Delayed Occurrence of Psychosis in an Older Patient with Temporal Lobe Epilepsy
Mrs. J is a 68-year-old divorced African-American woman with a history of depression and a seizure disorder who was admitted from the Emergency Department in the middle of the night to a geropsychiatry inpatient unit for treatment of increasing anxiety, religious and somatic preoccupation, paranoid delusions, and auditory hallucinations. She has no children and has been living alone in an apartment. Her only relatives in the area are a sister who has problems with drug addiction and was recently incarcerated and a brother. Her main social supports are members of the church, which she attends regularly.
While in the Emergency Department, Mrs. J complained of feeling “jumpy” and stated that her television and radio were talking to her and giving her special messages that she refused to describe. She reported good appetite and good sleep but added that occasionally she would not sleep for a few days at a time and had always considered this normal. She was not oriented to date or place. She displayed echolalia, mood lability, and irritability. Intermittently she mumbled to herself and repeated nonsensical words and phrases.
The patient acknowledged two previous psychiatric admissions, the first of which occurred in her mid-20s for “depression,” during which she was treated briefly with trifluoperazine. Subsequently, as an outpatient her depression had been treated with trazodone and then bupropion, which she believed caused her to have her first seizure sometime in the 1990s. Her second psychiatric admission occurred approximately 2 months prior to her current admission when the psychotic symptoms described above first appeared, and at which time she was diagnosed with “schizophrenia” and was started on haloperidol (unknown dose) and escitalopram 10 mg daily. Mrs. J denied any past or present problems with alcohol or drug use, and no toxicology studies were obtained. She had worked as a nurse until she was 63 years old.
The patient’s medical history was remarkable for hypertension, hypercholesterolemia, gastroesophageal reflux disease, and spinal stenosis. She reported that she had been taking opiate pain medication for pain “all over” her body and that she had been diagnosed with temporal lobe epilepsy (TLE) approximately 10 years previously, at which time treatment with phenytoin was initiated. She explained that after her first seizure, she experienced episodes of “confusion,” hypergraphia, and hyperreligiosity, which had never impaired her functioning. Four years ago, Mrs. J was hospitalized on a neurology service at a different hospital due to altered mental status following a witnessed episode of full body shakes, confusion, and inability to speak. This episode occurred after her primary care physician, for unknown reasons, had tapered her off phenytoin. A magnetic resonance imaging (MRI) scan of her brain at that time revealed minimal small vessel ischemic disease. Her electroencephalogram (EEG) showed moderate, diffuse, nonspecific abnormalities, and rare left temporal sharp waves, which appeared epileptiform in character. The possibility of an underlying epileptogenic area in the left temporal lobe was strongly suspected, and treatment with phenytoin was resumed with confirmation of a therapeutic serum level. Subsequently, for unknown reasons, her outpatient neurologist switched the patient to levetiracetam, but she continued to remain free of seizures. The above history and evaluation results confirmed Mrs. J’s seizure disorder diagnosis.
Patients with seizure disorders have high rates of comorbid behavioral conditions that may be especially severe in older adults.1 Table I outlines some of the recognized associations between seizures, seizure disorders, and behavioral symptoms. Zeber et al2 studied the rate of psychiatric disorders in patients with epilepsy and found that the rate of mood disorders varied according to seizure treatment responsiveness. In seizure treatment–resistant patients versus treatment-responsive patients, the rates of comorbid mood disorders were 60% and 10-20%, respectively. This research group also found that schizophrenia was six times more common in patients who had epilepsy than in patients who did not. A large Danish cohort study found that a family history of epilepsy was a significant risk factor for schizophrenia and that older age, later age of onset of epilepsy, and the number of admissions for epilepsy were all associated with greater vulnerability to psychotic illness.3
The overall prevalence of personality disorders in patients with epilepsy is estimated to be between 4% and 38%.4 Although there is no specific “epileptic personality,” patients with epilepsy may have a higher prevalence of dependent and avoidant traits, possibly due to underlying neurobiological factors as well as psychosocial difficulties.4-8 Some patients suffering from partial complex seizures with a temporal lobe focus (TLE) may be especially predisposed to psychosis, depression, and other psychopathology,9 and a subset of these patients display a group of personality disorder traits known as the Gastaut-Geschwind syndrome.
