DOCSLIB.ORG

Progressive Epilepsy Or… Why Might It Get Worse?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Progressive Epilepsy Or… Why Might It Get Worse? Diseases that provoke epilepsy Michael Doherty, MD FAAN Medical Director Swedish Epilepsy 1 Epilepsy ….a disorder characterized not only by epileptic seizures, but also by its associated biological, psychological, and social conditions. The comorbidities of epilepsy form the core of these associated conditions and contribute to our evolving conceptualization of epilepsy as a spectrum M.R. Keezer, S.M. Sisodiya, J.W. Sander. Comorbidities of epilepsy: current concepts and future perspectives Lancet Neurol.2016: 15.106–115 2 3 Hauser, W. A. & Kurland, L. T. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia. 16, 1–66 (1975). 4 Patrick Kwan, M.D., and Martin J. Brodie, M.D. N Engl J Med 2000; 342:314-319 DOI: 10.1056/NEJM200002033420503 5 36% of patients can’t control their seizure with medication(s)… Patrick Kwan, M.D., and Martin J. Brodie, M.D. N Engl J Med 2000; 342:314-319 DOI: 10.1056/NEJM200002033420503 6 BUT maybe 36% of patients do just about everything right and yet have an ongoing process. i.e. the epilepsy and its comorbidities are not static For one, seizures begat seizures, particularly in the hippocampi… 7 And disease is ubiquitous, will accumulate with age and may alter epilepsy control… 8 Is the epilepsy truly provoked or worsened… 9 EEG clarifies med choices Generalized onset patterns- Absence, myoclonic, primary generalized, MRI - Valproic acid, topiramate, zonisamide, levetiracetam, lamotrigine, phenobarbital excluding carbamazepine, gabapentin, lyrica Focal onset patterns- automatisms, unilateral findings, secondarily generalized, MRI + Most anticonvulsants but for ethosuxamide 10 Pharmacogenomics…if it ever is cheap enough- can lead to smarter med choices Lee SK Old versus New: why do we need new antiepileptic drugs J Epilepsy Res. 2014;4(2):39-44 doi: https://doi.org/10.14581/jer.140102014. 11 Fixing the provider medication error • Incorrect therapy for the incorrect diagnosis – EEG – VEEG- nonepileptic or other events – Cardiac – Proconvulsive meds (buproprion, tramadol, GABA withdrawals) • Not enough medication: Mg vs trough - med levels • Rational polypharmacy • Pharmacy and/or physician substitution or error 12 Fixing the patient medication error… A. Noncompliance B. Confusing regimen C. Cutting long acting? D. Other drugs and substances interact E. Role of all providers checking this https://lompocvmc.com/images/stories/mederrors/mederrors-1.jpg 13 Deeper than the sandbar seals Shark 14 Epilepsy ….a disorder characterized not only by epileptic seizures, but also by its associated biological, psychological, and social conditions. The comorbidities of epilepsy form the core of these associated conditions and contribute to our evolving conceptualization of epilepsy as a spectrum….that may change over time M.R. Keezer, S.M. Sisodiya, J.W. Sander. Comorbidities of epilepsy: current concepts and future perspectives Lancet Neurol.2016: 15.106–115 15 With time/age these diseases may trigger or worsen epilepsy: – tumor – radiation – stroke – trauma and its consequences 16 Tumors contribute to seizure and epilepsy a- swelling b- ischemia c- necrosis d- erosion of inhibitory controls e- proliferation 12 months Liubinas SV, O'Brien TJ, Moffat BM, Drummond KJ, Morokoff AP, Kaye AHTumour associated epilepsy and glutamate excitotoxicity in patients with gliomas.J Clin Neurosci. 2014;21:899-908. 