Adherence to antiseizure medications in an underserved population with epilepsy.

BACKGROUND AND PURPOSE: Antiseizure medications (ASM) effectively prevent seizures in about 70% of adult epilepsy patients, but nonadherence to medication is the primary cause of breakthrough seizures, accounting for 26% to 79% of cases. Factors such as age, education, dosing frequency, forgetfulness, fear of side effects, and socioeconomic status contribute to poor adherence, especially among underserved populations. This study aimed to assess medication adherence during routine follow-up visits and identify the role of education in reducing non adherence in an underserved patient population. METHODS: The study involved a retrospective chart review of adult epilepsy patients seen at the University of Illinois Hospital between December 2016 and April 2020. Data on patient demographics, epilepsy and seizure classification, medication details, emergency visits, and adherence were collected from electronic medical records using the RedCap system. Descriptive statistics and statistical tests were conducted using STATA 17.0 for data analysis, including chi-squared analysis for categorical data and t-tests for continuous data. RESULTS: The study enrolled a total of 286 adult epilepsy patients who met the eligibility criteria. Among them, 111 patients (38.81 %) were classified as nonadherent based on ASM levels. Caucasian/white race and income > $50,000 per year, were significantly associated with adherence (p = 0.009 and p = 0.006 respectively). Moreover, patients with weekly seizures were more likely to be adherent (p = 0.042). No significant differences were found regarding medication adherence and sex, education, employment, epilepsy type, age at diagnosis, seizure type or number of current ASM medications. Even though not significant, a trend towards college educated patients being more adherent was observed (70.37 %). Of self-reported adherent patients, 33.33 % were found to be nonadherent based on ASM levels. Nurse phone calls reminding 70 non adherent patients about adherence increased the chances of becoming adherent by 80.39 %. Finally, although not statistically significant, the majority of adherent patients had no history of hospitalizations for breakthrough seizures (73.89 %). CONCLUSION: More than a third of our patients were found to be non-adherent during routine follow-up visits. Lower socio-economic status and lower education were associated with increased chances of being non adherent. Rates of adherence were improved by nurse's phone calls discussing the importance of adherence and risks of SUDEP. The findings emphasize the importance of education in improving medication adherence among these populations, suggesting the need for social interventions, community outreach programs, and targeted educational initiatives.

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model.

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Multi-modal data integration platform combining clinical and preclinical models of post subarachnoid hemorrhage epilepsy.

Subarachnoid hemorrhage (SAH) is a devastating neurological injury that can lead to many downstream complications including epilepsy. Predicting who will get epilepsy in order to find ways to prevent it as well as stratify patients for future interventions is a major challenge given the large number of variables not only related to the injury itself, but also to what happens after the injury. Extensive multimodal data are generated during the process of SAH patient care. In parallel, preclinical models are under development that attempt to imitate the variables observed in patients. Computational tools that consider all variables from both human data and animal models are lacking and demand an integrated, time-dependent platform where researchers can aggregate, store, visualize, analyze, and share the extensive integrated multimodal information. We developed a multi-tier web-based application that is secure, extensible, and adaptable to all available data modalities using flask micro-web framework, python, and PostgreSQL database. The system supports data visualization, data sharing and downloading for offline processing. The system is currently hosted inside the institutional private network and holds [Formula: see text] of data from 164 patients and 71 rodents. Clinical Relevance-Our platform supports clinical and preclinical data management. It allows users to comprehensively visualize patient data and perform visual analytics. These utilities can improve research and clinical practice for subarachnoid hemorrhage and other brain injuries.

Two cases of focal status epilepticus in pregnancy.

The management of women with epilepsy (WWE) presents many challenges for physicians. The primary goal during pregnancy is to achieve the best possible control of seizures with the least adverse effects associated with exposure to antiseizure medications (ASMs). Even though the guidelines for managing pregnant WWE are expanding, no definitive guidelines exist for the treatment of status epilepticus (SE). Additionally, much of our data comes from the effect of generalized tonic clonic seizures on the fetus. There is very little data on the effect of focal seizures and even less on focal SE. Here we present two cases of pregnant WWE who presented in focal SE, who underwent simultaneous video-EEG monitoring and fetal heart tracing (FHT). During each focal seizure the FHT demonstrated a normal baseline heart rate with moderate variability. In the second case due to continuous seizures more aggressive treatment had to be started. This led to maternal relative autonomic instability as well as absent variability on FHT. These findings raise many questions on the management of focal SE during pregnancy including if the effect of treatment is worse than the seizures, and how do we balance our goals for both mother and fetus?

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.

Highly consistent temporal lobe interictal spike networks revealed from foramen ovale electrodes.

