Epilepsy

By:
Assistant Lecturer: Tasneem Ahmed Hamed
Definition:
increased tendency to have recurrent seizures, manifested by two or more
unprovoked events

Etiology:
1. Unknown (idiopathic epilepsy) 70% of cases.
2. Known (symptomatic epilepsy)
• Cerebrovascular disease
• Developmental
• Cerebral trauma
• Derebral tumor
• Infection
• Neurodegenerative
 Classification:
A. Epilepsy often classified as Eclectroclinical syndrome to:
►Generalized onset ►Focal (partial) onset seizure.

B. Epilepsy may be classified etiologically as follows:

Idiopathic Symptomatic Cryptogenic

possible genetic (structural abnormality (structural abnormality
predisposition with present on imaging suspected but not
normal development, studies) demonstrated)
neurological
examination and
neuroimaging studies.
Comparison between EEG in partial and Generalized
seizure
Clinical features:
• Seizures are paroxysmal, stereotypic events.
• Seizures usually last only several minutes, but they may be followed by a
more prolonged interval of transient drowsiness, confusion, or focal
deficits.

Triggers include:
• Alcohol
• Fatigue
• Sleep deprivation
• Infections and fever
• Hormonal fluctuations
A. Childhood absences
• Rare after age 10 years
• Brief loss of awareness (several seconds) many times a day.
• Triggered by hyperventilation
• Most cases remit in adulthood.
• EEG characteristic.

a) Normal b)absecnce
B. Juvenile myoclonic epilepsy
(JME):

• Onset before age 30 years.

• Myoclonic jerks in the morning.
• Remission rare;
• lifelong pharmacologic treatment
usually indicated
C. Complex partial seizures:

• Often associated with underlying structural abnormality, e.g., hippocampal

sclerosis (Fig. 1), dysembryoplastic neuroepithelial tumor (DNET; Fig.2)

• Automatisms (lip smacking, chewing, swallowing, stereotypical hand

movements)

• Olfactory or gustatory auras (unpleasant)

• Unusual behavior or emotionality

Fig.1 MRI of hippocampal sclerosis.
shows atrophy of the right hippocampal formation seizures (white arrow) in a
patient with refractory complex partial.
Fig. 2 MRI of dysembryoplastic neuroepithelial tumor (DNET). Coronal spoiled gradient
image (A) identifies a slightly bulky hyperintense lesion within the left hippocampal
formation (white arrow).
Investigations
• Blood investigations:
- CBC
- Renal, liver function, calcium, magnesium, glucose.

• MRI with specific views of both temporal lobes if complex partial seizures.

• EEG; consider sleep deprived and prolonged ambulatory recordings if a

routine study is negative.
 Management of epilepsy
Goals:
The management of patients with epilepsy is focused on three main goals:
• controlling seizures,
• avoiding treatment side effects
• maintaining or restoring quality of life

General advice:
1. Advise the patient not to drive.

2. Avoid unsafe activities:

Eg: take showers rather than baths
avoid swimming alone,
do not use power equipment or work at heights.
Starting treatment:

A. Single seizures:
 No treatment is indicated unless the EEG or MRI reveals an abnormality that
suggests a high risk of recurrence.
 If precipitating factors (e.g., sleep deprivation, alcohol) are identified, avoidance or
abstinence should be recommended.

ASM treatment is generally started after two or more unprovoked

seizures, because the recurrence proves that the patient has a substantially
increased risk for repeated seizures,

B. Prophylaxis
 There is no indication for starting treatment in patients with head injuries,
craniotomy, and brain tumors, unless seizures actually occur.
Choosing an antiseizure medication:
 Aim of treatment is to render the patient seizure free with minimal side
effects.

 Approximately half of patients with a new diagnosis of epilepsy will

become seizure free with the first ASM prescribed.

 Tolerability of side effects is as important as efficacy in determining the

overall effectiveness of treatment.

.
 No single ASM is optimal for every patient.

 The selection of a specific ASM for treating seizures must be

individualized considering:

● Drug effectiveness (spectrum) for the seizure type or types.

● Potential adverse effects of the drug.

● Interactions with other medications ASMs inducers (eg, phenytoin,

carbamazepine, and less so, oxcarbazepine and topiramate).

● Comorbid medical conditions, especially, but not limited to, hepatic and
renal disease.

● Age and gender, including childbearing plans

● Lifestyle and patient preferences
● Cost
Dosing frequency:
• The half-lives of antiseizure medications vary considerably.

• For many individuals, the frequency with which a drug must be taken
is an important factor in compliance (ie, adherence) and/or seizure
control.

