The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy

PubMed Central

Bouet, Romain; Delpuech, Claude; Ryvlin, Philippe; Isnard, Jean; Guenot, Marc; Bertrand, Olivier; Hammers, Alexander; Mauguière, François

2013-01-01

Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure

The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy.

PubMed

Jung, Julien; Bouet, Romain; Delpuech, Claude; Ryvlin, Philippe; Isnard, Jean; Guenot, Marc; Bertrand, Olivier; Hammers, Alexander; Mauguière, François

2013-10-01

Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure

Retention, dosing, tolerability and patient reported seizure outcome of Zonisamide as only add-on treatment under real-life conditions in adult patients with partial onset seizures: Results of the observational study ZOOM.

PubMed

Hamer, Hajo; Baulac, Michel; McMurray, Rob; Kockelmann, Edgar

2016-01-01

Zonisamide is licensed for adjunctive therapy for partial-onset seizures with or without secondary generalisation in patients 6 years and older and as monotherapy for the treatment of partial seizures in adult patients with newly diagnosed epilepsy, and shows a favourable pharmacokinetic profile with low interaction potential with other drugs. The aim of the present study was to gather real-life data on retention and modalities of zonisamide use when administered as only add-on treatment to a current AED monotherapy in adult patients with partial-onset seizures. This multicenter observational study was performed in 4 European countries and comprised three visits: baseline, and after 3 and 6 months. Data on patients' retention, reported efficacy, tolerability and safety, and quality of life was collected. Of 100 included patients, 93 could be evaluated. After 6 months, the retention rate of zonisamide add-on therapy was 82.8%. At this time, a reduction of seizure frequency of at least 50% was observed in 79.7% of patients, with 43.6% reporting seizure freedom over the last 3 months of the study period. Adverse events were reported by 19.4% of patients, with fatigue, agitation, dizziness, and headache being most frequent. Approximately 25% of patients were older than 60 years, many of whom suffered from late-onset epilepsy. Compared to younger patients, these patients showed considerable differences with regard to their antiepileptic drug regimen at baseline, and slightly higher responder and retention rates at 6 months. Despite limitations due to the non-interventional open-label design and the low sample size, the results show that zonisamide as only add-on therapy is well retained, indicating effectiveness in the majority of patients under real-life conditions. Copyright © 2015. Published by Elsevier Ltd.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

PubMed Central

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

2015-01-01

Objective The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70 – 110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. Approach We used 7 complex partial seizures recorded from 4 patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a directed transfer function measure. Main results We showed that a directed transfer function can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical seizure onset zone and the time from seizure onset, ictal propagation changed in directional characteristics over a 2 to 10 seconds time scale, with gross directionality limited to spatial dimensions of approximately 9mm2. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined seizure onset zone than inside. Significance This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices. PMID:26061006

Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial.

PubMed

Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício

2015-02-01

To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1-2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used. © 2014 The Authors. Epilepsia published by Wiley

The temporal relation between seizure onset and arousal-awakening in temporal lobe seizures.

PubMed

Gumusyayla, Sadiye; Erdal, Abidin; Tezer, F Irsel; Saygi, Serap

2016-07-01

Our main aim was to determine the time interval between the seizure onsets and arousal-awakening related to these seizures in patients with temporal lobe epilepsy (TLE) and to discuss the role of lateralization on arousal-awakening mechanisms. Thirty-three TLE patients who underwent video-EEG monitoring with simultaneous polysomnography (PSG) and had recorded nocturnal seizures were retrospectively examined. These TLE patients had 64 seizures during sleep. The onsets of seizures and arousal-awakening related to these seizures were marked according to clinical and electrophysiological features. The time interval between the seizure onset and arousal-awakening related to the seizure was compared in patients with right- or left-sided temporal lobe seizures. In our TLE patients nocturnal seizures mostly followed arousal-awakening (64%). The time interval between the seizure onset and arousal-awakening related to the seizure was significantly shorter in patients with left-sided temporal lobe seizures (p=0.01). Video-EEG monitoring and PSG with scalp electrodes in our TLE patients showed that nocturnal seizures mostly followed arousal-awakening, and it was more pronounced in those with left-sided seizures. Arousal-awakening might be a signal for subsequent seizures in patients with TLE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Photogenic partial seizures.

PubMed

Hennessy, M J; Binnie, C D

2000-01-01

To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

Localizing epileptic seizure onsets with Granger causality

NASA Astrophysics Data System (ADS)

Adhikari, Bhim M.; Epstein, Charles M.; Dhamala, Mukesh

2013-09-01

Accurate localization of the epileptic seizure onset zones (SOZs) is crucial for successful surgery, which usually depends on the information obtained from intracranial electroencephalography (IEEG) recordings. The visual criteria and univariate methods of analyzing IEEG recordings have not always produced clarity on the SOZs for resection and ultimate seizure freedom for patients. Here, to contribute to improving the localization of the SOZs and to understanding the mechanism of seizure propagation over the brain, we applied spectral interdependency methods to IEEG time series recorded from patients during seizures. We found that the high-frequency (>80 Hz) Granger causality (GC) occurs before the onset of any visible ictal activity and causal relationships involve the recording electrodes where clinically identifiable seizures later develop. These results suggest that high-frequency oscillatory network activities precede and underlie epileptic seizures, and that GC spectral measures derived from IEEG can assist in precise delineation of seizure onset times and SOZs.

Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial

PubMed Central

Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício

2015-01-01

Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Results Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Significance Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by

Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

PubMed Central

French, JA; Baroldi, P; Brittain, ST; Johnson, JK

2014-01-01

Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not

Heart rate changes in partial seizures: analysis of influencing factors among refractory patients

PubMed Central

2014-01-01

Background We analyzed the frequency of heart rate (HR) changes related to seizures, and we sought to identify the influencing factors of these changes during partial seizures, to summarize the regularity of the HR changes and gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. To date, detailed information on influencing factors of HR changes related to seizures by multiple linear regression analysis remains scarce. Methods Using video-electroencephalograph (EEG)-electrocardiograph (ECG) recordings, we retrospectively assessed the changes in the HR of 81 patients during a total of 181 seizures, including 27 simple partial seizures (SPS), 110 complex partial seizures (CPS) and 44 complex partial seizures secondarily generalized (CPS-G). The epileptogenic focus and the seizure type, age, gender, and sleep/wakefulness state of each patient were evaluated during and after the seizure onset. The HR changes were evaluated in the stage of epilepsy as time varies. Results Of the 181 seizures from 81 patients with ictal ECGs, 152 seizures (83.98%) from 74 patients were accompanied by ictal tachycardia (IT). And only 1 patient was accompanied by ictal bradycardia (IB). A patient has both IT and IB. We observed that HR difference was independently correlated with side, type and sleep/wakefulness state. In this analysis, the HR changes were related to the side, gender, seizure type, and sleep/wakefulness state. Right focus, male, sleep, and CPS-G showed more significant increases than that were observed in left, female, wakefulness, SPS and CPS. HR increases rapidly within 10 seconds before seizure onset and ictus, and typically slows to normal with seizure offset. Conclusion CPS-G, sleep and right focus led to higher ictal HR. The HR in the stage of epilepsy has regularly been observed to change to become time-varying. The risk factors of ictal HR need to be controlled along with sleep, CPS-G and right focus. Our study first

Earlier tachycardia onset in right than left mesial temporal lobe seizures.

PubMed

Kato, Kazuhiro; Jin, Kazutaka; Itabashi, Hisashi; Iwasaki, Masaki; Kakisaka, Yosuke; Aoki, Masashi; Nakasato, Nobukazu

2014-10-07

To clarify whether the presence and timing of peri-ictal heart rate (HR) change is a seizure lateralizing sign in patients with mesial temporal lobe epilepsy (mTLE). Long-term video EEGs were retrospectively reviewed in 21 patients, 7 men and 14 women aged 13 to 67 years, diagnosed as mTLE with MRI lesions in the mesial temporal structures (hippocampal sclerosis in 20 cases, amygdala hypertrophy in 1 case). Seventy-seven partial seizures without secondary generalization were extracted. Peri-ictal HR change was compared between 29 right seizures (9 patients) and 48 left seizures (12 patients). HR abruptly increased in all 29 right seizures and 42 of 48 left seizures. Onset time of HR increase in relation to ictal EEG onset was significantly earlier in right seizures than in left seizures (mean ± SD, -11.5 ± 14.8 vs 9.2 ± 21.7 seconds; p < 0.0001). Time of maximum HR was also significantly earlier in right seizures than in left seizures (36.0 ± 18.1 vs 58.0 ± 28.7 seconds; p < 0.0001). Maximum HR changes from baseline showed no significant difference between right and left seizures (47.5 ± 19.1 vs 40.8 ± 20.0/min). Significantly earlier tachycardia in right than left mTLE seizures supports previous hypotheses that the right cerebral hemisphere is dominant in the sympathetic network. No HR change, or delayed tachycardia possibly due to seizure propagation to the right hemisphere, may be a useful lateralizing sign of left mTLE seizures. © 2014 American Academy of Neurology.

Leaving tissue associated with infrequent intracranial EEG seizure onsets is compatible with post-operative seizure freedom

PubMed Central

Huang, Cyrus; Marsh, Eric D.; Ziskind, Daniela M.; Celix, Juanita M.; Peltzer, Bradley; Brown, Merritt W.; Storm, Phillip B.; Litt, Brian; Porter, Brenda E.

2013-01-01

Identify seizure onset electrodes that need to be resected for seizure freedom in children undergoing intracranial electroencephalography recording for treatment of medically refractory epilepsy. All children undergoing intracranial electroencephalography subdural grid electrode placement at the Children’s Hospital of Philadelphia from 2002-2008 were asked to enroll. We utilized intraoperative pictures to determine the location of the electrodes and define the resection cavity. A total of 15 patients had surgical fields that allowed for complete identification of the electrodes over the area of resection. Eight of 15 patients were seizure free after a follow up of 1.7 to 8 yr. Only one seizure-free patient had complete resection of all seizure onset associated tissue. Seizure free patients had resection of 64.1% of the seizure onset electrode associated tissue, compared to 35.2% in the not seizure free patients (p=0.05). Resection of tissue associated with infrequent seizure onsets did not appear to be important for seizure freedom. Resecting ≥ 90% of the electrodes from the predominant seizure contacts predicted post-operative seizure freedom (p=0.007). The best predictor of seizure freedom was resecting ≥ 90% of tissue involved in majority of a patient’s seizures. Resection of tissue under infrequent seizure onset electrodes was not necessary for seizure freedom. PMID:24563805

Mechanisms underlying different onset patterns of focal seizures

PubMed Central

Trevelyan, Andrew J; Valentin, Antonio; Alarcon, Gonzalo

2017-01-01

Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome. PMID:28472032

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

PubMed

Toledano, Rafael; Jovel, Camilo Espinosa; Jiménez-Huete, Adolfo; Bayarri, Pau Giner; Campos, Dulce; Gomariz, Elena López; Giráldez, Beatriz González; García-Morales, Irene; Falip, Mercé; Agredano, Paula Martínez; Palao, Susana; Prior, María José Aguilar Amat; Pascual, María Rosa Querol; Navacerrada, Francisco José; González, Francisco Javier López; Ojeda, Joaquín; Sáez, Aránzazu Alfaro; Bermejo, Pedro Emilio; Gil-Nagel, Antonio

2017-08-01

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Generalized onset seizures with focal evolution (GOFE) - A unique seizure type in the setting of generalized epilepsy.

PubMed

Linane, Avriel; Lagrange, Andre H; Fu, Cary; Abou-Khalil, Bassel

2016-01-01

We report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification. The adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology. Ten patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3-15years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with >50% reduction in seizure frequency. Generalized onset seizures may occasionally have focal evolution with semiology

Perampanel in the management of partial-onset seizures: a review of safety, efficacy, and patient acceptability

PubMed Central

Schulze-Bonhage, Andreas; Hintz, Mandy

2015-01-01

Perampanel (PER) is a novel antiepileptic drug recently introduced for the adjunctive treatment in epilepsy patients aged 12 years or older with partial-onset seizures with or without secondary generalization in the US and Europe. Its antiepileptic action is based on noncompetitive inhibition of postsynaptic AMPA receptors, decreasing excitatory synaptic transmission. Evaluation of efficacy in three placebo-controlled randomized Phase III studies showed that add-on therapy of PER decreased seizure frequencies significantly compared to placebo at daily doses between 4 mg/day and 12 mg/day. PER’s long half-life of 105 hours allows for once-daily dosing that is favorable for patient compliance with intake. Long-term extension studies showed a 62.5%–69.6% adherence of patients after 1 year of treatment, comparing favorably with other second-generation antiepileptic drugs. Whereas these trials demonstrated an overall favorable tolerability profile of PER, nonspecific central nervous system adverse effects like somnolence, dizziness, headache, and fatigue may occur. In addition, neuropsychiatric disturbances ranging from irritability to suicidality were reported in several case reports; both placebo-controlled and prospective long-term extension trials showed a low incidence of such behavioral and psychiatric complaints. For early recognition of neuropsychiatric symptoms like depression, anxiety, and aggression, slow titration and close monitoring during drug introduction are mandatory. This allows on the one hand to recognize patients particularly susceptible to adverse effects of the drug, and on the other hand to render the drug’s full potential of seizure control available for the vast majority of patient groups tolerating the drug well. PMID:26316718

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone.

PubMed

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J; Anderson, William S

2015-08-01

The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the [Formula: see text] Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately [Formula: see text]. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

Impaired consciousness in partial seizures is bimodally distributed.

PubMed

Cunningham, Courtney; Chen, William C; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T; Blumenfeld, Hal

2014-05-13

To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n = 552 test administrations, 184 patients). Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures.

Detection of recurrent activation patterns across focal seizures: Application to seizure onset zone identification.

PubMed

Vila-Vidal, Manel; Principe, Alessandro; Ley, Miguel; Deco, Gustavo; Tauste Campo, Adrià; Rocamora, Rodrigo

2017-06-01

We introduce a method that quantifies the consistent involvement of intracranially monitored regions in recurrent focal seizures. We evaluated the consistency of two ictal spectral activation patterns (mean power change and power change onset time) in intracranial recordings across focal seizures from seven patients with clinically marked seizure onset zone (SOZ). We examined SOZ discrimination using both patterns in different frequency bands and periods of interest. Activation patterns were proved to be consistent across more than 80% of recurrent ictal epochs. In all patients, whole-seizure mean activations were significantly higher for SOZ than non-SOZ regions (P<0.05) while activation onset times were significantly lower for SOZ than for non-SOZ regions (P<0.001) in six patients. Alpha-beta bands (8-20Hz) achieved the highest patient-average effect size on the whole-seizure period while gamma band (20-70Hz) achieved the highest discrimination values between SOZ and non-SOZ sites near seizure onset (0-5s). Consistent spectral activation patterns in focal epilepsies discriminate the SOZ with high effect sizes upon appropriate selection of frequency bands and activation periods. The present method may be used to improve epileptogenic identification as well as pinpoint additional regions that are functionally altered during ictal events. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models.

PubMed

Mahoney, Emily C; Zeng, Andrew; Yu, Wilson; Rowe, Mackenzie; Sahai, Siddhartha; Feustel, Paul J; Ramirez-Zamora, Adolfo; Pilitsis, Julie G; Shin, Damian S

2018-05-01

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit.

PubMed

Jenssen, Sigmund; Gracely, Edward J; Sperling, Michael R

2006-09-01

More information is needed regarding how long seizures typically last, since this influences treatment decisions. Seizure type and other factors could influence seizure duration. Data were collected from a random sample of patients being evaluated with continuous video and scalp EEG. Seizure duration was defined as time from early sign of seizure (clinical or EEG) until the end of seizure on EEG. Seizures were categorized as simple partial (SPS), complex partial (CPS), secondarily generalized tonic-clonic (SGTCS), primary generalized tonic-clonic (PGTCS) and tonic (TS). SGTCS were divided into a complex partial part (SGTCS/CP) and a tonic-clonic part (SGTCS/TC). Median and longest duration of each seizure type in each individual were used. Comparisons of seizure types, first and last seizure, area of onset, and state of onset were performed. Five hundred seventy-nine seizures were recorded in 159 adult patients. Seizures with partial onset spreading to both hemispheres had the longest duration. SGTCS were unlikely to last more than 660 s, CPS more than 600 s, and SPS more than 240 s. PGTCS and TS had shorter durations, but the number of subjects with those two types was small. CPS did not differ in duration according to sleep state at onset nor side of origin. A working definition of status epilepticus in adults with cryptogenic or symptomatic epilepsy can be drawn from these data for purposes of future epidemiologic research. More information is needed for the idiopathic epilepsies and in children.

Impaired consciousness in partial seizures is bimodally distributed

PubMed Central

Cunningham, Courtney; Chen, William C.; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P.; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T.

2014-01-01

Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale–Revised (n = 552 test administrations, 184 patients). Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures. PMID:24727311

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

NASA Astrophysics Data System (ADS)

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

2015-08-01

Objective. The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70-110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. Approach. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. Main results. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately 9 m{{m}2}. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. Significance. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

Detection of Epileptic Seizure Event and Onset Using EEG

PubMed Central

Ahammad, Nabeel; Fathima, Thasneem; Joseph, Paul

2014-01-01

This study proposes a method of automatic detection of epileptic seizure event and onset using wavelet based features and certain statistical features without wavelet decomposition. Normal and epileptic EEG signals were classified using linear classifier. For seizure event detection, Bonn University EEG database has been used. Three types of EEG signals (EEG signal recorded from healthy volunteer with eye open, epilepsy patients in the epileptogenic zone during a seizure-free interval, and epilepsy patients during epileptic seizures) were classified. Important features such as energy, entropy, standard deviation, maximum, minimum, and mean at different subbands were computed and classification was done using linear classifier. The performance of classifier was determined in terms of specificity, sensitivity, and accuracy. The overall accuracy was 84.2%. In the case of seizure onset detection, the database used is CHB-MIT scalp EEG database. Along with wavelet based features, interquartile range (IQR) and mean absolute deviation (MAD) without wavelet decomposition were extracted. Latency was used to study the performance of seizure onset detection. Classifier gave a sensitivity of 98.5% with an average latency of 1.76 seconds. PMID:24616892

Circulating neural antibodies in unselected children with new-onset seizures.

PubMed

Garcia-Tarodo, Stephanie; Datta, Alexandre N; Ramelli, Gian P; Maréchal-Rouiller, Fabienne; Bien, Christian G; Korff, Christian M

2018-05-01

The role of autoimmunity and neural antibodies is increasingly recognized in different forms of seizures and epilepsy. Their prevalence in new-onset epilepsy has also recently been the focus of several clinical cohorts in the adult and pediatric population, with positive titers in 10-11% of cases. Our aim was to determine the seropositivity at the first seizure onset in a non-selective group of children. We conducted a prospective multicenter cohort study recruiting children aged 0-16 years with new-onset seizures presenting at the In- and Outpatient Pediatric Neurology Departments of three Children's Hospitals in Switzerland between September 2013 and April 2016. Neural antibodies were screened within the first 6 months of a first seizure and when positive, repeated at 1 month and 6 months follow-up. A total of 103 children were enrolled with a mean age at presentation of 5 years (range 1 day-15 years 9 months). The majority (n = 75) presented with generalized seizures and 6 had status epilepticus lasting > 30 min. At the time of onset, 55% of patients had fever, 24% required emergency seizure treatment and 27% hospitalization. Epilepsy was diagnosed at follow-up in 18%. No specific antibody was found. Serum antibodies against the VGKC complex, without binding to the specific antigens LGI1 and CASPR2, were found in two patients. Four patients harbored not otherwise characterized antibodies against mouse neuropil. Specific neural antibodies are rarely found in an unselected population of children that present with a first seizure. Applying an extensive neuronal antibody profile in a child with new-onset seizures does not appear to be justified. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Juvenile and adult-onset psychogenic non-epileptic seizures.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad

2013-09-01

Psychogenic non-epileptic seizures (PNES) tend to begin in adolescence and young adulthood, although the seizures can occur in a wide range of ages. In the current study, we investigated the age of onset in patients with PNES and tried to determine the correlation between the age of onset and the demographic and clinical characteristics and factors potentially predisposing to PNES. In this cross-sectional study, all patients with a clinical diagnosis of PNES were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 to 2012. We dichotomized the patients into two groups; those with age of onset below 18 years (juvenile), and those with age of onset at 18-55 years (adult-onset). We studied the demographic and clinical characteristics and factors potentially predisposing to PNES between these two groups. Statistical analyses were performed using Chi square and Fisher's Exact tests and Mann-Whitney U test. Fifty-seven patients with juvenile and 129 people with adult-onset PNES were studied. Demographic characteristics of these two groups were not different significantly. Seizure characteristics and semiology in these two groups were not significantly different either. However, factors potentially predisposing to PNES were significantly different between these two groups. History of being abused, academic failure, epilepsy or family history of epilepsy were more frequently observed in juvenile PNES, while medical comorbidities were more frequent among patients with adult-onset PNES. Age of onset of PNES is not correlated with the clinical manifestations; however, factors potentially predisposing to PNES are significantly different in patients with juvenile compared to those with adult-onset PNES. Copyright © 2013 Elsevier B.V. All rights reserved.

Absence of simple partial seizure in temporal lobe epilepsy: its diagnostic and prognostic significance.

PubMed

Inoue, Y; Mihara, T; Matsuda, K; Tottori, T; Otsubo, T; Yagi, K

2000-02-01

The diagnostic and prognostic significance of the absence of simple partial seizures (SPS) immediately preceding complex partial seizures (CPS) was examined in patients with temporal lobe epilepsy. The status of self-reported SPS in 193 patients with temporal lobe epilepsy who had surgical therapy more than 2 years ago was reviewed. Before surgery, 37 patients never experienced SPS before CPS (Group A), 156 patients either always or occasionally had SPS before CPS (Group B). The frequency of mesial temporal sclerosis (MTS) was lower and the age at onset of epilepsy was higher in Group A. The seizure focus was in the language-dominant temporal lobe in 73% of the cases in Group A, compared with 40% in Group B. The surgical outcome did not differ between the two groups. The findings suggest that temporal lobe seizures without preceding SPS tend to originate in the language-dominant temporal lobe that contains a pathologic etiology other than MTS, especially in the lateral temporal lobe. The surgical outcome in patients without SPS is similar to that in patients with SPS.

Efficacy of Pregabalin in Childhood Refractory Partial Seizure

PubMed Central

Zamani, Gholamreza; Tavasoli, Alireza; Zare-Shahabadi, Ameneh; Rezaei, Nima; Ahmadvand, Alireza

2014-01-01

Objective: About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. Methods: In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Findings : Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. Conclusion: This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures. PMID:25793053

Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.

PubMed

Rudd, G D; Haverkamp, W; Mason, J W; Wenger, T; Jay, G; Hebert, D; Doty, P; Horstmann, R

2015-11-01

To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS). Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS. Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine. Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice.

PubMed

Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Afrin, Mst Rejina; Sreedhar, Remya; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nakamura, Takashi; Suzuki, Kenji; Nakamura, Masahiko; Ueno, Kazuyuki; Watanabe, Kenichi

2016-09-01

Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice. The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level. The time of first seizure onset in group 1 was 109.7±4.3min, group 2 was 46.50±3.9min and group 3 was 165.4±13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2. Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

PubMed Central

Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

2015-01-01

Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent

Neuropsychological status at seizure onset in children

PubMed Central

Fastenau, P S.; Johnson, C S.; Perkins, S M.; Byars, A W.; deGrauw, T J.; Austin, J K.; Dunn, D W.

2009-01-01

Objective: This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. Methods: We compared 282 children (ages 6–14 years, IQ ≥70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. Results: In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). Conclusions: A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition. GLOSSARY AED = antiepileptic drug; ANOVA = analysis of variance; CELF = Clinical Evaluation of Language Fundamentals; CI = confidence interval; CTOPP = Comprehensive Test of Phonological Processing; OR = odds ratio; PURS = prior unrecognized seizure; WCST = Wisconsin Card Sorting Test; WRAML = Wide Range Assessment of Memory and Learning

Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

PubMed

Simoens, Steven

2011-01-01

This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

Prediction of seizure-onset laterality by using Wada memory asymmetries in pediatric epilepsy surgery candidates.

PubMed

Lee, Gregory P; Park, Yong D; Hempel, Ann; Westerveld, Michael; Loring, David W

2002-09-01

Because the capacity of intracarotid amobarbital (Wada) memory assessment to predict seizure-onset laterality in children has not been thoroughly investigated, three comprehensive epilepsy surgery centers pooled their data and examined Wada memory asymmetries to predict side of seizure onset in children being considered for epilepsy surgery. One hundred fifty-two children with intractable epilepsy underwent Wada testing. Although the type and number of memory stimuli and methods varied at each institution, all children were presented with six to 10 items soon after amobarbital injection. After return to neurologic baseline, recognition memory for the stimuli was assessed. Seizure onset was determined by simultaneous video-EEG recordings of multiple seizures. In children with unilateral temporal lobe seizures (n = 87), Wada memory asymmetries accurately predicted seizure laterality to a statistically significant degree. Wada memory asymmetries also correctly predicted side of seizure onset in children with extra-temporal lobe seizures (n = 65). Although individual patient prediction accuracy was statistically significant in temporal lobe cases, onset laterality was incorrectly predicted in < or =52% of children with left temporal lobe seizure onset, depending on the methods and asymmetry criterion used. There also were significant differences between Wada prediction accuracy across the three epilepsy centers. Results suggest that Wada memory assessment is useful in predicting side of seizure onset in many children. However, Wada memory asymmetries should be interpreted more cautiously in children than in adults.

Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial.

PubMed

Zadeh, Wendy Waldman; Escartin, Antonio; Byrnes, William; Tennigkeit, Frank; Borghs, Simon; Li, Ting; Dedeken, Peter; De Backer, Marc

2015-09-01

To evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS). In this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400 mg/day) either as add-on to first AED monotherapy, or as later add-on to 1-3 concomitant AEDs after ≥ 2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24-week Maintenance Phase. 456 patients received ≥ 1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1 ± 16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment-emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks' treatment, respectively. 178/353 (50.4%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8 ± 14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%). Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Partial psychic seizures and brain organization.

PubMed

Ardila, A; Montañes, P; Bernal, B; Serpa, A; Ruiz, E

1986-08-01

This research was an attempt to determine the cerebral areas involved in focal epileptic seizures accompanied by psychic manifestations. Six types of partial seizures involving psychic symptomatology and phonatory seizures were included in the study. Sixty-one clinical records of focal epilepsy, which had been revealed by means of a CT-scan examination, were analyzed and a subsample of 25 patients with psychic symptoms was selected. The scans taken of the lesions were transferred to a six-level standard template built for this purpose. Subsequently, templates of patients with the same type of seizures were superimposed. The critical zones for the seven types of seizures studied are presented. A clear correlation was found between these results and our present knowledge of functional brain organization.

Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures.

PubMed

Villanueva, Vicente; Holtkamp, Martin; Delanty, Norman; Rodriguez-Uranga, Juan; McMurray, Rob; Santagueda, Patricia

2017-11-01

The Euro-Esli study was an exploratory pooled analysis of data from 14 European clinical practice studies, which was conducted to audit the real-world effectiveness, safety, and tolerability of eslicarbazepine acetate (ESL) as an adjunctive treatment for partial-onset seizures. Retention and effectiveness were assessed after 3, 6, and 12 months of ESL treatment, and at the final visit. Safety and tolerability were assessed throughout ESL treatment by evaluating adverse events (AEs) and ESL discontinuation due to AEs. Data from 2058 patients (52.1% male; mean age 44.0 years) were included. All 2058 patients were assessed for safety and 1975 (96.0%) patients were assessed for effectiveness. After 12 months, retention, responder (≥50% seizure frequency reduction), and seizure freedom rates were 73.4, 75.6, and 41.3%, respectively. AEs were reported for 34.0% of patients and led to discontinuation in 13.6% of patients. The most frequently reported AEs were dizziness (6.7% of patients), fatigue (5.4%), and somnolence (5.1%). No unexpected safety signals emerged over a median duration of follow-up of >5 years. Subgroup analyses revealed that ESL was significantly more effective in patients aged ≥65 versus <65 years, in patients who were not receiving treatment with other sodium channel blockers versus those who were receiving treatment with other sodium channel blockers, and in patients who were receiving <2 versus ≥2 concomitant antiepileptic drugs at baseline. Euro-Esli is the largest ESL clinical practice study conducted to date. This study provides strong and reassuring evidence of ESL's safety profile, and complements the data from clinical trials.

Intractable seizures after a lengthy remission in childhood-onset epilepsy.

PubMed

Camfield, Peter R; Camfield, Carol S

2017-12-01

To establish the risk of subsequent intractable epilepsy after ≥2, ≥5, and ≥10 years of remission in childhood-onset epilepsy. From the Nova Scotia childhood-onset epilepsy population-based cohort patients with all types of epilepsy were selected with ≥20 years follow-up from seizure onset (incidence cases). Children with childhood absence epilepsy were excluded. The rate of subsequent intractable epilepsy was then studied for patients with ≥5 years remission on or off AED treatment and compared with the rate for those with ≥2 and ≥10 years of remission. Three hundred eighty-eight eligible patients had ≥20 years follow-up (average 27.7 ± (standard deviation) 4 years) until they were an average of 34 ± 6.5 years of age. Overall, 297 (77%) had a period of ≥5 years of seizure freedom (average 21.2 ± 8 years), with 90% of these remissions continuing to the end of follow-up. Seizures recurred in 31 (10%) and were intractable in 7 (2%). For the 332 with a remission of ≥2 years seizure-free, 6.9% subsequently developed intractable epilepsy (p = 0.001). For the 260 with ≥10 years remission, 0.78% subsequently developed intractable epilepsy (p = 0.25 compared with ≥5 years remission). Even after ≥5 or ≥10 years of seizure freedom, childhood-onset epilepsy may reappear and be intractable. The risk is fortunately small, but for most patients it is not possible to guarantee a permanent remission. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Late onset seizures, hemiparesis and blindness in hemolytic uremic syndrome.

PubMed

Bennett, B; Booth, T; Quan, A

2003-03-01

Neurologic complications of hemolytic uremic syndrome, including seizures, usually occur early during the acute phase of the illness. We report a3-year-old girl with classic diarrhea-associated hemolytic uremic syndrome who developed late onset seizures, hemiparesis and transient blindness on the 17th hospital day, at which time her recovery was characterized by improvement in her blood pressure, serum electrolytes, renal function, hematocrit and platelet count. A CT and MR revealed brainstem and posterior parietal and occipital infarct/edema. The association of these radiologic findings within the posterior distribution along with visual loss and seizures are unique to posterior reversible encephalopathy syndrome. Within 7 days, she regained motor function and vision and had no further seizure activity. At 6 months follow-up, physical examination revealed normal motor function and vision and a repeat MR showed near resolution of the previous findings with minimal occipital lobe gliosis. This case report describes the uncommon finding of late onset seizures occurring during the recovery phase of hemolytic uremic syndrome with MR findings consistent with posterior reversible encephalopathy syndrome.

Seizure Clustering during Drug Treatment Affects Seizure Outcome and Mortality of Childhood-Onset Epilepsy

ERIC Educational Resources Information Center

Sillanpaa, Matti; Schmidt, Dieter

2008-01-01

To provide evidence of whether seizure clustering is associated with drug resistance and increased mortality in childhood-onset epilepsy, a prospective, long-term population-based study was performed. One hundred and twenty patients who had been followed since disease onset (average age 37.0 years, SD 7.1, median 40.0, range 11-42; incident cases)…

Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies

PubMed Central

Mameniškienė, Rūta; Quarato, Pier Paolo; Klein, Pavel; Gamage, Jessica; Schiemann, Jimmy; Johnson, Martin E.; Whitesides, John; McDonough, Belinda; Eckhardt, Klaus

2016-01-01

Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16–80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%–29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%–31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%–31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS. Classification of evidence: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures. PMID:27335114

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures.

PubMed

Steinhoff, Bernhard J; Eckhardt, Klaus; Doty, Pamela; De Backer, Marc; Brunnert, Marcus; Schulze-Bonhage, Andreas

2016-05-01

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were

Consciousness and epilepsy: why are complex-partial seizures complex?

PubMed Central

Englot, Dario J.; Blumenfeld, Hal

2010-01-01

Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral

Alterations in the contents of consciousness in partial epileptic seizures.

PubMed

Johanson, Mirja; Valli, Katja; Revonsuo, Antti; Chaplin, John E; Wedlund, Jan-Eric

2008-08-01

Epilepsy research suffers from a deficiency of systematic studies concerning the phenomenology of the contents of consciousness during seizures, partially because of the lack of suitable research methods. The Phenomenology of Consciousness Inventory (PCI), a standardized, valid, and reliable questionnaire, was used here to study which dimensions of the contents of consciousness are distorted during partial epileptic seizures compared with baseline. Further, the similarity of the altered pattern of subjective experiences across recurring seizures was also explored. Our results indicate that patients with epilepsy report alterations on most dimensions of the contents of consciousness in conjunction with seizures, but individual seizure experiences remain similar from one seizure to another. The PCI was found suitable for the assessment of subjective experiences during epileptic seizures and could be a valuable tool in providing new information about phenomenal consciousness in epilepsy in both the research and clinical settings.

Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

PubMed Central

de Curtis, Marco; Gnatkovsky, Vadym; Gotman, Jean; Köhling, Rüdiger; Lévesque, Maxime; Manseau, Frédéric; Shiri, Zahra; Williams, Sylvain

2016-01-01

Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80–200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250–500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF- or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well. PMID:27075542

Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

PubMed

Coppola, Giangennaro; Operto, Francesca Felicia; Auricchio, Gianfranca; D'Amico, Alessandra; Fortunato, Delia; Pascotto, Antonio

2007-06-01

A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring. Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].

Seizure-Onset Mapping Based on Time-Variant Multivariate Functional Connectivity Analysis of High-Dimensional Intracranial EEG: A Kalman Filter Approach.

PubMed

Lie, Octavian V; van Mierlo, Pieter

2017-01-01

The visual interpretation of intracranial EEG (iEEG) is the standard method used in complex epilepsy surgery cases to map the regions of seizure onset targeted for resection. Still, visual iEEG analysis is labor-intensive and biased due to interpreter dependency. Multivariate parametric functional connectivity measures using adaptive autoregressive (AR) modeling of the iEEG signals based on the Kalman filter algorithm have been used successfully to localize the electrographic seizure onsets. Due to their high computational cost, these methods have been applied to a limited number of iEEG time-series (<60). The aim of this study was to test two Kalman filter implementations, a well-known multivariate adaptive AR model (Arnold et al. 1998) and a simplified, computationally efficient derivation of it, for their potential application to connectivity analysis of high-dimensional (up to 192 channels) iEEG data. When used on simulated seizures together with a multivariate connectivity estimator, the partial directed coherence, the two AR models were compared for their ability to reconstitute the designed seizure signal connections from noisy data. Next, focal seizures from iEEG recordings (73-113 channels) in three patients rendered seizure-free after surgery were mapped with the outdegree, a graph-theory index of outward directed connectivity. Simulation results indicated high levels of mapping accuracy for the two models in the presence of low-to-moderate noise cross-correlation. Accordingly, both AR models correctly mapped the real seizure onset to the resection volume. This study supports the possibility of conducting fully data-driven multivariate connectivity estimations on high-dimensional iEEG datasets using the Kalman filter approach.

Management of focal-onset seizures: an update on drug treatment.