17 If the seizure type changes, surveillance imaging low grade tumors can transform to high grades… Much harder to dx are tumors that may lead to paraneoplastic issues- a process where the immune system keeps the tumor in check but may otherwise contribute to antibody-mediated neurologic worsening 18 Radiation: • About 5.5% of pedi brain tumors that were radiated will go on to develop late epilepsy • That does not include super long-term follow up or things like decades later meningioma formation • Meningioma and stroke are more common post radiation • Nasopharyngeal CA can be particularly nasty • J- shaped curve to gamma knife related epilepsy Passos J, Nzwalo H, Marques J, Azevedo A, Netto E, Nunes S, Salgado D. Late Cerebrovascular Complications After Radiotherapy for Childhood Primary Central Nervous System Tumors.Pediatr Neurol. 2015 Sep;53:211-5. doi: 10.1016/j.pediatrneurol.2015.05.015 19 From: A. Hauser. Incidence and Prevalence. In Epilepsy: A Comprehensive Textbook. Ed. Engel and Pedley 20 Stroke • 11.5% of patients with stroke dx with epilepsy • 11% of all epilepsy etiologies, probably higher if you lump in perinatal complications • Higher likelihood in men, cortical stroke, Afib, COPD, increased severity • Don’t forget “congenital” as potential stroke • Acute risks- increases in intracellular sodium and calcium • Lower threshold for glutamate excitotoxicity, metabolic dysfunction, hypo and hyper perfusion, hemorrhagic byproducts • Late risks: gliosis, hemosiderin, ongoing perfusion issues, MORE LIKELY TO BE recurrent Myint PK, Staufenberg EFA, Sabanathan K. Post‐stroke seizure and post‐stroke epilepsy. Postgraduate Medical Journal. 2006;82(971):568-572. doi:10.1136/pgmj.2005.041426. Lin C-S, Shih C-C, Yeh C-C, et al. Risk of Stroke and Post-Stroke Adverse Events in Patients with Exacerbations of Chronic Obstructive Pulmonary Disease. Cappello F, ed. PLoS ONE. 2017;12(1):e0169429. doi:10.1371/journal.pone.0169429. Kim HJ, Park KD, Choi K-G, Lee HW. Clinical predictors of seizure recurrence after the first post-ischemic stroke seizure. BMC Neurology. 2016;16:212. doi:10.1186/s12883-016-0729-6. 21 Seizures are worse or new? Why not screen for stroke with at minimum MRI or CT head AND consider evaluation of carotid/verterbral flows and other stroke risk factors like BP, lipids, smoking status, HTN etc From: A. Hauser. Incidence and Prevalence. In Epilepsy: A Comprehensive Textbook. Ed. Engel and Pedley Williams GR Incidence and Characteristics of Total Stroke in the United States. BMC Neurol. 2001 Dec 18;1:2. Epub 2001 Dec 18. 22 A 1- Whose epilepsy is likely to be worse and why? B 2- what one drug should both patients be on? 23 24 Trauma Annegers JF, Hauser WA, Coan SP, Rocca WA A polulation based study of seizures after TBI NEJM. 1998;338:20-24. 25 Trauma • 10-20% of epilepsy patients- (at some point it may be self fulfilling for tonic/atonic/drop attack patients) • Independent of consciousness, other predictors are bone fx or knocked-out teeth • Mechanisms – Hypoxia – Increased ICP – Edema – Hemorrhage – Glutamate excitotoxicity – Hippocampal interneurons are lost – Decreased GABA-ergic activities Lucke-Wolde B, Nguyen L et al TBI and Epilepsy, underlying mechanisms leading to seizure. Seizure.2015:33;13-23. 26 Trauma seizure more trauma WA state 6 months freedom from consciousness impairing events before driving . Illinois no set time frame before driving! Blues brothers, Universal Pictures, 1980 http://www.imfdb.org/images/thumb/5/54/BB-COPCAR-5.jpg/601px-BB-COPCAR-5.jpg 27 Trauma • Like stroke, may have early or late seizure, with later onset seizures more likely to become refractory epilepsy • Micro RNA disruption helps iron-induced glutamate toxicity • AKT activated, phosphorlyates MTOR1c- cell death • Toll-like receptors and Toll Ligands contribute to glutamate toxicity AND help promote gliosis • TAU hyperphosphorylizes- neurodegeneration – A-Type K channels disrupted, alter hippocampal functions Lucke-Wolde B, Nguyen L et al TBI and Epilepsy, underlying mechanisms leading to seizure. Seizure.2015:33;13-23. 