Epilepsy, it's types and treatment of epilepsy (Anti-epileptic drug) by Fazal Shaikh

EPILEPSY & ANTI-EPILEPTIC DRUG

1. Presented By: Shaikh Fazal Amir M.Pharm (Pharmacology 1 st Year) RGSCOP,Nashik EPILEPSY

2. Definitions Epileptic seizure : a transient occurrence of signs and/or symptoms due to abnormal excessive pattern of excitability and synchrony among neurons in select brain areas . Epilepsy: persistent epileptogenic abnormality of the brain that is able to spontaneously generate paroxysmal activity. [ Recurrent seizures (two or more)which are not provoked by systemic or acute neurologic insults.] Epilepsy syndrome: complex of signs and symptoms that define a unique epileptic condition.

3. Epilepsy is a disease of the brain defined by any of the following conditions. At least two unprovoked (or reflex) seizures occurring >24 hr apart. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years. Diagnosis of an epilepsy syndrome.

4. Seizure Vs Epilepsy Seizure A seizure is the event. Epilepsy Epilepsy is the disease associated with spontaneously recurring seizures.

5. Epilepsy Facts 1 in 26 people will develop epilepsy during their lifetime (3.85%). More common then autism, cerebral palsy, MS and Parkinson’s disease combined.

6. Risk of Epilepsy Highest at extremes of life ( 1st year of life and in elderly ). Risk of having at least 1 seizure in lifetime is 10%, and 1/3 will develop epilepsy.

7. Incidence and Prevalence in Pediatric Population 5 per 1000 in school-aged children. 1.5 per 1000 in preschool-aged children. Affects more then 300,000 children under age 15 yrs.

8. Cellular Mechanisms of Seizure Generation Excitation (too much) I onic --- inward Na+, Ca ++ currents Neurotransmitter --- Glutamate, Aspartate I nhibition (too little) Ionic --- inward Cl-, outward K+ currents Neurotransmitter --- GABA

9. Normal CNS Function

10. Hyper-excitability reflects both increased excitation and decreased inhibition

11. Seizure Classification International League Against Epilepsy (ILAE) 2010 revised classification Based on known causes of epilepsy Genetic Structural/metabolic Unknown cause

12. Seizure types Generalized: Seizures produced by widespread abnormal electrical impulses present throughout the entire brain. Partial (sometimes referred to as focal or Localized): Seizures produced by electrical impulses that generate from a relatively small or “localized” part of the brain (referred to as the focus).

13. Phases of Seizure Seizures take on many different forms and have a beginning (prodrome and aura) middle (ictal) & end (post-ictal) stage.

14. Any of these: Sudden falling Passing out Drooling, frothing at mouth Grunting, snorting Breathing stops temporarily Uncontrollable muscle Spasms Teeth clenching Eye movements Unusual behavior Staring What does a seizure look like?

15. Generalized tonic-clonic (GrandMal) Symptoms: The patient loses consciousness and usually collapses. The loss of consciousness is followed by generalized body stiffening (called the "tonic" phase of the seizure), then by violent jerking called the "clonic" phase of the seizure), after which the patient goes into a deep sleep (called the "postictal” or “after-seizure” phase). During grandmal seizures, injuries and accidents may occur, such as tongue biting and urinary incontinence. Generalized Epilepsy Classifications

16. Absence Symptoms: Brief loss of consciousness (just a few seconds) with few or no symptoms. The patient typically interrupts an actnvuty and stares blankly. These seizures begin and end abruptly and might occur several times a day. Patients are usually not aware that they are having a seizure, but may have a feeling of "losing time.” Generalized Epilepsy Classifications

17. Myoclonic Symptoms: Sporadic and brief jerking movements, usually on both sides of the body. Patients sometimes describe the jerks as brief electrical shocks. When violent, these seizures might result in dropping or involuntarily throwing objects. Generalized Epilepsy Classifications

18. Clonic Symptoms: Repetitive, rhythmic jerking movements that involve both sides of the body at the same time. Tonic Symptoms: Muscle stiffness and rigidity. Atonic Symptoms: Consist of a sudden and general loss of muscle tone, particularly in the arms and legs, which often results in a fall. Generalized Epilepsy Classifications

19. Simple partial (awareness maintained) Symptoms: Simple partial seizures are further divided into four groups according to the nature of their symptoms. 1. Motor Motor symptoms include movements such as jerking, stiffening, muscle rigidity,spasms and head-turning. 2. Sensory Sensory symptoms involve unusual sensations affecting any of the five senses (vision,hearing, smell, taste, or touch). The term “aura” is used to describe sensory symptoms that are present only (and not motor symptoms). Partial Epilepsy Classifications

20. Partial Epilepsy Classifications 3. Autonomic Autonomic symptoms most often involve an unusual sensation in the stomach termed “gastric uprising”. 4. Psychological Psychological symptoms are characterized by various experiences involving memory (the sensation of déja vu), emotions (such as fear or pleasure), or other complex psychological phenomena.

