Disturbances In Epilepsy Research Articles

Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients.

Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave-ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown. The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation. In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles "induced" by hIEDs, and (3) spindles without hIED co-occurrence. We found that spindles co-occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4± 3.2μV, and their frequency range shifted toward the higher frequencies within the 13-15-Hz range. Also, hIED-induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient-specific. We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle-hIED co-occurrence, but not in cases of hIED-initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory processes, and also provide a potential therapeutic target to treat memory disturbances in epilepsy.

Brainstem Functional Connectivity Disturbances in Epilepsy may Recover After Successful Surgery.

Focal seizures in temporal lobe epilepsy (TLE) are associated with widespread brain network perturbations and neurocognitive problems. To determine whether brainstem connectivity disturbances improve with successful epilepsy surgery, as recent work has demonstrated decreased brainstem connectivity in TLE that is related to disease severity and neurocognitive profile. We evaluated 15 adult TLE patients before and after (>1 yr; mean, 3.4 yr) surgery, and 15 matched control subjects using magnetic resonance imaging to measure functional and structural connectivity of ascending reticular activating system (ARAS) structures, including cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus (PPN), and ventral tegmental area (VTA). TLE patients who achieved long-term postoperative seizure freedom (10 of 15) demonstrated increases in functional connectivity between ARAS structures and fronto-parietal-insular neocortex compared to preoperative baseline (P=.01, Kruskal-Wallis), with postoperative connectivity patterns resembling controls' connectivity. No functional connectivity changes were detected in 5 patients with persistent seizures after surgery (P=.9, Kruskal-Wallis). Among seizure-free postoperative patients, larger increases in CSC, PPN, and VTA functional connectivity were observed in individuals with more frequent seizures before surgery (P<.05 for each, Spearman's rho). Larger postoperative increases in PPN functional connectivity were seen in patients with lower baseline verbal IQ (P=.03, Spearman's rho) or verbal memory (P=.04, Mann-Whitney U). No changes in ARAS structural connectivity were detected after successful surgery. ARAS functional connectivity disturbances are present in TLE but may recover after successful epilepsy surgery. Larger increases in postoperative connectivity may be seen in individuals with more severe disease at baseline.

Altered circadian rhythms and oscillation of clock genes and sirtuin 1 in a model of sudden unexpected death in epilepsy.

Circadian rhythms are affected in many neurological disorders. Although sleep disturbances are known in epilepsy, data on circadian rhythm disturbances in epilepsy are sparse. Here, we examined diurnal and circadian rest-activity and sleep-wake patterns inKcna1-null mice, which exhibit spontaneous recurrent seizures and are a model of sudden unexpected death in epilepsy. Furthermore, we sought to determine whether seizures or aberrant oscillation of core clock genes and a regulator, sirtuin 1 (Sirt1), is associated with disrupted rhythms. We used passive infrared actigraphy to assess rest-activity patterns, electroencephalography for seizure and sleep analysis, and reverse transcription polymerase chain reaction and Western blotting to evaluate expression of clock genes and Sirt1 inKcna1-null and wild-type mice. EpilepticKcna1-null animals have disrupted diurnal and circadian rest-activity patterns, tending to exhibit prolonged circadian periods.Electroencephalographic analysis confirmed disturbances in sleep architecture, with more time spent awake and less asleep. Although all epileptic mice manifested disrupted diurnal and circadian rest-activity patterns, we found no correlation between actual seizure burden and degree of sleep disruption. However, we found attenuated oscillations of several clock genes (ie,Clock, Bmal1, Per1, and Per2) and diurnal Sirt1 mRNA in the anterior hypothalamus. Attenuatedoscillation of several core clock genes correlates with, and may underlie, aberrant diurnal and circadian rest-activity and sleep-wake patterns observed inKcna1-null mice. This could contribute to late complications in epilepsy, such as sudden unexpected death in epilepsy. Sirt1 may represent a useful therapeutic target for rescuing circadian clock gene rhythmicity and sleep patterns in epilepsy.

