Epilepsia ppt

1. Calcified neurocysticercosis lesions and antiepileptic drug- resistant epilepsy: A surgically remediable syndrome? Chaturbhuj Rathore , Bejoy Thomas, Chandrasekharan Kesavadas , Mathew Abraham, and Kurupath Radhakrishnan Epilepsia , 54(10):1815-1822, 2013 doi : 10.1111/epi.12349 Publised october , 2013. Epilepsia

2. BACKGROUND In contrast to association between acute symptomatic seizures and neurocysticercosis , the association between antiepileptic drug (AED)-resistant epilepsy and calcified neurocysticercosis lesions (CNLs) is poorly understood and controversial. The association between AED-resistant epilepsy and CNLs, including the feasibility and outcome of resective surgery.

3. Objectives To assess the causative role of CNL in AED- resistant epilepsy To study the factors that contribute to AED-resistant epilepsy in patients with CNL To define the role of resective surgery in patients with CNL and AED-resistant epilepsy.

4. STUDY DESIGN Prospective database at epilepsy surgery Centery Care, SCTIMST.  Genders Eligible for Study:  Both AED-resistant epilepsy as persistent seizures( ≥1 seizures /month) despite two adequate and tolerated AED monotherapy trials and at least one duotherapy trial. After excluding patients with calcified tumors, vascular malformations, and tuberculomas .

5. Patients and Methods All the patients evaluated for AED-resistant epilepsy from January 2001 to July 2010 at SCIMT and found to have calcified lesion/s on imaging studies were selected for this study. Clinical, neuroimaging , and interictal , ictal , and intracranial electroencephalography (EEG) findings to determine the association between CNL and epilepsy.

6. PARTICIPANTS: 45 patients who had CNL in a resident of an endemic region.  18 patients had CNL plus unilateral HS and were classified as the  CNL with HS  group. 27 patients who did not have HS, 10 patients had causes other than CNL for their seizures ( five had malformations of cortical development, two had nonepileptic seizures, two had severe mental retardation, and one had benign rolandic epilepsy).

7. Continued……. 17 patients, in whom CNL was established to be the causative lesion for AED-resistant seizures, formed the  CNL without HS (CNL alone) group.  For the  HS without CNL (HS alone) group , randomly selected 36 patients with mesial temporal lobe epilepsy with HS (MTLE-HS) who had no other lesions on magnetic resonance imaging (MRI), pathologically verified HS after anterior temporal lobectomy , and were seizure-free for at least 5 years following surgery.

8. CNL was diagnosed as the presence of solid, dense, supratentorial calcification of  10 mm in diameter in a resident of an endemic region Clinical evaluation Age at onset of seizures. Age at initial precipitating injury ( IPI) its nature, duration of epilepsy. Clinical semiology of all seizure types, and any change in seizure semiology during the course of illness.

9. EEG At least 2 habitual seizures recorded . Minimum of 10 min of every hour during a 24-h period. Only definite spikes or sharp waves were considered as IEDs. F7, F8, T1, T2, T3, and T4 defined as temporal IEDs.

10. CT and MRI evaluation NCCT&CECT HEAD and a 1.5 T MRI Number and site of calcified lesion(s); size of lesions; presence of surrounding gliosis as determined on T2-weighted and FLAIR sequences; and presence of any other potentially epileptogenic lesion including hippocampal sclerosis (HS).

11. HS defined as the presence of unequivocal atrophy of the hippocampus with a corresponding increase in the signal on T2-weighted and FLAIR sequences.

12. Additional tests SPECT, and intracranial monitoring. For calcified lesions, removal of the lesion along with one centimeter of surrounding margin. All specimens histopathologically examined. Defined HS as the loss of neuronal cell population of ≥30% CA1 sector of the hippocampal formation with or without neuronal loss and gliosis involving other mesial temporal structures.

13. Follow-up and seizure outcome At 3 months,1 year following surgery then yearly afterwards. Seizure outcome at each year classified as seizure-free (free of all seizures and auras) or not seizure-free. All the operated patients had a minimum follow-up of 2 years.

14. RESULTS: From January 2001 to July 2010, a total of 3,895 patients with AED-resistant epilepsy . 51 patients had AED-resistant epilepsy and calcified granulomatous lesions on imaging studies. 6 patients have calcified lesions related to previous central nervous system tuberculosis, excluded from study . The remaining 45 patients (24 male, 21 female) fulfilled the inclusion criteria for CNL.

