CNS_L13_Epilepsy.pdf

Neurophysiological disorders (epilepsy) Dr. Jose Sapien, MD. Lecturer Seizure: Transient occurrence of signs and/or symptoms due to abnormal hyper-synchronization of neurons. Can be a symptom of acute insult to the brain such as: Alcohol and illicit drug use/withdrawal. Brain injury/abnormality (tum...

Neurophysiological disorders (epilepsy) Dr. Jose Sapien, MD. Lecturer Seizure: Transient occurrence of signs and/or symptoms due to abnormal hyper-synchronization of neurons. Can be a symptom of acute insult to the brain such as: Alcohol and illicit drug use/withdrawal. Brain injury/abnormality (tumor, trauma, vascular). CNS infection - fever (children). Metabolic (hypoglycemia, electrolyte abnormalities, liver/renal failure), medications, or be a genetic or inherited cause. 2 Epilepsy: Disorder of the brain predisposed to generate epileptic seizures. (transitory disturbance of the functions of the brain that develops suddenly, ceases spontaneously, and can be induced by several different provocations). The ILAE (The International League Against Epilepsy) and the International Bureau for Epilepsy (IBE) have recently agreed that epilepsy is best considered to be a disease. 3 4 Reflex: The tendency to respond repeatedly to such stimuli with seizures meets the conceptual definition of epilepsy = i.e. Fever or concussion vs Photo stimuli. Multiple seizures in 24h? Some authorities consider epilepsy to be present, but in remission, after 5 years of seizure freedom… but not for diagnosis. 5 After a single unprovoked seizure, the risk for another is 40–52%. With two unprovoked nonfebrile seizures, the chance by 4 years of having another is 73%. Epilepsy is considered to be resolved if a person has been seizure-free for the last 10 years, with at least the last 5 year off antiseizure medicines. 6 Classification Epilepsy classification is the key clinical tool in evaluating an individual who is presenting with seizures. Provide a framework for understanding: The type of seizures The other seizure types that are more likely to occur in that individual The potential triggers for their seizures Their prognosis The risks of comorbidities (intellectual disability, psychiatric features such as autism spectrum disorder, and mortality risk such as sudden unexpected death in epilepsy (SUDEP). The selection of antiepileptic therapies. 7 Classification Classification of seizure type and epilepsy type both take into account the results of investigations such as electroencephalography (EEG) and neuroimaging studies together with other studies exploring the underlying etiology of the epilepsy. 8 Classification of the Epilepsies The new Classification of the Epilepsies is a multilevel classification based on resources available: Seizure type Epilepsy type Epilepsy syndrome 9 Seizure Classification (textbook) Generalized or partial (focal) Simple or complex Copyright © 2024 Edmonton Epilepsy Association 10 11 12 Focal Epilepsies include unifocal and multifocal disorders as well as seizures involving one hemisphere. A range of seizure types can be seen including focal aware seizures, focal impaired awareness seizures, focal motor seizures, focal non-motor seizures, and focal to bilateral tonic–clonic seizures. Generalized epilepsies may have a range of seizure types (absence, myoclonic, atonic, tonic, and tonic– clonic seizures). 13 Diagnosis The diagnosis of epilepsy is made on clinical grounds + the finding of typical interictal EEG discharges. 14 Model for the generation of an epileptic discharge 1. Interictal Activity: Before a seizure occurs, there is an interictal activity characterized by a depolarizing shift in the membrane potential of neurons, accompanied by action potentials. This activity arises from a group of neurons firing together. 15 2. Hyperpolarization: Following the depolarization, there is a period of hyperpolarization during which the same neurons activate local inhibitory interneurons. This hyperpolarization phase temporarily suppresses neuronal activity in the affected area. 3. Shortened Hyperpolarization: With repeated interictal spikes, the period of hyperpolarization becomes shorter. This results in the activation of normally inactive ion channels within neurons and an increase in extracellular potassium ions, both of which further depolarize the neurons. 16 4. Synchronous Discharges: If a sufficient number of neurons become activated, and the inhibition from local inhibitory interneurons is overcome, synchronous discharges occur across populations of neurons. This synchronous activity spreads throughout the brain and leads to the manifestation of a seizure. 5. Termination of Seizure: The seizure is eventually terminated by active processes of inhibition within the neurons themselves, mediated by ion channels, and within the neuronal network by the activity of GABAergic interneurons. GABA is the primary inhibitory neurotransmitter in the brain and helps regulate neuronal excitability. 17 Seizure characteristics Automatisms such as chewing, swallowing, lipsmacking scratching, fumbling, running, disrobing, and other stereotypic movements Other forms: dysphasic, dysmnesic (déjà vu), cognitive (disorientation of time sense), affective (fear, anger), illusions, structured hallucinations (music, scenes, taste, smells), epigastric fullness. 18 Absence (petit mal): usually seen in children, unresponsive for 5-10 s with arrest of activity, staring, blinking or eye-rolling. Clonic: whole body repetitive rhythmic jerking movements Tonic: whole body muscle rigidity in flexion or extension Tonic-clonic (Grand mal) Myoclonic. 19 20 Treatment Avoid precipitating factors Enhancement of GABA-mediated inhibition (benzodiazepines, vigabatrin, phenobarbital, tiagabine). Use-dependent blockade of sodium channels (phenytoin, carbamazepine, valproate, lamotrigine). Inhibition of a spike generating Ca2+ current in thalamic neurones (ethosuximide, valproate and lamotrigine). 21 Treatment A small proportion of refractory patients benefit from a surgical approach, especially if an underlying structural lesion is identified. The most common operation is temporal lobe resection, which has a 60–70% chance of making the patient seizure-free. 22 What is Status Epilepticus?? 23 Additional bibliography Mirali, S., Ayesh Seneviratne, & Thieme Medical Publishers, Inc. (Im Thieme Verlag Kg. (2020). Essential Med Notes 2020 Comprehensive Medical Reference & Review for USMLE II and MCCQE. New York Thieme Medical Publishers. Fisher, R. S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J. H., Elger, C. E., Engel, J., Forsgren, L., French, J. A., Glynn, M., Hesdorffer, D. C., Lee, B. I., Mathern, G. W., Moshé, S. L., Perucca, E., Scheffer, I. E., Tomson, T., Watanabe, M., & Wiebe, S. (2014). ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia, 55(4), 475– 482. https://doi.org/10.1111/epi.12550 Scheffer, I. E., Berkovic, S., Capovilla, G., Connolly, M. B., French, J., Guilhoto, L., Hirsch, E., Jain, S., Mathern, G. W., Moshé, S. L., Nordli, D. R., Perucca, E., Tomson, T., Wiebe, S., Zhang, Y., & Zuberi, S. M. (2017). ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 58(4), 512–521. https://doi.org/10.1111/epi.13709 24