Dysfunctional Brain Networking among Autonomic Regulatory Structures in Temporal Lobe Epilepsy Patients at High Risk of Sudden Unexpected Death in Epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is common among young people with epilepsy. Individuals who are at high risk of SUDEP exhibit regional brain structural and functional connectivity (FC) alterations compared with low-risk patients. However, less is known about network-based FC differences among critical cortical and subcortical autonomic regulatory brain structures in temporal lobe epilepsy (TLE) patients at high risk of SUDEP. 32 TLE patients were risk-stratified according to the following clinical criteria: age of epilepsy onset, duration of epilepsy, frequency of generalized tonic-clonic seizures, and presence of nocturnal seizures, resulting in 14 high-risk and 18 low-risk cases. Resting-state functional magnetic resonance imaging (rs-fMRI) signal time courses were extracted from 11 bilateral cortical and subcortical brain regions involved in autonomic and other regulatory processes. After computing all pairwise correlations, FC matrices were analyzed using the network-based statistic. FC strength among the 11 brain regions was compared between the high- and low-risk patients. Increases and decreases in FC were sought, using high-risk > low-risk and low-risk > high-risk contrasts (with covariates age, gender, lateralization of epilepsy, and presence of hippocampal sclerosis). High-risk TLE patients showed a subnetwork with significantly reduced FC (t = 2.5, p = 0.029) involving the thalamus, brain stem, anterior cingulate, putamen and amygdala, and a second subnetwork with significantly elevated FC (t = 2.1, p = 0.031), which extended to medial/orbital frontal cortex, insula, hippocampus, amygdala, subcallosal cortex, brain stem, thalamus, caudate, and putamen. TLE patients at high risk of SUDEP showed widespread FC differences between key autonomic regulatory brain regions compared to those at low risk. The altered FC revealed here may help to shed light on the functional correlates of autonomic disturbances in epilepsy and mechanisms involved in SUDEP. Furthermore, these findings represent possible objective biomarkers which could help to identify high-risk patients and enhance SUDEP risk stratification via the use of non-invasive neuroimaging, which would require validation in larger cohorts, with extension to patients with other epilepsies and subjects who succumb to SUDEP.

Gestchwind syndrome and epileptic psychosis, beyond the schizophrenia frontier

During late 19th and early 20th century neuropsychiatrists began to identify common behavioral and cognitive disturbances in epilepsy, but it is not until 1973 that Norman Gestchwind described the basics of what we know as Gestchwind syndrome. This syndrome includes the triada of hyper-religiosity, hypergraphia and hypo/hypersexuality and it was mainly associated with temporal lobe epilepsy. Moreover, it is well known the association between epilepsy and psychotic symptoms, the so-called schizophrenia-like syndrome, which can lead us to a false diagnosis of schizophrenia. We report a 44-year-old man who was brought to the hospital with delusional ideation of prosecution and reference in his work environment with important behavioral disruption, as well as delusional ideation of religious content. He had a diagnosis of schizophrenia since he was 18-years-old and personal history of generalized tonic-clonic convulsions in his twenties. During the admission, he recovered ad integrum very rapidly with low doses of risperidone, but referred recurrence of déjà vu episodes. After reviewing his patobiography and past medical history, we identified the presence of hypergraphia, hypersexuality and a profound religious feeling, fulfilling the criteria for Gestchwind syndrome, in the context of which was later diagnosed as chronic epileptic psychosis. It is very important a careful approach to the patobiography and personal history. Also, we should include classic differential diagnosis such as Gestchwind syndrome, as they can lead us finally to the correct diagnosis, which in this case meant not only a different treatment but also a better prognosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study

