Finally, Some Neurophysiologic Good News-Favorable Prognosis in Coma.
Authors: Husain AM Abstract [Box: see text]. PMID: 31608668 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - October 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

When Monogenic Isn't Monogenic-Unravelling the Oligogenic Architecture of the Developmental and Epileptic Encephalopathies.
Authors: Scheffer IE, Liao J Abstract [Box: see text]. PMID: 31601119 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - October 13, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Is Spontaneity Overrated? The Value of Cortical Stimulation-Induced Seizures.
Authors: Velez-Ruiz N Abstract [Box: see text]. PMID: 31597457 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - October 11, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Guilty by Association: KCTD16 and GABABR Antibodies in Paraneoplastic Limbic Encephalitis.
Authors: Gaspard N Abstract [Box: see text]. PMID: 31578091 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - October 4, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

The Road to Diagnosis: Shortening the Diagnostic Odyssey in Epilepsy.
CONCLUSION: Whole-exome sequencing and EP are the most cost-effective genetic tests for epilepsy. Our analyses support for a broad population of patients with unexplained epilepsy, starting with these tests. Although less expensive, CMA has lower yield, and its use as the first-tier test is thus not supported from a cost-effectiveness perspective. PMID: 31476917 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - September 4, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Ripple While You Walk, and You May Get Lost: Pathological High-Frequency Activity Can Alter Spatial Navigation Circuits.
Authors: Brennan EKW, Ahmed OJ Abstract The Impact of Pathological High-frequency Oscillations on Hippocampal Network Activity in Rats With Chronic Epilepsy. Ewell LA, Fischer KB, Leibold C, Leutgeb S, Leutgeb JK. eLIFE. 2019;8:pii: e42148. doi: 10.7554/eLife.42148. PMID: 30794155 In epilepsy, brain networks generate pathological high-frequency oscillations (pHFOs) during interictal periods. To understand how pHFOs differ from normal oscillations in overlapping frequency bands and potentially perturb hippocampal processing, we performed high-density single unit and local field potential recordings from hippocampi o...
Source: Epilepsy Currents - September 4, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Epilepsy Therapy Goes Viral.
Authors: Lim BC, Hunt RF Abstract Epilepsy Gene Therapy Using an Engineered Potassium Channel Snowball A, Chabrol E, Wykes RC, Shekh-Ahmad T, Cornford JH, Lieb A, Hughes MP, Massaro G, Rahim AA, Hashemi KS, Kullmann DM, Walker MC, Schorge S. J Neurosci. 2019;39(16):3159-3169. Refractory focal epilepsy is a devastating disease for which there is frequently no effective treatment. Gene therapy represents a promising alternative, but treating epilepsy in this way involves irreversible changes to brain tissue, so vector design must be carefully optimized to guarantee safety without compromising efficacy. We set out to ...
Source: Epilepsy Currents - August 31, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

The Winner by a Nose: Intranasal Midazolam.
Authors: Faught E Abstract Safety and Efficacy of Midazolam Nasal Spray in the Outpatient Treatment of Patients With Seizure Clusters-A Randomized, Double-Blind, Placebo-Controlled Trial. Detyniecki K, Van Ess PJ, Sequeira DJ, Wheless JW, Meng TC, Pullmnaan WE. Epilepsia. 2019. doi:10.1111/epi.15159. Epub ahead of print. OBJECTIVE: To evaluate the safety and efficacy of a novel formulation of midazolam administered as a single-dose nasal spray (MDZ-NS) in the outpatient treatment of patients experiencing seizure clusters (SCs). METHODS: This was a phase III, randomized, double-blind, placebo-controlled tria...
Source: Epilepsy Currents - August 29, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