PubMed

Johannessen, Svein I; Ben-Menachem, Elinor

2006-01-01

Focal-onset seizures are manifestations of abnormal epileptic firing of brain cells in a localised area or areas of the brain. The diagnosis of focal-onset seizures initially entails an EEG, a detailed history from the patient and eyewitnesses, as well as computer tomographic or, preferably, magnetic resonance imaging scans. Video EEG to record ictal events may be necessary to establish the correct diagnosis. Focal seizures are classified according to the International Classification of Epileptic Seizures and International Classification of Epilepsies and Epilepsy Syndromes. It is important to try to decide how the seizure event fits into this system in order to successfully evaluate and optimise treatment, as well as to give detailed information to the patient about their seizures and prognosis. Once the decision to treat the seizures has been made, the physician must choose which medication is the most appropriate to begin with. Carbamazepine, phenytoin or valproic acid (sodium valproate) are often rated as first-line drugs, but factors such as adverse-effect profiles, age, possibility of pregnancy, and concomitant diseases and medication also need to be considered. Most of the newer antiepileptic drugs (AEDs) appear to have good efficacy and better tolerability than the older agents, but evidence to support their superiority is scarce and has led to conflicting advice in several guidelines. Among the newer AEDs, lamotrigine, gabapentin, topiramate and oxcarbazepine have obtained monotherapy indication in many countries. The higher costs of the newer AEDs may inhibit their wider use, especially in poorer countries.

Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy.

PubMed

Cilio, Maria Roberta; Bianchi, Roberto; Balestri, Martina; Onofri, Alfredo; Giovannini, Simona; Di Capua, Matteo; Vigevano, Federico

2009-09-01

To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI). IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months. EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up. MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

PubMed

Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

2014-12-01

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained. Copyright © 2014 Elsevier Inc. All rights reserved.

Angiogenic factors and pregnant woman with new onset seizures.

PubMed

Quant, Hayley; Arden, Deborah; Takoudes, Tamara; Rana, Sarosh

2012-01-01

In patients with new onset seizures during pregnancy, it can be challenging to differentiate between eclampsia and other etiologies. Soluble fms-like tyrosine kinase (sFlt1) is an antiangiogenic protein that is elevated in preeclampsia and eclampsia. A multiparous woman presented at 22 weeks gestation with seizures. The initial presentation was highly suspicious for eclampsia, but blood pressure and laboratory data were equivocal. Further investigation suggested primary seizure disorder. Serum sFlt1 was normal for gestational age, supporting the exclusion of eclampsia. History, physical exam, and traditional laboratory data are the mainstays of eclampsia diagnosis; however, sFlt1 may help clinicians when the diagnosis is uncertain at preterm gestational ages.

Seizure development after stroke.

PubMed

Misirli, H; Ozge, A; Somay, G; Erdoğan, N; Erkal, H; Erenoğlu, N Y

2006-12-01

Although there have been many studies on seizures following stroke, there is still much we do not know about them. In this study, we evaluated the characteristics of seizures in stroke patients. There were 2267 patients with a first-ever stroke, and after excluding 387 patients, 1880 were available for analysis. Of these 1880 patients, we evaluated 200 patients with seizures and 400 patients without seizures. We investigated the seizures according to age, gender, stroke type, the aetiology of ischaemic stroke and the localisation of the lesion. The seizures were classified as early onset and late onset and the seizure type as partial, generalised or secondarily generalised. Seizures occurred in 200 (10.6%) of 1880 strokes. The number of patients with seizures were 138 (10.6%) in ischaemic stroke group and 62 (10.7%) in haemorrhagic stroke group. Patients with ischaemic strokes had 41 embolic (29.7%) and 97 thrombotic (70.3%) origin, and these were not statistically significant in comparison with controls. Cortical involvement for the development of seizures was the most important risk factor (odds ratios = 4.25, p < 0.01). It was concluded that embolic strokes, being younger than 65 years old, and cortical localisation of stroke were important risks for developing seizures.

TEMPERAMENT, FAMILY ENVIRONMENT, AND BEHAVIOR PROBLEMS IN CHILDREN WITH NEW-ONSET SEIZURES

PubMed Central

Baum, Katherine T.; Byars, Anna W.; deGrauw, Ton J.; Johnson, Cynthia S.; Perkins, Susan M.; Dunn, David W.; Bates, John E.; Austin, Joan K.

2007-01-01

Children with epilepsy, even those with new-onset seizures, exhibit relatively high rates of behavior problems. The purpose of this study was to explore the relationships among early temperament, family adaptive resources, and behavior problems in children with new-onset seizures. Our major goal was to test whether family adaptive resources moderated the relationship between early temperament dimensions and current behavior problems in 287 children with new-onset seizures. Two of the three temperament dimensions (difficultness and resistance to control) were positively correlated with total, internalizing, and externalizing behavior problems (all p < 0.0001). The third temperament dimension, unadaptability, was positively correlated with total and internalizing problems (p < 0.01). Family adaptive resources moderated the relationships between temperament and internalizing and externalizing behavior problems at school. Children with a difficult early temperament who live in a family environment with low family mastery are at the greatest risk for behavior problems. PMID:17267291

Evolution of genuine cross-correlation strength of focal onset seizures.

PubMed

Müller, Markus F; Baier, Gerold; Jiménez, Yurytzy López; Marín García, Arlex O; Rummel, Christian; Schindler, Kaspar

2011-10-01

To quantify the evolution of genuine zero-lag cross-correlations of focal onset seizures, we apply a recently introduced multivariate measure to broad band and to narrow-band EEG data. For frequency components below 12.5 Hz, the strength of genuine cross-correlations decreases significantly during the seizure and the immediate postseizure period, while higher frequency bands show a tendency of elevated cross-correlations during the same period. We conclude that in terms of genuine zero-lag cross-correlations, the electrical brain activity as assessed by scalp electrodes shows a significant spatial fragmentation, which might promote seizure offset.

A prospective observational longitudinal study of new-onset seizures and newly diagnosed epilepsy in dogs.

PubMed

Fredsø, N; Toft, N; Sabers, A; Berendt, M

2017-02-16

Seizures are common in dogs and can be caused by non-epileptic conditions or epilepsy. The clinical course of newly diagnosed epilepsy is sparsely documented. The objective of this study was to prospectively investigate causes for seizures (epileptic and non-epileptic) in a cohort of dogs with new-onset untreated seizures, and for those dogs with newly diagnosed epilepsy to investigate epilepsy type, seizure type and the course of disease over time, including the risk of seizure recurrence. Untreated client-owned dogs experiencing new-onset seizures were prospectively enrolled in a longitudinal observational study including clinical investigations and long-term monitoring at the Copenhagen University Hospital for Companion Animals. A baseline clinical assessment was followed by investigator/owner contact every eight weeks from inclusion to death or end of study. Inclusion of dogs was conducted from November 2010 to September 2012, and the study terminated in June 2014. One hundred and six dogs were included in the study. Seventy-nine dogs (74.5%) were diagnosed with epilepsy: 61 dogs (77.2%) with idiopathic epilepsy, 13 dogs (16.5%) with structural epilepsy and five dogs (6.3%) with suspected structural epilepsy. A non-epileptic cause for seizures was identified in 13 dogs and suspected in 10 dogs. Four dogs in which no cause for seizures was identified experienced only one seizure during the study. In dogs with idiopathic epilepsy 60% had their second epileptic seizure within three months of seizure onset. Twenty-six dogs with idiopathic epilepsy (43%) completed the study without receiving antiepileptic treatment. The natural course of idiopathic epilepsy (uninfluenced by drugs) was illustrated by highly individual and fluctuating seizure patterns, including long periods of remission. Cluster seizures motivated early treatment. In a few dogs with a high seizure frequency owners declined treatment against the investigators advice. Epilepsy is the most likely

Genetics Home Reference: malignant migrating partial seizures of infancy

MedlinePlus

... of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures ... infantile epileptic encephalopathy 14 EIEE14 malignant migrating partial epilepsy of infancy migrating partial epilepsy of infancy migrating ...

Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes.

PubMed

Lagarde, Stanislas; Bonini, Francesca; McGonigal, Aileen; Chauvel, Patrick; Gavaret, Martine; Scavarda, Didier; Carron, Romain; Régis, Jean; Aubert, Sandrine; Villeneuve, Nathalie; Giusiano, Bernard; Figarella-Branger, Dominique; Trebuchon, Agnès; Bartolomei, Fabrice

2016-09-01

The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]). We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable. Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Epileptic seizure onset detection based on EEG and ECG data fusion.

PubMed

Qaraqe, Marwa; Ismail, Muhammad; Serpedin, Erchin; Zulfi, Haneef

2016-05-01

This paper presents a novel method for seizure onset detection using fused information extracted from multichannel electroencephalogram (EEG) and single-channel electrocardiogram (ECG). In existing seizure detectors, the analysis of the nonlinear and nonstationary ECG signal is limited to the time-domain or frequency-domain. In this work, heart rate variability (HRV) extracted from ECG is analyzed using a Matching-Pursuit (MP) and Wigner-Ville Distribution (WVD) algorithm in order to effectively extract meaningful HRV features representative of seizure and nonseizure states. The EEG analysis relies on a common spatial pattern (CSP) based feature enhancement stage that enables better discrimination between seizure and nonseizure features. The EEG-based detector uses logical operators to pool SVM seizure onset detections made independently across different EEG spectral bands. Two fusion systems are adopted. In the first system, EEG-based and ECG-based decisions are directly fused to obtain a final decision. The second fusion system adopts an override option that allows for the EEG-based decision to override the fusion-based decision in the event that the detector observes a string of EEG-based seizure decisions. The proposed detectors exhibit an improved performance, with respect to sensitivity and detection latency, compared with the state-of-the-art detectors. Experimental results demonstrate that the second detector achieves a sensitivity of 100%, detection latency of 2.6s, and a specificity of 99.91% for the MAJ fusion case. Copyright © 2016 Elsevier Inc. All rights reserved.

A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats--implications for treating complex partial seizures.

PubMed

Taha, Ameer Y; Trepanier, Marc-Olivier; Ciobanu, Flaviu A; Taha, Nadeen M; Ahmed, Muaz; Zeng, Qiudi; Cheuk, Waiyin I; Ip, Bryan; Filo, Elvis; Scott, Brian W; Burnham, W M; Bazinet, Richard P

2013-04-01

Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure.

PubMed

Sun, Jijun; Cheng, Weidong; Liu, Lifeng; Tao, Shuxin; Xia, Zhangyong; Qi, Lifeng; Huang, Min

2016-12-01

MicroRNAs (miRNAs) function as potential novel biomarkers for disease detection due to their marked stability in the blood and the characteristics of their expression profile in several diseases. In the present study, microarray‑based serum miRNA profiling was performed on serum obtained from three patients with epilepsy at diagnosis and from three healthy individuals as controls. This was followed by reverse transcription‑quantitative polymerase chain reaction analysis in a separate cohort of 35 health volunteers and 90 patients with epilepsy. The correlations between miRNAs and clinical parameters were analyzed. The array results showed that 15 miRNAs were overexpressed and 10 miRNAs were underexpressed (>2‑fold) in the patients with epilepsy. In addition, four miRNAs, including miR‑30a, miR‑378, miR‑106b and miR‑15a were found to be overexpressed in the serum of patients at seizure onset, compared with post‑seizure. When the patients were at seizure onset, the expression of miR‑30a was positively associated with seizure frequency. No significant differences were found between miR‑30a and gender, age or number of years following diagnosis. The expression levels of miR‑378, miR‑106b and mir‑15a were not associated with the clinical parameters in the patients with seizures. Calcium/calmodulin‑dependent protein kinase type IV was a target of miR‑30a, and its expression was increased following seizure and was negatively correlated with miR‑30a in the patients with epilepsy. The present study provided the first evidence, to the best of our knowledge, that the expression levels of miR‑378, miR‑30a, miR‑106b and miR‑15a were enhanced in epileptic patients with seizures. miR-30a may be useful for prognostic prediction in epilepsy.

Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.

PubMed

Biton, Victor; Gil-Nagel, Antonio; Brodie, Martin J; Derossett, Sarah E; Nohria, Virinder

2013-11-01

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG. Copyright © 2013 Elsevier B.V. All rights reserved.

Cerebral blood flow during paroxysmal EEG activation induced by sleep in patients with complex partial seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gozukirmizi, E.; Meyer, J.S.; Okabe, T.

1982-01-01

Cerebral blood flow (CBF) measurements were combined with sleep polysomnography in nine patients with complex partial seizures. Two methods were used: the 133Xe method for measuring regional (rCBF) and the stable xenon CT method for local (LCBF). Compared to nonepileptic subjects, who show diffuse CBF decreases during stages I-II, non-REM sleep onset, patients with complex partial seizures show statistically significant increases in CBF which are maximal in regions where the EEG focus is localized and are predominantly seen in one temporal region but are also propagated to other cerebral areas. Both CBF methods gave comparable results, but greater statistical significancemore » was achieved by stable xenon CT methodology. CBF increases are more diffuse than predicted by EEG paroxysmal activity recorded from scalp electrodes. An advantage of the 133Xe inhalation method was achievement of reliable data despite movement of the head. This was attributed to the use of a helmet which maintained the probes approximated to the scalp. Disadvantages were poor resolution (7 cm3) and two-dimensional information. The advantage of stable xenon CT method is excellent resolution (80 mm3) in three dimensions, but a disadvantage is that movement of the head in patients with seizure disorders may limit satisfactory measurements.« less

The ROME (Retrospective Observational Multicenter study on Eslicarbazepine) study: Efficacy and behavioural effects of Eslicarbazepine acetate as adjunctive therapy for adults with partial onset seizures in real life.

PubMed

Assenza, G; Mecarelli, O; Lanzone, J; Assenza, F; Tombini, M; Di Lazzaro, V; Pulitano, P

2018-05-01

Eslicarbazepine acetate (ESL) is a third-generation member of the dibenzazepine family approved in 2009 by the European Medicines Agency with the indication of adjunctive therapy in adult people with partial-onset seizures (PPOS). We aimed at assessing the ESL impact on seizure frequency and quality of life in PPOS with a particular attention to sleepiness and depression. We evaluated 50 adult PPOS (>18 years; 48 ± 14 years-old; 23 males) treated with adjunctive ESL for ≥2months with a retrospective multi-centric design. Clinical files of the last 2 years were reviewed checking for monthly seizure frequency, treatment retention rate, adverse drug reactions (ADRs), concomitant anti-epileptic drugs and behavioural scales for sleepiness (Stanford Sleepiness Scale, SSS, and Epworth Sleepiness Scale, ESS), depression (Beck Depression Inventory-II, BDI) and overall quality of life (QOLIE-31). At the end of 96 ± 28 days of ESL treatment, the mean seizure reduction was 56%; 60% of patients had seizure reduction above 50%, with a 31% of the whole population becoming seizure free. We reported 16 ADRs with 4 hyponatremia. Retention rate was 76%. Patient reported less sleepiness after ESL (SSS, p = 0.031; ESS, p = 0.0000002). Before ESL, 38% of patients had pathologic BDI scores, which normalized in most of them (73%) after ESL (BDI improvement, p = 0.000012). These scores resulted in an amelioration of quality of life (QOLIE-31, p = 0.000002). ESL is a safe and effective anti-epileptic drug in a real life scenario, with an excellent behavioural profile for the overall quality of life and, in particular, for sleepiness and depression. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Controlling Seizures

ERIC Educational Resources Information Center

Henderson, Nancy

2008-01-01

This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…

Towards prognostic biomarkers from BOLD fluctuations to differentiate a first epileptic seizure from new-onset epilepsy.

PubMed

Gupta, Lalit; Janssens, Rick; Vlooswijk, Mariëlle C G; Rouhl, Rob P W; de Louw, Anton; Aldenkamp, Albert P; Ulman, Shrutin; Besseling, René M H; Hofman, Paul A M; van Kranen-Mastenbroek, Vivianne H; Hilkman, Danny M; Jansen, Jacobus F A; Backes, Walter H

2017-03-01

The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure. We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs). We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences. The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

PubMed

Runge, Uwe; Arnold, Stephan; Brandt, Christian; Reinhardt, Fritjof; Kühn, Frank; Isensee, Kathleen; Ramirez, Francisco; Dedeken, Peter; Lauterbach, Thomas; Noack-Rink, Matthias; Mayer, Thomas

2015-12-01

Evidence for the efficacy and safety of adjunctive lacosamide in the treatment of partial-onset seizures (POS) was gained during placebo-controlled clinical trials in patients with treatment-resistant seizures who were taking one to three concomitant antiepileptic drugs (AEDs). The VITOBA study (NCT01098162) evaluated the effectiveness and tolerability of adjunctive lacosamide added to one baseline AED in real-world clinical practice. We conducted a 6-month observational study at 112 sites across Germany. Adult patients (≥ 16 years) with POS received lacosamide adjunctive to only one baseline AED. Seizure frequency reduction at the end of the observation period was compared with a 3-month retrospective baseline period. Five hundred seventy-one patients received lacosamide at least once (Safety Set [SS]); 520 provided evaluable seizure records (Full Analysis Set [FAS]); and 499 took in-label dosages of lacosamide (up to 400 mg) and were evaluated for effectiveness (modified FAS). Median baseline seizure frequency was 2.0 per 28 days: 47.1% of patients (235/499, mFAS) took a concomitant sodium channel-blocking (SCB) AED; 38.1% (190/499) had only one lifetime AED; and 18.4% (92/499) were aged ≥ 65 years (mFAS). At the final visit, 72.5% (358/494) of patients showed a ≥ 50% reduction in seizure frequency from baseline, 63.8% (315/494) showed a ≥ 75% reduction, and 45.5% (225/494) were seizure-free. Seizure freedom rates were higher in patients aged ≥ 65 years (56.7%) compared with patients aged <65 years (43.1%), in patients with ≤ 5 years epilepsy duration (52.5%) versus >5 years duration (41.0%), and when added to first monotherapy (60.5%) rather than as a later therapy option. Treatment-emergent adverse events (TEAEs) were reported by 48.5% (277/571) of patients (SS), with a profile similar to that observed in pivotal trials; 466 of patients (81.6%, SS) continued lacosamide therapy after the trial. These results suggest that lacosamide use, added to one

Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures

PubMed Central

Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10–30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca2+ channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%–11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical

Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures.

PubMed

Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10-30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical

Prediction of secondary generalization from a focal onset seizure in intracerebral EEG.

PubMed

Karthick, P A; Tanaka, Hideaki; Khoo, Hui Ming; Gotman, Jean

2018-05-01

We propose a system based on the first five seconds of intracerebrally recorded focal seizures to predict their evolution from focal to bilateral tonic-clonic seizure (FTC), to spread outside the onset zone but without tonic-clonic component (FS), or to a seizure remaining focal (F). Nineteen time and frequency domain features were extracted from 39 seizures of 32 patients and were subjected to support vector machine based classification. Three prediction approaches regarding seizure evolution were (1) FTC vs FS vs F, (2) FTC vs FS or F and (3) FTC or FS vs F. We used 21 seizures for training. Most features had significantly different distributions in the three seizure types (p < 0.05). Eighteen seizures were used for testing. We predicted the evolution of 12 seizures in FTC vs FS vs F, 13 seizures in FTC vs FS or F and 14 seizures in FTC or FS vs F. The first five seconds of a focal seizure contains information regarding the eventual evolution of the seizure, which could be predicted in most seizures. The proposed system could alert the health care team when a patient is hospitalized for intracerebral EEG and improve safety and eventually result in an implantable device. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Long-term add-on pregabalin treatment in patients with partial-onset epilepsy: pooled analysis of open-label clinical trials.

PubMed

Uthman, Basim M; Bazil, Carl W; Beydoun, Ahmad; Schulze-Bonhage, Andreas; Benabou, Reina; Whalen, Ed; Emir, Birol; Griesing, Teresa; Leon, Teresa

2010-06-01

To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59% completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was >or=300 mg/day; over half took >or=450 mg/day. There was a mean reduction in the 28-day seizure rate of 25-40%, and more than 40% of all patients had a >or=50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6% were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up.

Brivaracetam: a novel antiepileptic drug for focal-onset seizures.

PubMed

Stephen, Linda J; Brodie, Martin J

2018-01-01

Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy.

PubMed

Liu, Su; Gurses, Candan; Sha, Zhiyi; Quach, Michael M; Sencer, Altay; Bebek, Nerses; Curry, Daniel J; Prabhu, Sujit; Tummala, Sudhakar; Henry, Thomas R; Ince, Nuri F

2018-01-30

High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001. © The Author(s) (2018). Published by Oxford University Press on

Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study.

PubMed

Jacobson, Mercedes P; Pazdera, Ladislav; Bhatia, Perminder; Grinnell, Todd; Cheng, Hailong; Blum, David

2015-03-28

Eslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). It is extensively converted after oral administration to eslicarbazepine, and is believed to exert its effect through inhibition of voltage-gated sodium channels. The possible role of ESL as monotherapy to treat POS has not yet been established. This study was an 18-week, multicenter, randomized double-blind trial of gradual conversion to ESL monotherapy in adults with POS not well controlled by 1-2 antiepileptic drugs (AEDs), using historical data as the control. The study comprised an 8-week baseline period, a 2-week titration period, a 6-week AED conversion period, a 10-week monotherapy period, and either a 1-week taper period or optional entry to an open-label extension study. The primary endpoint compared the Kaplan-Meier (KM)-estimated 112-day exit rate with a threshold value calculated from the historical controls. There were 172 randomized patients; 154 (90%) entered the AED conversion period and 121 (70%) completed the study. The KM-estimated exit rates [confidence interval (CI)] were 15.6% [8.1-28.7%] for ESL 1200 mg, and 12.8% [7.5-21.5%] for ESL 1600 mg. The upper limits of the 95% CI KM-estimates were below the pre-specified threshold for historical control of 65.3%, indicating that ESL was efficacious in reducing seizure-related exits, compared with historical control. During the 18-week double-blind treatment period, median reductions in standardized seizure frequency occurred with ESL 1200 mg (36.1%) and ESL 1600 mg (47.5%). The responder rates (a 50% or greater reduction in seizure frequency from baseline) during the 18-week double-blind period and the monotherapy period, respectively, were 35.2% and 38.9% for ESL 1200 mg, and 46.0% and 46.0% for ESL 1600 mg. The overall adverse event profile was consistent with the known safety profile of ESL. These findings indicate that ESL monotherapy (1200 and

Epileptic seizures in Neuro-Behcet disease: why some patients develop seizure and others not?

PubMed

Kutlu, Gulnihal; Semercioglu, Sencer; Ucler, Serap; Erdal, Abidin; Inan, Levent E

2015-03-01

Behcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. All files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. The mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. CVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Psychosocial functioning in adolescents with complex partial seizures.

PubMed

Elliott, I

1992-03-01

This pilot study examined psychosocial functioning in adolescents (age 12.5-18.5 years) with complex partial seizures. Twenty-five subjects were divided into three groups: Group I (N = 11), medically treated with uncontrolled seizures; Group II (N = 6), medically managed with controlled seizures; and Group III (N = 8), epilepsy refractory to medical management with seizure control following surgery. Psychosocial functioning was measured using the "Adolescent Psychosocial Inventory" of Batzel and Dodrill. Findings revealed significant differences (F 4.80. p less than 0.02) in psychosocial functioning between the three groups. Group I showed the poorest overall adjustment; Group II, the best adjustment; Group III was better adjusted than Group I, but less than Group II. Significant difficulties were evident in the areas of school, interpersonal, emotional, seizure adjustment and overall psychosocial functioning in Group III. No problems were evident in Group II. School, emotional and overall adjustment were moderately problematic in Group III. Analysis of biological and demographic data revealed a significant association between increased numbers of medications and poorer psychosocial functioning (r = 58, p less than 0.02). The study results provide direction for clinic and community nurse specialists to set priorities with regard to assessment and supportive interventions.

Apparent complex partial seizures in a bipolar patient after withdrawal of carbamazepine.

PubMed

Garbutt, J C; Gillette, G M

1988-10-01

A 64-year-old woman with long-standing bipolar illness was treated with carbamazepine and clonazepam with minimal success. Discontinuation of carbamazepine and clonazepam was followed by episodic amnesia, purposeless behavior, déjà vu, and confusion. Although her EEG was normal, the episodes were compatible with complex partial seizures and ceased after carbamazepine and clonazepam were reinstituted. This case raises the question of whether discontinuing carbamazepine and clonazepam can induce complex partial seizures in bipolar patients.

Safety assessment for the postictal confusional phase following complex partial seizure.

PubMed

Tucker, C

1985-06-01

Misunderstanding of the postictal confusional state that follows the complex partial seizure has caused emotional and physical harm to patients. Concern about this phenomenon and its effects upon the patient prompted this study to explore, describe, and document one method of intervention to lessen these harmful effects. An evaluative descriptive research design was employed to assess patient safety during and after the postictal confusional phase following a complex partial seizure. A closed-structured questionnaire and participant observation were the methods used to collect data for this study. A Level of Safety Tool was specifically designed for this study.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

PubMed

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of

Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America.

PubMed

Sperling, Michael R; Harvey, Jay; Grinnell, Todd; Cheng, Hailong; Blum, David

2015-04-01

To assess the efficacy and safety of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial-onset seizures (POS). This multicenter, randomized, double-blind "withdrawal to monotherapy" study used historical control data as the comparator. Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy. Following an 8-week baseline period, patients were randomized 2:1 to receive ESL 1,600 mg (n = 128) or 1,200 mg QD (n = 65) for 18 weeks. The primary end point was the proportion of patients meeting predefined exit criteria (signifying worsening seizure control). Treatment was considered effective if the 95% upper confidence limit (UCL) for the Kaplan-Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control (65.3%). Kaplan-Meier estimated exit rates were: ESL 1,600 mg, 28.7% (95% CI 21.2-38.1%) and 1,200 mg, 44.4% (32.5-58.3%). The difference between doses was not significant (p = 0.07). For both doses, the 95% UCLs for the exit rate were ˂ 65.3%; ESL monotherapy was considered superior to the historical control. There was no statistically significant increase in the risk of study exit related to carbamazepine use. Nine (7.6%) and five patients (8.3%) remained seizure-free during the 10-week monotherapy period, while taking ESL 1,600 and 1,200 mg, respectively. The reductions in median standardized seizure frequency (seizures per 28 days) between baseline and the 18-week treatment period were: ESL 1,600 mg, 42% and 1,200 mg, 31%. Treatment-emergent adverse events (TEAEs) occurring in ≥ 10% of patients were dizziness, headache, fatigue, somnolence, nausea, and nasopharyngitis. The TEAE most frequently leading to discontinuation was hyponatremia (2.1%). ESL was efficacious and well tolerated as monotherapy in North American patients, and led to a reduction in seizure frequency. Exit rates for ESL 1,600 and 1,200 mg QD were superior to the

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study.

PubMed

Van Paesschen, W; King, M D; Duncan, J S; Connelly, A

2001-07-01

To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe

Daytime encopresis associated with gland mal epileptic seizures: case report.

PubMed

Oyatsi, D P

2005-08-01

Sphincteric incontinence of stool and urine are not unusual features of generalised epileptic seizures. Isolated secondary encopresis as a manifestation of an epileptic seizure is unusual. This report is of, a four year old boy, with daytime secondary non-retentive encopresis. The onset of encopresis was preceded by several episodes of nocturnal generalised tonic clonic epileptic seizures. An electroencephalogram showed features consistent with complex partial seizures. He was commenced on anti-epileptic treatment with phenytoin sodium, and by the third day of treatment, the patient had achieved stool control.

Emergency centre investigation of first-onset seizures in adults in the Western Cape, South Africa.

PubMed

Smith, A B; Van Hoving, D J; Wallis, L A

2013-08-21

Patients with first-onset seizures commonly present to emergency centres (ECs). The differential diagnosis is broad, potentially life-threatening conditions need to be excluded, and these patients need to be correctly diagnosed and appropriately referred. There are currently no data on adults presenting with first-onset seizures to ECs in South Africa. To review which investigations were performed on adults presenting with first-onset seizures to six ECs in the Western Cape Province. A prospective, cross-sectional study was conducted from 1 July 2011 to 31 December 2011. All adults with first-onset seizures were included; children and trauma patients were excluded. Subgroup analyses were conducted regarding HIV status and inter-facility variation. A total of 309 patients were included. Computed tomography (CT) scans were planned in 218 (70.6%) patients, but only performed in 169; 96 (56.8%) showed abnormalities judged to be causative (infarction, intracerebral haemorrhage and atrophy being the most common). At least 80% of patients (n=247) received a full renal and electrolyte screen, blood glucose testing and a full haematological screen. Lumbar puncture (LP) was performed in 67 (21.7%) patients, with normal cerebrospinal fluid findings in 51 (76.1%). Only 27 (8%) patients had an electroencephalogram, of which 5 (18%) were abnormal. There was a statistically significant difference in the number of CT scans (p=0.002) and LPs (p<0.001) performed in the HIV-positive group (n=49). This study demonstrated inconsistency and wide local variance for all types of investigations done. It emphasises the need for a local guideline to direct doctors to appropriate investigations, ensuring better quality patient care and potential cost-saving.

Lacosamide: A Review in Focal-Onset Seizures in Patients with Epilepsy.

PubMed

Hoy, Sheridan M

2018-05-01

Lacosamide (Vimpat ® ) is a functionalized amino acid (available orally and intravenously) approved in the EU and the USA for use as monotherapy and adjunctive therapy for the treatment of focal-onset seizures in adults, adolescents and children aged ≥ 4 years with epilepsy. In adults and adolescents (aged ≥ 16 years), oral lacosamide as adjunctive therapy to other antiepileptic drugs was generally effective in reducing seizure frequency during short-term (up to 18 weeks) treatment, with efficacy sustained over the longer-term (up to 8 years). Moreover, patients were effectively switched from adjunctive oral lacosamide to the same dosage of intravenous lacosamide. Oral lacosamide was an effective conversion to monotherapy agent in this patient population and as monotherapy demonstrated noninferiority to carbamazepine controlled release in terms of seizure freedom. Antiepileptic benefits were maintained during longer-term (≤ 2 years) monotherapy. The antiepileptic efficacy of lacosamide in children aged ≥ 4 years has been extrapolated from data from adults and adolescents, with a similar response expected provided paediatric dosage adaptations are used and safety is demonstrated. Indeed, preliminary data demonstrated the efficacy of short-term (16 weeks) adjunctive lacosamide in patients aged ≥ 4 to < 17 years. Oral lacosamide was generally well tolerated over the short- and longer-term when administered as adjunctive therapy, a conversion to monotherapy agent and monotherapy in adults and adolescents and when administered as adjunctive therapy in children aged ≥ 4 years. Thus, lacosamide is a useful option for the management of focal-onset seizures across a broad age range, starting as early as 4 years of age.

Interictal EEG spikes identify the region of seizure onset in some, but not all pediatric epilepsy patients

PubMed Central

Marsh, Eric D.; Peltzer, Bradley; Brown, Merritt W.; Wusthoff, Courtney; Storm, Phillip B.; Litt, Brian; Porter, Brenda E.

2010-01-01

Purpose The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial EEG (IEEG). While ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure onset location, though these studies were based upon relatively short EEG epochs. Methods We employ a previously validated, computerized spike detector, to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extra temporal lobe epilepsy. Approximately 8 hours of IEEG, randomly selected thirty-minute segments of continuous interictal IEEG per patient were analyzed over all intracranial electrode contacts. Results When spike frequency was averaged over the 16-time segments, electrodes with the highest mean spike frequency were found to be within the seizure onset region in 11 of 19 patients. There was significant variability between individual 30-minute segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure onset region. Conclusions Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori. PMID:19780794

Interictal EEG spikes identify the region of electrographic seizure onset in some, but not all, pediatric epilepsy patients.

PubMed

Marsh, Eric D; Peltzer, Bradley; Brown, Merritt W; Wusthoff, Courtney; Storm, Phillip B; Litt, Brian; Porter, Brenda E

2010-04-01

The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial electroencephalography (IEEG). Although ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure-onset location, although these studies were based upon relatively short EEG epochs. We employ a previously validated, computerized spike detector to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extratemporal lobe epilepsy. Approximately 8 h of IEEG, randomly selected 30-min segments of continuous interictal IEEG per patient, were analyzed over all intracranial electrode contacts. When spike frequency was averaged over the 16-time segments, electrodes with the highest mean spike frequency were found to be within the seizure-onset region in 11 of 19 patients. There was significant variability between individual 30-min segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low-voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure-onset region. Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori.

Academic problems in children with seizures: relationships with neuropsychological functioning and family variables during the 3 years after onset.

PubMed

Dunn, David W; Johnson, C S; Perkins, S M; Fastenau, P S; Byars, A W; deGrauw, T J; Austin, J K

2010-11-01

Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6-14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock-Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement (r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement (P ≤ 0.006), with stronger relationships among younger children (β = 0.25-0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety (P = 0.04; stronger for more anxious parents, β = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology

Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study

PubMed Central

Jung, Keun-Hwa; Sunwoo, Jun-Sang; Moon, Jangsup; Lim, Jung-Ah; Lee, Doo Young; Shin, Yong-Won; Kim, Tae-Joon; Lee, Keon-Joo; Lee, Woo-Jin; Lee, Han-Sang; Jun, Jinsun; Kim, Dong-Yub; Kim, Man-Young; Kim, Hyunjin; Kim, Hyeon Jin; Suh, Hong Il; Lee, Yoojin; Kim, Dong Wook; Jeong, Jin Ho; Choi, Woo Chan; Bae, Dae Woong; Shin, Jung-Won; Jeon, Daejong; Park, Kyung-Il; Jung, Ki-Young; Chu, Kon; Lee, Sang Kun

2016-01-01

Objective To evaluate the seizure characteristics and outcome after immunotherapy in adult patients with autoimmune encephalitis (AE) and new-onset seizure. Methods Adult (age ≥18 years) patients with AE and new-onset seizure who underwent immunotherapy and were followed-up for at least 6 months were included. Seizure frequency was evaluated at 2–4 weeks and 6 months after the onset of the initial immunotherapy and was categorized as “seizure remission”, “> 50% seizure reduction”, or “no change” based on the degree of its decrease. Results Forty-one AE patients who presented with new-onset seizure were analysed. At 2–4 weeks after the initial immunotherapy, 51.2% of the patients were seizure free, and 24.4% had significant seizure reduction. At 6 months, seizure remission was observed in 73.2% of the patients, although four patients died during hospitalization. Rituximab was used as a second-line immunotherapy in 12 patients who continued to have seizures despite the initial immunotherapy, and additional seizure remission was achieved in 66.6% of them. In particular, those who exhibited partial response to the initial immunotherapy had a better seizure outcome after rituximab, with low adverse events. Conclusion AE frequently presented as seizure, but only 18.9% of the living patients suffered from seizure at 6 months after immunotherapy. Aggressive immunotherapy can improve seizure outcome in patients with AE. PMID:26771547

High doses of pseudoephedrine hydrochloride accelerate onset of CNS oxygen toxicity seizures in unanesthetized rats.

PubMed

Pilla, R; Held, H E; Landon, C S; Dean, J B

2013-08-29

Pseudoephedrine (PSE) salts (hydrochloride and sulfate) are commonly used as nasal and paranasal decongestants by scuba divers. Anecdotal reports from the Divers Alert Network suggest that taking PSE prior to diving while breathing pure O₂ increases the risk for CNS oxygen toxicity (CNS-OT), which manifests as seizures. We hypothesized that high doses of PSE reduce the latency time to seizure (LS) in unanesthetized rats breathing 5 atmospheres absolute (ATA) of hyperbaric oxygen. Sixty-three male rats were implanted with radio-transmitters that recorded electroencephalogram activity and body temperature. After ≥7-day recovery, and 2 h before "diving", each rat was administered either saline solution (control) or PSE hydrochloride intragastrically at the following doses (mg PSE/kg): 0, 40, 80, 100, 120, 160, and 320. Rats breathed pure O₂ and were dived to 5ATA until the onset of behavioral seizures coincident with neurological seizures. LS was the time elapsed between reaching 5ATA and exhibiting seizures. We observed a significant dose-dependent decrease in the LS at doses of 100-320 mg/kg, whereas no significant differences in LS from control value were observed at doses ≤80 mg/kg. Our findings showed that high doses of PSE accelerate the onset of CNS-OT seizures in unanesthetized rats breathing 5ATA of poikilocapnic hyperoxia. Extrapolating our findings to humans, we conclude that the recommended daily dose of PSE should not be abused prior to diving with oxygen-enriched gas mixes or pure O₂. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

A new algorithm for epilepsy seizure onset detection and spread estimation from EEG signals

NASA Astrophysics Data System (ADS)

Quintero-Rincón, Antonio; Pereyra, Marcelo; D'Giano, Carlos; Batatia, Hadj; Risk, Marcelo

2016-04-01

Appropriate diagnosis and treatment of epilepsy is a main public health issue. Patients suffering from this disease often exhibit different physical characterizations, which result from the synchronous and excessive discharge of a group of neurons in the cerebral cortex. Extracting this information using EEG signals is an important problem in biomedical signal processing. In this work we propose a new algorithm for seizure onset detection and spread estimation in epilepsy patients. The algorithm is based on a multilevel 1-D wavelet decomposition that captures the physiological brain frequency signals coupled with a generalized gaussian model. Preliminary experiments with signals from 30 epilepsy crisis and 11 subjects, suggest that the proposed methodology is a powerful tool for detecting the onset of epilepsy seizures with his spread across the brain.

Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

PubMed Central

Inceoglu, Bora; Zolkowska, Dorota; Yoo, Hyun Ju; Wagner, Karen M.; Yang, Jun; Hackett, Edward; Hwang, Sung Hee; Lee, Kin Sing Stephen; Rogawski, Michael A.; Morisseau, Christophe; Hammock, Bruce D.

2013-01-01

In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders. PMID:24349022

Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

PubMed

Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

2012-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

PubMed

Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

2016-06-01

Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Efficacy of lacosamide by focal seizure subtype.

PubMed

Sperling, Michael R; Rosenow, Felix; Faught, Edward; Hebert, David; Doty, Pamela; Isojärvi, Jouko

2014-10-01

The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Benefit-risk assessment of levetiracetam in the treatment of partial seizures.

PubMed

Abou-Khalil, Bassel

2005-01-01

Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance. In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9-10.9% for levetiracetam-treated patients (all doses) compared with 5.3-8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12-15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500,000. In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse

A signal processing based analysis and prediction of seizure onset in patients with epilepsy

PubMed Central

Namazi, Hamidreza; Kulish, Vladimir V.

2016-01-01

One of the main areas of behavioural neuroscience is forecasting the human behaviour. Epilepsy is a central nervous system disorder in which nerve cell activity in the brain becomes disrupted, causing seizures or periods of unusual behaviour, sensations and sometimes loss of consciousness. An estimated 5% of the world population has epileptic seizure but there is not any method to cure it. More than 30% of people with epilepsy cannot control seizure. Epileptic seizure prediction, refers to forecasting the occurrence of epileptic seizures, is one of the most important but challenging problems in biomedical sciences, across the world. In this research we propose a new methodology which is based on studying the EEG signals using two measures, the Hurst exponent and fractal dimension. In order to validate the proposed method, it is applied to epileptic EEG signals of patients by computing the Hurst exponent and fractal dimension, and then the results are validated versus the reference data. The results of these analyses show that we are able to forecast the onset of a seizure on average of 25.76 seconds before the time of occurrence. PMID:26586477

Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures.

PubMed

Veerapandiyan, Aravindhan; Singh, Piyush; Mikati, Mohamad A

2012-03-01

Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic-clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one-year, six-month-old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.

CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

PubMed Central

Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

2006-01-01

Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

Variable expressivity of a likely pathogenic variant in KCNQ2 in a three-generation pedigree presenting with intellectual disability with childhood onset seizures.

PubMed

Hewson, Stacy; Puka, Klajdi; Mercimek-Mahmutoglu, Saadet

2017-08-01

KCNQ2 has been reported as a frequent cause of autosomal dominant benign familial neonatal seizures. De novo likely pathogenic variants in KCNQ2 have been described in neonatal or early infantile onset epileptic encephalopathy patients. Here, we report a three-generation family with six affected patients with a novel likely pathogenic variant (c.628C>T; p.Arg210Cys) in KCNQ2. Four family members, three adults and a child, presented with a childhood seizure onset with variability in the severity of seizures and response to treatment, intellectual disability (ID) as well as behavioral problems. The two youngest affected patients had a variable degree of global developmental delay with no seizures at their current age. This three-generation family with six affected members expands the phenotypic spectrum of KCNQ2 associated encephalopathy to KCNQ2 associated ID and or childhood onset epileptic encephalopathy. We think that KCNQ2 associated epileptic encephalopathy should be included in the differential diagnosis of childhood onset epilepsy and early onset global developmental delay, cognitive dysfunction, or ID. Furthermore, whole exome sequencing in families with ID and history of autosomal dominant inheritance pattern with or without seizures, may further broaden the phenotypic spectrum of KCNQ2 associated epileptic encephalopathy or encephalopathy. © 2017 Wiley Periodicals, Inc.

Multiple sensor integration for seizure onset detection in human patients comparing conventional disc versus novel tripolar concentric ring electrodes.

PubMed

Makeyev, Oleksandr; Ding, Quan; Martínez-Juárez, Iris E; Gaitanis, John; Kay, Steven M; Besio, Walter G

2013-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Closed-loop systems that apply electrical stimulation when seizure onset is automatically detected require high accuracy of automatic seizure detection based on electrographic brain activity. To improve this accuracy we propose to use noninvasive tripolar concentric ring electrodes that have been shown to have significantly better signal-to-noise ratio, spatial selectivity, and mutual information compared to conventional disc electrodes. The proposed detection methodology is based on integration of multiple sensors using exponentially embedded family (EEF). In this preliminary study it is validated on over 26.3 hours of data collected using both tripolar concentric ring and conventional disc electrodes concurrently each from 7 human patients with epilepsy including five seizures. For a cross-validation based group model EEF correctly detected 100% and 80% of seizures respectively with <0.76 and <1.56 false positive detections per hour respectively for the two electrode modalities. These results clearly suggest the potential of seizure onset detection based on data from tripolar concentric ring electrodes.

Intranasal nerve growth factor attenuating the seizure onset via p75R/Caspase pathway in the experimental epilepsy.

PubMed

Lei, Jing'an; Feng, Fang; Duan, Yuanyuan; Xu, Feng; Liu, Zhiguang; Lian, Lifei; Liang, Qiming; Zhang, Na; Wang, Furong

2017-09-01

Nerve growth factor (NGF) shows neuroprotection while it is hard to cross the blood-brain barrier due to its large molecular weight. Our study used intranasal delivery of NGF to treat the experimental epilepsy. The seizure was induced by injection of pentylenetetrazol (40mg/kg) into the rat. Based on the behavior performance, the successful models were randomized into control and NGF groups, given medium or NGF intranasally, respectively. The onset and duration of seizure were recorded. The neuron loss was assessed by immunohistochemistry and TUNEL staining. The expressions of Caspase-3, p75R and TrkA were measured by western blotting. Intranasal NGF significantly reduced the seizure onset and shortened the seizure duration. Intranasal NGF alleviated the neuron loss in the epileptic brain. The number of TUNEL-positive cells in the NGF group was less than that in the control group (P<0.05). Overexpression of Caspase-3 and activation of p75R induced by seizure were inhibited by intranasal NGF. Intranasal NGF protected neurons in the epileptic brain by inactivation of p75R/Caspase pathway. Intranasal NGF may be a novel therapeutic strategy for epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures.

PubMed

Nielsen, Jace C; Hutmacher, Matthew M; Wesche, David L; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G

2015-01-01

Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. © 2014, The American College of Clinical Pharmacology.

Dural arteriovenous fistula presenting with exophthalmos and seizures.

PubMed

Feyissa, Anteneh M; Ponce, Lucido L; Patterson, Joel T; Von Ritschl, Rudiger H; Smith, Robert G

2014-03-15

Concomitant seizures and exophthalmos in the context of a temporal dural arteriovenous fistula (dAVF) has not been described before. Here, we report a 55-year-old-male who presented with an 8-month history of progressive painless exophthalmos of his left eye, conjunctival chemosis, reduced vision and new onset complex partial seizures. Cerebral angiography demonstrated Cognard Type IIa left cerebral dAVF fed by branches from the left occipital artery and an accessory meningeal artery, with drainage to the superior ophthalmic vein. Following surgical obliteration of dAVF feeding vessels, our patient had dramatic improvement in visual acuity, proptosis and chemosis along with cessation of clinical seizures. Published by Elsevier B.V.

Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors.

PubMed

Uzbay, Tayfun I; Kayir, Hakan; Ceyhan, Mert

2007-02-01

Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.

Patient-Specific Early Seizure Detection from Scalp EEG

PubMed Central

Minasyan, Georgiy R.; Chatten, John B.; Chatten, Martha Jane; Harner, Richard N.

2010-01-01

Objective Develop a method for automatic detection of seizures prior to or immediately after clinical onset using features derived from scalp EEG. Methods This detection method is patient-specific. It uses recurrent neural networks and a variety of input features. For each patient we trained and optimized the detection algorithm for two cases: 1) during the period immediately preceding seizure onset, and 2) during the period immediately following seizure onset. Continuous scalp EEG recordings (duration 15 – 62 h, median 25 h) from 25 patients, including a total of 86 seizures, were used in this study. Results Pre-onset detection was successful in 14 of the 25 patients. For these 14 patients, all of the testing seizures were detected prior to seizure onset with a median pre-onset time of 51 sec and false positive rate was 0.06/h. Post-onset detection had 100% sensitivity, 0.023/hr false positive rate and median delay of 4 sec after onset. Conclusions The unique results of this study relate to pre-onset detection. Significance Our results suggest that reliable pre-onset seizure detection may be achievable for a significant subset of epilepsy patients without use of invasive electrodes. PMID:20461014

Influence of Time-Series Normalization, Number of Nodes, Connectivity and Graph Measure Selection on Seizure-Onset Zone Localization from Intracranial EEG.

PubMed

van Mierlo, Pieter; Lie, Octavian; Staljanssens, Willeke; Coito, Ana; Vulliémoz, Serge

2018-04-26

We investigated the influence of processing steps in the estimation of multivariate directed functional connectivity during seizures recorded with intracranial EEG (iEEG) on seizure-onset zone (SOZ) localization. We studied the effect of (i) the number of nodes, (ii) time-series normalization, (iii) the choice of multivariate time-varying connectivity measure: Adaptive Directed Transfer Function (ADTF) or Adaptive Partial Directed Coherence (APDC) and (iv) graph theory measure: outdegree or shortest path length. First, simulations were performed to quantify the influence of the various processing steps on the accuracy to localize the SOZ. Afterwards, the SOZ was estimated from a 113-electrodes iEEG seizure recording and compared with the resection that rendered the patient seizure-free. The simulations revealed that ADTF is preferred over APDC to localize the SOZ from ictal iEEG recordings. Normalizing the time series before analysis resulted in an increase of 25-35% of correctly localized SOZ, while adding more nodes to the connectivity analysis led to a moderate decrease of 10%, when comparing 128 with 32 input nodes. The real-seizure connectivity estimates localized the SOZ inside the resection area using the ADTF coupled to outdegree or shortest path length. Our study showed that normalizing the time-series is an important pre-processing step, while adding nodes to the analysis did only marginally affect the SOZ localization. The study shows that directed multivariate Granger-based connectivity analysis is feasible with many input nodes (> 100) and that normalization of the time-series before connectivity analysis is preferred.

Assessment of the Utility of Ictal Magnetoencephalography in the Localization of the Epileptic Seizure Onset Zone.

PubMed

Alkawadri, Rafeed; Burgess, Richard C; Kakisaka, Yosuke; Mosher, John C; Alexopoulos, Andreas V

2018-06-11

Literature on ictal magnetoencephalography (MEG) in clinical practice and the relationship to other modalities is limited because of the brevity of routine studies. To investigate the utility and reliability of ictal MEG in the localization of the epileptogenic zone. A retrospective medical record review and prospective analysis of a novel ictal rhythm analysis method was conducted at a tertiary epilepsy center with a wide base of referrals for epilepsy surgery evaluation and included consecutive cases of patients who experienced epileptic seizures during routine MEG studies from March 2008 to February 2012. A total of 377 studies screened. Data were analyzed from November 2011 to October 2015. Presurgical workup and interictal and ictal MEG data were reviewed. The localizing value of using extended-source localization of a narrow band identified visually at onset was analyzed. Of the 44 included patients, the mean (SD) age at the time of recording was 19.3 (14.9) years, and 25 (57%) were male. The mean duration of recording was 51.2 minutes. Seizures were provoked by known triggers in 3 patients and were spontaneous otherwise. Twenty-five patients (57%) had 1 seizure, 6 (14%) had 2, and 13 (30%) had 3 or more. Magnetoencephalography single equivalent current dipole analysis was possible in 29 patients (66%), of whom 8 (28%) had no clear interictal discharges. Sublobar concordance between ictal and interictal dipoles was seen in 18 of 21 patients (86%). Three patients (7%) showed clear ictal MEG patterns without electroencephalography changes. Ictal MEG dipoles correlated with the lobe of onset in 7 of 8 patients (88%) who underwent intracranial electroencephalography evaluations. Reasons for failure to identify ictal dipoles included diffuse or poor dipolar ictal patterns, no MEG changes, and movement artifact. Resection of areas containing a minimum-norm estimate of a narrow band at onset, not single equivalent current dipole, was associated with sustained

Right hemispheric reversible cerebral vasoconstriction syndrome in a patient with left hemispheric partial seizures.

PubMed

Perez, Gina S; McCaslin, Justin; Shamim, Sadat

2017-04-01

We report a right-handed 19-year-old girl who developed reversible cerebral vasoconstriction syndrome (RCVS) lateralized to the right hemisphere with simultaneous new-onset left hemispheric seizures. RCVS, typically more diffuse, was lateralized to one of the cerebral hemispheres.

Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide.

PubMed

Itakura, Ayako; Saito, Yoshiaki; Nishimura, Yoko; Okazaki, Tetsuya; Ohno, Koyo; Sejima, Hitoshi; Yamamoto, Toshiyuki; Maegaki, Yoshihiro

2016-08-01

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures.

PubMed

Maj, R; Fariello, R G; Pevarello, P; Varasi, M; McArthur, R A; Salvati, P

1999-11-01

PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drug (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation 1 day before drug treatment. PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose-dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose-related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

Right hemispheric reversible cerebral vasoconstriction syndrome in a patient with left hemispheric partial seizures

PubMed Central

Perez, Gina S.; McCaslin, Justin

2017-01-01

We report a right-handed 19-year-old girl who developed reversible cerebral vasoconstriction syndrome (RCVS) lateralized to the right hemisphere with simultaneous new-onset left hemispheric seizures. RCVS, typically more diffuse, was lateralized to one of the cerebral hemispheres. PMID:28405089

Optimized Seizure Detection Algorithm: A Fast Approach for Onset of Epileptic in EEG Signals Using GT Discriminant Analysis and K-NN Classifier

PubMed Central

Rezaee, Kh.; Azizi, E.; Haddadnia, J.

2016-01-01

Background Epilepsy is a severe disorder of the central nervous system that predisposes the person to recurrent seizures. Fifty million people worldwide suffer from epilepsy; after Alzheimer’s and stroke, it is the third widespread nervous disorder. Objective In this paper, an algorithm to detect the onset of epileptic seizures based on the analysis of brain electrical signals (EEG) has been proposed. 844 hours of EEG were recorded form 23 pediatric patients consecutively with 163 occurrences of seizures. Signals had been collected from Children’s Hospital Boston with a sampling frequency of 256 Hz through 18 channels in order to assess epilepsy surgery. By selecting effective features from seizure and non-seizure signals of each individual and putting them into two categories, the proposed algorithm detects the onset of seizures quickly and with high sensitivity. Method In this algorithm, L-sec epochs of signals are displayed in form of a third-order tensor in spatial, spectral and temporal spaces by applying wavelet transform. Then, after applying general tensor discriminant analysis (GTDA) on tensors and calculating mapping matrix, feature vectors are extracted. GTDA increases the sensitivity of the algorithm by storing data without deleting them. Finally, K-Nearest neighbors (KNN) is used to classify the selected features. Results The results of simulating algorithm on algorithm standard dataset shows that the algorithm is capable of detecting 98 percent of seizures with an average delay of 4.7 seconds and the average error rate detection of three errors in 24 hours. Conclusion Today, the lack of an automated system to detect or predict the seizure onset is strongly felt. PMID:27672628

Generalized versus partial reflex seizures: a review.

PubMed

Italiano, Domenico; Ferlazzo, Edoardo; Gasparini, Sara; Spina, Edoardo; Mondello, Stefania; Labate, Angelo; Gambardella, Antonio; Aguglia, Umberto

2014-08-01

In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between "generalized" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and "focal" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm. We discuss in particular evidence from animal, clinical, neurophysiological and neuroimaging studies supporting the concept that "generalized" reflex seizures, usually occurring in the setting of IGE, should be considered as focal seizures with quick secondary generalization. We also review recent advances in genetic and therapeutic approach of reflex seizures. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Prevalence and risk factors of seizure clusters in adult patients with epilepsy.

PubMed

Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Wong, Rebecca A; Jiang, Alfred; Kato, Kenneth; Buchsbaum, Richard; Detyniecki, Kamil

2017-07-01

In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. We reviewed medical records of 4116 adult (≥16years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P<0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P<0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also

Eslicarbazepine acetate for the treatment of partial epilepsy.

PubMed

Zelano, Johan; Ben-Menachem, Elinor

2016-06-01

Eslicarbazepine acetate (ESL) is a third generation AED structurally related to carbamazepine and oxcarbazepine, but without several of the drawbacks associated with these compounds. ESL is completely metabolized to its eslicarbazpine, which selectively binds inactivated voltage-gated sodium channels and thus selectively reduces the activity of rapidly firing (epileptic) neurons. In addition, ESL has pharmacokinetic properties allowing once daily dosing. This review summarizes data from the initial phase I to III studies, which demonstrated efficacy of ESL as add-on treatment in partial onset epilepsy, and more recent studies that demonstrate efficacy of ESL as monotherapy. Real-life observational studies are also reviewed, and seem to confirm the notion of ESL as a well-tolerated AED. As a new AED, ESL needs to be subject to close monitoring regarding long-term adverse events. Future independent studies will most likely clarify the role of ESL in the management of partial onset seizures. The role of ESL in management of partial onset seizures is discussed, as is the need for close monitoring and evaluation for broad-spectrum pharmacodynamics properties. The characteristics of the molecule and efficacy and safety profiles seem, however, very promising.

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

PubMed

Okazaki, Mitsutoshi; Adachi, Naoto; Akanuma, Nozomi; Hara, Koichiro; Ito, Masumi; Kato, Masaaki; Onuma, Teiichi

2014-11-01

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures.

PubMed

Fountain, Nathan B; Krauss, Gregory; Isojarvi, Jouko; Dilley, Deanne; Doty, Pamela; Rudd, G David

2013-01-01

To examine the safety and tolerability of rapidly initiating adjunctive lacosamide via a single intravenous loading dose followed by twice-daily oral lacosamide in lacosamide-naive adults with partial-onset seizures. This open-label, multicenter trial, enrolled patients with epilepsy who were taking 1-2 antiepileptic drugs (AEDs) in one of four sequential cohorts containing 25 subjects each. An intravenous lacosamide loading dose (200, 300, or 400 mg) was administered over 15 min followed 12 h later by initiation of oral dosing consisting of one-half of the loading dose administered twice daily for 6.5 days. The first cohort was administered lacosamide 200 mg/day, followed by a cohort at 300 mg/day, and then a cohort at 400 mg/day. The results from each cohort were evaluated before enrolling the next highest dose level. The fourth cohort enrolled patients at the highest dose with clinically acceptable safety and tolerability results. Safety evaluations included treatment-emergent adverse events (TEAEs), patient withdrawals due to TEAEs, and changes in vital signs, 12-lead electrocardiography (ECG) studies, laboratory parameters, and clinical examinations. Postinfusion lacosamide plasma concentrations were also evaluated. A total of 100 patients were enrolled, 25 in each cohort. The loading dose for the repeat cohort was 300 mg; therefore, 25 patients were enrolled at 200 mg/day, 50 at 300 mg/day, and 25 at 400 mg/day. Most TEAEs occurred within the first 4 h following infusion; dose-related TEAEs (incidence ≥10%) during this timeframe included dizziness, somnolence, and nausea. Seven patients withdrew, all due to TEAEs: three (6%) from the combined 300 mg group and four (16%) from the 400 mg group; four of these patients discontinued within 4 h following infusion. The most common TEAEs leading to discontinuation (overall incidence >1%) were dizziness (6%), nausea (5%), and vomiting (3%). No clinically relevant pattern of changes from baseline ECG, clinical

Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy

PubMed Central

Tambucci, Renato; Basti, Claudia; Maresca, Maria; Coppola, Giangennaro; Verrotti, Alberto

2016-01-01

Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine – a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC). ESL inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the VGSC, thus selectively reducing the activity of rapidly firing (epileptic) neurons. ESL reduces VGSC availability through enhancement of slow inactivation. In Phase III studies, adjunctive therapy with ESL 800 or 1,200 mg/day leads to a significant decrease in the seizure frequency in adults with refractory partial onset epilepsy. Based on these results, ESL has been approved in Europe (by the European Medicines Agency) and in the United States (by the US Food and Drug Administration) as add-on therapy. Data on efficacy and safety have been confirmed by 1-year extension and real life observational studies. Recently, based on results from two randomized, double-blind, historical control Phase III trials, ESL received US Food and Drug Administration approval also as a monotherapy for patients with partial onset epilepsy. In the pediatric setting, encouraging results have been obtained suggesting its potential role in the management of epileptic children. Overall ESL was generally well tolerated. The most common adverse events were dizziness, somnolence, headache, nausea, diplopia, and vomiting. Adverse events can be minimized by appropriate titration. In conclusion, ESL seems to overcome some drawbacks of the previous antiepileptic drugs, suggesting a major role of ESL in the management of focal onset epilepsy for both new onset and

Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy.

PubMed

Tambucci, Renato; Basti, Claudia; Maresca, Maria; Coppola, Giangennaro; Verrotti, Alberto

2016-01-01

Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine - a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC). ESL inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the VGSC, thus selectively reducing the activity of rapidly firing (epileptic) neurons. ESL reduces VGSC availability through enhancement of slow inactivation. In Phase III studies, adjunctive therapy with ESL 800 or 1,200 mg/day leads to a significant decrease in the seizure frequency in adults with refractory partial onset epilepsy. Based on these results, ESL has been approved in Europe (by the European Medicines Agency) and in the United States (by the US Food and Drug Administration) as add-on therapy. Data on efficacy and safety have been confirmed by 1-year extension and real life observational studies. Recently, based on results from two randomized, double-blind, historical control Phase III trials, ESL received US Food and Drug Administration approval also as a monotherapy for patients with partial onset epilepsy. In the pediatric setting, encouraging results have been obtained suggesting its potential role in the management of epileptic children. Overall ESL was generally well tolerated. The most common adverse events were dizziness, somnolence, headache, nausea, diplopia, and vomiting. Adverse events can be minimized by appropriate titration. In conclusion, ESL seems to overcome some drawbacks of the previous antiepileptic drugs, suggesting a major role of ESL in the management of focal onset epilepsy for both new onset and

Feasibility of imaging epileptic seizure onset with EIT and depth electrodes.

PubMed

Witkowska-Wrobel, Anna; Aristovich, Kirill; Faulkner, Mayo; Avery, James; Holder, David

2018-06-01

Imaging ictal and interictal activity with Electrical Impedance Tomography (EIT) using intracranial electrode mats has been demonstrated in animal models of epilepsy. In human epilepsy subjects undergoing presurgical evaluation, depth electrodes are often preferred. The purpose of this work was to evaluate the feasibility of using EIT to localise epileptogenic areas with intracranial electrodes in humans. The accuracy of localisation of the ictal onset zone was evaluated in computer simulations using 9M element FEM models derived from three subjects. 5 mm radius perturbations imitating a single seizure onset event were placed in several locations forming two groups: under depth electrode coverage and in the contralateral hemisphere. Simulations were made for impedance changes of 1% expected for neuronal depolarisation over milliseconds and 10% for cell swelling over seconds. Reconstructions were compared with EEG source modelling for a radially orientated dipole with respect to the closest EEG recording contact. The best accuracy of EIT was obtained using all depth and 32 scalp electrodes, greater than the equivalent accuracy with EEG inverse source modelling. The localisation error was 5.2 ± 1.8, 4.3 ± 0 and 46.2 ± 25.8 mm for perturbations within the volume enclosed by depth electrodes and 29.6 ± 38.7, 26.1 ± 36.2, 54.0 ± 26.2 mm for those without (EIT 1%, 10% change, EEG source modelling, n = 15 in 3 subjects, p < 0.01). As EIT was insensitive to source dipole orientation, all 15 perturbations within the volume enclosed by depth electrodes were localised, whereas the standard clinical method of visual inspection of EEG voltages, only localised 8 out of 15 cases. This suggests that adding EIT to SEEG measurements could be beneficial in localising the onset of seizures. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Identifying seizure onset zone from electrocorticographic recordings: A machine learning approach based on phase locking value.

PubMed

Elahian, Bahareh; Yeasin, Mohammed; Mudigoudar, Basanagoud; Wheless, James W; Babajani-Feremi, Abbas

2017-10-01

Using a novel technique based on phase locking value (PLV), we investigated the potential for features extracted from electrocorticographic (ECoG) recordings to serve as biomarkers to identify the seizure onset zone (SOZ). We computed the PLV between the phase of the amplitude of high gamma activity (80-150Hz) and the phase of lower frequency rhythms (4-30Hz) from ECoG recordings obtained from 10 patients with epilepsy (21 seizures). We extracted five features from the PLV and used a machine learning approach based on logistic regression to build a model that classifies electrodes as SOZ or non-SOZ. More than 96% of electrodes identified as the SOZ by our algorithm were within the resected area in six seizure-free patients. In four non-seizure-free patients, more than 31% of the identified SOZ electrodes by our algorithm were outside the resected area. In addition, we observed that the seizure outcome in non-seizure-free patients correlated with the number of non-resected SOZ electrodes identified by our algorithm. This machine learning approach, based on features extracted from the PLV, effectively identified electrodes within the SOZ. The approach has the potential to assist clinicians in surgical decision-making when pre-surgical intracranial recordings are utilized. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Exploring the time-frequency content of high frequency oscillations for automated identification of seizure onset zone in epilepsy.

PubMed

Liu, Su; Sha, Zhiyi; Sencer, Altay; Aydoseli, Aydin; Bebek, Nerse; Abosch, Aviva; Henry, Thomas; Gurses, Candan; Ince, Nuri Firat

2016-04-01

High frequency oscillations (HFOs) in intracranial electroencephalography (iEEG) recordings are considered as promising clinical biomarkers of epileptogenic regions in the brain. The aim of this study is to improve and automatize the detection of HFOs by exploring the time-frequency content of iEEG and to investigate the seizure onset zone (SOZ) detection accuracy during the sleep, awake and pre-ictal states in patients with epilepsy, for the purpose of assisting the localization of SOZ in clinical practice. Ten-minute iEEG segments were defined during different states in eight patients with refractory epilepsy. A three-stage algorithm was implemented to detect HFOs in these segments. First, an amplitude based initial detection threshold was used to generate a large pool of HFO candidates. Then distinguishing features were extracted from the time and time-frequency domain of the raw iEEG and used with a Gaussian mixture model clustering to isolate HFO events from other activities. The spatial distribution of HFO clusters was correlated with the seizure onset channels identified by neurologists in seven patient with good surgical outcome. The overlapping rates of localized channels and seizure onset locations were high in all states. The best result was obtained using the iEEG data during sleep, achieving a sensitivity of 81%, and a specificity of 96%. The channels with maximum number of HFOs identified epileptogenic areas where the seizures occurred more frequently. The current study was conducted using iEEG data collected in realistic clinical conditions without channel pre-exclusion. HFOs were investigated with novel features extracted from the entire frequency band, and were correlated with SOZ in different states. The results indicate that automatic HFO detection with unsupervised clustering methods exploring the time-frequency content of raw iEEG can be efficiently used to identify the epileptogenic zone with an accurate and efficient manner.

Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

2012-01-01

As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

Efficacy and safety of adjunctive lacosamide for the treatment of partial-onset seizures in Chinese and Japanese adults: A randomized, double-blind, placebo-controlled study.

PubMed

Hong, Zhen; Inoue, Yushi; Liao, Weiping; Meng, Hongmei; Wang, Xuefeng; Wang, Wenmin; Zhou, Liemin; Zhang, Liming; Du, Xinlu; Tennigkeit, Frank

2016-11-01

To evaluate the efficacy and safety of adjunctive lacosamide treatment in Chinese and Japanese adults with uncontrolled focal (partial-onset) seizures (POS), with or without secondary generalization. A 24-week, randomized, double-blind, placebo-controlled study (EP0008; NCT01710657) was conducted in patients (aged 16-70 years) with uncontrolled POS and taking 1-3 concomitant antiepileptic drugs from 72 sites across China and Japan. Following an 8-week Baseline period, randomized patients received lacosamide 200mg/day (100mg twice daily), 400mg/day (200mg twice daily), or placebo for 4-week Titration and 12-week Maintenance periods. The primary efficacy variable was the change in POS frequency per 28days from Baseline to Maintenance. Overall, 692 patients were screened; 548 were randomized to placebo (n=184), lacosamide 200mg/day (n=183), or lacosamide 400mg/day (n=181); 485 (88.5%) completed the study. The median change (range) in POS frequency per 28days from Baseline to Maintenance was -3.33 (-754.3 to 165.2), -4.50 (-97.5 to 28.2), and -1.22 (-93.0 to 39.8) in the lacosamide 200mg/day, 400mg/day, and placebo groups, respectively. Significant percentage reductions in POS frequency over placebo per 28days from Baseline to Maintenance were observed for lacosamide 200mg/day (29.4% [95% CI 18.7-38.7%], p<0.001) and 400mg/day (39.6% [30.5-47.6%], p<0.001). Higher ≥50% and ≥75% responder and seizure freedom rates were observed in lacosamide-treated patients vs placebo. Treatment-emergent adverse events reported by ≥10% of all lacosamide-treated patients occurring at ≥2% difference compared with placebo were dizziness (25.9% vs 9.2%) and somnolence (10.2% vs 3.8%). Dose-proportional pharmacokinetics were consistent with earlier global pivotal trials. Adjunctive lacosamide (200 and 400mg/day) was efficacious in reducing POS frequency in Chinese and Japanese patients with a safety and tolerability profile consistent with the three global pivotal studies. Copyright

Instruction manual for the ILAE 2017 operational classification of seizure types.

PubMed

Fisher, Robert S; Cross, J Helen; D'Souza, Carol; French, Jacqueline A; Haut, Sheryl R; Higurashi, Norimichi; Hirsch, Edouard; Jansen, Floor E; Lagae, Lieven; Moshé, Solomon L; Peltola, Jukka; Roulet Perez, Eliane; Scheffer, Ingrid E; Schulze-Bonhage, Andreas; Somerville, Ernest; Sperling, Michael; Yacubian, Elza Márcia; Zuberi, Sameer M

2017-04-01

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PubMed

Spencer, Susan S; Schramm, Johannes; Wyler, Allen; O'Connor, Michael; Orbach, Darren; Krauss, Gregory; Sperling, Michael; Devinsky, Orrin; Elger, Christian; Lesser, Ronald; Mulligan, Lisa; Westerveld, Michael

2002-02-01

Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Detection of early seizures by diffuse optical tomography

NASA Astrophysics Data System (ADS)

Zhang, Tao; Hajihashemi, M. Reza; Zhou, Junli; Carney, Paul R.; Jiang, Huabei

2015-03-01

In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Besides, preclinical seizure experiments need to be conducted in awake animals with images reconstructed and displayed in real-time. We demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking brain activities with high spatiotemporal resolution. We developed methods to conduct seizure experiments in fully awake rats using a subject-specific helmet and a restraining mechanism. For the first time, we detected early hemodynamic responses with heterogeneous patterns several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state both in anesthetized and awake rats. Using a novel time-series analysis of scattering images, we show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

Relationship of clinical and quality of life trajectories following the onset of seizures: findings from the UK MESS Study.

PubMed

Jacoby, Ann; Lane, Steven; Marson, Anthony; Baker, Gus A

2011-05-01

We defined a series of clinical trajectories represented among adult patients with new-onset seizures across a 4-year follow-up period; and linked these clinical trajectories to the quality of life (QOL) profiles and trajectories of those experiencing them. We examined both between- and within-group differences. Analyses were based on 253 individuals completing QOL questionnaires at baseline and 2 and 4 years subsequently. Based on patient self-report, we defined five "clinical trajectory" groups: individuals experiencing a single seizure only; individuals entering early remission; individuals experiencing late remission; individuals initially becoming seizure-free but subsequently relapsing; individuals with seizures persisting throughout follow-up. QOL profiles at each time point were compared using a validated QOL battery, NEWQOL. Even at baseline, there were significant between-group differences, with patients experiencing a single seizure only reporting the best QOL profile and those with seizures subsequently persisting across all time points reporting the worst. By 2 years, the QOL profiles of individuals experiencing early remission were similar to those of single seizure patients, as were those for late remission and relapse patients. A consistent pattern was seen, with "single seizure" individuals doing best and individuals with persistent seizures doing worst. Of particular concern is that even at baseline, individuals whose seizures persisted were doing poorly for QOL, suggesting the possibility that underlying neurobiologic mechanisms were operating. In contrast, our findings support previous reports of only short-lived and small QOL decrements for individuals experiencing a single or few seizures. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Glycolysis in energy metabolism during seizures.

PubMed

Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

2013-05-15

Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment.

Predicting Epileptic Seizures in Advance

PubMed Central

Moghim, Negin; Corne, David W.

2014-01-01

Epilepsy is the second most common neurological disorder, affecting 0.6–0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs) are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG) data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling), is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance. PMID:24911316

Behaviors induced or disrupted by complex partial seizures.

PubMed

Leung, L S; Ma, J; McLachlan, R S

2000-09-01

We reviewed the neural mechanisms underlying some postictal behaviors that are induced or disrupted by temporal lobe seizures in humans and animals. It is proposed that the psychomotor behaviors and automatisms induced by temporal lobe seizures are mediated by the nucleus accumbens. A non-convulsive hippocampal afterdischarge in rats induced an increase in locomotor activity, which was suppressed by the injection of dopamine D(2) receptor antagonist in the nucleus accumbens, and blocked by inactivation of the medial septum. In contrast, a convulsive hippocampal or amygdala seizure induced behavioral hypoactivity, perhaps by the spread of the seizure into the frontal cortex and opiate-mediated postictal depression. Mechanisms underlying postictal psychosis, memory disruption and other long-term behavioral alterations after temporal lobe seizures, are discussed. In conclusion, many of the changes of postictal behaviors observed after temporal lobe seizures in humans may be found in animals, and the basis of the behavioral change may be explained as a change in neural processing in the temporal lobe and the connecting subcortical structures.

Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

PubMed

Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

2017-08-01

Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Seizure semiology identifies patients with bilateral temporal lobe epilepsy.

PubMed

Loesch, Anna Mira; Feddersen, Berend; Tezer, F Irsel; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

2015-01-01

Laterality in temporal lobe epilepsy is usually defined by EEG and imaging results. We investigated whether the analysis of seizure semiology including lateralizing seizure phenomena identifies bilateral independent temporal lobe seizure onset. We investigated the seizure semiology in 17 patients in whom invasive EEG-video-monitoring documented bilateral temporal seizure onset. The results were compared to 20 left and 20 right consecutive temporal lobe epilepsy (TLE) patients who were seizure free after anterior temporal lobe resection. The seizure semiology was analyzed using the semiological seizure classification with particular emphasis on the sequence of seizure phenomena over time and lateralizing seizure phenomena. Statistical analysis included chi-square test or Fisher's exact test. Bitemporal lobe epilepsy patients had more frequently different seizure semiology (100% vs. 40%; p<0.001) and significantly more often lateralizing seizure phenomena pointing to bilateral seizure onset compared to patients with unilateral TLE (67% vs. 11%; p<0.001). The sensitivity of identical vs. different seizure semiology for the identification of bilateral TLE was high (100%) with a specificity of 60%. Lateralizing seizure phenomena had a low sensitivity (59%) but a high specificity (89%). The combination of lateralizing seizure phenomena and different seizure semiology showed a high specificity (94%) but a low sensitivity (59%). The analysis of seizure semiology including lateralizing seizure phenomena adds important clinical information to identify patients with bilateral TLE. Copyright © 2014 Elsevier B.V. All rights reserved.

Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

PubMed

Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

2016-02-01

This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. Copyright © 2015 Elsevier Inc. All rights reserved.

Epileptic Seizures Prediction Using Machine Learning Methods

PubMed Central

Usman, Syed Muhammad

2017-01-01

Epileptic seizures occur due to disorder in brain functionality which can affect patient's health. Prediction of epileptic seizures before the beginning of the onset is quite useful for preventing the seizure by medication. Machine learning techniques and computational methods are used for predicting epileptic seizures from Electroencephalograms (EEG) signals. However, preprocessing of EEG signals for noise removal and features extraction are two major issues that have an adverse effect on both anticipation time and true positive prediction rate. Therefore, we propose a model that provides reliable methods of both preprocessing and feature extraction. Our model predicts epileptic seizures' sufficient time before the onset of seizure starts and provides a better true positive rate. We have applied empirical mode decomposition (EMD) for preprocessing and have extracted time and frequency domain features for training a prediction model. The proposed model detects the start of the preictal state, which is the state that starts few minutes before the onset of the seizure, with a higher true positive rate compared to traditional methods, 92.23%, and maximum anticipation time of 33 minutes and average prediction time of 23.6 minutes on scalp EEG CHB-MIT dataset of 22 subjects. PMID:29410700

Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.

PubMed

Morrell, Martha J

2011-09-27

This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy. A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation. Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function. Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

PubMed Central

Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

2015-01-01

Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to

On the nature of seizure dynamics

PubMed Central

Stacey, William C.; Quilichini, Pascale P.; Ivanov, Anton I.

2014-01-01

Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between ‘normal’ and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical

Dynamic Imaging of Coherent Sources Reveals Different Network Connectivity Underlying the Generation and Perpetuation of Epileptic Seizures

PubMed Central

Anwar, Abdul Rauf; Deuschl, Günther; Stephani, Ulrich; Raethjen, Jan; Siniatchkin, Michael

2013-01-01

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis. PMID:24194931

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

The performance of the spatiotemporal Kalman filter and LORETA in seizure onset localization.

PubMed

Hamid, Laith; Sarabi, Masoud; Japaridze, Natia; Wiegand, Gert; Heute, Ulrich; Stephani, Ulrich; Galka, Andreas; Siniatchkin, Michael

2015-08-01

The assumption of spatial-smoothness is often used to solve the bioelectric inverse problem during electroencephalographic (EEG) source imaging, e.g., in low resolution electromagnetic tomography (LORETA). Since the EEG data show a temporal structure, the combination of the temporal-smoothness and the spatial-smoothness constraints may improve the solution of the EEG inverse problem. This study investigates the performance of the spatiotemporal Kalman filter (STKF) method, which is based on spatial and temporal smoothness, in the localization of a focal seizure's onset and compares its results to those of LORETA. The main finding of the study was that the STKF with an autoregressive model of order two significantly outperformed LORETA in the accuracy and consistency of the localization, provided that the source space consists of a whole-brain volumetric grid. In the future, these promising results will be confirmed using data from more patients and performing statistical analyses on the results. Furthermore, the effects of the temporal smoothness constraint will be studied using different types of focal seizures.

Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females.

PubMed

Bartnik, Magdalena; Derwińska, Katarzyna; Gos, Monika; Obersztyn, Ewa; Kołodziejska, Katarzyna E; Erez, Ayelet; Szpecht-Potocka, Agnieszka; Fang, Ping; Terczyńska, Iwona; Mierzewska, Hanna; Lohr, Naomi J; Bellus, Gary A; Reimschisel, Tyler; Bocian, Ewa; Mazurczak, Tadeusz; Cheung, Sau Wai; Stankiewicz, Paweł

2011-05-01

Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5. We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5. We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5. We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.

Efficacy of low to moderate doses of oxcarbazepine in adult patients with newly diagnosed partial epilepsy.

PubMed

Zou, Xue-Mei; Chen, Jia-Ni; An, Dong-Mei; Hao, Nan-Ya; Hong, Zhen; Hao, Xiao-Ting; Rao, Ping; Zhou, Dong

2015-07-01

The objective of this study was to explore the efficacy of low dose of oxcarbazepine (OXC) in adult patients with newly diagnosed partial epilepsy in an actual clinical setting. The associated factors influencing the poor control of seizures were also evaluated. The epilepsy database (2010-2014) from the Epilepsy Clinic of West China Hospital was retrospectively reviewed. A total of 102 adult patients with newly diagnosed, previously untreated partial epilepsy initially treated with OXC were included, and divided into good response group (64) and poor response group (38) according to whether they were seizure-free for at least 12 months. There were 27 (26.5%) patients becoming seizure-free with OXC 600 mg/day monotherapy. The remaining 75 patients had doses of either increasing OXC to 900 mg/day (n = 59) or the addition of another antiepileptic drug (AED) (n = 16), with another 20 (19.6%) and six (5.9%) patients becoming seizure-free, respectively (P = 0.788). In addition, two (2.0%) and nine (8.8%) patients became seizure-free with OXC > 900 mg/day monotherapy and OXC ≥ 900 mg/day combination therapy, respectively. Multivariate binary logistic regression analysis revealed that the time from onset of epilepsy to treatment initiation is significantly associated with seizure control (P = 0.02). Our results indicated that OXC at low to moderate doses is effective for the treatment of Chinese adult patients with newly diagnosed, previously untreated partial epilepsy, and a longer time interval from the onset of epilepsy to the start of treatment significantly predicts poor seizure control. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Children with New Onset Seizures: A Prospective Study of Parent Variables, Child Behavior Problems, and Seizure Occurrence

PubMed Central

Austin, Joan K.; Haber, Linda C.; Dunn, David W.; Shore, Cheryl P.; Johnson, Cynthia S.; Perkins, Susan M.

2015-01-01

Objective Parent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures, however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4 – 14 years) and their parents over a 24-month period (with data collected at baseline, 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. Methods The sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance. Results Relationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizures group. Conclusions Findings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life. PMID:26520879

Secondary generalization of focal-onset seizures: examining the relationship between seizure propagation and epilepsy surgery outcome.

PubMed

Tomlinson, Samuel B; Venkataraman, Arun

2017-04-01

Surgical intervention often fails to achieve seizure-free results in patients with intractable epilepsy. Identifying features of the epileptic brain that dispose certain patients to unfavorable outcomes is critical for improving surgical candidacy assessments. Recent research by Martinet, Ahmad, Lepage, Cash, and Kramer ( J Neurosci 35: 9477-9490, 2015) suggests that pathways of secondary seizure generalization distinguish patients with favorable (i.e., seizure free) vs. unfavorable (i.e., seizure persistent) surgical outcomes, lending insights into the network mechanisms of epilepsy surgery failure. Copyright © 2017 the American Physiological Society.

Valerenic acid and Valeriana officinalis extracts delay onset of Pentylenetetrazole (PTZ)-Induced seizures in adult Danio rerio (Zebrafish).

PubMed

Torres-Hernández, Bianca A; Del Valle-Mojica, Lisa M; Ortíz, José G

2015-07-14

Anticonvulsant properties have been attributed to extracts of the herbal medicine Valeriana officinalis. Our aims were to examine the anticonvulsant properties of valerenic acid and valerian extracts and to determine whether valerian preparations interact with the activity of other anti-epileptic drugs (phenytoin or clonazepam). To achieve these goals, we validated the adult zebrafish, Danio rerio, as an animal model for studying anticonvulsant drugs. All drug treatments were administered by immersion in water containing the drug. For assays of anticonvulsant activity, zebrafish were pretreated with: anti-epileptic drugs, valerenic acid, aqueous or ethanolic valerian extracts, or mixtures (phenytoin or clonazepam with valerenic acid or valerian extracts). Seizures were then induced with pentylenetetrazole (PTZ). A behavioral scale was developed for scoring PTZ-induced seizures in adult zebrafish. The seizure latency was evaluated for all pretreatments and control, untreated fish. Valerenic acid and both aqueous and ethanolic extracts of valerian root were also evaluated for their ability to improve survival after pentylenetetrazole-challenge. The assay was validated by comparison with well-studied anticonvulsant drugs (phenytoin, clonazepam, gabapentin and valproate). One-way ANOVA followed by Tukey post-hoc test was performed, using a p < 0.05 level of significance. All treatments were compared with the untreated animals and with the other pretreatments. After exposure to pentylenetetrazole, zebrafish exhibited a series of stereotypical behaviors prior to the appearance of clonic-like movements--convulsions. Both valerenic acid and valerian extracts (aqueous and ethanolic) significantly extended the latency period to the onset of seizure (convulsion) in adult zebrafish. The ethanolic valerian extract was a more potent anticonvulsant than the aqueous extract. Valerenic acid and both valerian extracts interacted synergistically with clonazepam to extended the

Children with new onset seizures: A prospective study of parent variables, child behavior problems, and seizure occurrence.

PubMed

Austin, Joan K; Haber, Linda C; Dunn, David W; Shore, Cheryl P; Johnson, Cynthia S; Perkins, Susan M

2015-12-01

Parent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures; however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4-14 years) and their parents over a 24-month period (with data collected at baseline and 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. The sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance. Relationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizure group. Findings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurodevelopmental comorbidities and seizure control 24 months after a first unprovoked seizure in children.

PubMed

Jason, Eva Åndell; Tomson, Torbjörn; Carlsson, Sofia; Tedroff, Kristina; Åmark, Per

2018-07-01

To follow children with newly diagnosed unprovoked seizures to determine (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy (CP) changed after the initial seizure, and (2) the association between studied comorbidities and seizures 13-24 months after seizure onset or initiation of treatment. Analyses were based on 750 children (28 days-18 years) with a first unprovoked seizure (index) included in a population-based Incidence Registry in Stockholm between 2001 and 2006. The children were followed for two years and their medical records were examined for a priori defined neurodevelopmental/psychiatric comorbidities and CP and seizure frequency. Baseline information was collected from medical records from before, and up to six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24 months after the first seizure or after initiation of anti-epileptic drug treatment was calculated by logistic regression and adjusted for age and sex. At baseline, 32% of the children had neurodevelopmental/psychiatric comorbidities or CP compared to 35%, 24 months later. Children with such comorbidities more often experienced seizures 13-24 months after the index seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention deficit hyperactivity disorder (ADHD). Children diagnosed at age <1 year exhibited the highest prevalence of comorbidities as well as OR for repeated seizures. A combination of young age and comorbidity was associated with an OR for repeated seizures of 5.12 (CI 3.03-8.65). Among the children without comorbidities 76% were seizure free 13-24 months after the index seizure or after initiation of AED treatment compared to 53% of children with comorbidities. This study indicates that neurodevelopmental comorbidities and CP in children with epilepsy tend to be present already at seizure onset and that such comorbidities are strong indicators of poor outcome regarding seizure control with or without

Pre-seizure state identified by diffuse optical tomography

PubMed Central

Zhang, Tao; Zhou, Junli; Jiang, Ruixin; Yang, Hao; Carney, Paul R.; Jiang, Huabei

2014-01-01

In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways. PMID:24445927

Physics of the Brain: Interaction of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams with the Epilepsy Topion, (the Seizure Onset Area)

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

A novel method for the possible prevention of epileptic seizures is proposed, based on the multi-ultraviolet-photon beam interaction with the epilepsy topion, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion lead, (within the 10s of milliseconds), to the onset of chaos, (seizure--excessive electrical discharge), and subsequent cascading into adjacent areas. The ultraviolet photons may control the imbalance of sodium and potassium ions and, consequently, may prove to be efficient in the prevention of epileptic seizures. Supported by Nikola Tesla Labs, Stefan University.

Integrating artificial intelligence with real-time intracranial EEG monitoring to automate interictal identification of seizure onset zones in focal epilepsy.

PubMed

Varatharajah, Yogatheesan; Berry, Brent; Cimbalnik, Jan; Kremen, Vaclav; Van Gompel, Jamie; Stead, Matt; Brinkmann, Benjamin; Iyer, Ravishankar; Worrell, Gregory

2018-08-01

An ability to map seizure-generating brain tissue, i.e. the seizure onset zone (SOZ), without recording actual seizures could reduce the duration of invasive EEG monitoring for patients with drug-resistant epilepsy. A widely-adopted practice in the literature is to compare the incidence (events/time) of putative pathological electrophysiological biomarkers associated with epileptic brain tissue with the SOZ determined from spontaneous seizures recorded with intracranial EEG, primarily using a single biomarker. Clinical translation of the previous efforts suffers from their inability to generalize across multiple patients because of (a) the inter-patient variability and (b) the temporal variability in the epileptogenic activity. Here, we report an artificial intelligence-based approach for combining multiple interictal electrophysiological biomarkers and their temporal characteristics as a way of accounting for the above barriers and show that it can reliably identify seizure onset zones in a study cohort of 82 patients who underwent evaluation for drug-resistant epilepsy. Our investigation provides evidence that utilizing the complementary information provided by multiple electrophysiological biomarkers and their temporal characteristics can significantly improve the localization potential compared to previously published single-biomarker incidence-based approaches, resulting in an average area under ROC curve (AUC) value of 0.73 in a cohort of 82 patients. Our results also suggest that recording durations between 90 min and 2 h are sufficient to localize SOZs with accuracies that may prove clinically relevant. The successful validation of our approach on a large cohort of 82 patients warrants future investigation on the feasibility of utilizing intra-operative EEG monitoring and artificial intelligence to localize epileptogenic brain tissue. Broadly, our study demonstrates the use of artificial intelligence coupled with careful feature engineering in

Imaging DC MEG Fields Associated with Epileptic Onset

NASA Astrophysics Data System (ADS)

Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

2004-10-01

Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

Soy infant formula and seizures in children with autism: a retrospective study.

PubMed

Westmark, Cara J

2014-01-01

Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR = 2.6, 95% CI = 1.3-5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR = 2.2, 95% CI = 1.1-4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR = 4.8, 95% CI = 1.0-23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. Despite these limitations, our results suggest that the use of soy-based infant formula may be associated with febrile seizures in both genders and with a diagnosis of epilepsy in males in autistic children. Given the lack of data on critical confounders and the retrospective nature of the study, a prospective study is required to confirm

Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

PubMed

Mintzer, Scott; Wechsler, Robert T; Rogin, Joanne B; Gidal, Barry E; Schwab, Matthias; Ben-Menachem, Elinor; Carreño, Mar; da Silva, Patrício Soares; Moreira, Joana; Li, Yan; Blum, David; Grinnell, Todd

2018-03-01

To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (<6 mg/dL) and ESL 1200 mg QD (<10 mg/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations. Copyright © 2018 The Authors. Published by Elsevier B.V. All

Early seizure detection in an animal model of temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Talathi, Sachin S.; Hwang, Dong-Uk; Ditto, William; Carney, Paul R.

2007-11-01

The performance of five seizure detection schemes, i.e., Nonlinear embedding delay, Hurst scaling, Wavelet Scale, autocorrelation and gradient of accumulated energy, in their ability to detect EEG seizures close to the seizure onset time were evaluated to determine the feasibility of their application in the development of a real time closed loop seizure intervention program (RCLSIP). The criteria chosen for the performance evaluation were, high statistical robustness as determined through the predictability index, the sensitivity and the specificity of a given measure to detect an EEG seizure, the lag in seizure detection with respect to the EEG seizure onset time, as determined through visual inspection and the computational efficiency for each detection measure. An optimality function was designed to evaluate the overall performance of each measure dependent on the criteria chosen. While each of the above measures analyzed for seizure detection performed very well in terms of the statistical parameters, the nonlinear embedding delay measure was found to have the highest optimality index due to its ability to detect seizure very close to the EEG seizure onset time, thereby making it the most suitable dynamical measure in the development of RCLSIP in rat model with chronic limbic epilepsy.

Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

2015-08-01

The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

Reversible MRI lesions after seizures.

PubMed

Aykut-Bingol, C; Tekin, S; Ince, D; Aktan, S

1997-06-01

After generalized or partial seizures, transient lesions may appear on magnetic resonance (MR) images. The mechanisms of MR changes might be a defect in cerebral autoregulation and blood-brain permeability. We report a patient with partial and secondary generalized tonic-clonic seizures. After her first seizure which was generalized tonic-clonic in nature, we detected multiple high signal intensities over the frontal cortical area on proton density images which were enhanced with gadolinium on T1-weighted images. The first and repeated EEGs showed no abnormalities or epileptic discharges. We started carbamezapine (600 mg/d) and excluded systemic diseases like vasculitis, infections, aetiological factors causing cerebrovascular diseases. In the follow-up, she was seizure free under antiepileptic therapy and no other neurological deficit. Repeated MR scans after 24 months from her first seizure revealed no pathologic signal intensities. Although the pathophysiology is unknown, recognition of reversible lesions helps diagnostic and therapeutic approaches to abnormal MR findings after seizures.

The new patient with a first seizure.

PubMed

King, Mark

2003-04-01

First seizures are common, with one in 20 people suffering a seizure at some time in their life. This article aims to outline the assessment of patients with a first seizure, including making an accurate diagnosis of both seizure type and an epilepsy syndrome, if present. Seizures are classified into generalised and partial (arising from a focal region in the brain) based on clinical and electroencephalogram findings. However, as a partial seizure may proceed to a tonic clonic phase, differentiation may be difficult. Inquiring directly about 'minor' epileptic symptoms before the episode such as absences, myoclonic jerks, visual or auditory hallucinations or feelings of déjà vu, is needed to attempt to make a epilepsy syndrome diagnosis, as this has practical implications for treatment, prognosis and genetic counselling. Generalised epilepsies should be treated initially with valproate, while partial epilepsies should be treated with carbamazepine and switched to newer agents if intolerance occurs.

Seizure ending signs in patients with dyscognitive focal seizures.

PubMed

Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

2015-09-01

Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

Using trend templates in a neonatal seizure algorithm improves detection of short seizures in a foetal ovine model.

PubMed

Zwanenburg, Alex; Andriessen, Peter; Jellema, Reint K; Niemarkt, Hendrik J; Wolfs, Tim G A M; Kramer, Boris W; Delhaas, Tammo

2015-03-01

Seizures below one minute in duration are difficult to assess correctly using seizure detection algorithms. We aimed to improve neonatal detection algorithm performance for short seizures through the use of trend templates for seizure onset and end. Bipolar EEG were recorded within a transiently asphyxiated ovine model at 0.7 gestational age, a common experimental model for studying brain development in humans of 30-34 weeks of gestation. Transient asphyxia led to electrographic seizures within 6-8 h. A total of 3159 seizures, 2386 shorter than one minute, were annotated in 1976 h-long EEG recordings from 17 foetal lambs. To capture EEG characteristics, five features, sensitive to seizures, were calculated and used to derive trend information. Feature values and trend information were used as input for support vector machine classification and subsequently post-processed. Performance metrics, calculated after post-processing, were compared between analyses with and without employing trend information. Detector performance was assessed after five-fold cross-validation conducted ten times with random splits. The use of trend templates for seizure onset and end in a neonatal seizure detection algorithm significantly improves the correct detection of short seizures using two-channel EEG recordings from 54.3% (52.6-56.1) to 59.5% (58.5-59.9) at FDR 2.0 (median (range); p < 0.001, Wilcoxon signed rank test). Using trend templates might therefore aid in detection of short seizures by EEG monitoring at the NICU.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

PubMed

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

Pretreatment seizure semiology in childhood absence epilepsy.

PubMed

Kessler, Sudha Kilaru; Shinnar, Shlomo; Cnaan, Avital; Dlugos, Dennis; Conry, Joan; Hirtz, Deborah G; Hu, Fengming; Liu, Chunyan; Mizrahi, Eli M; Moshé, Solomon L; Clark, Peggy; Glauser, Tracy A

2017-08-15

To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern. Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome. © 2017 American Academy of Neurology.

Audiogenic reflex seizures in cats

PubMed Central

Lowrie, Mark; Bessant, Claire; Harvey, Robert J; Sparkes, Andrew; Garosi, Laurent

2015-01-01

Objectives This study aimed to characterise feline audiogenic reflex seizures (FARS). Methods An online questionnaire was developed to capture information from owners with cats suffering from FARS. This was collated with the medical records from the primary veterinarian. Ninety-six cats were included. Results Myoclonic seizures were one of the cardinal signs of this syndrome (90/96), frequently occurring prior to generalised tonic–clonic seizures (GTCSs) in this population. Other features include a late onset (median 15 years) and absence seizures (6/96), with most seizures triggered by high-frequency sounds amid occasional spontaneous seizures (up to 20%). Half the population (48/96) had hearing impairment or were deaf. One-third of cats (35/96) had concurrent diseases, most likely reflecting the age distribution. Birmans were strongly represented (30/96). Levetiracetam gave good seizure control. The course of the epilepsy was non-progressive in the majority (68/96), with an improvement over time in some (23/96). Only 33/96 and 11/90 owners, respectively, felt the GTCSs and myoclonic seizures affected their cat’s quality of life (QoL). Despite this, many owners (50/96) reported a slow decline in their cat’s health, becoming less responsive (43/50), not jumping (41/50), becoming uncoordinated or weak in the pelvic limbs (24/50) and exhibiting dramatic weight loss (39/50). These signs were exclusively reported in cats experiencing seizures for >2 years, with 42/50 owners stating these signs affected their cat’s QoL. Conclusions and relevance In gathering data on audiogenic seizures in cats, we have identified a new epilepsy syndrome named FARS with a geriatric onset. Further studies are warranted to investigate potential genetic predispositions to this condition. PMID:25916687

Seizures in juvenile Huntington's disease: frequency and characterization in a multicenter cohort.

PubMed

Cloud, Leslie J; Rosenblatt, Adam; Margolis, Russel L; Ross, Christopher A; Pillai, Jagan A; Corey-Bloom, Jody; Tully, Hannah M; Bird, Thomas; Panegyres, Peter K; Nichter, Charles A; Higgins, Donald S; Helmers, Sandra L; Factor, Stewart A; Jones, Randi; Testa, Claudia M

2012-12-01

Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required. Copyright © 2012 Movement Disorder Society.

Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures.

PubMed

Andermann, Eva; Biton, Victor; Benbadis, Selim R; Shneker, Bassel; Shah, Aashit K; Carreño, Mar; Trinka, Eugen; Ben-Menachem, Elinor; Biraben, Arnaud; Rocha, Francisco; Gama, Helena; Cheng, Hailong; Blum, David

2018-05-01

To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400mg (studies 301 and 302 only), 800mg, or 1200mg once daily (QD) for 14weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. The analysis population included 1447 patients (ESL, n=1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p=0.802). The incidence of depression and suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p=0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p=0.023); incidences of memory impairment, attention disturbance, apathy, and aphasia were higher for ESL 1200mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs (SAEs) were 0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to

Understanding the Patient Perspective of Seizure Severity in Epilepsy: Development of a Conceptual Model.

PubMed

Borghs, Simon; Tomaszewski, Erin L; Halling, Katarina; de la Loge, Christine

2016-10-01

For patients with uncontrolled epilepsy, the severity and postictal sequelae of seizures might be more impactful than their frequency. Seizure severity is often assessed using patient-reported outcome (PRO) instruments; however, evidence of content validity for existing instruments is lacking. Our aim was to understand the real-life experiences of patients with uncontrolled epilepsy. A preliminary conceptual model was developed. The model was refined through (1) a targeted literature review of qualitative research on seizure severity; (2) interviews with four clinical epilepsy experts to evaluate identified concepts; and (3) qualitative interviews with patients with uncontrolled epilepsy, gathering descriptions of symptoms and impacts of epilepsy, focusing on how patients experience and describe "seizure severity." Findings were summarized in a final conceptual model of seizure severity in epilepsy. Twenty-five patients (12 who experienced primary generalized tonic-clonic seizures and 13 who experienced partial-onset seizures) expressed 42 different symptoms and 26 different impacts related to seizures. The final conceptual model contained a wide range of concepts related to seizure frequency, symptoms, and duration. Our model identified several new concepts that characterize the patient experience of seizure severity. A seizure severity PRO instrument should cover a wide range of seizure symptoms alongside frequency and duration of seizures. This qualitative work reinforces the notion that measuring seizure frequency is insufficient and that seizure severity is important in defining the patient's experience of epilepsy. This model could be used to assess the content validity of existing PRO instruments, or could support the development of a new one.

Electroencephalography after a single unprovoked seizure.

PubMed

Debicki, Derek B

2017-07-01

Electroencephalography (EEG) is an essential diagnostic tool in the evaluation of seizure disorders. In particular, EEG is used as an additional investigation for a single unprovoked seizure. Epileptiform abnormalities are related to seizure disorders and have been shown to predict recurrent unprovoked seizures (i.e., a clinical definition of epilepsy). Thus, the identification of epileptiform abnormalities after a single unprovoked seizure can inform treatment options. The current review addresses the relationship between EEG abnormalities and seizure recurrence. This review also addresses factors that are found to improve the yield of recording epileptiform abnormalities including timing of EEG relative to the new-onset seizure, use of repeat studies, use of sleep deprivation and prolonged recordings. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Camphor: an herbal medicine causing grand mal seizures

PubMed Central

MacKinney, Theodore G; Soti, Kamal Raj; Shrestha, Poojan; Basnyat, Buddha

2015-01-01

Camphor is usually used in the USA to repel insects, but it is widely used in other countries as an herb. We report the case of a 52-year-old previously healthy Nepali man who ingested approximately 10 g of pure camphor with therapeutic intention. He developed grand mal seizures, and was evaluated in an emergency room. He failed to recall the camphor ingestion initially, and was treated with phenytoin for new-onset idiopathic seizures. Examining physicians only later found out about his camphor ingestion. Finding the cause of new-onset seizures is often challenging for emergency room physicians, internists and neurologists. In addition to other well-reported causes of secondary seizures, herbal medications and supplements must also be explored. PMID:26065546

Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom.

PubMed

Tong, Man-Li; Liu, Li-Li; Zeng, Yan-Li; Zhang, Hui-Lin; Liu, Gui-Li; Zheng, Wei-Hong; Dong, Jie; Wu, Jing-Yi; Su, Yuan-Hui; Lin, Li-Rong; Yang, Tian-Ci

2013-04-01

A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS. Copyright © 2013 Elsevier Inc. All rights reserved.

The semiology of febrile seizures: Focal features are frequent.

PubMed

Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

2017-08-01

To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic timecourse of typical childhood absence seizures: EEG, behavior and fMRI

PubMed Central

Bai, X; Vestal, M; Berman, R; Negishi, M; Spann, M; Vega, C; Desalvo, M; Novotny, EJ; Constable, RT; Blumenfeld, H

2010-01-01

Absence seizures are 5–10 second episodes of impaired consciousness accompanied by 3–4Hz generalized spike-and-wave discharge on electroencephalography (EEG). The timecourse of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from 9 pediatric patients. We investigated behavior concurrently using a continuous performance task (CPT) or simpler repetitive tapping task (RTT). EEG time-frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5s before seizure onset, followed by profound fMRI decreases continuing >20s after seizure end. This timecourse differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long lasting sequence of fMRI changes in absence seizures, which are not detectible by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior. PMID:20427649

Effect of vaccinations on seizure risk and disease course in Dravet syndrome.

PubMed

Verbeek, Nienke E; van der Maas, Nicoline A T; Sonsma, Anja C M; Ippel, Elly; Vermeer-de Bondt, Patricia E; Hagebeuk, Eveline; Jansen, Floor E; Geesink, Huibert H; Braun, Kees P; de Louw, Anton; Augustijn, Paul B; Neuteboom, Rinze F; Schieving, Jolanda H; Stroink, Hans; Vermeulen, R Jeroen; Nicolai, Joost; Brouwer, Oebele F; van Kempen, Marjan; de Kovel, Carolien G F; Kemmeren, Jeanet M; Koeleman, Bobby P C; Knoers, Nine V; Lindhout, Dick; Gunning, W Boudewijn; Brilstra, Eva H

2015-08-18

To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific. © 2015 American Academy of Neurology.

Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

PubMed

Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

2013-12-01

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

PubMed

Taub, Katherine S; Kessler, Sudha Kilaru; Bergqvist, A G Christina

2014-04-01

Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

The New Classification of Seizures by the International League Against Epilepsy 2017.

PubMed

Fisher, Robert S

2017-06-01

This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types. The fundamental distinction is between seizures that begin focally in one hemisphere of the brain, generalized onset seizures that apparently originate in both hemispheres, and seizures of unknown onset. Focal seizures optionally can be subclassified according to whether awareness (a surrogate marker for consciousness) is intact or impaired. The next level of classification for focal seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic. Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The classification allows new types of focal seizures and a few new generalized seizures, and clarifies terms used to name seizures.

High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

PubMed

Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

2016-08-01

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.

Automatic and remote controlled ictal SPECT injection for seizure focus localization by use of a commercial contrast agent application pump.

PubMed

Feichtinger, Michael; Eder, Hans; Holl, Alexander; Körner, Eva; Zmugg, Gerda; Aigner, Reingard; Fazekas, Franz; Ott, Erwin

2007-07-01

In the presurgical evaluation of patients with partial epilepsy, the ictal single photon emission computed tomography (SPECT) is a useful noninvasive diagnostic tool for seizure focus localization. To achieve optimal SPECT scan quality, ictal tracer injection should be carried out as quickly as possible after the seizure onset and under highest safety conditions possible. Compared to the commonly used manual injection, an automatic administration of the radioactive tracer may provide higher quality standards for this procedure. In this study, therefore, we retrospectively analyzed efficiency and safety of an automatic injection system for ictal SPECT tracer application. Over a 31-month period, 26 patients underwent ictal SPECT by use of an automatic remote-controlled injection pump originally designed for CT-contrast agent application. Various factors were reviewed, including latency of ictal injection, radiation safety parameters, and ictal seizure onset localizing value. Times between seizure onset and tracer injection ranged between 3 and 48 s. In 21 of 26 patients ictal SPECT supported the localization of the epileptogenic focus in the course of the presurgical evaluation. In all cases ictal SPECT tracer injection was performed with a high degree of safety to patients and staff. Ictal SPECT by use of a remote-controlled CT-contrast agent injection system provides a high scan quality and is a safe and confirmatory presurgical evaluation technique in the epilepsy-monitoring unit.

Tiagabine in clinical practice: effects on seizure control and behavior.

PubMed

Vossler, David G; Morris, George L; Harden, Cynthia L; Montouris, Georgia; Faught, Edward; Kanner, Andres M; Fix, Aaron; French, Jacqueline A

2013-08-01

Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice. Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB. Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%). Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug. Copyright © 2013 Elsevier Inc. All rights reserved.

New onset paediatric epilepsy in 1-5 years age group children--approach to management in a tertiary care centre with newer anti-epileptic levetiracetam.

PubMed

Barik, Kanai Lal; Paul, Uttam Kumar; Bhattacharyya, Anup Kumar; Adhikary, Amit; Agarwal, Gajanand; Rana, Kriti Sundar

2014-02-01

Epilepsy is a common paediatric neurologic disorder that is difficult to manage in a substantial portion of children, highlighting the continued need for more effective and better tolerated drugs. A multicentric study was conducted from August, 2011 to July, 2013 using levetiracetam (LEV) in newely diagnosed epilepsy in 122 young children of 1-5 years age group to find its role in practical scenario depending upon the knowledge from prior literature available. It has been demonstrated effective as adjunctive therapy as well as monotherapy for new-onset partial seizures and generalised tonic-clonic seizures (GTCS) but it acts better as adjunctive therapy than the monotherapy. When LEV was used as adjunctive therapy 15.4% children with partial seizure were seizure-free as compared to 11.12% in GTCS and when LEV was used as monotherapy 16.17% children with partial seizure were seizure-free as compared to 15.38% in GTCS. When LEV was used as add on therapy 16.67% children < 2 years were seizure-free as compared to 17.85% in > 2 years. When LEV was used as monotherapy 25.00% children < 2 years were seizure-free as compared to 18.18% > 2 years. So, it was found more efficacious in partial group of seizures than the GTCS variety. It also shows more efficacy in older age group (> 2 years) than the younger ones (< 2 years). Somnolence and behavioural changes were noted as ad- verse effects in a few cases. So, LEV is an important addition to the treatment of paediatric epilepsy.

Seizures and epileptiform activity in the early stages of Alzheimer disease.

PubMed

Vossel, Keith A; Beagle, Alexander J; Rabinovici, Gil D; Shu, Huidy; Lee, Suzee E; Naasan, Georges; Hegde, Manu; Cornes, Susannah B; Henry, Maya L; Nelson, Alexandra B; Seeley, William W; Geschwind, Michael D; Gorno-Tempini, Maria L; Shih, Tina; Kirsch, Heidi E; Garcia, Paul A; Miller, Bruce L; Mucke, Lennart

2013-09-01

Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease. To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity. Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco. We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7). Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications. Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

PubMed

Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

2014-06-01

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

First seizure while driving (FSWD)--an underestimated phenomenon?

PubMed

Pohlmann-Eden, Bernd; Hynick, Nina; Legg, Karen

2013-07-01

Seizures while driving are a well known occurrence in established epilepsy and have significant impact on driving privileges. There is no data available on patients who experience their first (diagnosed) seizure while driving (FSWD). Out of 311 patients presenting to the Halifax First Seizure Clinic between 2008 and 2011, 158 patients met the criteria of a first seizure (FS) or drug-naïve, newly diagnosed epilepsy (NDE). A retrospective chart review was conducted. FSWD was evaluated for 1) prevalence, 2) clinical presentation, 3) coping strategies, and 4) length of time driving before seizure occurrence. The prevalence of FSWD was 8.2%. All 13 patients experienced impaired consciousness. Eleven patients had generalized tonic-clonic seizures, one starting with a déjà-vu evolving to visual aura and a complex partial seizure; three directly from visual auras. Two patients had complex partial seizures, one starting with an autonomic seizure. In response to their seizure, patients reported they were i) able to actively stop the car (n=4, three had visual auras), ii) not able to stop the car resulting in accident (n=7), or iii) passenger was able to pull the car over (n=2). One accident was fatal to the other party. Twelve out of 13 patients had been driving for less than one hour. FSWD is frequent and possibly underrecognized. FSWD often lead to accidents, which occur less if preceded by simple partial seizures. Pathophysiological mechanisms remain uncertain; it is still speculative if complex visuo-motor tasks required while driving play a role in this scenario.

A novel seizure detection algorithm informed by hidden Markov model event states

NASA Astrophysics Data System (ADS)

Baldassano, Steven; Wulsin, Drausin; Ung, Hoameng; Blevins, Tyler; Brown, Mesha-Gay; Fox, Emily; Litt, Brian

2016-06-01

Objective. Recently the FDA approved the first responsive, closed-loop intracranial device to treat epilepsy. Because these devices must respond within seconds of seizure onset and not miss events, they are tuned to have high sensitivity, leading to frequent false positive stimulations and decreased battery life. In this work, we propose a more robust seizure detection model. Approach. We use a Bayesian nonparametric Markov switching process to parse intracranial EEG (iEEG) data into distinct dynamic event states. Each event state is then modeled as a multidimensional Gaussian distribution to allow for predictive state assignment. By detecting event states highly specific for seizure onset zones, the method can identify precise regions of iEEG data associated with the transition to seizure activity, reducing false positive detections associated with interictal bursts. The seizure detection algorithm was translated to a real-time application and validated in a small pilot study using 391 days of continuous iEEG data from two dogs with naturally occurring, multifocal epilepsy. A feature-based seizure detector modeled after the NeuroPace RNS System was developed as a control. Main results. Our novel seizure detection method demonstrated an improvement in false negative rate (0/55 seizures missed versus 2/55 seizures missed) as well as a significantly reduced false positive rate (0.0012 h versus 0.058 h-1). All seizures were detected an average of 12.1 ± 6.9 s before the onset of unequivocal epileptic activity (unequivocal epileptic onset (UEO)). Significance. This algorithm represents a computationally inexpensive, individualized, real-time detection method suitable for implantable antiepileptic devices that may considerably reduce false positive rate relative to current industry standards.

