Continuing Education Activity
Complex partial seizures, also known as focal impaired awareness seizures or focal onset impaired awareness seizures, refers to focal seizures that start in one hemisphere of the brain and are associated with an impairment in consciousness. These seizures involve an epileptiform activity that starts in a particular focal region of the brain and impairment in a patient's level of consciousness occurring at some point during the seizure. Typically, consciousness is maximally impaired toward the beginning of a seizure.
- Describe the etiology of focal impaired awareness seizures.
- Outline the testing that should be done in patients who present with a history of impaired consciousness.
- Describe the management considerations for focal impaired awareness seizures.
- Explain the need for a well-integrated, interprofessional team approach to improve care for patients with focal impaired awareness seizures.
Complex partial seizures refer to focal seizures that start in one hemisphere of the brain and are associated with impairment in consciousness. Complex partial seizures are now preferably called "focal impaired awareness seizure" or "focal onset impaired awareness seizure." International League Against Epilepsy (ILAE) 2017 classification has categorized seizures based on three key features: the location of seizure onset, level of awareness during a seizure, and other features of seizures. Focal seizures refer to the epileptiform activity starting in one area on one side of the brain. If awareness is impaired or affected at any time during the seizure, it is called focal impaired awareness seizure. Focal seizures are further classified into motor onset (automatisms, atonic, clonic, myoclonic, tonic, epileptic spasms, hyperkinetic) and nonmotor onset (autonomic, emotional, sensory, cognitive, behavior arrest) types. A seizure that starts on one side or one part of the brain and then spreads to both sides, earlier referred to secondarily generalized seizures, is now preferably termed as "focal to bilateral seizure."
Focal seizures with impaired consciousness can present with or without an aura. Auras can last from a few seconds to as long as 1 to 2 minutes before the consciousness is impaired. Consciousness is maximally impaired in the beginning typically. Most of the seizures with automatisms last longer than 30 seconds, up to 1 to 2 minutes and sometimes can be as long as 10 minutes. Absence seizures can sometimes present with the same symptomatology however ictal EEG will show generalized 3-Hz spike-wave complexes. Symptoms of focal seizures with impaired awareness depend on the area of the brain it is arising from. Most of the complex partial seizures arise from the temporal lobe. Extratemporal origin has been reported in at least 10% to 30% of patients.
Seizures of Temporal Lobe Origin
These are the most common type of focal impaired awareness seizures. Stereotyped automatisms occur in about 40% to 80% of patients with temporal lobe epilepsies. Seizures with predominantly oral and manual automatisms in addition to some other motor manifestations are highly suggestive of temporal lobe origin. About 60% of temporal lobe seizures have a secondary generalization. Gradual recovery after several minutes of confusion occurs postictally in most patients, however, in some patients automatic behavior like running, walking about, the nondirected violent behavior may occur. Temporal lobe focal impaired seizures can have features similar to frontal seizures, but temporal lobe focal impaired seizures typically have slower onset and progression, and more pronounced confusion. Certain features can help in localizing the seizure onset to one hemisphere. Ictal vomiting, ictal speech, urinary urge, and automatisms with intact consciousness suggest seizure onset in the non-dominant hemisphere, and speech disturbance postictally is suggestive of seizure onset in the dominant hemisphere. Upper limb dystonia lateralizes seizure to the opposite hemisphere.
In young children with focal seizures of temporal lobe onset, behavioral arrest and unresponsiveness are common. Oroalimentary automatisms tend to occur in children older than age 5. In younger children, the symmetric motor movement of the limbs and head nodding is typical. In infants, these seizures may be subtle with few automatisms. In very young infants, central apnea can occur. Temporal focal impaired seizures can be confused with absence seizures as both may have automatisms, but temporal seizures are usually longer in duration and are associated with postictal confusion.
Seizures arising from the mesial temporal lobe are characterized by auras such as epigastric sensation, deja vu, a feeling of fear, and unpleasant smells. Autonomic features like tachycardia, flushing, and pallor are common. Auras may be followed by impaired awareness and manual and oroalimentary automatisms. Automatisms in the upper limb and /or pupillary dilatation unilaterally may lateralize seizure to the ipsilateral hemisphere. Dystonia in the upper limbs and head and eye version on the opposite side can occur.