A Brief Boost of Positive Energy When Young Makes for a Healthy Adult Interneuron.
We report that ambient glutamate levels are high (≈100 nm) in the neonatal cortex and decrease (to ≈50 nm) during the first weeks of life, coincident with increases in astrocytic glutamate uptake. Consistent with elevated ambient glutamate, putative parvalbumin-positive interneurons in the cortex (identified using G42: GAD1-eGFP reporter mice) exhibit a transient, tonic NMDA current at the end of the first postnatal week. GluN2C/GluN2D-containing NMDA receptors mediate the majority of this current and contribute to the resting membrane potential and intrinsic properties of developing putative parvalbumin intern...
Source: Epilepsy Currents - August 29, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Reigning in Excitatory Signaling in CDKL5 Deficiency.
Authors: Forcelli PA Abstract AMPA Receptor Dysregulation and Therapeutic Interventions in a Mouse Model of CDKL5 Deficiency Disorder Yennawar M, White RS, Jensen FE. J Neurosci. 2019;39(24):4814-4828. Pathogenic mutations in cyclin-dependent kinase-like 5 (CDKL5) result in CDKL5 deficiency disorder (CDD), a rare disease marked by early-life seizures, autistic behaviors, and intellectual disability. Although mouse models of CDD exhibit dendritic instability and alterations in synaptic scaffolding proteins, studies of glutamate receptor levels and function are limited. Here, we used a novel mouse model of CDD, the C...
Source: Epilepsy Currents - August 29, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Is it a Tie at This Point in the Game? Efficacy of Levetiracetam and Phenytoin for the Second-Line Treatment of Convulsive Status Epilepticus.
Authors: Vossler DG Abstract Levetiracetam Versus Phenytoin for Second-Line Treatment of Pediatric Convulsive Status Epilepticus (EcLiPSE): A Multicentre, Open-Label, Randomized Trial Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Woolfall K, Roper L, Nablet J, Lee ED, Potter S, Tate P, Iyer A, Evans V, Appleton RE. Lancet. 2019;393:2125-34. doi:10.1016/S0140-6736(19)30724-X. BACKGROUND: Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the United Kingdom; however, some evidence suggests that levetiracetam could be an ef...
Source: Epilepsy Currents - August 22, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Oligodendrocyte Kir4.1 Channels Clear Out Congested K.
Authors: Lyman KA, Chetkovich DM Abstract Oligodendrocytes Control Potassium Accumulation in White Matter and Seizure Susceptibility. Larson VA, Mironova Y, Vanderpool KG, Waisman A, Rash JE, Agarwal A, Bergles DE. Elife. 2018 Mar 29;7. pii: e34829. doi: 10.7554/eLife.34829. The inwardly rectifying K+ channel Kir4.1 is broadly expressed by central nervous system glia and deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here, we show that selective deletion of Kir4.1 fro...
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

What Is the Best Target for Ablation of Mesial Temporal Lobe Epilepsy?
Authors: King-Stephens D Abstract Effects of Surgical Targeting in Laser Interstitial Thermal Therapy for Mesial Temporal Lobe Epilepsy: A Multicenter Study of 234 Patients Wu C, Jermakowicz WJ, Chakravorti S, Cajigas I, Sharan AD, Jagid JR, Matias CM, Sperling MR, Buckley R, Ko A, Ojemann JG, Miller JW, Youngerman B, Sheth SA, McKhann GM, Laxton AW, Couture DE, Popli GS, Smith A, Mehta AD, Ho AL, Halpern CH, Englot DJ, Neimat JS, Konrad PE, Neal E, Vale FL, Holloway KL, Air EL, Schwalb J, Dawant BM, D'Haese PF. Epilepsia. 2019;60(6):1171-1183. doi:10.1111/epi.15565. OBJECTIVE: Laser interstitial thermal therap...
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Adult Neurogenesis in the Development of Epilepsy.
Authors: Danzer SC Abstract Compelling evidence indicates that hippocampal dentate granule cells are generated throughout human life and into old age. While animal studies demonstrate that these new neurons are important for memory function, animal research also implicates these cells in the pathogenesis of temporal lobe epilepsy. Several recent preclinical studies in rodents now suggest that targeting these new neurons can have disease-modifying effects in epilepsy. PMID: 31409149 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Goldilocks Zone of Ictal Onset: Partially Recovered Synapses Provide the Kindling to Fuel Ictal Activity.
Authors: Subramanian D, Santhakumar V Abstract A Proposed Mechanism for Spontaneous Transitions Between Interictal and Ictal Activity Jacob T, Lillis KP, Wang Z, Swiercz W, Rahmati N, Staley KJ. J Neurosci. 2019;39(3):557-575. doi:10.1523/JNEUROSCI.0719-17.2018. Epub 2018 Nov 16. PMID: 30446533 Epileptic networks are characterized by 2 outputs: brief interictal spikes and rarer, more prolonged seizures. Although either output state is readily modeled in silico and induced experimentally, the transition mechanisms are unknown, in part because no models exhibit both output states spontaneously. In silico, small-world...
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Reality Is in the Posterior Hippocampus: Who Knew?
In this study, we examined the volume of the total hippocampus, and the hippocampal head, body, and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy, and generalized epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). RESULTS: Compared to EC, the POE group had smaller total left hippocampus volume (13.5% decrease, P
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Predicting Response to Treatment of Epileptic Seizures: How Much Time and How Many AEDs Do We Need to Try?
CONCLUSION: Our approach generates up-to-date predictions of the patient's risk of not achieving seizure remission whenever new clinical information becomes available that could influence patient counseling and management decisions. PMID: 31409152 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Encapsulated Neuroprotection to the Rescue-or How to Safely Protect a Brain From Seizing.
Authors: Gross C Abstract Long-Term, Targeted Delivery of GDNF From Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy Paolone G, Falcicchia C, Lovisari F, et al. J Neurosci. 2019;39(11):2144-2156. doi:10.1523/JNEUROSCI.0435-18.2018. Epub 2019 Jan 21. Neurotrophic factors are candidates for treating epilepsy, but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted,...
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Mission: Control. How Can We Increase Highly Effective Contraception Use in Women With Epilepsy?
CONCLUSION: A total of 36.6% of WWE in the EBCR did not use highly effective contraception and 50.0% did not take FA in 2017 despite the important negative consequences of unintended pregnancy on pregnancy outcomes. There is a need for more readily available information and counseling on safe and effective contraception and FA use for this community. PMID: 31409154 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - August 15, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