Hypergraphia, hyperreligiosity, and hypermoralism are key features of Gastaut-Geschwind syndrome; however, these characteristics may also be present in patients without epilepsy who have psychiatric disorders or comparable physical disabilities.10 Research done by Bear and Fedio11 identified 18 personality characteristics in patients with TLE that differentiate them from normal controls: emotionality, elation, sadness, anger, aggression, altered sexual interest, guilt, hypermoralism, obsessionalism, circumstantiality, viscosity, sense of personal destiny, hypergraphia, religiosity, philosophic interest, dependence, humorlessness, and paranoia.12,13
Given all these potential intersections of epileptic and psychiatric illness, establishing causal relationships and optimal treatment of an older patient with neurological and behavioral problems may be challenging, especially if the patient presents with a number of comorbid medical illnesses. Adding to the difficulty of this task is the possibility that the terminology, methods of classification, and epidemiology of seizures and seizure disorders may seem somewhat confusing, especially for clinicians who have not specialized in the diagnosis and treatment of seizures and seizure disorders. For example, a person may have a seizure but not have a seizure disorder (epilepsy).
Seizures may be described as primary, secondary to a brain lesion, or symptomatic.1 Symptomatic seizures are those that result from acute situational conditions such as sleep deprivation, metabolic disturbance or alcohol withdrawal, or from acute insult to the brain from events like subdural hematomas, strokes, and infections.14 In the United Kingdom, symptomatic seizures are referred to as “acute symptomatic” (arising within 1 wk of a triggering event), “remote symptomatic” (occurring 1 wk beyond the triggering event), or “provoked,” while seizures without an obvious immediate cause are called “unprovoked.” The term epilepsy refers specifically to recurrent unprovoked seizures (primary seizures) or two or more remote symptomatic seizures (secondary seizures) but excludes acute symptomatic seizures.1 A stroke or a head injury may cause either or both a one-time seizure (a symptomatic or provoked seizure) and a permanent brain injury that results in a series of seizures (a secondary seizure disorder or remote symptomatic epilepsy).15
The incidence of seizures based on age groups has two peaks. The first peak is in individuals less than 4 years of age, when the incidence is approximately 100 per 100,000. The second peak occurs at the end of life (age 70 yr and older), when the incidence is over 140 per 100,000.16 A five-year study of 151 patients with a first seizure after age 60 found that 32% were caused by stroke, 14% by brain tumors, including meningiomas, malignant gliomas, and brain metastases, and 25% had no identifiable cause.17 The incidence of new-onset seizure disorders (epilepsy) is highest in the first year of life, falls to its nadir in the third through the fifth decades, but increases again in individuals over age 60 years to an annual incidence of 77-92 per 100,000.18,19 Although two-thirds of epilepsy cases in young adults are idiopathic, approximately half of older patients with epilepsy will have a known cause.18 Cerebrovascular disease is the most common cause of epilepsy in later life, accounting for approximately 50% of the cases. Other causes in descending order of frequency include tumor, head injury, and nonvascular dementia such as Alzheimer’s disease.20
In adults, the three most common types of seizures based on clinical appearance are: (1) generalized tonic-clonic seizures with convulsions (also known as grand mal seizures); (2) complex partial seizures with alterations of consciousness; and (3) simple partial seizures with isolated motor, somatosensory, autonomic, or psychic symptoms.1 Although approximately one-third of all patients with epilepsy have complex partial seizures, about one-half of elderly patients with epilepsy have complex partial seizures, which reflects an increase in the specific focal causes of their seizures.18
Outcome of the Case Patient
On current admission, escitalopram 10 mg was continued and treatment with quetiapine was initiated for Mrs. J’s psychosis, 50 mg in the morning and 150 mg at bedtime. She reported that prior to admission she had been taking oxycodone HCl controlled release 20 mg 3 times daily. This dose was confirmed by documentation from her primary care clinic dated approximately 6 weeks prior to her admission. For a variety of reasons, including not wanting to undertreat pain in a patient with spinal stenosis and not wanting to precipitate opiate withdrawal, but also not wanting to cause pain medication toxicity, she was initially treated with a moderately reduced dose of oxycodone HCl controlled release 20 mg 2 times daily. On her fourth hospital day, due to the absence of any visible pain behaviors and due to concern that this pain medication was contributing to mental status changes, the patient was tapered off of oxycodone by reducing her dose to 10 mg 2 times daily for 4 days, then once daily for 3 days, then discontinued. As a result of this taper, she experienced no re-emergence of pain nor any physical or psychological signs of withdrawal.
