Secondary Generalization Seizures Research Articles

High-resolution intraoperative infrared thermography for the functional imaging and tumor resection maximization of a low-grade glioma: Technical case report

Currently, it is widely recognized the role of the extent of resection on overall and progression-free survival for gliomas surgery. Brain mapping and intraoperative image guidance are generally required to attain such an objective. Infrared Thermography (IRT) has a potential role in the identification of surgical margins, but it has not been consistently assessed in the literature. We aim to demonstrate the use of intraoperative IRT to detect superficial and deep tumoral margins of low-grade glioma, to identify adjacent functional motor cortex, and to maximize surgical resection in a 45-year-old lady with a long history of partial and secondary generalization seizures.

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response.

Background and PurposePerampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel.MethodsEfficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed.ResultsMost patients (82/85) received perampanel doses of 4–8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%).ConclusionsPost hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

Medico-legal study of post-traumatic seizures and epilepsy in patients with traumatic brain injury in El Demerdash and Ain Shams Specialized Hospitals (2017 -2018)

Background: Traumatic brain injury (TBI) is one of the most leading causes of deaths and disability among youth worldwide. Post-traumatic seizures (PTS) and post-traumatic epilepsy (PTE) are important catastrophic complications of TBI. Epilepsy has important medico-legal aspects for both the patient and the physician. Aim of the study: to identify forms of post traumatic seizures (generalized, focal, or focal followed by secondary generalized), site of epileptic focus, nature of brain injury that caused their occurrence, risk factors for epilepsy occurrence and medico-legal importance of PTS. Methods: A prospective cross-sectional study was conducted including patients with PTS and PTE who presented to El Demerdash and Ain shams Specialized Hospitals during the study period. Data were collected from patients by a questionnaire and from clinical sheets. Patients were classified into three groups according to time of occurrence of PTS. Results: A total of 77 patients were included. Cases were mostly in the age group less than 45 years old. Male patients were more represented in the study (64.9%). Transportation injuries were the most prominent pattern of TBI followed by blunt trauma (29.9%), open head injuries (13%), fall from height (13%) and polytrauma (1.3%). The most common affected site was frontal area of the brain (51.9%) followed by temporal region (45.5%). Associated complications included intra-cranial hemorrhage (87%) and skull fracture (35.1%). Immediate seizures were recorded in 9.1 % of the studied patients compared to 26% with early PTS. Patients with late PTS were the majority accounting for 64.9% of study patients of whom 50% with late PTS from the start. Most cases experienced generalized seizures attacks (59.7%) followed by focal with secondary generalization seizures attacks in (27.3%) and the least were with focal seizures attacks (13.0%). EEG showed abnormal activity in (62.3%) of patients and normal activity in (37.7%). Conclusion: Post-traumatic seizures and epilepsy are an important well-known sequel of traumatic brain injury with important medico-legal aspects. Pattern of head injury and site of traumatic area are important risk factors in occurrence of PTS and EEG abnormal activity is an important predictor for occurrence of PTS as well.

Feline Epilepsy: An Update

Seizures are the most common neurological disorder in the clinical setting. Its etiology is multifactorial and is mainly divided into primary and secondary epilepsy. Secondary epilepsy can be caused by vascular events, inflammatory conditions (encephalitis), toxins, traumatic injuries, metabolic derangements, neoplasia, congenital and inherited (degenerative) disorders. Although primary (idiopathic) epilepsy was thought to be rare in cats, it is now established as a common cause. Seizures in cats appear with various clinical presentations including the typical generalized tonic-clonic, focal with or without secondary generalization seizures, or solely as behavioral changes. Type of seizures is not indicative of their etiology. Diagnostic investigation is crucial in order to establish final diagnosis and to determine the therapeutic plan. Diagnostics include physical and neurological examination with detailed history (drug or toxin exposure), routine hematology (CBC, biochemistry, urinalysis), specific laboratory tests if concurrent or metabolic disease are suspected, advanced diagnostic imaging (CT/MRI) whether intracranial disease is suspected and cerebrospinal fluid (CSF) analysis. Most commonly used antiepileptic drugs (AED) in cats are phenobarbital and levetiracetam. Bromide is contraindicated in cats due to severe respiratory disease caused as an adverse life-threatening reaction. Diazepam is an emergency AED used to eliminate cluster seizures or status epilepticus but it should be avoided as a long-term medication because it has been associated with fatal hepatotoxicity. Gabapentin in another potential antiepileptic drug however its long-term efficacy has to be evaluated. Prognosis depends on the underlying etiology and treatment response. In most cats quality of life is improved and (>50% reduction of seizures) regardless of etiology. The complete remission of seizures in cats is rare and most cats should be maintained on anti-epileptic therapy.