• Optimal dose frequency for individual drugs can vary between patients
 Treatment failure:
- Seizures in approximately half of patients with a new diagnosis of epilepsy
are successfully treated with the first ASM prescribed

- Treatment failure may result from breakthrough seizures or drug

intolerance. At this point, a second drug trial should be attempted

- Similar factors are considered when a second ASM is chosen as when the
first was selected.
Combination therapy:

 When possible, it is preferable to maintain a patient on a single ASM.

 This increases the probability of compliance, provides a wider

therapeutic index, and is more cost effective than combination drug
treatment.

 Monotherapy is also associated with fewer idiosyncratic reactions and a

lower incidence of teratogenic effects.

 Combination therapy can be associated with drug interactions between

ASMs making it difficult to dose and monitor patients.
Side effects of therapy
During the first six months of treatment, systemic toxicity and
neurotoxicity cause ASM failure.

The usual strategy in patients experiencing peak-level side effects from

a specific drug is to:

1. Alter the medication treatment schedule to minimize side effects; one alteration
may be to spread the medication over more doses throughout the day.

2. Obtaining levels when a patient is experiencing side effects and comparing them
with levels obtained when the patient is free from symptoms can be helpful in the
management of some patients.
3. Refer to the patient's seizure calendar in planning the timing of drug
levels in an attempt to prove a cause-and-effect relationship between peak
levels and side effects.

As an example, in a patient who experiences seizures only at night but

who has side effects in the afternoon from their morning dose of ASMs,
shifting part of the morning dose to the bedtime dose may eliminate these
side effects while improving seizure control.
Maximizing the likelihood of a successful outcome
1. Titration and monitoring:
a. Start treatment with a single drug
b. gradually titrate to the highest dose that is tolerated and/or produces seizure
freedom
c. then to titrate back down to a previously tolerable dose
d. Monitor treatment regularly. At regular office visits, clinicians should ask
and record seizure frequency and medication side effects
B. Seizure calendar:

• Patients and family members should be asked to record seizures and

ASM doses on a calendar or diary, which can then be brought or sent to
the clinician for review.

• Seizure triggers should be indicated. The patient and family should note
on the calendar the hour at which any symptoms occur.

• Electronic seizure diaries are also available

 Drug monitoring
• If seizures continue, increase dose as tolerated. If seizures persist, transition to
another first-line drug.

• If anticonvulsant monotherapy is unsuccessful, adjunctive treatment with a

second-line drug should be considered

Measuring drug levels is indicated in the following situations:

• Poor compliance.

• Symptoms of toxicity, e.g., nausea, ataxia, confusion, diplopia.

• There is little correlation between blood levels and therapeutic effect for
many newer anticonvulsants (e.g., lamotrigine, levetiracetam), so routine
therapeutic monitoring of blood levels may be unhelpful.
Prognosis with drug treatment:

By 12 months 60%–70% of treated patients will be seizure free.

After 2 years, withdrawal of drugs can be considered.

Predictive factors for relapse include the following:

• Syndromic epilepsy, e.g., JME
• Underlying structural pathology
• Continued epileptiform abnormality on EEG
• Severe prolonged epilepsy before remission
• Increased age.
 Resective surgery
 Any patient with focal epilepsy who has failed two or more trials of
anticonvulsant therapy should undergo inpatient video/EEG monitoring
and other evaluations (high-resolution MRI, neuropsychological testing,
in order to determine whether they are candidates for resective surgery.

 Patients with certain structural neuroimaging findings have a high (up to

80%) probability of seizure remission following surgery.
Intracranial Electrodes

In the absence of structural brain

pathology, implantation of intracranial
electrodes may be required to delineate
ictal onset and permit functional mapping
studies.
 Vagus nerve stimulation
• In patients with medically refractory epilepsy who are not good
candidates for surgical resection

• The vagus nerve stimulator is an implantable medical device implanted

subcutaneously under the left clavicle.

• Although complete remissions are unusual, many patients with severe

inoperable focal and generalized epilepsy experience significant
improvement.
 SPECIAL POPULATIONS
1. Women of childbearing age:
A number of issues are important in women of childbearing age, especially if
they are considering becoming or are already pregnant. Clinicians should
regularly review these issues with their female patients with epilepsy.
2.Effect of antiseizure medications on the fetus:
• There is an increased risk of both major and minor malformations in
fetuses exposed to antiseizure medications (ASMs).

• Anticonvulsant therapy during pregnancy may have deleterious effects on

cognitive and developmental outcomes of exposed children later in life.

