Functional or psychogenic seizures have proved a diagnostic and therapeutic challenge for centuries. Functional seizures can look and feel similar to epileptic seizures but are instead a common and highly disabling form of functional neurologic disorder, or conversion disorder. Consistent with the biopsychosocial model of mental illness, functional seizures are caused by biological, psychological, and social factors unrelated to epileptic discharges. People with functional seizures do not consciously fake their symptoms. Functional seizures can be differentiated from epileptic seizures through the clinical history, features of the seizures themselves, and electroencephalography findings. Psychotherapy is effective in treating functional seizures.
Functional seizures can look and feel like epileptic seizures, but are distinct in that they are a form of functional neurologic disorder or conversion disorder, with contributing biological, psychological, and social factors. Patients do not consciously produce or “fake” functional seizures.
The gold standard for distinguishing functional seizures from epileptic seizures is evaluation with long-term video-electroencephalogram (video-EEG) in an epilepsy monitoring unit, showing no epileptiform changes on the EEG immediately before, during, or following typical seizure events. Characteristics of the clinical history and the seizure events themselves are also important in diagnosing functional seizures.
Untreated functional seizures are associated with significantly elevated mortality and impaired function and quality of life.
Multiple randomized trials support the efficacy of cognitive behavioral therapy in treating functional seizures, and other forms of psychotherapy, such as mindfulness-based psychotherapy and psychodynamic psychotherapy, may be effective.
There is no evidence that antiseizure medications provide any benefit in the treatment of functional seizures.
Functional seizures are paroxysmal episodes of altered awareness that may resemble an epileptic seizure, but have no physiologic basis in epilepsy. These attacks are transient, usually involving significant stress, and have been associated with comorbid psychiatric and psychological difficulties, poor quality of life, elevated mortality rates, and frequent use of the health care system.
Multiple names have been used for this disorder, with the goals of accurately describing the pathophysiology, allowing for supportive and productive interaction with patients, and dispelling the perception that the patient is “faking” a seizure for alternate gain. The historical term “pseudoseizure” inadvertently created an environment of mistrust between patients and emergency clinicians, and perhaps given the inaccurate impression that the diagnosis itself is fraudulent. This has contributed to patients distrusting clinicians who recommend that psychotherapy is the generally accepted treatment of choice, which only serves to keep patients from successful treatment and improved quality of life. Other terms in use include psychogenic nonepileptic seizure, dissociative seizure, nonepileptic attack disorder, and conversion disorder with attacks or seizures. There is growing recognition that patients and families also find the term “psychogenic” pejorative, leading to a shift away from this terminology and efforts to identify a single unified terminology. For the purposes of this review, we use the term “functional seizures,” which is acceptable in surveys of patients and clinicians, and accords with the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), and the broader category of functional neurologic disorders (FND) or conversion disorders. This broader category includes functional seizures, functional movement disorders, functional paralysis, functional cognitive disorders, and other functional disorders The International Classification of Diseases (ICD)-11 uses the term “dissociative” to connote a compartmentalization or detachment of neurologic functioning from normal awareness. For the first time in the history of the ICD, FNDs were placed in the neurology section instead of the psychiatry section. This is groundbreaking in that it will allow neurologists to make functional seizures a positive diagnosis instead of a diagnosis of exclusion. It will also provide a stimulus for research, endorse a nomenclature that will allow for constructive patient-physician encounters, and give patients access to innovative treatments, such as specialist neurologic physiotherapy.
Functional seizures are a common and especially disabling type of FND, and in keeping with the biopsychosocial model of mental illness, are thought to have contributing biological, psychological, and social factors. Contributing psychological factors include severe adverse life events (such as neglect, abuse, and other psychological traumas), which are identified in 91% of people with FNDs. Functional MRI (fMRI) studies are beginning to demonstrate potentially predisposing biological factors, including decreased activity in the amygdala during distress conditions and increased resting state functional connectivity between areas of the brain involved in emotion (amygdala) and areas involved in motor planning (precentral gyrus).
