Mood and Anxiety Disorders and Suicidality in Patients With Newly Diagnosed Focal Epilepsy: An Analysis of a Complex Comorbidity.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Religious conversion in an older male with longstanding epilepsy.

Religious experiences in epilepsy patients have provoked much interest with suggestions that hyperreligiosity is associated with temporal lobe seizures. Extreme varieties of religious behavior may be more frequent in epilepsy patients during ictal activity or during post-ictal psychotic episodes. We report a 75 year-old man with epilepsy who developed a progressive decline in cognition and behavior following a religious conversion 15 years earlier. He subsequently developed religious delusions of increasing severity and symptoms of Capgras syndrome. Brain imaging revealed bilateral posterior cortical atrophy, chronic right parieto-occipital encephalomalacia, and right mesial temporal sclerosis. Electroencephalograms and neuropsychological testing revealed initial right temporal lobe abnormalities followed by progressive frontal and bilateral dysfunction. The case highlights how a history of seizures, superimposed on sensory deprivation and a progressive impairment of right posterior and bilateral anterior brain function, may have contributed to religious conversion, which was followed by dementia and delusions involving religious content.

Association Between Migraine Comorbidity and Psychiatric Symptoms Among People With Newly Diagnosed Focal Epilepsy.

OBJECTIVE: Little is known about psychiatric symptoms among patients with migraine and newly diagnosed focal epilepsy. The investigators compared symptoms of depression, anxiety, and suicidality among people with newly diagnosed focal epilepsy with migraine versus without migraine. METHODS: The Human Epilepsy Project is a prospective multicenter study of patients with newly diagnosed focal epilepsy. Depression (measured with the Center for Epidemiologic Studies Depression Scale), anxiety (measured with the 7-item Generalized Anxiety Disorder scale), and suicidality scores (measured with the Columbia-Suicide Severity Rating Scale [C-SSRS]) were compared between participants with versus without migraine. Data analysis was performed with the Kolmogorov-Smirnov test for normality assessment, the Mann-Whitney U test, chi-square test, and linear regression. RESULTS: Of 349 patients with new-onset focal epilepsy, 74 (21.2%) had migraine. There were no differences between the patients without migraine versus those with migraine in terms of age, race, and level of education. There were more women in the group with migraine than in the group without migraine (75.7% vs. 55.6%, p=0.0018). The patients with epilepsy and comorbid migraine had more depressive symptoms than the patients with epilepsy without migraine (35.2% vs. 22.7%, p=0.031). Patients with epilepsy with comorbid migraine had more anxiety symptoms than patients with epilepsy without migraine, but this relation was mediated by age in logistic regression, with younger age being associated with anxiety. Comorbid migraine was not associated with C-SSRS ideation or behavior. CONCLUSIONS: Among a sample of patients with newly diagnosed focal epilepsy, 21.2% had migraine. Migraine comorbidity was associated with higher incidence of depressive symptoms. Future studies should be performed to better assess these relationships and possible treatment implications.

Reliable Digit Span: Does it Adequately Measure Suboptimal Effort in an Adult Epilepsy Population?

OBJECTIVE: Assessment of performance validity is a necessary component of any neuropsychological evaluation. Prior research has shown that cutoff scores of ≤6 or ≤7 on Reliable Digit Span (RDS) can detect suboptimal effort across numerous adult clinical populations; however, these scores have not been validated for that purpose in an adult epilepsy population. This investigation aims to determine whether these previously established RDS cutoff scores could detect suboptimal effort in adults with epilepsy. METHOD: Sixty-three clinically referred adults with a diagnosis of epilepsy or suspected seizures were administered the Digit Span subtest of the Wechsler Adult Intelligence Scale (WAIS-III or WAIS-IV). Most participants (98%) passed Trial 2 of the Test of Memory Malingering (TOMM), achieving a score of ≥45. RESULTS: Previously established cutoff scores of ≤6 and ≤7 on RDS yielded a specificity rate of 85% and 77% respectively. Findings also revealed that RDS scores were positively related to attention and intellectual functioning. Given the less than ideal specificity rate associated with each of these cutoff scores, together with their strong association to cognitive factors, secondary analyses were conducted to identify more optimal cutoff scores. Preliminary results suggest that an RDS cutoff score of ≤4 may be more appropriate in a clinically referred adult epilepsy population with a low average IQ or lower. CONCLUSIONS: Preliminary findings indicate that cutoff scores of ≤6 and ≤7 on RDS are not appropriate in adults with epilepsy, especially in individuals with low average IQ or below.

Increased odds and predictive rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences.

OBJECTIVE: The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. METHOD: After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. RESULTS: The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. CONCLUSIONS: Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases.