28 Trauma The initial acute injury (hours– days) induces glutamate excitability and sclerosis. Reactive oxygen species are generated from the resulting hyperexcitability, which damage the cell. This process is regulated by microRNAs. In days–weeks inflammation occurs from activated toll-like receptors and non-NMDA glutamate receptors. These further insults exacerbate the damage caused by glutamate toxicity and allow free iron to enter the cell. In months to years this injury contributes to tau aggregation. Tau interacts with zinc to generate further free radical damage reducing the threshold for late onset seizure. Lucke-Wolde B, Nguyen L et al TBI and Epilepsy, underlying mechanisms leading to seizure. Seizure.2015:33;13-23. 29 Isn’t Tau more of a degenerative marker? • Tau changes from soluble to insoluble and accumulates in neurons, disrupts microtubules and ultimately cellular connections • Different patterns with Alzheimer disease and Chronic traumatic encephalopathy (CTE) AND patients with TLE and secondarily generalized seizures – tau pathologies in 33 patients aged 50-65 who had resection (subpial, hippocampal) • Neuropil threads • Neurofibrillary tangles • Neurofibrillary Pretangles – Ie a mix of Alzheimer and CTE findings in refractory epilepsy patients! – More tau, more verbal declines post-op Tai XY, Koepp M, Duncan JS, Fox N, Thompson P, Baxendale S, Liu JY, Reeves C, Michalak Z, Thom M. Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections Brain. 2016;139:2441-55 30 Not-so obvious things that can worsen epilepsy… • Genetics- expensive, rapidly evolving • Inflammatory • Respiratory- easy to screen • Mood and depression At the very end we are going to combine some of these multipliers into a very specific case study to show how complex these interactions get 31 2014 Thomas RH, Berkovic SF Thomas RH, Berkovic SF The Hidden genetics of Epilepsy- a clinically important new paradigm. Nature Reviews Neurology 2014;10:283-292 32 Genetics/pathways • JAK/STAT pathway- injury susceptible-
Load more

Recommended publications
  • Case Study: Right Temporal Lobe Epilepsy
    Case Study: Right temporal lobe epilepsy Group Members • Rudolf Cymorr Kirby P. Martinez • Yet dalen • Rachel Joy Alcalde • Siriwimon Luanglue • Mary Antonette Pineda • Khayay Hlaing • Luch Bunrattana • Keo Sereymonica • Sikanal Chum • Pyone Khant khant • Men Puthik • Chheun Chhorvy Advisers: Sudasawan Jiamsakul Janyarak Supat 2 Overview of Epilepsy 3 Overview of Epilepsy 4 Risk Factor of Epilepsy 5 Goal of Epilepsy Care 6 Case of Patient X Patient Information & Hx • Sex: Female (single) • Age: 22 years old • Date of admission: 15 June 2017 • Chief Complaint: Jerking movement of all 4 limbs • Past Diagnosis: Temporal lobe epilepsy • No allergies, family history & Operation Complete Vaccination. (+) Developmental Delay Now she can take care herself. Income: Helps in family store (can do basic calculation) History Workup Admission Operation ICU Female Surgery D/C 7 • Sex: Female Case of Patient X • Age: 22 years old • CC: Jerking movement of all 4 limbs History Past Present History Workup Admission Operation ICU Female Surgery D/C 8 • Sex: Female Case of Patient X • Age: 22 years old • CC: Jerking movement of all 4 limbs Past Present (11 mos) (+) high fever. Prescribed AED for 2-3 Treatment at Songkranakarin Hosp. mos. After AED stops, no further episode Prescribe AED but still with 4-5 ep/mos 21 yrs 6 yrs Present PTA PTA (15 y/o) (+) jerking movement (15 y/o) (+) aura as jerking Now 2-3 ep/ mos both arms and legs with LOC movement at chin & headache Last attack 2 mos for 5 mins. Drowsy after attack ago thus consult with no memory of attack 15-17 episode/ mos History Workup Admission Operation ICU Female Surgery D/C 9 • Sex: Female Case of Patient X • Age: 22 years old • CC: Jerking movement of all 4 limbs Past Present 2 months prior to admission, she had jerking movement both arms and legs, blinking both eyes, corner of the mouth twitch, and drool.
