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.     

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).     

Clinical effects of topiramate against secondarily generalized tonic--clonic seizures

OBJECTIVE: Intensive and quantitative evaluation of the duration, intensity and frequency of tonic and clonic signs of secondarily generalized tonic-clonic seizures (GTCS) in patients with pharmacoresistant partial seizures during topiramate (TPM) treatment. METHODS: Thirty patients suffering from refractory partial seizures with secondarily GTCS 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 (15 patients for each group). Study phases included a 3 days baseline video-EEG phase, a 10 days TPM titration phase without video-EEG and a 3 days 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 for each recorded secondarily generalized tonic and clonic signs: duration (lasting seconds), intensity (on a 0-3 scale), frequency (numbers per 24 h). RESULTS: A total of 46 complex partial seizures with secondarily generalized tonic-clonic signs during the baseline phase and 20 during the dose maintenance phase were intensively analyzed. More patients in the medium dosage group than in the low dosage groups were free from secondarily GTCS during the dose maintenance phase (nine vs. two, P<0.05). Intergroup comparison suggested that the duration of all tonic signs 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 and intensity of clonic signs in the medium dosage group (P<0.05). CONCLUSION: TPM has an early dose-dependant effect on secondarily GTCS in patients with pharmacoresistant partial seizures. SHORT COMMUNICATION: The present study intensively analyzed the duration, intensity, and frequency of secondarily generalized tonic and clonic signs in patients with pharmacoresistant partial seizures. The quantitative data suggested that TPM had a robust early inhibitory effect on secondarily generalized tonic-clonic signs; effects were more prominent in the medium dosage group (200 mg daily) than in the low dosage group (100 mg daily).     

Aggravation of epilepsy by valproate sodium in a child with cryptogenic localization-related epilepsy

We report a paradoxical effect of valproate sodium (VPA) observed in a 3-year-old girl with cryptogenic localization-related epilepsy. On admission she experienced two types of seizures that were confirmed by ictal EEGs : complex partial seizures (CPSs) originating from the left hemisphere and combined seizures that began with repetitive myoclonic seizures immediately followed by a CPS. These myoclonic seizures did not possess asymmetrical features, but the ictal EEGs showed left-side dominant multiple spike-waves. The patent's interictal EEGs on admission showed left posterior temporal- parietal spikes during wakefulness and frequent diffuse spike-waves during sleep. In the process of introduction and increase in the dosage of VPA, an aggravation of epileptic discharges, especially a dramatic increase in diffuse spike-waves during sleep, was observed. In the same period of time, myoclonic seizures not followed by CPS newly appeared, and there was an increase in the frequency of CPSs and combined seizures. Marked improvement of epileptic discharges, namely the disappearance of diffuse discharges, and complete suppression of all types of seizures were achieved by the introduction of carbamazepine (CBZ) along with the withdrawal of VPA. During the clinical course, the patient did not display any signs or symptoms of VPA encephalitis, overdose of VPA or metabolic aberration. The paradoxical effect of CBZ in localization-related epilepsy is well-known, yet in this case, VPA displayed a similar paradoxical effect. Additionally, CBZ was efficacious in the suppression of secondary bilateral synchrony on EEG and also successfully controlled CPSs, combined seizures and myoclonic seizures.     

Prognostic value of the consistency of lateralizing ictal features and ictal EEG in patients undergoing temporal lobectomy for refractory complex partial seizures.

PURPOSE: Ictal and postictal clinical manifestations have lateralizing value in the presurgical evaluation of intractable seizures. The consistency and frequency of these signs during seizures and the associated implications for postoperative seizure outcome are unknown. METHODS: The videotaped complex partial seizures of 49 patients with known postoperative outcomes greater than 2 years after temporal lobectomy were blindly reviewed for: (1) unilateral hand posturing (UHP), (2) unilateral hand automatism (UHA), (3) forced and nonforced head turning (HT), and (4) postictal dysphasia (PID). The presence and laterality of each assessable sign were recorded. Data were analyzed as follows: (1) the prevalence of each sign in patients with Engel class 1 and Engel class 2-4, and (2) the postsurgical outcome when the sign was present in more than or less than 50% of the seizures for each patient. We reviewed patients' presurgical work-up, specifically ictal EEG and MRI. RESULTS: The prevalence of UHP, UHA, HT, and PID was similar for Engel class 1 and Engel class 2-4 patients. Engel class 1 outcome when UHP, UHA, HT, and PID were present for greater than 50% of seizures was no different compared to when these signs were present for less than 50% of seizures. Patients who had concordant ictal EEG and MRI abnormalities had the best postsurgical outcome. CONCLUSIONS: The consistency and frequency of ictal manifestations in the presurgical evaluation of complex partial seizures does not predict seizure outcome. The presence of any specific lateralizing sign need not be present in every complex partial seizure for the sign to hold predictive value. Concordant ictal EEG and MRI abnormalities are still the best predictors of outcome.     

Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine

A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE).     

脑干起源肌阵挛模型的建立

目的 探讨建立在发生机制、发作行为、神经电生理学及药效学特征等方面均与临床脑干起源肌阵挛更为一致的实验动物模型.方法 以5-羟色胺(5-HT)的前体L-5-羟色胺酸(L-5-HTP)在健康幼年豚鼠脑桥背侧定点微量注射诱发肌阵挛(同步记录的脑电图暴发活动≤400 ms),观察肌阵挛发作潜伏期、达峰时间、最大发作频率、高峰持续时间和总持续时间等行为学特征.以多导电生理同步记录肌阵挛发作期脑电图、肌电图以及抽动逆向锁定的脑电叠加分析(JLA),论证及认定肌阵挛为脑干起源,并选择对控制肌阵挛具不同效力的丙戊酸(VPA)、氯硝西泮(CZP)和卡马西平(CBZ)等抗癫(癎)药物(AEDs),按达到半数有效浓度(EC_(50))的剂量预处理实验动物后,根据各自药效学特征择时诱导肌阵挛发作,观测抗癫(癎)药物预处理后肌阵挛发作行为及电生理学的变化特征.结果 (1)在一定剂量范围内,L-5-HTP在8只豚鼠脑桥背侧部微量注射,全部一次性诱发单纯性肌阵挛发作,诱发成功率100%.(2)行为学特征:脑桥起源肌阵挛发作表现为两侧或全身性肌阵挛,并显示对触摸、声音刺激的敏感性.(3)脑桥起源肌阵挛肌电暴发时程较长,达(208.75±81.42)ms,同步脑电图中,有散在不规则棘、尖波发放,但与肌电图活动不存在锁时关联.(4)脑桥起源肌阵挛发作中脑电图虽然时有散在棘、尖波发放,但经JLA叠加后无锁时关联的脑电图叠加波.(5)在一次性给药后达到EC_(50)浓度下,VPA和CZP使脑桥起源肌阵挛的最大发作频率[VPA组(28.13±3.79)次/min;CZP组(37.17±4.67)次/min]较对照组[(56.25±6.96)次/min]减少、高峰持续时间[VPA组(55.00±14.14)min;CZP组(50.00±11.73)min]和总持续时间[VPA组(124.17±40.04)min;CZP组(156.88±30.71)min]较对照组[高蜂持续时间(80.00±16.01)min;总持续时间(218.75±17.63)min]显著缩短(F=23.41～35.44,P＜0.01或P＜0.05),对肌阵挛的肌电图时程未有显著影响;CBZ使肌阵挛发作的高峰持续时间[(98.75±13.86)min]和总持续时间[(257.50±14.79)min]较对照组明显延长(P＜0.05、0.01).结论 本模型不仅保证了脑干肌阵挛纯起源,同时因使模型肌阵挛暴发时程显著缩短至400 ms以内,对触觉敏感和对CZP治疗显著有效等优点,较既往L-5-HTP全身注射造模更接近临床实际,从而成功获得在发作行为、神经电生理及药效学特性均与临床更趋一致的脑干起源肌阵挛模型.     

Outpatient EEG monitoring in the presurgical evaluation of patients with refractory temporal lobe epilepsy.

