Understanding Postictal Psychosis: A Complex Case of Seizure-Related Psychiatric Symptoms

Table of Contents

• Background and Introduction
• Case Presentation: A 41-Year-Old Man with Seizures and Agitation
• Medical History and Initial Symptoms
• Hospital Course and Symptom Progression
• Diagnostic Testing and Imaging Results
• Differential Diagnosis: Exploring Possible Causes
• Key Findings and Final Diagnosis
• Clinical Implications for Patients with Epilepsy
• Risk Factors for Postictal Psychosis
• Treatment Approaches and Management
• Limitations and Considerations
• Recommendations for Patients and Families
• Source Information

Background and Introduction

This case from Massachusetts General Hospital illustrates the complex relationship between epilepsy and psychiatric symptoms. Approximately 7.8% of patients admitted to epilepsy monitoring units experience postictal psychosis, a condition where psychotic symptoms emerge after seizures. Patients with epilepsy face an 8 times higher risk of psychosis compared to the general population, making this an important area of understanding for both patients and healthcare providers.

The bidirectional relationship means that people with chronic psychotic disorders also have a 2-3 times higher risk of developing epilepsy. This case demonstrates how seizure activity can directly influence mental health symptoms and why comprehensive neurological and psychiatric care is essential for patients with treatment-resistant epilepsy.

Case Presentation: A 41-Year-Old Man with Seizures and Agitation

A 41-year-old man was admitted to the epilepsy monitoring unit (EMU) of Massachusetts General Hospital due to increased seizure frequency. The patient had experienced possible seizure activity since age 4 when his mother noticed episodes of staring and unresponsiveness. At age 19, he was involved in a single-vehicle accident where the car rolled over, though he didn't recall the events or seek medical evaluation afterward.

Approximately 15 years before this admission, he received a formal epilepsy diagnosis when he began experiencing episodes of staring to the left with unresponsiveness. These seizures were preceded by a "bad feeling" in the epigastric region (upper abdomen) and followed by confusion, agitation, or sleepiness. His initial electroencephalogram (EEG) showed bitemporal sharp waves, and magnetic resonance imaging (MRI) revealed possible asymmetry in the temporal horns of the brain.

Medical History and Initial Symptoms

The patient's focal seizures began occurring weekly and progressed to generalized tonic-clonic seizures (full-body convulsive seizures). Over 15 years, he received treatment with various antiseizure medications at adjusted doses, experiencing seizures approximately once per month despite treatment.

During the 3 months before admission, his seizure frequency increased to up to three times monthly despite adherence to his prescribed medications, which included:

• Carbamazepine
• Levetiracetam
• Topiramate

Four weeks before admission, he experienced five seizures within 2 weeks. Two weeks before admission, coworkers witnessed shaking of his arms and legs, prompting emergency medical services to transport him to another hospital's emergency department. He received a prescription for diazepam for insomnia and was discharged.

Hospital Course and Symptom Progression

The day after discharge, the patient's neurologist spotted him stumbling on the side of the road during his commute. The patient was behaving erratically and not responding to questions or commands. Law enforcement was called, and the patient tried to run away before being restrained and taken to the emergency department.

After his behavior and confusion resolved, he was referred to the EMU for additional evaluation. On admission day, the patient reported work stress, inadequate sleep, but adherence to his antiseizure medications. He described "blurriness" of memory for a few days after each seizure but maintained his work functioning.

During the admission interview, he reported that "something strange was about to happen," experienced blurred vision, and had nonrhythmic movements in both thighs while remaining aware of these events—symptoms not typical of his usual seizures.

Diagnostic Testing and Imaging Results

Initial MRI of the head revealed decreased volume of the left hippocampus and parahippocampal gyrus with increased signal intensity. Ex-vacuo dilatation (enlargement due to tissue loss) of the left temporal horn was present, likely secondary to volume loss. Interictal positron-emission tomography (PET) scanning showed subtle reduction of 18F-fluorodeoxyglucose uptake in the left mesial temporal lobe, indicating reduced metabolic activity in this region.

During hospitalization, continuous EEG monitoring captured five seizures with staring and subtle movements in both legs lasting up to 3 minutes. Most electroclinical seizure events originated from the left temporal lobe focus, while one event originated from the right temporal lobe, indicating bilateral independent seizure foci.

Between seizures, the patient experienced severe behavioral changes including attempts to remove EEG electrodes, biting and kicking clinicians, requiring security intervention and medication administration. He later expressed paranoid thoughts, believing staff were trying to kill him, and auditory hallucinations of a keyboard playing.

