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Advances in the Diagnosis and Treatment of Epilepsy

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Presentation on theme: "Advances in the Diagnosis and Treatment of Epilepsy"— Presentation transcript:

1 Advances in the Diagnosis and Treatment of Epilepsy
Marcelo E. Lancman, M.D. Director, Epilepsy Program Northeast Regional Epilepsy Group

2 Advances in the Diagnosis and Treatment of Epilepsy
Epilepsy concepts Diagnosing Epilepsy What causes Epilepsy Treating Epilepsy New developments

3 Epilepsy Concepts What is epilepsy? What is a seizure?

4 Incidence Epilepsy 0.5-1% Seizures 5-10%

5 Classification of Seizures
Partial Simple Complex Secondary Generalized Generalized Absence Atonic Clonic Tonic Tonic-clonic Myoclonic

6 Classification of Epilepsy
By Localization Partial Generalized By Cause Idiopathic (unknown) Symptomatic

7 Classification of Epilepsy
Idiopathic Partial Epilepsy Symptomatic Partial Epilepsy Idiopathic Generalized Epilepsy Symptomatic Generalized Epilepsy

8 Idiopathic Generalized Epilepsy
Benign Neonatal Familial Epilepsy Benign Myoclonic Epilepsy of Infancy Generalized epilepsy with febrile seizures plus Epilepsy with myoclonic absence Epilepsy with myoclonic-astatic seizures Childhood absence epilepsy Juvenile absence epilepsy Epilepsy with GTCS only

9 Idiopathic Partial Epilepsy
Benign Rolandic Epilepsy Benign Occipital Epilepsy

10 Symptomatic Generalized Epilepsy
Infantile spasms (West syndrome) Dravet syndrome Lennox-Gastaut syndrome

11 Symptomatic Partial Epilepsy
Temporal Lobe Epilepsy Frontal Lobe Epilepsy Parietal Lobe Epilepsy Occipital Lobe Epilepsy

12 Type of Epilepsy The importance of knowing

13 Diagnosis of Epilepsy Medical History Physical exam

14 Testing Testing Imaging EEG, AEEG, VEEG Labs Genetics
CT, MRI (high definition)

15 Diagnosis Diagnosis is clear: treatment is initiated
Diagnosis unclear: Video-EEG

16 Video-EEG Monitoring Continuous EEG monitoring along with continuous audio-video recording Mostly requires inpatient admission

17 Goals of Video-EEG Monitoring
Epilepsy vs. non-epileptic events Characterize epilepsy type Pre-surgical evaluation

18 Non-Epileptic Events 20 to 30% of patients referred with diagnosis of intractable epilepsy Events that do not have electrical source in brain May have physical or psychological causes that are not epilepsy But CAN also occur in patients who have epilepsy

19 Non-epileptic events Physiologic (other medical conditions)
Fainting, low sugar, changes in electrolytes, toxins, fever. Psychological Referred to psychiatry and neuropsychologist who work with this type of stress-seizure Psychiatric medication, psychotherapy, education

20 Non-epileptic events Conditions that may look like seizures:
TIAs, complicated migraines, movement disorders, sleep disorders, anxiety/panic disorder, vertigo, cardiac disorders, rage attacks, breath-holding spells,

21 What causes of Epilepsy?
The seizure threshold Causes: Genetics, head injury, stroke, tumors, infections, malformations, metabolic disorders (diabetes, thyroid, parathyroid, adrenal), degenerative disorders, perinatal factors and other less common (cardiac, GI, blood, inflammatory, poisons, etc)

22 Seizure Triggers Alcohol, stress, environmental temperature, lights, fever/illness, hormonal changes, hyperventilation, sleep deprivation, medications and supplements, missing medication doses and travel across time zones

23 Treating Epilepsy What is intractable epilepsy?
Despite medical management, patient continues to have frequent, debilitating seizures

24 Seizure Control I discussed on the earlier slide drug resistant epilepsy, or seizures that are hard to controll with medicine, puts a person at higher risk for SUDEP. About 1/3 of people with epilepsy have drug resistant epilepsy. The definition of DRE is where seizures keep occuring despite 2 good trials of seizure medication. A good trial of a seizue medication means that an appropriate medication was used for the patient’s epilepsy and an appropriate dose was achieved. The medication failed because of persistent seizures and not side effects. For example, if the patient was still in the procress of increasing the medication to the target dose, and then had to stop it because of side effects, we wouldn’t call this a drug failure. Also, there are many types of epilepsy, and not all doctors specialize in epilepsy. Different medications work for each type of epilepsy. Sometimes doctors, despite their best intentions, prescribe the wrong seizure medication for a patient’s epilepsy. For example, tegretol for absence seizures, which can make it worse. So, a patient is only drug resistant only if they have tried two or more appropriate medications for their epilepsy and failed them because of persistent seizures.