"Chance Takers Are Accident Makers": Are Patients With Epilepsy Really Taking a Chance When They Drive?
"Chance Takers Are Accident Makers": Are Patients With Epilepsy Really Taking a Chance When They Drive? Epilepsy Curr. 2019 Jul 22;:1535759719858647 Authors: Joshi CN, Vossler DG, Spanaki M, Draszowki JF, Towne AR, Members of the Treatments Committee of the American Epilepsy Society Abstract This review compiles scientific data about the real dangers faced by people with epilepsy (PWE) who drive. Those include risks of motor vehicle accidents (MVA) in PWE as compared with controls (individuals without epilepsy) and as compared with persons with other medical conditions that impact fitness to ...
Source: Epilepsy Currents - July 23, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

SCN8A: When Neurons Are So Excited, They Just Can't Hide It.
Authors: Gertler TS, Carvill GL Abstract Neuronal Mechanisms of Mutations in SCN8A Causing Epilepsy or Intellectual Disability Liu Y, Schubert J, Sonnenberg L, Helbig KL, Hoei-Hansen CE, Koko M, Rannap M, Lauxmann S, Huq M, Schneider MC, Johannesen KM, Kurlemann G, Gardella E7, Becker F, Weber YG, Benda J, Møller RS, Lerche H. Brain. 2019;142(2):376-390. doi:10.1093/brain/awy326. De novo mutations of the sodium channel gene SCN8A result in an epileptic encephalopathy with refractory seizures, developmental delay, and elevated risk of sudden death. p.Arg1872Trp is a recurrent de novo SCN8A mutation reported i...
Source: Epilepsy Currents - July 12, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Mechanisms of Epilepsy and Neuronal Synchronization Gordon Research Conference Power Hour Summary.
Authors: Isom LL, Wilcox KS, Brooks-Kayal A PMID: 31282199 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - July 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

