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Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Epileptic seizure semiology adds important information to the formulation of the hypothesis of the epileptogenic zone. Seizure semiology in infants and children are simple and elementary, becoming more complex with maturation of brain. Also in this age group, seizure semiology may be generalized in a setting of a focal lesion or may show focal signs with misleading localization values. We review seizure semiology of patients aged one month to ten years with respect to lateralization and localization of the epileptogenic zone.

Dr Fisher and colleagues have recently provided a commentary on our critique of the 2017 International League Against Epilepsy (ILAE) classification of epileptic seizures and epilepsies. The commentary was disappointing in that it did not depart from their original views and suggests a lack of engagement to consider an alternative framework that might improve the ILAE classifications of epileptic seizures and the epilepsies. Epileptologists actively dealing with people with epilepsy must provide feedback and express their views on any official ILAE position, as the latter would only be valid if it succeeds in striking a balance between the perspectives of any ILAE commission and that of the practitioners. It is evident that thoughtful critiques of ILAE position papers can only be forwarded once a text is published and their directions put into use, which is what we did in our critique, in an effort to achieve the best synthesis of accumulated knowledge that could result in a practical, useful, and forward-looking classification of epileptic seizures and the epilepsies.

For the treatment of mesial temporal lobe epilepsy on the language-dominant side in patients at high risk of memory decline, we propose a minimally invasive diagnostic and treatment technique, adopting the principles of multiple hippocampal transections (MHT) using stereo-electroencephalography-guided radiofrequency (SEEG-guided-RF-MHT). This new technique allows targeting of the longitudinal fibers in the hippocampus critical for seizure spreading, while sparing the transverse circuits which are considered important for memory processing and avoiding discomfort and longer post-operatory recovery time associated with craniotomies. We report the efficacy and safety of this procedure in a preliminary observational study of cases. Five patients at high risk of memory decline, including three with non-lesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. A new strategy of SEEG electrode placement was used to mimic MHT. After confirming hippocampal seizure onset, all the patients had three linear ablations perpendicular to the amigdalohippocampal complex. The procedure was performed at the patient's bedside with the patient awake during the full length of the procedure. Four out of five patients were seizure-free (average follow up: 14-18 months). There were no associated complications. Visual inspection of brain MRI of patients at six months following SEEG-guided RF-MHT showed significant hippocampal volume preservation. Subjects who received the procedure in the dominant side reported no subjective memory complaints in the follow-up clinic assessments at six months. Our preliminary seizure outcome seems very promising since the majority of our patients (four out of five patients) were seizure-free. Since no lesions are made outside the amygdalo-hippocampal complex using this technique and the temporal stem remains intact, more favorable memory and language outcome is expected in patients at high risk of memory decline.

Prof. Hans Lüders organized the first International Electroencephalography (EEG)/Epilepsy course in Cleveland (Ohio, United States) in 1979. His vision was to impart a framework of basic knowledge in EEG and epilepsy. The course participants are assumed to have no prior knowledge of EEG or epilepsy. As such, the course is structured and paced to meet the expectations set forth by the organizing committee at the completion of the course. The curriculum has evolved over the years to reflect advancement of the field. There is an added emphasis on semiology (seizure semiology) and epileptic disorders. Also, the course content has expanded to include broader topics such as the intersection between epilepsy and sleep medicine for both adults and children. The course lasts 8 weeks and is offered twice a year, free of charge, in winter and summer at the University Hospital in Cleveland, Ohio, United States. The average class size ranges from 25 to 30, composed of individuals from around the world. The class hours are generally from 8 a.m. to 3:30 p.m. Daily attendance is expected as new concepts quickly build on previous ones. Midterm and final examinations are used for evaluations. Both written and verbal feedbacks on homework assignments are given daily. At the end of the course, a certificate of completion is awarded. The purpose of this article is to discuss the structural details of this intensive educational course that has been offered for 40 years.

