Topiramate on ictal seizure semiology: a quantitative, randomized, low and medium dose-controlled study

OBJECTIVE: Intensive and quantitative evaluation of the severity and frequency of seizures and ictal signs during topiramate (TPM) treatment. METHODS: Twenty patients with refractory partial seizures undergoing presurgical evaluation were randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg daily) group of TPM add-on medication. Study phases included a 3-day baseline video-EEG phase, a 10-day TPM titration phase without video-EEG and a 3-day TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured: duration (lasting seconds of each seizure and ictal sign), intensity (on a 0-3 scale), N/24 h (numbers of attacks per 24 h), D/24 h (duration per 24 h) of both seizures and defined ictal signs. RESULTS: A total of 399 seizures during the baseline phase and the dose maintenance phase were intensively analyzed. Intergroup comparison suggested that duration, N/24 h and D/24 h of all seizures decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P<0.05). There were statistically more significant reductions in the duration, intensity and N/24 h of ictal signs like hypermotoric movements, fumbling and vocalization in the medium dosage group (P<0.05). CONCLUSION: Topiramate has an early dose-dependent effect on ictal seizures. SHORT COMMUNICATION: The present study intensively analyzed the duration, intensity, N/24 h and D/24 h of ictal seizure manifestations. The quantitative data suggested that topiramate had an early effect on ictal phenomena like ictal hypermotoric movements, fumbling and vocalization (P<0.05); effects were more prominent in the medium dosage group (200 mg daily) than the low dosage group (100 mg daily).     

Influence on ictal seizure semiology of rapid withdrawal of carbamazepine and valproate in monotherapy

PURPOSE: To quantify changes in ictal seizure semiology during rapid withdrawal of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical evaluation. METHODS: Therapeutic intensive seizure analysis (TISA) with video-EEG monitoring was used in 33 patients with pharmacoresistant partial epilepsy undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a monoregimen. Monitoring phases included a 3-day baseline phase, a 3-day rapid antiepileptic drug (AED) withdrawal phase, and another 3-day AED-free phase with AEDs in subtherapeutic levels. Seizure variables as complete processes and their various elements (ictal signs) were analyzed, including duration (seconds), intensity (on a scale of 0 to 3), frequency (number per 3 days), and total duration of seizures and ictal signs in 3 days (seconds). The localization of seizure patterns on ictal EEG recording (EEG seizure onset) and the first appearing clinical ictal phenomena (initial ictal signs) were recorded. RESULTS: A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were investigated. Compared with the baseline phase, the CBZ group showed increases in duration, frequency of seizures, various ictal signs, and secondarily generalized tonic and clonic signs during the following two phases. Significantly increased values of the VPA group were observed in seizure duration and frequency of hypermotoric phenomena during the AED-free phase. More patients in the CBZ group had secondarily generalized clonic signs during the AED-free phase. EEG seizure onset and initial ictal signs showed no obvious changes between study phases. CONCLUSIONS: Withdrawal of CBZ is followed more quickly by an increase of seizure frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA withdrawal influences seizure propagation rather than the seizure-onset characteristics, which speaks in favor of its use in presurgical evaluation.     

Changes of seizures activity during rapid withdrawal of lamotrigine

Quantitatively evaluating the rapid withdrawal effects of lamotrigine (LTG) and carbamazepine (CBZ) on seizure activity during pre-surgical evaluation in patients with pharmacoresistant complex partial epilepsy. The duration and frequency of seizure activities and electrographic seizure onset of 41 patients totally withdrawing from CBZ monotherapy (n = 20), LTG monotherapy (n = 10) and CBZ + LTG combined therapy (n = 11) were intensively studied by therapeutic intensive seizure analysis (TISA) method. Study phases ran from the baseline phase to the antiepileptic drug (AED) withdrawal phase until the AED free phase, 3 days for each phase. Seizure duration and frequency obviously increased during the withdrawal process in each group (P < 0.05). The duration of secondarily generalized clonic signs markedly increased with the tapering of each drug; tonic signs, however, only in the AED free phase (P < 0.05). The frequency of secondary tonic and clonic signs only increased in the CBZ and CBZ + LTG group. Intergroup comparisons of all variables were insignificant (P > 0.05). There was no change of ictal EEG localization during all withdrawal protocols. All patients experienced more severe seizures during the withdrawal processes. An earlier aggravation of the clonic signs than the tonic signs was observed in each group. Difference between the withdrawal effects of LTG and CBZ monotherapy and LTG + CBZ polytherapy was mainly in the frequency change of ictal signs. The withdrawal process did not influence the ictal EEG localization. This study justified the withdrawal in pre-surgical localization, rationalized precautions for possible accompanying risks, and also aroused attentions in clinical anticonvulsant trials and substitutions involving withdrawal process.     