A Hit, a Hit-A Very Palpable Hit: Mild TBI and the Development of Epilepsy.
Authors: Danzer SC Abstract Repetitive Diffuse Mild Traumatic Brain Injury Causes An Atypical Astrocyte Response and Spontaneous Recurrent Seizures Shandra O, Winemiller AR, Heithoff BP, et al. J Neurosci. 2019;39(10):1944-1963. doi:10.1523/JNEUROSCI.1067-18.2018. Epub 2019 Jan 21. PMID: 30665946 . Focal traumatic brain injury (TBI) induces astrogliosis, a process essential to protecting uninjured brain areas from secondary damage. However, astrogliosis can cause loss of astrocyte homeostatic functions and possibly contributes to comorbidities such as posttraumatic epilepsy (PTE). Scar-forming astrocytes seal focal...
Source: Epilepsy Currents - June 19, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Cutting the Losses of Pregnant Women With Epilepsy.
Authors: Velez-Ruiz N Abstract Association of Unintended Pregnancy With Spontaneous Fetal Loss in Women With Epilepsy: Findings of the Epilepsy Birth Control RegistryHerzog AG, Mandle HB, MacEachern DB. JAMA Neurol. 2018. doi:10.1001/jamaneurol.2018.3089. [Epub ahead of print] PMID: 30326007. IMPORTANCE: If unintended pregnancy is common among women with epilepsy and is associated with increased risk of spontaneous fetal loss (SFL), it is important to develop guidelines for safe and effective contraception for this community. OBJECTIVE: To assess whether planned pregnancy is a determinant of SFL in women wi...
Source: Epilepsy Currents - June 19, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

When a Good Cop Turns Bad: The Pro-Ictal Action of Parvalbumin Expressing Interneurons During Seizures.
Authors: Raimundo JV, Dulla C Abstract KCC2 Overexpression Prevents the Paradoxical Seizure-Promoting Action of Somatic Inhibition Magloire, V., Cornford, J., Lieb, A., Kullmann, D. M., and Pavlov, I. Nat. Commun. 10, 1225. doi:10.1038/s41467-019-08933-4. Although cortical interneurons are apparently well-placed to suppress seizures, several recent reports have highlighted a paradoxical role of perisomatic-targeting parvalbumin-positive (PV+) interneurons in ictogenesis. Here, we use an acute in vivo model of focal cortical seizures in awake behaving mice, together with closed-loop optogenetic manipulation of PV+ i...
Source: Epilepsy Currents - June 6, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Finding the Sweet Spot: Fine-Tuning DBS Parameters to Cure Seizures While Avoiding Psychiatric Complications.
CONCLUSION: The majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes. PMID: 31068005 [PubMed - as supplied by publisher] (Source: Epilepsy Currents)
Source: Epilepsy Currents - May 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Astrocyte Receptor Rebirth.
Authors: Salvati K, Beenhakker M Abstract Conditional Knockout of mGluR5 From Astrocytes During Epilepsy Development Impairs High-Frequency Glutamate Uptake Umpierre AD, West PJ, White JA, et al. J Neurosci. 2019;39(4):727-742. doi:10.1523/JNEUROSCI.1148-18.2018 Astrocyte expression of metabotropic glutamate receptor 5 (mGluR5) is consistently observed in resected tissue from patients with epilepsy and is equally prevalent in animal models of epilepsy. However, little is known about the functional signaling properties or downstream consequences of astrocyte mGluR5 activation during epilepsy development. In the rode...
Source: Epilepsy Currents - May 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Inhibition Gets a New KAR Smell.
Authors: Courtney CD, Christian CA Abstract Ionotropic and metabotropic kainate receptor signaling regulates Cl- homeostasis and GABAergic inhibition Garand D, Mahadevan V, Woodin MA. J Physiol. 2018. doi:10.1113/JP276901 Potassium chloride cotransporter 2 (KCC2) plays a critical role in the regulation of chloride (Cl-) homeostasis within mature neurons. The KCC2 is a secondarily active transporter that extrudes Cl- from the neuron, which maintains a low intracellular Cl-concentration [Cl-]. This results in a hyperpolarized reversal potential of GABA ( E GABA), which is required for fast synaptic inhibition in the ...
Source: Epilepsy Currents - April 30, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