Creutzfeldt-Jakob disease with Alzheimer pathology, presenting with status epilepticus following repeated partial seizures: a case report and literature review.

PubMed

Miyake, Keita; Hara, Takashi; Oshima, Etsuko; Kawada, Kiyohiro; Ishizu, Hideki; Yamauchi, Yuko; Satoh, Katsuya; Kitamoto, Tetsuyuki; Takenoshita, Shintaro; Terada, Seishi; Yamada, Norihito

2018-04-25

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease. Common first symptoms are dementia, cerebellar ataxia, visual disturbance, and psychiatric symptoms. Seizure as the first symptom of CJD is a very rare finding. We experienced an elderly woman who presented initially with status epilepticus following repeated partial seizures in the course of Alzheimer disease (AD) dementia. Anti-convulsive therapy had no effect. Autopsy revealed definite CJD with AD pathology. This is the first reported CJD case presenting with status epilepticus in the course of AD dementia.

Seizure outcome in 175 patients with juvenile myoclonic epilepsy--a long-term observational study.

PubMed

Höfler, Julia; Unterberger, Iris; Dobesberger, Judith; Kuchukhidze, Giorgi; Walser, Gerald; Trinka, Eugen

2014-12-01

Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. We retrospectively studied 242 patients with JME at the Department of Neurology, Medical University Innsbruck, Austria (1975-2006). We analyzed age at seizure onset, age at last follow up, seizure types, photosensitivity, seizure outcome and neuroimaging findings; inclusion criterion was a medical treatment period of >2 years; exclusion criteria were traumatic or infectious brain injury before the onset of JME and/or gross structural pathology on neuroimaging. We identified 175 patients (111 women) with a median age at seizure onset of 15 years, (range 3-46) and a median age at follow-up (FU) of 38 years (range 14-87; median FU 8 years, range 2-38). Fourteen percent showed (24/175) photosensitivity on routine EEG. Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for >1 year, and 53% (94/175) for >2 years, including 16 patients (9%) without AEDs. Thirty-one percent (54/175) were seizure-free between 2 and 5 years, 15% (26/175) between 6 and 10, and 8% (14/175) >10 years; 38% (66/175) were not seizure-free. Not seizure-free patients had more often MS, AS and GTCS within the first year of epilepsy than those who were seizure-free at last FU (11% vs. 3%, Chi(2)=4.679, df=1, p=0.043). Seizure-free patients had more often MS and GTCS as last seizure types in the year before becoming seizure-free (37% vs. 15%, p=0.003), whereas in not seizure-free group MS only and GTCS only persisted. JME does not always need lifelong treatment, as a substantial minority of patients remain seizure-free without AEDs. AS, MS and GTCS at onset of the disease are indicators of poor long-term seizure control. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature.

PubMed

Nemos, C; Lambert, L; Giuliano, F; Doray, B; Roubertie, A; Goldenberg, A; Delobel, B; Layet, V; N'guyen, M A; Saunier, A; Verneau, F; Jonveaux, P; Philippe, C

2009-10-01

The CDKL5 gene has been implicated in the molecular etiology of early-onset intractable seizures with infantile spasms (IS), severe hypotonia and atypical Rett syndrome (RTT) features. So far, 48 deleterious alleles have been reported in the literature. We screened the CDKL5 gene in a cohort of 177 patients with early-onset seizures, including 30 men and 10 girls with Aicardi syndrome. The screening was negative for all men as well as for women with Aicardi syndrome, excluding the CDKL5 gene as a candidate for this neurodevelopmental disorder. We report 11 additional de novo mutations in CDKL5 in female patients. For the first time, the MLPA approach allowed the identification of a partial deletion encompassing the promoter and the first two exons of CDKL5. The 10-point mutations consist of five missenses (with recurrent amino acid changes at p.Ala40 and p.Arg178), four splicing variants and a 1-base pair duplication. We present a review of all mutated alleles published in the literature. In our study, the overall frequency of mutations in CDKL5 in women with early-onset seizures is around 8.6%, a result comparable with previous reports. Noteworthy, the CDKL5 mutation rate is high (28%) in women with early-onset seizures and IS.

Laser-Bioplasma Interaction: The Epilepsy-Topion-Bioplasma, (the Seizure Onset Area) Upon the Action of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

2016-10-01

The ultraviolet photons may control the imbalance of sodium and potassium ions in the brain bioplasma and, consequently, may prove to be efficient in the prevention of epileptic seizures. A novel method is based on the multi-ultraviolet-photon beam interaction with the epilepsy-topion-bioplasma, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion-bioplasma lead, (within the 10s of milliseconds), to the onset of chaos, (seizure-excessive electrical discharge), and subsequent cascading into adjacent areas.

High frequency oscillations (80–500 Hz) in the preictal period in patients with focal seizures

PubMed Central

Jacobs, Julia; Zelmann, Rina; Jirsch, Jeffrey; Chander, Rahul; Châtillon, Claude-Édouard; Dubeau, François; Gotman, Jean

2013-01-01

Summary Purpose Intracranial depth macroelectrode recordings from patients with focal seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80–500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and reported to be linked to seizure genesis. We evaluated whether HFO activity changes in a systematic way during the preictal period. Methods Fifteen minutes of preictal intracranial electroencephalography (EEG) recordings were evaluated in seven consecutive patients with well-defined SOZ. EEG was filtered at 500 Hz and sampled at 2,000 Hz. Ripples (80–250 Hz) and fast ripples (250–500 Hz) were visually marked, and spectral analysis was performed in seizure-onset as well as nonseizure-onset channels. Linear regressions fitted to the power trends corresponding to intervals of 1, 5, and 15 min before the seizure onset was calculated. Results Total rates of HFOs were significantly higher in the SOZ than outside. Preictal increases and decreases in HFO rates and band power could be detected in all patients, and they were not limited to the SOZs. These measures were very variable, and nosystematic trends were observed when comparing patients or seizures in the same patient. Discussion High frequencies in the range of 80–500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80–500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes. PMID:19400871

The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures.

PubMed

Donati, Filippo; Gobbi, Giuseppe; Campistol, Jaume; Rapatz, Guenter; Daehler, Maja; Sturm, Yvonne; Aldenkamp, Albert P

2007-12-01

To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to <17 years) with newly diagnosed partial seizures. A multicentre, open-label, randomised, active-control, three-arm, parallel-group, 6-month study. The primary cognitive variable, the Computerized Visual Searching Task (CVST), assessed mental information processing speed and attention. Secondary variables included additional tests assessing psychomotor speed, alertness, memory and learning, and non-verbal intelligence. Of 112 patients randomised, 99 completed the study. The dropout rate was 11.6%; 13 patients discontinued due to adverse events (n=5) or unsatisfactory therapeutic effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

PubMed

Gerlach, Anthony T; Thomas, Sheela; Stawicki, Stanislaw P; Whitmill, Melissa L; Steinberg, Steven M; Cook, Charles H

2011-03-01

In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Case series. Tertiary care surgical intensive care unit. In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Intravenous pyridoxine followed by oral pyridoxine. In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

Ketogenic diet: Predictors of seizure control.

PubMed

Agarwal, Nitin; Arkilo, Dimitrios; Farooq, Osman; Gillogly, Cynthia; Kavak, Katelyn S; Weinstock, Arie

2017-01-01

The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings.

The utility score of epilepsy with partial seizure measured by TTO, VAS, and EQ-5D in the general Korean population.

PubMed

Kang, Hee-Jin; Kang, Eunjeong; Jo, Min-Woo; Park, Eun-Ja; Yoon, Seonyoung; Lee, Eui-Kyung

2014-07-01

This study aimed to measure utilities, which are quantitative terms incorporating preferences, for various health states of epilepsy with partial seizure in the general population in South Korea. It also aimed to find socio-demographic characteristics associated with the utility scores. Utility scores using Time Trade-Off (TTO), Visual Analog Scale (VAS), and EuroQol five Dimension (EQ-5D) were obtained from 300 people aged 16 and over by face-to-face interviews. We measured utilities for three hypothetical health states of epilepsy for which scenarios were defined based on the frequency of partial seizure: seizure-free, seizure reduction, and withdrawal. We compared utilities with varying seizure frequency using a repeated-measures ANOVA, and analyzed the association between utilities and socio-demographic characteristics using a generalized estimating equation (GEE). The mean utility scores for withdrawal state, seizure reduction state, and seizure-free state were 0.303, 0.493, and 0.899, respectively, when measured by TTO. VAS yielded the mean utility scores of 0.211, 0.424, and 0.752 for respective health states, and corresponding scores with EQ-5D were 0.261, 0.645, and 0.959. The utility scores for the three health states were statistically different in TTO, VAS, and EQ-5D. The withdrawal state had the lowest utility scores. There were differences in mean utilities for the three health states across the three methods. Utilities by EQ-5D tended to have higher values than those by TTO and VAS. Utilities by VAS had the lowest values. In GEE analysis, the severity of epilepsy and household income were significantly related to utility scores. The withdrawal state of epilepsy had the lowest utility value and the seizure-free state had the highest by all three techniques of utility measurement used. There were significant differences in utilities between one severity level of epilepsy and another. Utility was associated with household income and the severity of

Seizures in hospitalized cocaine users.

PubMed

Choy-Kwong, M; Lipton, R B

1989-03-01

We reviewed the records of 283 cocaine abusers consecutively admitted to a municipal hospital, and identified eight patients (2.8%) who presented with seizures. Four (1.4%) had focal or generalized seizures temporally associated with cocaine use. Based on these four cases and five previous reports, we conclude that although seizures are relatively rare in hospitalized cocaine users, they are provoked by all major routes of administration, and may be partial or generalized.

Electrographic waveform structure predicts laminar focus location in a model of temporal lobe seizures in vitro.

PubMed

Adams, Christopher; Adams, Natalie E; Traub, Roger D; Whittington, Miles A

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is 'victim' or 'perpetrator': The structure is ideally placed to 'broadcast' epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin - a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.

Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

PubMed Central

Adams, Christopher; Adams, Natalie E.; Traub, Roger D.; Whittington, Miles A.

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role. PMID:25799020

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PubMed

Boon, Paul; Vonck, Kristl; van Rijckevorsel, Kenou; El Tahry, Riem; Elger, Christian E; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate; Hamer, Hajo; Reuber, Markus; Kostov, Hrisimir; Legros, Benjamin; Noachtar, Soheyl; Weber, Yvonne G; Coenen, Volker A; Rooijakkers, Herbert; Schijns, Olaf E M G; Selway, Richard; Van Roost, Dirk; Eggleston, Katherine S; Van Grunderbeek, Wim; Jayewardene, Amara K; McGuire, Ryan M

2015-11-01

This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

PubMed

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Seizure Freedom in Children With Pathology-Confirmed Focal Cortical Dysplasia.

PubMed

Mrelashvili, Anna; Witte, Robert J; Wirrell, Elaine C; Nickels, Katherine C; Wong-Kisiel, Lily C

2015-12-01

We evaluated the temporal course of seizure outcome in children with pathology-confirmed focal cortical dysplasia and explored predictors of sustained seizure freedom. We performed a single-center retrospective study of children ≤ 18 years who underwent resective surgery from January 1, 2000 through December 31, 2012 and had pathology-proven focal cortical dysplasia. Surgical outcome was classified as seizure freedom (Engel class I) or seizure recurrence (Engel classes II-IV). Fisher exact and nonparametric Wilcoxon ranksum tests were used, as appropriate. Survival analysis was based on seizure-free outcome. Patients were censored at the time of seizure recurrence or seizure freedom at last follow-up. Thirty-eight patients were identified (median age at surgery, 6.5 years; median duration of epilepsy, 3.3 years). Median time to last follow-up was 13.5 months (interquartile range, 7-41 months). Twenty patients (53%) were seizure free and 26 patients (68%) attained seizure freedom for a minimum of 3 months. Median time to seizure recurrence was 38 months (95% confidence interval, 6-109 months), and the cumulative seizure-free rate was 60% at 12 months (95% confidence interval, 43%-77%). Clinical features associated with seizure freedom at last follow-up included older age at seizure onset (P = .02), older age at surgery (P = .04), absent to mild intellectual disability before surgery (P = .05), and seizure freedom for a minimum of 3 months (P < .001). Favorable clinical features associated with sustained seizure freedom included older age at seizure onset, older age at surgery, absent or mild intellectual disability at baseline, and seizure freedom for a minimum of 3 months. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

PubMed

Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

2009-02-01

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. (c) 2009 Wiley-Liss, Inc.

Seizures induced by music.

PubMed

Ogunyemi, A O; Breen, H

1993-01-01

Musicogenic epilepsy is a rare disorder. Much remains to be learned about the electroclinical features. This report describes a patient who has been followed at our institution for 17 years, and was investigated with long-term telemetered simultaneous video-EEG recordings. She began to have seizures at the age of 10 years. She experienced complex partial seizures, often preceded by elementary auditory hallucination and complex auditory illusion. The seizures occurred in relation to singing, listening to music or thinking about music. She also had occasional generalized tonic clonic seizures during sleep. There was no significant antecedent history. The family history was negative for epilepsy. The physical examination was unremarkable. CT and MRI scans of the brain were normal. During long-term simultaneous video-EEG recordings, clinical and electrographic seizure activities were recorded in association with singing and listening to music. Mathematical calculation, copying or viewing geometric patterns and playing the game of chess failed to evoke seizures.

Seizure Disorders: An Alternative Explanation for Students' Inattention.

ERIC Educational Resources Information Center

Agnew, Christina M.; Nystul, Michael S.; Conner, Mary Catherine

1998-01-01

Provides an overview of seizure disorders. They are more common than previously thought, and most have their onset in adolescence. Types of seizure disorders common in children, their symptoms, and treatment are described. A case example illustrates behavior in school and a paradoxical medication effect. (EMK)

Comparative sensitivity of quantitative EEG (QEEG) spectrograms for detecting seizure subtypes.

PubMed

Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

2018-02-01

To assess the sensitivity of Persyst version 12 QEEG spectrograms to detect focal, focal with secondarily generalized, and generalized onset seizures. A cohort of 562 seizures from 58 patients was analyzed. Successive recordings with 2 or more seizures during continuous EEG monitoring for clinical indications in the ICU or EMU between July 2016 and January 2017 were included. Patient ages ranged from 5 to 64 years (mean = 36 years). There were 125 focal seizures, 187 secondarily generalized and 250 generalized seizures from 58 patients analyzed. Seizures were identified and classified independently by two epileptologists. A correlate to the seizure pattern in the raw EEG was sought in the QEEG spectrograms in 4-6 h EEG epochs surrounding the identified seizures. A given spectrogram was interpreted as indicating a seizure, if at the time of a seizure it showed a visually significant departure from the pre-event baseline. Sensitivities for seizure detection using each spectrogram were determined for each seizure subtype. Overall sensitivities of the QEEG spectrograms for detecting seizures ranged from 43% to 72%, with highest sensitivity (402/562,72%) by the seizure detection trend. The asymmetry spectrogram had the highest sensitivity for detecting focal seizures (117/125,94%). The FFT spectrogram was most sensitive for detecting secondarily generalized seizures (158/187, 84%). The seizure detection trend was the most sensitive for generalized onset seizures (197/250,79%). Our study suggests that different seizure types have specific patterns in the Persyst QEEG spectrograms. Identifying these patterns in the EEG can significantly increase the sensitivity for seizure identification. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Predictors of spontaneous transient seizure remission in patients of medically refractory epilepsy due to mesial temporal sclerosis (MTS).

PubMed

Dhiman, Vikas; Sinha, Sanjib; Arimappamagan, Arivazhagan; Mahadevan, Anita; Bharath, Rose Dawn; Saini, Jitender; Rajeswaran, Jamuna; Rao, Malla Bhaskar; Shankar, Susrala K; Satishchandra, Parathasarthy

2015-02-01

To analyze the predictors of spontaneous transient seizure remission for ≥1 year in patients with drug-resistant epilepsy (DRE) due to mesial temporal sclerosis (MTS). This analysis included 38 patients with DRE (M:F = 20:18, age: 31.7 ± 10.9 years) diagnosed with unilateral MTS (right:left = 16:22). Group I ('remission' group) comprised of patients with seizure remission (M:F = 10:8, age: 32.8 ± 12.3 years, mean seizure free period: 2.2 ± 1.1 years; median: 2.1 years). Group II ('non-remission' group) comprised of age and gender matched 20 patients (M:F = 10:10, age: 30.7 ± 9.7 years) with unilateral MTS who never had seizure remission and subsequently underwent epilepsy surgery. Groups I and II were compared to find the predictors associated with transient seizure remission. The age at onset of seizures in group I was 13.2 ± 11.8 years and in group II was 12.0 ± 7.6 years. The duration of seizure was: group I - 19.7 ± 12.5 years and group II - 19.3 ± 7.7 years. Past history of seizure remissions (p < 0.001), frequent periods of remissions (p < 0.001), first remission within a year of onset of seizures (p = 0.04) and normal EEG (p = 0.04) were the important clinical predictors associated with seizure remission in this cohort. Fifteen patients in group I (83.3%) experienced remission following either change in AED (p ≤ 0.001) or increase in AED dosages (p < 0.001). There was no difference between the two groups regarding the type of semiology (partial vs. secondarily generalized) (p = 0.50), family history of seizures (p = 1.0), side of the lesion (p = 0.34), history of febrile seizures (p = 1.0) and the number of AEDs used (p = 0.53). The present study unfolds, some of the clinically relevant predictors associated with transient seizure remission in patients with DRE and MTS. Future molecular and network studies are required to understand its mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamic, cell type-specific roles for GABAergic interneurons in a mouse model of optogenetically inducible seizures

PubMed Central

Khoshkhoo, Sattar; Vogt, Daniel; Sohal, Vikaas S.

2016-01-01

SUMMARY GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later. Optogenetically inhibiting VIP interneurons consistently increased seizure threshold and reduced seizure duration. Inhibiting PV+ and SOM+ interneurons had mixed effects on seizure initiation, but consistently reduced seizure duration. Thus, while their roles may evolve during seizures, PV+ and SOM+ interneurons ultimately help maintain ongoing seizures. These results show how an optogenetically-induced seizure model can be leveraged to pinpoint a new target for seizure control: VIP interneurons. PMID:28041880

Reflex seizures in Rett syndrome.

PubMed

Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

2011-12-01

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

Functional definition of seizure provides new insight into post-traumatic epileptogenesis.

PubMed

D'Ambrosio, Raimondo; Hakimian, Shahin; Stewart, Tessandra; Verley, Derek R; Fender, Jason S; Eastman, Clifford L; Sheerin, Aaron H; Gupta, Puneet; Diaz-Arrastia, Ramon; Ojemann, Jeffrey; Miller, John W

2009-10-01

Experimental animals' seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8-2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8-2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8-2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed, with

Functional definition of seizure provides new insight into post-traumatic epileptogenesis

PubMed Central

Hakimian, Shahin; Stewart, Tessandra; Verley, Derek R.; Fender, Jason S.; Eastman, Clifford L.; Sheerin, Aaron H.; Gupta, Puneet; Diaz-Arrastia, Ramon; Ojemann, Jeffrey; Miller, John W.

2009-01-01

Experimental animals’ seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8–2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8–2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8–2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed

Microscale Spatiotemporal Dynamics during Neocortical Propagation of Human Focal Seizures

PubMed Central

Wagner, Fabien B.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.; Truccolo, Wilson

2015-01-01

Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4 × 4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) A newly developed stage segmentation method, applied to local field potentials (LFPs) and multi-unit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~ 2–3Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25–60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the

Evaluating the Anti-Seizure Efficacy of Novel Adenosine Treatment Regimens in a Soman Rat Model

DTIC Science & Technology

2015-06-01

activity following DPCPX treatment. However, 9 of the 12 rats proceeded to develop seizures and entered status epilepticus (Figure 4). This reaction was...onset. However, stopping status epilepticus once it develops is much more difficult than preventing its onset. The mechanism for terminating seizure...sarin. J Pharmacol Exp Ther 304(3): 1307- 1313. Compton, J. R. (2004). Adenosine Receptor Agonist Pd 81,723 Protects Against Seizure/ Status

Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures.

PubMed

Jóźwiak, Sergiusz; Veggiotti, P; Moreira, J; Gama, H; Rocha, F; Soares-da-Silva, P

2018-04-01

This was a phase-II, randomized, double-blind (DB), placebo-controlled study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS). Children (6-16years old) with FOS were randomized (2:1) to ESL or placebo. Treatment started at 10mg/kg/day, was up-titrated up to 30mg/kg/day (target dose), and maintained for 8weeks, followed by one-year open-label follow-up. The primary endpoint was change from baseline to the end of maintenance period in the composite Power of Attention assessed with the Cognitive Drug Research (CDR) system. Behavioral and emotional functioning and quality of life (QOL), secondary endpoints, were assessed with Child Health Questionnaire-Parent Form 50 (CHQ-PF50), Child Behavior Checklist (CBCL), and Raven's Standard Progressive Matrices (SPM). Efficacy was evaluated through changes in standardized seizure frequency (SF), responder rate, and proportion of seizure-free patients. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). One hundred and twenty-three patients were randomized. A noninferiority analysis failed to reject the null hypothesis that the change from baseline in the Power of Attention score in the ESL group was at least 121ms inferior to the placebo group for all age groups. The CDR scores showed no differences between placebo and ESL in Power of Attention (1868.0 vs 1759.5), Continuity of Attention (1.136 vs -1.786), Quality of Working Memory (-0.023 vs -0.024), and Speed of Memory (-263.4 vs -249.6). Nonsignificant differences between placebo and ESL were seen for CHQ-PF50, CBCL scores, and Raven's SPM. Episodic Memory Index showed significant negative effect on ESL. Efficacy results favored the ESL group (SF least square [LS] means 1.98 vs 4.29). The TEAEs had a similar incidence between treatment groups (41.0% vs 47.5%). Overall ESL did not produce statistically significant effects on

Seizures and epilepsy in Alzheimer's disease.

PubMed

Friedman, Daniel; Honig, Lawrence S; Scarmeas, Nikolaos

2012-04-01

Many studies have shown that patients with Alzheimer's disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome, and progression vary widely between studies. We performed a literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG) studies, and treatment responses. Finally, we consider limitations and methodological issues. There is considerable variability in the reported prevalence and incidence of seizures in patients with AD-with reported lifetime prevalence rates of 1.5-64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. © 2011 Blackwell Publishing Ltd.

Early seizures predict the development of epilepsy in children and adolescents with stroke.

PubMed

Breitweg, Ina; Stülpnagel, Celina von; Pieper, Tom; Lidzba, Karen; Holthausen, Hans; Staudt, Martin; Kluger, Gerhard

2017-05-01

To identify risk factors for the development of epilepsy after pediatric stroke. Retrospective analysis of hospital charts of 93 children and adolescents with post-neonatal non-traumatic stroke and a minimum follow-up of two years. Seizures during the first 48 h after onset of stroke symptoms were defined as "early seizures"; when two or more seizures occurred after this period, the patient was classified as "epileptic". Early seizures, young age at stroke and MRI evidence of cortical involvement were observed more frequently in the children who developed epilepsy. These factors were, however, significantly interrelated; a stepwise multiple regression analysis in 46/93 patients with complete datasets identified only the occurrence of early seizures as a significant risk factor: 15/19 (79%) children with early seizures developed epilepsy, as opposed to only 7/53 (13%) without early seizures. Children with stroke who show seizures during the first 48 h after onset of stroke symptoms have a high risk to develop post-stroke epilepsy, whereas in children without early seizures, post-stroke epilepsy is rare. Copyright © 2016. Published by Elsevier Ltd.

Incidence of seizure exacerbation and seizures reported as adverse events during adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three Phase III controlled trials.

PubMed

Carreño, Mar; Benbadis, Selim; Rocha, Francisco; Blum, David; Cheng, Hailong

2017-12-01

To investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients. Post-hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial-onset seizures (POS). Following an 8-week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off periods). Patient seizure diary data and seizure treatment-emergent adverse event (TEAE) reports were pooled for analysis. The modified intent-to-treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. Titration period : Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. Maintenance period : Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic-clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. Tapering-off period : Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo. Treatment with adjunctive ESL does not appear to

Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials

PubMed Central

Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

2014-01-01

The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm2 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant’s left middle temporal gyrus. In this participant, spectral power in 0.3–10 Hz, 20–55 Hz, and 125–250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly

Intelligence and cortical thickness in children with complex partial seizures.

PubMed

Tosun, Duygu; Caplan, Rochelle; Siddarth, Prabha; Seidenberg, Michael; Gurbani, Suresh; Toga, Arthur W; Hermann, Bruce

2011-07-15

Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6-18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores. Copyright © 2011 Elsevier Inc. All rights reserved.

The changes of HRV in refractory epilepsy: The potential index to predict the onset of epilepsy in children.

PubMed

Gong, Xuehao; Mao, Xuhua; Chen, Yan; Huang, Leidan; Liu, Weizong; Huang, Xian; Tan, Zheng; Wang, Xianming; Wu, Wanqing; Chen, Qian; Li, Rong

2016-01-01

In this study, we examine the potential of heart rate variability (HRV) as an efficient tool for predicting the onset of epilepsy in children. We totally collected 53 seizures EEG and ECG data using Video - EEG - ECG monitoring system. We then separated the ECG data into three segments: ten-minute before onset of each seizure, five-minute before onset of each seizure, and five-minute from the onset of each seizure. After the HRV parameters in all segments were calculated, we compared the differences between pre-ictal period and ictal period. We found that the values of meanHR, LF and LF/HF were greater in onset period. And the values of meanRR and the HF were less in ictal period. And it presented the similar changes when seizures occurred in the daytime and seizures occurred in the nighttime. In brief, we found that the sympathetic nervous system was under a more active status during onset period. We speculated that the HRV parameters such as the LF, HF or LF/HF could have potential to predict the seizures in children with epilepsy.

Vigabatrin pediatric dosing information for refractory complex partial seizures: results from a population dose-response analysis.

PubMed

Nielsen, Jace C; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G; Wesche, David L

2014-12-01

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Focal seizure symptoms in idiopathic generalized epilepsies.

PubMed

Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

2015-08-18

We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

A Stochastic Framework for Evaluating Seizure Prediction Algorithms Using Hidden Markov Models

PubMed Central

Wong, Stephen; Gardner, Andrew B.; Krieger, Abba M.; Litt, Brian

2007-01-01

Responsive, implantable stimulation devices to treat epilepsy are now in clinical trials. New evidence suggests that these devices may be more effective when they deliver therapy before seizure onset. Despite years of effort, prospective seizure prediction, which could improve device performance, remains elusive. In large part, this is explained by lack of agreement on a statistical framework for modeling seizure generation and a method for validating algorithm performance. We present a novel stochastic framework based on a three-state hidden Markov model (HMM) (representing interictal, preictal, and seizure states) with the feature that periods of increased seizure probability can transition back to the interictal state. This notion reflects clinical experience and may enhance interpretation of published seizure prediction studies. Our model accommodates clipped EEG segments and formalizes intuitive notions regarding statistical validation. We derive equations for type I and type II errors as a function of the number of seizures, duration of interictal data, and prediction horizon length and we demonstrate the model’s utility with a novel seizure detection algorithm that appeared to predicted seizure onset. We propose this framework as a vital tool for designing and validating prediction algorithms and for facilitating collaborative research in this area. PMID:17021032

Potent anti-seizure effects of D-leucine

PubMed Central

Hartman, Adam L.; Santos, Polan; O’Riordan, Kenneth J.; Stafstrom, Carl E.; Hardwick, J. Marie

2015-01-01

There are no effective treatments for millions of patients with intractable epilepsy. High-fat ketogenic diets may provide significant clinical benefit but are challenging to implement. Low carbohydrate levels appear to be essential for the ketogenic diet to work, but the active ingredients in dietary interventions remain elusive, and a role for ketogenesis has been challenged. A potential antiseizure role of dietary protein or of individual amino acids in the ketogenic diet is understudied. We investigated the two exclusively ketogenic amino acids, L-leucine and L-lysine, and found that only L-leucine potently protects mice when administered prior to the onset of seizures induced by kainic acid injection, but not by inducing ketosis. Unexpectedly, the D-enantiomer of leucine, which is found in trace amounts in the brain, worked as well or better than L-leucine against both kainic acid and 6 Hz electroshock-induced seizures. However, unlike L-leucine, D-leucine potently terminated seizures even after the onset of seizure activity. Furthermore, D-leucine, but not L-leucine, reduced long-term potentiation but had no effect on basal synaptic transmission in vitro. In a screen of candidate neuronal receptors, D-leucine failed to compete for binding by cognate ligands, potentially suggesting a novel target. Even at low doses, D-leucine suppressed ongoing seizures at least as effectively as diazepam but without sedative effects. These studies raise the possibility that D-leucine may represent a new class of anti-seizure agents, and that D-leucine may have a previously unknown function in eukaryotes. PMID:26054437

Unit Activity of Hippocampal Interneurons before Spontaneous Seizures in an Animal Model of Temporal Lobe Epilepsy

PubMed Central

Toyoda, Izumi; Fujita, Satoshi; Thamattoor, Ajoy K.

2015-01-01

Mechanisms of seizure initiation are unclear. To evaluate the possible roles of inhibitory neurons, unit recordings were obtained in the dentate gyrus, CA3, CA1, and subiculum of epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Most interneurons in the dentate gyrus, CA1, and subiculum increased their firing rate before seizures, and did so with significant consistency from seizure to seizure. Identification of CA1 interneuron subtypes based on firing characteristics during theta and sharp waves suggested that a parvalbumin-positive basket cell and putative bistratified cells, but not oriens lacunosum moleculare cells, were activated preictally. Preictal changes occurred much earlier than those described by most previous in vitro studies. Preictal activation of interneurons began earliest (>4 min before seizure onset), increased most, was most prevalent in the subiculum, and was minimal in CA3. Preictal inactivation of interneurons was most common in CA1 (27% of interneurons) and included a putative ivy cell and parvalbumin-positive basket cell. Increased or decreased preictal activity correlated with whether interneurons fired faster or slower, respectively, during theta activity. Theta waves were more likely to occur before seizure onset, and increased preictal firing of subicular interneurons correlated with theta activity. Preictal changes by other hippocampal interneurons were largely independent of theta waves. Within seconds of seizure onset, many interneurons displayed a brief pause in firing and a later, longer drop that was associated with reduced action potential amplitude. These findings suggest that many interneurons inactivate during seizures, most increase their activity preictally, but some fail to do so at the critical time before seizure onset. PMID:25904809

Seizure Termination by Acidosis Depends on ASIC1a

PubMed Central

Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

2008-01-01

SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.

PubMed

Y Ho, E C; Truccolo, Wilson

2016-10-01

How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K (+)] o ) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30-60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2-3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10-20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K (+)] o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K (+)] o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K (+)] o glial buffering under

Control of epileptic seizures in WAG/Rij rats by means of brain-computer interface

NASA Astrophysics Data System (ADS)

Makarov, Vladimir V.; Maksimenko, Vladimir A.; van Luijtelaar, Gilles; Lüttjohann, Annika; Hramov, Alexander E.

2018-02-01

The main issue of epileptology is the elimination of epileptic events. This can be achieved by a system that predicts the emergence of seizures in conjunction with a system that interferes with the process that leads to the onset of seizure. The prediction of seizures remains, for the present, unresolved in the absence epilepsy, due to the sudden onset of seizures. We developed an algorithm for predicting seizures in real time, evaluated it and implemented it into an online closed-loop brain stimulation system designed to prevent typical for the absence of epilepsy of spike waves (SWD) in the genetic rat model. The algorithm correctly predicts more than 85% of the seizures and the rest were successfully detected. Unlike the old beliefs that SWDs are unpredictable, current results show that they can be predicted and that the development of systems for predicting and preventing closed-loop capture is a feasible step on the way to intervention to achieve control and freedom from epileptic seizures.

Seizures induced by carbachol, morphine, and leucine-enkephalin: a comparison.

PubMed

Snead, O C

1983-04-01

The electrical, behavioral, and pharmacological properties of seizures induced by morphine, leucine-enkephalin, and the muscarinic cholinergic agonist carbachol were examined and compared. Low-dose carbachol given intracerebroventricularly (ICV) produced seizures similar electrically to those produced by ICV morphine and leucine-enkephalin, although there was some difference in site of subcortical origin of onset. Carbachol and morphine were similar in that they had the same anticonvulsant profile, produced similar behavioral changes, caused generalized absence seizures in low doses and generalized convulsive seizures in high doses, and were capable of chemical kindling. However, opiate-induced seizures were not overcome by cholinergic antagonists, nor were carbachol seizures blocked by opiate antagonists. These data suggest that there may be a common noncholinergic, nonopiatergic system involved in mediating carbachol- and morphine-induced seizures but not enkephalin seizures.

Seizures and Epilepsy in Alzheimer’s Disease

PubMed Central

Friedman, Daniel; Honig, Lawrence S.; Scarmeas, Nikolaos

2013-01-01

Introduction Many studies have shown that patients with Alzheimer’s disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome and progression vary widely between studies. Methods Literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG)studies, and treatment responses. Finally, we consider limitations and methodological issues. Results There is considerable variability in the reported prevalence and incidence of seizures in patients with AD - with reported lifetime prevalence rates of 1.5 - 64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. Conclusions The literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. PMID:22070283

Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

PubMed

Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

2015-11-23

Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

[The efficacy of lacosamide in relation to antiepileptic drug history. Clinical experiences in adult partial epilepsy].

PubMed

Barcs Gábor; Szűcs, Anna; Horváth, András; Kamondi, Anita

2015-01-30

A retrospective study in adult partial epilepsy on the efficacy of lacosamide in relation to previous antiepileptic drug experiences. We analysed 3-65 months' data on epilepsy-care of 43 pharmacoresistant partial epilepsy patients treated with lacosamide. Further analysis of antiepileptic drug history was carried out in strictly selected subgroups of patients with good and poor therapeutic response to lacosamide (10 and 9 patients, respectively) for 2-10 years long retrospective follow up. Adult patients with partial-onset seizures had been treated previously with three or more lifetime antiepileptic drugs without permanent success. Six patients (14%) were seizure free, eleven patients (25%) have experienced important improvement (their seizure-frequency decreased by at least 50%) for more than 12 months. Fourteen patients (32%) improved for less than 6 months and then have relapsed; and add-on lacosamide proved ineffective in 12 patients (28%). Those selected 10 patients successfully treated with lacosamide (seizure free for at least six months) favourably responded to carbamazepine or oxcarbazepine earlier and levetiracetam was ineffective or even caused worsening. The selected lacosamide-unresponsive nine patients responded unfavourably to carbamazepine or oxcarbazepine earlier. Fifteen patients (35%) suffered side effects as dizziness or sleepiness, in 11 of them lacosamide was combined with a "traditional" sodium-channal blocker antiepileptic drug. Lacosamide is an effective add-on antiepileptic drug in difficult-to treat adult partial epilepsy patients. Our data suggest that good lacosamide response may be expected in those patients who reacted favourably to "traditional" sodium-channel blocker carbamazepine or oxcarbazepine earlier.