ObjectiveSleep disturbance is reported to be frequent in epilepsy. The role of comorbidity, which is frequently accompanied by sleep disturbance, has not been investigated. The present study assessed sleep disorders and circadian rhythm in patients with epilepsy, in whom relevant comorbidity was carefully excluded. MethodsTwo hundred patients with epilepsy (100 generalized, 100 partial), without relevant psychiatric, neurological or internal comorbidity, were compared with 100 matched controls. The questionnaire contained specifically tailored questions to address the association between epilepsy and sleep disturbance, and validated questionnaires aimed at sleep quality, excessive daytime sleepiness (EDS), circadian rhythm, sleep disorders, and quality of life. ResultsForty-one percent of the participants reported on the acute effects of present or past seizures on sleep-wake rhythm, whereas chronic effects were not evident. Participants and controls did not differ in the rates of chronic sleep disturbance, EDS, and presence of sleep disorders (all p-values non-significant or n.s.). Apart from earlier sleep times on workdays (p = 0.001) in those with epilepsy, circadian variables were similarly distributed. Epilepsy was well controlled, with 75.9% being seizure free for ≥1 year. Longer durations of epilepsy showed a negative correlation with sleep quality (rho = −0.256, p < 0.001). Participants with generalized and partial epilepsies did not differ in rates of sleep disturbance, EDS, sleep disorders, and variables of circadian rhythm (all p-values n.s.). ConclusionThe present study demonstrated that chronic sleep disturbance is not increased in patients with well-controlled epilepsy without relevant comorbidity. This supports comorbidity and insufficient seizure control as major contributors of sleep disturbance in epilepsy.

Treatment issues for personality disorders in epilepsy

This article supports a view that certain personality disturbances in epilepsy should be viewed as associated with the cerebral abnormalities that also lead to seizures. Herein I discuss two main variants: that related to temporal lobe epilepsy and that associated with juvenile myoclonic epilepsy. In view of its controversial nature, I also comment on the link between aggression and epilepsy. Recommendations for treatment include psychological and social therapies with further advice about the use of antiepileptic drugs (AEDs) and psychotropic medications in these conditions.

Sleep apnea and epilepsy: Who's at risk?

Obstructive sleep apnea (OSA) is highly prevalent, affecting 25% of men and 10% of women. Treatment reduces seizures in some patients. Awareness of the comorbidity of sleep disturbances in epilepsy has been increasing. No study has explored OSA predictors in patients unselected for epilepsy severity and sleep disorder symptoms. We assessed cross-sectional OSA prevalence and predictors (apnea–hypopnea index [AHI] ≥10) in 130 consecutive adults using structured interview, subjective assessments, and polysomnography. Obstructive sleep apnea prevalence was 30%, 16% having moderate–severe disease, rates that markedly exceed general population estimates. Obstructive sleep apnea predictors in multivariate modeling included age, dental problems, and standardized AED dose. Male gender, older age, higher BMI, hypertension, and dental problems were associated with higher AHI. Adults with epilepsy appear at increased risk for OSA, increasing with age and AED load, regardless of gender, BMI, and seizure frequency. These findings support the implementation of routine OSA screening in adult epilepsy clinics.

Periictal heart rate variability analysis suggests long‐term postictal autonomic disturbance in epilepsy

One of the possible pathomechanisms of sudden death in epilepsy (SUDEP) is a postictal dysregulation of autonomic nervous system. We performed a heart rate variability (HRV) analysis of the periictal state to analyze whether a cardiac autonomic disturbance exists after an epileptic seizure. We included 31 periictal video-EEG-ECG recordings of 31 patients with epilepsy who had consecutively undergone pre-surgical evaluation. Nine generalized tonic-clonic (GTCS), 15 complex partial, and seven simple motor seizures were included. HRV was evaluated by analyzing 5-min-long ECG epochs, sampling from baseline, direct preictal, early-postictal (<15 min after the seizure), and late-postictal (5-6 h after the seizure) periods. The heart rate was elevated immediately after the seizures, but 5-6 h postictally returned to the baseline level. Time-domain components of HRV decreased after the seizure and this decrease lasted for 5-6 h. Low-frequency power decreased in the early-postictal phase and high-frequency power of HRV dropped in the late-postictal phase. GTCS had an impact on short-term but not on long-term postictal HRV decrease. We found decreased HRV immediately after the seizures, which lasted at least 5-6 h postictally, indicating a long-term postictal disturbance of the autonomous nervous system. GTCS were accompanied by a more decreased HRV than other seizures. Our results may have relevance in explaining pathomechanism of SUDEP.

