Psychosis of Epilepsy: Psychosis in a Patient With a Negative Continuous Electroencephalogram

It has been well established that patients with epilepsy have an increased rate of developing a psychotic disorder (1). In the general population, the risk of a psychotic disorder is 0.4%–1%, but this risk is increased to 5.6% among patients with epilepsy (2, 3). Of interest, the reverse is also true: among patients with a psychotic disorder, the risk of developing a psychotic disorder is 2.3 times greater risk than in the general population (4).

The following case highlights the need for clinicians to be vigilant for psychosis in patients with epilepsy and to recognize risk factors for development of psychosis when seizures are poorly controlled. Literature pertaining to psychosis of epilepsy is also reviewed and discussed.

Case

Ms. U is a 44-year-old woman with a past medical history of focal seizures with impaired awareness starting at age 4 and with no psychiatric history. She was admitted to our facility’s epilepsy monitoring unit (EMU) for continuous electroencephalogram (cEEG) monitoring for poorly controlled seizures. The patient was transferred from an outside hospital emergency department when she presented with a fear that her mother was trying to kill her. During her EMU admission, no seizures were observed, and her cEEG showed no epileptic discharges. No obvious paranoia was observed during hospitalization, and after 3 days of no clinical seizure activity she was discharged to outpatient follow-up.

Six days after discharge, the patient was readmitted for new involuntary movements. Her behavior was now more disorganized: her thought associations were loose, and she exhibited frequent episodes of facial grimacing, irregular complex bilateral upper-extremity flailing, and speech arrest. Her home antiepileptic drug (AED) serum levels were all subtherapeutic, as was a levetiracetam level (not in her home regimen). Her treatment team believed that shortly after she was discharged from her initial EMU admission, she must have stopped taking her medications and had a seizure. Psychiatry was consulted for concern of psychosis.

Psychiatry evaluated Ms. U and obtained collateral information from her sister suggesting that the patient did not have psychosis at baseline. However, immediately preceding her first admission to the EMU and after receiving levetiracetam at an outside hospital, she had stopped sleeping and started believing that her family was trying to poison her food. The patient had a similar paranoid episode several years prior, also immediately following treatment with levetiracetam, which led to psychiatric hospitalization at an outside hospital.

A review of outside records indicated that Ms. U was hospitalized 5 years prior. A cEEG at the time suggested temporal lobe epilepsy, with possible interictal or postictal psychosis because of her paranoid delusions. History from the patient’s sister at that time suggested that the patient had a history of psychosis, occurring exclusively when seizures were not controlled.

On the evening of Ms. U’s second EMU admission, her cEEG showed bitemporal intermittent sharp activity with right temporal slowing. She said that her sleep was irregular and that she woke hourly. On hospital day 2, shortly after falling asleep, she had a 3.5-minute seizure captured on cEEG and video monitoring. During this seizure, the patient remembered awaking from sleep and feeling "scared." She then lost consciousness and exhibited bilateral upper-extremity straightening into a fencer pose, with subsequent lower-extremity bicycling motions. The cEEG at this time revealed a frontal lobe seizure with right more than left temporal spikes, suggestive of bilateral independent epileptiform foci.

Throughout her admission, Ms. U’s mental status exam was significant for impaired abstract thinking, concentration, calculation, and short-term memory. She consistently denied paranoia. On hospital day 4, she started to refuse treatment recommendations such as AEDs and antipsychotics and began to focus on her need to go home immediately. Her sister and mother were not available by phone after several attempts.

On hospital day 5, the patient demanded discharge. She did not meet inpatient psychiatric admission criteria and was minimally able to express the risks of discharge, so she signed out against medical advice.

After Ms. U was discharged, her moth­er told the neurology team that she had avoided answering phone calls from the team because the patient was calling from the hospital dozens of times throughout the day. Prior to admission, the patient was refusing to eat because she was worried that her family was poisoning her, and she would eat only cereal from sealed containers at home. The patient was also not compliant with antiseizure medications at home because of her suspicion.

Discussion

Ms. U’s case of psychosis and poorly controlled seizures highlights the importance for neurologist and psychiatrists to be cognizant of the four categories included in psychosis of epilepsy (POE). The onset of psychosis in relation to an ictal event is the basis for how different types of POE are categorized. The two main categories of POE are interictal psychosis and postictal psychosis (5). Other phenomena described in the literature include "forced normalization," in which psychosis worsens the further from an ictal event an individual gets (6), and AED-induced psychosis (notoriously associated with levetiracetam) (5, 7). As shown in Ms. U’s history of psychosis after receiving levetiracetam, risk factors for AED-induced psychosis include female gender and temporal lobe involvement (7). However, Ms. U’s psychosis continued even after a negative levetiracetam serum level was detected. It is not clear from the literature if a history of postictal psychosis predisposes an individual to AED-induced psychosis, or vice-versa.

Postictal psychosis is diagnosed when there is a 24- to 48-hour—but no more than 7-day—delay between a seizure and the onset of psychosis and when the psychosis lasts between 15 hours and 2 months and there is not a more obvious reason for the psychosis (AED induced, status epilepticus, etc.). Postictal psychosis occurs in 3.7% of persons with epilepsy and is a self-limiting phenomenon (3). Generally, patients tend to experience features suggestive of mania, such as grandiose, religious delusions (5). It tends to be preceded by a period of insomnia, as seen in Ms. U (6).

Interictal psychosis is characterized by psychosis independent of the timing of seizure activity, and it occurs in 2.2% of persons with epilepsy (3). Phenomenologically, interictal psychosis closely resembles primary psychotic disorders, but it is differentiated by the psychosis beginning after the onset of epilepsy. Interictal psychosis presents with disorganized thought, paranoia, command auditory hallucinations, and negative symptoms (3).

The risk factors for postictal psychosis include temporal lobe epilepsy, bilateral seizure foci, earlier epilepsy onset, impaired intellectual function, and presence of ictal fear, all of which were present in Ms. U, with the exception of impaired intellectual function (8). Neuroimaging of POE suggests enlarged bilateral amygdala (9). A theory proposed regarding the similar neurobiology of POE and schizophrenia suggests that an overactivation of the temporal lobes and limbic system, coupled with a dysfunction of the frontal cortex, may lead to the resultant psychotic experiences in both syndromes (9).

In drug-induced psychosis, the offending agent should be avoided. In postictal and interictal psychosis, seizure control with antiepileptic drugs is reasonable; however, antipsychotics are also indicated because these agents decrease the duration of the psychotic episodes (1, 8, 10). Risperidone and quetiapine are relatively safe for patients with a history of seizures (1, 10).

Conclusions

Ms. M’s initial presentation of psychosis after levetiracetam and a negative cEEG was suggestive of an AED-induced psychosis, possibly with psychogenic nonepileptic seizures; however, she continued to have psychosis with a negligible levetiracetam serum level. Ultimately, she was found to have bilateral temporal and frontal seizures on subsequent cEEG. The onset of her psychosis shortly after noncompliance with antiepileptics, recent insomnia, and bilateral seizure foci suggest a POE, likely postictal psychosis. This case highlights the importance of a clinician’s familiarity with the clinical characteristics of the various POE types, especially as the timeline of seizure to psychosis can be difficult to elucidate in a brief hospitalization.

Key Points/Clinical Pearls