OBJECTIVE: A major challenge that limits understanding and treatment of epileptic events from mesial temporal structures comes from our inability to detect and map interictal networks reproducibly using scalp electrodes. Here, we developed a novel approach to map interictal spike networks and demonstrate their relationships to seizure onset and lesions in patients with foramen ovale electrode implantations. METHODS: We applied the direct Directed Transfer Function to reveal interictal spike propagation from bilateral foramen ovale electrodes on 10 consecutive patients and co-registered spatially with both seizure onset zones and temporal lobe lesions. RESULTS: Highly reproducible, yet unique interictal spike networks were seen for each patient (correlation: 0.93 ±â€¯0.13). Interictal spikes spread in both anterior and posterior directions within each temporal lobe, often reverberating between sites. Spikes propagated to the opposite temporal lobe predominantly through posterior pathways. Patients with structural lesions (N = 4), including tumors and sclerosis, developed reproducible spike networks adjacent to their lesions that were highly lateralized compared to patients without lesions. Only 5% of mesial temporal lobe spikes were time-locked with scalp electrode spikes. Our preliminary observation on two lesional patients suggested that along with lesion location, Interictal spike networks also partially co-registered with seizure onset zones suggesting interrelationship between seizure onset and a subset of spike networks. CONCLUSIONS: This is the first demonstration of patient-specific, reproducible interictal spike networks in mesial temporal structures that are closely linked to both temporal lobe lesions and seizure onset zones. SIGNIFICANCE: Interictal spike connectivity is a novel approach to map epileptic networks that could help advance invasive and non-invasive epilepsy treatments.

Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain.

As a means to understand human neuropsychiatric disorders from human brain samples, we compared the transcription patterns and histological features of postmortem brain to fresh human neocortex isolated immediately following surgical removal. Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval. Within a few hours, a selective reduction in the number of neuronal activity-dependent transcripts occurred with relative preservation of housekeeping genes commonly used as a reference for RNA normalization. Gene clustering indicated a rapid reduction in neuronal gene expression with a reciprocal time-dependent increase in astroglial and microglial gene expression that continued to increase for at least 24 h after tissue resection. Predicted transcriptional changes were confirmed histologically on the same tissue demonstrating that while neurons were degenerating, glial cells underwent an outgrowth of their processes. The rapid loss of neuronal genes and reciprocal expression of glial genes highlights highly dynamic transcriptional and cellular changes that occur during the postmortem interval. Understanding these time-dependent changes in gene expression in post mortem brain samples is critical for the interpretation of research studies on human brain disorders.

Enhancing epilepsy self-management and quality of life for adults with epilepsy with varying social and educational backgrounds using PAUSE to Learn Your Epilepsy.

PURPOSE: People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. METHODS: Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8-12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. RESULTS: The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. CONCLUSION: This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.

Seizures Do Not Affect Disability and Mortality Outcomes of Stroke: A Population-Based Study.

Although seizures are frequently seen after cerebrovascular accidents, their effects on long-term outcome in stroke patients are still unknown. Therefore, the aim of this study was to investigate the relationship between post-stroke seizures and the risk of long-term disability and mortality in stroke patients. This study is part of a larger population-based study. All patients were prospectively followed up by a face-to-face interview or a structured telephone interview. We enrolled 635 patients with first-ever stroke and without a history of seizures. Prevalence of ischemic stroke (IS) was 85.2%, while the remaining 14.8% of patients were affected by intracerebral hemorrhage (ICH). During the study period, 51 subjects (8%) developed post-stroke seizures. Patients with post-stroke seizures were younger, had a higher prevalence of ICH, had a more severe stroke at admission, were more likely to have an IS involving the total anterior circulation, and were more likely to have a lobar ICH than patients without seizures. Moreover, subjects with seizures had more frequently hemorrhagic transformation after IS and cortical strokes. At 24 months, the risk of disability in patients with seizures was almost twice than in those without seizures. However, the negative effect of seizures disappeared in multivariate analysis. Kaplan-Meier survival curves at 12 years were not significantly different between patients with and without post-stroke seizures. Using the Cox multivariate analysis, age, NIHSS at admission, and pre-stroke mRS were independently associated with all-cause long-term mortality. In our sample, seizures did not impair long-term outcome in patients affected by cerebrovascular accidents. The not significant, slight difference in favor of a better survival for patients with seizures may be attributed to the slight age difference between the two groups.

Self-management skills and behaviors, self-efficacy, and quality of life in people with epilepsy from underserved populations.

PURPOSE: People with epilepsy (PWE) from underserved populations face significant barriers to epilepsy management and therefore may lack knowledge about epilepsy and self-management (SM) of epilepsy. This paper evaluates SM practices, self-efficacy, outcome expectancy, quality of life, and personal impact of epilepsy in PWE from underserved populations as compared with all PWE. METHODS: Recruitment for the Managing Epilepsy Well (MEW) Network PAUSE to Learn Your Epilepsy study occurred from October 2015 to March 2019. Participants were assessed at baseline; after SM education intervention; and 6-, 9-, and 15-month postbaseline assessment. Baseline data from 112 PWE were analyzed for this report. RESULTS: Study population was diverse: 63% were women, 47.3% were non-Hispanic black, 24.1% were Hispanic, and 57.4% had public healthcare coverage. Participants on average had epilepsy for 14 years, and 49.1% reported at least one seizure within the past month, but only 27% reported having used a seizure diary or calendar for seizure tracking. Self-management practices & behaviors were significantly lower among PWE from underserved populations than all PWE, though self-efficacy among PWE from underserved populations was significantly higher. CONCLUSION: This study identifies the unique epilepsy SM needs of PWE from underserved populations. We discuss the need for a personalized approach for developing SM skills and behaviors among these PWE.

Treatment of Juvenile Myoclonic Epilepsy in Patients of Child-Bearing Potential.

Juvenile myoclonic epilepsy (JME) is both a frequent and a very characteristic epileptic syndrome with female preponderance. Treatment of JME in women of childbearing potential must consider multiple factors such as desire for pregnancy, use of contraception, seizure control and previously used antiepileptic drugs (AEDs). Approximately 85% of cases are well controlled with valproate, which remains the reference AED in JME but is nowadays considered unsafe for the expecting mother and her fetus. The prescription of valproate is now severely restricted in women of childbearing potential but may still be considered, at the lowest possible dose and when pregnancies can be reliably planned, with temporary alternatives to valproate prescribed before fertilization. Alternatives have emerged, especially lamotrigine and levetiracetam, but also topiramate, zonisamide, and recently perampanel, but none of these AEDs can be considered fully safe in the context of pregnancy. In special settings, benzodiazepines and barbiturates may be useful. In some cases, combination therapy, especially lamotrigine and levetiracetam, may be useful or even required. However, lamotrigine may have the potential to aggravate JME, with promyoclonic effects. Carbamazepine, oxcarbazepine and phenytoin must be avoided. Valproate, levetiracetam, zonisamide, topiramate if the daily dose is ≤ 200 mg and perampanel if the daily dose is ≤ 10 mg do not affect combined hormonal contraception. Lamotrigine ≥ 300 mg/day has been shown to decrease levonorgestrel levels by 20% but does not compromise combined hormonal contraception. Patients with JME taking oral contraceptive should be counselled on the fact that the estrogenic component can reduce concentrations of lamotrigine by over 50%, putting patients at risk of increased seizures. Pregnancy is a therapeutic challenge, and the risk/benefit ratio for the mother and fetus must be considered when choosing the appropriate drug. Lamotrigine (< 325 mg daily in the European Registry of Antiepileptic Drugs in Pregnancy) and levetiracetam seem to be comparatively safer in pregnancy than other AEDs, especially topiramate and valproate. Plasma concentration of lamotrigine and levetiracetam decreases significantly during pregnancy, and dosage adjustments may be necessary. With persisting generalized tonic-clonic seizures, the combination of lamotrigine and levetiracetam offer the chance of seizure control and lesser risks of major congenital malformations. The risk of malformation increases when valproate or topiramate are included in the drug combination. In one study, the relative risk of autism and autism spectrum disorders (ASD) in children born to women with epilepsy (WWE) treated with valproate were, respectively, 5.2 for autism and 2.9 for ASD versus 2.12 for autism and 1.6 for ASD in WWE not treated with valproate. More studies are needed to assess the risk of autism with AEDs other than valproate. The current knowledge is that the risk appears to be double that in the general population. In patients with JME, valproate remains an essential and life-changing agent. The consequences of a lifetime of poorly controlled epilepsy need to be balanced against the teratogenic risks of valproate during limited times in a woman's life. The management of JME in WWE should include lifestyle interventions, with avoidance of sleep deprivation, and planned pregnancy.

Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study.

BACKGROUND: Stroke is one of the leading causes of acquired epilepsy in adults. An instrument to predict whether people are at high risk of developing post-stroke seizures is not available. We aimed to develop and validate a prognostic model of late (>7 days) seizures after ischaemic stroke. METHODS: In this multivariable prediction model development and validation study, we developed the SeLECT score based on five clinical predictors in 1200 participants who had an ischaemic stroke in Switzerland using backward elimination of a multivariable Cox proportional hazards model. We externally validated this score in 1169 participants from three independent international cohorts in Austria, Germany, and Italy, and assessed its performance with the concordance statistic and calibration plots. FINDINGS: Data were complete for 99·2% of the predictors (99·2% for Switzerland, 100% for Austria, 97% for Germany, and 99·7% for Italy) and 100% of the outcome parameters. Overall, the risk of late seizures was 4% (95% CI 4-5) 1 year after stroke and 8% (6-9) 5 years after stroke. The final model included five variables and was named SeLECT on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). The lowest SeLECT value (0 points) was associated with a 0·7% (95% CI 0·4-1·0) risk of late seizures within 1 year after stroke (1·3% [95% CI 0·7-1·8] within 5 years), whereas the highest value (9 points) predicted a 63% (42-77) risk of late seizures within 1 year (83% [62-93] within 5 years). The model had an overall concordance statistic of 0·77 (95% CI 0·71-0·82) in the validation cohorts. Calibration plots indicated high agreement of predicted and observed outcomes. INTERPRETATION: This easily applied instrument was shown to be a good predictor of the risk of late seizures after stroke in three external validation cohorts and is freely available as a smartphone app. The SeLECT score has the potential to identify individuals at high risk of seizures and is a step towards more personalised medicine. It can inform the selection of an enriched population for antiepileptogenic treatment trials and will guide the recruitment for biomarker studies of epileptogenesis. FUNDING: None.

Clinical implications of interictal epileptiform discharges in cognitive functioning in CEC syndrome with evolution into epileptic encephalopathy.

In epileptic encephalopathies (EE), interictal epileptiform discharges (IEDs) contribute to cognitive impairment. The EE process has been studied in a patient affected by epilepsy with occipital calcification and celiac disease (CEC syndrome) by combining the administration of brain area stimulus specific (visual and auditory) reaction times (RT) during continuous EEG monitoring with the off-line reconstruction of auditory and visual evoked potentials (EP). Visual RT and VEP were abnormal only if recorded concomitantly to the IEDs. Auditory RT and EP were normal. When the EE process is going on, IEDs transiently disrupt aspects of cortical functioning, contributing to the cognitive impairment.

TIRDA Originating From Lateral Temporal Cortex in a Patient With mTLE Is Not Related to Hippocampal Activity.

Electrophysiological studies have suggested that temporal intermittent rhythmic delta activity (TIRDA) has a localizing value similar to interictal spikes in patients with temporal lobe epilepsy and is associated with a favorable outcome after temporal lobectomy. However, it remains controversial whether TIRDA is an EEG marker for mesial or lateral temporal epileptogenesis. We simultaneously recorded scalp EEG and stereoencephalography in a patient with mesial temporal lobe epilepsy during epilepsy presurgical evaluation. Seizure onset was localized to the hippocampus. However, TIRDA originated from the lateral temporal cortex, and rhythmic delta activity was not observed concomitantly in the hippocampus. In addition, TIRDA was not associated with repetitive interictal spikes or subclinical seizures in the hippocampus as previously speculated. This case suggests that TIRDA can be an EEG marker that is independent of hippocampal activity and can represent temporal neocortical epileptogenesis.

Paraneoplastic epilepsy.

Epilepsy can be a manifestation of paraneoplastic syndromes which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting other organs and tissues. The antibodies commonly found in paraneoplastic encephalitis can be divided into two main groups depending on the target antigen: 1) antibodies against neuronal cell surface antigens, such as against neurotransmitter (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid (GABA)) receptors, ion channels (voltage-gated potassium channel (VGKC)), and channel-complex proteins (leucine rich, glioma inactivated-1 glycoprotein (LGI1) and contactin-associated protein-2 (CASPR2)) and 2) antibodies against intracellular neuronal antigens (Hu/antineuronal nuclear antibody-1 (ANNA-1), Ma2/Ta, glutamate decarboxylase 65 (GAD65), less frequently to CV2/collapsin response mediator protein 5 (CRMP5)). In this review, we provide a comprehensive survey of the current literature on paraneoplastic epilepsy indexed by the associated onconeuronal antibodies. While a range of seizure types can be seen with paraneoplastic syndromes, temporal lobe epilepsy is the most common because of the association with limbic encephalitis. Early treatment of the paraneoplastic syndrome with immune modulation/suppression may prevent the more serious potential consequences of paraneoplastic epilepsy.

Are Early Seizures Predictive of Epilepsy after a Stroke? Results of a Population-Based Study.

BACKGROUND: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures. METHODS: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study. RESULTS: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS. CONCLUSIONS: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation.

Transcranial magnetic stimulation in sleep fragmentation: a model to better understand sleep disorders.

OBJECTIVE: To investigate practice-dependent plasticity and cortical inhibition/excitability in good sleepers after a night of sleep fragmentation (SF), by means of transcranial magnetic stimulation (TMS). METHODS: In basal condition (BC), after a full night of spontaneous sleep, and in fragmented condition (FC), after a fragmented night of sleep, motor evoked potential (MEP) amplitude, motor threshold (MT), silent period (SP), and intracortical inhibition were assessed. In both conditions subjects performed, also, a bimanual motor task: MEPs were recorded before and after exercise, and after rest. We evaluated the presence of post-exercise facilitation and delayed facilitation. Subjects reported their alertness level (Stanford Sleepiness Scale-SSS). RESULTS: MT and SSS were significantly increased in SF. Instead, no significant differences for MEP amplitude or SP or intracortical inhibition were found. In both conditions post-exercise facilitation and delayed facilitation were present. CONCLUSION: SF produces disruption of nocturnal sleep and increases daytime sleepiness. Confirmatory features of this clinical behaviour could be that in FC we observed a significant increase in SSS and in MT. SF was unable to modify cortical inhibition\excitability and\or to influence plasticity-related parameters. These results seem inconsistent with some of TMS alterations observed in sleep deprivation (SD) and restless legs syndrome (RLS). We suggest that SD and SF represent different phenomena that can depend on various networks acting on motor cortex. We speculate that alterations in cortical excitability found in RLS are intrinsically related to the underlying disease itself and are not instead directly associated with the SF present in RLS.

Zonisamide for refractory juvenile absence epilepsy.

PURPOSE: To examine the clinical effect of zonisamide (ZNS) in patients with drug-resistant juvenile absence epilepsy (JAE). METHODS: Between 2006 and 2010, 13 JAE patients were successively treated with add-on ZNS. Safety and efficacy were assessed according to the patient and caregiver reports at visits every 3 months. Response rate was defined as a 50% or greater reduction in seizure frequency. RESULTS: Mean age was 42 years. No patient had been seizure free for a period ≥12 months before ZNS. The mean follow-up was 34 months. The mean dosage of ZNS was 388 mg. ZNS was effective for absence seizures (AS) in all patients (more than 50% AS reduction). Four patients reached seizure reduction on 550-600 mg/day. Three (23%) had a reduction in AS frequency >75% and five (38.5%) between 50% and 75%. Seizure freedom was achieved in five patients (38.5%) (three patients with AS only and two with AS plus generalized tonic-clonic seizures (GTCS)). Before ZNS, four patients had AS evolving to absence status. After ZNS, three of them were in the seizure-free group, the later never experienced this type of complication. Among seven patients with AS plus GTCS, two of them did not report any improvement in the frequency of GTCS (29%). CONCLUSION: This observational post-marketing study confirms the broad-spectrum activity of ZNS that includes GTCS, myoclonic seizures and now AS. This study provides evidence that add-on ZNS is efficient and well tolerated in adult patients with refractory JAE, even at high doses.

Neurophysiology of juvenile myoclonic epilepsy.

Juvenile myclonic epilepsy (JME) can be firmly diagnosed by a careful interview of the patient focusing on the seizures and by the EEG with the help, if necessary, of long-term video-EEG monitoring using sleep and/or sleep deprivation. Background activity is normal. The interictal EEG shows diffuse or generalized spike-wave (SW) and polyspike-wave (PSW) discharges. In some patients, non-specific changes or misleading features such as focal changes are found. Changes are mostly seen at sleep onset and at awakening. Provoked awakenings are more likely to activate interictal paroxysmal abnormalities than spontaneous awakenings. The presence of a photoparoxysmal response with or without myoclonic jerks (MJ) is common (30% of the cases). Myoclonic jerks are associated with a discharge of fast, irregular, generalized PSWs that predominate anteriorly. Myoclonic jerks appear to be associated with rhythmic EEG (spike) potentials at around 20Hz. These frequencies are in the range of movement-related fast sensorimotor cortex physiological rhythms. The application of jerk-locked averaging technique has provided findings consistent with a cortical origin of MJ. Paired TMS (transcranial magnetic stimulation) studies showed a defective intracortical inhibition, due to impaired GABA-A mediated mechanisms. In this review, we present the EEG characteristics of JME with particular emphasis on the pathophysiology of MJ and on the role of sleep deprivation on interictal and ictal changes.

Consensus on diagnosis and management of JME: From founder's observations to current trends.

An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?