Psychiatric disorders in epilepsy. Communication II

Аnalysis of various chronic psychiatric disturbances in epilepsy – characteristic personality changes, aggressiveness and cognitive abnormalities – is presented. Relevant risk factors and mechanisms of chronic psychiatric disorders in different clinical variants of epilepsy are assessed. An extensive personal experience of the author and literature data are summarized concerning urgent therapy of acute psychotic manifestations and severe depressive disorders in patients with epilepsy. Psychiatric syndromes that are in cause and effect relation with current medication of epilepsy and with prescription of particular antiepileptic drugs are discussed in detail.

The Evaluation of Behavioral Disturbances in Epilepsy

The evaluation of behavioral disturbances in epilepsy is an area fraught with complexity. On the one hand, there are no instruments that have been developed specifically for the assessment of behavioral disturbances in epilepsy. On the other hand, the phenomenology and pathophysiology of behavioral disturbances in epilepsy are unique and defy conventional descriptions in the psychiatric literature. The vast majority of studies have used instruments that have not been validated for this purpose. Studies with a psychiatric orientation generally tend to employ unvalidated semistructured or structured tools except for the Structured Clinical Interview for DSM, which has been validated for epilepsy. Studies with a neurological orientation generally use screening questionnaires and interpret the results of these as diagnostic. Neither approach is valid and both generally fail to measure potential confounders, such as seizure frequency, seizure severity, temporality of seizure occurrence in relation to time of assessment, life events, disablement, quality of life, and other socioeconomic indicators. Furthermore, instruments are generally employed using cutoff scores that may not be valid for epilepsy populations; the emphasis is often on symptom severity rather than symptom multiplicity (or load), which may also have an impact on the patient's outcome. In addition, instruments that have a basis in psychiatric criteria as opposed to symptomatology have inherent pitfalls at the interface between epilepsy and behavior. These and other issues in evaluating behavioral disturbances in people with epilepsy are reviewed and some solutions for the future are proposed.

Delivered at the Royal College of Pysicians, London. By Robert Bentley Todd, M.D., F.R.S. ON THE PATHOLOGY AND TREATMENT OF CONVULSIVE DISEASES

Delivered at the Royal College of Pysicians, London. By Robert Bentley Todd, M.D., F.R.S. ON THE PATHOLOGY AND TREATMENT OF CONVULSIVE DISEASES

Daytime Behavior and Sleep Disturbance in Epilepsy

Daytime Behavior and Sleep Disturbance in Epilepsy

Daytime Behavior and Sleep Disturbance in Epilepsy

Daytime behavior and sleep disturbance in 30 children with epilepsy, mean age 10.3 +/- 2.1 years, were evaluated by parent-rating questionnaires and child symptom self-report measures in a study at the University of Florida, Gainesville, FL.

Epilepsy and sleep disturbance

Sleep disturbance is common in epilepsy, the nature of sleep disturbances in epilepsy is diverse, and the etiologies are complex. Evidence suggests that having epilepsy and the occurrence of seizures, as well as some AEDs, are associated with significant sleep disruption. The occurrence of seizures can have profound effects on sleep architecture lasting much longer than the postictal period. Persistent daytime drowsiness in patients with epilepsy is not always due to the side effects of some AEDs and may be independently linked with sleep fragmentation. Significant sleep disruption in epilepsy has been associated with impaired quality of life and impaired seizure control. All aspects of sleep medicine are important in the management of epilepsy and are confounded by the occurrence of seizures, the location of seizures, and the beneficial and detrimental effects of AEDs. Sleep should be proactively evaluated, and sleep disturbances should be treated as part of the total care of patients with epilepsy.

Psychiatric complications in patients with epilepsy: a review

At least 50–60% of patients with epilepsy develop psychiatric disturbances, particularly mood, anxiety, and psychotic disorders. This article, aimed at the non-psychiatric clinician, reviews the differential diagnosis and treatment of psychiatric disturbances in epilepsy and focuses on the evaluation of psychiatric phenomena relative to the ictal state or the periictal and interictal periods. Pharmacological and non-pharmacological therapies are reviewed. A final section discusses potential interactions between antiepileptic and psychiatric medications.