Identifying Seizure Onset Zone From the Causal Connectivity Inferred Using Directed Information

NASA Astrophysics Data System (ADS)

Malladi, Rakesh; Kalamangalam, Giridhar; Tandon, Nitin; Aazhang, Behnaam

2016-10-01

In this paper, we developed a model-based and a data-driven estimator for directed information (DI) to infer the causal connectivity graph between electrocorticographic (ECoG) signals recorded from brain and to identify the seizure onset zone (SOZ) in epileptic patients. Directed information, an information theoretic quantity, is a general metric to infer causal connectivity between time-series and is not restricted to a particular class of models unlike the popular metrics based on Granger causality or transfer entropy. The proposed estimators are shown to be almost surely convergent. Causal connectivity between ECoG electrodes in five epileptic patients is inferred using the proposed DI estimators, after validating their performance on simulated data. We then proposed a model-based and a data-driven SOZ identification algorithm to identify SOZ from the causal connectivity inferred using model-based and data-driven DI estimators respectively. The data-driven SOZ identification outperforms the model-based SOZ identification algorithm when benchmarked against visual analysis by neurologist, the current clinical gold standard. The causal connectivity analysis presented here is the first step towards developing novel non-surgical treatments for epilepsy.

[Epilepsy and psychic seizures].

PubMed

Fukao, Kenjiro

2006-01-01

Various psychic symptoms as ictal manifestation have been found in epileptic patients. They are classified as psychic seizures within simple partial seizures, and subclassified into affective, cognitive, dysmnesic seizures and so on, although the subclassification is not yet satisfactory and almost nothing is known about their relationships with normal brain functions. In this presentation, the speaker picked ictal fear, déjà vu and out-of-body experience (OBE) from them and suggested that studies on these symptoms could uniquely contribute to the progress of cognitive neuroscience, presenting some results from the research and case study that he had been engaged in. Psychic seizures are prone to be missed or misdiagnosed unless psychiatrists with sufficient knowledge and experience on epilepsy care would not treat them, because they are subjective symptoms that are diverse and subtle, while they have some characteristics as ictal symptoms.

Unsupervised EEG analysis for automated epileptic seizure detection

NASA Astrophysics Data System (ADS)

Birjandtalab, Javad; Pouyan, Maziyar Baran; Nourani, Mehrdad

2016-07-01

Epilepsy is a neurological disorder which can, if not controlled, potentially cause unexpected death. It is extremely crucial to have accurate automatic pattern recognition and data mining techniques to detect the onset of seizures and inform care-givers to help the patients. EEG signals are the preferred biosignals for diagnosis of epileptic patients. Most of the existing pattern recognition techniques used in EEG analysis leverage the notion of supervised machine learning algorithms. Since seizure data are heavily under-represented, such techniques are not always practical particularly when the labeled data is not sufficiently available or when disease progression is rapid and the corresponding EEG footprint pattern will not be robust. Furthermore, EEG pattern change is highly individual dependent and requires experienced specialists to annotate the seizure and non-seizure events. In this work, we present an unsupervised technique to discriminate seizures and non-seizures events. We employ power spectral density of EEG signals in different frequency bands that are informative features to accurately cluster seizure and non-seizure events. The experimental results tried so far indicate achieving more than 90% accuracy in clustering seizure and non-seizure events without having any prior knowledge on patient's history.

Efficacy and tolerability of lacosamide as an adjunctive therapy in children with refractory partial epilepsy.

PubMed

Pasha, Ismail; Kamate, Mahesh; Didagi, Suresh K

2014-10-01

A unicentre, prospective study was performed to investigate the efficacy of lacosamide as adjunctive therapy in children with refractory partial epilepsy. The study was performed at a tertiary care hospital over a period of 30 months between November 2011 and May 2014. Seventy-nine children with refractory partial epilepsy (age 5-15 years) who had failed two or more antiepileptic drugs and in whom lacosamide was used as an add-on drug were enrolled. Lacosamide tablets were administered orally, at a dose of 25 mg for 1 week followed by 50 mg twice daily for the remaining period. Efficacy and tolerability evaluation was performed at every visit of titration, maintenance period (3 months), and two follow-up visits at monthly interval. Electrocardiogram and liver function tests were performed before enrollment and at the end of 3 months of lacosamide therapy. Patient's caregiver or investigator observed adverse events were recorded in a predesigned pro forma. A total of 79 patients with uncontrolled partial epilepsy screened from 531 epileptic children were enrolled, after they satisfied the inclusion and exclusion criteria. The mean age of children enrolled was 8.8 ± 3.1 years (range 5-15 years); 53 children (67.0%) were boys. Mean weight of the patients was 24.2 ± 9.8 kg. The mean age at the onset of seizures was 6.4 ± 3.5 years. The mean dose of lacosamide administered was 4.1 mg/kg. Three patients (3.8%) dropped out of the study, because of vomiting, aggressive behavior, and poor response, respectively. Of 76 patients (96.2%) entering the maintenance period, 35 patients (44.3%) were seizure free, 32 patients (40.6%) indicated ≥50% reduction in seizure frequency, 3 patients (3.8%) indicated 25-49% seizure reduction, and 9 patients (11.4%) either had no change in seizure frequency or experience increase in seizure frequency. Lacosamide is an effective add-on antiepileptic drug for children with refractory partial epilepsy and is well tolerated. Copyright © 2014

A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia.

PubMed

Rowland, Nathan C; Englot, Dario J; Cage, Tene A; Sughrue, Michael E; Barbaro, Nicholas M; Chang, Edward F

2012-05-01

Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature. A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol. Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery. Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected.

A statistical method for predicting seizure onset zones from human single-neuron recordings

NASA Astrophysics Data System (ADS)

Valdez, André B.; Hickman, Erin N.; Treiman, David M.; Smith, Kris A.; Steinmetz, Peter N.

2013-02-01

Objective. Clinicians often use depth-electrode recordings to localize human epileptogenic foci. To advance the diagnostic value of these recordings, we applied logistic regression models to single-neuron recordings from depth-electrode microwires to predict seizure onset zones (SOZs). Approach. We collected data from 17 epilepsy patients at the Barrow Neurological Institute and developed logistic regression models to calculate the odds of observing SOZs in the hippocampus, amygdala and ventromedial prefrontal cortex, based on statistics such as the burst interspike interval (ISI). Main results. Analysis of these models showed that, for a single-unit increase in burst ISI ratio, the left hippocampus was approximately 12 times more likely to contain a SOZ; and the right amygdala, 14.5 times more likely. Our models were most accurate for the hippocampus bilaterally (at 85% average sensitivity), and performance was comparable with current diagnostics such as electroencephalography. Significance. Logistic regression models can be combined with single-neuron recording to predict likely SOZs in epilepsy patients being evaluated for resective surgery, providing an automated source of clinically useful information.

Clinicodemographic Profile of Children with Seizures in a Tertiary Care Hospital: A Cross-Sectional Observational Study.

PubMed

Chaudhary, Nagendra; Gupta, Murli Manohar; Shrestha, Sandeep; Pathak, Santosh; Kurmi, Om Prakash; Bhatia, B D; Agarwal, K N

2017-01-01

Seizures are one of the common causes for hospital admissions in children with significant mortality and morbidity. This study was conducted to study the prevalence and clinicodemographic profile of children with seizures in a tertiary care hospital of western Nepal. This prospective cross-sectional study conducted over a period of 2 years included all admitted children (2 months-16 years) with seizures. Among 4962 admitted children, seizures were present in 3.4% ( n = 168) of children, with male preponderance. 138 (82.1%) children had generalized tonic-clonic seizures (GTCS) and 30 (17.9%) children had partial seizures. GTCS were more common than partial seizures in both sexes (male = 82.7%; female = 81.2%) and age groups. There was no statistical significance in the distribution of seizures (GTCS and partial seizures) with sexes ( P = 0.813) and age groups ( P = 0.955). Mean ages of children having GTCS and partial seizures were 8.2 ± 4.6 years and 8.2 ± 4.2 years, respectively. Loss of consciousness (55.4%), fever (39.9%), vomiting (35.1%), and headache (16.1%) were common complaints in seizure patients. Significant number of GTCS cases had fever ( P = 0.041) and neurocysticercosis ( n = 72; 43%) was the most common etiology in seizure patients. Idiopathic epilepsy (38 (22.6%)), meningoencephalitis (26 (15.5%)), and febrile convulsions (14 (8.33%)) were other leading disorders in children with seizures.

Effect of epileptic seizures on the cerebrospinal fluid--A systematic retrospective analysis.

PubMed

Tumani, Hayrettin; Jobs, Catherine; Brettschneider, Johannes; Hoppner, Anselm C; Kerling, Frank; Fauser, Susanne

2015-08-01

Analyses of the cerebrospinal fluid (CSF) are obligatory when epileptic seizures manifest for the first time in order to exclude life-threatening causes or treatable diseases such as acute infections or autoimmune encephalitis. However, there are only few systematic investigations on the effect of seizures themselves on CSF parameters and the significance of these parameters in differential diagnosis. CSF samples of 309 patients with epileptic and 10 with psychogenic seizures were retrospectively analyzed. CSF samples were collected between 1999 and 2008. Cell counts, the albumin quotient, lactate and Tau-protein levels were determined. Findings were correlated with seizure types, seizure etiology (symptomatic, cryptogenic, occasional seizure), and seizure duration. Pathological findings were only observed in patients with epileptic but not with psychogenic seizures. The lactate concentration was elevated in 14%, the albumin quotient in 34%, and the Tau protein level in 36% of CSF samples. Cell counts were only slightly elevated in 6% of patients. Different seizure types influenced all parameters except for the cell count: In status epilepticus highest, in simple partial seizures lowest values were seen. Symptomatic partial and generalized epileptic seizures had significantly higher Tau-protein levels than cryptogenic partial seizures. In patients with repetitive and occasional epileptic seizures, higher Tau-protein levels were seen than in those with psychogenic seizures. Duration of epileptic seizures was positively correlated with the albumin quotient, lactate and Tau-protein levels. High variability of investigated CSF parameters within each subgroup rendered a clear separation between epileptic and psychogenic seizures impossible. Elevated cell counts are infrequently observed in patients with epileptic seizures and should therefore not uncritically be interpreted as a postictal phenomenon. However, blood-CSF barrier disruption, increased glucose metabolism

Out-of-body experiences associated with seizures

PubMed Central

Greyson, Bruce; Fountain, Nathan B.; Derr, Lori L.; Broshek, Donna K.

2014-01-01

Alterations of consciousness are critical factors in the diagnosis of epileptic seizures. With these alterations in consciousness, some persons report sensations of separating from the physical body, experiences that may in rare cases resemble spontaneous out-of-body experiences. This study was designed to identify and characterize these out-of-body-like subjective experiences associated with seizure activity. Fifty-five percent of the patients in this study recalled some subjective experience in association with their seizures. Among our sample of 100 patients, 7 reported out-of-body experiences associated with their seizures. We found no differentiating traits that were associated with patients' reports of out-of-body experiences, in terms of either demographics; medical history, including age of onset and duration of seizure disorder, and seizure frequency; seizure characteristics, including localization, lateralization, etiology, and type of seizure, and epilepsy syndrome; or ability to recall any subjective experiences associated with their seizures. Reporting out-of-body experiences in association with seizures did not affect epilepsy-related quality of life. It should be noted that even in those patients who report out-of-body experiences, such sensations are extremely rare events that do not occur routinely with their seizures. Most patients who reported out-of-body experiences described one or two experiences that occurred an indeterminate number of years ago, which precludes the possibility of associating the experience with the particular characteristics of that one seizure or with medications taken or other conditions at the time. PMID:24592228

Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

PubMed

Trump, Natalie; McTague, Amy; Brittain, Helen; Papandreou, Apostolos; Meyer, Esther; Ngoh, Adeline; Palmer, Rodger; Morrogh, Deborah; Boustred, Christopher; Hurst, Jane A; Jenkins, Lucy; Kurian, Manju A; Scott, Richard H

2016-05-01

We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype-phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Subjective and objective characteristics of altered consciousness during epileptic seizures.

PubMed

Campora, Nuria; Kochen, Silvia

2016-02-01

Conscious states are inner states and processes of awareness. These states are by definition subjective. We analyzed subjective and objective characteristics of alteration of consciousness (AOC) during epileptic seizures, including its involvement in both the level of awareness and subjective content of consciousness. We evaluated AOC using the Consciousness Seizure Scale, the Ictal Consciousness Inventory, and a new structured survey developed by our group: the Seizure Perception Survey, which incorporates patients' subjective experiences before and after they watch a video-electroencephalographic recording of their own seizure. We included 35 patients (105 seizures) with drug-resistant epilepsy. Most seizures caused profound AOC. The content of consciousness was lower during temporal seizures with profound AOC. We uncovered a correlation between the subjective perception and objective duration of a seizure using the Seizure Perception Survey regarding memory; the patients had a better recall of ictal onset during wakefulness regardless of the epileptogenic zone, laterality, or magnitude of AOC. Nonetheless, the recovery of memory at the end of a seizure took more time in patients who showed greater AOC, less vivid content of consciousness, or a longer seizure. For 85% of the patients, this was the first time they were able to view their own seizures. The majority of the patients requested to view them again because this procedure allowed them to compare the recordings with their own memories and emotions during a seizure and to verify the real duration of the seizure. Alteration of consciousness is one of the most dramatic clinical manifestations of epilepsy. Usually, practitioners or relatives assume that the patients with AOC may not have any knowledge on their seizures. In this study, however, we found that most patients with AOC had a fairly accurate perception of the duration of a seizure and retained their memory of ictal onset. In contrast, for the

Ictal electroencephalograms in neonatal seizures: characteristics and associations.

PubMed

Nagarajan, Lakshmi; Ghosh, Soumya; Palumbo, Linda

2011-07-01

The characteristics of ictal electroencephalograms in 160 neonatal seizures of 43 babies were correlated with mortality and neurodevelopmental outcomes. Neonatal seizures are focal at onset, most frequently temporal, and often occur during sleep. Twenty-one percent of babies with seizures died, and 76% of survivors manifested neurodevelopmental impairment during 2-6-year follow-up. A low-amplitude ictal electroencephalogram discharge was associated with increased mortality, and a frequency of <2 Hz with increased morbidity. Status epilepticus, ictal fractions, multiple foci, and bihemispheric involvement did not influence outcomes. Of 160 seizures, 99 exhibited no associated clinical features (electrographic seizures). Neonatal seizures with clinical correlates (electroclinical seizures) exhibited a higher amplitude and frequency of ictal electroencephalogram discharge than electrographic seizures. During electroclinical seizures, the ictal electroencephalogram was more likely to involve larger areas of the brain and to cross the midline. Mortality and morbidity were similar in babies with electroclinical and electrographic seizures, emphasizing the need to diagnose and treat both types. Ictal electroencephalogram topography has implications for electrode application during limited-channel, amplitude-integrated electroencephalograms. We recommend temporal and paracentral electrodes. Video electroencephalograms are important in diagnosing neonatal seizures and providing useful information regarding ictal electroencephalogram characteristics. Copyright © 2011 Elsevier Inc. All rights reserved.

Multi-modal intelligent seizure acquisition (MISA) system--a new approach towards seizure detection based on full body motion measures.

PubMed

Conradsen, Isa; Beniczky, Sandor; Wolf, Peter; Terney, Daniella; Sams, Thomas; Sorensen, Helge B D

2009-01-01

Many epilepsy patients cannot call for help during a seizure, because they are unconscious or because of the affection of their motor system or speech function. This can lead to injuries, medical complications and at worst death. An alarm system setting off at seizure onset could help to avoid hazards. Today no reliable alarm systems are available. A Multi-modal Intelligent Seizure Acquisition (MISA) system based on full body motion data seems as a good approach towards detection of epileptic seizures. The system is the first to provide a full body description for epilepsy applications. Three test subjects were used for this pilot project. Each subject simulated 15 seizures and in addition performed some predefined normal activities, during a 4-hour monitoring with electromyography (EMG), accelerometer, magnetometer and gyroscope (AMG), electrocardiography (ECG), electroencephalography (EEG) and audio and video recording. The results showed that a non-subject specific MISA system developed on data from the modalities: accelerometer (ACM), gyroscope and EMG is able to detect 98% of the simulated seizures and at the same time mistakes only 4 of the normal movements for seizures. If the system is individualized (subject specific) it is able to detect all simulated seizures with a maximum of 1 false positive. Based on the results from the simulated seizures and normal movements the MISA system seems to be a promising approach to seizure detection.

Early Activation of Ventral Hippocampus and Subiculum during Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Toyoda, Izumi; Bower, Mark R.; Leyva, Fernando

2013-01-01

Temporal lobe epilepsy is the most common form of epilepsy in adults. The pilocarpine-treated rat model is used frequently to investigate temporal lobe epilepsy. The validity of the pilocarpine model has been challenged based largely on concerns that seizures might initiate in different brain regions in rats than in patients. The present study used 32 recording electrodes per rat to evaluate spontaneous seizures in various brain regions including the septum, dorsomedial thalamus, amygdala, olfactory cortex, dorsal and ventral hippocampus, substantia nigra, entorhinal cortex, and ventral subiculum. Compared with published results from patients, seizures in rats tended to be shorter, spread faster and more extensively, generate behavioral manifestations more quickly, and produce generalized convulsions more frequently. Similarities to patients included electrographic waveform patterns at seizure onset, variability in sites of earliest seizure activity within individuals, and variability in patterns of seizure spread. Like patients, the earliest seizure activity in rats was recorded most frequently within the hippocampal formation. The ventral hippocampus and ventral subiculum displayed the earliest seizure activity. Amygdala, olfactory cortex, and septum occasionally displayed early seizure latencies, but not above chance levels. Substantia nigra and dorsomedial thalamus demonstrated consistently late seizure onsets, suggesting their unlikely involvement in seizure initiation. The results of the present study reveal similarities in onset sites of spontaneous seizures in patients with temporal lobe epilepsy and pilocarpine-treated rats that support the model's validity. PMID:23825415

Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis.

PubMed

Cusmai, Raffaella; Moavero, Romina; Bombardieri, Roberta; Vigevano, Federico; Curatolo, Paolo

2011-12-01

In tuberous sclerosis complex, early seizure onset is associated with high risk of intractable epilepsy and cognitive/behavioral impairment. We retrospectively evaluated the long-term outcome of 44 infants presenting with seizures in the first 12 months who received vigabatrin, and were followed up for at least 3.5 years. At the final evaluation 55% of patients were still having seizures, 80% had intellectual disability, and 30% had autism. Sixty-five percent of children who had been treated earlier with vigabatrin after seizure onset achieved seizure freedom, compared with 24% of subjects who received vigabatrin treatment later (P<0.01). Intellectual disability was present in 61% of the children treated early (group A) and in 100% of the children treated later (group B). Nine percent of group A and 52% of group B had autism (P≈0.001). A shorter gap between seizure onset and start of treatment could reduce the risk of epileptic encephalopathy, minimizing the deleterious effect of seizures, but is not able to completely reverse the tuberous sclerosis complex-associated cognitive impairment. Copyright © 2011 Elsevier Inc. All rights reserved.

Phenomenology of hallucinations, illusions, and delusions as part of seizure semiology.

PubMed

Kasper, B S; Kasper, E M; Pauli, E; Stefan, H

2010-05-01

In partial epilepsy, a localized hypersynchronous neuronal discharge evolving into a partial seizure affecting a particular cortical region or cerebral subsystem can give rise to subjective symptoms, which are perceived by the affected person only, that is, ictal hallucinations, illusions, or delusions. When forming the beginning of a symptom sequence leading to impairment of consciousness and/or a classic generalized seizure, these phenomena are referred to as an epileptic aura, but they also occur in isolation. They often manifest in the fully awake state, as part of simple partial seizures, but they also can be associated to different degrees of disturbed consciousness. Initial ictal symptoms often are closely related to the physiological functions of the cortical circuit involved and, therefore, can provide localizing information. When brain regions related to sensory integration are involved, the seizure discharge can cause specific kinds of hallucinations, for example, visual, auditory, gustatory, olfactory, and cutaneous sensory sensations. In addition to these elementary sensory perceptions, quite complex hallucinations related to a partial seizure can arise, for example, perception of visual scenes or hearing music. By involving psychic and emotional spheres of human perception, many seizures also give rise to hallucinatory emotional states (e.g., fear or happiness) or even more complex hallucinations (e.g., visuospatial phenomena), illusions (e.g., déjà vu, out-of-body experience), or delusional beliefs (e.g., identity change) that often are not easily recognized as epileptic. Here we suggest a classification into elementary sensory, complex sensory, and complex integratory seizure symptoms. Epileptic hallucinations, illusions, and delusions shine interesting light on the physiology and functional anatomy of brain regions involved and their functions in the human being. This article, in which 10 cases are described, introduces the fascinating

The temporal characteristics of seizures in neonatal hypoxic ischemic encephalopathy treated with hypothermia.

PubMed

Lynch, Niamh E; Stevenson, Nathan J; Livingstone, Vicki; Mathieson, Sean; Murphy, Brendan P; Rennie, Janet M; Boylan, Geraldine B

2015-12-01

The characteristics of electrographic seizures in newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) are poorly described. This retrospective, observational study provides reference data on the characteristics of seizures and their evolution over time in newborns with HIE receiving whole-body TH. The cohort under analysis included 23 infants with HIE and seizures defined by multi-channel EEG recordings. Clinical presentation, details of TH and antiepileptic drugs used were recorded. Time from first to last-recorded electrographic seizure (seizure period) was calculated. Temporal characteristics of seizures - total burden, duration, number, burden in minutes per hour, distribution of burden over time (temporal evolution), time from seizure onset to maximum seizure burden (Tmsb), T1, and time from Tmsb to seizure offset, T2 - were analysed. The median age at electrographic seizure onset was 13.1h (IQR: 11.4 to 22.0). Tmsb was reached at a median age of 19.4 hours (IQR: 12.2 to 29.7). Median seizure period was 16.5h (IQR: 7.0 to 49.7), median number of seizures per hour was 1.9 (IQR: 1.0 to 3.3). The seizure burden was 4.0 min/h (IQR: 2.0 to 7.0). There was no consistent pattern in the temporal evolution of seizures in neonates treated with TH. The skewness was neither positive nor negative (p-value=0.15), there was no difference between the duration of T1 and T2 (p-value=0.09) and no difference in the seizure burden between T1 and T2 (p=0.09). There was an association between Tmsb and Phenobarbital (PB) administration (r=0.76, p-value<0.001). There is no consistent temporal evolution of seizure burden in neonates treated with TH. Seizures are diffuse, and their characteristics are variable. Copyright © 2015. Published by Elsevier Ltd.

Long-term seizure outcome in patients with juvenile absence epilepsy; a retrospective study in a tertiary referral center.

PubMed

Danhofer, Pavlína; Brázdil, Milan; Ošlejšková, Hana; Kuba, Robert

2014-06-01

The study aim was to evaluate pharmacotherapy effects and long-term seizure outcomes in patients with juvenile absence epilepsy (JAE) during a five-year follow-up period. The secondary aim was to identify factors from patient history and determine their influence on seizure control. We retrospectively studied 46 patients with JAE in the period between 2006 and 2011. The age at seizure onset, onset seizure type, family history of epilepsy, status epilepticus in history, medication history, and the rate of seizure control were studied. There were 30 females (65.2%) and 16 males (34.8%) in the study. The mean age at seizure onset was 12.9±5.6 years (ranged from 3 to 28 years). In 30 patients (65.2%), seizure onset was with absences, in 15 patients (32.6%) with generalized tonic-clonic seizure (GTCS), and in 1 patient (2.2%) with absence status. In 43 patients (93.5%), GTCS occurred in the course of the disease. Family history for epilepsy was positive in 10 patients (21.7%). In the five-year follow-up period, seizure freedom (Group 1) was achieved in 7 patients (15.2%). In total, 22 patients (47.8%) were classified into the groups involving very poor seizure control and antiepileptic drug resistance (Groups 5 and 6). The mean number of antiepileptic drugs (AEDs) used in the course of the disease in appropriate therapeutic doses was 3.8±2.3 (1-10 AEDs). The study results show that almost half of JAE patients have poor seizure control with a high rate of pharmacoresistance. The outcome of JAE can be very uncertain. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

PubMed

Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

2016-07-01

Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Hippocampal effective synchronization values are not pre-seizure indicator without considering the state of the onset channels

PubMed Central

Shayegh, Farzaneh; Sadri, Saeed; Amirfattahi, Rassoul; Ansari-Asl, Karim; Bellanger, Jean-Jacques; Senhadji, Lotfi

2014-01-01

In this paper, a model-based approach is presented to quantify the effective synchrony between hippocampal areas from depth-EEG signals. This approach is based on the parameter identification procedure of a realistic Multi-Source/Multi-Channel (MSMC) hippocampal model that simulates the function of different areas of hippocampus. In the model it is supposed that the observed signals recorded using intracranial electrodes are generated by some hidden neuronal sources, according to some parameters. An algorithm is proposed to extract the intrinsic (solely relative to one hippocampal area) and extrinsic (coupling coefficients between two areas) model parameters, simultaneously, by a Maximum Likelihood (ML) method. Coupling coefficients are considered as the measure of effective synchronization. This work can be considered as an application of Dynamic Causal Modeling (DCM) that enables us to understand effective synchronization changes during transition from inter-ictal to pre -ictal state. The algorithm is first validated by using some synthetic datasets. Then by extracting the coupling coefficients of real depth-EEG signals by the proposed approach, it is observed that the coupling values show no significant difference between ictal, pre-ictal and inter-ictal states, i.e., either the increase or decrease of coupling coefficients has been observed in all states. However, taking the value of intrinsic parameters into account, pre-seizure state can be distinguished from inter-ictal state. It is claimed that seizures start to appear when there are seizure-related physiological parameters on the onset channel, and its coupling coefficient toward other channels increases simultaneously. As a result of considering both intrinsic and extrinsic parameters as the feature vector, inter-ictal, pre-ictal and ictal activities are discriminated from each other with an accuracy of 91.33% accuracy. PMID:25061815

Gelastic seizures with dancing arising from the anterior prefrontal cortex.

PubMed

Neilson, John; Snyder, Tom; Pugh, Jeff; Wheatley, Matt; Tang-Wai, Richard

2014-06-01

This case report provides insight into the function of the anterior prefrontal cortex (aPFC), specifically Brodmann Area 10 (BA10), and its interconnectivity. We present a 10-year-old patient with lesional epilepsy and ictal onset, localised to BA10 in the aPFC. Thirty-four seizures were recorded. All seizures involved a demonstration of elation with laughter that was associated with a variety of different patterns of complex motor behaviour that included performing specific celebratory movements and acting out a Michael Jackson dance move. Electrographically, the seizures were all stereotyped and arose from the right frontal region, followed by a distinct left temporal ictal rhythm that corresponded with the onset of the behaviours. The lesion in the right aPFC was identified as a mixed lesion with both dysembryoplastic neuroepithelial tumour cells and type II cortical dysplasia. The electrographic analysis and unique seizure semiology suggest a connection between the aPFC and the contralateral temporal lobe. This neural pathway appears to be involved in the activation of previously formed procedural memories, creating an intensely positive emotional experience.

Ictal high frequency oscillations distinguish two types of seizure territories in humans

PubMed Central

Weiss, Shennan A.; Banks, Garrett P.; McKhann, Guy M.; Goodman, Robert R.; Emerson, Ronald G.; Trevelyan, Andrew J.

2013-01-01

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80–150 Hz) amplitude, phase-locked to the low-frequency (1–25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1–25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and

Assortative mixing in functional brain networks during epileptic seizures

NASA Astrophysics Data System (ADS)

Bialonski, Stephan; Lehnertz, Klaus

2013-09-01

We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.

Safety and tolerability of lacosamide as adjunctive therapy for adults with partial-onset seizures: Analysis of data pooled from three randomized, double-blind, placebo-controlled clinical trials.

PubMed

Biton, Victor; Gil-Nagel, Antonio; Isojarvi, Jouko; Doty, Pamela; Hebert, David; Fountain, Nathan B

2015-11-01

The objective of this study was to describe a priori protocol-defined analyses to evaluate the safety and tolerability of adjunctive oral lacosamide (200-600 mg/day) in adults (ages 16-70 years) with partial-onset seizures (POS) using data pooled from three similarly designed randomized, double-blind, placebo-controlled trials (SP667, SP754 [NCT00136019], SP755 [NCT00220415]). Patients with POS (≥2 years' duration, ≥2 previous antiepileptic drugs [AEDs]) uncontrolled by a stable dosing regimen of 1-3 concomitant AEDs were randomized to treatment with lacosamide at doses of 200 mg/day, 400 mg/day, or 600 mg/day, or placebo. Studies comprised a 4- to 6-week titration phase to target dose followed by a 12-week maintenance phase. Safety outcomes included treatment-emergent adverse events (TEAEs) of particular relevance to patients with POS, overall TEAEs, and discontinuations due to TEAEs. Post hoc analyses included evaluation of TEAEs potentially related to cognition and TEAEs leading to discontinuation analyzed by concomitant AEDs. One thousand three hundred eight patients were randomized to and received treatment; 944 to lacosamide and 364 to placebo. Most patients (84.4%) were taking 2 or 3 concomitant AEDs. The most common drug-associated TEAEs (reported by ≥5% of patients in any lacosamide dose group and with an incidence at least twice that reported for placebo during the treatment phase) were dizziness (30.6% for lacosamide vs 8.2% for placebo), nausea (11.4% vs 4.4%), and diplopia (10.5% vs 1.9%). Common drug-associated TEAEs generally appeared to be dose-related, and the incidence of each was lower during the 12-week maintenance phase than during the titration phase. Most TEAEs were either mild or moderate in intensity; severe TEAEs were predominantly observed with lacosamide 600 mg/day. No individual serious TEAE occurred in ≥1% of all lacosamide-treated patients. Treatment-emergent adverse events led to discontinuation in 8.1%, 17.2%, and 28.6% of

Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention

PubMed Central

Ewell, Laura A.; Liang, Liang; Armstrong, Caren; Soltész, Ivan; Leutgeb, Stefan

2015-01-01

Neural dynamics preceding seizures are of interest because they may shed light on mechanisms of seizure generation and could be predictive. In healthy animals, hippocampal network activity is shaped by behavioral brain state and, in epilepsy, seizures selectively emerge during specific brain states. To determine the degree to which changes in network dynamics before seizure are pathological or reflect ongoing fluctuations in brain state, dorsal hippocampal neurons were recorded during spontaneous seizures in a rat model of temporal lobe epilepsy. Seizures emerged from all brain states, but with a greater likelihood after REM sleep, potentially due to an observed increase in baseline excitability during periods of REM compared with other brains states also characterized by sustained theta oscillations. When comparing the firing patterns of the same neurons across brain states associated with and without seizures, activity dynamics before seizures followed patterns typical of the ongoing brain state, or brain state transitions, and did not differ until the onset of the electrographic seizure. Next, we tested whether disparate activity patterns during distinct brain states would influence the effectiveness of optogenetic curtailment of hippocampal seizures in a mouse model of temporal lobe epilepsy. Optogenetic curtailment was significantly more effective for seizures preceded by non-theta states compared with seizures that emerged from theta states. Our results indicate that consideration of behavioral brain state preceding a seizure is important for the appropriate interpretation of network dynamics leading up to a seizure and for designing effective seizure intervention. SIGNIFICANCE STATEMENT Hippocampal single-unit activity is strongly shaped by behavioral brain state, yet this relationship has been largely ignored when studying activity dynamics before spontaneous seizures in medial temporal lobe epilepsy. In light of the increased attention on using single

Precipitating factors and therapeutic outcome in epilepsy with generalized tonic-clonic seizures.

PubMed

Bauer, J; Saher, M S; Burr, W; Elger, C E

2000-10-01

The aim of the study was to evaluate the influence of precipitating factors and therapy on the outcome of epilepsy with generalized tonic-clonic seizures. Retrospective analysis of data from 34 patients (mean age at seizure onset 19 years; mean duration of follow-up 9.2 years) suffering from epilepsy of either cryptogenic or remote symptomatic (n = 19), or idiopathic (n = 15) etiology. The total number of seizures in all patients was 146. Without treatment 97 seizures manifested during 90.5 years without treatment (1.07 seizures/year), during treatment with carbamazepine or valproate 49 seizures occurred within 224 years (0.2 seizures/year). The frequency of seizures was significantly lower during treatment. Precipitating factors were found in relation to 31% of seizures in patients with remote symptomatic or cryptogenic epilepsy, and for 51% of seizures in patients with idiopathic epilepsy. There was a low frequency of seizures in patients with generalized tonic-clonic seizures. Precipitating factors are common. Antiepileptic drug treatment is effective.

Stability of Synchronization Clusters and Seizurability in Temporal Lobe Epilepsy

PubMed Central

Palmigiano, Agostina; Pastor, Jesús; García de Sola, Rafael; Ortega, Guillermo J.

2012-01-01

Purpose Identification of critical areas in presurgical evaluations of patients with temporal lobe epilepsy is the most important step prior to resection. According to the “epileptic focus model”, localization of seizure onset zones is the main task to be accomplished. Nevertheless, a significant minority of epileptic patients continue to experience seizures after surgery (even when the focus is correctly located), an observation that is difficult to explain under this approach. However, if attention is shifted from a specific cortical location toward the network properties themselves, then the epileptic network model does allow us to explain unsuccessful surgical outcomes. Methods The intraoperative electrocorticography records of 20 patients with temporal lobe epilepsy were analyzed in search of interictal synchronization clusters. Synchronization was analyzed, and the stability of highly synchronized areas was quantified. Surrogate data were constructed and used to statistically validate the results. Our results show the existence of highly localized and stable synchronization areas in both the lateral and the mesial areas of the temporal lobe ipsilateral to the clinical seizures. Synchronization areas seem to play a central role in the capacity of the epileptic network to generate clinical seizures. Resection of stable synchronization areas is associated with elimination of seizures; nonresection of synchronization clusters is associated with the persistence of seizures after surgery. Discussion We suggest that synchronization clusters and their stability play a central role in the epileptic network, favoring seizure onset and propagation. We further speculate that the stability distribution of these synchronization areas would differentiate normal from pathologic cases. PMID:22844524

Emergence of semiology in epileptic seizures.

PubMed

Chauvel, Patrick; McGonigal, Aileen

2014-09-01

Semiology, the manifestation of epilepsy, is dependent upon electrical activity produced by epileptic seizures that are organized within existing neural pathways. Clinical signs evolve as the epileptic discharge spreads in both time and space. Studying the relation between these, of which the temporal component is at least as important as the spatial one, is possible using anatomo-electro-clinical correlations of stereoelectroencephalography (SEEG) data. The period of semiology production occurs with variable time lag after seizure onset and signs then emerge more or less rapidly depending on seizure type (temporal seizures generally propagating more slowly and frontal seizures more quickly). The subset of structures involved in semiological production, the "early spread network", is tightly linked to those constituting the epileptogenic zone. The level of complexity of semiological features varies according to the degree of involvement of the primary or associative cortex, with the former having a direct relation to peripheral sensory and motor systems with production of hallucinations (visual and auditory) or elementary sensorimotor signs. Depending on propagation pattern, these signs can occur in a "march" fashion as described by Jackson. On the other hand, seizures involving the associative cortex, having a less direct relation with the peripheral nervous system, and necessarily involving more widely distributed networks manifest with altered cognitive and/or behavioral signs whose neural substrate involves a network of cortical structures, as has been observed for normal cognitive processes. Other than the anatomical localization of these structures, the frequency of the discharge is a crucial determinant of semiological effect since a fast (gamma) discharge will tend to deactivate normal function, whereas a slower theta discharge can mimic physiological function. In terms of interaction between structures, the degree of synchronization plays a key role in

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly.

PubMed

Tanaka, Akihiro; Akamatsu, Naoki; Shouzaki, Taisaku; Toyota, Tomoko; Yamano, Mitsuhiko; Nakagawa, Masanori; Tsuji, Sadatoshi

2013-11-01

Epidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan. We searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded. We identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n=33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n=50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n=51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year. The most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The prevalence of thyrotoxicosis-related seizures.