    [Show full text]
  • Long-Term Results of Vagal Nerve Stimulation for Adults with Medication-Resistant
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Seizure 22 (2013) 9–13 Contents lists available at SciVerse ScienceDirect Seizure jou rnal homepage: www.elsevier.com/locate/yseiz Long-term results of vagal nerve stimulation for adults with medication-resistant epilepsy who have been on unchanged antiepileptic medication a a, b a c a Eduardo Garcı´a-Navarrete , Cristina V. Torres *, Isabel Gallego , Marta Navas , Jesu´ s Pastor , R.G. Sola a Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Universidad Auto´noma, Madrid, Spain b Division of Neurosurgery, Hospital Nin˜o Jesu´s, Madrid, Spain c Department of Physiology, University Hospital La Princesa, Madrid, Spain A R T I C L E I N F O A B S T R A C T Article history: Purpose: Several studies suggest that vagal nerve stimulation (VNS) is an effective treatment for Received 15 July 2012 medication-resistant epileptic patients, although patients’ medication was usually modified during the Received in revised form 10 September 2012 assessment period. The purpose of this prospective study was to evaluate the long-term effects of VNS, at Accepted 14 September 2012 18 months of follow-up, on epileptic patients who have been on unchanged antiepileptic medication. Methods: Forty-three patients underwent a complete epilepsy preoperative evaluation protocol, and Keywords: were selected for VNS implantation. After surgery, patients were evaluated on a monthly basis, Vagus nerve increasing stimulation 0.25 mA at each visit, up to 2.5 mA. Medication was unchanged for at least 18 Epilepsy months since the stimulation was started.
    [Show full text]
  • God and the Limbic System from Phantoms in the Brain, by V.S
    Imagine you had a machine, a helmet of sorts that you could ... http://www.historyhaven.com/TOK/God and the Limbic Syst... God and the Limbic System From Phantoms in the Brain, by V.S. Ramachandran Imagine you had a machine, a helmet of sorts that you could simply put on your head and stimulate any small region of your brain without causing permanent damage. What would you use the device for? This is not science fiction. Such a device, called a transcranial magnetic stimulator, already exists and is relatively easy to construct. When applied to the scalp, it shoots a rapidly fluctuating and extremely powerful magnetic field onto a small patch of brain tissue, thereby activating it and providing hints about its function. For example, if you were to stimulate certain parts of your motor cortex, different muscles would contract. Your finger might twitch or you'd feel a sudden involuntary, puppetlike shrugging of one shoulder. So, if you had access to this device, what part of your brain would you stimulate? If you happened to be familiar with reports from the early days of neurosurgery about the septum-a cluster of cells located near the front of the thalamus in the middle of your brain-you might be tempted to apply the magnet there. Patients "zapped" in this region claim to experience intense pleasure, "like a thousand orgasms rolled into one." If you were blind from birth and the visual areas in your brain had not degenerated, you might stimulate bits of your own visual cortex to find out what people mean by color or "seeing." Or, given the well-known clinical observation that the left frontal lobe seems to be involved in feeling "good," maybe you'd want to stimulate a region over your left eye to see whether you could induce a natural high.