FNDs have challenged clinicians and patients alike, due to the perception that a diagnosis without an associated structural cause must have an intentional or willful component, thus placing “blame” on the patient for the disorder. This mind-body dualism has persisted throughout history, and it is generally accepted that FNDs are involuntary, with symptoms occurring even when patients believe themselves to be unobserved. Therefore, functional seizures and other FNDs should be distinguished from disorders that involve conscious production of symptoms such as malingering or factitious disorder.
The DSM-5 includes functional seizures in the category of FND or conversion disorder with the following criteria:
One or more symptoms of altered voluntary motor or sensory function
Clinical findings provide evidence of incompatibility between the symptom and recognized neurologic or medical conditions
The symptom or deficit is not better explained by another medical or mental disorder
The symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation
Of note, the DSM-5 does not include a requirement that an adverse life event or other psychological stressor be identified to make the diagnosis of functional seizures or other FND. This is important because psychological stressors are often not identified by clinicians or patients until extensive psychotherapy is completed. Historically, the average delay to diagnosis of functional seizures has been 7 to 10 years. In that time, the impact to the patient and family can be devastating, including multiple hospital admissions, failed medication trials with concomitant side effects, social ostracization, lost wages, depression, and increased mortality. Therefore, in cases of suspected functional seizures, it is critical to actively seek supporting evidence through neurologic evaluation and video electroencephalography (vEEG). Diagnosis should not be delayed until a psychological stressor is identified or until all other possible diagnoses are definitively ruled out.
There are an estimated 2 to 33 patients with functional seizures per 100,000 persons annually. However, this relatively small number of patients has frequent recurrent contact with the health care system: functional seizures are diagnosed in 25% of all patients evaluated in epilepsy monitoring units and FND more generally are diagnosed in 16% of patients evaluated in neurology clinics. , The diagnosis of functional seizures can be challenging, with significant overlap; 12% of people with epilepsy also have functional seizures and 22% of people with functional seizures also have epilepsy.
Most patients with functional seizures are female, with initial presentation in the late teens to early twenties. They typically have a history of trauma or psychological stressors, such as sexual or physical abuse, neglect, and social or family conflict. Because this is a difficult diagnosis affected by clinical presentation, clinician and patient perceptions and lack of access or willingness to pursue psychotherapeutic treatment, most patients presenting to the emergency department (ED) with functional seizures have had multiple related visits and hospital admissions, and have been unsuccessfully treated with antiseizure medications.
The costs of functional seizures are real and devastating for patients, families, and society. In a study of more than 5000 patients diagnosed with vEEG monitoring, mortality for patients with functional seizures was 2.5 times that of the general population, not significantly different from that of patients with drug-resistant epilepsy, and 8.3 times higher in those younger than 30 years. Notably, 20% of deaths in those younger than 50 years were attributed to suicide. Quality of life associated with functional seizures is worse than quality of life in epilepsy, fraught with avoidance of emotions, poor management of internal anger, depression, and dysfunctional family life. Patients with functional seizures have higher health-related social welfare costs, and lower levels of employment. The diagnosis also has a significant impact on partners and family. In a cohort of 698 adults with functional seizures, 67% of patients were unemployed, 56% were receiving disability payments, and more than half lived in economically deprived areas at the time of diagnosis.
Because a delay in diagnosis predicts worse outcomes, functional seizures should be part of the differential diagnosis for seizure and considered with respect to history, clinical presentation, and EEG if available and appropriate. The International League Against Epilepsy offers guidelines for diagnosing functional seizures with increasing levels of diagnostic certainty on the basis of clinical history, EEG findings, and semiology (what the seizures look and feel like). The diagnosis of functional seizures can be categorized as possible if patient or witness reported the event with typical functional seizure semiology, probable if a clinician witnessed the event in person or by video, clinically established if an experienced epileptologist witnessed an event that was also captured on EEG, or documented if an experienced epileptologist witnessed an event with typical functional seizure semiology while the patient was on vEEG to disprove epileptiform activity.