Neuropsychiatric autoimmune encephalitis without VGKC-complex, NMDAR, and GAD autoantibodies: case report and literature review.

We report a patient with a seronegative autoimmune panencephalitis, adding a subtype to the emerging spectrum of seronegative autoimmune encephalitis, and we review the sparse literature on isolated psychiatric presentations of autoimmune encephalitis. (A PubMed search for "seronegative autoimmune encephalitis," "nonvasculitic autoimmune inflammatory meningoencephalitis," and related terms revealed <25 cases.) A 15-year-old girl developed an acute-onset isolated psychosis with prominent negative symptoms and intermittent encephalopathy. Despite clinical worsening, her brain magnetic resonance imaging (MRI) scans remained normal for 7 years. Serology was negative for voltage-gated potassium channel (VGKC)-complex, N-methyl-D-aspartate receptor (NMDAR), and glutamic acid decarboxylase (GAD) autoantibodies. We excluded genetic, metabolic, paraneoplastic, degenerative, and infectious etiologies. The patient's symptoms remitted fully with immune therapy, but recurred in association with widespread bihemispheric brain lesions. Brain biopsy revealed mild nonvasculitic inflammation and prominent vascular hyalinization. Immune therapy with plasma exchanges cleared the MRI abnormalities but, 10 years after onset, the patient still suffers neuropsychiatric sequelae. We conclude that autoimmune panencephalitis seronegative for VGKC-complex, NMDAR, and GAD autoantibodies is a subtype of autoimmune encephalitis that can present with pure neuropsychiatric features and a normal brain MRI. Immunologic mechanisms may account for psychiatric symptoms in a subset of patients now diagnosed with classical psychotic disorders. Delay in starting immune therapy can lead to permanent neuropsychiatric sequelae. We propose a standardized classification system for the autoimmune encephalitides, integrating earlier pathology-oriented terms with more recently defined serologic and clinical phenotypes.

Psychosis in epilepsy patients.

Epileptic psychoses reflect a fundamental disruption in the fidelity of mind and occur during seizure freedom or during or after seizures. The psychotic symptoms in epilepsy share some qualities with schizophrenic psychosis, such as positive symptoms of paranoid delusions and hallucinations. Psychotic syndromes in epilepsy are most common but not exclusively associated with temporal lobe epilepsy. De Novo psychosis following epilepsy surgery is rare. Forced normalization-psychosis associated with dramatic reduction of epileptiform activity or seizures is described in small series only. Ictal and postictal psychosis can be prevented with seizure control, but postictal and chronic interictal psychoses require multidisciplinary and psychopharmacologic management.

Anterior cingulate epilepsy in an 18-year-old woman.

Anterior cingulate epilepsy is a diagnostic and therapeutic challenge, with a broad range of nonspecific symptoms. Seizures can arise from any region of the anterior cingulate cortex (ACC) and manifest distinctive features based on the area of onset and pattern of spread. These features may provide insight as to the origin of the seizures, but because the ACC integrates information from several networks involving emotional and executive functions and has a diverse cytoarchitecture, functional-structural correlates are complex. Further, the location of the ACC within the interhemispheric fissure limits the capacity of scalp electrodes to record seizure activity from this region. This case review illustrates one part of the spectrum of cingulate epilepsy and discusses clinical features of the disorder.

Psychotropic effects of antiepileptic drugs.

Antiepileptic drugs are important psychotropic agents that are commonly used to treat psychiatric disorders. The behavioral effects of antiepileptic drugs may differ between epilepsy and psychiatric patient populations. Randomized, double-blind, controlled data on the psychotropic efficacy of antiepileptic drugs are limited mainly to bipolar disorder.

Current treatments of epilepsy.

Medical therapy is the mainstay for epilepsy, with most patients well controlled on a single antiepileptic drug (AED). In this non-refractory group, many patients have medication side effects and occasional seizures. Approximately 30% of patients with partial epilepsy and 25% of patients with generalized epilepsy are not well controlled on medications. These patients are often receiving multiple AEDs, with disabling seizures and side effects. Although second-generation AEDs are safer and better tolerated than the older AEDs, there are scant data to support significant advantages in efficacy. In VA studies with older AEDS, therapy with two AEDs improved seizure control in 40% of patients but seizure freedom was achieved in only 9%. A meta-analysis of the second-generation AEDs used as adjunctive therapies shows that 12% to 29% of patients had a 50% or greater reduction in seizure frequency. Surgery and the vagus nerve stimulator provide important therapeutic options in patients whose seizures are not controlled by AEDs. Special considerations about epilepsy care must be made in pediatric populations, those with developmental delays, women, and the elderly.