    [Show full text]
  • Surgical Alternatives for Epilepsy (SAFE) Offers Counseling, Choices for Patients by R
    UNIVERSITY of PITTSBURGH NEUROSURGERY NEWS Surgical alternatives for epilepsy (SAFE) offers counseling, choices for patients by R. Mark Richardson, MD, PhD Myths Facts pilepsy is often called the most common • There are always ‘serious complications’ from Epilepsy surgery is relatively safe: serious neurological disorder because at epilepsy surgery. Eany given time 1% of the world’s popula- • the rate of permanent neurologic deficits is tion has active epilepsy. The only potential about 3% cure for a patient’s epilepsy is the surgical • the rate of cognitive deficits is about 6%, removal of the seizure focus, if it can be although half of these resolve in two months identified. Chances for seizure freedom can be as high as 90% in some cases of seizures • complications are well below the danger of that originate in the temporal lobe. continued seizures. In 2003, the American Association of Neurology (AAN) recognized that the ben- • All approved anti-seizure medications should • Some forms of temporal lobe epilepsy are fail, or progressive and seizure outcome is better when efits of temporal lobe resection for disabling surgical intervention is early. seizures is greater than continued treatment • a vagal nerve stimulator (VNS) should be at- with antiepileptic drugs, and issued a practice tempted and fail, before surgery is considered. • Early surgery helps to avoid the adverse conse- parameter recommending that patients with quences of continued seizures (increased risk of temporal lobe epilepsy be referred to a surgi- death, physical injuries, cognitive problems and cal epilepsy center. In addition, patients with lower quality of life. extra-temporal epilepsy who are experiencing • Resection surgery should be considered before difficult seizures or troubling medication side vagal nerve stimulator placement.
    [Show full text]
  • Temporal Lobe Epilepsy: Clinical Semiology and Age at Onset
    Original article Epileptic Disord 2005; 7 (2): 83-90 Temporal lobe epilepsy: clinical semiology and age at onset Vicente Villanueva, José Maria Serratosa Neurology Department, Fundacion Jimenez Diaz, Madrid, Spain Received April 23, 2003; Accepted January 20, 2005 ABSTRACT – The objective of this study was to define the clinical semiology of seizures in temporal lobe epilepsy according to the age at onset. We analyzed 180 seizures from 50 patients with medial or neocortical temporal lobe epilepsy who underwent epilepsy surgery between 1997-2002, and achieved an Engel class I or II outcome. We classified the patients into two groups according to the age at the first seizure: at or before 17 years of age and 18 years of age or older. All patients underwent intensive video-EEG monitoring. We reviewed at least three seizures from each patient and analyzed the following clinical data: presence of aura, duration of aura, ictal and post-ictal period, clinical semiology of aura, ictal and post-ictal period. We also analyzed the following data from the clinical history prior to surgery: presence of isolated auras, frequency of secondary generalized seizures, and frequency of complex partial seizures. Non-parametric, chi-square tests and odds ratios were used for the statistical analysis. There were 41 patients in the “early onset” group and 9 patients in the “later onset” group. A relationship was found between early onset and mesial tempo- ral lobe epilepsy and between later onset and neocortical temporal lobe epilepsy (p = 0.04). The later onset group presented a higher incidence of blinking during seizures (p = 0.03), a longer duration of the post-ictal period (p = 0.07) and a lower number of presurgical complex partial seizures (p = 0.03).