Lateral temporal seizures may have vertigo, auditory (buzzing, ringing), or visual symptoms as initial aura symptoms. Auditory aura in only one ear may lateralize seizure to the contralateral hemisphere. Initial aura is usually not prolonged, and impaired awareness is an early feature. Seizures are of shorter duration and progression to bilateral convulsions is more common than those arising from the mesial temporal lobe.
Seizures of Frontal Lobe Origin
Up to 30% of the patients with focal epilepsy have seizures arising from the frontal lobe. It is the most common extratemporal type. Seizures are accompanied by loss of consciousness in about half of the patients with frontal lobe epilepsy. Focal impaired awareness seizures can arise from various locations within the frontal lobe, except the rolandic strip. These seizures typically are brief, lasting about 30 seconds, occurring in clusters, multiple times a day, are often nocturnal occurring during sleep and have minimal postictal confusion. Motor symptoms are predominant and range from hypermotor thrashing episodes like pelvic thrusting, bicycling movements to asymmetric tonic posturing. Sexual automatisms, bizarre behavior, and vocalizations are common. These seizures often have a stereotypical pattern for each patient. Nocturnal frontal lobe seizures may be mistaken for parasomnias. The ictal EEG may be difficult to interpret because of movement artifacts. Identification based on semiology alone and differentiating from mesial temporal lobe epilepsy may be difficult, however earliest signs and symptoms and their order of appearance may help in distinction. Seizures with hypermotor features are more likely to have an ictal focus in the orbitofrontal and frontopolar regions. Temporal lobe seizures have more oroalimentary automatisms, gesturing and fumbling semiology.
Epileptiform activity in frontal convexity can cause clonic seizures, and in the supplementary motor area can cause tonic seizures. Unique semiology of the supplementary sensorimotor cortex includes deviation of head and eye to the side contralateral to seizure onset, the asymmetrical posturing of upper limbs with an extension of arm contralateral to the side of seizure onset and flexion of ipsilateral arm. Orbitofrontal region seizures are automotor type and manifest prominently with autonomic phenomena like flushing, vocalization, and automatisms. Anterior cingulate gyrus seizures have predominant motor manifestations like hypermotor seizures and complex motor seizures. Posterior cingulate cortex epilepsies predominantly have altered consciousness and automotor seizures as main clinical manifestations. Antero-lateral dorsal convexity seizures may manifest with auras such as dizziness, epigastric sensation, behavioral arrest and speech arrest.
Seizures of Parietal Lobe Region
Seizures arising from the parietal lobe may be difficult to diagnose because of their subjective nature. Positive and /or negative sensory features are common. Sensorimotor phenomenon and vestibular hallucinations suggest onset in the parietal lobe. Paresthesias, visual hallucinations, visual illusions, somatic illusions, vertiginous features can occur. Seizures arising from the dominant hemisphere can cause receptive language impairment. Parietal lobe complex partial seizures can have auras like epigastric sensations, visual hallucinations, panic attacks, and behavioral arrest. Often there is an involvement of other lobes as the seizure spreads. When focal seizures from the parietal lobe spread and involve the temporal lobe, loss of consciousness and automatisms may occur.
Seizures of occipital lobe origin
Seizures with ictal origin in the occipital lobe are characterized by a visual aura and are difficult to diagnose especially in young children. Visual auras, typically of elementary sensations, ictal blindness, versions of the head and eyes to the opposite side, rapid and forced blinking, oculoclonic activity are some features suggesting occipital lobe as an origin of focal seizure with impaired consciousness. Seizures from the primary visual cortex can cause bilateral loss of vision in the form of white-out or black-out. Shorter duration of the visual aura (less than 2 minutes) can help to differentiate from migraine aura which is typically longer (5 to 15 minutes). Complex, formed visual hallucinations like pictures of people, animals, etc. are associated with seizure onset in the extra-striate cortex. Other symptoms may result from spread to temporal or parietal lobes.
Seizures of Insular Lobe Origin
Seizures arising from the insula can mimic frontal, temporal, parietal lobe seizures. Origin from the insula is suspected when viscerosensitive symptoms (nausea, vomiting, salivation), motor symptoms (tonic, hypermotor or generalized tonic-clonic movements), and/or sensory symptoms (numbness, tightness, vibration, pain, vertigo) occur at seizure onset.