Characteristics of symptomatic epilepsy with schizencephaly

Objective: Study and compare the clinical and electrophysiological and neuroimaging findings in children with symptomatic epilepsy with schizencephaly. Methods: The study included 11 patients with schizencephaly. There are five boys (45.45%) and six girls (54.55%). Results: Compliance with focal changes in the EEG (electroencephalography) and localization revealed morphological changes in the group of children with schizencephaly is 80%. The clinical picture of epilepsy dominated by focal seizures in eight patients (72,72%), epileptic spasms – two patients (18,18%), focal with secondary generalization seizures – two (18,18%), atonic – one (9,09%). Simple focal seizures were observed in two boys (18.18%) and two girls (18.18%). Complex focal seizures recorded a boy (9.09%) and three girls (27.27%), focal seizures with secondary generalization – a boy (9.09%) and one girl (9.09%), epileptic spasms – a boy (9.09%) and one girl (9.09%). Seizures are not registered with one girl (9.09%). In the group of children with schizencephaly have four boys and four girls diagnosed with focal epilepsy (72.73%), one boy and one girl – focal epilepsy with secondary generalization (18.18%), one boy and one girl – multifocal (18 ,18%). Epileptic Encephalopathy – one girl (9.09%). Epilepsy is not diagnosed in one girl (9.09%). Eleven patients (100%) identified a variety of changes in neurological status. Severe motor impairment with the formation of palsy, a violation of the innervation of the bulbar group cranial nerves – in six patients (54.55%). Muscular hypotonia – two patients (18.18%). Eleven children of this group noted intellectual-mental disorders in varying degrees of severity (100%). In the treatment of epilepsy in nine patients (81.81%) with schizencephaly used valproate. Topiramate was used in two patients (18.18%) carboxamide derivatives, phenobarbital, hormones were used at least in one case (9,09%). Conclusion: Malformations of the brain are one of the frequent causes of epilepsy in children.

Poor versus rich children with epilepsy have the same clinical course and remission rates but a less favorable social outcome: A population-based study with 25years of follow-up.

To explore the influence of several estimates of family socioeconomic status on the long-term clinical course and social outcomes of children with epilepsy. The Nova Scotia childhood epilepsy cohort is population based and includes all children in this Canadian province who developed epilepsy between 1977 and 1985. Eligible patients had ≥10years of follow-up. Children with childhood absence epilepsy were excluded. Total family income at seizure onset was assessed at seizure onset and classified as "poor" (first quintile), "adequate" (second to third quintiles), and "well-off" (fourth to fifth quintiles). We also assessed parental education and home ownership. Social outcome was assessed in those with normal intelligence who were ≥18years of age at the end of follow-up using a semistructured interview that explored eight adverse effects. Of 584 patients, 421 (72%) were included. Average follow-up was 26±5.6years. Overall 137 families (33%) had "poor" income, 159 (38%) had "adequate income," and 125 (30%) were "well-off." Terminal remission of epilepsy occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off (p=ns). Intractable epilepsy, status epilepticus, number of antiepileptic drugs (AEDs) used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Home ownership did not predict remission. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes including failure to graduate from high school, unemployment, personal poverty, inadvertent pregnancy, and psychiatric diagnoses. In Nova Scotia with universal health care, coming from a poor or more affluent family does not seem to affect the clinical course or long-term seizure outcome of childhood epilepsy. Unfortunately children from poor families are less likely to have a good social outcome.