A collaborative research team lead by an investigator from the Lyon Neuroscience Research Center and Lyon University Hospital and Lyon 1 University studied epileptogenicity of tuber and its surrounding cortex using stereoelectroencephalography (SEEG) in patients diagnosed with tuberous sclerosis complex (TSC) (genetic or clinical).

Pediatric cardiac arrest is a significant cause of death and neurologic disability; however, there is a paucity of literature specifically evaluating the utility of prognostic factors in the pediatric population. This retrospective chart review examines clinical, laboratory, and electroencephalographic (EEG) data in children following cardiopulmonary arrest to better characterize findings that may inform prognosis. Pre-arrest clinical characteristics, resuscitation details, and post-arrest hospital course variables were analyzed and neurologic outcome was determined using the Pediatric Cerebral Performance Category scale. Forty-one patients were identified who had cardiac arrest from March, 2011 to January, 2015. Duration of cardiopulmonary resuscitation (p = 0.013), out-of-hospital arrest (p = 0.005), arterial pH (0.014), arterial lactate (0.004), lack of pupil reactivity to light (p

Rationale: Posttraumatic epilepsy (PTE) is a common cause of morbidity in children after a traumatic brain injury (TBI), occurring in 10–20% of children following severe TBI. PTE is diagnosed after two or more unprovoked seizures occurring 1-week post TBI. More often, studies have focused on children with epilepsy due to severe TBI. We aim to understand the utility of head computed tomography (HCT), EEG, and the risk of developing drug-resistant epilepsy in children after mild TBI. Method: We retrospectively studied 321 children with TBI at a tertiary pediatric referral center during a 10-year period. Mild TBI was defined as loss of consciousness (LOC) or amnesia < 30 min, moderate TBI as LOC or amnesia between 30 min and 1 day, and severe TBI as LOC or amnesia > 1 day, subdural hemorrhage, or contusion. Multiple clinical variables were reviewed, including past and present antiepileptic drug(s), seizure control, and mode of injury. First and subsequent post-TBI EEGs/prolonged video-EEGs were obtained acutely, subacutely, and/or chronically (range, day 1–3 years, median 1 month). Descriptive analyses were conducted using medians and ranges for continuous data. Categorical data were reported using frequencies and percentages, while comparisons between groups were made using Fisher’s exact test for small sample sizes. Results: Forty-seven children were diagnosed with posttraumatic epilepsy: eight children (17%) due to mild TBI, 39 children (83%) due to severe TBI. For the eight children with mild TBI whom all had an accidental trauma (non-inflicted), the median follow-up time was 25 months (range 1.5 months–84 months). The median age was 10 years (range 4–18 years), and the median age at the time of injury was seven years (range: 23 months–13 years). No relevant previous medical history was present for six patients (80%), and two patients’ (20%) relevant previous medical histories were unknown. Seven patients (88%) had no history of seizures, and patient #6 (12%) had unknown seizure history. Six patients (75%) had normal routine EEG(s). Patient #6 (13%) had an abnormal VEEG 3 months after the initial normal routine EEG, while patient #1 (13%) had an initial prolonged EEG 8 months after TBI. Compared to the 39 patients with severe TBI, 31 (79%) of whom had abnormal EEGs (routine and/or prolonged with video), mild TBI patients were more likely to have normal EEGs, p = 0.005. Head CT scans were obtained acutely for seven patients (90%), all of which were normal. One patient only had brain magnetic resonance imaging (MRI) 8 months after the injury. Compared to the 39 patients with severe TBI, all of whom had abnormal HCTs, mild TBI patients were less likely to have abnormal HCTs, p < 0.0001. In patients with mild TBI, no patient had both abnormal EEG/VEEG and HCT, and no one was on more than one Antiepileptic drug (AED), p < 0.005. Six patients (75%) had MRIs, of which five (63%) were normal. Two patients (#1, 7) did not have MRIs, while one patient’s (#4) MRI was unavailable. Five patients (63%) had a seizure

