Is the Hemodynamic Response to Scalp Interictal Epileptic Discharges the Onset Zone of Intracerebral Interictal Discharges?

Transcription

1 Is the Hemodynamic Response to Scalp Interictal Epileptic Discharges the Onset Zone of Intracerebral Interictal Discharges? Hui Ming Khoo, MD, PhD 1,2 Nicolás von Ellenrieder, PhD 1, Natalja Zazubovits, MSc 1, Daniel He 1, François Dubeau, MD 1, Jean Gotman, PhD 1 1 Montreal Neurological Institute, McGill University, Canada 2 Department of Neurosurgery, Osaka University, Japan

2 Presenter Disclosure Presenter: Hui Ming Khoo Relationships with commercial interests: None Grants/Research Support: Mark Rayport & Shirley Ferguson Rayport Fellowship (MNI), Uehara Memorial Foundation Research Fellowship Speakers Bureau/Honoraria: None. Consulting Fees: None. Other: None

3 Introduction The brain region where interictal epileptic discharges (IEDs) are present in patients with focal epilepsy (the irritative zone), is often widespread and thus considered a poor marker of the epileptogenic zone. The fact that IEDs are often recorded at multiple brain regions with barely distinguishable latency suggested that IEDs could propagate rapidly across the cortex. Despite their observation that good surgical outcome was associated with removal of the brain regions where IEDs were originated, Jasper and Penfield noted the apparent impossibility to differentiate reliably the original IEDs (red spikes) and the propagated IEDs (green spikes). 1 1 Penfield W, Jasper H. Epilepsy and the functional anatomy of the human brain. 1954

4 Introduction EEG-fMRI of scalp IEDs is a non-invasive tool resulting in hemodynamic responses that can contribute to localize the generator of epileptic activity. A few studies with small number of patients had found some correspondence between EEG-fMRI hemodynamic response and intracerebral IED but did not derived the general principle of correspondence. Indeed, we have demonstrated that the maximum BOLD response often localizes the seizure onset zone defined by SEEG. Removal of the maximum BOLD response was also correlated with good surgical outcome.

5 Objectives We hypothesize that the maximum hemodynamic response to scalp IEDs reflects the region in which these widespread IEDs originated. We sought to determine if IED recorded close to the maximum EEG-fMRI hemodynamic response indeed correspond to the earliest IED during a widespread intracranial IED. medial LCa LCp lateral medial LCp LCa lateral

6 Subjects/Materials All patients with focal epilepsy that participated in EEG-fMRI studies (April July 2017) and then underwent SEEG implantation N=68 Patients excluded No IED during EEG-fMRI, N=18 Technical issues, N=7 No post-implantation imaging, N=3 Patients included N=41 Each patient can have multiple studies Studies N=79 Studies excluded Closest channel located > 10 mm, N=41 No significant BOLD response, N=12 Main channel Studies included N=26 D = 1 cm Each study can have up to two maxima Maximum BOLD response analyzed N=28

7 Methods - To obtain averaged traces and latency IEDs Averaged traces of each channel Main channel Latency Channel N-2 Channel N-1 Channel N

8 Results Example of interictal epileptic discharge (IED) recorded closest to the maximum hemodynamic response being the earliest. Fp1-F3 F3-C3 L R t-value C3-P3 P3-O1 Fp1-F7 F7-T3 ROF T3-T5 T5-O1 Fp1-F9 F9-T9 T9-P9 P9-O1 Fp2-F4 F4-C4 RHp C4-P4 P4-O2 Fp2-F8 F8-T4 T4-T6 T6-O2 Fp2-F10 F10-T10 T10-P10 P10-O2 75μV 1s RH RHp P RCm RSMAa RSMAa RCa RIm RA ROF A S I RSMAa RCa ROF CLAE 2017 Oct 13th 15 th 2017 Vancouver, BC, Canada

9 Results Example of interictal epileptic discharge (IED) recorded closest to the maximum hemodynamic response among the earliest. Fp1-Avg F3-Avg C3-Avg P3-Avg O1-Avg F7-Avg T3-Avg T5-Avg Fp2-Avg F4-Avg C4-Avg P4-Avg O2-Avg F8-Avg T4-Avg T6-Avg Fz-Avg Cz-Avg Pz-Avg F9-Avg T9-Avg P9-Avg F10-Avg T10-Avg P10-Avg 100μV 1s L P RS RP RPH RH RA RP RO A R RS RO RP t-value S I RPH RH RA RS RP

10 Latency (ms) Latency (ms) CLAE 2017 Oct 13th 15 th 2017 Vancouver, BC, Canada Results Latency between the IED of the first channel and the (1) IED of the main channel; (2) IED of any random channel Peak 15.5 Main channel P = P = Any random channel Beginning 46.5 Main channel Any random channel permutation test (1 million repetitions ) 118.4

11 Distance (mm) CLAE 2017 Oct 13th 15 th 2017 Vancouver, BC, Canada Results Distance between the BOLD maxima and location of (1) the main channel; (2) any random channel 80 Distance from BOLD maxima Main channel 6.25 Any random channel

12 Results Latency of an intracerebral IED is correlated to the distance between the location of its recording channel and the BOLD maximum. Distance to BOLD maximum (mm) Distance to BOLD maximum (mm) Pearson correlation The closer the channel is located to a BOLD maximum, the earlier the IED.

13 Discussion/Conclusion 1. Widespread IEDs occur as the result of an IED originating in a small region and propagating within 20 to 50 ms over wide regions. 2. EEG-fMRI is a non-invasive tool that points to this region of IED origin, which we call the spike onset zone. The IEDs recorded close to the EEG-fMRI maximum hemodynamic response are more likely to precede the IEDs recorded in remote locations. The IED delay in a particular channel is correlated with distance of its location to the maximum response. 3. The spike onset zone found by EEG-fMRI is the neuronal source or origin of an IED. It is different from the source obtained by EEG/MEG analysis of the instantaneous electrical field.

14 Special Thanks to Nicolás von Ellenrieder Natalja Zazubovits Daniel He François Dubeau Jean Gotman Funded by Supported by