Is antiepileptic drug use related to depression and suicidal ideation among patients with epilepsy?

Depression and suicide are increased in patients with epilepsy. The U.S. Food and Drug Administration warns that antiepileptic drugs (AEDs) are associated with increased risk of suicidality. This study examines the relationship among depression, suicidal ideation, and AEDs in a prospective cohort of 163 patients with epilepsy from a registry at the University of Florida (January 2006 to August 2008). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was used to measure mood and suicidal ideation across two time points (median = 154 days). Groups included: (1) No AED Change, (2) New AED Added, (3) AED Dose Increased, (4) AED Reduced/Stopped, (5) Multiple AED Changes, and (6) Combined Any AED Change (groups 2-5 combined). No group had worsening mood or suicidal ideation. Significant improvements in proportions of depression and suicidal ideation were seen only for the No AED Change group, which differed only with the AED Dose Increased group with respect to suicidal ideation.

Kernel Fisher discriminant for shape-based classification in epilepsy.

In this paper, we present the application of kernel Fisher discriminant in the statistical analysis of shape deformations that indicate the hemispheric location of an epileptic focus. The scans of two classes of patients with epilepsy, those with a right and those with a left anterior medial temporal lobe focus (RATL and LATL), as validated by clinical consensus and subsequent surgery, were compared to a set of age and sex matched healthy volunteers using both volume and shape based features. Shape-based features are derived from the displacement field characterizing the non-rigid deformation between the left and right hippocampi of a control or a patient as the case may be. Using the shape-based features, the results show a significant improvement in distinguishing between the controls and the rest (RATL and LATL) vis-a-vis volume-based features. Using a novel feature, namely, the normalized histogram of the 3D displacement field, we also achieved significant improvement over the volume-based feature in classifying the patients as belonging to either of the two classes LATL or RATL, respectively. It should be noted that automated identification of hemispherical foci of epilepsy has not been previously reported.

Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year observation.

A retrospective review of the safety, tolerability, and efficacy of vagus nerve stimulation (VNS) in 48 patients with intractable partial epilepsy was performed. Side effects were few and mild to moderate. Mean seizure frequency decreased by 26% after 1 year, 30% after 5 years, and 52% after 12 years with VNS treatment.

Botulinum toxin-induced paralysis of frontotemporal muscles improves seizure focus localization.

BACKGROUND: Scalp EEG localization of epileptic foci may be obscured by electromyographic (EMG) artifact produced by ictal contraction of cranial muscles. Injection of botulinum toxin type A (BTX-A) into frontotemporal scalp muscles reduces EMG activity. Initial scalp video-EEG monitoring in three patients suggested partial seizures, but definitive lateralization or localization was precluded by EMG artifact. METHODS: EMG-guided BTX-A injection to bilateral frontotemporal muscles was performed. When artifact persisted, BTX-A administration was selectively repeated. Patients subsequently underwent scalp video-EEG monitoring 1 week later. RESULTS: All patients had reduction of EMG artifact during subsequent scalp video-EEG monitoring. No patient had adverse effects after BTX-A administration. All three patients had localization to either frontal or temporal lobes and definitive lateralization. Two of the three patients were able to proceed to invasive placement of frontotemporal subdural grid electrodes based on the BTX-A scalp video-EEG localization, and the third patient was determined to have a multifocal seizure disorder. CONCLUSIONS: Paralysis of frontotemporal scalp muscle after BTX-A administration reduces EMG artifact and may improve localization and lateralization of a seizure focus, providing a noninvasive technique for advancement toward epilepsy surgery.

Proximal myotonic myopathy: clinical, neuropathologic, and molecular genetic features.

The primary genetic abnormality in myotonic dystrophy (DM) is an expansion of the CTG trinucleotide repeat on chromosome 19q. Recently, patients with similar clinical features, but without this genetic alteration, have been designated as proximal myotonic myopathy (PROMM). We describe two additional cases of PROMM, both of whom presented with clinical features suggestive of myotonic dystrophy. The patients had electromyographic (EMG) evidence of myotonia, normal cardiac evaluation, and no cataracts. Genetic analysis of peripheral blood leukocytes revealed no expansion of the trinucleotide repeat by polymerase chain reaction (PCR) and Southern blot analysis. Muscle biopsies in both cases were significant with features suggestive of myotonic dystrophy, such as large numbers of fibers containing multiple internal nuclei, occasional nuclear chains, and fiber atrophy, although sarcoplasmic masses and ring fibers were absent. These cases illustrate the clinical and neuropathologic findings of PROMM and underline the importance of correlating these aspects with genetic studies in patients with myotonic muscle disorders.