To recognize epileptic spasms (ES) as a seizure type after traumatic brain injury (TBI), accidental or non-accidental, in infants and children. In the process, we aim to gain some insight into the mechanisms of epileptogenesis in ES. A retrospective electronic chart review was performed at the Children's Hospital of Michigan from 2002 to 2012. Electronic charts of 321 patients were reviewed for evidence of post-traumatic epilepsy. Various clinical variables were collected including age at TBI, mechanism of trauma, severity of brain injury, electroencephalography/neuroimaging data, and seizure semiology. Six (12.8%) of the 47 patients diagnosed with post-traumatic epilepsy (PTE) had ES. Epileptic spasms occurred between two months to two years after TBI. All patients with ES had multiple irritative zones, manifesting as multifocal epileptiform discharges, unilateral or bilateral. Cognitive delay and epileptic encephalopathy were seen in all six patients, five of whom were free of spasms after treatment with vigabatrin or adrenocorticotropic hormone. The risk of PTE is 47/321(14.6%) and the specific risk of ES after TBI is 6/321 (1.8%). The risk of ES appears to be high if the age at which severe TBI occurred was during infancy. Non-accidental head trauma is a risk factor of epileptic spasms. While posttraumatic epilepsy (not ES) may start 10 years after the head injury, ES starts within two years, according to our small cohort. The pathophysiology of ES is unknown, however, our data support a combination of previously proposed models in which the primary dysfunction is a focal or diffuse cortical abnormality, coupled with its abnormal interaction with the subcortical structures and brainstem at a critical maturation stage.

In clinical practice, the diagnosis of focal vs generalized epilepsy dictates the management of the patient. The distinction between generalized and focal epilepsy is at times imperfect and some epilepsies have features that fall in between these two extremes. An example is the occurrence of focal interictal and focal ictal abnormalities in generalized epilepsies. As a part of the special issue on "The epileptogenic zone in pediatric epilepsy surgery", this focused narrative review will discuss different focal abnormalities seen in generalized epilepsy. An overlap of focal and generalized epileptiform abnormalities may support a continuum between focal and generalized epilepsy. When evaluating patients in the "gray zone", other factors such as ictal semiology, neuroimaging, genetic testing and functional deficits may need to be considered to reach an accurate diagnosis. Being aware of possible occurrence of focal clinical and EEG features in generalized epilepsy will help clinicians select more preferred AED (s), avoiding potential iatrogenic side effects and inappropriate consideration for epilepsy surgery.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.

Schizencephaly associated with extensive malformation of cortical developments frequently cause medically intractable epilepsy in pediatric patients. Because of the extent of the structural abnormality, which is often bihemispheric and multifocal, epileptic surgery in these group of patients is typically not considered or indicated. We report a 10-year-old boy with medically intractable epilepsy and multifocal epileptiform discharges associated with bilateral malformation of cortical developments, schizencephaly, and agenesis of the corpus callosum, initially thought to be not a candidate for epilepsy surgery. All of the seizures localized to the right posterior head region. Seizure freedom was achieved after a right temporoparietooccipital (TPO) disconnection. He was followed postoperatively for 22 months at which time he remained on oxcarbazepine monotherapy. We emphasize that medically intractable epileptic patients with unilateral schizencephaly, bilateral colpocephaly, and multifocal epileptiform discharges must be evaluated with a video electroencephalography (VEEG) to characterize the seizures before ruling out epilepsy surgery as a therapeutic option. TPO disconnection surgery, instead of multilobar resections, can result in favorable seizure outcome in patients with localized seizure onset in the posterior head region.