25 Options for the Intractable Seizure Patient
Medications (combinations) Diets Surgical procedures Stimulators Resections

26 Medications Choices based on epilepsy type, patient profile, side effect profile, cost Best to have patient on single antiepileptic drug (AED) May need polytherapy (combination of medications) Adding meds requires going up slowly with the new agent before discontinuing previous drug Polytherapy requires deep knowledge of interactions

27 How to use polytherapy rationally
Pharmacodynamics (what the medication does to the body) Pharmacokinetics (what the body does to the medications) Absorption Distribution Elimination Half life Liver Kidneys

28 How to use polytherapy rationally
Side effects Dose-related Idiosyncratic (each person is different)

29 Older Medications Carbamazepine (Tegretol) Phenobarbital
Ethosuximide (Zarontin) Phenytoin (Dilantin/Cerebyx) Valproic acid (Depakote) Primidone (Mysoline)

30 Newer AED’s Gabapentin (Neurontin) Lamotrigine (Lamictal)
Topiramate (Topamax) Felbamate (Felbatol) Diastat (Diazepam) Vigabatrin (Sabril) Ezogabine (Potiga) Oxcarbazepine (Trileptal) Pregabalin (Lyrica) Zonisamide (Zonegran) Levetiracetam (Keppra) Lacosamide (Vimpat) Rufinamide (Banzel) Clobazam (Onfi)

31 Medication choices based on epilepsy type…

32 AED’s for Partial Epilepsy
All but Zarontin and Banzel

33 Best AED’s for Generalized Epilepsy
Depakote Keppra Lamictal Topamax Zonegran Banzel

34 Future Medications Brivaracetam Carisbamate Eslicarbazepine Ganaxalone
Losigamone Nitrfazepam Perampanel Piracetam Progabide Remacemide Retigabine Seletracetam Stiripentol

35 What Are Some Promising New Medical Treatments?
Maintenance Treatment Ezogabine (Potiga) Perampanel Vertex Emergency Treatment Intranasal Midazolam

36 Potiga Potassium Channel Opener Partial Seizures
Rare but serious side effects Trial and Error: Every pt is different. We don’t now until we try which will be the right receptors to open and right ones to block Side effects: when you block too many neurotransmitters, channels- you disturb normal brain function and you get side effect. For example if too many NT are blocked you get sleepy and dizzy 1/3: New medication are not any better than old

37 Peramapanel Glutamate Blocker Effective in trials for partial seizures
Side effects: Dizziness, Sleepiness Approved in Europe Under study in US for Generalized Seizure types Under FDA review for Partial Seizures

38 Vx-765 for Partial Epilepsy
New approach to Epilepsy Rx Anti-Inflammatory Short Duration of therapy (weeks instead of years) Oral Medicine Early Clinical Trials Completed Early results encouraging but longer treatment duration to be studied Headache, dizziness, GI most common side effects Only studied for 6 weeks

39 Emergency Treatment Rectal Diastat Clinically proven Hard to give
Adults don’t like Can’t self administer

40 Intranasal Midazolam Easy to give Preferred route
Can be self-administered or given by caretaker Under study Efficacy and Side Effects unknown

41 Advances in Treatment Newermedications Brivaracetam Carisbamate
Clobazam Eslicarbazepine Ganaxalone Losigamone Nitrfazepam Perampanel Piracetam Progabide Remacemide Retigabine Seletracetam Stiripentol

42 For patients that do not respond to medication
Ketogenic diet Surgeries

43 Ketogenic Diet (@1920) High fat, low carbohydrate/protein diet
Requires hospitalization to start it NPO until patient in ketosis Parent education Meds to be taken into account Recommended mainly for young children due to compliance and efficacy

44 Epilepsy Surgery The goals are:
To determine where the seizures are coming from To make sure is safe

45 Epilepsy Surgery To determine where the seizures are coming from
Video-EEG monitoring MRI MRS: PET: SPECT: MEG:

46 Epilepsy Surgery To make sure that it is safe
Wada test: to study speech and memory Neuropsychological testing: mental functions (IQ, memory, attention) and personality assessment Psychological evaluation Ophthalmologic evaluation

47 Epilepsy Surgery Some cases in which the localization is not clear or where function could be affected will require INVASIVE ELECTRODES Depth electrodes Subdural electrodes

48 Types of Epilepsy Surgery
Temporal Lobectomy Extratemporal Resections Hemispherectomy Corpus Callosotomy

49 Outcome after epilepsy surgery
Anterior temporal lobectomy 70-80% seizure free Neocortical resection With lesion: 50-80% seizure free Without lesion: 30-50% seizure free Hemispherectomy Significant improvement Corpus Callosotomy Significant improvement for drop attacks

50 Complications of surgery
Low rate of complications Infections Bleeding Anesthesia Function

51 Vagus Nerve Stimulator (1997)
Intractable epilepsy patient without focus or desires interim step before epilepsy surgery Goal is to reduce amount/severity of seizures vs. cure Device surgically implanted in left chest/axilla area Coils around left vagus nerve Stimulation is automatic; patient can additionally stimulate device if aura

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