Lateralization of temporal lobe foci: depth versus subdural electrodes.

OBJECTIVES: Definitive localization of an epileptic focus correlates with a favorable outcome following epilepsy surgery. This study was undertaken to determine the incremental value of data yielded for surgical decision making when using subdural electrodes alone and in addition to depth electrodes for temporal lobe epilepsy. METHODS: Standardized placement for intracranial electrodes included: (1) longitudinal placement of bilateral temporal lobe depth electrodes; (2) bilateral subtemporal subdural strips; and (3) bilateral orbitofrontal subdural strips. Sixty-three events were randomly reviewed for: (1) subdural electrodes alone; and (2) depth electrodes in conjunction with subdural electrodes. RESULTS: Of the 63 seizures, 54 (85.7%) demonstrated congruent lateralization to ipsilateral subtemporal subdural strip electrodes (based on depth electrode localization) when subdural strip electrodes were utilized alone. In 3 of 22 patients, 7 seizures demonstrated 'false localization' on subdural electrode analysis alone when compared with depth recording and post-surgical outcome. For these 3 patients, retrospective review of neuroimaging demonstrated suboptimal ipsilateral placement of subtemporal subdural electrodes with the most mesial electrode lateral to the collateral sulcus. Four additional patients had suboptimal placement of subtemporal subdural electrodes. Two of these 4 patients had congruent localization with subdural electrodes to ipsilateral depth electrodes despite suboptimal placement. Subtemporal subdural electrodes accurately localized for all seizures from the mesial temporal lobe when the mesial electrodes of the subtemporal subdural strip recorded mesial to the collateral sulcus from the parahippocampal region. CONCLUSION: We conclude that although there are high concordance rates between subdural and depth electrodes, localization of seizure onset based on subdural strip electrodes alone may result in inaccurate focus identification with potential for possible suboptimal treatment of temporal lobe epilepsy. When subtemporal subdural electrodes provide recording from the parahippocampal region, there is accurate localization of the seizure focus. If suboptimal placement occurs lateral to the collateral sulcus, the electroencephalographer cannot make a definitive identification of the seizure focus.

Strategies for successful management of older patients with seizures.

The incidence of seizures increases dramatically with age, making epilepsy in the older patient a common clinical presentation in the primary care practice. In the case of a single seizure or when the underlying cause can be corrected, antiepileptic drug (AED) therapy may not be warranted. For recurrent seizures, single AED therapy should be initiated at a low dose and gradually titrated upward. Control of seizure frequency is dependent on appropriate AED selection and compliance, drug-drug interactions, and minimization of side effects. Monitoring of AED serum levels is imperative for effective AED therapy. Conventional AEDs remain the standard initial anticonvulsants for epilepsy in older patients. The newer AEDs have demonstrated efficacy as adjunctive therapy and may offer reduced side-effect profiles and fewer drug-drug interactions.

Adult-onset seizures: clinical solutions to a challenging patient work-up.

The age-related increase in the incidence of seizures in older persons is directly related to the increase in prevalence of causative factors such as cardiovascular disease and stroke, primary and metastatic brain tumors, toxic-metabolic disturbances, and medications. Because the treatment plan depends on seizure etiology, comprehensive evaluation of each of these causes is imperative. Reliable history and thorough physical examination remain the most important steps for diagnosis and effective treatment. Nevertheless, assessment and treatment of new-onset paroxysmal events can be problematic, because numerous morbidities and syndromes--including transient ischemic attack, syncope, drug intoxication, amnesia, movement disorders, and psychiatric disorders--can present with similar symptomology.

Reduced density of parvalbumin- and calbindin D28-immunoreactive neurons in experimental cortical dysplasia.

Cortical dysplasia (CD) is a congenital brain malformation in humans that is closely associated with intractable epilepsy. This study utilized an animal model of CD, in utero irradiation in rats, to determine if experimental dysplastic cortex demonstrates a reduction in the density of inhibitory interneurons. Fetal rats were exposed to external irradiation on gestational day 17 to produce diffuse CD and heterotopic grey matter. As adults, these rats were processed for immunohistochemistry using primary antibodies for parvalbumin (PA), calbindin D28k (CA), the 67 kD subunit of glutamic acid decarboxylase (GAD67), and cresyl violet staining. Quantitative methods were used to determine the density of immunoreactive neurons and cresyl violet-stained neurons in the neocortex at the rostro-caudal level of the anterior commissure. Compared to control values, the density of PA- and CA-immunoreactive neurons was reduced in dysplastic cortex. Density of glutamic acic decarboxylase-immunoreactive neurons was not different between control and dysplastic cortex. Overall neuronal density, measured in cresyl violet-stained sections, was not significantly different between control and dysplastic cortex. These data suggest a selective reduction in inhibitory interneurons in experimental CD cortex or an impaired ability for these neurons to produce PA and CA.

