A 14-year-old girl was seen in the pediatric neurology clinic because of the acute onset of visual and auditory hallucinations.

One month prior to presentation, the patient began to experience brief episodes of visual hallucinations, in which the “devil” appeared to her. At times, “Jesus with horns” would also appear. She also described auditory hallucinations, which were accompanied by the visual ones, in which she heard a “deep male voice” that she believed to be that of the devil; however, she did not report any words or phrases in that experience. The patient sometimes heard her own voice outside of her body. She feared during these episodes that she was “selling her soul to the devil.” Initially, the episodes occurred exclusively at night; they subsequently occurred during wakefulness and became more frequent during the course of the month, eventually occurring multiple times during daytime as well. The episodes were not related to menses. The patient attempted to dispel the hallucinations with prayer, but eventually disclosed them to her parents. Fervent Roman Catholics, they first brought her to their parish priest, who advised the use of prayer and medals to ward off the phenomena. The hallucinations persisted and became more frequent, leading to worsening insomnia and anxiety. The patient became increasingly withdrawn, and insisted that she be permitted to sleep with her parents. Despite these disturbances, she continued to go to school.

Before this illness she had been an honors student in her eighth grade parochial school class and had many friends. Over the course of the month, her schoolwork deteriorated and she had difficulty concentrating. She became increasingly fearful with depressed mood and believed she was “going insane.”

She had focal seizures, first diagnosed when she was 9 years old, which were frequently heralded by an aura of blurry vision and a “thumping” sensation on the left side of the head. One to 2 minutes after the aura, the seizures progressed to right-sided facial twitching, grunting, and retroversion of the eyes. The movements were followed by 1 to 2 minutes of whole body stiffening and shaking. The seizures occurred predominantly at night and were followed by postictal confusion, headache, and aphasia. They occurred two to three times per month with increased frequency during menses. Infrequently, a flurry of seizures would occur several times in a day, requiring treatment with lorazepam. The seizures had been refractory to carbamazepine therapy. Two prior magnetic resonance imagings (MRIs) showed hyperintense signal abnormality on the FLAIR sequences in the posterior and medial aspect of the left temporal lobe. The differential diagnosis of this finding includes cortical dysplasia versus a low-grade neoplasm.

The patient also had a history of asthma in the past but was on no medications for the asthma at the time of presentation.

There is no family history of psychiatric disorders. There is a history of seizure disorder (type unknown) in a paternal cousin.

The patient was being treated with oxcarbazepine 600 mg every morning and 900 mg every evening and lorazepam 2 mg as needed at the time of the current presentation.

On examination, the patient was a well-appearing, well-related adolescent girl. She was cooperative and pleasant. Her vital signs were blood pressure (BP) 113/57 mm Hg, temperature (T) 98.7°F, pulse (P) 68 beats per minute, and respiratory rate (RR) 20 breaths per minute. Mental status showed completely normal orientation, memory, reality testing, and concentration.

The general physical examination showed no abnormalities.

A complete laboratory workup, including electrolytes, complete blood count (CBC), thyroid function tests, and liver function tests, was normal. Urine pregnancy and serum toxicology tests were negative, but her urine drug screen was positive for benzodiazepines.

The patient was admitted to the epilepsy monitoring unit and a psychiatric consultation was requested.

What is the differential diagnosis of the acute onset of psychosis in an adolescent girl with epilepsy?

1. New seizure manifestation. Because this adolescent has a history of complex partial seizures, we must consider that her new complaints may be related to her seizures. Her current symptoms could represent either a new seizure manifestation or a psychosis occurring in the postictal or interictal period Alternatively, these symptoms may have resulted from “forced normalization.” That is, in some patients with complex partial seizures, attaining seizure control leads paradoxically to deterioration of their neuropsychiatric status, including a schizophrenia-like psychosis (1, 2).

Seizures arising from the occipital lobe may produce visual symptoms including hallucinations. Elementary visual symptoms, the most common, consist of colored or multicolored circular patterns, such as spots, circles, and balls. Patients typically describe seeing multiple figures, and other shapes less frequently. Often they see an increased number of figures as the seizure progresses. The figures are usually unilateral, mainly in the temporal visual hemifield. Episodes of epileptic-induced visual hallucinations are brief, lasting anywhere from a few seconds through several minutes (3). Rarely, patients may have status epilepticus with prolonged visual symptoms. In this variant, visual hallucinations are stereotyped. Seizures that produce visual hallucinations may remain as simple partial seizures with only visual symptoms or they may progress to express other ictal symptoms, such as tonic and/or clonic motor activity.

Less commonly, patients may experience more complex visual hallucinations that can take the form of people, animals, objects figures, or scenes. The hallucinations may be familiar or unfamiliar, friendly or frightening. These hallucinations probably originate in the occipital parietal or occipital temporal junction areas (3). There are also rare reports of auditory and complex visual hallucinations associated with seizures of frontal or orbitofrontal origin (4,5).

Seizures arising from the temporal lobe, particularly the uncus, may cause olfactory or gustatory hallucinations. Seizures arising from neocortical temporal cortex may result in auditory hallucinations consisting of a buzzing sound, a voice or voices, or a muffling of ambient sounds.