    [Show full text]
  • National Institute of Mental Health & Neurosciences
    National Institute of Mental Health & Neurosciences (Institute of National Importance), Bengaluru-560029 राष्ट्रि य मानष्ट्िक स्वास्थ्य एवं तंष्ट्िका ष्ट्वज्ञान िंथान, (राष्ट्रि य महत्व का िंथान), बᴂगलूर - 560029 ರಾಷ್ಟ್ರೀಯ ಮಾನಸಿಕ ಆರ ೀಗ್ಯ ಮ郍ತು ನರ 풿ಜ್ಞಾನ ಸಂ ೆ, (ರಾಷ್ಟ್ರೀಯ ꣍ಾಾಮತಖ್ಯತಾ ಸಂ )ೆ , ಬ ಂಗ್ಳೂರತ- 560029 FAQ on Epilepsy What is Seizure? Seizure is a general term and people call their seizures by different names – such as a fit, convulsion, funny turn, attack or blackout. It can happen due to variety of reasons like low blood sugar, liver failure, kidney failure, and alcohol intoxication among others. A person with epilepsy can also manifest with seizure. What is epilepsy? Epilepsy is a neurological disorder of the brain (not mental illness) where in patients have a tendency to have recurrent seizures. Seizure is like fever – due to various causes; while epilepsy is a definite diagnosis like fever due to typhoid, malaria. How many people have epilepsy? Epilepsy is the one of the most common neurological condition and may affect 1% of the population. Which means there are at least 10 million epilepsy patients in our country. What causes epilepsy? Anyone can develop epilepsy; it occurs in all ages, races and social classes. It is due to sudden burst of abnormal electrical discharges from the brain. In a great majority of patients, one does not know the cause for this. The causes of epilepsy can be put into three different groups: a) Symptomatic epilepsy: when there is a known cause for a person's epilepsy starting it is called symptomatic epilepsy.
    [Show full text]
  • Transcriptome Analysis Reveals Higher Levels of Mobile Element-Associated Abnormal Gene Transcripts in Temporal Lobe Epilepsy Patients
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.14.444199; this version posted May 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Transcriptome analysis reveals higher levels of mobile element-associated abnormal gene transcripts in temporal lobe epilepsy patients Kai Hu a,b,*, Ping Liang b,** a Department of Neurology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, Hunan 410008, China b Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, L2S 3A1, Ontario, Canada * Corresponding author at: Department of Neurology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, Hunan, China 410008 ** Corresponding author at: Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario, Canada, L2S 3A1 Email addresses: [email protected] (Kai Hu), [email protected] (Ping Liang). bioRxiv preprint doi: https://doi.org/10.1101/2021.05.14.444199; this version posted May 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract: Objective: To determine role of abnormal splice variants associated with mobile elements in epilepsy. Methods: Publicly available human RNA-seq-based transcriptome data for laser- captured dentate granule cells of post-mortem hippocampal tissues from temporal lobe epilepsy patients with (TLE, N=14 for 7 subjects) and without hippocampal sclerosis (TLE-HS, N=8 for 5 subjects) and healthy individuals (N=51), surgically resected bulk neocortex tissues from TLE patients (TLE-NC, N=17).
    [Show full text]
  • Advances in the Surgical Management of Epilepsy Drug-Resistant Focal Epilepsy in the Adult Patient
    Advances in the Surgical Management of Epilepsy Drug-Resistant Focal Epilepsy in the Adult Patient a, b Gregory D. Cascino, MD *, Benjamin H. Brinkmann, PhD KEYWORDS Epilepsy Drug-resistant Neuroimaging Surgical treatment KEY POINTS Pharmacoresistant seizures may occur in nearly one-third of people with epilepsy, and Intractable epilepsy is associated with an increased mortality. Medial temporal lobe epilepsy and lesional epilepsy are the most favorable surgically remediable epileptic syndromes. Successful epilepsy surgery may render the patient seizure-free, reduce antiseizure drug(s) adverse effects, improve quality of life, and decrease mortality. Surgical management of epilepsy should not be considered a procedure of “last resort.” Epilepsy surgery despite the results of randomized controlled trials remains an underutil- ized treatment modality for patients with drug-resistant epilepsy. INTRODUCTION Epilepsy is one of the most common chronic neurologic disorders affecting nearly 65 million people in the world.1 It is estimated that approximately 1.2% of individuals in the United States, or approximately 3.4 million people, have seizure disorders.1 This includes almost 3 million adults and 470,000 children.1,2 More than 200,000 individuals in the United States will experience new-onset seizure disorders each year. Nearly 10% of people will have 1 or more seizures during their lifetime.1–3 The 2012 Institute of Medicine of the National Academy of Sciences report indicated that 1 in 26 Amer- icans will develop a seizure disorder during their lifetime; this is double the risk of those with Parkinson disease, multiple sclerosis, and autism spectrum disorder combined.3 The diagnosis of epilepsy may include patients with 2 or more unprovoked seizures or a Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; b Mayo Clinic, Depart- ment of Neurology, 200 First Street Southwest, Rochester, MN 55905, USA * Corresponding author.