Topographic differences in task-dependent facilitation of magnetic motor evoked potentials.

OBJECTIVE: To look for differences in task-dependent facilitation of magnetic motor evoked potentials (MEPs) in proximal and distal upper extremity muscles. BACKGROUND: Postexercise facilitation of MEPs has been demonstrated repeatedly in forearm muscles. Proximal muscles are prominently involved in limb stabilization, a largely isometric activity. In contrast, distal hand muscles specialize in precision movements. Based on these functional differences between proximal and distal muscles, we postulated that there might be topographic differences in task-dependent facilitation of MEPs. METHODS: We studied the effects of isometric exercise and a precision grip task on MEPs in proximal and distal upper extremity muscles. RESULTS: Isometric exercise of the target muscle was associated with significant facilitation of MEPs in biceps and extensor carpi radialis muscles, but not in first dorsal interosseous or abductor digiti minimi muscles. In contrast, a precision grip task was associated with significant post-task facilitation of MEPs in first dorsal interosseous, but not in extensor carpi radialis. CONCLUSIONS: These differences in the facilitation of MEPs depending on the motor task and whether the muscle is proximal or distal may reflect the relative importance of proximal muscles in maintaining posture.

The effect of LINAC stereotactic radiosurgery on epilepsy associated with arteriovenous malformations.

Reduction of seizures associated with arteriovenous malformations (AVMs) following radiosurgery has been reported. This investigation assessed the effect of LINAC radiosurgical treatment of AVMs on the associated epilepsies correlated to AVM location, size, seizure type, and postradiosurgical thrombosis. Of 100 patients with AVMs, 33 presented with seizures (11 generalized tonic-clonic seizures, 8 simple partial seizures, and 14 complex partial seizures with or without secondary generalization). Patients with AVMs >/=25.0 mm were more likely to have seizures. Patients with frontal lobe AVMs were the most likely to have associated epilepsy (72.7%). Following radiosurgery, 59% were seizure-free and 19% had marked reduction of seizure frequency. Seizure remission was most frequent for AVMs of the centrum (83.3%). Of 14 patients with 2-year follow-up angiography, 9 had complete thrombosis and 6 became seizure-free. Four of 5 patients without thrombosis also became seizure-free. We conclude that LINAC radiosurgery is effective for epilepsies associated with AVMs. Radiosurgery was most effective for generalized tonic-clonic and complex partial seizures. There was no statistically significant correlation between reduction in epilepsy and original AVM size. Four of 5 patients without thrombosis became seizure-free, suggesting that structural or biochemical alterations of epileptogenic neurons following radiosurgery may reduce epileptogenicity.

Hippocampal volumetrics differentiate patients with temporal lobe epilepsy and extratemporal lobe epilepsy.

OBJECTIVE: To determine whether the occurrence of hippocampal formation (HF) volumetric asymmetry can reliably discriminate between complex partial seizures (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a prospective study of patients with intractable CPSs (approximately 70% of patients have electrographic foci in the temporal lobe [HF volumetric asymmetry on magnetic resonance imaging scans has been shown to lateralize such foci reliably)]. DESIGN: We examined HF volumetrics on magnetic resonance imaging scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared rapid gradient echo three-dimensional sequences (producing a gapless series of high-contrast 1.25-mm images). These data were compared with ictal, interictal, invasive, and noninvasive videoelectroencephalographic monitoring data, functional imaging data, and outcome data to define each patient's type of epilepsy. SETTING AND PATIENTS: Forty-one patients were recruited from a tertiary university comprehensive epilepsy program, and 22 control subjects were recruited from the neurologically normal university community. RESULTS: Among the control subjects, the difference in HF volumetrics (right-left HF volumetrics) was + 0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the upper limit had CPSs of a temporal lobe origin. Of the patients with temporal lobe epilepsy, only three fell within normal limits. No patient with CPSs of an extratemporal lobe origin fell beyond the upper limit. CONCLUSION: The presence of significant HF volumetric asymmetry makes it highly unlikely that a patient's CPSs are of an extratemporal lobe origin.