Catastrophic epilepsy in infants, often due to extensive cortical dysplasia, has devastating consequences with respect to brain development. Conventional lobar, multilobar, or hemispheric resection in these infants is challenging, carrying an increased operative risk compared with that in older children. Removing a larger tissue volume versus removing or disconnecting the epileptogenic region does not always guarantee better seizure outcome. The authors describe 2 infants with catastrophic epilepsy who benefited from individually tailored disconnections based on a hypothesized epileptogenic zone following intensive presurgical evaluation. Two infants with catastrophic epilepsy and epileptic spasms underwent leukotomies between 3 and 12 months of age. They were followed up postoperatively for 19–36 months. Both patients had 90%–100% seizure reduction and a significantly improved neurodevelopmental outcome without postoperative complication. Cortical malformation was seen in both patients. Modifications of established surgical disconnection techniques, tailored to each patient's specific epileptogenic zone, optimized seizure and neurodevelopmental outcomes while minimizing the risks associated with more extensive resections.

Seizure semiology provides information about the eloquent cortex involved during a seizure and helps to generate a hypothesis regarding the localization of the epileptogenic zone (EZ), a prerequisite for surgical management of epilepsy. We aimed to study the seizure semiology among all different age groups to better characterize semiological changes that occur with age. We performed a retrospective review of video-EEG data in paediatric and adult patients admitted to the Epilepsy Monitoring Unit over a three-year period. Authors independently reviewed and classified the seizure semiology while blinded to clinical, EEG, and neuroimaging data. A total of 270 patients were included in the study. The most frequent EZ in patients who were one month to three years old was undetermined. Focal epilepsy became more frequent in patients older than 10 years. Among patients with focal epilepsy, a posterior quadrant EZ was most frequent in children younger than three years old, a temporal EZ between three and six years old, and a frontal EZ between six and 10 years old. The temporal lobe was the most frequent location for focal EZ in patients older than 18 years. Auras, automotor seizures, and generalized tonic-clonic seizures were extremely infrequent in patients younger than 10 years old. The youngest patient with auras was 5.7 years old. The youngest patient with automotor seizures was 3.7 years old. We identified only three patients with generalized tonic-clonic seizures who were younger than 10 years (aged six months, 6.6 years, and nine years, respectively). Patients younger than three years exhibited mostly generalized simple motor seizures and hypomotor seizures. Generalized epileptic spasms, generalized tonic seizures, and generalized clonic seizures were infrequent in patients older than 10 years. Seizure semiology and electroencephalographic changes most likely reflect the maturation of cortical functions.

Background Catastrophic epilepsy results in severe neurodevelopmental delay in infants because of frequent and/or long seizures. Therefore, consideration of early epilepsy surgery is essential for neurodevelopmental outcome. Once an infant with catastrophic seizures is identified as a surgical candidate, it is important that the surgical plan be carefully defined based on detailed presurgical evidence to minimize surgical complications in this age group. Case Description We present 2 infants with catastrophic epilepsy, epileptic spasms, and bihemispheric electroencephalographic abnormalities who underwent one-stage disconnection surgery based on a sound hypothesis of the epileptogenic zone. Each patient underwent an extensive noninvasive presurgical investigation followed by stereotactic disconnection leucotomy in a single stage. After the 2 children were followed for 24–36 months. A seizure reduction by at least 90% (Engel class I) was achieved in both cases with subsequent improvement in neurodevelopmental progress. There were no perioperative complications. Both patients had widespread cortical dysplasia on pathologic evaluation. Conclusions Careful consideration of the noninvasive presurgical workup can identify focal onset even in the presence of catastrophic epilepsy with widespread bilateral abnormalities. Single-stage lobar leucotomy for disconnection of the epileptogenic zone can lead to excellent outcome in these patients.

