Staging of Seizures According to Current Classification Systems December 10, 2013

Transcription

1 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

2 Disclosure Name of Commercial Interest Type of Financial Relationship UCB Eisai Bial Lundbeck Electrocore Biocontrol Acta Neurologica Scnadinavica Research Grant, Consult Research Grant, Consult Research Grant Consult Consult Consult Chief Editor American Epilepsy Society 2013 Annual Meeting

3 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 To use staging to determine if antiseizure drugs should be started in new patients or withdrawn in seizure free patients 3.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

4 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

5 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

6 For Cancer (National Cancer National Cancer Institute: 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

7 Previous Attempts at a Scoring System to Predict Seizure freedom and Success of Withdrawal 7

8 Recurrence Following No aetiology, normal EEG a First Seizure No aetiology, abnormal EEG Symptomatic, normal EEG Symptomatic, abnormal EEG Berg AT, Shinnar S. Neurology. 1991;41(7): Percentage Recurrence

9 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):

10 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):

11 Recurrence Risk MESS Study Treatment Policy 1-Year Recurrence Risk (%) 3-Year Recurrence Risk (%) 5-Year Recurrence Risk (%) Low Risk Start Delay Medium Risk Start Delay High Risk Start Delay Kim LG, et al. Lancet Neurol. 2006;5(4):

12 Newly diagnosed epilepsy Categories of treatment outcome (N= 1098) Responders 75,3% Remission 68,4% Relapse 6,9 % Non responders 24,7% Immediate Responders 28,7% Refractory 31,7% Brodie et al. Epilepsia 2009;50 (Suppl 11):411-2

13 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:

14 Discontinuation of AED Therapy in Children Dooley J et al. Neurology 1996:4:

15 Multivariate predictors of recurrence Female 1 point Abnormal neuro exam 1 point Age of onset <120 months 1 point Focal seizures 2 points Points # of patients Seizure free at 24 months % % % % % Dooley J et al. Neurology 1996; 46:

16 Predicitng Long-Term Outcome of Childhood Epilepsy in Nova Scotia Canada and Turku Finland. Sillanpåå M, Camfield P, Camfield C. Arch Neurol 1995:52: 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%).

17 Scoring System Variable Score Age at first seizure, mo < >144 0 Intellignece Normal 111 Retardation 0 Previous Neonatal Seizure No 218 Yes 0 # seizures before treatment 1 or to >20 0 Sillanpåå M, Camfield P, Camfield C. Arch Neurol 1995:52:

18 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:

19 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:

20 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:

21 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.).

22 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.).

23 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 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 % are successful; 39% will

24 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

25 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

26 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).

27 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.

28 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.

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30 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

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