What are the most common psychiatric diagnoses associated with nonepileptic seizures?

Nonepileptic seizures are classified as a conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Conversion disorder is included in the broader category of somatoform disorders. Essentially, the patient presents with symptoms suggestive of a neurologic or other general medical condition, preceded by conflicts or other stressors. The symptom is not feigned, and appropriate investigations fail to reveal evidence of a causative organic condition. The symptoms cause significant distress and interfere with the patient's general functioning.

In some patients, NESs are part of a symptom complex subsumed under the rubric somatization disorder. In this condition, the patient has a pattern of recurring multiple and significant somatic complaints beginning under the age of 30 and extending for a prolonged period, sometimes many years.

Patients with NESs also suffer from associated psychiatric disorders. More than one condition is often present. Anxiety disorders are commonly encountered, often unrecognized by patient or physician. In particular, many patients fulfill DSM-IV diagnostic criteria for panic disorder, with or without agoraphobia. The symptom complex of NESs may be due solely to panic attacks, or the attacks may coexist with NESs. Careful inquiry is essential in order to establish the diagnosis.

Depression is often seen in patients with NESs. In some, it has been proposed that the pain of depression has been unrecognized or unaddressed by family or others. As a result, the development of NESs may constitute a mechanism of bringing the patient's problems to the attention of the medical profession.

Psychotic disorders such as schizophrenia are considered uncommon accompaniments of NESs, although they may be seen.

Other conditions that are even less common include malingering and factitious disorder.

A detailed psychiatric interview will usually bring out any associated psychiatric disorders. In some cases, however, application of the Structured Clinical Interview for DSM-IV (SCID) may be required to determine the number and extent of the patient's problems.

Numerous studies have evaluated the clinical differentiation between nonepileptic seizures (NESs) and epileptic seizures. This section addresses the evaluation, diagnosis and treatment of NESs, and provides a guide for discussing the diagnosis of NES with patients.

Generally, there are many differences between the histories of patients with nonepileptic seizures (NESs) and those of patients with epilepsy.

NESs may occur only in the presence of others or, conversely, may never have been observed. In the latter case the clinician is dependent on the patient's description, which may be fragmentary and incomplete. Indeed, only loss of consciousness may be reported. If such a patient has a history of epilepsy, the probability of misdiagnosis is high.

The interview may reveal a clear emotional trigger for NESs. This criterion is not at all definitive, however, because patients with epilepsy often ascribe seizures to "stress."

The patient's reaction to his or her seizures may offer clues to the diagnosis. The demeanor of the patient with NESs classically has been described as la belle indifference, but many authors have found such indifference to be atypical. More commonly, the patient is quite concerned about the seizures, sometimes excessively so. In fact, an exaggerated emotional response may provide a clue to NESs but should be considered in context with other information.

Treatment with AEDs, regardless of types or combinations, is rarely successful, although transient responses are not uncommon. In fact, increasing doses of AEDs may lead to a paradoxical increase in seizure frequency. Patients with NESs sometimes complain of intolerable side effects at low doses or slow dose escalation of AEDs.

A history of physical or sexual abuse is common in patients with NESs. At an appropriate time the clinician should inquire into this sensitive subject. Drawing firm conclusions from a history of abuse is perilous, however, because abuse is common in people with epilepsy and in the general population. Many people with epilepsy also have poignant histories of childhood or marital abuse.

Finally, suspicion is sometimes kindled by the patient's previous experience with other people who have epilepsy. The person may have encountered seizures in a professional capacity-for example, in a hospital setting. A family member or friend may have seizures, or the patient's own previous or current epileptic seizures may serve as templates for NESs. In addition, cultural influences may play a role in some cases.

Do patients with nonepileptic seizures have a typical psychologic profile?

Patients with NESs have no characteristic psychologic profile. Perhaps the most consistent results have resulted from the application of the Minnesota Multiphasic Personality Inventory (MMPI). In particular, Dodrill has reported that MMPI profiles differ between patients with epilepsy and those with NESs (Dodrill 1993). The typical findings in many NES patients are relatively high scores on the hysteria and hypochondriasis scales, with a lower score on the depression scale. These characteristics differentiated NESs from epilepsy in about 80% of cases.

Thus, the MMPI offers useful information but cannot be said to have sufficient power for diagnostic certainty. The results of psychologic testing, therefore, must be taken in concert with the results of other testing and considered supportive or nonsupportive of the diagnosis of NES.

If the clinician observes one or more NESs, the phenomenology of the event may raise suspicion that the patient does not have epilepsy. Nothing in the clinical expression of NESs can be considered definitively pathognomonic, however. Only by recording the behavioral and electrographic characteristics can the event be diagnosed confidently.