Resection of the hippocampus ipsilateral to the verbal memory–dominant hemisphere frequently results in severe memory deficits. In adults with epilepsy, multiple hippocampal transections (MHTs) have resulted in excellent seizure outcome with preservation of verbal memory. The authors report the first detailed case of a child undergoing MHTs for mesial temporal lobe epilepsy. A 13-year-old right-handed boy had intractable seizures characterized by epigastric discomfort evolving to unresponsiveness and chewing automatisms, lasting 1 minute and occurring 2–3 times weekly, sometimes ending in a generalized tonic-clonic seizure. He had no seizure risk factors and nonfocal examination results. Interictal electroencephalography (EEG) showed frequent left temporal epileptiform discharges (maximum FT9) and intermittent slowing. Video EEG, FDG-PET, and 1.5-T MRI were nonlocalizing. Neuropsychological evaluation suggested left temporal lobe dysfunction. A stereo-EEG investigation using 8 electrodes localized the seizure onset zone to the anterior mesial temporal region, immediately involving the hippocampus. The temporal pole and amygdala were resected en bloc with 3 MHTs. Comparison of neuropsychological tests 4 months before and 6 months after the surgery showed a significant decline only in confrontational naming and no significant change in verbal memory. Six and a half years later, the patient remains seizure free with no antiepileptic drugs. In children with established hemispheric dominance suffering from mesial temporal lobe epilepsy, MHTs may be an option.

The objective of this study was to determine the outcome of psychogenic nonepileptic seizures (PNES) in children seen at a level 4 epilepsy center.We retrospectively analyzed patients under the age of 18 years who were diagnosed with PNES based on evaluation in the epilepsy monitoring unit and had a follow-up of at least 2 years postdiagnosis. Remission of events was noted at 6 months, 12 months, and 24 months of follow-up, and patient and disease variables affecting outcome were studied.Ninety patients met inclusion criteria (58 females; mean age: 14.03 ± 3.3 years). Thirty-two out of ninety (36%) patients had early (within 6 months) and sustained remission (until 2 years of follow-up) of their events ("favorable outcome"), while 30/90 patients (33%) never achieved remission during the study period ("unfavorable outcome"). The factors that were associated with "unfavorable outcome" included the presence of comorbid epilepsy [12/30 (40%) vs 0/32, p0.0001] and prolonged duration of symptoms before establishment of the diagnosis (median 365 days vs 60 days, p0.0001). Patient's age, gender, frequency of events, the presence of major psychosocial stressors, and comorbid psychiatric conditions had no significant impact on the disease outcome.About a third of children with PNES achieve early and sustained remission of symptoms, while another third continue to manifest seizure-like events until at least two years after the diagnosis. The presence of comorbid epilepsy and prolonged duration of PNES are associated with a poor two-year outcome. Early suspicion and diagnosis of PNES, especially in patients with epilepsy, is essential.

Focal status epilepticus and catastrophic epilepsy are not rare in infants. Epilepsy surgery can be safely done in selected infants to cure epilepsy.We report on an infant who began having drug-resistant status epilepticus at 2 weeks of age and developed epileptic spasms. We discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives.Presurgical evaluation consisted of 32-channel scalp video EEG using the standard 10-20 system of electrodes, 3-Tesla brain magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. The surgery consisted of resection of the extensive epileptogenic lesion, in addition to disconnection of the left frontal lobe anterior to the motor strip.The infant underwent epilepsy surgery at three months of age. At two-year follow up, she remained seizure free, with no focal motor deficit and the epileptic encephalopathy resolved. The disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue.We highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy. In the process, we demonstrate how epileptic spasms, although clinically and electrographically generalized, resolved after disconnecting the epileptogenic zone.

Uncontrolled seizures in children can contribute to irreversible cognitive impairment and developmental delay, in addition to placing them at risk for sudden unexplained death in epileptic patients (SUDEP). Since its introduction at Saint Ann Hospital in Paris in the 1960s, stereoelectroencephalography (SEEG) is increasingly being utilized at epilepsy centers in the United States as an invasive tool to help localize the seizure focus in drug-resistant focal epilepsy.Children with symptomatic epilepsy, commonly due to cortical dysplasia and dysembryoplastic neuroepithelial tumor (DNET), may benefit from SEEG investigation. The arrangement of SEEG electrodes is individually tailored based on the suspected location of the epileptogenic zone (EZ). The implanted depth electrodes are used to electrically stimulate the corresponding cortices to obtain information about the topography of eloquent cortex and EZ. Morbidity: Surgical morbidity in these children undergoing SEEG investigation is low, but not negligible. The number of electrodes directly correlates with the risk of intraoperative complication. Thus a risk and benefit analysis needs to be carefully considered for each patient. Neurodiagnostic technology: Both during and after the SEEG electrode implantation, the intraoperative monitoring and EEG technologists play a vital role in the successful monitoring of the patient.SEEG is an important tool in the process of epilepsy surgery in children with symptomatic epilepsy, commonly due to cortical dysplasia and DNET.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