    [Show full text]
  • Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy
    The Journal of Neuroscience, July 15, 2002, 22(14):5797–5802 Brief Communication Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy Carola A. Haas,1 Oliver Dudeck,2 Matthias Kirsch,1 Csaba Huszka,1 Gunda Kann,1 Stefan Pollak,3 Josef Zentner,2 and Michael Frotscher1 1Institute of Anatomy, 2Department of Neurosurgery, and 3Institute of Forensic Medicine, University of Freiburg, D-79001 Freiburg, Germany The reelin signaling pathway plays a crucial role during the lobe epilepsy. These results suggest that reelin is required for development of laminated structures in the mammalian brain. normal neuronal lamination in humans, and that deficient reelin Reelin, which is synthesized and secreted by Cajal–Retzius expression may be involved in migration defects associated cells in the marginal zone of the neocortex and hippocampus, is with temporal lobe epilepsy. proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin mRNA by hip- Key words: human hippocampus; extracellular matrix; neuro- pocampal Cajal–Retzius cells correlates with the extent of mi- nal migration disorder; Cajal–Retzius cells; dentate gyrus; Am- gration defects in the dentate gyrus of patients with temporal mon’s horn sclerosis Newborn forebrain neurons migrate from their site of origin to reelin pathway underlie neuronal migration defects in reeler mu- their definitive positions in the cortical plate. Defects in neuronal tants and in humans with TLE. migration are often associated with epileptic disorders (Palmini et To this end, we have studied the expression of reelin, VLDLR, al., 1991). Temporal lobe epilepsy (TLE), one of the most com- ApoER2, and dab1 in tissue samples of hippocampus removed mon neurological disorders in humans (Margerison and Corsellis, from TLE patients for therapeutic reasons.
    [Show full text]
  • Surgical Treatment of Mesial Temporal Lobe Epilepsy: Selective
    dos Santos et al. Neurosurg Cases Rev 2018, 1:006 Volume 1 | Issue 1 Open Access Neurosurgery - Cases and Reviews ORIGINAL ARTICLE Surgical Treatment of Mesial Temporal Lobe Epilepsy: Selective Amygdalohippocampectomy Using Niemeyer’s Approach Adriana Rodrigues Libório dos Santos1*, Gabriel Mufarrej1, Priscila Oliveira da Conceição2, Paulo Luiz da Costa Cruz1, Daniel Dutra Cavalcanti1, Leila Chimelli3 and Paulo Niemeyer Filho1 1Department of Neurosurgery, State Brain Institute Paulo Niemeyer, Rio de Janeiro, Brazil 2Department of Neurology, State Brain Institute Paulo Niemeyer, Rio de Janeiro, Brazil Check for 3Department of Neuropathology, State Brain Institute Paulo Niemeyer, Rio de Janeiro, Brazil updates *Corresponding author: Adriana Rodrigues Libório dos Santos, MD, Institution: State Brain Institute Paulo Niemeyer/ Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Neurosurgery Department, Rio de Janeiro, Brazil to treat pathology. Seizure is derived from the Greek Abstract and seize means “capture” or “take ownership”. Epi- Objective: Selective Amygdalohippocampectomy (SAH) is lepsy encompasses several types of disorders with dif- a widespread technique for Mesial Temporal Lobe Epilepsy (MTLE) treatment. Dr. Niemeyer was the first to describe ferent symptoms, and clinical manifestations [1-3]. The SAH using transventricular approach technique in 1958. In International League Against Epilepsy (ILAE) defines ep- 2018, we celebrate 60 years of the original description of ilepsy as “two or more recurrent seizures over a period Niemeyer’s approach. This study reviews the approach in greater than 24 hours, without a clear set cause”. The light of currently technology and shows the results achieved with patients submitted to SAH following Niemeyer’s ap- Term Temporal Lobe Epilepsy (TLE) was introduced in proach at Instituto Estadual do Cérebro Paulo Niemeyer the ILAE classification in 1989 as the group of “Symp- (IECPN)*.