Over her first several days in the hospital, Mrs. J was noted to have recurring episodes of echolalia, severe paranoia, disorganization, and irritability alternating with periods of lucidity and organized behavior. Her psychiatric differential diagnosis included bipolar mood disorder, mixed episode; mood disorder or psychosis secondary to a general medical condition including epilepsy; cognitive disorder not otherwise specified; and delirium. Her medical evaluation included a brain MRI, which showed mild global parenchymal loss and “diminutive” bilateral medial temporal lobes. The consulting geriatric internist noted that the patient’s potassium was periodically elevated and, after additional medical evaluation, diagnosed mild familial hypoaldosteronism. No other medical problems were identified. Her history of a seizure disorder prompted an EEG and a neurology consultation. No epileptiform or slow-wave activity was noted, and her neurological examination was unremarkable. In order to target both seizures and mood lability, she was cross-titrated from levetiracetam to valproic acid. Tables II and III present information on some of the medications commonly used for the treatment of seizure disorders.
Due to persistent psychotic symptoms that frequently triggered problem behaviors (eg, in the middle of the night, angrily and loudly accusing staff of ingesting her pain medications), over a period of 15 days her quetiapine dose was incrementally titrated to 250 mg twice daily. In spite of this, Mrs. J continued to have severely disordered thought (eg, making bizarre statements, accusing staff of taking her belongings, and writing disorganized notes that often included religious themes), even though her sleep, appetite, and activation level improved. Therefore, she was switched from quetiapine to risperidone 3 mg twice daily which, due to continued paranoia, hypergraphia, and religious preoccupation, was subsequently increased to 4 mg twice daily. In addition, she continued taking valproic acid 1500 mg at bedtime, achieving a trough serum level of 72 µg/mL.
Once the patient had stabilized, neuropsychological testing revealed mild deficits in naming, psychomotor speed, cognitive set shifting, and visuospatial abilities. She also had difficulty with problem solving, hypothesis testing, and using visual information. Mrs. J’s Dementia Rating Scale score of 137 out of 144 was not consistent with dementia.21 Her areas of impaired performance may have been due to her preoccupation with internal stimuli, and she was given the additional diagnosis of cognitive disorder not otherwise specified. At the time of discharge, 28 days after her admission, the patient’s delusions, irritability, and mood lability had resolved, but she continued to have hypergraphia and hyperreligiosity.
Mrs. J returned to the outpatient clinic accompanied by her brother for her first follow-up appointment 2 weeks after she had been discharged back to her apartment. No psychotic symptoms were reported or observed. She scored 30 points on the Mini-Mental State Examination.22 The patient did endorse a number of persistent mood symptoms including irrational worry about her finances, anergia, apathy, middle insomnia, and social withdrawal and, therefore, her escitalopram dose was increased to 20 mg daily. Four months after her discharge, she was continuing to live successfully and independently in her apartment and mailed a “thank-you” card to the inpatient unit, which included a clipping of a prayer titled “Giving Hearts,” and it was signed “Love, patience, peace, and prayers.”
In summary, this patient demonstrated the gamut of psychiatric symptoms frequently associated with TLE, including depression, hyperreligiosity, hypergraphia, and emotional lability. Establishing an accurate diagnosis was difficult, in part, due to historical information being unavailable as a result of the patient’s imprecise memory, the imprecise memory of other informants, and the inability to obtain outside medical records despite repeated attempts. For example, the physicians were unable to be certain about the nature of the episodes of “confusion” that she reported experiencing for the past 10-20 years prior to admission.
Reaching a correct diagnosis was also challenging due to the presence of a number of other factors that might have been the cause of at least some, if not all, of her presenting symptoms. She had a number of actual or possible conditions that could have triggered delirium and associated psychotic symptoms. These conditions included episodic hypokalemia secondary to familial hypoaldosteronism and opiate intoxication. Unfortunately, due to the combination of dramatic and persistent complaints of pain in the setting of spinal stenosis, opiate pain medication was administered shortly after admission and prior to recognizing the potential diagnostic value of toxicology studies. Mrs. J’s EEG, however, did not show the diffuse slowing that is often seen in delirium. Psychiatrically, she gave a history of both a mood disorder and schizophrenia, and either of these conditions were plausible explanations for her symptoms. Lastly, her age and other factors put her at risk for psychosis secondary to either Alzheimer’s dementia or vascular dementia.
