Temporal Lobe Epilepsy

1. Conferinta Nationala de Epileptologie a SRIE 19 Noiembrie 2016 – Bucuresti Temporal Lobe Epilepsy Lorella Minotti, MD

2. The spectrum of TL seizures Insularspread Isnard et al. 2000 Blauwblomme et al. 2013 Temporal + subtype Barba et al. 2007 Bartolomei et al. 2010 Thalamicinvolvement Guye et al. 2006 Rosenberg et al. 2006 Sinjab et al. 2013 Lateral subtype Bartolomei 1999 Maillard et al. 2004 Mesial subtype A-Hc-PHcG Wennberg et al. 2002 Entorhinal cortex Spencer & Spencer 1994 Bartolomei et al. 2005 Temporo-polar subtype Chabardès et al. 2005 Mesio-lateral subtype Bartolomei 1999 Maillard et al. 2004

3. The spectrum of TL seizures Insularspread Isnard et al. 2000 Blauwblomme et al. 2013 Temporal + subtype Auditory, gustatory, vestibular aura Piloerection Ipsilateral motor tonic, contraversion Postical dysphoria Barba et al. 2007 Thalamicinvolvement Guye et al. 2006 Rosenberg et al. 2006 Sinjab et al. 2013 Lateral subtype Auditory, visual, vestibular auras Rare automatisms Short duration of seizure Frequent secondary generalisation Maillard et al. 2004 Mesial subtype High frequency of auras (epigastric, fear, experiential) Frequent automatisms (oroalimentary, gestural) Long duration of seizure Maillard et al. 2004 Temporo-polar subtype Short delay to first sign Short delay to loss of contact Chabardès et al. 2005 Mesio-lateral subtype Initial loss of contact Early oral and verbal automatisms Maillard et al. 2004

4. The spectrum of TL seizures

5. The spectrum of TL seizures

6. The spectrum of TL seizures Insularspread Isnard et al. 2000 Blauwblomme et al. 2013 Temporal + subtype Barba et al. 2007 Bartolomei et al. 2010 Barba et al. 2016 Thalamicinvolvement Guye et al. 2006 Rosenberg et al. 2006 Sinjab et al. 2013 Lateral subtype Bartolomei 1999 Maillard et al. 2004 Mesial subtype A-Hc-PHcG Wennberg et al. 2002 Entorhinal cortex Spencer & Spencer 1994 Bartolomei et al. 2005 Temporo-polar subtype Chabardès et al. 2005 Mesio-lateral subtype Bartolomei 1999 Maillard et al. 2004

7. TLE surgery results Engel class I pooled from 100 centers 1 - 3579 Ant. temp. lobectomies ≥ 1986 68% - 413 Amygdalo-hippocampectomies 69% 126 published series from 1991 to 2001 2 - Median Engel class I 70% (33-93%) 40 TLE surgery series with median FU ≥ 5y 3 - Median Engel class I (n=3895) 66% Recent reviews on epilepsy surgery outcome 4 - Engel class I in mTLE 53-84% - Engel class I in TLE with ≥10 years FU 49-83% 1 Engel 1996; 2 McIntosh et al. 2001; 3 Tellez-Zenteno et al. 2005;4 Spencer and Hu 2008.

8. Possible causes of TLE surgery failures within the ipsilateral temporal lobe 2d TL surgery result in a 17-63% class I outcome 1-7 within the controlateral temporal lobe accounts for <20% of failed TL resections 8 outside the temporal lobe pseudo-temporal : very poor outcome with TL surgery 9,10 dual pathology : extraT lesion and HcS are epileptogenic 11 temporal plus Incomplete removal of epileptogenic tissue (1) Wyler et al. 1989; (2)Awad et al. 1991; (3) Germano et al. 1994; (4) Schwartz and Spencer 2001; (5) Siegel et al., 2004; (6) Salanova et al. 2005; (7) Jehi et al. 2010; (8) Hennessy et al. 2000; (9) Fish et al. 1991; (10) Aghakhani et al. 2004; (11) Li et al. 1999

9. Temporal • Prominent ictal involvement of the temporal lobe • Electroclinical features suggestive of TLE • MRI un remarkable / hippocampal sclerosis • Early ictal signs and symptoms suggesting the initial involvement : • Perisylvian region • Orbitofrontal cortex • TPO jonction

10. TLE : an observational concept Temporal Frontal Rolandic Parietal Occipital Perisylvian Parieto-temporal Temporo-occipital Pariéto-temporo-occipital Parieto-occipital Fronto-temporal Fronto-parietal 48 20 10 17 6 3 6 2 4 4 3 5 SEEG studies Epilepsy type Pts N° Fronto-centro-T 1 Fronto-central 2 Temporo-sylvian 5 Temporo-frontal 9 T-P-O 6 FromMunari et al. 1995 From Talairach, Bancaud et al. 1974