One common clue is that NESs often have a gradual onset, but epileptic seizures typically start and end suddenly. For example, a simple absence seizure (formerly known as petit mal) begins with sudden loss of awareness, which continues for several seconds and then ends abruptly, at which time the person is fully aware and functional. Similarly, a tonic-clonic epileptic seizure begins suddenly with a fall, loss of consciousness, and frequently a cry. Motor activity continues for a minute or so, progressing predictably and ending abruptly. At that point the patient is deeply comatose and flaccid. With NESs, on the other hand, consciousness may be preserved during the peri-ictal phase.

In contrast, a nonepileptic seizure characterized by vigorous motor activity frequently builds in intensity as the event progresses. The event itself is often of longer duration than its epileptic counterpart, sometimes lasting many minutes or even hours. Moreover, the motor movements may have a waxing and waning quality through the course of the seizure. (Some NESs with motor manifestations are characterized by vigorous motor activity and intervening periods of quiet unresponsiveness.) The event tends to subside gradually, and the postictal state-whether unresponsiveness or apparent confusion-is less profound than in the case of a tonic-clonic convulsion.

Although it is often said that tongue biting and incontinence do not occur with NESs, some patients with documented NESs have reported these symptoms. Bladder and bowel incontinence and self-injury are rare but can occur. When biting occurs, it tends to involve the tongue tip, arms, or other body areas more than the sides of the tongue.

NESs that resemble true absence attacks are more difficult to differentiate from epilepsy than motor events. The staring, unresponsive state provides no obvious clues concerning the nature of the attack. However, if such attacks are of long duration, one might suspect that the diagnosis is other than epilepsy. The only way to confirm the true diagnosis is to record the event in question by EEG monitoring, preferably with simultaneous video monitoring.

Patients with NESs resembling complex partial seizures also present diagnostic difficulties, owing to the protean manifestations of the epileptic events. Such patients may exhibit confusional states with or without apparent automatic activities. Again, recording of the event is essential to confirm the diagnosis.

Another feature suggestive of NESs is an emotional response during or after an event. Crying and other emotional vocalizations are common. Although crying occurs in rare patients with epilepsy, it is more frequent in those with NES.

Typical NESs, especially motor events, do not seem to follow a "physiologic" progression. The motor activity tends to be chaotic, sometimes with flinging movements. Alternation of the movements, opisthotonus, pelvic thrusting, and dystonic posturing may be present. One important distinguishing feature of NESs is that, in contrast to epileptic seizures, the face is often not involved.

Some patients with NES exhibit avoidance behavior during events, especially during quiescent phases. For example, if the patient's arm is held aloft and released, the patient may avoid striking himself or herself in the face. Such behavior suggests that the attack is nonepileptic.

In some cases NESs can be initiated and ended by suggestion and verbal intervention.

What is the diagnostic role of prolactin levels?

Elevations in serum prolactin occur in the postictal phase (20 to 25 minutes after the seizure subsides) after some types of epileptic seizures. The most consistent increase is found after generalized tonic-clonic convulsions.

The "gold standard" in the diagnosis of nonepileptic seizures (NESs) is a recording of a typical event during video-EEG monitoring. This procedure is available at all centers specializing in epilepsy and is increasingly available at general hospitals and even in some neurologic group practices.

During this procedure, the EEG is recorded for a prolonged period, accompanied by continuous closed-circuit video observation. The digitized EEG and recorded behavior are displayed simultaneously, allowing point-to-point correlations of recorded events and any accompanying electrographic changes.

Types of monitoring

Two types of monitoring are in general use:

• an outpatient procedure with a duration of 6 to 8 hours (Daytime Monitoring, or DAYMON)
• inpatient monitoring, which continues for 24 hours or more

Outpatient studies are less expensive and more convenient than inpatient monitoring. DAYMON is most appropriate for patients with relatively high seizure frequencies-at least three events per week. To increase yield, DAYMON should be carried out when the patient is sleep-deprived.

If the patient's seizure frequency is relatively low, inpatient video-EEG monitoring for 24 hours or more is indicated. This procedure requires hospital admission and a dedicated staff. Although more costly than DAYMON, inpatient monitoring is effective. More than one event may be recorded, increasing diagnostic certainty if the events are stereotyped. Inpatient monitoring also allows recording of a full night's sleep, increasing the possibility of recording sleep-provoked epileptiform activity as well as nocturnal clinical events. Several days of monitoring may be required before the diagnosis is made.