It's All About the Networks.
Authors: Shih J Abstract Interictal stereotactic-EEG functional connectivity in refractory focal epilepsies Lagarde S, Roehri N, Lambert I, et al. Brain. 2018;141(10):2966-2980. Drug-refractory focal epilepsies are network diseases associated with functional connectivity alterations both during ictal and interictal periods. A large majority of studies on the interictal/resting state have focused on functional magnetic resonance imaging (MRI)-based functional connectivity. Few studies have used electrophysiology, despite its high-temporal capacities. In particular, stereotactic-electroencephalogram (EEG) is highly s...
Source: Epilepsy Currents - April 30, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Human Microglia Seize the Chance to be Different.
Authors: Brewster AL Abstract Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry Böttcher C, Schlickeiser S, Sneeboer MAM, et al. Nat Neurosci. 2019;22(1):78-90. Microglia, the specialized innate immune cells of the central nervous system, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we ap...
Source: Epilepsy Currents - April 30, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

High-Frequency Activity During Stereotyped Low-Frequency Events Might Help to Identify the Seizure Onset Zone.
Authors: Ahmed OJ, Sudhakar SK Abstract Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy. Liu S, Gurses C, Sha Z, Quach MM, Sencer A, Bebek N, et al. Brain. 2018;141(3):713-730. doi:10.1093/brain/awx374. PMID: 29394328 . High-frequency oscillations in local field potentials recorded with intracranial electroencephalogram are putative biomarkers of seizure-onset zones in epileptic brain. However, localized 80- to 500-Hz oscillations can also be recorded from normal and nonepileptic cerebral structures. When defined only by rate or frequency, ph...
Source: Epilepsy Currents - April 25, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Treatment Works, So Who's Afraid of PNES?
CONCLUSIONS: Our study is limited in that it cannot establish a causal relationship between adherence to psychotherapy and outcomes, and the results may not generalize beyond the single quaternary care center study site. Among participants with documented PNES, adherence to psychotherapy was associated with reduction in PNES frequency, improvement in quality of life, and decrease in ED visits. PMID: 31012324 [PubMed] (Source: Epilepsy Currents)
Source: Epilepsy Currents - April 25, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Fast-Spiking Interneurons Exposed in Tumor-Associated Epilepsy.
Authors: Maguire J Abstract Perineuronal Nets Decrease Membrane Capacitance of Peritumoral Fast Spiking Interneurons in a Model of Epilepsy Tewari BP, Chaunsali L, Campbell SL, Patel DC, Goode AE, and Sontheimer H. Nat Commun. 2018;9(1):4724. Patients with brain tumor commonly present with epileptic seizures. We show that tumor-associated seizures are the consequence of impaired GABAergic inhibition due to an overall loss of peritumoral fast-spiking interneurons (FSNs) concomitant with a significantly reduced firing rate of those that remain. The reduced firing is due to the degradation of perineuronal nets (PNNs) ...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Are the Breaks Breaking Down?
Authors: Ewell LA Abstract Altered Hippocampal Interneuron Activity Precedes Ictal Onset Miri ML, Vinck M, Pant R, Cardin JA. Elife. 2018;7. pii: e40750. doi:10.7554/eLife.40750. Although failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitates a rapid shift from healthy to ictal activity remains unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Comparative Risk of Major Congenital Malformations With 8 Different Antiepileptic Drugs: A Prospective Cohort Study of the EURAP Registry.
Authors: Vossler DG Abstract Teratogenesis of 8 Antiepileptic Drugs in Multinational Experience Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, Sabers A, Thomas SV, Vajda F for the EURAP Study Group. Lancet Neurol. 2018;17(6):530-538. BACKGROUND: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the 8 most commonly used antiepileptic drugs in monotherapy. METHODS: We did a longitudinal, prospective co...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Making Rash Decisions in Epilepsy: Evaluating Hypersensitivity Reactions to Anti-seizure Medications.
Authors: Bermeo-Ovalle A Abstract The Frequency and Clinical Features of Hypersensitivity Reactions to Antiepileptic Drugs in Children: A Prospective Study Guvenir H, Dibek Misirlioglu E, Civelek E. J Allergy Clin Immunol Pract. 2018;6(6):2043-2050. BACKGROUND: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions during childhood. Studies report a wide clinical spectrum of reactions with AED use, ranging from a mild rash to severe cutaneous reactions. OBJECTIVE: To determine the prevalence and clinical features of AED hypersensitivity reactions during childhood. METHODS: Patients in our pedia...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Don't Fear the Reefer-Evidence Mounts for Plant-Based Cannabidiol as Treatment for Epilepsy.
CONCLUSIONS: Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 or 20 mg/kg/d to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560.) Long-Term Safety and Treatment Effects of Cannabidiol in Children and Adults With Treatment-Resistant Epilepsies: Expanded Access Program Results Szaflarski JP, Bebin EM, Comi AM, et al; CBD EAP Study Group. Ep...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

