2. Def: Epilepsy is a central nervous system
(neurological) disorder in which brain activity
becomes abnormal, causing seizures or periods
of unusual behavior, sensations and sometimes
loss of awareness
4. Periods of blackout or confused memory
Occasional “fainting spells”
Episodes of blank staring in children
Sudden falls for no apparent reason
Episodes of blinking or chewing at
inappropriate times
A convulsion, with or without fever
Clusters of swift jerking movements in babies
5. • Seizure—transient involuntary alteration of consciousness, behavior,
motor activity, sensation and/or autonomic function due to abnormal
discharge of cortical neurons; an episodic event, may have provoking
factors, e.g. anoxia, alcohol, drugs
• Convulsion– seizure with prominent alteration of motor activity
• Epilepsy—a disorder with recurrent seizures(2 or more), unprovoked by
a specific event such as fever, trauma, infection, or chemical change,
stereotypic
• Aura—a component of seizure which occurs before consciousness is lost
and for which memory is retained afterwards; it localizes attack to the
point of origin in the CNS
• Automatisms--coordinated adapted involuntary motor activity occurring
during the state of clouding of consciousness; usually followed by
amnesia of the event
6. •Tonic seizure: excessive motor outflow, giving rise to
a tetanic state of the muscles involved.
•Atonic seizure: muscle tone drops to a very low
values resulting in a sudden fall of the body
•Clonic seizure: a tonic seizure with periodic
interruptions
•Tonic-clonic seizure: starts as a generalized tonic
seizure and then interrupted during clonic phase and
ending in complete relaxation.
•Myoclonic seizure: short involuntary contraction of
one or more muscles (local or generalized)
9. •Partial: if only one hemisphere is involved
➢Simple—no impairment of consciousness, features depend on the region of the
brain that is affected
➢Complex—consciousness impaired, may have automatisms e.g. chewing, wandering
off, dressing, undressing
•Generalized: most or both hemispheres
are involved, loss of consciousness
10. • Preserved consciousness (“aura”)
• Symptoms related to involved brain region
• Frontal lobe: movement, thought, speech
• Temporal lobe: memory, speech, smell, taste, abdominal
sensations
• Parietal lobe: body sensations
• Occipital lobe: vision
11. •Altered consciousness
•Unresponsive or less responsive, staring
•Impaired memory after seizure
-Automatisms: hand and mouth movements
(lip smacking, grabbing)
•Hypermotor: wild flailing movements
(frontal)
12. •Most have abnormal, unnatural movements
•Tonic (stiffening)
•Clonic (repetitive jerking)
•Tonic-clonic (“grand mal”)
•Atonic (limp)
•Myoclonic (irregular jerking, may retain
awareness)
•Atonic (falling suddenly)
•Absence (“petit mal”): staring, may blink, arrest of
activity
13.
14. ➢Same underlying pathology responsible for epilepsy and psychiatric
disorder.
➢Seizures produce pathogenic electrical / biochemical changes.
➢Effects of treatment.
➢Psychosocial correlates of epilepsy (disability/ stigma / family
background
15. Related to underlying cause of the epilepsy
•Related to seizures
•Pre-ictal- this is the time before the
seizure. It can last from minutes to days and
make people act and feel differently. Not
everyone experiences something at this stage
of a seizure. Some people who do experience
a preictal stage use it as a warning so they
can prepare for the seizure.
16. •Ictal -The middle (ictal) stage of a seizure is
called the ictal phase. It's the time from the first
symptom to the end of the seizure activity. It is
during this time that intense electrical activity is
occurring in the brain. Some common signs of this
phase include: Loss of awareness.
•Post-ictal -The postictal state is the altered state
of consciousness after an epileptic seizure. It
usually lasts between 5 and 30 minutes, but
sometimes longer in the case of larger or more
severe seizures, and is characterized by
drowsiness, confusion, nausea, hypertension,
headache or migraine, and other disorienting
symptoms
17. •Inter–ictal disorders-Interictal EEG is defined as an
electroencephalographic recording that does not
contain seizures or ictal manifestations and is
therefore obtained in the intervals between clinical
attacks. It is the most frequent recording type in
the clinical practice
18. • Related to underlying cause of the epilepsy
• Related to seizures
• Pre-ictal
• Ictal
• Post-ictal
• Inter–ictal disorders
• Non-epileptic (dissociative) seizures
19. • PRE-ICTAL
1. Depression
2. Anxiety
• ICTAL: psychiatric manifestations of seizure activity
1. Automatisms
2. Non-convulsive status epilepticus
3. Panic Disorder
• POSTICTAL 1. Delirium This is the altered state of
consciousness following an epilepsy The onset of seizure is abrupt , but regaining of consciousness is
gradual.To an observer it will seem like a person who Is arousing from sleep.