Introduction The concept of Secondary Epileptogenesis (SE) was introduced by Frank Morrell (Morrell, 1989). The secondary epileptogenic zone (SEZ) is a cortical area that has become epileptogenic due to the influence of epileptogenic activity in a primary epileptogenic zone (PEZ). The most likely mechanism responsible for secondary epileptogenesis is kindling, which is the tendency of the brain to become progressively more epileptogenic when stimulated repeatedly. It is difficult to provide conclusive proof of kindling and secondary epileptogenesis in humans (Luders, 2001). We present a case of a patient with refractory epilepsy and ictal intermediate secondary epileptogenesis proven by stereotactically placed depth electrodes and 8 years of clinical follow up. Methods A 52 year-old, right-handed, woman with intractable epilepsy since age 45 was referred to our center for presurgical evaluation. She described her seizures as a sudden sensation of familiarity and abdominal rising sensation lasting for seconds to 1 min. Next, she remembered being confused and tired. Her husband describes these episodes as unresponsiveness associated with repetitive mouth and tongue movements. Her seizure frequency was 2–3 times every month which evolved into a generalized tonic- clonic seizure once a month. Multiple antiepileptic medications failed to control her seizures. Her only risk factor for epilepsy was a motor vehicle accident with a severe closed head injury at age 17. Results Her MRI showed areas of cystic encephalomalacia and gliosis of the right inferior frontal lobe and anterior aspect of the right insula (Images 1). Scalp VEEG showed automotor seizures with ictal onset zone, maximum over F8-T8. No interictal epileptiform abnormalities were recorded on scalp EEG. She underwent stereotactic implantation of depth electrodes located around the right frontal cystic encephalomalacia, right insula and temporal lobe (mesial structures, lateral and tip) (Image 2). Irritative zone was extensive (frontal- around the lesion, insular cortex, and mesial temporal structures). She had 6 automotor seizures arising from the right orbitofrontal area- anterior, medial, and lateral to the lesion (Image 2A), and multiple electrographic seizures arising from the right mesial temporal areas (Image 2B). After a discussion in a multidisciplinary conference, the following was recommended: resection of the right orbitofrontal epileptogenic lesion, leaving the right temporal lobe intact. She has remained seizure free for a total of 8 years, completely off all antiepileptic medications. Conclusion The epileptogenic zone in our patient was the right orbitofrontal lesion. Nevertheless, depth electrodes clearly showed an additional seizure onset zone in the right amygdala and hippocampus. Only the right frontal epileptogenic lesion was removed preserving the right mesial temporal lobe. This patient has been seizure free, off AEDs, for 8 years. This suggests the right mesial temporal structure is a SEZ.

We surveyed 23 antibody-related marketing applications for glycoform analytical and functional information. Our database analysis shows a clear trend of increasing sophistication of analytical methods used to identify and quantify glycans. These have revealed a high degree of complexity and heterogeneity of glycans attached to antibody products. The nature of the complexity is influenced by product type and expression system, and may be associated with functional consequences in some but not all cases.

Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common epilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly encountered. BRE remits by age 16 years with many children requiring no treatment. Seizures in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also present with seizures that are self-limited with no associated psychomotor disturbances. Benign familial neonatal convulsions caused by a channelopathy, and inherited in an autosomal dominant manner, have a favorable outcome with spontaneous resolution. Benign idiopathic neonatal seizures, also referred to as “fifth-day fits,” are an example of another epilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy are characterized as “benign” idiopathic age-related epilepsies as they have favorable implications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, and have no associated psychomotor disturbances. However, sometimes selected patients may have associated comorbidities such as cognitive and language delay for which the term “benign” may not be appropriate. [ Pediatr Ann . 2015;44(2):e30–e35.]