PubMed

Song, Tae-Jin; Kim, Sun-Jung; Kim, Gyu Sik; Choi, Young-Chul; Kim, Won-Joo

2010-09-01

Central nervous system dysfunction, such as hyperexcitation, irritability, and disturbance of consciousness, may occur in patients with thyrotoxicosis. There are also a few case reports of seizures attributed to thyrotoxicosis. The objective of the present study was to determine the prevalence of seizures that appeared to be related to the thyrotoxic state in patients with thyrotoxicosis. We retrospectively determined the prevalence and clinical features of seizures in 3382 patients with hyperthyroidism. Among patients with seizures, we excluded those with other causes of seizures or a history of epilepsy. We did not exclude two patients in whom later work-up showed an abnormal magnetic resonance imaging, as their seizures resolved after they became euthyroid. Among the 3382 patients with hyperthyroidism, there were seven patients (0.2%) with seizures who met our criteria. Primary generalized tonic-clonic seizures occurred in four patients (57%), complex partial seizures with secondary generalized tonic-clonic seizures occurred in two patients (29%), and one patient had a focal seizure (14%). The initial electroencephalography (EEG) was normal in two patients (29%), had generalized slow activity in four patients (57%), and had diffuse generalized beta activity in one patient (14%). On magnetic resonance imaging, one patient had diffuse brain atrophy, and one had an old basal ganglia infarct. After the patients became euthyroid, the EEG was repeated and was normal in all patients. During follow-up periods ranging from 18 to 24 months, none of the patients had seizures. Hyperthyroidism is the precipitating cause of seizures in a small percentage of these patients. In these patients, the prognosis is good if they become euthyroid. The prevalence of thyrotoxicosis-related seizures reported here can be used in conjunction with the prevalence of thyrotoxicosis in the population to estimate the prevalence of thyrotoxicosis-related seizures in populations.

The effect of albendazole treatment on seizure outcomes in patients with symptomatic neurocysticercosis.

PubMed

Romo, Matthew L; Wyka, Katarzyna; Carpio, Arturo; Leslie, Denise; Andrews, Howard; Bagiella, Emilia; Hauser, W Allen; Kelvin, Elizabeth A

2015-11-01

Randomized controlled trials have found an inconsistent effect of anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The objective of this study was to further explore the effect of albendazole treatment on long-term seizure outcomes and to determine if there is evidence for a differential effect by seizure type. In this trial, 178 patients with active or transitional neurocysticercosis cysts and new-onset symptoms were randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both with prednisone, and followed for 24 months. We used negative binomial regression and logistic regression models to determine the effect of albendazole on the number of seizures and probability of recurrent or new-onset seizures, respectively, over follow-up. Treatment with albendazole was associated with a reduction in the number of seizures during 24 months of follow-up, but this was only significant for generalized seizures during months 1-12 (unadjusted rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95% CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing the number of focal seizures or on the probability of having a seizure, regardless of seizure type or time period. Albendazole treatment may be associated with some symptomatic improvement; however, this association seems to be specific to generalized seizures. Future research is needed to identify strategies to better reduce long-term seizure burden in patients with neurocysticercosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Retinoschisis and hyperopia associated with partial monosomy of 6q and partial trisomy of 11q.

PubMed

Bagheri, Nika; Bahl, Reecha S; Singh, Arun D; Rychwalski, Paul J

2014-06-01

Retinoschisis, or retinal lamellar splitting, can occur in a number of hereditary conditions. The most common cause of congenital or childhood onset retinoschisis is the clinical entity known as juvenile retinoschsis, which is caused by mutations in the X-linked retinoschisis 1 gene. Genes other than X-linked retinoschisis 1 gene have rarely been implicated in association with hereditary retinoschisis. We describe a 9-year-old male who presented with several phenotypic features associated with partial monosomy of chromosome 6q and partial trisomy of chromosome 11q, including myelomeningocele, mental and growth retardation, seizures, microcephaly, scoliosis, and facial dysmorphisms, as well as novel ocular findings including bilateral retinoschisis and hyperopia. This case report highlights the necessity for a detailed ophthalmic examination of patients with both 6q deletions as well as 11q duplications to ensure accurate and timely diagnosis and treatment of the complications associated with the described ocular conditions.

Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

PubMed

Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

2015-01-01

Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P < 0.01), while intracerebroventricular methysergide lowered the seizure threshold (P < 0.05 vs. saline). The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

Pharmacotherapy of focal epilepsy in children: a systematic review of approved agents.

PubMed

Arya, Ravindra; Glauser, Tracy A

2013-04-01

Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation. This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children. Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors' files. Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria. Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data. Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partial-onset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures. This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug's efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.

Anticipating epileptic seizures: from mathematics to clinical applications.

PubMed

Le Van Quyen, Michel

2005-02-01

The study of dynamical changes in the neural activity preceding an epileptic seizure allows the characterization of a preictal state several minutes prior to seizure onset. This opens new perspectives for studying the mechanisms of ictogenesis as well as for possible therapeutic interventions that represent a major breakthrough. In this review we present and discuss the results from our group in this domain using nonlinear analysis of brain signals, as well as its limitation and open questions.

Predictors of seizure freedom after resection of supratentorial low-grade gliomas. A review.

PubMed

Englot, Dario J; Berger, Mitchel S; Barbaro, Nicholas M; Chang, Edward F

2011-08-01

Seizures are the most frequent presenting symptom in patients with low-grade gliomas (LGGs), and significantly influence quality of life if they are uncontrolled. Achieving freedom from seizures is of utmost importance in surgical planning, but the factors associated with seizure control remain incompletely understood. The authors performed a systematic literature review of seizure outcomes after resection of LGGs causing seizures, examining 773 patients across 20 published series. Rates of seizure freedom were stratified across 7 variables: patient age, tumor location, preoperative seizure control with medication, seizure semiology, epilepsy duration, extent of resection, and the use of intraoperative electrocorticography (ECoG). Gross-total resection was most predictive of complete seizure freedom, when compared with subtotal resection (OR 3.41, 95% CI 2.36-4.93). Other predictors of seizure freedom included preoperative seizure control on antiepileptic medication (OR 2.12, 95% CI 1.33-3.38) and duration of seizures of ≤ 1 year (OR 1.85, 95% CI 1.22-2.79). Patients with simple partial seizure semiology achieved seizure freedom less often than those with complex partial, generalized, or mixed seizure types (OR 0.46, 95% CI 0.26-0.80). No significant differences in seizure outcome were observed between adults versus children, patients with temporal lobe versus extratemporal tumors, or with the use of intraoperative ECoG. Seizure control is one of the most important considerations in planning surgery for low-grade brain tumors. Gross-total resection is a critical factor in achieving seizure freedom.

Through Diffusion Tensor Magnetic Resonance Imaging to Evaluate the Original Properties of Neural Pathways of Patients with Partial Seizures and Secondary Generalization by Individual Anatomic Reference Atlas

PubMed Central

Peng, Syu-Jyun; Harnod, Tomor; Tsai, Jang-Zern; Huang, Chien-Chun; Ker, Ming-Dou; Chiou, Jun-Chern; Chiueh, Herming; Wu, Chung-Yu; Hsin, Yue-Loong

2014-01-01

To investigate white matter (WM) abnormalities in neocortical epilepsy, we extract supratentorial WM parameters from raw tensor magnetic resonance images (MRI) with automated region-of-interest (ROI) registrations. Sixteen patients having neocortical seizures with secondarily generalised convulsions and 16 age-matched normal subjects were imaged with high-resolution and diffusion tensor MRIs. Automated demarcation of supratentorial fibers was accomplished with personalized fiber-labeled atlases. From the individual atlases, we observed significant elevation of mean diffusivity (MD) in fornix (cres)/stria terminalis (FX/ST) and sagittal stratum (SS) and a significant difference in fractional anisotropy (FA) among FX/ST, SS, posterior limb of the internal capsule (PLIC), and posterior thalamic radiation (PTR). For patients with early-onset epilepsy, the diffusivities of the SS and the retrolenticular part of the internal capsule were significantly elevated, and the anisotropies of the FX/ST and SS were significantly decreased. In the drug-resistant subgroup, the MDs of SS and PTR and the FAs of SS and PLIC were significantly different. Onset age was positively correlated with increases in FAs of the genu of the corpus callosum. Patients with neocortical seizures and secondary generalisation had microstructural anomalies in WM. The changes in WM are relevant to early onset, progression, and severity of epilepsy. PMID:24883310

Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy.

PubMed

Lv, Rui-Juan; Ren, Hai-Tao; Guan, Hong-Zhi; Cui, Tao; Shao, Xiao-Qiu

2018-02-01

The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size. This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period. A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%), anti-GABA B -R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures. This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new-onset seizures in isolation or with a seizure-predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural-specific autoantibodies does not rule out AE.

The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months.

PubMed

Åndell, Eva; Tomson, Torbjörn; Carlsson, Sofia; Hellebro, Eva; Andersson, Tomas; Adelöw, Cecilia; Åmark, Per

2015-07-01

To evaluate the incidence of unprovoked seizures in children and the prevalence of related neurodevelopmental comorbidities at the time of the presumed first seizure and six months thereafter. The medical records of all children (0-18 years of age) seeking medical attention as the result of a first unprovoked seizure between September 1, 2001 and December 31, 2006, and registered in the population-based Stockholm Incidence Registry of Epilepsy (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the basis of the medical records from this first visit and from other healthcare during the following six months. The incidence of unprovoked seizures was between 30 and 204/100,000 person years (n=766) in the different age groups. It was highest among the youngest children and lowest among the 18-year-olds with small gender differences. The most common neurodevelopment comorbidities were developmental delay (22%, CI: 19-25%), speech/language and learning difficulties (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of neurodevelopmental comorbidity varied by age at the time of seizure onset, with cerebral palsy being more common among the 0-5-year-olds, attention deficits among the 6-16-year-olds, and autism and psychiatric diagnosis among the older children. An associated neurodevelopmental comorbidity was more common among those experiencing recurrent than single seizures during follow-up six months from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children there was no known or suspected neurodevelopmental comorbidity. The incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were common already at the time of onset of the seizure disorder, indicating that neither seizure treatment nor seizures were the underlying cause of other neurodevelopmental symptoms in these patients during the period studied. Copyright �

Seizure prognosis of patients with low-grade tumors.

PubMed

Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

2012-09-01

Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

Late-onset Rasmussen Encephalitis: A literature appraisal.

PubMed

Dupont, Sophie; Gales, Ana; Sammey, Serge; Vidailhet, Marie; Lambrecq, Virginie

2017-08-01

Rasmussen Encephalitis (RE) is classically described as a childhood encephalopathy due to a unilateral inflammation of the cerebral cortex with a presumed immune-mediated pathophysiological basis. Unusual variant forms, including adolescent and adult-onset RE have been described but there is still a doubt whether these atypical cases correspond to classical RE patients. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing late onset RE to assess (i) the positivity rate of classical childhood-onset diagnostic criteria for RE in late-onset RE, (ii) the specific clinical and radiological features that could help earlier diagnosis and therapeutic interventions, (iii) the arguments for an autoimmune pathophysiology including (iiia) the association with autoimmune markers or diseases and (iiib) the effects of immunomodulatory or immunosuppressive treatments. A total of 50 papers were considered. We identified 102 late-onset RE patients with a sex ratio of 8 women for 2 men. 67% fulfilled the consensus diagnostic criteria for RE. As compared to classical RE, the late-onset RE patients exhibited: i) more frequent focal complex partial seizures, ii) less frequent epilepsia partialis continua throughout evolution, iii) a slower evolution with a delayed occurrence of cortical deficit, iv) less cognitive deterioration and v) a better outcome. A specific association with autoimmune markers or diseases was not found. Immunomodulatory therapies, even performed in a late stage, improved late-onset RE patients in 61% of cases. This review proves that late-onset RE is a reality with specific clinical and radiological features. The good response to immunomodulatory treatments brings further arguments for an immune-regulated process. Copyright © 2017 Elsevier B.V. All rights reserved.

Pre-stroke seizures: A nationwide register-based investigation.

PubMed

Zelano, Johan; Larsson, David; Kumlien, Eva; Åsberg, Signild

2017-07-01

The relationship between cerebrovascular disease and seizures is clearly illustrated by poststroke epilepsy. Seizures can also be the first manifestation of cerebrovascular disease and case-control studies have demonstrated that seizures carry an increased risk of subsequent stroke. Thus, seizures could serve as a marker for vascular risk that merits intervention, but more data is needed before proper trials can be conducted. The occurrence of pre-stroke seizures has not been assessed on a national scale. We asked what proportion of strokes in middle-aged and elderly patients was preceded by seizures. All patients over 60 years of age with first-ever stroke in 2005-2010 (n=92,596) were identified in the Swedish stroke register (Riksstroke) and cross-sectional data on a history of a first seizure or epilepsy diagnosis in the ten years preceding stroke were collected from national patient registers with mandatory reporting. 1372 patients (1.48%) had a first seizure or epilepsy diagnosis registered less than ten years prior to the index stroke. The mean latency between seizure and stroke was 1474days (SD 1029 days). Seizures or epilepsy preceded 1.48% of strokes in patients >60years of age. Based on recent national incidence figures, 5-20% of incident cases of seizures or epilepsy after 60 years of age could herald stroke, depending on age group. These proportions are of a magnitude that merit further study on how to reduce the risk of stroke in patients with late-onset seizures or epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Seizures in Pediatric Patients With Liver Transplant and Efficacy of Levetiracetam.

PubMed

Kılıç, Betül; Güngör, Serdal; Arslan, Müjgan; Selimoğlu, Mukadder Ayşe; Yılmaz, Sezai

2017-07-01

The aim of this study was to evaluate the risk factors, clinical implications, and prognosis of new-onset seizures that occurred after pediatric liver transplantation, and to assess the efficacy of levetiracetam treatment. The clinical and laboratory data of liver transplanted 28 children who had seizures after liver transplantation and specifically of 18 children who received levetiracetam were analyzed retrospectively. Sixteen patients (88.9%) remained seizure-free and in 2 (11.1%), more than 50% reduction in seizures were detected with levetiracetam treatment. In conclusion, seizures are generally the most common complication by a spectrum of seizure types, and sometimes cause symptomatic epilepsy. The most common risk factors for seizures in transplant recipients is immunosuppressant toxicity. Currently, there isn't a specific treatment involving the transplant patient population. Levetiracetam may be preferable in pediatric patients as it's reliable for liver disease and has advantages in the treatment of postoperative seizures due to its intravenous usage.

Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials.

PubMed

Kerr, Wesley T; Janio, Emily A; Le, Justine M; Hori, Jessica M; Patel, Akash B; Gallardo, Norma L; Bauirjan, Janar; Chau, Andrea M; D'Ambrosio, Shannon R; Cho, Andrew Y; Engel, Jerome; Cohen, Mark S; Stern, John M

2016-08-01

The average delay from first seizure to diagnosis of psychogenic non-epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2-3.5 years) based on an exponential model as 10 to the mean of log10 delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t=3.6, p=0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t=-0.9, p=0.38). Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A Functional-Genetic Scheme for Seizure Forecasting in Canine Epilepsy.

PubMed

Bou Assi, Elie; Nguyen, Dang K; Rihana, Sandy; Sawan, Mohamad

2018-06-01

The objective of this work is the development of an accurate seizure forecasting algorithm that considers brain's functional connectivity for electrode selection. We start by proposing Kmeans-directed transfer function, an adaptive functional connectivity method intended for seizure onset zone localization in bilateral intracranial EEG recordings. Electrodes identified as seizure activity sources and sinks are then used to implement a seizure-forecasting algorithm on long-term continuous recordings in dogs with naturally-occurring epilepsy. A precision-recall genetic algorithm is proposed for feature selection in line with a probabilistic support vector machine classifier. Epileptic activity generators were focal in all dogs confirming the diagnosis of focal epilepsy in these animals while sinks spanned both hemispheres in 2 of 3 dogs. Seizure forecasting results show performance improvement compared to previous studies, achieving average sensitivity of 84.82% and time in warning of 0.1. Achieved performances highlight the feasibility of seizure forecasting in canine epilepsy. The ability to improve seizure forecasting provides promise for the development of EEG-triggered closed-loop seizure intervention systems for ambulatory implantation in patients with refractory epilepsy.

Delayed seizures after intracerebral haemorrhage

PubMed Central

Rattani, Abbas; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand

2016-01-01

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5–1

Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice.

PubMed

Roundtree, Harrison M; Simeone, Timothy A; Johnson, Chaz; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Kristina A

2016-02-01

Comorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy. Rest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography. Kcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice. Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in other epilepsy models. © 2016 Associated

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Severe Hypoglycemia in a Juvenile Diabetic Rat Model: Presence and Severity of Seizures Are Associated with Mortality

PubMed Central

Maheandiran, Margaret; Mylvaganam, Shanthini; Wu, Chiping; El-Hayek, Youssef; Sugumar, Sonia; Hazrati, Lili; del Campo, Martin; Giacca, Adria; Zhang, Liang; Carlen, Peter L.

2013-01-01

It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14–16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4±1.3 mM) than in CON rodents (6.3±0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8±0.2 mM) and CON animals (1.6±0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical outcome of recurrent afebrile seizures in children with benign convulsions associated with mild gastroenteritis.

PubMed

Chen, Boman; Cheng, Min; Hong, Siqi; Liao, Shuang; Ma, Jiannan; Li, Tingsong; Jiang, Li

2018-05-30

To assess the clinical outcome and evolution of recurrent afebrile seizures in children initially diagnosed with benign convulsions associated with mild gastroenteritis (CwG). We reviewed and analyzed the medical records of 37 patients who were diagnosed as CwG at onset, followed by recurrent afebrile seizures and followed up for at least 24 months. The follow-up period ranged from 2 to 7 years (median, 40.1 months).Three patterns of recurrent afebrile seizures were recorded: afebrile seizures associated with gastrointestinal infection (AS-GI, n = 25), afebrile seizures associated with non-gastrointestinal infection (AS-nGI, n = 9), and unprovoked seizures (US, n = 3). Twenty eight patients (75.7%) had a second episode within 6 months after the first seizures. Five cases (13.5%) suffered three episodes of afebrile seizures. Seizure characteristics of the three patterns were similar, manifesting as clustered seizures in the majority. Focal epileptic activities in interictal EEG were found in 3 cases (9.4%) at onset, 10 cases (28.6%) at the second episode, respectively. Six patients were prescribed anti-epileptic drugs with apparently good responses. During at least 2 years' follow-up, all the cases showed normal psychomotor development. Only one patient was diagnosed with epilepsy. All the recurrent afebrile seizures initially diagnosed as CwG, irrespective of the kinds and frequency of relapses, showed favorable prognoses. CwG maybe falls within the category of situation-related seizures, rather than epilepsy. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Vagus nerve stimulation therapy in partial epilepsy: a review.

PubMed

Panebianco, Mariangela; Zavanone, Chiara; Dupont, Sophie; Restivo, Domenico A; Pavone, Antonino

2016-09-01

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy

PubMed Central

Sunkaraneni, Soujanya; Passarell, Julie A; Ludwig, Elizabeth A; Fiedler-Kelly, Jill; Pitner, Janet K; Grinnell, Todd A; Blum, David

2017-01-01

Purpose Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. Patients and methods A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. Results For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold. Conclusion This model-based assessment supports conversion to ESL 800 mg QD monotherapy

Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy.

PubMed

Sunkaraneni, Soujanya; Passarell, Julie A; Ludwig, Elizabeth A; Fiedler-Kelly, Jill; Pitner, Janet K; Grinnell, Todd A; Blum, David

2017-01-01

Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration ( C min ) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted C min as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure-response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold. This model-based assessment supports conversion to ESL 800 mg QD monotherapy for POS in adults taking 1 AED. For patients

Peri-ictal ECG changes in childhood epilepsy: implications for detection systems.

PubMed

Jansen, Katrien; Varon, Carolina; Van Huffel, Sabine; Lagae, Lieven

2013-10-01

Early detection of seizures could reduce associated morbidity and mortality and improve the quality of life of patients with epilepsy. In this study, the aim was to investigate whether ictal tachycardia is present in focal and generalized epileptic seizures in children. We sought to predict in which type of seizures tachycardia can be identified before actual seizure onset. Electrocardiogram segments in 80 seizures were analyzed in time and frequency domains before and after the onset of epileptic seizures on EEG. These ECG parameters were analyzed to find the most informative ones that can be used for seizure detection. The algorithm of Leutmezer et al. was used to find the temporal relationship between the change in heart rate and seizure onset. In the time domain, the mean RR shows a significant difference before compared to after onset of the seizure in focal seizures. This can be observed in temporal lobe seizures as well as frontal lobe seizures. Calculation of mean RR interval has a high specificity for detection of ictal heart rate changes. Preictal heart rate changes are observed in 70% of the partial seizures. Ictal heart rate changes are present only in partial seizures in this childhood epilepsy study. The changes can be observed in temporal lobe seizures as well as in frontal lobe seizures. Heart rate changes precede seizure onset in 70% of the focal seizures, making seizure detection and closed-loop systems a possible therapeutic alternative in the population of children with refractory epilepsy. © 2013.

Generalized seizures and transient contralateral hemiparesis following retrobulbar anesthesia: a case report.

PubMed

Dettoraki, Maria; Dimitropoulou, Chrisafoula; Nomikarios, Nikolaos; Moschos, Marilita M; Brοuzas, Dimitrios

2015-07-28

Retrobulbar block is a local anesthetic technique widely used for intraocular surgery. Although retrobulbar anesthesia is considered to be relatively safe, a number of serious adverse events have been reported. To our knowledge, immediate onset of generalized seizures with contralateral hemiparesis after retrobulbar anesthesia has not been reported. A 62-year-old Caucasian healthy male with a right eye retinal detachment was admitted for pars plana vitrectomy. During retrobulbar anesthesia with ropivacaine and before needle withdrawal, the patient developed twitching of the face which rapidly progressed to generalized tonic-clonic seizures. Arterial oxygen saturation decreased to 75 %. Chin lift was performed and 100 % oxygen was administrated via face mask, which increased saturation to 99 %. Midazolam 2 mg was administrated intravenously to control seizures. After cessation of seizures, left-sided hemiparesis was evident. Brain computed tomography and electroencephalogram were normal 3 h later. The patient underwent pars plana vitrectomy under general anesthesia 4 days later. Serious complications of local anesthesia for ophthalmic surgery are uncommon. We present a case in which generalized tonic-clonic seizures developed during retrobulbar anesthesia, followed by transient contralateral hemiparesis. The early onset of seizures indicated intra-arterial injection of the anesthetic. Our case suggested the need for close monitoring during the performance of retrobulbar anesthesia and the presence of well-trained personnel for early recognition and immediate management of the complications.

Seizure drawings: insight into the self-image of children with epilepsy.

PubMed

Stafstrom, Carl E; Havlena, Janice

2003-02-01

Epilepsy is a chronic disorder that is associated with numerous psychological challenges, especially in children. Drawings have been underutilized as a method to obtain insight into psychological issues in children with epilepsy. We asked 105 children with epilepsy, ages 5 to 18 years, to draw a picture of what it is like to have a seizure. Across ages and epilepsy syndromes, the drawings showed evidence of impaired self-concept, low self-esteem, and a sense of helplessness and vulnerability. Overall, the drawings of human figures were less developed than expected for chronological age. In some drawings, indicators of underlying depression were found. When considered by epilepsy syndrome or seizure type, some specific artistic features were noted. Children with simple partial (motor) seizures drew distorted body parts, especially limbs. Those with complex partial seizures depicted sensory symptoms and mental status changes such as confusion. Children with generalized tonic-clonic seizures showed shaking extremities. Drawings by children with absence seizures illustrated mainly staring. In conclusion, drawings are a powerful method to examine the self-concept of children with epilepsy and gain insight into their feelings about themselves and their world.

Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice

PubMed Central

Roundtree, Harrison M.; Simeone, Timothy A.; Johnson, Chaz; Matthews, Stephanie A.; Samson, Kaeli K.; Simeone, Kristina A.

2016-01-01

Study Objective: Comorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy. Methods: Rest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography. Results: Kcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice. Conclusion: Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in

Periictal activity in cooled asphyxiated neonates with seizures.

PubMed

Major, Philippe; Lortie, Anne; Dehaes, Mathieu; Lodygensky, Gregory Anton; Gallagher, Anne; Carmant, Lionel; Birca, Ala

2017-04-01

Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming. We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events. Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence. This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Post-traumatic seizure disorder following acquired brain injury.

PubMed

Teasell, Robert; Bayona, Nestor; Lippert, Corbin; Villamere, James; Hellings, Chelsea

2007-02-01

The present study aimed to evaluate the effectiveness of prophylactic anticonvulsant pharmacological strategies for the prevention of seizure disorders following acquired brain injury (ABI) to provide guidance for clinical practice based on the best available evidence. A systematic review of the literature from 1980-2005 was conducted focusing on treatment interventions available for post-traumatic seizures following ABI. The evidence for the efficacy of a given intervention was ranked as strong (supported by at least two randomized controlled trials (RCTs), moderate (supported by a single RCT), or limited (supported by other types of studies in the absence of RCTs). Based on a previous meta-analysis and the findings of this review, there is strong evidence that prophylactic anticonvulsant therapy decreases the occurrence of early seizures but only within the first week post-injury. Moreover, the evidence indicates that prophylactic anticonvulsant therapy does not decrease the incidence of seizure onset more than one week post-injury. In children, there is moderate evidence that prophylactic phenytoin does not reduce the incidence of early or late seizures. The efficacy of anticonvulsants after the development of seizures has not been specifically studied in ABI. Prophylactic anti-convulsants are effective in reducing seizures in the first week post-injury in adults. However, they do not reduce the occurrence of seizures after the first week.

Early Seizure Frequency and Aetiology Predict Long-Term Medical Outcome in Childhood-Onset Epilepsy

ERIC Educational Resources Information Center

Sillanpaa, Matti; Schmidt, Dieter

2009-01-01

In clinical practice, it is important to predict as soon as possible after diagnosis and starting treatment, which children are destined to develop medically intractable seizures and be at risk of increased mortality. In this study, we determined factors predictive of long-term seizure and mortality outcome in a population-based cohort of 102…

Focal BOLD-fMRI changes in bicuculline-induced tonic-clonic seizures in the rat

PubMed Central

DeSalvo, Matthew N.; Schridde, Ulrich; Mishra, Asht M.; Motelow, Joshua E.; Purcaro, Michael J.; Danielson, Nathan; Bai, Xiaoxiao; Hyder, Fahmeed; Blumenfeld, Hal

2010-01-01

Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG) these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABAA receptor antagonist, was injected systemically and seizure activity was observed on EEG as high amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which “generalized” tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans. PMID:20079442

Seizures in Fragile X Syndrome: Characteristics and Comorbid Diagnoses

ERIC Educational Resources Information Center

Berry-Kravis, Elizabeth; Raspa, Melissa; Loggin-Hester, Lisa; Bishop, Ellen; Holiday, David; Bailey, Donald B., Jr.

2010-01-01

A national survey of caregivers of individuals with fragile X syndrome addressed characteristics of epilepsy and co-occurring conditions. Of the 1,394 individuals (1,090 males and 304 females) with the full mutation, 14% of males and 6% of females reported seizures. Seizures were more often partial, began between ages 4 and 10 years, and were…

Smoking prevalence and seizure control in Chinese males with epilepsy.

PubMed

Gao, Hui; Sander, Josemir W; Du, Xudong; Chen, Jiani; Zhu, Cairong; Zhou, Dong

2017-08-01

Smoking has a negative effect on most diseases, yet it is under-investigated in people with epilepsy; thus its role is not clear in the general population with epilepsy. We performed a retrospective pilot study on males with epilepsy to determine the smoking rate and its relationship with seizure control using univariate analysis to calculate odds ratios (ORs) and also used a multi-variate logistic regression model. The smoking rate in our sample of 278 individuals was 25.5%, which is lower than the general Chinese population smoking rate among males of 52.1%. We used two classifications: the first classified epilepsy as generalized, or by presumed topographic origin (temporal, frontal, parietal and occipital). The second classified the dominant seizure type of an individual as generalized tonic clonic seizure (GTCS), myoclonic seizure (MS), complex partial seizure (CPS), simple partial seizure (SPS), and secondary GTCS (sGTCS). The univariable analysis of satisfactory seizure control profile and smoking rate in both classifications showed a trend towards a beneficial effect of smoking although most were not statistically significant. Considering medication is an important confounding factor that would largely influence seizure control, we also conducted multi-variable analysis for both classifications with drug numbers and dosage. The result of our model also suggested that smoking is a protective factor. Our findings seem to suggest that smoking could have a potential role in seizure control although confounders need exploration particularly in view of the potential long term health effects. Replication in a much larger sample is needed as well as case control studies to elucidate this issue. Copyright © 2017 Elsevier Inc. All rights reserved.

Phenobarbital for Neonatal Seizures: Response Rate and Predictors of Refractoriness.

PubMed

Spagnoli, Carlotta; Seri, Stefano; Pavlidis, Elena; Mazzotta, Silvia; Pelosi, Annalisa; Pisani, Francesco

2016-10-01

Background Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p  ≤  0.005) correlated with response to phenobarbital. However, EEG (p  ≤  0.02) and seizure type (p  ≤  0.001) were the only independent predictors. Conclusion Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns. Georg Thieme Verlag KG Stuttgart · New York.

Predictors of Poor Seizure Control in Children Managed at a Tertiary Care Hospital of Eastern Nepal

PubMed Central

POUDEL, Prakash; CHITLANGIA, Mohit; POKHAREL, Rita

2016-01-01

Objective Various factors have been claimed to predict outcome of afebrile seizures in children. This study was aimed to find out the predictors of poor seizure control in children at a resource limited setting. Materials & Methods This prospective study was done from July 1st, 2009 to January 31st, 2012 at B.P. Koirala Institute of Health Sciences, Nepal. Children (1 month-20 yr of age) with afebrile seizures presenting to pediatric neurology clinic were studied. Significant predictors on bivariate analysis were further analyzed with binary logistic model to find out the true predictors. Positive predictive values (PPVs) and negative predictive values (NPVs) for the true predictors were calculated. Results Out of 256 patients (male: female ratio 3:2) with afebrile seizures followed up for median duration of 27 (IQR 12-50) months, seizure was poorly controlled in 20% patients. Three factors predicted poor seizure control. They were frequent (≥1 per month) seizures at onset (OR 12.76, 95% CI 1.44-112.73, PPV 25%, NPV 98%); remote symptomatic etiology (OR 3.56, 95% CI 1.04-12.17, PPV 36%, NPV 92%); and need of more than one anticonvulsant drug (polytherapy) (OR 12.83, 95% CI 5.50-29.9, PPV 56%, NPV 96%). The strongest predictor was need of polytherapy. When all three factors were present, PPV and NPV for prediction of poor seizure control were 70% and 90% respectively. Conclusion Frequent seizures at onset, remote symptomatic etiology of seizure and need of polytherapy were associated with poor seizure control in children with afebrile seizures. PMID:27375756

Role of subdural electrocorticography in prediction of long-term seizure outcome in epilepsy surgery

PubMed Central

Juhász, Csaba; Shah, Aashit; Sood, Sandeep; Chugani, Harry T.

2009-01-01

Since prediction of long-term seizure outcome using preoperative diagnostic modalities remains suboptimal in epilepsy surgery, we evaluated whether interictal spike frequency measures obtained from extraoperative subdural electrocorticography (ECoG) recording could predict long-term seizure outcome. This study included 61 young patients (age 0.4–23.0 years), who underwent extraoperative ECoG recording prior to cortical resection for alleviation of uncontrolled focal seizures. Patient age, frequency of preoperative seizures, neuroimaging findings, ictal and interictal ECoG measures were preoperatively obtained. The seizure outcome was prospectively measured [follow-up period: 2.5–6.4 years (mean 4.6 years)]. Univariate and multivariate logistic regression analyses determined how well preoperative demographic and diagnostic measures predicted long-term seizure outcome. Following the initial cortical resection, Engel Class I, II, III and IV outcomes were noted in 35, 6, 12 and 7 patients, respectively. One child died due to disseminated intravascular coagulation associated with pseudomonas sepsis 2 days after surgery. Univariate regression analyses revealed that incomplete removal of seizure onset zone, higher interictal spike-frequency in the preserved cortex and incomplete removal of cortical abnormalities on neuroimaging were associated with a greater risk of failing to obtain Class I outcome. Multivariate logistic regression analysis revealed that incomplete removal of seizure onset zone was the only independent predictor of failure to obtain Class I outcome. The goodness of regression model fit and the predictive ability of regression model were greatest in the full regression model incorporating both ictal and interictal measures [R2 0.44; Area under the receiver operating characteristic (ROC) curve: 0.81], slightly smaller in the reduced model incorporating ictal but not interictal measures (R2 0.40; Area under the ROC curve: 0.79) and slightly smaller

The charges for seizures in the pediatric emergency room: a single center study.

PubMed

Caron, Elena; Wheless, Catherine E; Patters, Andrea B; Wheless, James W

2015-05-01

The direct charges for emergency department visits resulting from recurrent seizures are significant, and home intervention with abortive medications can be cost-saving. Over a 1-year period, we evaluated children with seizures who were seen in the emergency department, stabilized, and released. The information is necessary to assess the pharmacoeconomic advantages of at-home interventions for seizure emergencies. We did a retrospective chart review of 90 patients and divided them into febrile versus nonfebrile seizures and existing versus new-onset seizure disorder. The hospital accounting department performed a charge analysis. The total charges for all 90 patients treated for seizures in the emergency department were $219,945. The minimum was $370, for a patient with no history of febrile seizures. The maximum was $17,126, for a patient with a nonfebrile seizure and a history of seizures. This information allows a comparison with the cost of preventive medications, such as diazepam rectal gel or intranasal midazolam. Copyright © 2015 Elsevier Inc. All rights reserved.

Electroencephalograms in epilepsy: analysis and seizure prediction within the framework of Lyapunov theory

NASA Astrophysics Data System (ADS)

Moser, H. R.; Weber, B.; Wieser, H. G.; Meier, P. F.

1999-06-01

Epileptic seizures are defined as the clinical manifestation of excessive and hypersynchronous activity of neurons in the cerebral cortex and represent one of the most frequent malfunctions of the human central nervous system. Therefore, the search for precursors and predictors of a seizure is of utmost clinical relevance and may even guide us to a deeper understanding of the seizure generating mechanisms. We extract chaos-indicators such as Lyapunov exponents and Kolmogorov entropies from different types of electroencephalograms (EEGs): this covers mainly intracranial EEGs (semi-invasive and invasive recording techniques), but also scalp-EEGs from the surface of the skin. Among the analytical methods we tested up to now, we find that the spectral density of the local expansion exponents is best suited to predict the onset of a forthcoming seizure. We also evaluate the time-evolution of the dissipation in these signals: it exhibits strongly significant variations that clearly relate to the time relative to a seizure onset. This article is mainly devoted to an assessment of these methods with respect to their sensitivity to EEG changes, e.g., prior to a seizure. Further, we investigate interictal EEGs (i.e., far away from a seizure) in order to characterize their more general properties, such as the convergence of the reconstructed quantities with respect to the number of phase space dimensions. Generally we use multichannel reconstruction, but we also present a comparison with the delay-embedding technique.

Paradoxical Seizure Response to Phenytoin in an Epileptic Heroin Addict.

PubMed

Vasagar, Brintha; Verma, Beni R; Dewberry, Robert G; Pula, Thaddeus

2015-06-01

Phenytoin has a narrow therapeutic window and seizures can occur at both ends of the spectrum. A 41-year-old man with a history of a seizure disorder and heroin addiction presented with dizziness following 2 generalized tonic-clonic seizures that occurred earlier that day. The patient had received a loading dose of phenytoin for seizures associated with a subtherapeutic level 5 days previously. Initial evaluation revealed an elevated phenytoin level of 32.6 mcg/mL and an opiate-positive toxicology screen. Levetiracetam was started on the day of presentation and phenytoin was held until the level returned to the therapeutic range. The patient's dizziness resolved and he had no additional seizures. Evaluation for reversible causes of seizure activity along with anticonvulsant administration is generally the standard of care for breakthrough seizures. Phenytoin blood levels, if supratherapeutic, may be at least partially responsible for breakthrough seizure activity; in this circumstance, holding phenytoin and temporarily adding another anticonvulsant may be indicated.