• 2.Psychosis
21. • The term ‘postictal psychosis’ refers to brief self-limiting episodes of
psychosis that are of abrupt onset and follow seizures.
• Postictal psychosis is probably the most common psychotic disorder
seen in epilepsy- 6%
• CLINICAL FEATURES
• Most patient had TLE, but it can also follow other localised ,or
generalised epilepsy.
• Most had a seizure duration of over 10 years.
• Precipitated by an exacerbation of seizure ,may be complex partial or
generalised .
23. • Include patients who have epilepsy of known aetiology in whom the
underlying brain pathology is itself associated with psychiatric,
cognitive or behavioural manifestations.
• The neurobehavioral manifestations are judged to be a consequence
primarily of the underlying brain disorder rather than of epilepsy
24. 1. Learning disability
2. Specific epileptic syndromes Gastaut syndrome
3. 3.Epilepsy with continuous spike-and-wave during slow-wave
sleep 4.Progressive myoclonic epilepsies
4. Cognitive and behavioural manifestations of other acquired
causes of Epilepsy like dementia and brain tumours
25. • definition which states that an automatism is ‘a more or less
coordinated, repetitive motor activity usually occurring when
cognition is impaired and for which the subject is usually amnesic
afterwards.
• Automatisms have conventionally been regarded as the behavioural
concomitants of ictal or postictal delirium.
• But recently oro facial automatisms have now been documented
during simple partial seizures in patients who show no evidence of
clouding of consciousness.
• The great majority of automatisms are brief, lasting from a few
seconds to several minutes.
• Occasional examples have lasted for up to 1 hour.
26. • Atypical presentations
• Most of the time fall short of diagnostic criteria ,yet associated with a
higher morbidity.
• The terms ‘interictal dysphoric disorder’ (Blumer 1991) and
‘dysthymia-like disorder of epilepsy’ (Kanner 2003) have been
proposed to describe these presentations.
• The clinical picture is one of chronic dysthymia which is interrupted
at frequent intervals by brief periods of normal mood.
• Affective symptoms are pleomorphic, with prominent irritability and
endogenous somatic symptoms.
27. 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.
30. Dr. Maj . J. Chinyama
Antiseizure
(antiepileptic)
drugs
31. EPILEPSY affects 5–10‰ of the general population.
It is due to sudden, excessive depolarization of
some or all cerebral neurons. This may be:
• localized (focal or partial seizure);
• spread to cause a secondary generalized seizure;
• may affect all cortical neurons simultaneously
(primary generalized seizure).
32.
33. EEG
Cortex:
F – frontal
O – occipital
T – temporal
Classification of seizures
Rang et al.
Pharmacology
– 5th Ed. (2003)
35. MECHANISM OF ACTION OF ANTIEPILEPTIC DRUGS
Antiepileptics inhibit the neuronal discharge or its spread in one or
more of the following ways:
(1) Enhancing GABA synaptic transmission: barbiturates, benzo-
diazepines, gabapentin, levetiracetam, tiagabine, vigabatrin, topira-
mate, valproate; the result is increased permeability to chloride ion,
which reduces neuronal excitability. Valproate and topiramate block
GABA transaminase and tiagabine blocks reuptake of GABA.
(2) Reducing cell membrane permeability to voltage-dependent
sodium channels: carbamazepine, lamotrigine, oxcarbazepine,
phenytoin, topiramate, valproate.
(3) Reducing cell membrane permeability to calcium T-channels:
valproate, ethosuximide; the result is diminishing of the generation
of action potential.
(4) Inhibiting excitory neurotransmitter glutamate: lamotrigine.
38. Antiseizure drugs, enhanced Na+ channel inactivation
Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)
39. Antiseizure drugs, induced reduction of
current through T-type Ca2+ channels.
Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)
40. Effects of three antiseizure drugs on sustained high-frequency firing of action
potentials by cultured neurons. Intracellular recordings were made from
neurons while depolarizing current pulses, approximately 0.75 s in duration,
were applied (on-off step changes indicated by arrows). In the absence of a
drug, a series of high-frequency repetitive action potentials filled the
entire duration of the current pulse. Phenytoin, carbamazepine, and
sodium valproate all markedly reduced the number of action potentials
elicited by the current pulses.
Goodman & Gilman's The Pharmacologic Basis of Therapeutics – 11th Ed. (2006)
41. INDIVIDUAL ANTIEPILEPTICS
▼CARBAMAZEPINE. Dosage 200mg BD. blocks voltage-dependent s
reducing membrane excitability. The t1/2 of the drug falls from 35 to
20 h over the first few weeks of therapy due to the induction of hepatic
enzymes that metabolize it as well as other drugs (including adrenal
corticosteroids, hormonal contraceptives, theophylline and warfarin.
Standard tablets are taken twice a day. Carbamazepine is a drug of
first choice for focal and secondary generalized epilepsy but
aggravates myoclonic and absence seizure. It is useful for the
treatment of trigeminal neuralgia, postherpetic pains, etc.
Adverse reactions (ARs): reversible blurring of vision, diplopia,
dizziness, ataxia, depression of AV conduction, skin rashes, liver, and
kidney dysfunction.
42. ▼VALPROIC ACID (Sodium valproate) 400mg OD acts by
inhibiting GABA
transaminase and increases the concentration of inhibitory neuro-
transmitter GABA at its receptors. Valproic acid has t1/2 13 h and
90% bound to plasma albumin. It is a nonspecific inhibitor of meta-
bolism, and inhibits its own metabolism, and that of lamotrigine,
phenobarbital, phenytoin and carbamazepine. Valproic acid is
effective for treatment of generalized and partial epilepsy, febrile
convulsion and post-traumatic epilepsy.
ARs can be troublesome: weight gain, teratogenicity, polycystic
ovary syndrome, and loss of hair which grows back curly.
Nausea can be a problem, rarely, liver failure (risk maximal at
2–12 weeks). Ketone metabolites may cause confusion in urine
testing in diabetes mellitus.
43. ▼PHENYTOIN 100mg TDS (t1/2 6–24 h) has saturation kinetics. It is
extensively
hydroxylated in the liver and this process becomes saturated at the
doses needed for therapeutic effect (therapeutic plasma concentration
range is 10–20 mg/L). Phenytoin is a potent inducer of hepatic metabo-
lizing enzymes affecting itself and other drugs (carbamazepine, war-
farin, adrenal and gonadal steroids, thyroxine, tricyclic antidepressant,
doxycycline, vitamin D, folate). Drugs that inhibit phenytoin metabolism
include: valproic acid, cimetidine, co-trimoxazole, isoniazid, chloram-
phenicol, some NSAIDs, disulfiram. Phenytoin is 90% bound to plasma
albumin and small changes in binding will result in a higher concentra-
tion of free active drug. It is used to prevent all types of partial seizure,
generalized seizure, and st. epilepticus. It is not used for absence attacks.
ARs: impairment of cognitive function (which has led many physicians to
prefer carbamazepine and valproate), sedation, hirsutism, skin rashes,
gum hyperplasia (due to the inhibition of collagen metabolism),
44. Saturation kinetics. Phenytoin is extensively hyd-
roxylated in the liver and this process becomes
saturated at about the doses needed for therapeutic
effect. Thus phenytoin at low doses exhibits first-
order kinetics but saturation or zero-order kinetics
develop as the therapeutic plasma concentration
range (10–20 mg/L) is approached, i.e. the dose
increments of equal size produce disproportional rise
in steady-state plasma concentration.
45. Nonlinear relationship of phenytoin dosage and plasma concentrations.
Five different patients (identified by different symbols) received increasing
dosages of phenytoin by mouth, and the steady-state serum concentration
was measured at each dosage. The curves are not linear, since, as the
dosage increases, the metabolism is storable. Note also the marked
variation among patients in the serum levels achieved at any dosage.
Basic & Clinical
Pharmacology –
10th Ed. (2007)
46. ▼BENZODIAZEPINES
•Diazepam given intravenously or rectally is highly effective for
stopping continuous seizure activity, especially generalized tonic-
clonic status epilepticus. The drug is occasionally given orally on
a long-term basis, although it is not considered very effective in
this application, probably because of the rapid development of
tolerance. A rectal gel is available for refractory patients who need
acute control of bouts of seizure activity.