Any seizure event can be broadly categorized as epileptic seizure, functional seizures, or physiologic nonepileptic events, such as a convulsive syncope, hypoglycemic seizure, transient ischemic attack, stroke, sleep disorders, transient global amnesia, and/or migraine. Accurate diagnosis is important to reduce the risk of delayed diagnosis, and to give the patient an opportunity for improved quality of life. The gold standard diagnostic test is vEEG, which is not always available.
In addition to demographic characteristics of patients with functional seizures, other historic and clinical evidence make functional seizures a more likely diagnosis than epileptic seizure. Seventy percent to 80% of people with functional seizures are female, 80% to 90% have additional psychiatric comorbidities, and most have a history of adverse life events. Patients with functional seizures may report a precipitating event such as trauma including mild traumatic brain injury or concussion (75%) or sexual trauma (40%). Patients with functional seizures tend to have a higher frequency of events and recurrent associated hospital admissions. Functional seizures may be triggered by a stressful situation, or medical situation such as a computed tomography scan or EEG. The disorder in general may be triggered by surgery or physical trauma, and up to 40% of patients may exhibit a partial or transient response to antiseizure medications.
In one study, patients who had at least 2 events per week, were not responsive to 2 antiseizure medications, and had 2 normal EEG studies showed 85% positive predictive value for functional seizures. A history of fibromyalgia or chronic pain in a patient presenting for evaluation of seizures also carries a positive predictive value of 75% for functional seizures. Of note, no single historical feature is 100% sensitive or specific for functional seizures. Rather, clusters of multiple historical features can make functional seizures more or less likely.
A functional seizure is more likely to be hyperkinetic, similar to an epileptic seizure, but less commonly can be hypokinetic, similar to a vasovagal or cardiac syncope event. In the hyperkinetic event, there is typically eye closure, fluctuating movements, asynchronous movements of different body parts, pelvic thrusting, side to side head or body movement, closed eyes, partially retained awareness, ictal crying, and prolonged duration (≥2 minutes). One of the most specific discriminatory signs is ictal crying, which can occur during or after the event, may be complex and affective, differentiated from an epileptic seizure in which and ictal cry occurs at the beginning of the event, and is primitive in nature with no emotional expression. As with historical features, no semiological feature is 100% sensitive or specific for functional seizures. Although rare, frontal lobe epileptic seizures can present with many of the characteristics typical of functional seizures, including pelvic thrusting, opisthotonic posturing, bicycling movements, and asynchronous movements. This reinforces the requirement for vEEG for definitive diagnosis.
During a functional seizure, ictal heart rate is typically appropriate for the level of physical activity noted during the event, as opposed to an epileptic seizure, that can have a rapid as well as a rapid increase in heart rate during the seizure.
It is important to note that patients should not be subjected to aggressive or harmful stimuli such as aggressive sternal rub, exposure to ammonia capsules, or other painful stimuli in order to “differentiate” between an epileptic and functional seizure. , Patients with functional seizures have a high likelihood of traumatic events including abuse, and the aggressive infliction of pain and/or noxious stimulus is not diagnostically helpful, and only serves to potentially create distrust and fear.
A rise in serum prolactin level to twice normal, if drawn within 20 minutes of the event and compared with a baseline level can be useful to rule out epileptic generalized tonic-clonic seizure but not focal seizures. The absence of a rise in the prolactin level may suggest functional seizures, but not with great sensitivity or specificity, and in particular cannot rule out a focal epileptic seizure. Some have investigated serum white blood cell count, cortisol levels, creatinine kinase, neuron-specific enolase, and dexamethasone suppression testing to identify functional seizures, but none has proven to be sensitive or specific in the diagnosis.
Although there is a growing body of evidence that research protocol MRI can identify subtle functional and structural differences between groups of people with functional seizures and groups of healthy controls, such techniques are not yet clinically useful in diagnosing individual patients. , At this time, clinical imaging findings cannot be used in the clinical diagnosis or exclusion of functional seizures.