Symptoms of Psychiatric Disturbance in Epilepsy

To assess the severity and nature of symptoms of psychiatric distress among tertiary center epilepsy patients, we administered the Brief Symptom Inventory (BSI) and Center for Epidemiologic Studies-Depression Scale (CES-D) to adult patients evaluated at our tertiary center who were diagnosed with Epilepsy (EPI; n = 37), or Chronic Lyme Disease (CLD, n = 38). We compared results in these groups to published studies in normal healthy adults (NHA) and psychiatric outpatients (Psych). Mean global BSI and CES-D scores were both markedly elevated in the EPI and CLD groups compared to NHA but less than Psych. Subscores of the BSI varied among the EPI and CLD groups with higher obsessive compulsive symptoms among CLD patients ( p = .014), higher paranoid symptoms in the EPI group ( p = .021), and a trend toward higher somatization subscores in the CLD group ( p = .054). Symptoms of psychiatric distress including depression are common among tertiary epilepsy center patients as well as patients with CLD.

Book Reviews

Book reviewed in this article:Autism: An Inside Out Approach: D. WilliamsChallenging Behaviour: Analysis and Intervention in People with Learning Disabilities: E. EmersonPsychological Disturbances in Epilepsy: J. Chris Sackellares and Stanley BerentInvisible Victims: Crime and Abuse against People with Learning Difficulties Christopher WilliamsDisabled Children and Developing Countries: Pam Zinkin and Helen McConachie (eds)The Nature of Learning Disabilities: Kenneth A. Kavale and Steven R. FornessChildren with Autism: Diagnosis and Interventions to Meet their Needs: C. Trevarthen, K. Aitken, D. Papoudi and J. Robarts

Disruption of light-induced c-Fos immunoreactivity in the suprachiasmatic nuclei of chronic epileptic rats

Photic stimulation during specific day periods may induce Fos oncoprotein expression within the ventrolateral part of the suprachiasmatic nucleus (SCN) in the hypothalamus of rodents. This phenomenon appears to be a major molecular mechanism for environmental light/dark cycle entrainment of the mammalian circadian clock. Light-dependent synchronization of circadian rhythmicity may be disrupted in epilepsy, a chronic neurological disorder often associated with chronobiological features such as seizure periodicity and disruption of endogenous biological rhythms. The present work examined the light-induced Fos protein expression on the SCN in the pilocarpine model of chronic epilepsy. Fos-like immunoreactivity was significantly reduced in the SCN of chronic epileptic rats after photic stimulation during the subjective night. These results indicate an altered Fos protein expression in the SCN of chronic epileptic rats. The present findings reveal that pathological neural events underlying epileptogenesis may disturb circadian rhythm regulation. The experimental study of circadian clock activity in the SCN may clarify the molecular bases of chronobiological disturbances in epilepsy.

Economical screening for emotional disturbance in epilepsy: Anticipating Minnesota multiphasic personality inventory profile elevations by means of the Washington psychosocial seizure inventory

This study examined the ability of the Washington Psychosocial Seizure Inventory (WPSI) to identify patients with elevated (abnormal) scores on scales of the Minnesota Multiphasic Personality Inventory (MMPI). A sample of 407 adults with epilepsy who were administered both inventories was randomly divided into principal (n = 250) and cross-validation (n = 157) subsamples. Scores of 5 or more on the WPSI Emotional Adjustment Scale best identified the presence of one or more MMPI scale elevations, with 82% accuracy on cross-validation. Scores on the Emotional Adjustment Scale of 12 or more best identified the presence of two or more MMPI scale elevations, with 80% accuracy on cross-validation. High correlations were obtained between several WPSI and MMPI scales. This study suggests that the 132-item WPSI may be useful in screening for emotional disturbances in adults with epilepsy, and in determining when further emotional evaluation via clinical interview or additional testing may be warranted.