FOCAL EPILEPTIC MYOCLONUS IN KOZHEVNIKOV–RASMUSSEN SYNDROME

The article presents the clinical, electroencephalographic (EEG) and neuroimaging features, as well as the results of treatment of patients with focal epileptic myoclonus (FEM) with the Kozhevnikov–Rasmussen syndrome (KRS). FEM in KRS-patients was identified in 11 cases, accounting for 0.9 % of all the cases of epilepsy with the onset of seizures up to 18 years (n = 1261). The age at onset of KRS ranged from 3 to 21 years (average – 9.2 ± 5.7 years). In the active period of the disease of all patients in the clinical picture the active FEM appeared and increasing frequency of the secondary generalized seizures (SGS). In addition SGS and FEM, the clinical picture of the disease in most patients (91 %) the focal motor (clonic) and the somatosensory focal seizures were observed. As the disease progressed, the FEM became more pronounced in frequency and intensity, seized more muscle groups, localizing mainly in the muscles of the trunk and limbs. The typical EEG pattern of FEM patients with KRS was regional epileptiform activity that occurs in the structure of the continued regional slowing localizing maximum of the fronto-central-temporal region. During the magnetic resonance tomography of the brain in dynamics all the patients observed the increase in total cortical hemiatrophy. In all the cases, the appointment of antiepileptic therapy resulted in a slowing of the FEM, however, a complete remission was reached at none of the patients. Two patients were made surgical treatment of epilepsy. In one case remission of epileptic seizures was observed after right-side hemispherotomy. Our study showed that FEM is very resistant type of epileptic seizures. This fact calls for the identification of the FEM at the early stages of the disease with the purpose to improve the prognosis, as well as for an earlier surgical treatment.

The efficacy of intravenous lacosamide in psychiatric hospital

To evaluate the efficacy and tolerability of intravenous lacosamide (vimpat) in inpatients with frequent partial-onset seizures and affective and cognitive disorders. Fifteen patients were enrolled including 14 patients diagnosed with «organic personality disorder associated with epilepsy» (cryptogenic or symptomatic epilepsy with frequent partial-onset and/or secondary-generalized seizures (serial seizures in some cases) and 1 patient with a preliminary diagnosis of «organic schizophrenia-like disorder», which was changed for «organic personality disorder associated with epilepsy» after examination. Patients were treated with 2--3 antiepileptic drugs (AEDs), but no one of them received earlier lacosamide. Lacosamide was used intravenously in drops in the dose of 200 or 400 mg daily during 5 days. In 4 patients with marked personality disorders, the frequency of seizures decreased by 75%, no seizures were noted after 2--3 days of treatment in 11 patients. A positive effect of lacosamide on the affective sphere and quality-of-life was observed in 11 (73.4%) patients with epilepsy. Mild and moderate adverse effects were found only in 2 patients. It has been concluded that lacosamide demonstrates the high efficacy in patients with frequent drug-resistant seizures.

P203 – 2949: Seizures persistence's prognosis in children with arterial ischemic stroke

Objective To investigate clinical and electroencephalographic features of seizures during acute and recovery periods of arterial ischemic stroke (AIS) in children. Methods Type of study: case series. Inclusion criteria Children 0–15 y.o. with seizures during AIS's debut. We identified the type of episodes and EEG features in acute and recovery periods after one year. Results 152 children with AIS were examined. Seizures occurred during the acute period of stroke in 39 (25.7%) cases and antiepileptic therapy was prescribed for all of them. Generalized seizures type was registered in 56.4% (n=22), focal type in 23% (n=9), focal type with secondary generalization – in 20.6% (n=8) children. Epileptiform activity was registered in 31% (n=9) patients. Disorganized changes on background EEG without signs of paroxysmal activity were predominant in most children – 75.9% (n=22) as well as background activity was normal only in 13.8% (n=4) of them. In the recovery period seizures persisted in 10.5% (n=16). Generalized seizures of acute period pass to recovery period in 27.2% (n=6, RR=0.56 95%CI 0.3–1.0), and focal seizures with secondary generalization – in 75% (n=6, RR=2.75 95%CI 1.2–6.0). Seizures accompanied by epileptiform activity on EEG during acute period persisted in the recovery period in 55.6% (n=5, RR=2.7 95%CI 1.1–6.1), without activity – in 30% (n=9, RR=0.5 95%CI 0.2–1.1). At the same time generalized seizures of acute period combined with epileptiform activity on EEG persist in recovery period in 50% (n=2, RR=2.2 95%CI 0.6–8.3), without it – in 22.2% (n=4, RR=0.6 95%CI 0.2–1.7). Conclusion The presence of epileptiform activity on EEG and the development of focal with secondary generalization seizures type in children with AIS and seizures in the acute period increase the risk of seizure persistence in the recovery period in spite of antiepileptic therapy have been prescribed.

