epilepsy--prof. fareed minhas
TRANSCRIPT
Understanding Epilepsy
Fareed A. MinhasProf. & Head
Institute of PsychiatryRawalpindi Medical College
Introduction
• Seizure: the result of excessive synchronous discharge of cortical neurons
• Convulsion: violent, involuntary contraction of voluntary muscles
• Epilepsy: a clinical condition characterized by recurrent unprovoked seizures
Definitions
Seizure
A paroxysmal and time-limited neurological event that results from abnormal neuronal activity in the brain
Epilepsy
Recurrent seizures
Prevalence
• 1.4 M in USA with 8.4 M visits to office-based neurologists
• i% in Pakistan• Chronic seizure disorder in 1-2% of general
population (6.1 per 1000)• Ten percent of general population have at least one
seizure in their lifetime• Minority groups may have higher rate
– Acquired (symptomatic) epilepsy– Socioeconomic status
Epileptic Neuron Stimulus
Repeated influx of sodium ions
Excessive Glutamate &Aspartate release
Excessive stimulation leadingto a seizure
An increase in the presynaptic release of glutamate and aspartatemay lead to excessive stimulation of the postsynaptic membrane.
PresynapticNeuron
Triggers
• Hyperventilation (absence)• Too much sleep• Too little sleep• Sensory stimuli• Emotional stress • Hormonal changes• Drug overdose or withdrawal
Classification
• Partial (focal, local)– Simple (w/o impairment of consciousness)
• With motor symptoms• With special sensory or somatosensory
symptoms• With psychic symptoms
– Complex (consciousness impaired)• Simple partial onset followed by impairment• Impaired consciousness at onset
– Secondarily generalized
Classification
• Generalized (convulsive or non-convulsive)– Onset occurs bilaterally and symmetrically – absence, atonic, clonic, myoclonic, tonic,
tonic-clonic, infantile spasms
• Unclassified seizures• Status epilepticus
Diagnosis of Seizure
History and observation
EEG
Diagnosis
• Seizure characteristics– Frequency and duration– Precipitating factors– Time of occurrence– Aura– Ictal and post-ictal state
• Laboratory– CBC – Chem panel with Mg and Ca– UA– Lumbar puncture
• PE and NE• EEG• MRI or CT
Features suggestive of seizure
Impairment of consciousness Deviation of the eyes Facial automatisms Rhythmic jerking of body parts Bladder or bowel incontinence Physical injury (e.g., tongue-biting) Pre-episode aura Post-episode confusion Family history of epilepsy
Role of EEG
Only test of brain function available in routine clinical use
Can reveal interictal “signature” of underlying epilepsy through the appearance of epileptiform discharges (spikes, sharp waves, and spike and slow-wave complexes)
Single EEG has sensitivity of 60% Sensitivity can be enhanced by repeating the test
(up to 90% for 3 EEGs) and by sleep deprivation
Evaluation of a patient with suspected seizure
Careful history Thorough neurological examination Standard labs (CBC, glucose, lytes, BUN/Cr, UA)
EEG
Brain MRI in case of abnormal exam CSF analysis in case of suspected infection
Differential diagnosis of seizures
Breathholding spells (children)REM sleep behavior (children)TicsConfusional migraineSyncopePanic attacksNarcolepsyTransient ischemic attackTransient global amnesiaPsychogenic seizures (pseudoseizures)
Management: Central issues
Destigmatization Judicious use of AEDs Recommendations about driving Pregnancy and epilepsy First-aid advice to family Options for refractory cases
Destigmatization
Demystifying superstitions Educating about nature of epilepsy Counseling about marriage and pregnancy Reassuring that epilepsy is compatible with a
normal and productive life
Driving recommendations
No driving after a seizure until seizure-free for 6 months
No driving after medication decrement until seizure-free for 6 months
Also applies to swimming, water sports and other activities in which seizure could be lethal
Pregnancy & Epilepsy
Epilepsy is compatible with marriage and motherhood
Pre-conception control is best predictor of seizure control during pregnancy
All AEDs are potentially teratogenic but seizure may carry greater risk to fetus
If possible, have patient controlled on lamotrigine prior to conception and stay the course
First-aid for acute seizure
Turn the patient on to his or her side Remove eyeglasses if any Clear the area of harmful objects Do not try to restrain movements Loosen neckwear like necktie or dupatta Do not force anything into the patient’s
