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.

Antiepileptic drugs (AEDs) are psychotropic agents; that is, they act on the mind and can positively or negatively influence behavior. This result is expected, given their mechanisms of action, which are to alter ion channel and neurotransmitter system functions and, thereby, modulate the electrochemical systems that underlie behavior. Behavioral effects (e.g., cognitive and mood) associated with AEDs are complex and can vary dramatically between patients. It is currently not possible to predict which patient with epilepsy will tolerate an AED and which one will develop adverse, as opposed to positive, psychotropic effects.

SUMMARYEpileptic 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.

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.

Rationale and aim of the study: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 is 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 to 60 years old 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, while suicidal ideation (lifetime, current, active and passive) and suicidal attempts (lifetime, current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included T-test, Chi-square statistics and logistic regression analyses.Results:A total of 151 (43.5%) subjects had a psychiatric diagnosis; 134 (38.6%) met 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, while both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDD) had a slightly higher prevalence than bipolar disorders (BPD) (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.Conclusions:In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders and suicidality are 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.