Video-EEG monitoring procedures

During video-EEG monitoring, the patient wears an EEG transmitter connected to a wall outlet by coaxial cable. Wall-mounted video cameras provide continuous behavioral observation. Both EEG and video signals are transmitted to a control room, where the EEG is reformatted and conducted to a video monitor. The EEG signal and video are displayed simultaneously for on-line observation, and both are recorded on videotape. The EEG may be recorded on paper or stored on optical disc.

The patient can move about and carry out normal activities, such as napping, talking, and watching television. Participation by a family member or friend is encouraged, especially someone who has observed the patient's events in the past. Hyperventilation and photic stimulation are carried out. These may cause clinical or diagnostic changes in patients with epileptic seizures but not NESs. Although NESs may occur spontaneously, the application of these procedures appears to increase diagnostic yield.

An important diagnostic aid is suggestion techniques to precipitate one of the patient's usual events. These techniques may take the form of placing alcohol pads over the carotid arteries or administering intravenous saline. The patient is told that the procedure will be carried out to induce a seizure and that only by recording an event will a diagnosis be possible. If an event is precipitated and the event is typical of the patient's usual seizure, a diagnosis of NESs is highly likely. False positives are rare. When DAYMON is performed in this manner, an overall success rate of approximately 60% may be expected (French 1993). There are some ethical concerns about the use of deception, although definitive diagnosis can allow patients to obtain proper therapy and avoid unnecessary antiepileptic drugs, with their side effects.

Video-EEG findings

During NESs, the EEG will show:

• no epileptiform activity
• no initial change such as premonitory spikes
• no postseizure slowing

Although the EEG tracing is frequently obscured by movement artifact, small interpretable segments containing alpha activity may be apparent, indicating that consciousness is preserved.

A normal or nonepileptiform EEG during a seizure may suggest a NES, but it can also occur during a simple partial seizure or frontal lobe complex partial seizure undetected by surface leads. A normal EEG during a seizure in which the patient is displaying generalized motor movements would not be expected in a true epileptic seizure, however.

The most important task is to ensure that the recorded event(s) are typical of the patient's spontaneous attacks. This task can be accomplished only by reviewing the recorded attack with a person who has witnessed such events. If it is determined that the recorded and spontaneous attacks are similar, a presumptive diagnosis of NESs can be made.

Some clinicians require that more than one attack be recorded, but this is not always possible. Nonetheless, it appears that a single recorded event similar to previous attacks is sufficient to consider NESs the most likely diagnosis.

This diagnosis, of course, does not exclude the possibility of coexisting epilepsy, especially if the patient has attacks with different clinical features. Some epilepsy patients experience psychogenic nonepileptic seizures at some point, and patients with psychogenic nonepileptic seizures can have neurologic illness.

The interictal EEG is not useful in making the distinction because it may be normal or abnormal in either case. The interictal EEG of patients with NESs may contain epileptiform discharges, even though the ictal record does not reveal electrographic seizure activity.

Alternatives to intensive video-EEG monitoring

If intensive video-EEG monitoring is not available, a diagnosis of NESs can be made with reasonable assurance using commonly available tools. Probably the best method is to obtain an EEG after the patient is sleep-deprived. A video camera can be set up in the EEG room. During the recording, and after explaining the procedure, apply techniques of suggestion, emphasizing the importance to the patient of recording an event.

The use of 24-hour ambulatory cassette EEG recording to diagnose NESs is not recommended unless a home video unit is available. Unless the behavioral aspects of the attack are recorded, there is too little diagnostic information. Moreover, excessive EEG artifacts during an attack often makes it very difficult to interpret the cassette EEG. If the patient has attacks characterized by staring with little motor activity, a cassette EEG can be useful. Certainly, differentiation of absence seizures from NESs characterized by loss of awareness is relatively easy. Again, simultaneous video recording greatly enhances diagnostic power.

Telling the patient about nonepileptic seizures

When the diagnosis of nonepileptic seizures (NESs) is confirmed, it must be presented in a positive, supportive, and nonthreatening manner. The physician must have an empathetic, compassionate attitude to ensure the patient's allegiance and offer hope for the future.

NESs should be described as a disorder that cannot be treated with anticonvulsant medication. Emphasize the disability associated with NESs and discuss the effect of the attacks on the patient's life. Also stress that NESs have psychosocial consequences as profound as those of epilepsy but point out that they do not require chronic treatment with drugs that produce side effects.

Outline the availability and indeed the success of treatment for NESs. Explain that many others suffer from NESs but that each person is unique, requiring tailor-made treatment. Reassure the patient that the outlook for improvement or complete recovery is excellent-even better than in the case of epilepsy.

Such a conference is time-consuming but rewarding. Most patients are willing to accept a diagnosis of NESs if it is presented in this manner, and they are eager to pursue an appropriate course of therapy.

