Epilepsy

EPILEPSY & ANTIEPILEPTIC DRUGS

Definitions

Seizure: The clinical manifestation of an abnormal, excessive excitation and synchronization of a population of cortical neurons

Epilepsy: Recurrent seizures (two or more) which are not provoked by systemic or acute neurologic insults

Epilepsy: the 2014 Operational Definition (ILAE) At least two unprovoked (or reflex) seizures occurring >24 h apart One unprovoked seizure and a (estimated) probability of occurrence

of further seizures of (approximately) 60% over the next 10 years. Diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who had an

age-dependent epilepsy syndrome but are now past the applicable age or those whohave remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years.

Indians with Epilepsy

Estimated that there are 6 to 8 million Indian citizens with epilepsy.

Approximately 50,000 new cases are added annually 3 to 4 million (assuming a national average treatment gap of 50

%) remain untreated

Global epilepsy prevalence in 2005

Epilepsy - India

It is estimated that there are >10 million persons with epilepsy in India

Prevalence: about 1% of population, this being higher in the rural (1.9%) as compared with the urban population (0.6%)

In the Bangalore Urban Rural Neuro-Epidemiological Survey (BURNs), a prevalence rate of 8.8/1,000 population was observed, with the rate in rural communities being twice that of urban

PARTIAL ONSET IMPLIES FOCAL CORTICAL ORIGIN SIMPLE PARTIAL (including aura)

No alteration of consciousness/amnesia Focal features (motor/sensory/higher cort.)

COMPLEX PARTIAL Altered consciousness/amnesia Motor arrest, automatisms

SPS -> CPS, SPS -> GTCS SPS -> CPS -> GTCS

Seizure Etiology according to Age

Age group Common CauseNeonates(<1 month) Perinatal hypoxia, metabolic disturbances,

intracranial hemorrhageInfants and children (>1 month and <12 years)

Febrile seizures, genetic disorders, developmental disoders

Adolescents (12–18 years) Infection, Trauma, Genetic disorders, Brain tumor

Young adults (18–35 years) Trauma, Alcohol withdrawalIllicit drug use, Brain tumor

Older adults (>35 years) Cerebrovascular disease, Brain tumor, Alcohol withdrawalMetabolic disorders, Alzheimer’s disease

When obtaining a history of epilepsy or suspected epilepsy, the following points must be clarified:

1. What is the first event in the seizure (aura, initial movement or sensation)?

2. Subsequent evolution of the episode. 3. Postictal manifestations: Focal (Todd’s palsy) or diffuse and non-

specific. 4. Is there more than one seizure type? Patients will come for medical

care with their first GTC but may well ignore previous minor seizures (myoclonic or focal).

5. Onset and duration of the disorder. 6. Precipitating or triggering factors (alcohol, sleep deprivation,

menstrual phase). 7. Medications, if any, and response to them. 8. Family history (parents, offspring, siblings) of epilepsy or other

neurological or psychiatric disease. 9. Is there a history of neonatal or febrile seizures? Previous brain injury?

When obtaining a history of epilepsy or suspected epilepsy, the following points must be clarified:

The following conditions can be mistaken for seizures: • Syncope • Panic attacks • Hypoglycaemic attacks • Transient ischaemic attacks • Physiological jerks during sleep • Breath holding spells in children

Difference between seizures and syncope

Epilepsy management

Epilepsy management

Pharmacotherapy Surgery Lifestyle

modification

Management of epilepsy

Management of epilepsy involves control of seizures with the most appropriate anti-epileptic drug (AED) without causing any significant side effects.

Treatment is started after confirmation of diagnosis of epilepsy. Treatment is initiated after the occurrence of two or more

unprovoked seizures, after discussion about the risks and benefits with the family members of the patients.

Goals & Principles in Treatment of Epilepsy

Multimodal Therapy

Treatment of underlying conditions

Avoidance of precipitating factors eg. Sleep deprivation, alcohol intakeSuppression of recurrent seizures by prophylactic therapy with antiepileptic medications or surgery

Addressing a variety of psychological and social issues

When to initiate antiepileptic drug therapy

Antiepileptic drug therapy should be started in any patient with recurrent seizures of unknown etiology or a known cause that cannot be reversed

Balance needs to be established between potential negative consequences of seizure recurrence and potential adverse effects of antiepileptic drugsThe overall goal is to completely prevent seizures without causing any untoward side effects, preferably with a single medication and a dosing schedule that is easy for the patient to follow

The following are the circumstances where single seizure may need treatment:

1. Prolonged focal seizure 2. First seizure presenting as status epilepticus (SE) 3. Presence of focal neurological deficits 4. Family history of seizures 5. Electroencephalogram (EEG) abnormality 6. Abnormal brain imaging 7. High-risk jobs 8. The individual and family do not accept the expected risk of recurrence

Anti epileptic drugs

AEDs primarily act by blocking the initiation of spread of seizures. This occurs through a variety of mechanisms that modify the activity

of ion channels or neurotransmitters. The mechanisms include: Inhibition of Na dependent action potential in a frequency dependent manner

(e.g., PH, CBZ, LTG, TP, ZN) Inhibition of voltage gated Ca channel (PH) Decrease of glutamate release (LTG) Potentiation of GABA receptor function (BZDs and Barbiturates), Increasing the availability of GABA (VPA, GB, TB)

Modes of Action of AEDs

ANTI EXCITATORY: Na CHANNEL BLOCKADE

PRO-INHIBITORY: ENHANCE GABA

CALCIUM CHANNEL BLOCKADE

Phenytoin Phenobarb EthosuximideCarbamazepine BZDs (Clobazam) GabapentinOxcarbazepine Valproate (VAL,TPM)Lamotrigine Topiramate(VAL,TPM) Tiagabine

Efficacy of first-line AEDs in different types of epilepsy

Efficacy of newer AEDs in different types of epilepsy

Starting dosage, maintenance dosage and important side effects of commonly used AEDs

Starting dosage, maintenance dosage and important side effects of commonly used AEDs

Antiepileptic Drug Mechanism of Action and Metabolism


Continuum (Minneap Minn) 2013;19(3):643–655



Narrow- and Broad-Spectrum Agents


Challenging Drug Combinations


Key points

Both drugs and patients have unique characteristics. The treating physician must consider all of these when

determining the best fit for a particular patient. The ultimate goal is freedom from seizures as well as from side

effects. Since AEDs are taken long term in many cases, present and

future effects need to be considered

Citations

1. Continuum (Minneap Minn) 2013;19(3):643–655

2. Gouri-devi M, Singh V, Bala K. Knowledge, attitude and practices among patients of epilepsy attending tertiary hospital in Delhi, India

and a review of Indian studies. Neurology 2010; 15(3) : 225 – 32.

3. Clinical epilepsy .AMERICAN EPILEPSY SOCIETY – 10/04 C

4. Fisher RS et al. A practical Clinical Definition of Epilepsy. Epilepsia. 2014; 55(4): 475-82

5. Lowensein D. Seizures and Epilepsies. In: Longo D, Kasper D, Jameson J, Fauci A, Hauser S, Loscalzo J eds.

Harrison’s Principles of Internal Medicine. 18th ed. USA: McGraw Hill Inc; 2012. p 2498-3021

6. Mrinal Kanti Roy, Dhiman Das. Indian Guidelines on Epilepsy

7. Data on file

Healthcare

Epilepsy