1. The document discusses prognostic groups in epilepsy, including spontaneous remission in certain syndromes, remission with antiepileptic drugs in focal and myoclonic epilepsies, and persistent seizures despite treatment in 30-40% of patients. 2. It defines refractory or drug-resistant epilepsy as failure of two appropriate antiepileptic drugs to achieve seizure freedom, and notes these patients are at higher risk for neurological and psychosocial issues as well as increased mortality. 3. Common errors in diagnosis and treatment that can lead to apparent treatment resistance include misdiagnosis of seizure type, unrecognized brain diseases, and issues like improper drug choice, dose, or combination. Further evaluation including video

1. 1
Khaled SaadKhaled Saad, MD
Assiut University

2. 2
Agenda

3. • (1) Spontaneous remissionSpontaneous remission (20-30%) -
benign epilepsy with centrotemporal spikes
or childhood absences.
• (2) Remission on AEDs (20-30%) - most
focal epilepsy and myoclonic juvenile
epilepsy syndromes.
• (3) Persistent seizures under AEDs (30-
40%). EurNeurol 2009;62:65-71
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PROGNOSTIC GROUPS IN EPILEPSY

4. 4

5. 5
Old definitions:
--Uncontrolled seizures despite plasma
concentrations of AEDs within the
therapeutic range (Scott, 1984).
--Uncontrolled seizures despite relevant
therapy (Juul-Jensen, 1986).
--Seizures intractable to all therapeutic
trials with single or combined drugs for a
sufficient time (Aicardi, J. 1997) .

6. • Uncontrolled seizures for at least 18 m, with
a frequency of 1 fit or more/m. During that
peroid at least 2 or more AEDs had to have
been used as mono-or poly-therapy (Berg et al,
2006)
• Drug Resistant Epilepsy {ILAE 2009}:
Failure of informative trials of two
tolerated and appropriately chosen and
used AED schedules (whether as
monotherapies or in combination) to
achieve sustained seizure freedom. (Kwan et al
Epilepsia 2009)
6

7. • Our definition: (a) One or
more seizure per month for a
period of 6 months or more.
(b) No more than a 3-month
seizure-free during those 6
months. (c) Failure of at least
two appropriately selected
AEDs with proper doses, good
compliance, and within the
therapeutic range of AEDs.
7

8. Refractory epileptic patients are more prone to:
*Neurological and Psychosocial retardation.
*Risk of injury(seizure related).
*High mortality: 1.37 per 100 person-years.
Sudden unexplained death in epilepsy patients (SUDEP) is
40 times more likely among patients who continue to
have seizures than in those who are seizure free.
• Epilepsy Res. 2005;65(1-2):101-15 & J Neurol. 2000;247(1):15.
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How Serious Is The Problem?

9. 1- Early onset & Neonatal convulsions.
2-Mental subnormality.
3-Organic brain damage, Abnormal CT.
4- Poor initial response to AED.
5.Presentation with status epilepticus. 9
Predictors For Refractory
Epilepsy

10. 6. Long duration of epilepsy before diagnosis.
7. Poor psychological and or socio-economic
background.
8. Family history of epilepsy.
9. Abnormal neurological examination.
10. Partial seizures at diagnosis, mixed seizure
types. CNS Spectr. 2004;9:110-119. 10

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Aicardi, J.1988Aicardi, J.1988
*Medically intractable epilepsy:
1.Pseudo intractable.
2.True intractable.
*Medically and surgically intractable:
3.Candidates unfit for surgery.
4.Candidates with failed surgery.
Classification of Intractable Epilepsy

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Common Errors In Diagnosis and
Treatment of Epilepsy
(pseudo refractory)

13. 1. Misdiagnosis of non-epileptic seizures.
2. Misclassification of epileptic seizures.
3. Unrecognized progressive brain disease.
4. Failure to uncover precipitating factors.
Misdiagnosis is common; 26% of individuals thought to have
DRE were incorrectly diagnosed most often as a result of
incomplete history-taking and/or EEG misinterpretation13
Diagnostic errors

14. • Improper choice of drug.
• Inadequate drug dose.
• Inappropriate combination of drugs.
• Drug interaction.
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Treatment errors

