between seizures, or they are not getting enough treatment for seizures that show up on tests but don’t cause physical symptoms.
When a patient’s interictal patterns get treated too much, they can experience side effects like becoming drowsy, worsening brain disorders, and negative side effects from seizure medication. These side effects can include slowed breathing, allergic reactions, and becoming resistant to the medication. Intense treatment could also lead to the patient needing help breathing with a machine, which has its own risks like lung infection, lung damage, and heart problems.
On the other hand, not treating IIC patterns enough can increase the risk of damage to the nerves from a patient’s body not getting enough nutrients or oxygen. It could also make the body resist treatment more and lead to severe seizures, which can have serious health risks and even lead to death. However, it’s important to note that some studies have found that patients who have experienced seizures without physical symptoms have good long-term brain function and memory outcomes. The tests suggest that these types of seizures don’t cause permanent damage unless there’s an existing medical problem that makes it worse.
Common Side Effects:
- Drowsiness
- Worsening brain disorders
- Negative side effects from seizure medication
- Slowed breathing
- Allergic reactions
- Resistance to medication
- Potential need for mechanical breathing assistance
- Lung infection
- Lung damage
- Heart problems
- Potential nerve damage
- Resistance to treatment
- Severe seizures
- Death
Preventing Ictal-Interictal Continuum
Although it’s recognized that certain health problems can be linked to an irregular brain wave pattern known as IIC, it’s still a mystery why some people develop this pattern and others don’t, even when they have similar health issues. Presently, there’s no proven way to reduce the risk of this pattern showing up in an EEG, a test that measures electrical activity in the brain.
If there’s worry that these unusual brain wave patterns might indicate ongoing, yet unseen seizures, doctors may consider treatments based on the patient’s overall health condition. It’s important for doctors to be careful when trying to figure out the cause of the pattern. They need to understand the risks associated with both providing treatment and not providing treatment to the patients.