Most epilepsy centers obtain ictal EEG recordings to localize the epileptogenic zone during presurgical evaluations. Inpatient monitoring is standard practice but is expensive and can be inconvenient. The authors sought to determine whether outpatient monitoring can be safe and effective as the sole method of recording seizures in the presurgical evaluation of patients with refractory temporal lobe epilepsy. They reviewed the data of seven temporal lobectomy patients whose presurgical monitoring was performed entirely outside the hospital. Mean baseline seizure frequency was at least 9.1 seizures per week. An average of 7.4 seizures was recorded over 9.4 days of monitoring. Only one patient had any antiepileptic drug taper; none suffered any complications. After temporal lobectomy on the side of demonstrated ictal onset, postoperative follow-up averaged 5.5 years. At the most recent follow-up, all patients were either seizure free or had only rare disabling or nocturnal seizures (four patients had outcomes in Engel's class I and three patients in Engel's class II). A comparison group who underwent standard inpatient monitoring was similar in average seizure frequency, monitoring duration, number of seizures recorded, and postoperative outcome, although all but one had antiepileptic drugs tapered during monitoring. The authors conclude that there is a subset of patients for whom solely outpatient presurgical EEG monitoring can be used to help plan successful temporal lobectomy.     

Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP

Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesian statistics, we compared seizure control in pregnancies where VPA was withdrawn (withdrawal group, n = 93), switched to another AED (switch group, n = 38), or maintained (maintained‐therapy group, n = 1,588) during the first trimester. The probability of primarily or secondarily generalized tonic–clonic seizures (GTCS) was lower in the maintained‐therapy group compared with the other two groups, both in the first trimester and for the entire duration of pregnancy. GTCS were twice as common during pregnancy in the withdrawal (33%) and switch groups (29%) compared with the maintained‐treatment group (16%). Limitations in the data and study design do not allow to establish a cause–effect relationship between treatment changes and seizure outcome, but these observations provide a signal that withdrawal of, or switch from, VPA during the first trimester could lead to loss of seizure control, and highlight the need for a specifically designed prospective observational study.     

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.     

Clinical and electroencephalographic features of simple partial seizures

The clinical and electroencephalographic features of 87 simple partial seizures in 14 patients were studied with video-EEG telemetry. The patients were able to respond to verbal stimuli during all seizures and, later, could clearly recall ictal events. To determine whether the EEG changes in simple partial seizures could be reliably observed, a reader blindly reviewed four EEGs of equal duration for each seizure. These EEGs consisted of one ictal and three nonictal recordings obtained at predetermined times before the seizure. There were 27 motor seizures (mean duration, 86 seconds; range, 2 to 250 seconds), all involving clonic movements of the head and/or upper extremities; 8 (30%) of these had a sensory component (pain in 6, paresthesia in 2). An EEG change, usually localized spikes or sharp waves over the contralateral or both rolandic regions, was identifiable in nine (33%) of the motor seizures. The 60 nonmotor seizures (mean duration, 63 seconds; range, 8 to 375 seconds) involved a variety of symptoms, including somatosensory/special sensory (3 seizures), autonomic (26 seizures), cognitive (1 seizure), affective (14 seizures), and mixed, or more than one category of nonmotor symptoms (16 seizures). In only nine (15%) of the nonmotor seizures was there an ictal EEG change, usually localized spikes or paroxysmal theta activity over the temporal region. Overall, among the 87 simple partial seizures, only 18 (21%) revealed ictal EEG changes. Thus, a normal EEG is common during simple partial seizures and does not exclude the diagnosis.     

Therapeutic intensive seizure analysis (TISA) in presurgical evaluation of Losigamone

OBJECTIVE: The new method TISA was used to evaluate Losigamone efficacy. METHODS: Sixteen patients with pharmacoresistant partial seizures undergoing presurgical evaluation were randomized in this double-blind, placebo-controlled, parallel-group Losigamone monotherapy study under continuous video-EEG monitoring. Duration (in s, of each seizure and each ictal sign), intensity (grade zero to three), N/24h (number of seizures and ictal signs per 24 h), D/24h (seconds per 24 h covered by seizures and ictal signs) and seizure free intervals were recorded. RESULTS: A total of 246 seizures were intensively analyzed. The duration and intensity of all seizures improved more in the active treatment group than in the placebo group. There was a statistically significant superiority in the duration of the seizure free interval in the Losigamone group. Ictal signs such as oro-alimentary automatisms and fumbling were improved during Losigamone treatment. CONCLUSION: Losigamone has a preferred inhibitory effect on propagated epileptic activity. TISA is a sensitive method for evaluation of the selective effects of AEDs.     