Background Post-traumatic epilepsy after a traumatic brain injury occurs in 10%-20% of children. Unfortunately, a biomarker that could provide prognostic information about both post-traumatic epilepsy and cognitive development is lacking. In this first of a series of studies, we have reviewed and analyzed clinical variables in children following traumatic brain injury to understand the epidemiologic and clinical characteristics of post-traumatic epilepsy in our urban population. Methods We performed a retrospective electronic chart review of patients who had suffered traumatic brain injury and subsequently evaluated at Children's Hospital of Michigan from 2002 to 2012. Various epidemiologic and clinical variables were analyzed. Results Patients who had severe traumatic brain injury and post-traumatic epilepsy had an abnormal acute head computed tomography. These patients had increased number of different seizure types, increased risk of intractability of epilepsy, and were on multiple antiepileptic drugs. Hypomotor seizure was the most common seizure type in these patients. There was a high prevalence of patients who suffered nonaccidental trauma, all of whom had severe traumatic brain injury. Conclusions This study demonstrates a need for biomarkers in children following traumatic brain injury to reliably evaluate the risk of post-traumatic epilepsy.

The conformation of polysaccharide PGG-Glucan, isolated from yeast cell walls, in aqueous solution was investigated by small angle x-ray scattering (SAXS) and multidetector gel permeation chromatography coupled with postcolumn delivery (GPC/PCD) techniques in comparison with scleroglucan. It was shown that both polysaccharides exhibit a rigid rod-like conformation in aqueous solution by SAXS experiments. The mass per unit length (M/L) and radius (R) of rod cross section of PGG-Glucan were measured to be 6300 daltons/nm and 1.89 nm, while those of scleroglucan are 2300 and 0.83, respectively. Utilizing a GPC/light scattering technique, the average aggregation number of PGG-Glucan is 9, while that of scleroglucan is around 3. From the comparison of the M/L and R of the respective rod cross sections as well as their aggregation number data, it is concluded that PGG-Glucan is composed of triple helices, which tend to aggregate as triplets in solution, whereas scleroglucan is composed of a single triple helix. The aggregation number distribution of PGG-Glucan was found to range from 1 to about 25 determined by GPC/PCD. From the observation of a Debye–Scherrer ring type of peak in the macroscopic scattering cross section of PGG-Glucan by SAXS, the existence of a small amount of ordered clusters of PGG-Glucan can be deduced. The “lattice parameter” of these ordered fasces-like clusters is consistent with the radius of the individual triple-helical rods forming a microfibrillar superstructure. These results indicate that higher aggregated forms of PGG-Glucan containing up to 8 triple helices behave as ordered fasces-like clusters. We conclude that PGG-Glucan is triple-helix aggregates formed by rigid rods stacking together side by side. We propose a molecular structural model for PGG-Glucan conformations. © 1999 John Wiley & Sons, Inc. Biopoly 50: 569–578, 1999

The main concepts of the quality by design (QbD) initiative and applicability to biomanufacturing are described. QbD can lead to a future where product quality will be assured by flexible, science-based approaches. QbD is an umbrella of related concepts and approaches that include quality target product profiles, risk assessments, design spaces, control strategies using process analytical technology, continuous process improvement and others. We will also discuss the regulatory structure supporting the QbD initiative, including the International Conference on Harmonization Quality documents ICH Q8(R1) (Pharmaceutical Development), ICH Q9 (Risk Assessments), ICH Q10 (Quality Systems) and FDA's Process Analytical Technology (PAT) Guidance. A case study is presented for applying QbD to a biopharmaceutical process, viral clearance by anion exchange chromatography. It is believed that QbD will lead to more flexible processes which are justified based on risk and science rather than on a solely empirical approach. Keywords: QbD; ICH; biopharmaceutical development; risk management; design space; PAT; anion exchange chromatography

