Staging of Seizures According to
Current Classification Systems
December 10, 2013
Elinor Ben-Menachem, M.D.,Ph.D,
Instituet of Clinical Neuroscience and
Physiology,
Sahlgren Academy, Goteborg University,
Sweden
American Epilepsy Society | Annual Meeting
1
Disclosure
Name of Commercial
Interest
American Epilepsy Society | 2013 Annual Meeting
Type of Financial
Relationship
UCB
Eisai
Bial
Lundbeck
Electrocore
Biocontrol
Acta Neurologica
Scnadinavica
Research Grant, Consult
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Chief Editor
Learning Objectives
1. To understand the previous staging attempts for new-onset epilepsies that might be applied to patients with refractory epilepsies.
2. To use staging to determine if antiseizure drugs should be started in new patients or withdrawn in seizure free patients
3. Understand how a staging process might work in determining refractoriness
American Epilepsy Society | 2013 Annual Meeting
Impact on Clinical Care and
Practice • The physician, by staging refractory
epilepsy, can help define prognosis and
make management decisions based on this
assessment for the individual patient.
• Help patients understand his/her condition
which will also facilitate decision making
Purposes of Staging
• Staging describes the extent or severity of a person’s epilepsy. Knowing the stage of disease helps the doctor plan treatment and estimate prognosis.
• Staging systems for epilepsy should continually evolve over time and continue to change as knowledge about the epilepsies advances
• Lacking a measure of the severity of epilepsy("staging"), prognosis cannot be established
For Cancer (National Cancer
National Cancer Institute: http://www.cancer.gov/cancertopics/factsheet/detect
ion/staging
• The staging system is based on the size and/or extent (reach) of the primary tumor (T), whether cancer cells have spread to nearby (regional) lymph nodes (N), and whether metastasis (M), or the spread of the cancer to other parts of the body, has occurred.
• Physical exams, imaging procedures, laboratory tests, pathology reports, and surgical reports provide information to determine the stage of a cancer
Previous Attempts at a Scoring
System to Predict Seizure freedom
and Success of Withdrawal
7
Berg AT, Shinnar S. Neurology. 1991;41(7):965-972.
No aetiology, normal EEG
No aetiology, abnormal EEG
Symptomatic, normal EEG
Symptomatic, abnormal EEG
0 20 40 60 80 100
Percentage Recurrence
Recurrence Following
a First Seizure
MESS Trial (Multicentre Study of
Early Epilepsy and Single Seizures)
• Multicenter study of early epilepsy and single seizures
• Randomized controlled trial comparing policies of – Immediate AED treatment
– Deferred AED treatment
• 1443 patients over 5 years were recruited where the clinician and patient were uncertain about the need for AED treatment – 56% with a single seizure
– 44% with 2 or more seizures
• Immediate treatment – 45% carbamazepine
– 45% valproate
– 10% other AEDs
Marson A, et al. Lancet. 2005;365(9476):2007-2013.
Predicting Recurrence
Risk For Individuals
Prognostic Index
Starting Value
Single seizure 0
2 or 3 seizures 1
4 or more seizures 2
Add if Present
Neurological disorder
of deficit 1
Abnormal EEG 1
Risk Classification Group Final score
Low risk 0
Medium risk 1
High risk 2-4
Kim LG, et al. Lancet Neurol. 2006;5(4):317-322.
Treatment
Policy
1-Year
Recurrence
Risk (%)
3-Year
Recurrence
Risk (%)
5-Year
Recurrence
Risk (%)
Low Risk Start
Delay
26
19
35
28
39
30
Medium Risk Start
Delay
24
35
35
50
39
56
High Risk Start
Delay
36
59
46
67
50
73
Recurrence Risk
MESS Study
Kim LG, et al. Lancet Neurol. 2006;5(4):317-322
Newly diagnosed epilepsy Categories of treatment outcome (N= 1098)
Non responders
24,7% Relapse
6,9 %
Immediate
Responders
28,7%
Remission
68,4%
Responders 75,3%
Refractory
31,7%
Brodie et al. Epilepsia 2009;50 (Suppl 11):411-2
Epilepsy Surgery Seizure free at 5 years postsurgery
Type of surgery No. of patients
(studies)
% seizure free at 5
years (95% CI)
Temporal 3895 (40) 66 (62 – 71)
Temporal +
extratemporal
2334 (25) 59 (56 – 62)
“Extratemporal” 169 (2) 34 (28 – 40)
Frontal 486 (7) 27 (23 – 30)
Parietal 82 (1) 46 (56 – 62)
Occipital 35 (1) 46 (29 – 63)
Téllez-Zenteno et al. Brain 2005; 128:1188-1898 13
Discontinuation of AED Therapy
in Children
Dooley J et al. Neurology 1996:4:969-974
Points # of patients Seizure free
at 24 months
0 1 100%
1 15 95%
2 32 80%
3 35 45%
4 10 5%
Multivariate predictors of recurrence
Female 1 point
Abnormal neuro exam 1 point
Age of onset <120 months 1 point
Focal seizures 2 points
Dooley J et al.
Neurology 1996;
46:969-974
Predicitng Long-Term Outcome of Childhood
Epilepsy in Nova Scotia Canada and Turku
Finland. Sillanpåå M, Camfield P, Camfield C. Arch Neurol 1995:52:589-592
• Scoring system to predict remission in
childhood epilepsy ( n=486) developed in
Canada and tested and validated in Turku,
Finland (n=141) and followed for 30 years
• Nova Scotia scoring system predicted
outcome in 61% of Finnish cases with
positive predictive value of 84%, sensitivity
43%, specificity 88%).