21. Complex partial (awareness impaired) Symptoms: Includes impairment of awareness.Patients seem to be "out of touch," "out of it," or "staring into space" during these seizures. Symptoms may also involve some complex symptoms called automatisms. Automatisms consist of involuntary but coordinated movements that tend to be purposeless and repetitive. Common automatisms include lip smacking, chewing, fidgeting, and walking around. Partial Epilepsy Classifications

22. Partial seizure with secondary generalization Symptoms: A partial seizure that evolves into a generalized seizure(typically a generalized tonic-clonic seizure). Approximately 70% of patients with partial seizures can be controlled with medication. Partial seizures that cannot be controlled with medication can often be treated surgically. Partial Epilepsy Classifications

23. Detailed history and physical examination. EEG, video EEG Imaging ( CT, MRI, PET) Diagnosing Epilepsy

24. History Precipitating factors Aura Area of body first involved Progression of activity Pecific activity observed (head or eye deviation, type of movement or posturing) level of consciousness Incontinence Apnea or cyanosis Duration of seizure Postictal symptoms ( confusion, hemiplegia, aphasia)

25. Missed dose of medication Sleep deprivation IllIness Stress, anxiety, overstimulation Hormonal changes Alcohol and drugs of abuse Hyperventilation Flashing lights Temperature extremes dehydration Seizure Triggers

26. Migraine headache Syncope Behavioral outbursts Breath holding spells Tics Sleep disorders Not everything that looks like a seizure is a seizure

27. Epilepsy is now considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now Fast the applicable age or those who have remained seizure- ree for the last 10 years, with no seizure medicines for the last 5 years. “Resolved" has the connotation of “no longer present,” but it does not guarantee that epilepsy will never come back. Epilepsy Resolved

28. Despite the fact that seizures are “provoked” in reflex epilepsies,these are considered epilepsy, because.., If the seizure threshold were not altered, these precipitants would typically not cause seizures. e.g., photosensitive epilepsy, eating epilepsy Reflex Epilepsies

29. Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B). Clinicians’ recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the adverse events of AED therapy. Management Guideline

30. Management Guideline

31. Febrile seizures in children age 0.5 — 6 years old. Alcohol-withdrawal seizures. Metabolic seizures (sodium, calcium, magnesium, glucose,oxygen) Toxic seizures (drug reactions or withdrawal, renal failure) Convulsive syncope. Acute concussive convulsion. Seizures within first week after brain trauma, infection or stroke These are not Epilepsy because there is small risk of a seizure in the absence of a precipitating factor

32. Acute symptomatic seizures are events, occurring in close temporal relationship with an acute CNS insult, which may be metabolic,toxic, structural, infectious, or due to inflammation. The interval between the insult and seizure may vary due to the underlying clinical condition. Acute symptomatic seizures have also been called: Reactive seizures Provoked seizures Situation-related seizures ILAE Definition of Acute Symptomatic Epilepsy

33. A seizure that lasts longer than 5 minutes, or having more than 1 seizure within a 5 minutes period, without returning to a normal level of consciousness between episodes is called status epilepticus. This is a medical emergency that may lead to permanent brain damage or death. In children, the main cause of status epilepticus is an infection with a fever. Children with severe, refractoryseizure disorders can also have status epilepticus. In adults, the common causes are Stroke. Status Epilepticus

34. References Essentials of medical Pharmacology by KD Tripathi ed.6 th (2008) published by jaypee brothers medical publishers.ltd Lippincott’s Illustrated reviews by Richard D.Howland & Mary J.Mycek ed.3 rd (2006) printed in India by Gopsons Papers Ltd,Noida,India. Rang and Dale’s Pharmacology by HP Rang,M M Dale, J M Ritter, R J Flower & G Henderson, ed.7 th (2012) printed by ELSEVIER CHURCHILI LIVINGSTONE,New york.

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