The timing of the onset of her psychosis, which was at least 10 years after the original diagnosis of TLE, and its character, which was more consistent with schizophrenia than with depression or mania, helped establish the diagnosis. According to Slater et al,23 schizophrenia-like psychosis usually occurs 10-20 years after the onset of TLE, and it is characterized by delusions and religious experiences with a lack of negative symptoms.4 Given that the patient’s first episode of depression occurred decades before her diagnosis of TLE, it appears that this illness may have been primary and not secondary to TLE. Her cognitive testing revealed only relatively mild deficits. Taking all of the above into consideration, the most likely diagnoses were believed to be major depression, recurrent; psychosis secondary to temporal lobe epilepsy; and cognitive disorder not otherwise specified.
This work was supported, in part, by grants from the National Institute of Mental Health, Department of Veterans Affairs, and the John A. Hartford Foundation.
The authors report no relevant financial relationships.
1. Mendez MF: Epilepsy. In: Coffey CE, Cummings JL, eds. Textbook of Geriatric Neuropsychiatry. 2nd ed. Washington, DC: American Psychiatric Press, Inc.; 2000:655-667.
2. Zeber JE, Copeland LA, Amuan M, et al. The role of comorbid psychiatric conditions in health status in epilepsy. Epilepsy Behav 2007;10(4):539-546. Published Online: April 6, 2007.
3. Qin P, Xu H, Laursen TM, et al. Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: Population based cohort study. BMJ 2005;331(7507):23. Published Online: June 17, 2005.
4. Swinkels WA, Kuyk J, van Dyck R, Spinhoven P. Psychiatric comorbidity in epilepsy. Epilepsy Behav 2005;7(1):37-50.
5. Mendez MF, Doss RC, Taylor JL, Arguello R. Relationship of seizure variables to personality disorders in epilepsy. J Neuropsychiatry Clin Neurosci 1993;5(3):283-286.
6. Perini GI, Tosin C, Carraro C, et al. Interictal mood and personality disorders in temporal lobe epilepsy and juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry 1996;61:601-605.
7. Swanson SJ, Rao SM, Grafman J, et al. The relationship between seizure subtype and interictal personality. Results from Vietnam Head Injury Study. Brain 1995;118 (Pt 1):91-103:91-103.
8. Testa SM, Schefft BK, Szaflarski JP, et al. Mood, personality, and health-related quality of life in epileptic and psychogenic seizure disorders. Epilepsia 2007;48(5):973-982. Published Online: February 5, 2007.
9. Mendez MF, Engebrit B, Doss R, Grau R. The relationship of epileptic auras and psychological attributes. J Neuropsychiatry Clin Neurosci 1996;8(3):287-292.
10. Rodin E, Schmaltz S. The Bear-Fedio personality inventory and temporal lobe epilepsy. Neurology 1984;34:591-596.
11. Bear DM, Fedio P. Quantitative analysis of interictal behavior in temporal lobe epilepsy. Arch Neurol 1977;34(8):454-467.
12. Trimble M, Freeman A. An investigation of religiosity and the Gastaut-Geschwind syndrome in patients with temporal lobe epilepsy. Epilepsy Behav 2006;9(3):407-414. Published Online: August 17, 2006.
13. Waxman SG, Geschwind N. The interictal behavior syndrome in temporal lobe epilepsy. Arch Gen Psychiatry 1975;32(12):1580-1586.
14. Velez L, Selwa LM. Seizure disorders in the elderly. Am Fam Physician 2003;67:325-332.
15. Brodie MJ, Kwan P. Epilepsy in elderly people. BMJ 2005;331:1317-1322.
16. Craig I, Tallis R. General practice management of adult-onset epilepsy analysed. Care Elderly 1991;3:69-72.
17. Luhdorf K, Jensen LK, Plesner AM. Etiology of seizures in the elderly. Epilepsia 1986;27:458-463.
18. Hauser WA. Seizure disorders: The changes with age. Epilepsia 1992;33(Suppl 4):S6-S14.
19. Annegers JF. Epidemiology of epilepsy. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, MD: Williams & Wilkins; 1997:165-172.
20. Stephen LJ, Brodie MJ. Epilepsy in elderly people. Lancet 2000;355:1441-1446.
21. Mattis S. Mental status exam for organic mental syndrome in the elderly patient. In: Bellak L, Karasu TB, eds. General Psychiatry. New York: Grune and Stratton; 1976:77-121.
22. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
23. Slater E, Beard AW. The schizophrenia-like psychoses of epilepsy, V: Discussion and conclusions. 1963. J Neuropsychiatry Clin Neurosci 1995;7(3):371-378.