Scoring System
• Variable Score
Age at first seizure, mo
<12 99
12-144 142
>144 0
Intellignece
Normal 111
Retardation 0
Previous Neonatal Seizure
No 218
Yes 0
# seizures before treatment
1 or 2 72
3 to 20 123
>20 0
Sillanpåå M, Camfield P, Camfield C.
Arch Neurol 1995:52:589-592
Prediction
• A score of 495 will predict remission of epilepsy
• Seven of the cases were incorrectly predicted to remit at 10 years
• 166 cases, which were predicted NOT to remit, did so at 10 years
• Limitations:
Children with absence seizures were not included
The Turku Cohort included very few cases <12 years of age
Sillanpåå M, Camfield P, Camfield C. Arch Neurol 1995:52:589-592
• Remarkable that 4 predictors available on
the day of diagnosis could be so strong
predictors of outcome 30 years later.
• EEG did not contribute
• Predictors of persistent epilepsy were: Fine
motor deficiets , neonatal asphyxia, poor
coordination, high freq of initial seizures,
status epilepsticus, poor mental
development
Sillanpåå M, Camfield P, Camfield C. Arch Neurol 1995:52:589-592
Unfavorable Prognostic Factors
for Antiepileptic Drug Withdrawal • Age at onset >12 y • Symptomatic vs idiopathic etiology • Mental retardation • Abnormal neurologic examination • Family history of epilepsy • Poor initial response to treatment • More than 1 drug being used at time of withdrawal • Epileptiform EEG changes • Slowing on EEG • Emergence of EEG abnormalities during drug withdrawal • Juvenile myoclonic epilepsy
J.Britton. Antiepileptic drug withdrawal. Mayo Clin Proc. 2002;77:1378-1388
Withdrawal of AEDs in Adults:
Medical Research Council (MRC)
Antiepileptic Drug Withdrawal Study
• 409 patients who were seizure free for 2 years or more.
• Randomized to withdrawal or staying on AED
• At the time of randomization 83% of patients were
receiving monotherapy with carbamazepine (237 patients),
phenobarbitone/primidone (72 patients), phenytoin (184
patients) or valproate (228 patients)
Chadwick D et al: Epilepsia. 1996, Lancet 1991; 337: 1177.).
Withdrawal of AEDs in Adults:
Medical Research Council (MRC)
Antiepileptic Drug Withdrawal Study
• By 3 years after a seizure, 95% of patients have
experienced a further 1-year remission of their epilepsy
and by 5 years 90% of patients have experienced a further
2-year remission.
• Most important factors contributing to the risk of further
seizures after a first seizure after randomization were:
• 1. Previous seizure-free interval
• 2. Partial seizures at recurrence
• 3. Previously experienced seizures while receiving
treatment.
Chadwick D et al: Epilepsia. 1996, Lancet 1991; 337: 1177.).
AED Withdrawal: what is the chance
of success? 1994 AAN Practice
Parameter
• 52 Class 11 studies, 1 Class 1 study
• Pooled estimates (weighted average) –
Children 69% are successful; 31% will
recur.
Adults 61% are successful; 39% will
recur.
American Academy of Neurology quality standards
subcommittee. Practice parameter: a guideline for
discontinuing antiepileptic drugs in seizure-free patients.
American Academy of Neurology Practice Parameters 1994.
When to discontinue (AAN
Practice Parameter • Seizure freedom >2 years implies 60% chance of success
in certain epilepsy syndromes
Favorable factors :
1. Control easily achieved on a low dose of one drug
2. No previous unsuccessful attempts at withdrawal
3. Normal neurological exam and EEG
4. Primary generalized epilepsy except JME
5. Benign syndromes
Considerations: driving, pregnancy, work, family
Conclusion
• Very few studies have attempted to use
staging as a means for prediciton or
information
• Only helpful for determing risk for seizure
recurrence if AEDs are withdrawn or risk of
remaining seizure free after intiating drug
therapy in new onset patients
How to apply Cancer Staging to
Epilepsy
Proposal: The FEDS staging system could be based on
• The size and/or extent (reach) of the primary focus or foci
(F)
• Pathological EEG and the extent of interictal pathology (E)
• Whether the patient is drug resistant in a true sense (D), or
has not had or is able to have successful epilepsy surgery
• A history of refractory status epilepticus (S).
How to apply Cancer Staging to Epilepsy
• Neurological exams, imaging procedures,
genetic tests, EEGs, pathology reports, and
surgical reports would provide information
to determine the stage of epilepsy.
Advantages of Staging – Staging helps to plan the appropriate treatment.
– Epilepsy stage can be used in estimating prognosis .
– Knowing the stage of EPILEPSY would be important in identifying clinical trials that may be a suitable treatment option for a patient.
– Staging would help health care providers and researchers exchange information about patients; it provides common terminology for evaluating and comparing the results of clinical trials and different treatment approaches.
Hot Topics Symposium
Conclusions
Elinor Ben-Menachem, M.D.,Ph.D,
Instituet of Clinical Neuroscience and
Physiology,
Sahlgren Academy, Goteborg University,
Sweden
American Epilepsy Society | Annual Meeting
31
Conclusions
• Staging of epilepsy can bring us to a new level in understanding epilepsy severity and prognosis.
• This is a first initiative to try to jumpstart a process which could be successfully implented to aid in better understanding epilepsy and stimulate focused research