The adult seizure and social outcomes of children with partial complex seizures

Most intellectually normal children with focal epilepsy have partial complex or focal with secondary generalization seizures without a precise epilepsy syndrome. Their long-term outcome is largely unknown. Cases were identified from the population-based Nova Scotia Childhood Epilepsy cohort. Those eligible had seizure onset at 1 month to 16 years between 1977 and 1985, normal intelligence, ≥10 years of follow-up, only focal seizures and no benign epilepsy syndromes. There were 108 patients with partial complex with or without secondary generalization as the only seizure type(s) throughout (partial complex group) and 80 with secondary generalization as the only seizure type (secondary generalization group). Average age ± standard deviation at onset was 7.3 ± 4.5 years and follow-up was 27.9 ± 5.4 years. At follow-up, 57% of the partial complex group were in remission versus 81% of the secondary generalization group (P = 0.001). The partial complex group was more likely to be intractable or have undergone epilepsy surgery (36% versus 5%, P = 0.000). In the partial complex group, 28% had <5 years seizure free versus 5% in the secondary generalized group (P = 0.000). More patients in the partial complex group had undergone mental health assessments (59% versus 32%, P = 0.000), and 33% had a psychiatric diagnosis versus 15% in the secondary generalized group (P = 0.004). More patients with partial complex seizures had specific learning disorders (63% versus 45%, P = 0.03). Seven markers of poor social outcome were more common in patients with partial complex seizures (>2 markers: 34% versus 10%, P = 0.000). During 25-30 years of follow-up, >50% of intellectually normal patients with childhood-onset partial complex seizures had difficult-to-control seizures and learning and psychiatric/social problems. Most with secondary generalized seizures only had remission and better academic and psychiatric/social outcomes.

Increased metallothionein I/II expression in patients with temporal lobe epilepsy.

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.

Different levels of MT-I/II between patients with MTLE with or without seizure generalization: does hippocampal MT-I/II affects seizure spread, or does seizure spread promotes differential expression of MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns.

Rash in four patients with brain tumor-related epilepsy in monotherapy with oxcarbazepine, during radiotherapy

Antiepileptic drug (AED)-related rash is well documented with older AEDs such as carbamazepine, phenobarbital, and phenytoin, and recent studies have implicated newer AEDs such as lamotrigine, oxcarbazepine (OXC), and zonisamide [1–4]. In patients with brain tumor-related epilepsy (BTRE) treated with old AEDs, the appearance of rash may be severe during radiotherapy (RT). The frequency is approximately 20% of cases where traditional AEDs such as carbamazepine, phenobarbital, and phenytoin are used [4]. The appearance of rash during RT among the new AEDs has not yet been described in the literature. Skin rash is an idiosyncratic adverse drug reaction that can vary from mild maculopapular to life-threatening hypersensitivity [2]. According to the FDA, the incidence of OXC-related serious dermatological reactions including Stevens–Johnson syndrome and toxic epidermal necrolysis is estimated to range between 0.5 and 6/10 early in the non-oncological epileptic population [5]. Although rare, this potential life-threatening adverse reaction should be recognized and treated promptly. The toxicity is unpredictable for the most part. The pathogenesis appears to be multi-factorial and has been explained by drug hyper sensitivity, which implies both metabolic and immunological mechanisms [2]. Literature data show that AEDs containing aromatic rings, phenytoin, and carbamazepine, are associated with a higher incidence of adverse cutaneous skin reactions [2, 3]. A lower incidence was found with levetiracetam, gabapentin, valproic acid, primidone, felbamate, topiramate, and vigabatrin. Clobazam, OXC, phenobarbital, tiagabine, and zonisamide produced intermediate reactions [3]. In the literature, descriptions of OXC-induced Stevens–Johnson syndrome are rare [3]. OXC has recently been demonstrated efficacious in reducing seizure frequency in BTRE with scarce appearance of side-effects both mild and severe [6]. Here, we present four patients with BTRE treated with OXC monotherapy, who, during brain radiation therapy, presented a major skin reaction that disappeared after OXC suspension. The study included three males and one female, with a mean age of 54.8 years, affected by epilepsy secondary to cerebral high-grade glioma, with simple partial seizures (n = 3) and simple partial with secondary generalization seizures (n = 1). We introduced OXC monotherapy (mean dose = 1,050 mg/day) with a good effect on seizure control during the treatment period (monthly mean seizure frequency at baseline = 18; monthly mean seizure frequency before OXC withdrawal = 3; responder rate [50%) (see Table 1). For the treatment of oncological disease, patients underwent brain RT (total dose 60 Gy), in association with concomitant temozolomide treatment dose of 75 mg/m per day in three patients (Stupp protocol) [7]. All patients were on steroids. After the start of RT (min 2 days, max 14 days), all patients presented a major skin reaction characterized by macules, papules, and boils at departure from the scalp, which spread to the face, shoulders, and M. Maschio (&) L. Dinapoli Department of Neuroscience and Cervical-Facial Pathology, Center for Tumor-related Epilepsy, National Institute for Cancer ‘‘Regina Elena’’, Via Elio Chianesi 53, 00144 Rome, Italy e-mail: maschio@ifo.it