A process for the rapid development and optimization of the fermentation process for an antibotulinum neurotoxin antibody fragment (bt-Fab) production expressed in Escherichia coli was achieved via a high-throughput process proteomics and statistical experimental design. This process, using retentate chromatography-surface enhanced laser desorption/ionization mass spectrometry (RC-SELDI MS), was employed for identifying and quantifying bt-Fab antibody in complex biological samples for the optimization of microbial fermentation conditions. Five variables (type of culture media, glycerol concentration, post-induction temperature, IPTG concentration, and incubation time after induction) were statistically combined using an experimental 2(5)(-1) fractional factorial design and tested for their effects on maximal bt-Fab antibody production. When the effects of individual variables and their interactions were assessed, type of media and post-induction temperature showed statistically significant increase in yield of the fermentation process for the maximal bt-Fab antibody production. This study establishes an integral approach as a valuable tool for the rapid development of manufacturing processes for producing various biological materials. To verify the RC-SELDI MS method, a Fab-specific immuno-affinity HPLC assay developed here was also employed for the quantification of the bt-Fab antibody in crude lysate samples obtained during the fermentation optimization process. Similar results were obtained.

Enzymatic depolymerization of polysaccharides with alpha-amylase has been studied in mixed aqueous dimethylsulfoxide (DMSO)/water solvents. Polysaccharide substrate chemical compositions, configurational structures, and bonding pattersn are known to affect observed enzymatic reaction kinetics. The branching structures of polysaccharides and their effects on the kinetic mechanisms of depolymerization reactions via endo-acting hydrolyzing enzyme was studied via size exclusion chromatography coupled to low angle laser light scattering (SEC/LALLS). The glycogen branching structure is a heterogeneously distributed "cluster" structure rather than a homogeneously distributed "treelike" structure. The action pattern of alpha-amylase on glycogen, which is composed of highly branched clusters, as end-products, has a "pseudo-exo-attack" in contrast to an expected "endoattack" as seen in the hydrolysis of amylose or amylopectin substrates. These effects of branched substrates for mixed amylose/glycogen alpha-amylolysis have been predicted and demonstrated by both experimental and theoretical analysis using the kinetic model presented in this report. The "lumped" kinetic model employed, assumes that the enzyme simultaneously attacks both linear and branched substrates. In general, excellent agreement between the model predictions and the experimental observations, both qualitatively and quantitatively, was obtained. (c) 1995 John WileySons, Inc.

L'etude des parametres cinetiques, biochimiques et une technique alliant chromatographie d'exclusion et utilisation d'un laser a petit angle, permettent de montrer que l'hydrolyse de trois polysaccharides (amylose, amylopectine et glycogene), pourtant de meme composition chimique, est fonction du nombre de ramification de chaines polysaccharidiques

Amylose depolymerization kinetics, catalysed with α-amylase, have been studied in mixed aqueous-dimethyl sulfoxide (DMSO) solvents and similar aqueous-DMSO solvents containing butanol. It is determined that the observed depolymerization kinetics are affected by biopolymeric substrate conformations. It is found that substrate conformation strongly influences measured enzymatic activity. Soluble substrates exhibit rapid hydrolysis rates compared to insoluble substrates. Moreover, enzymatic activity is also affected by biopolymeric substrate structure (particularly crystalline structure) in precipitated states. Both the crystalline type and the degree of crystallinity are shown to contribute to the observed kinetics. Of these two parameters, crystalline type is shown to be a more dominant effect than degree of crystallinity in reducing reaction rates. Relative rates of depolymerization for various amylose substrate conformations are presented. The results imply an interrelationship between enzyme action and polymeric substrate conformation. These results suggest that enzymes can “recognize” substrate ternary and quaternary structures and that their catalytic activities reflect this recognition.