What professionals should be involved in treatment?

Neurologists usually have little interest in continuing to care for patients in whom NESs are diagnosed, considering most of these patients not to have neurologic disease. Further, many psychiatrists are reluctant to care for patients with somatoform disorders. This reluctance is a problem for these patients, who suffer from significant disability. The psychiatrist should cooperate closely with the referring neurologist. The patient thus gains by receiving continuing support on the medical side while exploring the root causes of the psychiatric disability.

Probably the best approach to treatment for most patients is offered by a multidisciplinary team composed of specialists in the fields of

• neurology
• psychiatry
• psychology
• social work

Such a group addresses the multidimensional nature of NESs. Besides diagnosing and managing the underlying psychiatric condition, the treatment can also address problems of psychosocial functioning, occupational issues, and family interactions. Coordination of efforts in these several spheres is key to the team approach. The goal is to restore the patient to normal functioning in the shortest possible time.

Types of programs

The patient can be treated as either an inpatient or an outpatient. The goals for both approaches are the same and in the long run they probably produce similar outcomes.

Inpatient programs are usually associated with epilepsy centers. Two excellent ones are located in Minneapolis and St. Paul, Minnesota. On discharge, the patient is referred to a local psychiatrist, who carries out longer-term intervention. The major advantage to the inpatient approach is the intensity and focus that is possible at the onset of treatment. A major disadvantage is the cost associated with hospitalization.

The outpatient approach is less intense but cost-effective. The outpatient approach combines regular team meetings with ongoing therapy. The principal therapist may be the psychiatrist, psychologist, or social worker, depending on the nature and extent of the patient's particular problem.

Each patient with NESs requires an individualized treatment program. Those with significant depression may be treated with antidepressants along with ongoing psychotherapy. Patients with panic disorder may receive appropriate pharmacotherapy with an agent such as desipramine. Some will require only short-term psychotherapy.

For patients with somatoform disorder, supportive treatment and encouragement can aid overall functioning and stop "doctor shopping" for multiple somatic complaints. NESs are likely to continue in this group, however.

Prognosis

The prognosis for patients with NESs is variable. Even without specific treatment, NESs tend to decline over time. A 1-year follow-up study of 80 patients in whom NESs were diagnosed during EEG-video monitoring revealed that 59% had become seizure-free in the interval, and an additional 20% reported a decline in event frequency. Other studies have found that even with specific intervention, fewer than 50% become seizure-free, and some who become seizure-free develop other (substitution) conversion symptoms.

The literature is sparse with respect to the effectiveness of psychotherapy, but some improvement occurs in up to 60% of patients. Success rates appear to depend on the severity and duration of the psychiatric illness. Those with NESs of relatively short duration, perhaps related to an intercurrent situation such as an acute loss, have a favorable prognosis. Short-term psychotherapy may be highly effective in these cases.

On the other hand, prolonged duration of NESs associated with severe psychopathology may be refractory to treatment. In these cases, supportive treatment may be all that can be offered.

An optimistic attitude on the part of the caregivers is important and indeed justified. This attitude should be conveyed to the patient at the outset and continually reinforced.

Dodrill CB, Wilkus RJ, Batzel LW. The MMPI as a diagnostic tool in non-epileptic seizures. In: Rowan AJ, Gates JR, eds. Non-epileptic seizures. Boston: Butterworth-Heinemann; 1993, pgs 211-219.

Ettinger AB, Dhoon A, Weisbrot DM, Devinsky O. Outcome in psychogenic nonepileptic seizures: 1 to 10-year follow-up in 164 patients. Ann Neurol. 2003;53:305-11.

Ettinger AB, Dhoon A, Weisbrot DM, Devinsky O. Predictive factors for outcome of nonepileptic seizures after diagnosis. J Neuropsychiatry Clin Neurosci. 1999;11:458-63.

French JA. The use of suggestion as a provocative test in the diagnosis of psychogenic non-epileptic seizures. In: Rowan AJ, Gates JR, eds. Non-epileptic seizures. Boston: Butterworth-Heinemann; 1993, pgs 101-109.

Pritchard PB. The role of prolactin in the diagnosis of non-epileptic seizures. In: Rowan AJ, Gates JR, eds. Non-epileptic seizures. Boston: Butterworth-Heinemann; 1993, pgs 93-100.

Ramsay RD, Cohen A, Brown MC. Coexisting epilepsy and non-epileptic seizures. In: Rowan AJ, Gates JR, eds. Non-epileptic seizures. Boston: Butterworth-Heinemann; 1993, pgs 47-54.

Reuber M, Pukrop R, Bauer J, et al. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav. 2003;4(3):205-16.