15. C ohort divided into three groups: CNL was the only imaging abnormality and it was considered as the causative lesion for AED-resistant epilepsy (group 1, n = 17) CNL associated with unilateral HS (group 2, n = 18) CNLs were considered as incidental lesions (group 3, n = 10)

16. Characteristic Patient groups Intergroup comparisons p-value a CNL with HS N = 18 CNL alone N = 17 HS alone N = 36 CNL with HS vs. CNL alone CNL with HS vs. HS alone Febrile seizures, N (%) 4 (22.2) 19 (52.8) 0.103 0.043 Age at initial precipitating injury, years (mean ± SD) (95% CI) 5.8 ± 5.7 (3.0–8.6) 12.7 ± 6.8 (9.2–16.2) 1.4 ± 1.0 (1.1–1.7) 0.003 0.041 Age at onset of habitual seizures, years (mean ± SD) (95% CI) 15.8 ± 6.7 (12.5–19.1) 12.7 ± 6.8 (9.2–16.2) 9.8 ± 5.8 (7.8–11.8) 0.183 0.002 Seizure clustering, N (%) 5 (27.8) 7 (41.2) 2 (5.6) 0.488 0.034 Secondary generalized seizures, N (%) b 4 (22.2) 14 (82.4) 10 (27.8) 0.001 0.751 CNL within temporal lobe, N (%) 11 (61.1) 2 (11.8) – 0.004 – Extratemporal/bitemporal IED on EEG, N (%) 9 (50.0) 15 (88.2) 3 (8.3) 0.027 0.001 Perilesional gliosis on MRI, N (%) 12 (66.7) 12 (70.6) – 1.000 – Comparison of group characteristics of patients

17. CNL with HS versus HS alone CNL with HS had a lower incidence of typical febrile seizures, older age at initial precipitating injury (IPI), more frequent clustering of seizures, and older age of onset of habitual complex partial seizures as compared with HS . CNL with HS had more extratemporal and bitemporal interictal epileptiform discharges EEG as compared with patients with HS alone. No difference between CNL with HS and HS alone groups in frequency of secondary generalized seizures.

18. CNL with HS versus CNL alone CNL with HS had a lower age at the initial precipitating injury and less frequent secondary generalized seizures as compared with HS alone. 61.1% of patients with CNL with HS had the CNL within the I/L temporal lobe, only 11.8% in the CNL alone had CNL within the temporal lobe. More CNL alone patients had extratemporal / bitemporal interictal epileptiform discharges as compared to those with CNL with HS.

19. Characteristics of patients with AED-resistant epilepsy and calcified neurocysticercal lesion, who underwent surgery. Age Location of CNL Age at 1 st seizure Interictal epileptiform Ictal localization Associated lesion Type of surgery & outcome 27 Right frontal 9 Right frontal Right frontal none Seizure-free following lesionectomy 29 Right frontal 16 Right frontal Right frontal none Seizure-free following lesionectomy 19 Left posterior temporal 11 Left temporal Left posterior none Not seizure-free following temporal lesionectomy 17 Right parietal 13 Bilateral temporal Right hemispheric none Seizure-free following intracranial EEG and lesionectomy 24 Left parietal 12 Left parietal ,left temporal Left parietal none Seizure-free following lesionectomy 47 Left occipital 7 Right temporal Left temporal Left HS Left ATL; not seizure-free 23 Right occipital 9 Right temporal Right temporal Right HS Right ATL; not seizure-free

20. Continued… Age Location of CNL Age at 1 st seizure Interictal epileptiform Ictal localization Associated lesion Type of surgery & outcome 22 Right parietal 5 Right temporal Right temporal Right HS Right ATL; not seizure-free 33 Right frontal,right occipital,left temporal 10 Right temporal Right temporal Right HS Right ATL; seizure-free 21 Right hippocampus 11 Bilateral temporal Right temporal Right HS Right ATL with esionectomy ; seizure-free 25 Left hippocampus 16 Left temporal Left temporal Left HS Left ATL with lesionectomy ; seizure-free 26 Right fusiform gyrus 4 Right temporal Right temporal Right HS Right ATL with lesionectomy; seizure-free 21 Right occipital 13 Right occipital,bilateral temporal Right hemispheric Right HS Intracranial EEG showed seizure origin from the lesion and hippocampus; seizure-free following tempora resection and lesionectomy 26 Left parietal 8 bilateral temporal,left parietal uncertain Left HS Intracranial EEG showed seizure origin from the lesion and hippocampus; seizure-free following temporal resection a nd lesionectomy 25 Right parietal 10 Right parietal, right temporal Right parietal Right HS Lesionectomy alone;, not seizure-free

21. 15 patients underwent resective surgery. Group 1 4 of 5 became seizure-free following lesionectomy alone. Group 2 4 patients underwent anterior temporal lobectomy (ATL) alone, of whom 1 became seizure-free; 5 underwent ATL combined with removal of CNL all of them became seizure-free, whereas 1 patient underwent lesionectomy alone and did not become seizure-free.