Some known causes of seizures include:
- Infectious: The most common cause of epilepsy in developing countries and overall worldwide is infectious. Infections can cause both acute seizures and epilepsy. Tuberculosis, neurocysticercosis, cerebral toxoplasmosis, HIV, cerebral malaria, SSPE, and bacterial and viral meningoencephalitis are some infections known to cause seizures.
- Structural: Any structural brain abnormality like stroke, trauma, infection, tumor, hippocampal sclerosis, AVM, postsurgical changes can increase the risk of seizures and epilepsy
- Metabolic: Several inherited enzymatic disorders like GLUT-1 deficiency, cerebral folate deficiency, among others can cause seizures. Other acquired disorders like electrolyte imbalance - hyponatremia, hypocalcemia, and hypoglycemia can cause seizures.
- Genetic/chromosomal abnormalities: Several chromosomal disorders (e.g., AKT3, Fragile X syndrome) and gene defects (e.g., Down's syndrome, Klinefelter's syndrome, Angelman syndrome) have been associated with epilepsy.
- Traumatic brain injury
- Hypoxic brain injury
Etiology cannot be determined in more than half of all individuals with epilepsy. A congenital anomaly is the most common known etiology in children, and head trauma in young adults. In people, age 35 to 64 years, head trauma, tumors, and vascular disorders are common causes. In people age 65 years or more, cerebrovascular disease, and degenerative disorders are the most commonly known etiologies.
Certain situations or triggers cause seizures. Some common triggers include tiredness and lack of sleep, stress, alcohol, fever, acute medical illness, hormonal changes, substance abuse, certain medications, bright and flashing lights, and medication noncompliance.
After the first year of life, complex partial seizures are the most common seizure type in patients with epilepsy. It is estimated that around 36% of people with epilepsy have complex partial seizures. It affects all ages. Incidence is highest in children and older adults. No predilection for gender or race is known.
The most common pathological feature of temporal lobe epilepsy is hippocampal sclerosis. Hippocampal sclerosis (HS) consists of neuronal loss and gliosis in the dentate nucleus and pyramidal layer of the hippocampus. Mechanism of damage in HS is glutamate discharge during the seizure episode. The most frequent site of damage is in the CA1 area of the hippocampus. It is controversial whether HS is a result of seizures or a cause of seizures.
Both cortical and subcortical structures play an important role in controlling the level of consciousness. Higher-order association cortices on both sides have a role in maintaining an overall level of attention and awareness, and they interact reciprocally with the subcortical arousal structures. Subcortical arousal systems contain numerous neurotransmitter systems that act in conjunction to maintain the level of consciousness.
The characteristic feature of the complex partial seizure (focal impaired awareness seizure) is impaired awareness, referring to decreased overall arousal and responsiveness. These seizures most commonly arise from the temporal lobe. Simple responses like visual tracking may be preserved in complex partial seizures. However higher-order processing tasks like a verbal response, decision making are profoundly impaired.
Several mechanisms of altered consciousness in the setting of focal seizures have been proposed.
Network Inhibition Hypothesis
Focal ictal activity in the temporal lobe produces abnormal polyspike discharges. Abnormal seizure activity is carried to subcortical structures with pools of GABAergic inhibitory neurons via known anatomical connections. This may inhibit the subcortical arousal systems in the upper brainstem, thalamus, hypothalamus and basal forebrain. Inhibition of subcortical arousal leads to slow-wave activity in regions of the frontoparietal association cortex bilaterally, producing impaired consciousness.
Epileptic Activation of Subcortical Structures, Mainly Thalamus and Upper Brainstem
The prefrontal cortex and the nonspecific thalamic nucleus and the midline regions of the intralaminar thalamic complex have close connections. It is hypothesized that the rapid epileptic spread from all the frontal regions of the reticular formation may be responsible for the impaired consciousness observed in frontal lobe epilepsy. A similar mechanism has been suggested in temporal lobe epilepsy with additional spread to the upper brainstem structures.
Epileptic Disturbance of the Normal Balance Between Excitation and Inhibition of Cortical/Subcortical Networks
Interference with the normal activity of primary motor cortex or epileptic activation of the negative motor areas during frontal lobe involvement, or both, may be responsible for the arrest of activity during a seizure, has been suggested by some authors.