Postictal generalized electroencephalographic suppression is associated with generalized seizures

Postictal generalized electroencephalographic suppression (PGES) may be involved in sudden unexpected death in epilepsy (SUDEP). We examined whether the occurrence of PGES depends on seizure type and whether PGES occurs more frequently in people with epilepsy who died suddenly. EEG recordings of people with pharmacoresistant focal epilepsies who died from SUDEP after presurgical video/EEG telemetry were compared with recordings of living controls. To test if PGES depends on seizure type, EEG recordings of people with temporal lobe epilepsy who had complex partial seizures (CPS) and secondarily generalized tonic-clonic seizures (GTCS) were reviewed. A total of 122 seizures in 57 individuals have been included. PGES was observed in 15% of all seizures in 26% of all individuals. Secondarily GTCS were significantly associated with PGES. Neither presence nor duration of PGES differed between the SUDEP and control groups. In conclusion, PGES is facilitated by secondarily GTCS, but does not seem to be an independent risk factor for SUDEP.     

The generalized tonic-clonic seizure in partial versus generalized epilepsy: semiologic differences

PURPOSE: To study differences in the clinical manifestations of generalized tonic-clonic seizures (GTCS) of partial versus generalized onset. METHODS: We studied 10 GTCSs in nine patients with idiopathic generalized epilepsy (IGE) and 10 GTCSs in 10 patients with temporal lobe epilepsy (TLE). Videotaped seizures were reviewed for all clinical features, focusing on asymmetries during different phases of each seizure. RESULTS: In the IGE group, focal features were seen before generalized motor activity in seven seizures. The most common was adversive head turn (six seizures). One patient had opposite direction of head turning in two recorded seizures. The tonic phase was always symmetric. In the last generalized clonic phase, asymmetry or asynchrony of motor activity was seen transiently in three seizures. The TLE group showed focal features before generalization in all seizures. Adversive head turning occurred in nine patients and was always contralateral to the focus. Focal clonic activity occurred before generalization in three and was always contralateral to the focus. The generalized tonic phase was usually asymmetric, and in the last clonic phase, motor activity was asymmetric or asynchronous in eight seizures (p<0.05, IGE vs. TLE). CONCLUSIONS: Brief focal features or asymmetry at onset are common in the GTCSs of IGE. However, asymmetry or asynchrony during the last clonic phase are uncommon in IGE, in contrast to TLE.     

Anticonvulsant action of topiramate against motor seizures in developing rats

PURPOSE: To study the anticonvulsant action of topiramate (TPM) in developing rats. METHODS: Motor seizures were elicited by administering pentylenetetrazol (100 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 to 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-old rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated. RESULTS: TPM did not influence minimal seizures (clonus of forelimb and head muscles with preserved righting ability). Generalized tonic-clonic seizures, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited generalized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80-mg/kg doses in the 7-day-old rat pups. The specific suppression of the tonic phase of generalized seizures was observed up to 12 hours in the 12-day-old rat pups. The same result was obtained over 6 hours after TPM administration in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group. CONCLUSIONS: TPM exhibits stable anticonvulsant action against the tonic phase of generalized tonic-clonic seizures throughout development. In addition, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action.     

Lateralizing value of asymmetric tonic limb posturing observed in secondarily generalized tonic-clonic seizures

PURPOSE: A striking asymmetry of limb posture occurs during secondarily generalized tonic-clonic (GTC) seizures wherein one elbow is extended while the other is flexed during the tonic phase of the GTC seizure. We have named this phenomenon asymmetric tonic limb posturing (ATLP) or the "Figure 4 Sign." METHODS: Fifty-nine secondarily GTC seizures from 31 patients with partial epilepsy who underwent successful epilepsy surgery were analyzed, in addition to another group of 64 GTC and generalized clonic seizures from 26 patients collected prospectively over a 7-month period. Three observers reviewed these seizures blinded to the side of ictal EEG onset and other clinical data. RESULTS: The extended elbow was contralateral to the side of ictal onset in 35 of 39 patients who had ATLP during their seizures. The kappa index, a measure of interobserver agreement, was calculated, and ATLP was found to have very good agreement between observers. CONCLUSIONS: In secondarily generalized tonic-clonic seizures, ATLP (Figure 4 Sign) may sometimes be only available lateralizing sign.     