15. Incorrect drug choice is most commonly a
consequence of diagnostic errors.
It derives from the misclassification of the
type of epilepsy.
e.g., carbamazepine and phenytoin will not be
effective in patients with absence seizures
or myoclonic seizures.
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Incorrect drug choice

16. • Patients with RE should have further
testing to confirm the diagnosis of epilepsy
and also to better define the epilepsy
syndrome and underlying classification in
order to best direct treatment. In most
cases, the evaluation of RE will include
video-EEG monitoring and magnetic
resonance imaging. Lancet Neurol. 2008;7(6):514
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EVALUATION

17. • Video EEG monitoring combines both a
video and EEG recording of clinical events.
This test is used primarily to determine
whether epilepsy is the cause of recurrent
seizure-like events. In some series, more than
25 percent of individuals referred for
monitoring for refractory epilepsy are found
to have nonepileptic events. EEG monitoring
can also aid in seizure classification and is
used for presurgical evaluation of epilepsy
patients. QJM. 1999;92(1):15.
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18. • Neuroimaging — By the time a patient is
considered to have IE, a magnetic resonance
imaging (MRI) study will usually have been
performed. In many cases, this should be
repeated, particularly if the original study
was unrevealing. In some cases, follow-up
MRI reveals an etiology for epilepsy (such as
cerebral neoplasm, autoimmune
encephalitis) that was not seen on the initial
study and requires specific therapies in
addition to AEDs.
• Arch Neurol. 2012;69(5):582.
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19. • The following measures should beThe following measures should be
considered in succession.considered in succession.
1. Increase the dose of the 1st
line antiepileptic
drug has been chosen for the patient, up to
the maximum clinically tolerated dose
N.B* we have to treat the patient not the
serum level, On failure→
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Therapeutic strategy for management
of intractable epilepsy

20. 2. Change for another drug of the first line
drugs, and also increase its dose
gradually up to the maximum tolerated
dose, on failure →
3. Permanent addition of a second drug, on
failure →
4. At that point we have to re-evaluate the
patient even with previous normal
investigations.
20

21. Some questions should be asked now as:
- Can too much of one drug or too
many drugs may not only produce side
effects, but also increase seizures
frequency?
- Can certain drug precipitate certain
seizure types? 21

22. 5. Return to single drug therapy with the best
clinically tolerated of the previously used
antiepileptic drugs (avoid sedative and
hypnotic drugs).
6. Addition of one of the new antiepileptic
drugs can be considered now as add on
therapy or as monotherapy, on failure→
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23. 7. We have to consider the following:
A} Alternative non antiepileptic drug
therapy as add on therapy under strict
clinical selective criteria such as:
a. Vagal nerve stimulation, b. ketogenic
diet., c. Melatonin, d. Calcium
antagonists, e. IV immunoglobulins.
B} Epileptic surgery.
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24. Treatment Algorithm For Medical Management of Epilepsy
Patients with newly diagnosed, previouslyPatients with newly diagnosed, previously
untreated epilepsyuntreated epilepsy
MonotherapyMonotherapy
(drug 1)(drug 1)
Consider withdrawal after 2- yearsConsider withdrawal after 2- years
of complete seizure controlof complete seizure control
Alternative monotherapyAlternative monotherapy
(drug 2)(drug 2)
Consider withdrawal after 2 or moreConsider withdrawal after 2 or more
years of complete seizure controlyears of complete seizure control
PolytherapyPolytherapy
(drug 1 and 2)(drug 1 and 2)
Substitution and transfer toSubstitution and transfer to
monotherapy with drug 3monotherapy with drug 3
Presurgical evaluation?Presurgical evaluation?
Diagnostic re-evaluationDiagnostic re-evaluation
SuccessSuccess FailureFailure
SuccessSuccess FailureFailure
SuccessSuccess FailureFailure
SuccessSuccess FailureFailure
Months ofMonths of
treatmenttreatment
00
44
88
1212
1616
Consider withdrawal after 2-5 yearsConsider withdrawal after 2-5 years
(with patient considerations)(with patient considerations)
Consider withdrawal after 2-5 yearsConsider withdrawal after 2-5 years