11. TLE : an observational concept Temporo-frontal epilepsies Bancaud and Talairach 1992; Babtain et al. 2008; Serletis et al. 2014; Vaugier et al. 2010

12. TLE : an observational concept Temporo-parieto-occipital epilepsies Marossero et al. 1980; Bancaud et al. 1991; Palmini et al. 1993; Zhu et al., 2013

13. TLE : an observational concept Temporo-perisylvian epilepsies Munari et al. 1980; Kahane et al. 2001; Bartolomei et al. 2010

14. TLE : an observational concept Differential diagnosis between temporal and « perisylvian » epilepsy in a surgical perspective Munari et al. 1980 Post-operative seizures after TL surgery Auditory hallucinations Epigastric aura Sialorrhea, dizziness Somatomotor Somatosensitive Impairment of consciousness Tonic-clonic generalization 1 3 4 7 8 lateralized

15. HcS in 4/8 25% TLE : an observational concept Perisylvian involvement in seizures affecting the temporal lobe Kahane et al. 2001 32 ‘TLE’ patients studied by SEEG SSOC involvement initial < 5” > 5” = 0 initial 3 - - - < 5’’ - 5 - - > 5’’ - 4 1 - = 0 2 11 2 4 STG involvemt

16. TLE : an observational concept • prominentinvolvement of the TL • electro-clinicalfeaturesprimarily suggestive of TLE • MRI either normal or showingsigns of HS • IEEG recordingswhich demonstrate • either simultaneous involvement of TL and extraT structures • or 2 co-existing seizure types with TL and extra-T ictal onset Current definition

17. TLE : an observational concept 40 year-old right-handed female Epilepsy onset : 22 years (nocturnal sz) - secondary generalized sz - PB -> partial sz (diurnal) Sz semiology : - LOC, mild OAA, mild GA - postictal aphasia and amnesia EEG interictal : bi-temporal L>R Neurological Ex: normal Comorbidity : depression MRI : normal VEEG : L > R Temporal

18. TLE : an observational concept

19. B. Flo. Right-handed female, 15 year-old • Pregnancy, delivery, psychomotor development : N • Mother : left motor seizures - Brother : dyspraxia • Onset of current manifestations : 7 years (10/m - night +) • Interictal EEG : R post T (-C) spikes • Ictal EEG : R ant T -> R C-P • NPyschological exam : N - fMRI : bilateral (L>R) HD • 18-FDG-PET : unrelevant (post-ictal)

20. B. Flo. SEEG scheme X Y S S V V R R P P W W U D D T T L B L B I O I E O E F F V V P P W L O B O F E

21. B. Flo. SEEG : spontaneous seizure (type 1) iTP aHc pHcG LG FG eTP mT2 mT3 pT2 pT3 eT-O aT1 pT1 pT1 T-P Ins Ins Ins Ins cOp pOP PCG preC sousC iPar P-O eOcc Fz-Cz EKG No warning, LOC, gestural, verbal and oral automatisms, tachypnea, salivation, agitation, urination. Postictal : aphasia, amnesia.

22. B. Flo. SEEG : spontaneous seizure (type 1) iTP aHc pHcG LG FG eTP mT2 mT3 pT2 pT3 eT-O aT1 pT1 pT1 T-P Ins Ins Ins Ins cOp pOP PCG preC sousC iPar P-O eOcc Fz-Cz EKG No warning, LOC, gestural, verbal and oral automatisms, tachypnea, salivation, agitation, urination. Postictal : aphasia, amnesia.

23. B. Flo. SEEG : spontaneous seizure (type 2) iTP aHc pHcG LG FG eTP mT2 mT3 pT2 pT3 eT-O aT1 pT1 pT1 T-P Ins Ins Ins Ins cOp pOP PCG preC sousC iPar P-O eOcc Fz-Cz EKG Pharyngeal constriction, suffocation, tachycardia, vomiting

24. B. Flo. SEEG results B. Flo. Postoperative MRI

25. TLE : an observational concept T+ seizuresvs TL seizurespropagating to juxta-temporal areas Isnard et al. 2000 Nobili et al. 2004 Chabardès et al. 2005

26. TLE : practical considerations T+ group (n=22, 27.5%) 73% Engel I TL (n=58) 88% Engel I TF (n=9) TS (n=7) TPO (n=6) Barba et al. Brain 2007; 130: 1957-1967

27. TLE : practical considerations Sex (M : F) Age at seizure onset (yrs) Age at SEEG (yrs) Disease duration (yrs) Seizure frequency (/mths) Occasional 2d GTC (n°pts) Occasional noct. szrs (n°pts) Febrile seizures (n°pts) HcS (n°pts) Epileptogenic side (R : L) TL (n=58) 27 : 31 9.7 +/- 7.8 29.1 +/- 7.0 19.3 +/- 7.5 14.4 +/- 20.0 16 22 27 49 4 : 54 T+ (n=22) 11 : 11 11.4 +/- 8.1 29.9 +/- 12.4 18.4 +/- 9.4 11.4 +/- 7.8 2 9 10 17 20 : 2 p ns ns ns ns ns ns ns ns ns <0.0001 Barba et al. Brain 2007; 130: 1957-1967