•Lorazepam appears in some studies to be more effective and
longer-acting than diazepam in the treatment of status epilepticus
and is preferred by some experts.
•Clonazepam (t1/2 25 h) is a benzodiazepine used as a
second line drug for treatment of primary generalized epilepsy
and status epilepticus.
48. ▼BARBITURATES (enzyme inducers)
Antiepilepsy members include phenobarbital 100mg OD
(phenobarbitone –
( t1/2 100 h), methylphenobarbital and primidone (which is
largely metabolized to phenobarbital, i.e. it is a prodrug). They are
still used for generalized seizures; sedation is usual.
Primidone and its
active metabolites
Basic & Clinical
Pharmacology –
10th Ed. (2007)
49. ▼LAMOTRIGINE 500mg OD (t1/2 6–24 h) inhibits excitory
neurotransmitter
glutamate. Lamotrigine is effective for the treatment of partial and
secondarily generalized tonic-clonic seizure. It is generally well
tolerated but may cause serious ARs of the skin, including
Stevens–Johnson syndrome and toxic epidermal necrolysis.
▼ETHOSUXIMIDE 500mg OD (t1/2 55 h) blocks T-type calcium ion
channels. It is active in absence seizures (petit mal).
ARs: gastric upset, CNS effects and allergic reactions.
50. Morning Dose Evening Dose
Week 1 25 mg 25 mg
Week 2 50 mg 50 mg
Week 3 75 mg 75 mg
Week 4 100 mg 100 mg
Week 5 150 mg 150 mg
Week 6 200 mg 200 mg
TOPIRAMATE (t1/2 21 h) is used as adjunctive treatment for
partial seizure, with or without secondary generalization. ARs:
sedation, weight loss, acute myopia, raised intraocular pressure Monotherapy
Titration Schedule for Adults and Pediatric Patients 10 years and older
52. PRINCIPLES OF MANAGEMENT
(Clinical Parmacology)
• Any causative factor must be treated (cerebral neoplasm etc).
• Educate the patient about the disease, duration of treatment
and need for compliance.
• Avoid precipitating factor (alcohol, sleep deprivation, emotional
stress, and caffeine).
• Anticipate natural variation: fits may occur around menstrual
periods in women – catamenial (monthly) epilepsy.
• Give antiepileptics only if seizure type and frequency require it
(e.g. more than one fit every 6–12 months).
54. Anticonvulsive drugs of choice
Grand mal: I choice – valproate or Lamotrigine
Alternative – Carbamazepine, Topiramate or Phenytoin
Petit mal: I choice – Ehosuximide or valproate
Alternative – Clonazepam or Lamotrigine
Partial seizures: I choice – Carbamazepine or
valproate
Alternative – Phenytoin, Lamotrigine, Vigabatrin, Topiramate
Status epilepticus: I choice – Diazepam or Lorazepam (i.v.)
Alternative – Phenobarbital (i.m./i/v.)
55. GENERAL GUIDE TO ANTIEPILEPSY PHARMACOTHERAPY
(1) The decision whether or not to initiate drug therapy after a
single seizure remains controversial since approximately 25%
of patients may not have another seizure.
(2) Therapy should start with a single drug (70% of patients can
be controlled on one drug (monotherapy).
(3) Anticonvulsant drug therapy should be appropriate to the type
of seizure.
(4) The choice of drugs is also determined by the patient’s age
and sex.
(5) If the attempt to control epilepsy by use of a single drug is
unsuccessful, it should be withdrawn and replaced by a second
line drug, though these are effective in only 10% of patients.
56. There is little evidence that 2 or 3 drugs are better than one,
but more drugs often mean more ARs.
(6) Effective therapy must never be stopped suddenly,
only gradually.
(7) After a period of at least 2–3 years free from seizures, with-
drawal of anticonvulsants can be considered. In general, dis-
continuing the antiepileptic drug therapy is associated with
about 20% relapse during withdrawal and a further 20% relapse
over the following 5 years. It is recommended that the antiepi-
leptic drug be withdrawn over a period of 6 months. If a fit
occurs during this time, full therapy must begin again until the
patient has been free from seizure for a further 2–3 years.