Differential Diagnosis: Exploring Possible Causes

The medical team considered several possible explanations for the patient's behavioral changes:

• Postictal agitation: More common with temporolimbic seizures, typically occurring immediately after seizures without a lucid interval
• Nonconvulsive status epilepticus: Continuous seizure activity without convulsions, but ruled out by continuous EEG monitoring
• Functional or nonepileptic seizures: Psychological rather than neurological seizures, but the patient had documented epileptic seizures on EEG
• Interictal psychosis: Psychosis occurring between seizures rather than related to them
• Ictal psychosis: Psychosis as a direct manifestation of seizures, but typically brief (20 seconds to 3 minutes)
• Postictal psychosis: Psychosis following seizures after a return to normal mental function
• Forced normalization: Paradoxical normalization of EEG with emergence of psychiatric symptoms when seizures are controlled

Key Findings and Final Diagnosis

The medical team diagnosed postictal psychosis based on several key factors:

The psychosis began 16 hours after a return to normal mental function following a cluster of five focal impaired awareness seizures. The patient had bilateral independent seizure foci (both left and right temporal lobes), documented by EEG monitoring. His epilepsy history spanned at least 15 years (possibly 22 or 37 years if counting early symptoms), consistent with the typical timeline for postictal psychosis development.

He exhibited characteristic symptoms including auditory hallucinations, paranoia, aggression, and peculiar verbalizations. The Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR) diagnosis was "psychotic disorder due to another medical condition (epilepsy) with delusions."

The team also noted possible "poriomania"—a specific form of postictal delirium involving wandering with amnesia—based on his behavior of wandering confused on the roadside before admission.

Clinical Implications for Patients with Epilepsy

This case highlights several important implications for patients with epilepsy:

Psychiatric symptoms can emerge as a direct consequence of seizure activity, not just as a separate condition. Seizure clusters (multiple seizures within a short time) significantly increase the risk of postictal psychosis. Medication adjustments, particularly rapid changes to antiseizure medications, may contribute to psychiatric symptoms through forced normalization.

Patients with bilateral seizure foci (seizures originating from both sides of the brain) face higher risk of psychiatric complications. The timeline for psychosis development typically involves many years of epilepsy before psychiatric symptoms emerge.

Risk Factors for Postictal Psychosis

Based on research and this case, several factors increase the risk of postictal psychosis:

1. Treatment-resistant epilepsy that doesn't respond well to medications
2. Seizure clusters (at least three seizures within 24 hours)
3. Male sex (postictal psychosis is more common in men than women)
4. Seizure duration exceeding 10 years
5. Experience of seizure aura (warning sensations before seizures)
6. Bilateral independent seizure foci (seizures originating from both brain sides)
7. History of previous postictal psychosis episodes
8. Family history of psychosis (though not present in this case)

This patient exhibited all these risk factors except family history of psychosis, making him particularly vulnerable to developing postictal psychosis.

Treatment Approaches and Management

The medical team employed multiple treatment strategies:

They adjusted antiseizure medications, initially decreasing then increasing carbamazepine doses, stopping and restarting levetiracetam, and eventually transitioning to intravenous lacosamide. For acute agitation, they used antipsychotic medications including haloperidol and risperidone, plus benzodiazepines (lorazepam) for anxiety and agitation.

For autonomic symptoms including increased blood pressure (160/100 mm Hg) and rapid pulse (120 beats per minute), they implemented labetalol treatment. Safety measures included temporary use of two-point and four-point restraints during extreme agitation to protect both patient and staff.

The treatment approach emphasized that managing postictal psychosis requires both seizure control and psychiatric symptom management simultaneously.

Limitations and Considerations

This case study has several important limitations:

As a single case report, the findings cannot be generalized to all patients with epilepsy. The retrospective nature means some information might be incomplete or subject to recall bias. The complex medication changes during hospitalization make it difficult to isolate specific treatment effects.

The possibility of functional or nonepileptic seizures coexisting with epileptic seizures couldn't be completely ruled out, as approximately 20% of people with drug-resistant epilepsy also have functional seizures. The long history of possible seizure activity beginning in childhood makes precise timeline determination challenging.

Recommendations for Patients and Families

Based on this case, patients with epilepsy and their families should:

• Monitor for behavioral changes following seizures, particularly after seizure clusters
• Report any new psychiatric symptoms (paranoia, hallucinations, aggression) to healthcare providers immediately
• Understand that medication adjustments may temporarily worsen psychiatric symptoms
• Maintain consistent communication between neurology and psychiatry providers
• Develop safety plans for managing agitation or confusion after seizures
• Keep detailed seizure diaries noting both seizure activity and behavioral changes
• Seek comprehensive care that addresses both neurological and psychiatric aspects of epilepsy

Families should particularly note that postictal psychosis typically emerges after a return to normal mental function following seizures, not immediately afterward. This lucid interval can range from hours to days before psychiatric symptoms appear.

Source Information

Original Article Title: Case 37-2024: A 41-Year-Old Man with Seizures and Agitation

Authors: Sheldon Benjamin, M.D., Lara Basovic, M.D., Javier M. Romero, M.D., Alice D. Lam, M.D., Ph.D., and Caitlin Adams, M.D.

Publication: The New England Journal of Medicine, November 28, 2024, Volume 391, Issue 21, Pages 2036-2046

DOI: 10.1056/NEJMcpc2402500

This patient-friendly article is based on peer-reviewed research from Massachusetts General Hospital case records published in The New England Journal of Medicine.