28. TLE : practical considerations Interictal & ictal EEG Bilateral interictal spikes and/or slow waves (% of pts) Precentral interictal spikes and/or slow waves (% of pts) Frontal anterior onset (% of pts) T-parietal onset (% of pts) Precentral onset (% of pts) TL (n=58) 8.5% 1.7% 0% 8.5% 0% T+ (n=22) 43.5% 43.5% 8.7% 26.1% 21.7% p <0.0001 <0.0001 0.002 0.004 <0.0001 Barba et al. Brain 2007; 130: 1957-1967

29. TLE : practical considerations

30. TLE : practical considerations

31. TLE : practical considerations TL GROUP • Seizure duration (>1’) • Consciousness impairement • Ability to warn at onset p=0.02 • Aura • none • somatosensory • visual • auditory illusions • olfactory • gustatory hallucinations • rotatory vertigo • dysmnesic • emotional • other psychic • cephalic • digestive p=0.02 • urogenital • Staring • Lookingaround • Autonomic changes • cardiovascular • respiratory • piloerection • pupillary changes • vomiting • sialorrhea • urination • Simple motorsigns • dystonicposturing • ipsilateral tonic • clonic • contraversion • giratory • Complexbehaviours • oroalimentaryaut • gesturalautp=0.02 • noserubbing • verbal aut • laughing or crying • moaning • hypermotorbehaviour • Postictalsigns • confusion • motordeficit • langage deficit • automatisms • dysphoria • amnesiap=0.02 Barba et al. Brain 2007; 130: 1957-1967

32. TS p=0.009 TPO p=0.02 TLE : practical considerations T+ GROUP • Seizure duration (>1’) • Consciousness impairement • Ability to warn at onset • Aura • none • somatosensory • visual • auditory illusions p=0.02 • olfactory • gustatory hallucinations p=0.02 • rotatory vertigo p=0.02 • dysmnesic • emotional • other psychic • cephalic • digestive • urogenital • Staring • Looking around • Autonomic changes • cardiovascular • respiratory • piloerection p=0.03 • pupillary changes • vomiting • sialorrhea • urination • Simple motor signs • dystonic posturing • ipsilateral tonic p=0.05 • clonic • contraversion p=0.001 • giratory • Complex behaviours • oroalimentary aut • gestural aut • nose rubbing • verbal aut • laughing or crying • moaning • hypermotor behaviour • Postictal signs • confusion • motor deficit • langage deficit • automatisms • dysphoria p=0.0001 • amnesia Barba et al. Brain 2007; 130: 1957-1967

33. TLE : practical considerations 32 year-old right-handed female Epilepsy onset : 25 years (nocturnal sz) - secondary generalized sz - PB -> partial sz (diurnal) Sz semiology : - rising epigastric sensation, LOC, OAA, salivation, bilateral UL dystonia Neurological Examination : normal EEG interictal : bi-temporal R>L VEEG : R > L Temporal MRI : R Temporal lesion (DNET) AT Lobectomy : 10 months seizure free

34. TLE : practical considerations J Neurosurg 2008 Predictors of relapse were the presence of bilateral interictal sharp waves and versive seizures.

35. TLE : practical considerations T-S exploration T-F exploration T-P-O exploration

36. TLE : practical considerations 368 patients operated on (1990-1998)(Kahane et al. 2001, Ryvlin et al. 2001) SURGERY TLE 221 T+ 60 ET 87 TLE T+ 92% 65% 17% 26% 89% 9% Complete removal Incomplete removal TF 21 TS 11 TP 28 ATL in MRI negative & HcS positive cases class I patients

37. 168 ATL surgeries Stereo-EEG in 108 (63.7%) Temporal + : 18 (10.7%) Unilat TLE : 74.5% (95% CI: 70.6-78.4) All patients : 67.3% (95% CI: 63.4-71.2) T+ patients : 14.8% (95% CI: 5.9-23.7) Risk of TLS failure was 5.06 (95% CI: 2.36-10.38) greater in T+E than in uni-TLE Barba et al. Brain 2016; 139: 444-451

38. Class I of Engel following standard anterior temporal lobectomy Main predictor of temporal lobe surgery outcome is the presence of a temporal plus epileptogenic zone Barba et al. Brain 2016; 139: 444-451

39. TLE : conclusions • Does exist - about 10% of TLS cases • T-perisylvian type is the most frequent • Difficult to distinguish from TLE • May account for a significant number of TLS failures • Does T+ surgery work ?

40. Multumesc Thank you