EEG is the gold standard for the diagnosis of functional seizures. The diagnosis of even possible functional seizures requires at minimum a routine EEG, obtained interictally (between seizure events), without epileptiform abnormalities, such as sharp and slow-wave discharges. More extensive EEG data can support a greater level of diagnostic certainty, such as clinically established or documented functional seizures. In particular, to make the most definitive diagnosis of documented functional seizures, it is necessary capture of all typical seizure events without epileptiform abnormalities immediately before, during, or following seizures. In many cases, normal awake brain electrical activity, including a normal posterior dominant rhythm, can be seen during impaired or lost consciousness in functional seizures. Important caveats to keep in mind include frontal lobe epileptic seizures, and focal seizures without impaired awareness, both of which can appear to have no epileptiform correlate on surface EEG. In such cases, it is necessary for experienced neurologists to make the diagnosis solely on the basis of clinical history and semiology. For example, frontal lobe epileptic seizures can be distinguished from functional seizures because frontal lobe seizures are usually much shorter than functional seizures (<30 seconds rather than ≥2 minutes), stereotyped (with similar movements occurring in each seizure), with bicycling movements and dystonic posturing of the arms and legs, and frequently occur during sleep.
Extended vEEG evaluations are often accomplished during an extended elective admission in an epilepsy monitoring unit. For patients whose episodes are so infrequent as to make evaluation in an epilepsy monitoring unit difficult or impossible (usually less than 1 seizure per 2 weeks), other modalities of evaluation are under development. Single-channel electromyography (EMG) obtained at home over weeks or months through a wearable device, has shown some promise in distinguishing functional seizures from focal and generalized epileptic seizures, but is not yet widely clinically available.
The first step in a successful treatment plan for the patient with functional seizures is to carefully and effectively explain to him or her that this is a neurologic diagnosis, it can be definitively established (with vEEG), and is potentially reversible with treatment. This approach will reassure the patient that he or she is being taken seriously, is not being accused of “faking” symptoms, and that the clinician is invested in helping to improve outcome. Communication of the diagnosis is understandably challenging. Demonstrating sincere compassion and empathy for the patient’s experiences, and avoiding an accusing or judgmental demeanor are especially important in delivering a diagnosis of functional seizures. Patients with functional seizures have exceptionally high rates of adverse life events, such as neglect and abuse, contributing to distrust and a feeling that clinicians are not taking them seriously when suggesting that their events are not epileptic seizures. Retrospective studies have shown that a significant number of patients stop having functional seizures when the diagnosis is carefully explained, most notably in those who had recent onset, absence of coexisting anxiety, depression, personality disorder, or abuse history and in those who were employed, and not on state benefits.
Most patients diagnosed with or suspected to have functional seizures in the ED will benefit from outpatient neurologic and psychiatric follow-up. Emergency medicine physicians play a vital role in the diagnosis and treatment of patients with functional seizures by avoiding unnecessary and potentially harmful treatments with antiseizure medications, by referring patients for outpatient diagnosis and treatment if the patient does not already have outpatient neurologic and psychiatric care, and by compassionate treatment to support the therapeutic alliance between the patient and their long-term outpatient clinicians.
The accepted standard of care for a patient with functional seizures includes description of the diagnosis with the patient with family or trusted friends present, weaning the patient from antiseizure medications unless indicated for concomitant epilepsy, and referral to an experienced psychiatrist or psychologist.
In a recent multicenter trial, 313 patients with functional seizures were randomized to functional seizure-specific cognitive behavioral therapy (CBT) plus standardized medical care versus standardized medical care alone. The primary outcome, monthly functional seizure frequency, was not different between the groups (both of which showed significant improvement). However, multiple secondary outcomes did show greater improvement in the CBT group, including less bothersome seizure activity, longer period of functional seizure freedom, better health-related quality of life, less impairment in psychosocial functioning, less overall psychological distress, fewer somatic symptoms, and patient-reported greater clinical improvement and treatment satisfaction. This is the largest randomized study to investigate the effectiveness of any treatment for functional seizures, and its positive findings are supported by 2 smaller prior single center randomized trials. , The improvement in secondary outcomes gives clinicians impetus to consider outcomes other than seizure frequency as markers of improved outcome. Previous research has shown that quality of life for patients with functional seizures is closely linked to mood, anxiety and illness perceptions. It also encourages researchers to pursue further study in CBT, considering the types of symptoms that patients are having to further stratify the type of psychotherapy that might benefit, as opposed to a “one-size-fits-all” categorization of patients with functional seizures.