History and Physical
As with other types of seizures, diagnosis of focal impaired awareness seizure is based on clinical history. Epilepsy is a clinical diagnosis. As with any other seizure, it is most important to make sure that the episode is truly a seizure. Obtaining a detailed history from the patient and family members is important. A detailed description of the spell, for example, the sequence of events, nature of onset, loss of consciousness, any motor or convulsive activity, bilateral involvement, tongue bite, incontinence, stare, automatisms, eye movements, postictal confusion, recovery, and duration of events are very important to elicit. It is important to elicit a detailed medical history to identify possible risk factors.
The clinical semiology depends on the location of the seizure focus. A detailed neurological examination is important. Even subtle findings on the neurological exam can support the diagnosis of seizures. Also, certain lateralizing abnormalities on the neurological exam can help predict the epileptic focus.
Some specific features associated with focal seizures can help in lateralizing the seizure origin to one hemisphere. These features provide a good clue for lateralization but can be falsely lateralizing.
- Dystonic limb posturing: Unilateral dystonic posturing is the most reliable lateralizing sign in the temporal lobe automotor seizures. Unilateral hand/arm dystonic posturing in conjunction with automatisms of the opposite limb and head-turning is highly suggestive of temporal lobe onset contralateral to the dystonic upper extremity.
- Head version: Classical head version (defined as a tonic, unnatural, forced lateral gyratory head movement) is highly suggestive of seizure onset to the contralateral side. It can occur in both temporal and extratemporal seizures. Seizures spread to the premotor areas may be the cause.
- Automatisms: Oroalimentary automatisms like lip-smacking, chewing, or swallowing may occur without loss of consciousness at seizure onset in temporal lobe seizures with seizures confined to the amygdala and anterior hippocampus. Most automatisms are usually accompanied by impaired consciousness and have no lateralizing value, but preserved responsiveness during automatisms lateralize to the nondominant hemisphere. Eye blinking or fluttering at seizure onset may indicate occipital lobe onset. Aversion of the eyes to the opposite side suggests seizures arising from the occipital region. Focal seizures with impaired consciousness arising from mesial frontal and orbitofrontal regions can cause bicycling or pedaling movements of the leg. Mimetic automatisms and crying have been reported in focal seizures with impaired consciousness arising from the non-dominant temporal lobe. Vomiting during seizure lateralizes to the non-dominant hemisphere. Sexual or genital automatisms (like pelvic thrusting, masturbation) can occur in focal seizures with the impaired consciousness of frontal lobe origin and temporal lobe origin.
- Postictal nose wiping: Postictal nose-wiping that occurs within 60 seconds of the seizure occurs in about 50% to 85% of temporal lobe epilepsy patients and is performed with the ipsilateral hand in a majority of the cases.
Clinical data alone is often not enough to precisely diagnose and localize focal seizures.
- A comprehensive metabolic profile, complete blood count (CBC), urine analysis, urine toxicology screen is usually checked initially to rule out metabolic causes and infections.
- Electroencephalography (EEG) is an important test for evaluating patients with seizures, although not essential for diagnosis. Some patients may require video EEG or prolonged EEG monitoring.
Interictal EEG: Thirty percent to 40% of the patients may have normal interictal findings on a single routine EEG recording. Temporal intermittent rhythmic delta activity is predictive of temporal lobe epilepsy. Bitemporal sharp wave foci may be noted in 25% to 30% of the patients. Intermittent rhythmic slowing may be the only clue as mesial temporal spikes may not be seen well at the surface. The amplitude of mesial temporal spikes is maximal at the anterior temporal scalp electrodes, and nasopharyngeal and sphenoidal electrodes when used. Sharp wave foci are seen in the mid-temporal and posterior temporal regions less frequently. Extratemporal focus (most commonly frontal lobes) is seen in 10% to 30% of patients with focal seizures with impaired consciousness. The interictal discharge may take the form of a bifrontal spike and wave discharge in some patients with mesial frontal foci.
Ictal EEG: Ictal EEG is abnormal in about 95% of the patients with focal impaired awareness seizures. About two-thirds of the patients with focal seizures with impaired consciousness have an electrodecremental pattern at the onset. A prototype pattern consisting of 5 to 7 Hz rhythmic theta discharge in the temporal regions is seen in about 50% to 70% of patients with temporal lobe epilepsy. This pattern has shown high accuracy in localizing the onset to the ipsilateral mesial temporal structures on depth electrode studies. Lateralization from scalp EEG is usually satisfactory however localization within a lobe may sometimes be incorrect. Scalp ictal changes are difficult to appreciate with some frontal lobe seizures because of movement artifacts.