Secondary generalization in seizures of temporal lobe origin: Ictal EEG pattern in a stereo-EEG study

Objective We tested the hypothesis that secondary generalized seizures (SGS) are not truly generalized and may involve selective regions. Methods The spread from focal to generalized seizures in temporal lobe epilepsy (TLE) was studied in 20 SGS recorded via stereo-EEG (SEEG) in 15 candidates for surgery. Electrodes were assigned to fronto-orbital, prefrontal, and temporal cortex, cingulate, hippocampus, and amygdala. The onset of SGS was ascertained by behavioral analysis of the video recordings. EEG recordings were evaluated using the rating scale developed by Blumenfeld [Blumenfeld H, Rivera M, McNally KA, Davis K, Spencer DD, Spencer SS. Ictal neocortical slowing in temporal lobe epilepsy. Neurology 2004;63:1015–21]. The seizure rating in each region was compared with the rating in the hippocampus. Results Ranking significantly differed in the cingulate and fronto-orbital cortex; there was a trend toward significance in the prefrontal cortex. In these regions, slow activity dominated. Conclusion The onset of secondary generalization, when the head, face and all limbs are involved, does not implicate global cortical involvement.

The Value of Postictal Electroencephalogram in Temporal Lobe Seizures

Background: The ictal changes on scalp electroencephalogram (EEG) helps in lateralizing and localizing the seizure origin, however, the value of postictal EEG has received limited study. Objectives: To examine the value of postictal EEG in simple partial (SP), complex partial (CP), and secondary generalized (SG) temporal lobe seizures. Methods: Patients with detailed Video EEG monitoring who were seizure free for a minimum of 2 years following a temporal lobectomy were identified. Up to 3 seizures per patient were classified as SP, CP, or SG based on the patient description and video-tape review. The ictal EEGs were masked and the postictal EEG segments were randomly reviewed by one electroencephalographer (EEGer), who was blind to all clinical and EEG data. He assigned each segment to unilateral, bilateral, or no postictal delta activity (PDA). Results: 53 seizures and accompanying EEGs from 20 patients were studied. The age at temporal lobectomy ranged between 19-45 years (mean 29.5). Pathology revealed mesial temporal sclerosis in 16 (80%). PDA was identified in 55%, 85%, and 100% of postictal EEG segments of SP, CP, and SG seizures respectively. Unilateral PDA was identified in 36%, 76%, and 44% of postictal EEG segments of SP, CP, and SG seizures respectively. Unilateral PDA was ipsilateral to the side of surgery in 94% of EEGs. Conclusion: The postictal EEG may be helpful in the identification and lateralization of all types of seizures originating from the temporal lobe.