A New Hose to Extinguish the FIRES?
Authors: Gaspard N Abstract Tocilizumab Treatment for New Onset Refractory Status Epilepticus Jun JS, Lee ST, Kim R, Chu K, Lee SK. Ann Neurol. 2018;84(6):940-945. doi:10.1002/ana.25374. We investigated the therapeutic potential of the interleukin-6 receptor inhibitor tocilizumab in 7 patients with new-onset refractory status epilepticus (NORSE) who remained refractory to conventional immunotherapy with rituximab (n = 5) or without rituximab (n = 2). Status epilepticus (SE) was terminated after 1 or 2 doses of tocilizumab in 6 patients with a median interval of 3 days from the initiation. They had no recurrence of ...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

When Epilepsy Grows Up ….
When Epilepsy Grows Up…. Epilepsy Curr. 2019 Mar-Apr;19(2):99-100 Authors: Boyer K Abstract Neurocognition in Childhood Epilepsy: Impact on Mortality and Complete Seizure Remission 50 Years Later Sillanpää M, Saarinen MM, Karrasch M, Schmidt D, Hermann BP. Epilepsia. 2019;60(1):131-138. doi:10.1111/epi.14606. Epub 2018 Nov 22. OBJECTIVE: To study associations of the severity of impairment in childhood neurocognition (NC) with long-term mortality and complete seizure remission. METHODS: A population-based cohort of 245 subjects with childhood-onset epilepsy was followed up for 5...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Current Controversy: Spikes, Bursts, and Synchrony in Generalized Absence Epilepsy: Unresolved Questions Regarding Thalamocortical Synchrony in Absence Epilepsy.
Authors: Huguenard J Abstract Absence epilepsy is a disorder of thalamocortical networks. Animal models have provided detailed information regarding the core cellular, synaptic, and network features that contribute to the electroencephalogram spike and wave discharge characteristic of typical absence epilepsy. Understanding of seizure networks and dynamics is a critical step toward improving treatments, yet competing conceptual models have evolved to explain seizure initiation and propagation. Recent studies have questioned 2 key model concepts: (1) T-type Ca2+ channel-dependent burst firing in thalamic relay neuro...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Valproic Acid Leads New Neurons Down the Wrong Path.
Authors: Danzer SC Abstract Ectopic Neurogenesis Induced by Prenatal Antiepileptic Drug Exposure Augments Seizure Susceptibility in Adult Mice Sakai A, Matsuda T, Doi H, Nagaishi Y, Kato K, Nakashima K. Proc Natl Acad Sci U S A. 2018;115(16):4270-4275. Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocal...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

PUMILIO1 Links Epilepsy to Spinocerebellar Ataxia.
Authors: Lyman KA, Chetkovich DM Abstract A Mild PUM1 Mutation Is Associated With Adult-Onset Ataxia, Whereas Haploinsufficiency Causes Developmental Delay and Seizures Gennarino VA, Palmer EE, McDonell LM, et al. Cell. 2018;172(5):924-936.e11. doi:10.1016/j.cell.2018.02.006. Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore searched for human patients with...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

The Theta Stone: 3 to 10 Hz Oscillations to Decipher the Human Brain Code.
Authors: de la Prida LM Abstract Lateralized Hippocampal Oscillations Underlie Distinct Aspects of Human Spatial Memory and Navigation Miller J, Watrous AJ, Tsitsiklis M, et al. Nat Commun. 2018;9(1):2423. doi:10.1038/s41467-018-04847-9. The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including ...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Subacute Encephalopathy With Seizures in Alcoholics Syndrome: A Subtype of Nonconvulsive Status Epilepticus.
Authors: Fernández-Torre JL, Kaplan PW Abstract A recent assessment of the classification of nonconvulsive status epilepticus (NCSE) has incorporated the specific electroencephalographic (EEG) patterns on a syndromic basis. Such a clinical EEG syndromic approach may enable more accurate and expedited diagnosis of particular subtypes of NCSE so as to improve therapy. Herein, we review the characteristics of subacute encephalopathy with seizures in alcoholics syndrome, a subtype of focal NCSE occurring in chronic alcoholism with specific features, including encephalopathy, lateralized periodic discharges on th...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