Effect of precollicular transection on audiogenic seizures in genetically epilepsy-prone rats

Previous studies have demonstrated that generalized tonic-clonic seizures (GTCS) consisting of running/bouncing clonic and tonic extension can still be elicited in rats after brain transections which separate forebrain from brain stem, showing that forebrain circuitry is not required for GTCS. Inasmuch as sound-induced generalized tonic-clonic seizures in rodents are characterized by running-bouncing clonic and tonic convulsions, we have hypothesized that these are brain stem seizures that can occur independently of the forebrain. To test this hypothesis, we examined the response of two strains of genetically epilepsy-prone rats (GEPR-3s and GEPR-9s) to seizure-evoking auditory stimuli 3 h after a precollicular transection or sham surgery performed under ether anesthesia. In addition, the effect of a precollicular transection on audiogenic seizures was evaluated in normal rats made susceptible to such seizures by infusing NMDA into the inferior colliculus. Following the transection 58% of GEPR-9s displayed a sound-induced tonic-clonic convulsion and the remaining 42% exhibited a sound-induced seizure when subjected to stimulation 5 min after a subconvulsant dose of pentylenetetrazol (PTZ). While sham surgery and the precollicular transection both reduced sound-induced seizure severity in GEPR-3s, the full seizure response could be elicited by sound stimulation following a subconvulsant dose of PTZ. Moreover, the audiogenic seizures in normal rats rendered susceptible by NMDA were unaltered by the precollicular transection. These findings show that the anatomical circuitry required for generalized tonic-clonic seizures evoked by sound stimulation in rodents resides within the brain stem.     

Differential effects of NMDA antagonists microinjections into the nucleus reticularis pontis caudalis on seizures induced by pentylenetetrazol in the rat

It has been shown that NMDA antagonists block the tonic but not the clonic component of seizures when they are injected in the oral region of the rat pontine reticular formation (PRF). The participation of the caudal PRF in the effects of NMDA antagonists upon the tonic and the clonic components of generalized seizures induced by pentylenetetrazol (PTZ) is unknown. The aim of the present study was to evaluate the effects of unilateral microinjections of competitive and non-competitive NMDA antagonists, 2-amino-7-phosphonoheptanoic acid (AP-7) and dizocilpine (MK-801), respectively, into the nucleus reticularis pontis caudalis of the rat PRF upon seizures induced by PTZ (70 mg/kg i.p.). MK-801 induced a dose-related decrease both in the incidence of generalized tonic-clonic seizures (GTCS) and in the presence of spikes in the EEG. MK-801 also increased GTCS latency. On the contrary, AP-7 did not have effects on GTCS. Interestingly, it induced ipsilateral circling behavior. These results suggest that in the caudal region of the rat PRF only non-competitive NMDA antagonists should block the generation of tonic and clonic components of generalized seizures.     

A detailed analysis of symptomatic posterior cortex seizure semiology in children younger than seven years

PURPOSE: To analyze the semiology of seizure onset and evolution in young children with posterior cortex epilepsy (PCE), compare this with adult reports, and assess age-related differences. METHODS: We videotaped and analyzed 110 seizures from 18 patients with PCE, aged 3-81 months. All had a good prognosis after posterior epileptogenic zone removal. Ictal events were categorized by behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included myoclonic, tonic, clonic, unclassified motor seizures, and epileptic spasm. A time-scaled data sheet was developed to record each epileptic event as onset, very early, early, or late manifestation. RESULTS: Patients had a high seizure frequency with < or =100 attacks/day; one third of them showed a cluster tendency. The mean duration of seizures was 67 s. The most common seizure components were motor manifestations (with myoclonic and tonic seizures), but psychomotor (automotor), hypomotor attacks, and isolated auras also were frequently observed. Clinical seizure spread was frequent; auras and visual sensory signs were difficult to record in this age. Typical phenomena during seizures included behavioral changes, ictal vocalization, smile, flush, head nod, oculomotor features, and late-appearing oral automatisms, whereas hypermotor and secondarily generalized tonic-clonic seizures were not seen. CONCLUSIONS: Our results suggest that PCE in infants and young children is very heterogeneous but shows important age-related features. Compared with adults, children with PCE have shorter but more frequent seizures; they rarely report aura or visual sensory signs, only sporadically develop hypermotor and secondarily generalized tonic-clonic seizures, whereas ictal smile, flush, head nod, and behavioral change are typical features at this age. Because of frequent subtle ictal phenomena, long-term video-EEG monitoring is a useful diagnostic tool with infants and young children with PCE.     