2. Older patients:
• ASM use in older adult patients is complicated by several factors,
including:
1. Age-related alterations in protein binding,
2. Reduced hepatic metabolism
3. Diminished renal clearance of medications.
4. Medical comorbidities
5. Polypharmacy are more often a concern in older adults
3. Comorbid medical conditions:
• Many antiseizure medications are either metabolized by the liver,
excreted by the kidneys, or both.
• When a person has hepatic or renal disease, it may be necessary to avoid
certain antiseizure medications or to adjust the dose

4. Renal disease:
• Renally excreted drugs include gabapentin, topiramate, zonisamide,
lacosamide, levetiracetam, oxcarbazepine, and pregabalin.
• The dose of these drugs should be adjusted based on the severity of
renal impairment.
5.Hepatic disease:
• Some antiseizure medications are associated with hepatic toxicity and
should be avoided in patients with preexisting liver disease as (valproate
and phenytoin and carbamazepine)

• Many other antiseizure medications are metabolized fully or partially

in the liver requiring caution and dose adjustment when used in patients
with chronic liver disease as lamotrigine, phenobarbital, clobazam.

• Drugs that do not undergo hepatic metabolism and are less problematic
for use in patients with chronic liver disease as (Levetiracetam,
gabapentin, pregabalin).
 6. Psychiatric disorders:
• Persons with epilepsy have a higher than expected prevalence of
comorbid psychiatric disorders.

• Eg: valproate, lamotrigine, carbamazepine, oxcarbazepine appear to

have mood-stabilizing properties so useful in case of bipolar disorder

7. Diabetes:
• Because of its association with weight gain, insulin resistance, and
polycystic ovarian syndrome, use of valproate in individuals with diabetes or
obesity should be carefully considered.
• Carbamazepine, gabapentin are also, but much less frequently, associated
with weight gain.
• Gabapentin, pregabalin, have efficacy in treating pain associated with
diabetic neuropathy.
 DISCONTINUING ANTISEIZURE MEDICATION
THERAPY
• After a two- to four-year seizure-free interval, it is reasonable to begin a
discussion about continued antiseizure medication (ASM) therapy versus a
trial of discontinuation.

• This decision must be individualized and weighs the risks of seizure

recurrence against the possible benefits of drug withdrawal, all of which
may vary significantly across patients

• The main disadvantage is the possibility that seizures will recur.

• The psychosocial implications may be particularly significant for adults

who are employed, who drive, and whose lifestyle would be adversely
affected by recurrent seizures
Case 1
A. What is your diagnosis at this point?

B. Regarding this patient what is your advice regarding pregnancy?

 Case 2
70 y/o patient admitted to ER with history of single seizure 2 days ago.
His wife was awakened at 5:30 am by her husband making odd gurgling noise
with head deviated to left and right and arm tonically stiffed.
Again today this event recurred and was followed by generalized body jerking.
Event lasted for 2 minutes until full recovery.
His lab values was:

Scr 2.1 mg/dl

BUN 75
Sodium 141mEq/L
Potassium 4.2 mEq/L
WBCs 9500
Platlets 180 000
1. Is the patient considered to be Epileptic?

2. What is your treatment plan for this patient?

3. What are the considerations to be taken into account during prescribing the
medications?
 Case 3
An 18-year-old University student was admitted to the Acute Medical Unit after a
tonic-clonic seizure that was witnessed by his girlfriend. While making breakfast in the
kitchen, he was observed to let out a cry and then fall rigid to the ground, followed by
30 seconds of jerking of the limbs. He bit the side of his tongue. He was unresponsive
for several minutes afterwards. His girlfriend called an ambulance. He had not had a
seizure before, but she had noticed his right arm and head tended to twitch in the
mornings, especially when he was tired. He had no past medical or family history and
was not taking any medication. On examination he was back to normal. The
cardiovascular and neurological examination were normal. Blood results and a 12-lead
ECG were also normal.

What treatment should be offered before discharge from hospital?

A Carbemazepine
B Clonazepam
C Leveteracitam
D No treatment
E Sodium valproate
 Case 4 Assignment
A 50-year-old self-employed joiner was admitted to the Acute Medical Unit
following a tonic-clonic seizure. and was taking several medications for COPD,
depression and low back pain.
He had recently started antibiotics for a chest infection. There was no family history
of collapses. On examination he was back to normal.
The cardiovascular and neurological examination was normal. A12-lead ECG and a
CT scan of the head performed in the Emergency Department were also normal.
He was examined by internal medicine physician and found to has ascites, Liver
function tests were very high. Serum albumin and platlets were very low.

A. What is your treatment plan for this case?

B. What are the considerations to be taken into account during prescirbing his
medications?

C. Give example with the dose and dosing frequency frequency of the drug/s you
prescribe?