If psychotherapy is beneficial to patients with functional seizures, one of the major obstacles has been patient adherence. In a prospective study of 105 patients with functional seizures who were referred to receive psychotherapy, adherence to at least 8 sessions in 16 weeks was associated with a reduction in functional seizure frequency, improved quality of life, and fewer ED visits. Self-identified minority status and a history of child abuse contributed to patient nonadherence. Motivational interviewing, before referral to psychotherapy, has been shown in a randomized trial to improve adherence with psychotherapy, functional seizure frequency, and quality of life.
Psychiatric and psychotherapeutic treatment starts with a formal assessment to exclude other psychiatric disorders. This is best accomplished when the psychiatrist is experienced with functional seizures and part of a team of clinicians.
Although CBT is the most extensively studied psychotherapeutic modality in the treatment of functional seizures, and the only modality supported by evidence from randomized trials, observational studies also support other psychotherapeutic modalities: these include hypnotherapy, , eye movement desensitization (EMDR), EEG biofeedback, mindfulness-based psychotherapy, and group therapy and/or family therapy.
Randomized trials have not shown consistent benefit of psychopharmaceuticals such as selective serotonin reuptake inhibitors in the treatment of functional seizures, but these and other psychopharmaceuticals may be effective in the treatment of comorbid psychiatric conditions such as mood and anxiety disorders.
It is important to wean patients from antiseizure medications unless they are being administered for concomitant epilepsy, mood or anxiety disorder, or psychiatric diagnosis. A randomized trial has demonstrated that patients benefit more from rapid titration off antiseizure medications at the time of diagnosis than from a prolonged titration over weeks or months.
Recent data showing the value of CBT, and the transition of functional seizures as a diagnosis from psychiatry to neurology in the ICD sets the stage for increased involvement of neurology and a collaborative partnership between neurologists, emergency physicians, psychiatrists and psychologists in approaching the patient with functional seizures. Future research may target specific subgroups of patients with functional seizures, using an individualized approach based on their propensity to engage with a particular method. Randomized trials of other psychotherapeutic modalities beyond CBT are needed to guide treatment of functional seizures. The development and testing of effective teletherapy and computerized CBT regimens will be important in providing psychotherapy to patients in areas where specialized expertise in CBT is not widely available.
It has also become apparent that frequency of seizures is only one quality of life indicator, and future research may target other outcomes such as quality of life, psychosocial function, pain, fatigue or other mental health symptoms that accompany this diagnosis.
Other tools such as wearable devices, fMRI for diagnosis, and neurostimulation for treatment are potential avenues that may dramatically expand the diagnosis and treatment of functional seizures in the years to come.
The role of the emergency clinician in the diagnosis and treatment of functional seizures includes maintaining a compassionate and nonjudgmental relationship, referring the patient to neurology or psychiatry clinicians and minimizing iatrogenic or psychological harm.
Clinical care points
Avoid judgment or minimize the presentation of a patient who presents for seizure, especially if he or she carries a presumed diagnosis of functional seizures
Do not inflict noxious or painful stimuli to attempt to disprove an event as a seizure
Understand the potential diagnosis and make an attempt to explain it carefully and nonjudgmentally to the patient, with family present if possible
Do not attempt to diagnose this in the ED; work in tandem with neurology and psychiatry.
Working collaboratively with neurology and psychiatry, attempt to wean ineffective medications
Educate prehospital and emergency medicine learners in this diagnosis, which has a strong history of being misunderstood