    [Show full text]
  • Topiramate and Temporal Lobe Epilepsy: an Open-Label Study
    Original article Epileptic Disord 2012; 14 (2): 163-6 Topiramate and temporal lobe epilepsy: an open-label study Angelo Labate 1, Antonio Siniscalchi 2, Laura Mumoli 1, Umberto Aguglia 1, Aldo Quattrone 1, Antonio Gambardella 3 1 Institute of Neurology, University Magna Græcia, Catanzaro 2 Department of Neuroscience, Neurology Division, Annunziata Hospital, Cosenza 3 Institute of Neurological Sciences, National Research Council, Cosenza, Italy Received November 12, 2011; Accepted February 29, 2012 ABSTRACT – Purpose. To evaluate the efficacy and tolerability of topiramate (TPM) as monotherapy for patients with temporal lobe epileptic seizures based on an observational study. Methods. We evaluated 41 patients (20 female, mean age 54+18 years) with temporal lobe epilepsy (TLE) referred to the Epilepsy Unit, University of Catanzaro, Italy.Patients received TPM as monotherapy directly or after having taken other antiepileptic drugs. Seizure frequency changes and adverse events were recorded. Follow-up was conducted for a period of at least two years after treatment. Results. Patients received TPM, 50-600 mg/day, de novo (n=29) or initially as add-on therapy before the switch (n=12). In total, 28 of 41 patients achieved seizure freedom, whereas 10 showed a ≥50% reduction of seizure fre- quency. Two patients did not respond well and one patient discontinued TPM due to adverse effects. Conclusions. Our results confirm that TPM as either monotherapy or add-on therapy at doses of 50-600 mg/day effectively reduces seizure frequency in TLE. TPM is particular effective and very well tolerated in patients with mild TLE. Key words: topiramate, temporal lobe epilepsy, antiepileptic drugs Topiramate (TPM) is derived from tive therapy with standard AEDs D-fructose, initially used as an have demonstrated that TPM has antidiabetic drug.
    [Show full text]
  • Brains, Minds, and Computers in Literary and Science Fiction Neuronarratives
    BRAINS, MINDS, AND COMPUTERS IN LITERARY AND SCIENCE FICTION NEURONARRATIVES A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy. by Jason W. Ellis August 2012 Dissertation written by Jason W. Ellis B.S., Georgia Institute of Technology, 2006 M.A., University of Liverpool, 2007 Ph.D., Kent State University, 2012 Approved by Donald M. Hassler Chair, Doctoral Dissertation Committee Tammy Clewell Member, Doctoral Dissertation Committee Kevin Floyd Member, Doctoral Dissertation Committee Eric M. Mintz Member, Doctoral Dissertation Committee Arvind Bansal Member, Doctoral Dissertation Committee Accepted by Robert W. Trogdon Chair, Department of English John R.D. Stalvey Dean, College of Arts and Sciences ii TABLE OF CONTENTS Acknowledgements ........................................................................................................ iv Chapter 1: On Imagination, Science Fiction, and the Brain ........................................... 1 Chapter 2: A Cognitive Approach to Science Fiction .................................................. 13 Chapter 3: Isaac Asimov’s Robots as Cybernetic Models of the Human Brain ........... 48 Chapter 4: Philip K. Dick’s Reality Generator: the Human Brain ............................. 117 Chapter 5: William Gibson’s Cyberspace Exists within the Human Brain ................ 214 Chapter 6: Beyond Science Fiction: Metaphors as Future Prep ................................. 278 Works Cited ...............................................................................................................
    [Show full text]