Some patients with epilepsy exhibit delusions and/or hallucinations as a postictal phenomenon, although this has rarely been reported in children (6). In these cases, the hallucinations and delusions occur following one or a cluster of seizures. These patients are often confused and subsequently amnestic for events that occur during the seizure episode and postictal period (7,8). Seizures arising from the temporal lobe are most often associated with the development of postictal psychosis, but postictal psychosis has also been reported in association with frontal lobe seizures (9).

In this case, postictal psychosis is unlikely because there was no known change in the patient’s seizure frequency prior to the onset of the symptoms, and she had very good recollection of the hallucinations. In addition, her cognition and consciousness were not impaired even during her hallucinations.

Likewise, as there was no reduction in her seizure frequency prior to the onset of these symptoms, forced normalization is not a likely explanation.

2. Psychiatric side effects of anticonvulsants. Some antiepileptic drugs (AEDs) cause psychiatric side effects, including psychosis (Table 19.1). In most cases of medicationinduced neurocognitive and psychiatric reactions, the problems occur within a short time after the initiation of the AED. These adverse reactions occur with the newer AEDs as well as those that have been in long-term use. In this patient, as there was no recent change in the AED regimen, AED side effects are not a likely explanation of her symptoms.

This case presents a problem familiar to neurologists and psychiatrists who treat children and adolescents with epilepsy: the onset of mental status changes and altered behavior that involves perceptual disturbances, emotional activation, and functional and vegetative deterioration. These symptoms are seen in a number of psychiatric disorders that have their onset in childhood and adolescence as well as in complex partial seizures (CPS) and AED side effects (see previous). The ability to differentiate (a) the onset of a new psychiatric disorder in an epileptic adolescent from (b) the onset of PCS in an adolescent with epilepsy is further complicated by the fact that, like seizures, some psychiatric disorders have an episodic course.

Does epilepsy predispose to psychiatric problems? If so, does the chronicity of epilepsy and its psychosocial impact cause psychiatric comorbidity, much as would complicate other life-altering chronic illnesses? One of the problems in analyzing this case is the paucity of data on children and adolescents with epilepsy. If one considers only studies with children and adolescents, the data is scant. Yet, to extrapolate from the adult literature to children and adolescents has many pitfalls. The psychiatric diagnostic possibilities are different in children and adolescents compared with adults. The child’s developing brain leads to variation in the expression of psychiatric symptoms compared to adults. In addition, adults with epilepsy who present for psychiatric assessment usually have had a longer duration of illness than children with epilepsy and thus have had more time to accumulate the psychosocial distress and psychiatric comorbidity associated with the disease. Given all these considerations, in this discussion, reference to the adult literature will be made only when there is a paucity of data pertaining to the child and adolescent population.

Several studies have demonstrated that children and adolescents with epilepsy have greater psychopathology compared to children with other chronic diseases (11,12). The prevalence of psychiatric comorbidity in children and adolescents with epilepsy was recently examined in a large population-based retrospective study (13). In this study of newly diagnosed cases of epilepsy, the prevalence of psychiatric comorbidities in patients 16 years of age or younger was 51%. When patients with mental retardation and pervasive developmental disorder (PDD) were eliminated from the group, the prevalence of psychiatric disorders was 40.4%. The most common psychiatric disorders in these children were attention deficit hyperactivity disorder (ADHD) (17%), and mood and adjustment disorders (10%). No cases of psychotic disorder were identified in this study. It is important to note, however, that as these children were newly diagnosed, the burden of coping with a chronic illness during development would not yet have delivered its full impact. A recent meta-analysis of 46 studies including 2,434 children with epilepsy (14) found that children with epilepsy were at increased risk for psychopathology, including internalizing and externalizing behavior problems compared with healthy controls and children with chronic diseases that did not involve the central nervous system. In these children with epilepsy, somatic complaints and attention problems were the most common symptoms. Although valuable, a weakness of this study is that the length of time from epilepsy diagnosis to assessment inevitably varies among the 46 studies culled, thereby conferring a nonuniform effect of the duration of chronic illness and its contribution to the development of secondary psychopathology. Overall, these more recent findings are in line with Rutter’s Isle of Wight Study (15) that examined the entire child population of the Isle of Wight and found that the rate of psychiatric comorbidity for children with epilepsy to be 34.3%. Of note, in the Isle of Wight study, there were no cases of psychosis identified in children with epilepsy.

The differential diagnosis of the acute onset of psychotic symptoms in a teenager with epilepsy also includes schizophreniform disorder, anxiety and affective disorders, conversion disorder, and substance abuse disorder. In this case, the presence of severe anxiety, depressed mood, and alteration in vegetative functioning helps to narrow the diagnostic focus.

In a retrospective study, the prevalence of interictal psychosis in patients with epilepsy was 4.7% (17) with a correlation between epilepsy originating in the temporal lobes and interictal psychosis. Caplan et al. (18) reported that 10% of children with complex partial seizures had interictal schizophrenia-like psychosis.

Several features of the history and diagnostic workup are helpful in determining whether this patient is presenting with a new seizure manifestation or a schizophreniform disorder: