Postencephalitic epilepsy and drug‐resistant epilepsy after infectious and antibody‐associated encephalitis in childhood: Clinical and etiologic risk factors

To define the risk factors for postencephalitic epilepsy (PE) and drug‐resistant epilepsy (DRE) in childhood following infectious and autoimmune encephalitis, we included 147 acute encephalitis patients with a median follow‐up of 7.3 years (range 2–15.8 years). PE was defined as the use of antiepileptic drugs (AEDs) for ≥24 months, and DRE was defined as the persistence of seizures despite ≥2 appropriate AEDs at final follow‐up. PE and DRE were diagnosed in 31 (21%) and 15 (10%) of patients, respectively. The features during acute encephalitis predictive of DRE (presented as odds ratio [OR] with confidence intervals [CIs]) were status epilepticus (OR 10.8, CI 3.4–34.3), visual disturbance (6.4, 1.4–29.9), focal seizures (6.2, 1.9–20.6), magnetic resonance imaging (MRI) hippocampal/amygdala involvement (5.0, 1.7–15.4), intensive care admission (4.7, 1.4–15.4), use of >3 AEDs (4.5, 1.2–16.1), MRI gadolinium enhancement (4.1, 1.2–14.2), any seizure (3.9, 1.1–14.4), and electroencephalography (EEG) epileptiform discharges (3.9, 1.3–12.0). On multivariable regression analysis, only status epilepticus remained predictive of DRE in all models. DRE was common in herpes simplex virus (3/9, 33%) and unknown (8/40, 20%) encephalitis, but absent in acute disseminated encephalomyelitis (ADEM) (0/32, 0%), enterovirus (0/18), and anti‐N‐methyl‐d ‐aspartate receptor–NMDAR encephalitis (0/9). We have identified risk factors for DRE and demonstrated “high‐risk,” and “low‐risk” etiologies.     

Seizure clustering during epilepsy monitoring

PURPOSE: To identify risk factors associated with seizure clustering during epilepsy monitoring and to assess the effect of clustering on localization of the epileptogenic zone. METHODS: Patients undergoing presurgical epilepsy monitoring at Montefiore Medical Center or Yale-New Haven Hospital were recruited. Seizure clustering was defined as three or more seizures within 24 h. Risk factors for seizure clustering were examined by using regression analysis. The effect of clustering on localization was examined by Student's t test evaluation of mean interseizure interval for consecutive concordant and discordant seizures. RESULTS: Of 91 patients, clustering was present in 56 (61.5%). Variables significantly associated with clustering included a history of seizure clustering at home (p = 0.0003) and the presence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI; p = 0.0172). Clustering was present in nine of 10 patients with more than one seizure-onset zone. Ictal EEG localization was not associated with clustering, nor was rapid medication withdrawal. Mean interseizure intervals were not significantly different for concordant and discordant seizures. CONCLUSIONS: Seizure clustering during epilepsy monitoring is common. Risk factors include history of clustering at home, MTS on MRI, and possibly more than one seizure focus. In this study, seizures that occurred in clusters had as important a role in localization as did nonclustered seizures.     

Seizure precipitants in children with intractable epilepsy

PURPOSE: To investigate the seizure precipitants in children with intractable epilepsy, and to determine any distinctive clinical features contributing to seizures in these patients. METHODS: A questionnaire and seizure diary prepared by the parents of the patients. Demographic and seizure data were reviewed. RESULTS: Of 120 patients with intractable epilepsy, 74 (62%) had one (n=43), two (n=23), or three seizure precipitants (n=8). The three most common precipitants were illness or fever (32%), sleep deprivation (13%), and menstruation (10%). Of these precipitants, inducing factors (endogenous origin) were more common than triggering factors (exogenous origin): 73% versus 27%, respectively. Three distinctive clinical features - neurological abnormalities (P=0.01), status epilepticus (P=0.017), and abnormal neuroimaging (P=0.007) - were significantly more common in patients with than in patients without precipitants. CONCLUSIONS: Prompt recognition and management of seizure precipitants has practical implications for treating patients with refractory epilepsy. Such patients can be counseled to avoid specific precipitants.     

Long-term seizure outcome and its predictors in patients with recurrent seizures during the first year aftertemporal lobe resective epilepsy surgery

Purpose: The existing data on the implications of the characteristics of seizures that recur during the first year following epilepsy surgery on subsequent seizure outcome are conflicting. We investigated the impact of recurrent seizures in the first postoperative year and their attributes on long‐term seizure outcome. Methods: We studied the postoperative courses of 492 patients who had completed two or more years of follow‐up after temporal lobe resective epilepsy surgery. We used Kaplan‐Meier survival curves to define long‐term seizure outcome and assessed the predictive value of recurrent seizure characteristics on the outcome by univariate and multivariate proportional hazards regression models. Key Findings: In our patients, seizure recurrences during the first postoperative year, irrespective of the attributes of recurrent seizures (such as provoked vs. unprovoked, and timing and number of recurrences), imparted fourfold to sevenfold increased hazards for continued seizures beyond the first postoperative year. Although patients with complex partial seizures with or without secondary generalized tonic–clonic seizures (CPS/GTCS) had a sixfold increased risk, those with auras alone had only a borderline risk for seizures beyond the first postoperative year. In the multivariate model, CPS/GTCS as the predominant seizure type and three or more seizure recurrences during the first postoperative year independently predicted unfavorable long‐term seizure outcome. Significance: Our study provides valuable information that is helpful in prognosticating and counseling patients, and in making rational decisions on the withdrawal of antiepileptic drugs following surgery. Our findings enhance the general understanding of the etiopathogenesis of surgical failure.     

Seizure prediction in patients with focal hippocampal epilepsy

Objective

We evaluated the performance of our previously developed seizure prediction approach on thirty eight seizures from ten patients with focal hippocampal epilepsy.

Outcomes after surgery for focal epilepsy in children

Object Surgery is an effective treatment for selected patients with intractable epilepsy. The authors report the outcomes of focal resection in a series of children suffering from intractable focal epilepsy treated at a single institution. Methods The authors retrospectively analyzed a series of 58 consecutive children who underwent surgery between 1998 and 2006 for intractable localized epilepsy at Primary Children’s Medical Center. Evaluation for surgery and follow-up was performed by the authors in the combined Pediatric Epilepsy Surgery Clinic. Results Preoperative seizure duration ranged from 6 months to 15 years. The cause of epilepsy was mesial temporal sclerosis (MTS) in 16 patients, dual pathology (MTS plus another lesion) in 3 patients, low-grade tumors in 16 patients, cortical dysplasia (CD) in 13 patients, cavernous malformation (CM) in 5 patients, and other conditions in 5 patients. In 33 cases, the lesions were in the temporal lobe, and in 25 cases, the lesions were extratemporal. At last follow-up, 74% (43/58) of all patients were seizure-free; seizure-free rates for specific conditions were 88% (14/16) for MTS, 33% (1/3) for dual pathology, 81% (13/16) for tumor, 62% (8/13) for CD, and 80% (4/5) for CM. Seizure-free rates were 85% (28/33) for temporal locations and 60% (15/25) for extratemporal locations. There were no permanent neurological complications or deaths. Conclusion Surgery for localized epilepsy in carefully selected children has good seizure control rates with minimal complications. Outcomes for patients with resections in temporal locations were better than those for patients with extratemporal resections.     

Connectome biomarkers of drug‐resistant epilepsy

Drug‐resistant epilepsy (DRE) considerably affects patient health, cognition, and well‐being, and disproportionally contributes to the overall burden of epilepsy. The most common DRE syndromes are temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal epilepsy related to cortical malformations. Both syndromes have been traditionally considered as "focal," and most patients benefit from brain surgery for long‐term seizure control. However, increasing evidence indicates that many DRE patients also present with widespread structural and functional network disruptions. These anomalies have been suggested to relate to cognitive impairment and prognosis, highlighting their importance for patient management. The advent of multimodal neuroimaging and formal methods to quantify complex systems has offered unprecedented ability to profile structural and functional brain networks in DRE patients. Here, we performed a systematic review on existing DRE network biomarker candidates and their contribution to three key application areas: (1) modeling of cognitive impairments, (2) localization of the surgical target, and (3) prediction of clinical and cognitive outcomes after surgery. Although network biomarkers hold promise for a range of clinical applications, translation of neuroimaging biomarkers to the patient's bedside has been challenged by a lack of clinical and prospective studies. We therefore close by highlighting conceptual and methodological strategies to improve the evaluation and accessibility of network biomarkers, and ultimately guide clinically actionable decisions.     

A reduction of sleep spindles heralds seizures in focal epilepsy

ObjectivesSleep has profound effects on epilepsy. It may alter the occurrence of interictal discharges (IEDs) and seizures. Vice versa, an active epilepsy changes sleep. Sleep spindles are typically associated with an increase of IEDs. We examined whether seizures change the number and power of spindles preceding nightly seizures.MethodsWe retrospectively examined the nightly EEG recordings of presurgical epilepsy patients from our EEG-video-monitoring unit. We evaluated the 200 s before the EEG seizure onset for spindle density (spindles per minute) and spindle power and compared that to the interictal baseline sleep.ResultsThe spindle density and the spindle power decreased significantly before the first seizure. The reduction before secondarily generalized seizures (8.7 ± 2.5; p = 0.001) was more pronounced than before focal seizures (10.5 ± 2.5; p = 0.003) compared to baseline (12.2 ± 2.7). This finding was more pronounced in extratemporal lobe epilepsies than in temporal lobe epilepsies. The reduction of spindle power was also significant and was more pronounced in XTLE. These results were consistent for all other seizures during sleep, the mean spindle density decreased significantly in all focal (10.2 ± 1.9; p = 0.001) and generalized preictal period (8.8 ± 2.4; p = 0.001) compared to the mean interictal period (12.1 ± 2.1). These were also more significant in XTLE than TLE group.ConclusionsOur data demonstrate that the occurrence of seizures and propensity of seizure generalisation in focal epilepsy is modulated by specific characteristics of light sleep such as sleep spindles.SignificanceThis study supports the notion that changes in the epileptic network precede the seizure onset and have an influence on seizure generation and termination.     

Perception of seizure severity and bothersome in refractory focal epilepsy

IntroductionA better understanding of the perception of the severity and bothersome caused by seizure phases (warning, ictal, and postictal phases) can contribute to the orientation strategies for adult people with epilepsy (PWEs).ObjectiveTo assess the seizure severity and bothersome and relate them to the clinical aspects of epilepsy and quality of life (QoL).MethodsThe Seizure Severity Questionnaire (SSQ) was associated with clinical variables and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the QOLIE–31 of 98 PWEs, with a significance level of P < 0.05.ResultsMost patients reported that seizure warnings helped them prepare for the event, with the postictal phase was the most bother symptom. Higher scores on the SSQ were associated with movements in the ictal phase, a prolonged duration, and the presence of mental and physical effects in the postictal phase. No difference was found in the SSQ, according to the seizure type and frequency. There was an association between the NDDI-E > 15 and the SSQ. Higher scores on the SSQ were significantly related to an NDDI-E > 15 (P = 0.013), in the linear regression model. Seizure severity and bothersome compromise the perception of QoL.ConclusionThe SSQ was useful in the assessment of the perception of seizure severity in PWEs. The postictal phase was the most bothersome one. The perception of seizure severity is associated with the presence of depression. Seizure severity correlates inversely with QoL.     

Seizure remission and relapse in adults with intractable epilepsy: a cohort study

Purpose: To investigate the cumulative probabilities of ≥12 month seizure remission and seizure relapse following remission, and to test the associations of clinical characteristics with these two study end points in a prevalence cohort of intractable adult epilepsy patients during medical management.
Methods: A retrospective cohort study of intractable epilepsy patients seen in 2001 at a single center was conducted. Kaplan–Meier analysis was used to estimate the cumulative probabilities of seizure remission and subsequent seizure relapse. Cox proportional hazards models were used to estimate the association (1) between clinical factors and ≥12 month seizure remission and (2) between clinical factors and seizure relapse following remission.
Results: One hundred eighty-seven subjects met the eligibility criteria for intractable epilepsy. The estimate of probability of remission was about 4% per year. Seizure remission was temporary for some individuals, as 5 out of 20 subjects with remission ultimately relapsed. No clinical factors predicted the likelihood of achieving ≥12 month seizure remission or subsequent seizure relapse.
Discussion: Some people with intractable epilepsy achieve ≥12 month seizure remission during medical treatment. Remission, however, is only temporary for some individuals. We were unable to identify clear predictors for remission.