- Neuroimaging is often needed to rule out structural causes.
MRI head is a very sensitive and specific imaging technique for localization-related epilepsy. The use of high-resolution MRI and specific seizure protocols can enhance the detection of abnormalities like hippocampal atrophy. The likelihood of finding an epileptic focus on neuroimaging studies is higher in patients with focal seizures than in generalized seizures. Common MRI findings are mesial temporal sclerosis, congenital anomalies, brain tumors, sequelae of head injury, vascular lesions, neurocysticercosis. Many MRI findings may be nonspecific and should be interpreted in a clinical context.
Sometimes further imaging with PET scan, ictal and interictal SPECT may be utilized to identify the ictal onset zone, especially in patients with refractory seizures.
Treatment / Management
The goal of treatment is no seizure and no side effects or acceptable side effects. Antiepileptic medications are the mainstay of treatment, but other approaches are available for refractory seizures.
Except for ethosuximide, all other currently available AEDs can be used in the treatment of complex partial seizures. The choice of medication depends on the patient's preference, comorbid conditions, drug interactions and side effect profile of the drug. Monotherapy is preferred initially. An increased dose of a single agent may be required to achieve seizure control before adding another agent. Classical AEDs used for complex partial seizures include carbamazepine, valproate, phenytoin, and phenobarbital. Newer agents available are levetiracetam, topiramate, lamotrigine, gabapentin, oxcarbazepine, zonisamide, felbamate, tiagabine, pregabalin, and lacosamide. The most common first-line drugs are carbamazepine, phenytoin, valproic acid, and oxcarbazepine.
More than half of the patients with complex partial seizures will require more than one AED. The use of more than one antiepileptic drug creates a potential for drug interactions, often necessitating constant monitoring and adjustment in doses. Seizures are considered refractory when two or more AEDs have failed to control the seizures. Only about half of the patients with complex partial seizures have epilepsy fully controlled with medications.
The ketogenic diet is a specialized high fat, low carb, and controlled protein diet that should be considered in children with intractable seizures when at least two AEDs have been ineffective.
Surgical intervention is considered for refractory complex partial seizures. Resection surgery is considered when the seizure focus is localized and solo. An ideal candidate for respective surgery is a patient with refractory complex partial seizures who have failed trial of at least two or three AEDs, have features suggesting mesial temporal onset and MRI shows mesial temporal sclerosis. Surgical procedures for refractory complex partial seizures include amygdalohippocampectomy, temporal lobectomy, and gamma knife radiation.
Vagus Nerve Stimulation
Patients with refractory seizures who are not candidates for surgery should be considered for implantation of vagal nerve stimulation (VNS) device. Response rates of 35% to 45% have been reported with VNS therapy. Antiepileptic drugs should always be used along with it. If VNS therapy is effective, it may be possible to reduce the medications slowly.
Some conditions that can initially present like complex partial seizures include the following:
- Absence seizures
- Benign childhood epilepsy
- Benign neonatal convulsions
- Complicated migraine
- Juvenile myoclonic epilepsy
- Paroxysmal movement disorders
- Psychogenic nonepileptic seizures
- Vasovagal syncope
Patients with focal seizures have a higher risk of seizure recurrence than those with generalized seizures. Recurrence rates of simple and complex partial seizures appear to be the same. Loss of consciousness can cause trauma, aspiration, burns, and accidents. Associated anxiety, limitations in work, and driving add to significant morbidity. The mortality rate in patients with epilepsy is 2 to 3-times higher than the general population. Most deaths are due to underlying etiology and accidents. Sudden unexpected death in epilepsy (SUDEP) is more in patients with medically intractable seizures.
Enhancing Healthcare Team Outcomes
Seizures are best managed by an interprofessional team that includes a nurse practitioner, primary care provider, neurologist, pharmacist, and a neurosurgeon. Once treated, these patients are often followed as outpatients by the primary care provider. It is vital that the nurse and primary care provider educate the patient on safety and compliance with treatment. Depending on the medication, drug levels may need to be obtained regularly. In addition, the pharmacist should keep track of the patient medications to ensure that no drug interactions occur. The outlook for patients with seizures depends on the chronicity.