Nap polygraphic recordings after partial sleep deprivation in patients with suspected epileptic seizures.

PubMed

Peraita-Adrados, R; Gutierrez-Solana, L; Ruiz-Falcó, M L; García-Peñas, J J

2001-02-01

A review of the literature shows that nap recordings make a significant contribution to epilepsy studies, providing evidence of specific EEG findings in patients suspected of having epilepsy. In addition, sleep deprivation can cause paroxysmal EEG activity and clinical seizures. We studied retrospectively 686 patients, 51.8% males and 48.2% females, who had experienced at least one episode classified from the clinical point of view as epileptic in origin. They were divided into six age groups. Patients underwent a two-hour (1 P.M.-3 P.M.) nap-video-polygraphic recording (EEG 13 channels using the standard 10-20 system, EOG, ECG, EMG and respiration), following a partial sleep deprivation (1 to 3 h) the night before. A second recording was made in 40 patients. In 35.3% of patients, a complete sleep cycle was obtained; in 64.6% sufficient light and deep NREM sleep was obtained, but not REM stage; in 9.3%, we only observed drowsiness and stage 1 of sleep, and this group was excluded from the analysis. Interictal and/or ictal epileptic discharges were observed during the first nap recording in 245 patients (40.4% of the sample). In addition, in 40 patients (11%) with normal or inconclusive first nap EEG, a second recording was able to demonstrate epileptic abnormalities in 35% of cases. Because of its good cost/benefit ratio and availability in most western laboratories, we consider the 'nap plus partial sleep deprivation' method as advantageous over other activation procedures.

Quality of life, mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group.

PubMed

Maschio, Marta; Zarabla, Alessia; Maialetti, Andrea; Fabi, Alessandra; Vidiri, Antonello; Villani, Veronica; Giannarelli, Diana

2017-08-01

Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n=19) treated with Levetiracetam as an add-on. We recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3months and at 6months. This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28-70) with uncontrolled partial-onset seizures treated with LEV as add-on. The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency. Twelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400mg/die (mean final dose 300mg/die). Four patients dropped out due to poor

Evaluation of the effect of jobelyn(®) on chemoconvulsants-induced seizure in mice.

PubMed

Umukoro, Solomon; Omogbiya, Itivere Adrian; Eduviere, Anthony Taghogho

2013-01-01

Epilepsy is a common central nervous system (CNS) disorder characterized by seizures resulting from episodic neuronal discharges. The incidence of toxicity and refractoriness has compromised the clinical efficacy of the drugs currently used for the treatment of convulsions. Thus, there is a need to search for new medicines from plant origin that are readily available and safer for the control of seizures. Jobelyn(®) (JB) is a unique African polyherbal preparation used by the natives to treat seizures in children. This investigation was carried out to evaluate whether JB has anti-seizure property in mice. The animals received JB (5, 10 and 20 mg/kg, p.o) 30 min before induction of convulsions with intraperitoneal (i.p.) injection of picotoxin (6 mg/kg), strychnine (2 mg/kg) and pentylenetetrazole (85 mg/kg) respectively. Diazepam (2 mg/kg, p.o.) was used as the reference drug. Anti-seizure activities were assessed based on the ability of test drugs to prevent convulsions, death or to delay the onset of seizures in mice. JB (5, 10 and 20 mg/kg, p.o) could only delay the onset of seizures induced by pentylenetetrazole (85 mg/kg, i.p.) in mice. However, it did not did not offer any protection against seizure episodes, as it failed to prevent the animals, from exhibiting tonic-clonic convulsions caused by pentylenetetrazole (85 mg/kg, i.p.), strychnine (2 mg/kg) or picrotoxin (6 mg/kg, i.p.). On the other hand, diazepam (2 mg/kg, i.p.), offered 100% protection against convulsive seizures, induced by pentylenetetrazole (85 mg/kg, i.p.). However, it failed to prevent seizures produced by strychnine (2 mg/kg, i.p.) or picrotoxin (6 mg/kg, i.p.). Our results suggest that JB could not prevent the examined chemoconvulsants-induced convulsions. However, its ability to delay the latency to seizures induced by pentylenetetrazole suggests that JB might be effective in the control of the seizure spread in epileptic brains.

Unfavorable surgical outcomes in partial epilepsy with secondary bilateral synchrony: Intracranial electroencephalography study.

PubMed

Sunwoo, Jun-Sang; Byun, Jung-Ick; Moon, Jangsup; Lim, Jung-Ah; Kim, Tae-Joon; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Kyung-Il; Chu, Kon; Kim, Manho; Chung, Chun-Kee; Jung, Ki-Young; Lee, Sang Kun

2016-05-01

Secondary bilateral synchrony (SBS) indicates bilaterally synchronous epileptiform discharges arising from a focal cortical origin. The present study aims to investigate SBS in partial epilepsy with regard to surgical outcomes and intracranial EEG findings. We retrospectively reviewed consecutive patients who underwent epilepsy surgery following extraoperative intracranial electroencephalography (EEG) study from 2008 to 2012. The presence of SBS was determined based upon the results of scalp EEG monitoring performed for presurgical evaluations. We reviewed scalp EEG, neuroimaging, intracranial EEG findings, and surgical outcomes in patients with SBS. We found 12 patients with SBS who were surgically treated for intractable partial epilepsy. Nine (75%) patients had lateralized ictal semiology and only two (16.6%) patients showed localized ictal onset in scalp EEG. Brain MRI showed epileptogenic lesion in three (25%) patients. Intracranial EEG demonstrated that ictal onset zone was widespread or non-localized in six (50%) patients. Low-voltage fast activity was the most common ictal onset EEG pattern. Rapid propagation of ictal onset was noted in 10 (83.3%) patients. Eleven patients underwent resective epilepsy surgery and only two patients (18.2%) achieved seizure-freedom (median follow-up 56 months). MRI-visible brain lesions were associated with favorable outcomes (p=0.024). Patients with SBS, compared to frontal lobe epilepsy without SBS, showed lesser localization in ictal onset EEG (p=0.029) and more rapid propagation during evolution of ictal rhythm (p=0.015). The present results suggested that resective surgery for partial epilepsy with SBS should be decided carefully, especially in case of nonlesional epilepsy. Poor localization and rapid spread of ictal onset were prominent in intracranial EEG, which might contribute to incomplete resection of the epileptogenic zone and poor surgical outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Frequency of seizures and epilepsy in neurological HIV-infected patients.

PubMed

Kellinghaus, C; Engbring, C; Kovac, S; Möddel, G; Boesebeck, F; Fischera, M; Anneken, K; Klönne, K; Reichelt, D; Evers, S; Husstedt, I W

2008-01-01

Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on

Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone

PubMed Central

Ren, Liankun; Kucewicz, Michal T.; Cimbalnik, Jan; Matsumoto, Joseph Y.; Brinkmann, Benjamin H.; Hu, Wei; Marsh, W. Richard; Meyer, Fredric B.; Stead, S. Matthew

2015-01-01

Objective: To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG. Methods: Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro- and research microelectrodes were analyzed using time-frequency spectral analysis. Results: Gamma frequency oscillations (30–100 Hz) often preceded IEDs in spatially confined brain areas. The gamma-IEDs were consistently observed 35 to 190 milliseconds before the epileptiform spike waveforms on individual macro- and microelectrodes. The gamma oscillations associated with IEDs had longer duration (p < 0.001) and slightly higher frequency (p = 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were strongly associated with electrodes in the seizure onset zone (SOZ) compared with the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without preceding gamma oscillations that were often also detected outside of the SOZ. Similar to prior studies, isolated pathologic high-frequency oscillations in the gamma (30–100 Hz) and higher (100–600 Hz) frequency range, not associated with an IED, were also found to be associated with SOZ. Conclusions: The occurrence of locally generated gamma oscillations preceding IEDs suggests a mechanistic role for gamma in pathologic network activity generating IEDs. The results show a strong association between SOZ and gamma-IEDs. The potential clinical application of gamma-IEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies. PMID:25589669

Correlation between shaking behaviors and seizure severity in five animal models of convulsive seizures.

PubMed

Rodrigues, Marcelo Cairrão Araújo; Rossetti, Franco; Foresti, Maira Licia; Arisi, Gabriel Maisonnave; Furtado, Márcio Araújo; Dal-Cól, Maria Luiza Cleto; Bertti, Poliana; Fernandes, Artur; Santos, Francisco Leite; Del Vecchio, Flávio; Garcia-Cairasco, Norberto

2005-05-01

Wet dog shakes (WDS) and head shakes (HS) are associated with experimentally induced convulsive seizures. We sought to determine whether these behaviors are correlated or not with major (status epilepticus (SE) or fully kindled animals) or minor (non-SE or partially kindled animals) seizure severity. WDS are directly correlated with SE induced by intracerebral star fruit extract (Averrhoa carambola) injection and with kindled animals in the amygdala fast kindling model. On the other hand, WDS are inversely correlated with SE induced by intracerebral bicuculline and pilocarpine injections. Systemic pilocarpine in animals pretreated with methyl-scopolamine barely induced WDS or HS. The role of shaking behaviors may vary from ictal to anticonvulsant depending on the experimental seizure model, circuitries involved, and stimulus intensity. The physical presence of acrylic helmets may per se inhibit the HS response. Also, methyl-scopolamine, a drug incapable of crossing the blood-brain barrier, can induce HS in animals without acrylic helmets.

The similarities between the hallucinations associated with the partial epileptic seizures of the occipital lobe and ball lightning observations

NASA Astrophysics Data System (ADS)

Cooray, G. K.; Cooray, V.

2007-12-01

Ball Lightning was seen and described since antiquity and recorded in many places. Ball lightning is usually observed during thunderstorms but large number of ball lightning observations is also reported during fine weather without any connection to thunderstorms or lightning. However, so far no one has managed to generate them in the laboratory. It is photographed very rarely and in many cases the authenticity of them is questionable. It is possible that many different phenomena are grouped together and categorized simply as ball lightning. Indeed, the visual hallucinations associated with simple partial epileptic seizures, during which the patient remains conscious, may also be categorized by a patient unaware of his or her condition as ball lightning observation. Such visual hallucinations may occur as a result of an epileptic seizure in the occipital, temporo-occipital or temporal lobes of the cerebrum [1,2,3]. In some cases the hallucination is perceived as a coloured ball moving horizontally from the periphery to the centre of the vision. The ball may appear to be rotating or spinning. The colour of the ball can be red, yellow, blue or green. Sometimes, the ball may appear to have a solid structure surrounded by a thin glow or in other cases the ball appears to generate spark like phenomena. When the ball is moving towards the centre of the vision it may increase its intensity and when it reaches the centre it can 'explode' illuminating the whole field of vision. During the hallucinations the vision is obscured only in the area occupied by the apparent object. The hallucinations may last for 5 to 30 seconds and rarely up to a minute. Occipital seizures may spread into other regions of the brain giving auditory, olfactory and sensory sensations. These sensations could be buzzing sounds, the smell of burning rubber, pain with thermal perception especially in the arms and the face, and numbness and tingling sensation. In some cases a person may experience only

Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures.

PubMed

Kay, Lara; Reif, Philipp S; Belke, Marcus; Bauer, Sebastian; Fründ, Detlef; Knake, Susanne; Rosenow, Felix; Strzelczyk, Adam

2015-09-01

To evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video-electroencephalography (EEG) monitoring. Medical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ. In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h after in-MDZ, the number of seizures was significantly lower (p = 0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83 h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h; IQR 4.87, range 0.03-21.87; p = 0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually after 12 h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41-15.45; p = 0.009). Ictal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12 h period and of generalized tonic

Seizures presenting as incessant laughter: a case of gelastic epilepsy.

PubMed

Holmes, Christina M; Goldman, Mitchell J

2012-12-01

Gelastic seizures are defined as seizure activity manifesting as laughter inappropriate to the situation, with supporting evidence on electroencephalogram or magnetic resonance imaging. Gelastic seizures are most commonly reported in patients with hypothalamic hamartomas causing precocious puberty. The differential diagnosis of incessant laughter is important to recognize in the Emergency Department, as some conditions warrant immediate treatment and others require further diagnostic work-up with implications for the entire family. The background and pathophysiology of gelastic epilepsy will be discussed. The case of a previously healthy girl with acute onset of incessant laughter is reported. This patient was diagnosed with a clinical case of gelastic seizures. This case illustrates the importance of recognizing this form of seizures for accurate treatment and follow-up. This case report illustrates the importance of a broad differential for a patient presenting emergently with uncontrollable laughter. Gelastic epilepsy is relatively rare but requires further work-up and often may require chronic therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

PubMed

Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G

2013-05-01

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

Longitudinal changes in seizure outcomes after resection of cerebral cavernous malformations in patients presenting with seizures: a long-term follow-up of 46 patients.

PubMed

Kim, Jiha; Kim, Chi Heon; Chung, Chun Kee

2014-08-01

Seizure is the most common presentation in patients with cerebral cavernous malformations (CCMs). Although many articles have documented seizure outcomes after resection of CCM, few have conducted long-term follow-ups; thus, the fluctuating seizure outcomes have been neglected. The purpose of this study is to describe long-term postoperative seizure outcomes in patients with CCM and to compare seizure outcomes between patients with sporadic seizures and those with chronic seizures. Forty-six patients with CCM presenting with seizures underwent surgery. The male-to-female ratio was 1:1, and the average age at initial seizure onset was 27.6 years. The mean preoperative seizure duration was 42.7 months. Patients were divided into two groups: a chronic group (N = 20) and a sporadic group (N = 26) according to seizure frequency and duration. The mean postoperative follow-up duration was 96.3 months, and the postoperative seizure outcomes were checked annually based upon Engel's classification. After the first year of follow-up, 80.8 % of the sporadic group and 75.0 % of the chronic group were evaluated as Engel class I. These rates increased to 100.0 % and 90.0 %, respectively, at the eighth year of follow-up. Overall, 29 (63.0 %) of the 46 patients experienced changes in seizure outcomes over the follow-up period. Despite their delayed improvements, the chronic group showed less favorable outcomes throughout follow-up (p = 0.025). Long-term follow-up is indispensable for accurately assessing postoperative seizure outcomes because these outcomes change continuously. We recommend earlier surgery to achieve seizure-free status in patients with CCM. However, even in the chronic group, surgery is recommended, considering the overall delayed improvement.

Unilateral or bilateral punctate hippocampal hyperintensities on DW-MRI: seizures, amnesia, or both?

PubMed

Bocos-Portillo, Jone; Escalza-Cortina, Inés; Gómez-Beldarrain, Marian; Rodriguez-Sainz, Aida; Garcia-Monco, Juan Carlos

2018-06-02

The presence of small hippocampal hyperintense lesions on diffusion-weighted (DW) MRI can respond to different etiologies and represents a challenge where clinical judgment is imperative, since therapeutic approach may be quite different.We here report three patients with similar neuroradiological findings, i.e., hyperintense punctate hippocampal lesions on diffusion-weighted MRI sequences, yet of different origin. The first one presented with isolated amnesia (transient global amnesia), the second one with amnesia and seizures, and the third one with seizures.Thus, hippocampal punctate lesions appear after transient global amnesia, but the same pattern may be present after seizures, either focal-onset or generalized seizures. This peculiar radiological MRI pattern could indicate a pathogenic link between transient global amnesia (TGA) and seizures which should be further studied.

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, M.K.; Wright, L.K.M.; Stone, M.F.

2012-03-15

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min followingmore » seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY

Refractory seizures due to a dural-based cavernoma masquerading as a meningioma.

PubMed

Zeng, Xianwei; Mahta, Ali; Kim, Ryan Y; Saad, Ali G; Kesari, Santosh

2012-04-01

A 37-year-old female presented with medically intractable complex partial seizures with secondary generalization. She was found to have a dural-based lesion with radiologic features of meningioma. A gross total resection was performed and pathology confirmed a diagnosis of cavernous angioma and she became seizure free after the surgical resection. Cavernous angioma should be considered in differential diagnosis of a dural-based lesion manifesting with refractory seizures.

Preictal dynamics of EEG complexity in intracranially recorded epileptic seizure: a case report.

PubMed

Bob, Petr; Roman, Robert; Svetlak, Miroslav; Kukleta, Miloslav; Chladek, Jan; Brazdil, Milan

2014-11-01

Recent findings suggest that neural complexity reflecting a number of independent processes in the brain may characterize typical changes during epileptic seizures and may enable to describe preictal dynamics. With respect to previously reported findings suggesting specific changes in neural complexity during preictal period, we have used measure of pointwise correlation dimension (PD2) as a sensitive indicator of nonstationary changes in complexity of the electroencephalogram (EEG) signal. Although this measure of complexity in epileptic patients was previously reported by Feucht et al (Applications of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures. Med Biol Comput. 1999;37:208-217), it was not used to study changes in preictal dynamics. With this aim to study preictal changes of EEG complexity, we have examined signals from 11 multicontact depth (intracerebral) EEG electrodes located in 108 cortical and subcortical brain sites, and from 3 scalp EEG electrodes in a patient with intractable epilepsy, who underwent preoperative evaluation before epilepsy surgery. From those 108 EEG contacts, records related to 44 electrode contacts implanted into lesional structures and white matter were not included into the experimental analysis.The results show that in comparison to interictal period (at about 8-6 minutes before seizure onset), there was a statistically significant decrease in PD2 complexity in the preictal period at about 2 minutes before seizure onset in all 64 intracranial channels localized in various brain sites that were included into the analysis and in 3 scalp EEG channels as well. Presented results suggest that using PD2 in EEG analysis may have significant implications for research of preictal dynamics and prediction of epileptic seizures.

Mutation in an alternative transcript of CDKL5 in a boy with early-onset seizures.

PubMed

Bodian, Dale L; Schreiber, John M; Vilboux, Thierry; Khromykh, Alina; Hauser, Natalie S

2018-06-01

Infantile-onset epilepsies are a set of severe, heterogeneous disorders for which clinical genetic testing yields causative mutations in ∼20%-50% of affected individuals. We report the case of a boy presenting with intractable seizures at 2 wk of age, for whom gene panel testing was unrevealing. Research-based whole-genome sequencing of the proband and four unaffected family members identified a de novo mutation, NM_001323289.1:c.2828_2829delGA in CDKL5, a gene associated with X-linked early infantile epileptic encephalopathy 2. CDKL5 has multiple alternative transcripts, and the mutation lies in an exon in the brain-expressed forms. The mutation was undetected by gene panel sequencing because of its intronic location in the CDKL5 transcript typically used to define the exons of this gene for clinical exon-based tests (NM_003159). This is the first report of a patient with a mutation in an alternative transcript of CDKL5 This finding suggests that incorporating alternative transcripts into the design and variant interpretation of exon-based tests, including gene panel and exome sequencing, could improve the diagnostic yield. © 2018 Bodian et al.; Published by Cold Spring Harbor Laboratory Press.

Mutation in an alternative transcript of CDKL5 in a boy with early-onset seizures

PubMed Central

Bodian, Dale L.; Schreiber, John M.; Vilboux, Thierry; Khromykh, Alina; Hauser, Natalie S.

2018-01-01

Infantile-onset epilepsies are a set of severe, heterogeneous disorders for which clinical genetic testing yields causative mutations in ∼20%–50% of affected individuals. We report the case of a boy presenting with intractable seizures at 2 wk of age, for whom gene panel testing was unrevealing. Research-based whole-genome sequencing of the proband and four unaffected family members identified a de novo mutation, NM_001323289.1:c.2828_2829delGA in CDKL5, a gene associated with X-linked early infantile epileptic encephalopathy 2. CDKL5 has multiple alternative transcripts, and the mutation lies in an exon in the brain-expressed forms. The mutation was undetected by gene panel sequencing because of its intronic location in the CDKL5 transcript typically used to define the exons of this gene for clinical exon-based tests (NM_003159). This is the first report of a patient with a mutation in an alternative transcript of CDKL5. This finding suggests that incorporating alternative transcripts into the design and variant interpretation of exon-based tests, including gene panel and exome sequencing, could improve the diagnostic yield. PMID:29444904

Congenital Perisylvian Syndrome presenting as Post-partum Seizures with Preeclampsia.

PubMed

Agarwal, Arun; Goyal, Manju; Jain, Jainendra; Agarwal, Aakanksha

2017-06-01

Whether preceded by preeclampsia, or occuring without antecedent warning symptoms, eclamptic seizures usually occur in the antepartum period between 20 and 40 weeks of gestation or within a few hours to 2 days postpartum. We report the case of a patient with pre-eclampsia who developed seizures after more than 2 days of delivery. In view of late onset postpartum seizures and non-responsiveness to magnesium sulphate, she was further evaluated and diagnosed to have congenital perisylvian syndrome(CPS). In CPS, polymicrogyric cortex is distributed in variable extensions around the sylvian fissure i.e. a structural malformation of the brain with underlying anomaly of polymicrogyria. © Journal of the Association of Physicians of India 2011.

Naloxone fails to prolong seizure length in ECT.

PubMed

Rasmussen, K G; Pandurangi, A K

1999-12-01

Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy

PubMed Central

Lattanzi, Simona; Brigo, Francesco; Cagnetti, Claudia; Verrotti, Alberto; Zaccara, Gaetano; Silvestrini, Mauro

2018-01-01

Introduction Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies. Aim The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures. Evidence review ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up. Conclusion Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was

Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy.

PubMed

Lattanzi, Simona; Brigo, Francesco; Cagnetti, Claudia; Verrotti, Alberto; Zaccara, Gaetano; Silvestrini, Mauro

2018-01-01

Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies. The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures. ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up. Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was effective to reduce the seizure frequency and

Reflex epilepsy and reflex seizures of the visual system: a clinical review.

PubMed

Zifkin, B G; Kasteleijn-Nolst Trenité, D

2000-09-01

Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.

Psychosocial and seizure factors related to depression and neurotic-disorders among patients with chronic epilepsy in Nigeria.

PubMed

Olley, B O

2004-03-01

To establish the effect of psychosocial and seizure factors on Depression and Neurotic Disorders among clinically diagnosed Nigerian patients, with epilepsy. This study utilized the multivariate statistical design to evaluate the associations between some psychosocial and seizure factors on increase depression and neurotic disorders. The Neurology outpatient clinics of two tertiary facilities in Nigeria: Aro Neuro-psychiatric Hospital/World Health Organization Collaborating Centre, Abeokuta and the University College Hospital Ibadan, were used for the study. Two hundred and sixty four (264) consecutive clinic attendees with a clinical diagnosis of epilepsy participated in the study. Perceived Stigma Scale (PSS); Washington Psychosocial Seizure Inventory (WPSI-Modified): Becks Depression Inventory (BDI) and Crown-Crisp Experiential Index (CCEI). Significant main effect for seizure control, stigma, emotional adjustment, vocational adjustment, interpersonal adjustment, adjustment to seizures but not for age at onset of epilepsy, financial adjustment and gender, were recorded on depression. Similarly significant main effect for seizure control, stigma, emotional adjustment, adjustment to seizures but not for age at onset of epilepsy, gender, vocational adjustment, financial adjustment and interpersonal adjustment were recorded for neurotic disorders. The study highlights some of the factors, which may contribute to the understanding of epilepsy-related psychopathologies and implication for psychotherapeutic intervention among individuals with epilepsy in Nigeria.

Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

PubMed

Symonds, Joseph D; Joss, Shelagh; Metcalfe, Kay A; Somarathi, Suresh; Cruden, Jamie; Devlin, Anita M; Donaldson, Alan; DiDonato, Nataliya; Fitzpatrick, David; Kaiser, Frank J; Lampe, Anne K; Lees, Melissa M; McLellan, Ailsa; Montgomery, Tara; Mundada, Vivek; Nairn, Lesley; Sarkar, Ajoy; Schallner, Jens; Pozojevic, Jelena; Parenti, Ilaria; Tan, Jeen; Turnpenny, Peter; Whitehouse, William P; Zuberi, Sameer M

2017-04-01

The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Standardized assessment of seizures in patients with juvenile neuronal ceroid lipofuscinosis.

PubMed

Augustine, Erika F; Adams, Heather R; Beck, Christopher A; Vierhile, Amy; Kwon, Jennifer; Rothberg, Paul G; Marshall, Frederick; Block, Robert; Dolan, James; Mink, Jonathan W

2015-04-01

To evaluate seizure phenomenology, treatment, and course in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL). Data from an ongoing natural history study of JNCL were analyzed using cross-sectional and longitudinal methods. Seizures were evaluated with the Unified Batten Disease Rating Scale, a disease-specific quantitative assessment tool. Eighty-six children (44 males, 42 females) with JNCL were assessed at an average of three annual visits (range 1-11). Eighty-six percent (n=74) experienced at least one seizure, most commonly generalized tonic-clonic, with mean age at onset of 9 years 7 months (SD 2y 10mo). Seizures were infrequent, typically occurring less often than once every 3 months, and were managed with one to two medications for most participants. Valproate (49%, n=36) and levetiracetam (41%, n=30) were the most commonly used seizure medications. Myoclonic seizures occurred infrequently (16%, n=14). Seizure severity did not vary by sex or genotype. Seizures showed mild worsening with increasing age. The neuronal ceroid lipofuscinoses (NCLs) represent a group of disorders unified by neurodegeneration and symptoms of blindness, seizures, motor impairment, and dementia. While NCLs are considered in the differential diagnosis of progressive myoclonus epilepsy, we show that myoclonic seizures are infrequent in JNCL. This highlights the NCLs as consisting of genetically distinct disorders with differing natural history. © 2014 Mac Keith Press.

GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures.

PubMed

Wang, Dian; Wang, Xingxing; Kong, Jing; Wu, Jiayan; Lai, Minchao

2016-10-01

Understanding the overall and common metabolic changes of seizures can provide novel clues for their control and prevention. Here, we aim to investigate the global metabolic feature of serum for three types of seizures. We recruited 27 patients who had experienced a seizure within 48h (including 11 who had a generalized seizure, nine who had a generalized seizure secondary to partial seizure and seven who had a partial seizure) and 23 healthy controls. We analyzed the global metabolic changes of serum after seizures using gas chromatography-mass spectrometry-based metabolomics. Based on differential metabolites, the metabolic pathways and their potential to diagnose seizures were analyzed, and metabolic differences among three types of seizures were compared. The metabolic profiles of serum were distinctive between the seizure group and the controls but were not different among the three types of seizures. Compared to the controls, patients with seizures had higher levels of lactate, butanoic acid, proline and glutamate and lower levels of palmitic acid, linoleic acid, elaidic acid, trans-13-octadecenoic acid, stearic acid, citrate, cysteine, glutamine, asparagine, and glyceraldehyde in the serum. Furthermore, these differential metabolites had common change trends among the three types of seizures. Related pathophysiological processes reflected by these metabolites are energy deficit, inflammation, nervous excitation and neurotoxicity. Importantly, transamination inhibition is suspected to occur in seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid in serum jointly enabled a precision of 92.9% for diagnosing seizures. There is a common metabolic feature in three types of seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid levels jointly enable high-precision seizure diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Probability of detection of clinical seizures using heart rate changes.

PubMed

Osorio, Ivan; Manly, B F J

2015-08-01

Heart rate-based seizure detection is a viable complement or alternative to ECoG/EEG. This study investigates the role of various biological factors on the probability of clinical seizure detection using heart rate. Regression models were applied to 266 clinical seizures recorded from 72 subjects to investigate if factors such as age, gender, years with epilepsy, etiology, seizure site origin, seizure class, and data collection centers, among others, shape the probability of EKG-based seizure detection. Clinical seizure detection probability based on heart rate changes, is significantly (p<0.001) shaped by patients' age and gender, seizure class, and years with epilepsy. The probability of detecting clinical seizures (>0.8 in the majority of subjects) using heart rate is highest for complex partial seizures, increases with a patient's years with epilepsy, is lower for females than for males and is unrelated to the side of hemisphere origin. Clinical seizure detection probability using heart rate is multi-factorially dependent and sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the role that these factors play in shaping said probability will enhance its applicability and usefulness. Heart rate is a reliable and practical signal for extra-cerebral detection of clinical seizures originating from or spreading to central autonomic network structures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.

PubMed

Barron, Daniel S; Fox, Peter T; Pardoe, Heath; Lancaster, Jack; Price, Larry R; Blackmon, Karen; Berry, Kristen; Cavazos, Jose E; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas

2015-01-01

Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

Seizures after Onyx embolization for the treatment of cerebral arteriovenous malformation.

PubMed

de Los Reyes, K; Patel, A; Doshi, A; Egorova, N; Panov, F; Bederson, J B; Frontera, J A

2011-09-01

Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common. We explored the risk of seizures after Onyx use.A retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009. Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not. MRIs were reviewed for edema following Onyx treatment.Of 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8). The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%). A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization. Seizur post-Onyx embolization occurred in 45% (N=9). The median time to seizur post-Onyx was seven days (range 0.3-210). Four patients (20%) with seizures post-Onyx had no seizure history. Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization. Seizures in these two patients occurred within 24 hours of Onyx administration. Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0.091) and lower percent obliteration (P=0.062). Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizures.New onset seizures post-Onyx embolization are not uncommon. Further study of seizure prevention is warranted.

Seizures after Onyx Embolization for the Treatment of Cerebral Arteriovenous Malformation

PubMed Central

de los Reyes, K.; Patel, A.; Doshi, A.; Egorova, N.; Panov, F.; Bederson, J.B.; Frontera, J.A.

2011-01-01

Summary Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common. We explored the risk of seizures after Onyx use. A retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009. Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not. MRIs were reviewed for edema following Onyx treatment. Of 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8). The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%). A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization. Seizur post-Onyx embolization occurred in 45% (N=9). The median time to seizur post-Onyx was seven days (range 0.3-210). Four patients (20%) with seizures post-Onyx had no seizure history. Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization. Seizures in these two patients occurred within 24 hours of Onyx administration. Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0.091) and lower percent obliteration (P=0.062). Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizures. New onset seizures post-Onyx embolization are not uncommon. Further study of seizure prevention is warranted. PMID:22005695

Recording the adult zebrafish cerebral field potential during pentylenetetrazole seizures

PubMed Central

Pineda, Ricardo; Beattie, Christine E.; Hall, Charles W.

2017-01-01

Although the zebrafish is increasingly used as a model organism to study epilepsy, no standard electrophysiological technique for recording electrographic seizures in adult fish exists. The purpose of this paper is to introduce a readily implementable technique for recording pentylenetetrazole seizures in the adult zebrafish. We find that we can consistently record a high quality field potential over the zebrafish cerebrum using an amplification of 5000 V/V and bandpass filtering at corner frequencies of 1.6 and 16 Hz. The cerebral field potential recordings show consistent features in the baseline, pre-seizure, seizure and post-seizure time periods that can be easily recognized by visual inspection as is the case with human and rodent electroencephalogram. Furthermore, numerical analysis of the field potential at the time of seizure onset reveals an increase in the total power, bandwidth and peak frequency in the power spectrum, as is also the case with human and rodent electroencephalogram. The techniques presented herein stand to advance the utility of the adult zebrafish in the study of epilepsy by affording an equivalent to the electroencephalogram used in mammalian models and human patients. PMID:21689682

A KCNQ channel opener for experimental neonatal seizures and status epilepticus

PubMed Central

Raol, YogendraSinh H.; Lapides, David A.; Keating, Jeffery; Brooks-Kayal, Amy R.; Cooper, Edward C.

2009-01-01

Objective Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage-gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures. Methods We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures. Results Unlike phenobarbital or diazepam, flupirtine prevented animals from developing status epilepticus (SE) when administered prior to kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate-induced SE. Flupirtine caused dose-related sedation and suppressed EEG activity, but did not result in respiratory suppression or result in any mortality. Interpretation Flupirtine appears more effective than either of two commonly used anti-epileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children. PMID:19334075

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

PubMed Central

Dubey, Mohit; Brouwers, Eelke; Hamilton, Eline M.C.; Stiedl, Oliver; Bugiani, Marianna; Koch, Henner; Kole, Maarten H.P.; Boschert, Ursula; Wykes, Robert C.; Mansvelder, Huibert D.; van der Knaap, Marjo S.

2018-01-01

Objective Loss of function of the astrocyte‐specific protein MLC1 leads to the childhood‐onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. Methods We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole‐cell patch‐clamp recordings and K+‐sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. Results An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. Interpretation Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636–649 PMID:29466841

Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats

PubMed Central

Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G.

2012-01-01

Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect. PMID:22692938

75 FR 4407 - The Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... premarket approval application for the Deep Brain Stimulation System for Epilepsy sponsored by Medtronic...-onset seizures (affecting only a part of the brain when they begin), with or without secondary... a partial-onset seizure that later spreads to the whole brain. ``Refractory'' to antiepileptic...

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks

PubMed Central

Soper, Colin; Wicker, Evan; Kulick, Catherine V.; N’Gouemo, Prosper; Forcelli, Patrick A.

2016-01-01

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. PMID:26721319

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks.

PubMed

Soper, Colin; Wicker, Evan; Kulick, Catherine V; N'Gouemo, Prosper; Forcelli, Patrick A

2016-03-01

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

PubMed

Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

2016-07-01

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. © The Author(s) 2016.

Brivaracetam Injection

MedlinePlus

... along with other medications to control partial onset seizures (seizures that involve only one part of the brain) ... mood. If you suddenly stop using brivaracetam, your seizures may become worse. Your doctor will probably decrease ...

Ictal SPECT using an attachable automated injector: clinical usefulness in the prediction of ictal onset zone.

PubMed

Lee, Jung-Ju; Lee, Sang Kun; Choi, Jang Wuk; Kim, Dong-Wook; Park, Kyung Il; Kim, Bom Sahn; Kang, Hyejin; Lee, Dong Soo; Lee, Seo-Young; Kim, Sung Hun; Chung, Chun Kee; Nam, Hyeon Woo; Kim, Kwang Ki

2009-12-01

Ictal single-photon emission computed tomography (SPECT) is a valuable method for localizing the ictal onset zone in the presurgical evaluation of patients with intractable epilepsy. Conventional methods used to localize the ictal onset zone have problems with time lag from seizure onset to injection. To evaluate the clinical usefulness of a method that we developed, which involves an attachable automated injector (AAI), in reducing time lag and improving the ability to localize the zone of seizure onset. Patients admitted to the epilepsy monitoring unit (EMU) between January 1, 2003, and June 30, 2008, were included. The definition of ictal onset zone was made by comprehensive review of medical records, magnetic resonance imaging (MRI), data from video electroencephalography (EEG) monitoring, and invasive EEG monitoring if available. We comprehensively evaluated the time lag to injection and the image patterns of ictal SPECT using traditional visual analysis, statistical parametric mapping-assisted, and subtraction ictal SPECT coregistered to an MRI-assisted means of analysis. Image patterns were classified as localizing, lateralizing, and nonlateralizing. The whole number of patients was 99: 48 in the conventional group and 51 in the AAI group. The mean (SD) delay time to injection from seizure onset was 12.4+/-12.0 s in the group injected by our AAI method and 40.4+/-26.3 s in the group injected by the conventional method (P=0.000). The mean delay time to injection from seizure detection was 3.2+/-2.5 s in the group injected by the AAI method and 21.4+/-9.7 s in the group injected by the conventional method (P=0.000). The AAI method was superior to the conventional method in localizing the area of seizure onset (36 out of 51 with AAI method vs. 21 out of 48 with conventional method, P=0.009), especially in non-temporal lobe epilepsy (non-TLE) patients (17 out of 27 with AAI method vs. 3 out of 13 with conventional method, P=0.041), and in lateralizing the

The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome

PubMed Central

Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J.; Duffy, Frank H.; Pearl, Phillip L.; Treves, S. Ted

2016-01-01

Objective Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Methods Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age = 11 years, (25th, 75th) quartiles = (6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Results Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p = 0.02) but not MRI findings (p = 0.33), epilepsy etiology (p ≥ 0.27) or seizure duration (p = 0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Significance Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to