Neuron-Specific Enolase Is Increased After Single Seizures During Inpatient Video/EEG Monitoring

Neuron-specific enolase (NSE) is a marker of brain injury after acute neurologic insults. We report changes in serum NSE (s-NSE) in 25 patients (15 with epilepsy and 10 patients with nonepileptic events) during continuous inpatient video/EEG monitoring. s-NSE was significantly increased as compared with baseline and normal controls after the first ictal event in the epileptic group, especially in patients with secondarily generalized tonic-clonic seizures (p = 0.01), but s-NSE was not increased in patients with nonepileptic events. These preliminary data indicate that s-NSE may be increased after complex partial seizures-and generalized tonic-clonic seizures (GTCS).     

Variation of seizure frequency with ovulatory status of menstrual cycles

Purpose: To determine if seizure frequency differs between anovulatory and ovulatory cycles. Methods: The data came from the 3‐month baseline phase of an investigation of progesterone therapy for intractable focal onset seizures. Of 462 women who enrolled, 281 completed the 3‐month baseline phase and 92 had both anovulatory and ovulatory cycles during the baseline phase. Midluteal progesterone levels ≥5 ng/ml were used to designate cycles as ovulatory. Among the 92 women, average daily seizure frequency (ADSF) for all seizures combined and each type of seizure considered separately (secondary generalized tonic–clonic seizures – 2°GTCS, complex partial seizures – CPS, simple partial seizures – SPS) were compared between anovulatory and ovulatory cycles using paired t‐tests. A relationship between the proportional differences in ADSF and estradiol/progesterone (EP) serum level ratios between anovulatory and ovulatory cycles was determined using bivariate correlational analysis. Key Findings: ADSF was 29.5% greater for 2°GTCS during anovulatory than during ovulatory cycles. ADSF did not differ significantly for CPS or SPS or for all seizures combined. Proportional differences in anovulatory/ovulatory 2°GTCS ADSF ratios correlated significantly with differences in anovulatory/ovulatory EP ratios. Among the 281 women, the three seizure types did not differ in ovulatory rates, but EP ratios were greater for cycles with 2°GTCS than partial seizures only. Significance: Seizure frequency is significantly greater for 2°GTCS, but not CPS or SPS, during anovulatory cycles than ovulatory cycles. Because the proportional increases in 2°GTCS frequency during anovulatory cycles correlate with the proportional increases in EP level ratios, these findings support a possible role for reproductive steroids in 2°GTCS occurrence.     

Topiramate Monotherapy for Partial Onset Seizures

Summary: Purpose: Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.
Methods: A total of 48 patients were evaluated in a doubleblind, parallel-group trial. During a 56-day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs). After 1–2 weeks of open-label treatment with TPM 100 mg/day, patients were randomly assigned, in equal proportions, to receive double-blind therapy with TPM 100 or 1,000 mg/day in a 5-week conversion and an 11-week monotherapy period. The study endpoint was completion of 112 study days (success) or fulfillment of one or more exit criteria: doubling of average 28- day or highest 2-day baseline seizure rate, a generalized tonic-clonic seizure (GTCS) if none had occurred at baseline, or significant prolongation of generalized seizure duration.
Results: Time until exit was longer (p = 0.002) and success frequency was higher (p = 0.005) with TPM 1,000 as compared with 100 mg/day. Seizure-rate reductions of 50, 75, or 100% were achieved by 46, 25, and 13% of the 1,000-mg/day group, respectively, as compared with 13, 8, and 0% of the 100-mg/day group, respectively. Most adverse events (AE) were mild or moderate in severity.
Conclusions: Monotherapy with TPM 1,000 mg/day for partial onset seizures with or without secondarily generalized seizures was effective, with a favorable safety profile.     