22. Pathology H/E of lesions showed dense calcifications ,chronic inflammatory infiltrates and reactive gliosis . All the hippocampal specimens showed classical hippocampal sclerosis without inflammation.

23. DISCUSSION Genetic, parasitic, and environmental factors contribute to the epileptogenesis in CNL, Intense inflammation and perilesional gliosis associated with a higher risk of seizures and epilepsy. These results shows DRE caused by CNLs is a potentially surgically remediable syndrome with a very good chance of seizure freefollowing lesionectomy . Epileptogenicity in these patients is usually restricted to the perilesional tissue .

24. LACUNAE Highly selected group of patients. These results cannot be generalized. Only presence of CNL not responsible for epilepsy. Not establish the definite cause-effect relationship. Not provide the true estimate of AED-resistant epilepsy caused by CNL. Longitudinal long-term follow-up studies of patients with acute neurocysticercosis in endemic areas are required to estimate of the AED-resistant epilepsy caused by CNL.

25. TAKE HOME MESSAGE This study highlights and supports surgical therapy in patients of AED-drug resistant epilepsy with CNL with HS and calcified NCC.

26. Applicability and application Is the study population relevant to my practice and patients? Yes Are the patients in my practice similar to those in the study? Yes

27. Relevance Is this problem common in my practice? Yes Will this information require to change my current practice? Yes

28. CRITICAL APPRAISAL Did study address the focused question ? yes Was there a control group? yes Were the groups comparable at baseline ? No Was outcome measured by blind assessors ? no

29. CRITICAL APPRAISAL Did the surgery make any significant difference in the study? yes How precise were the results ? Precise enough. Are all clinically relevant outcome considered? yes Can results be applied on our population ? yes

30. CNL & HS: Surgical Outcome   Author Country Follow up HS-CNL (n) HS alone(n) CNL alone(n) Leite et al 2000 Brazil 30 months 26 / 32 (81%) 23 / 30 Velasco et .al 2006 Brazil 2 yrs 72% 78% Chandra et al 2010 India ? 4 / 4 (100%) 2/2 Ooi et al 2011 USA 5 yrs 0/1 Chung et 1998 Korea 2yrs 1 /1

31. CNL & Intractable Epilepsy Chung, C.K., Lee, S.K., Chi, J.G., 1998. Temporal lobe epilepsy caused by intrahippocampal calcified cysticercus : a case report. Journal of Korean medical science 13, 445-448. ;1 Rathore , C., Thomas, B., Kesavadas , C., Radhakrishnan , K., 2012. Calcified neurocysticercosis lesions and hippocampal sclerosis: potential dual pathology? Epilepsia 53, e60-62. ;6 /18. Chandra, P.S., Bal, C., Garg , A., Gaikwad , S., Prasad, K., Sharma, B.S., Sarkar , C., Singh, M.B., Padma , V.M., Tripathi , M., 2010. Surgery for medically intractable epilepsy due to postinfectious etiologies. Epilepsia 51, 1097-1100. ; 4 /6 Leite , J.P., Terra-Bustamante, V.C., Fernandes , R.M., Santos, A.C., Chimelli , L., Sakamoto, A.C., Assirati , J.A., Takayanagui , O.M., 2000. Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy. Neurology 55, 1485-1491 .; 3/32 Velasco, T.R., Zanello , P.A., Dalmagro , C.L., Araujo , D., Jr., Santos, A.C., Bianchin , M.M., Alexandre , V., Jr., Walz , R., Assirati , J.A., Carlotti , C.G., Jr., Takayanagui , O.M., Sakamoto, A.C., Leite , J.P., 2006. Calcified cysticercotic lesions and intractable epilepsy: a cross sectional study of 512 patients. Journal of neurology, neurosurgery, and psychiatry 77, 485-488 .; some cases .

32. Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy J.P. Leite , MD, PhD ,  V.C. Terra–Bustamante, MD ,  R.M. F. Fernandes , MD, PhD ,  A.C. Santos, MD, PhD ,  L. Chimelli , MD, PhD ,  A.C. Sakamoto, MD, PhD ,  J.A. Assirati , MD  and O.M. Takayanagui , MD, PhD doi : 10.1212/WNL.55.10.1485Neurology November 28, 2000 vol. 55 no. 10 1485-1491 The presence of CCL does not influence the clinical and pathologic profile of patients with hippocampal atrophy. Clinical histories and postsurgical outcomes were similar to those of patients with classic HS, suggesting that the CCL is probably, in this set of patients, a coincidental pathology and does not have a role in epileptogenesis .

33. Thank you