Suppression of Interictal Spikes and Seizures by Stimulation of the Vagus Nerve

The effects of electrical stimulation of the vagus nerve, a proposed treatment for patients with intractable epilepsy, on focal interictal spikes produced by penicillin and EEG secondarily generalized seizures induced by pentylenetetrazol were assessed in rats. Interictal spike frequency was reduced by 33% during 20 s of stimulation (p < 0.001) and remained low for ≤3 min. Amplitude of residual spikes was also decreased. Cardiac and respiratory rates were suppressed. Cooling the nerve proximal to the point of stimulation abolished the EEG and respiratory effects. A similar reduction in spike frequency of 39% was obtained by heating the animals' tail (p < 0.01). Vagal stimulation at onset of seizures reduced mean seizure duration from 30.2 ± 15.7 s without stimulation to 5.0 ± 1.8 s (p < 0.01). Only the EEG equivalent of the clonic phase of the seizure was affected. These findings suggest that vagus nerve stimulation can be a potent but nonspecific method to reduce cortical epileptiform activity, probably through an indirect effect mediated by the reticular activating system.     

Duration of epileptic seizure types: A data-driven approach

Objective

To determine the duration of epileptic seizure types in patients who did not undergo withdrawal of antiseizure medication.

Methods

From a large, structured database of 11 919 consecutive, routine video-electroencephalograpy (EEG) recordings, labeled using the SCORE (Standardized Computer-Based Organized Reporting of EEG) system, we extracted and analyzed 2742 seizures. For each seizure type we determined median duration and range after removal of outliers (2.5–97.5 percentile). We used surface electromyography (EMG) for accurate measurement of short motor seizures.

Results

Myoclonic seizures last <150 ms, epileptic spasms 0.4–2 s, tonic seizures 1.5–36 s, atonic seizures 0.1–12,5 s, when measured using surface EMG. Generalized clonic seizures last 1–24 s. Typical absence seizures are rarely longer than 30 s (2.75–26.5 s) and atypical absences last 2–100 s. In our patients, the duration of focal aware (median: 27 s; 1.25–166 s) and impaired awareness seizures (median: 42.5 s; 9.5–271 s) was shorter than reported previously in patients undergoing withdrawal of antiseizure medication. All focal seizures terminated within 10 min. Median duration of generalized tonic–clonic seizures was 79.5 s (57–102 s) and of focal-to-bilateral tonic–clonic seizures was 103.5 (77.5–237 s). All tonic–clonic seizures terminated within 5 min.

Significance

This comprehensive list of seizure durations provides important information for characterizing seizures and diagnosing patients with epilepsy. The upper limits of seizure durations are helpful in early recognition of imminent status epilepticus.     

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.     

Induction of partial epileptic seizures by flumazenil

PURPOSE: This study addressed the efficacy of flumazenil (FMZ) to induce or activate interictal or ictal epileptic discharges in patients with medically intractable partial epilepsies. METHODS: Flumazenil, 1 mg, was injected intravenously in 67 patients undergoing presurgical monitoring for epilepsy surgery, 49 of whom had been treated with benzodiazepines (BZDs) before flumazenil was given. Continuous video electroencephalogram (EEG) monitoring with surface or intracranial electrodes was used to evaluate interictal EEG activity, ictal discharges, and the occurrence and semiology of clinically manifest epileptic seizures. RESULTS: Interictal epileptiform potentials did not change in frequency or distribution after FMZ. In patients not pretreated with BZDs, epileptic seizures could not be provoked. In eight of the 49 patients pretreated with BZDs, epileptic seizures occurred within 30 min of FMZ application. Seizure semiology and regional EEG onset were identical to seizures recorded without FMZ. Patients operated on according to seizure-onset localization with FMZ had a >75% reduction in seizure frequency or became seizure free. CONCLUSIONS: Seizure induction by FMZ seems to be a valid method for evaluating seizure semiology and localization of the seizure-onset zone during presurgical monitoring of patients with medically intractable localization-related epilepsies.     