Serum serotonin levels in patients with epileptic seizures

Profound cardiovascular and/or respiratory dysfunction is part of the terminal cascade in sudden unexpected death in epilepsy (SUDEP). Central control of ventilation is mediated by brainstem rhythm generators, which are influenced by a variety of inputs, many of which use the modulatory neurotransmitter serotonin to mediate important inputs for breathing. The aim of this study was to investigate epileptic seizure–induced changes in serum serotonin levels and whether there are potential implications for SUDEP. Forty‐one epileptic patients were pooled into 2 groups based on seizure type as (1) generalized tonic–clonic seizures (GTCS) of genetic generalized epilepsy and focal to bilateral tonic–clonic seizures (FBTCS; n = 19) and (2) focal seizures (n = 26) based on clinical signs using surface video‐electroencephalography. Postictal serotonin levels were statistically significantly higher after GTCS and FBTCS compared to interictal levels (P = .002) but not focal seizures (P = .941). The change in serotonin (postictal‐interictal) was inversely associated with a shorter duration of tonic phase of generalized seizures. The interictal serotonin level was inversely associated with a shorter period of postictal generalized electroencephalographic suppression. These data suggest that peripheral serum serotonin levels may play a role in seizure features and earlier postseizure recovery; these findings merit further study.     

Topiramate: effect on EEG interictal abnormalities and background activity in patients affected by focal epilepsy

PURPOSE: To evaluate the effects of topiramate (TPM) on interictal epileptiform abnormalities (IEA) and background activity by means of a computerized EEG analysis, in adult patients affected by focal epilepsy, with or without secondarily generalization, treated with TPM as adjunctive therapy or monotherapy. METHODS: Twenty-four patients affected by symptomatic or cryptogenic focal epilepsy underwent long-term video-EEG recording before and after TPM addition (mean dose 175+/-25 mg per day). RESULTS: TPM addition induced a significant reduction of both partial and secondarily generalized tonic-clonic (SGTC) seizures; treatment responder patients (seizure reduction > or = 50%) were 19 out of 24 patients (79.1%), of whom 5 were seizure-free. Quantitative analysis of IEA showed a significant decrease in the mean number of spikes/10 min during TPM therapy ( 4.2+/-4.2 versus 2.2+/-4.4; P<0.003 ). The analysis of spatial distribution of interictal spikes showed that such reduction was more evident at the level of the epileptogenic area rather than on the spreading component. Statistical analysis revealed only a significant decrease of mean relative power of alpha band in the EEG spectral content, recorded at rest in a group of 18 out of 24 epileptic patients during TPM therapy. In addition, during TPM treatment we observed a significant reduction in alpha reactivity without any important changes of alpha indexes (peak frequency and median frequency). CONCLUSION: These findings suggest that TPM has a strong inhibitory effect on IEA, probably acting on the generating processes, and, if used at low dosage and gradually titrated, seems to have only mild interferences with EEG background activity.     

Clinical Efficacy of Topiramate as Add-On Therapy in Refractory Partial Epilepsy: The European Experience

Summary: In three randomized, double-blind, placebo-controlled add-on European trials, target daily topiramate (TPM) dosages of 400, 600, and 800 mg/day (200, 300, and 400 mg bid) were evaluated in adults with refractory partial seizures with or without becoming secondarily generalized. Median reductions from baseline in monthly seizure rate were 41% with TPM 400 mg/day vs. 1% with placebo ( n = 0.065), 46% with TPM 600 mg/day compared to -12% (a 12% increase) with placebo ( p ≤ 0.005), and 36% with TPM 800 mg/day versus –18% (an 18% increase) with placebo ( p ≤ 0.001). Differences between TPM and placebo with respect to percent responders (percent of patients demonstrating a 50% or greater reduction in seizures) significantly favored TPM ( p ≤ 0.05) at all three target dosages. Significant reductions in secondarily generalized tonic-clonic seizures compared to placebo were also observed with 400 mg/day ( p = 0.002) and 800 mg/day ( p < 0.05) of TPM. TPM appears to be a promising new antiepileptic drug for use as adjunctive therapy in adults with refractory partial epilepsy.     