mouth
No need for emergency medical help unless …Seizure doesn’t stop in 3 min., another seizure happens, or an injury has occurred
Options for refractory cases
Add 2nd or, if necessary, 3rd AED Consider surgical treatment
Requires specialized evaluation Options include temporal lobectomy,
lesionectomy (corticectomy), callosal commissurotomy, hemispherectomy
Consider Vagal Nerve Stimulator Implanted electrical stimulator of vagus,
effective as adjunct to AEDs
Treatment Goals
• Normal lifestyle • Reduce frequency of seizures
– Balance between suppression and AEs
• Encourage compliance• Assess the concerns of the patient
– Driving– Education– Relationships– Housing– Social stigma
• Epilepsy Foundation of America
Principles of Pharmacotherapy
• Positive correlation between the early initiation of therapy and the ability to control seizure activity
• Failure to control seizures may lead to an increase in seizure activity and also the occurrence of other seizure types
• “No regimen like the first regimen”
Principles of Pharmacotherapy
• Drug choice is based on seizure type and side effect profile
• Always start with monotherapy– ~70% of patients can be maintained with one
drug– Of 35% with unsatisfactory control, 10% will be
well-controlled on two drugs– ~20% will be medically refractory– 15% will become surgery candidates
• Success rate is 80-90% in properly selected patients• Risks include learning,memory, and general intellectual
impairment
Principles of Pharmacotherapy
• Seizure control may be achieved at doses corresponding to less than “normal” therapeutic serum levels; likewise, doses corresponding to higher than “normal” therapeutic serum levels may be tolerated and required by some patients
• Begin dosing at 1/3 to ¼ anticipated maintenance dose and titrate over 3-4 weeks
Judicious use of AEDs
Do not treat single uncomplicated seizure If AEDs are needed, use monotherapy as
much as possible (e.g: Tegral) Classic AEDs (phenytoin, Tegral and valproic
acid) have long experience but significant side-effects, esp. valproic acid in women
Newer agents very expensive & 2nd line therapy
Gabapentin is a weaker AED but almost no interactions and best for medically complex patients
Treatment Failure
• Number one cause of treatment failure is • AED is not considered ineffective until
patient has continued seizures AND some concentration-dependent side effects
• Substitute• Generics (Low bioavailability)• Mixed seizure types are more likely to
require more than one AED• Seizure chart a must
Principles of Pharmacotherapy
• Kinetics– Plasma protein binding
• Measure free instead of total– DPH
– Age• Neonates• Infants, children• Elderly
– Metabolism• Induction or inhibition of the CYP450 enzyme
system• Many AEDs have active metabolites
Principles of Pharmacotherapy
• Female patients– Enzyme-inducing AEDs
• PHT, PHB, Tegral , primidone
• VPA is an inhibitor
– Seizures before or during menses or at time of ovulation
• All female patients should take PNV with folate
Principles of Pharmacotherapy
• Pregnancy– 25-30% increased or decreased frequency– Increased VD and clearance– Altered protein binding– Increased incidence of adverse outcomes– Twice the incidence of congenital malformations
(4-6%)• PB and PHT – congenital heart malformations, facial
clefts• CBZ and VPA – spina bifida and hypospadias
– Monotherapy preferred
Principles of Pharmacotherapy
• Discontinuation of AEDs– Seizure-free for 2-5 years – Single type of primary GTC or partial– Neurological exam and IQ are normal– EEG normalized with treatment
• Not possible in all patients– High frequency– Repeated SE– Combination of seizure types– Development of abnormal functioning
Drugs of Choice – First Line
• Partial Seizures– Tegral , PHT, VPA– Lamotrigine, oxcarbazepine
• Generalized Seizures– Tonic-Clonic
• CBZ, PHT, VPA
– Absence• VPA, ethosuximide
– Myoclonic• Clonazepam, VPA
Summary
Seizures and epilepsy are a common problem in primary care medicine
Diagnosis relies on careful history and examination, supplemented by EEG
Treatment involves educating about the illness, judicious use of AEDs, instructions about driving and similar activities
Treatment options exist for refractory cases
Tegral is the first line therapy Tegral is effective & has low side effects
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