Pharmacology of Cortical Epileptic Afterdischarges in Rats

Summary: Afterdischarges (ADS) elicited by electrical stimulation of the sensorimotor cortical area are characterized by rhythmic spikes and spike-wave complexes in the EEG and by clonic face and forelimb seizures. We studied the sensitivity of such ADS to phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), primidone (PRM), and valproate (VPA) in 78 adult male Wistar rats with implanted electrodes. Neither PHT (30 and 60 mg/kg intraperitoneally, i.p.) nor CBZ (25 and 50 mg/kg i.p.) suppressed cortical ADS. Indeed, ADS were prolonged by higher doses of both drugs. PRM had a similar effect: A dose of 40 mg/kg transiently shortened ADS, but a dose of 80 mg/kg prolonged ADS. PB (20 and 40 mg/kg) and VPA (200 and 400 mg/kg) were effective in suppressing ADS. Higher doses of VPA and PB reduced the intensity of motor phenomena related to the stimuli but had no effect on the motor correlates of ADS. These findings suggest that cortically induced ADS are not a good model of secondarily generalized seizures. The response to VPA and PB suggests that cortical ADS may represent a model of myoclonic seizures.     

Characteristic phasic evolution of convulsive seizure in PCDH19‐related epilepsy

PCDH19‐related epilepsy is a genetic disorder that was first described in 1971, then referred to as “epilepsy and mental retardation limited to females”. PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video‐EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19‐related epilepsy. To do this, ictal video‐EEG recordings of 26 convulsive seizures in three girls with PCDH19‐related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: “jerk”, “reactive”, “mild tonic”, “fluttering”, “mild clonic”, and “postictal”. Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic‐clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19‐related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19‐related epilepsy when occurring in clusters with or without high fever in girls. [Published with video sequences online]     

Outcome of electroclinical, electrographic, and clinical seizures in the newborn infant

Three seizure types have been described in the neonate: electroclinical, electrographic, and clinical only. Controversy still exists about whether the episodic abnormal movements seen in some infants, which are not accompanied by simultaneous ictal discharges on the EEG, are true seizures. Twenty-four infants with seizures were studied, 17 had purely electrographic and/or electroclinical seizures, seven had clinical-only seizures; six of these seven had clonic seizures, without facial manifestations or autonomic change. The three seizure types were investigated using video-EEG and a Griffiths neurodevelopmental assessment was performed in each seizure group. Of the seven infants with clinical-only seizures, six had clonic seizures with a normal background EEG, neuroimaging studies and neurodevelopmental follow-up assessment were normal in five. In the remaining 17 infants with electrographic and/or electroclinical seizures, seizure discharges were often associated with ocular phenomena, apnoea, or tonic posturing, and the background EEG was abnormal in all but one subject. Neurodevelopmental follow-up assessments revealed a poor outcome (14 of 17) in this group. In otherwise healthy infants, purely clonic seizures involving only the limbs may be a benign phenomenon and an EEG should be obtained to avoid unnecessary treatment. Infants with seizures superimposed on an abnormal background EEG pattern had a poor outcome.     

From Clinical Observation to Long-Term Monitoring: Diagnostic Developments in Conservative Epileptology

Summary: The diagnostic goals in nonsurgical (conservative) epileptology differ from presurgical diagnostic aims. The resulting development of diagnostic methods in a tertiary-level epilepsy center is shown and the major technical and organizational consequences of this difference for diagnostic long-term monitoring (LTM) as opposed to presurgical LTM are investigated. A total of 133 consecutive daytime LTM investigations using radio telemetry were reviewed and seizure parameters such as type, duration, method of seizure detection, and need of mobility were evaluated and compared to presurgical LTM. Compared to presurgical LTM, partial seizures were relatively rare (17·8%) and short epileptic or nonepileptic motor events lasting <1 s, such as myoclonic, atonic, short tonic seizures, spasms, ties, or startle reactions, are frequent (34·9%). Of all seizures, 23% had no or minor ictal EEG changes, subtle symptomatology without signaling by a patient or accompanying person, and could be detected only by continuous online surveillance by an experienced EEG technician. Due to the nature of the patient population in diagnostic LTM, there is an increased need for ictal and interictal mobility (radio telemetry). LTM in conservative epileptology requires more intense human surveillance for seizure detection and increased patient mobility compared to presurgical LTM.