The Dilemma of the Chicken or the Egg-What Appears First in TLE-Seizures or Morphometric Changes in the Temporal Lobe?
Authors: Szaflarski JP Abstract Abnormal Temporal Lobe Morphology in Asymptomatic Relatives of Patients With Hippocampal Sclerosis: A Replication Study Yaakub SN, Barker GJ, Carr SJ, et al. Epilepsia. 2019;60(1):e1-e5. doi:10.1111/epi.14575. We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE + HS) and first-degree asymptomatic relatives of patients with mTLE+HS. Using T1-weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asympt...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

The Cost of the Second Seizure: Rethinking the Treatment Decision.
CONCLUSION: Our model determined that immediate AED treatment is preferable to deferred treatment in adult first-seizure patients over a wide and clinically relevant range of variables. Furthermore, our analysis suggests that the 10-year seizure recurrence rate that justifies AED treatment (38.0%) is substantially lower than the 60% threshold used in the current definition of epilepsy. PMID: 30955429 [PubMed] (Source: Epilepsy Currents)
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Losing Balance Over a Fatty Acid.
Authors: Gross C Abstract Deficiency of AMPAR-Palmitoylation Aggravates Seizure Susceptibility Itoh M, Yamashita M, Kaneko M, Okuno H, Abe M, Yamazaki M, Natsume R, Yamada D, Kaizuka T, Suwa R, Sakimura K, Sekiguchi M, Wada K, Hoshino M, Mishina M, Hayashi T. J Neurosci. 2018;38(47):10220-10235. doi:10.1523/JNEUROSCI.1590-18.2018. Epub 2018 Oct 24. PMID: 30355633. Synaptic AMPAR expression controls the strength of excitatory synaptic transmission and plasticity. An excess of synaptic AMPARs leads to epilepsy in response to seizure-inducible stimulation. The appropriate regulation of AMPARs plays a crucial role in t...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Cracklin' Fish Brains.
Authors: Beenhakker MP Abstract Whole-Brain Neuronal Activity Displays Crackling Noise Dynamics Ponce-Alvarez A, Jouary A, Privat M, Deco G, Sumbre G. Neuron. 2018;100(6):1446-1459.e6. Previous studies suggest that the brain operates at a critical point in which phases of order and disorder coexist, producing emergent patterned dynamics at all scales and optimizing several brain functions. Here, we combined light-sheet microscopy with GCaMP zebrafish larvae to study whole-brain dynamics in vivo at near single-cell resolution. We show that spontaneous activity propagates in the brain's 3-dimensional space, generatin...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Connecting Mind, Brain, and Seizures by Default Mode.
Authors: Salpekar J Abstract Effective Connectivity Within the Default Mode Network in Left Temporal Lobe Epilepsy: Findings From the Epilepsy Connectome Project Cook CJ, Hwang G, Mathis J, et al. Brain Connect. 2018. doi:10.1089/brain.2018.0600. [Epub ahead of print]; PMID: 30398367 The Epilepsy Connectome Project examines the differences in connectomes between patients with temporal lobe epilepsy (TLE) and healthy controls. Using these data, the effective connectivity of the default mode network (DMN) in patients with left TLE compared to healthy controls was investigated using spectral dynamic causal modeling of...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research

Seizing Sequencing Data to Consider Cell and Circuit Complexity.
Authors: Wick ZC, Krook-Magnuson E Abstract Classes and Continua of Hippocampal CA1 Inhibitory Neurons Revealed by Single-Cell Transcriptomics Harris K, Hochgerner H, Skene NG, et al. PLoS Biol. 2018;16(6):e2006387. doi:10.1371/journal.pbio.2006387. Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes of GABAergic neurons have been proposed to date. However, this list may be incomplete; additionally, it is unclear whether discrete classes are sufficient to describe the diversity of cortical inhibitory neurons or whether continuous mod...
Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research