Valproate Monotherapy in 30 Patients with Partial Seizures

This retrospective pilot study describes 30 patients diagnosed and treated for complex partial seizures (CPS) and simple partial seizures (SPS) with and without generalization who received valproate (VPA) monotherapy after lack of response or allergic reaction for carbamazepine (CBZ), phenytoin (PHT), or phenobarbital (PB). Seizures were tabulated daily on seizure calendars by the patients. Three time periods were examined for seizure frequency, 90 days before VPA treatment and 90 and 180 days after VPA treatment. Twenty-two were "controlled" or "improved" (reduction of seizure activity by greater than or equal to 51%) 6 months following the initiation of VPA. VPA was particularly effective in 17 patients who had secondarily generalized tonic-clonic seizures (GTCS) as a subtype of partial seizures. Failure of response to VPA in eight patients appears to be related to their type of partial seizure (SPS or CPS alone, without GTCS) and duration of uncontrolled recurrent seizures. Etiology and compliance were not related to treatment failure. This study supports the need for a double-blind controlled trial with VPA in patients with partial seizures.     

Strategies for non‐EEG seizure detection and timing for alerting and interventions with tonic–clonic seizures

Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic–clonic seizures (GTCS). Non–electroencephalography (EEG) seizure detection systems using mobile sensor devices permit caregivers to assist patients during seizures and may reduce risks for complications of seizures such as injuries and SUDEP. We review changes in accelerometry, electrodermal activity, and heart rate associated with tonic–clonic seizures and their use in detection systems, including multimodal detectors. We reviewed current and past publications reporting data on linkage between GTCS, post‐ictal generalized EEG suppression (PGES), and ventilatory dysfunction. The timing and duration of postictal immobility and respiratory dysfunction associated with convulsions help identify which patients might benefit the most from seizure monitoring and from benchmarks for the timing of seizure detection, caregiver alerting, and interventions.     

Side‐to‐side axial movements

Aim. To study new semiological signs which help distinguish between primary and secondarily generalised tonic‐clonic seizures (GTCS). Methods. We retrospectively studied 86 GTCS, 13 primary and 73 secondary, in 58 patients who underwent video‐EEG (vEEG) evaluation in our epilepsy monitoring unit. Eleven patients had generalised epilepsy and 47 focal epilepsy. Two expert epileptologists, blinded to diagnosis, examined the vEEGs independently for the presence of five semiological signs. Results. Asymmetry of limb movements in clonic phase, side‐to‐side axial movements, and asymmetric seizure termination occurred more frequently (p<0.05) in secondary GTCS compared to primary GTCS. Combining asymmetry of limb movements in clonic phase and side‐to‐side axial movements provided the greatest value in differentiating secondary GTCS from primary GTCS. Conclusion. Careful examination of GTCS seizure semiology can help differentiate primary from secondary GTCS. The semiological sign of side‐to‐side axial movements, which has not previously been studied in this context, may add to existing literature of semiological signs and be of value for the evaluation of surgical patients in the epilepsy monitoring unit. In the out‐patient setting, a clear history of these signs may help guide drug treatment choices. [Published with video sequences].     

Safety and efficacy of perampanel in children and adults with various epilepsy syndromes: A single-center postmarketing study

IntroductionPerampanel is an AMPA receptor antagonist recently approved for the treatment of partial and generalized epilepsies with tonic–clonic seizures as an add-on therapy.MethodsThis single-center postmarketing study retrospectively evaluated the efficacy of perampanel in patients with partial onset and other seizure types, with a special emphasis on its efficacy, safety, and tolerability.ResultsReview of medical records revealed that adequate data were available on 101 patients taking perampanel. Fifty-seven patients were female. Sixteen patients were of pediatric age range. The average dose of perampanel was 6.5 mg, and average treatment duration was 8.2 months. After treatment, median seizure frequency reduction was 50% overall, 50% in children, and 33% in adults; 44% in primary generalized, 38% in secondarily generalized, and 33% in partial seizures. Responder rate (50% seizure frequency reduction) was 51% overall, 63% in children, and 49% in adults; 60% in partial seizures, 43% in secondarily generalized tonic–clonic seizures, 53% in primary generalized tonic–clonic seizures, and 56% in other seizure types. Seizure freedom was attained in 6% of cases. Most common adverse events were sleepiness/fatigue (35%), behavioral problems (30%), and dizziness (22%). Adverse events were correlated with dosage. Average dose was 7.3 mg in patients with adverse events vs. 5.5 mg in those without adverse events. Patients who developed fatigue, cognitive decline, headaches, and weight gain were more likely to discontinue perampanel than those patients who experienced coordination issues and behavioral problems.ConclusionsThese findings suggest that perampanel is safe, well-tolerated, and effective in treatment of various types of adult and pediatric epilepsy syndromes. Fatigue, cognitive decline, headache and weight gain were the main causes of perampanel discontinuation.