High Frequency Oscillations in Temporal Lobe Epilepsy

Transcription

1 High Frequency Oscillations in Temporal Lobe Epilepsy Paolo Federico MD, PhD, FRCPC Departments of Clinical Neurosciences and Diagnostic Imaging University of Calgary 7 June 2012

2 Learning Objectives Understand the difference between physiological and pathological HFOs Understand the mechanisms underlying HFOs Understand the association of HFOs with disease activity in patients Understand the association of HFOs with seizure outcome Understand how to record and detect HFOs 2

3 Disclosure Statement þ Dr. Federico has received speaker fees from UCB. 3

4 Background Iden0fying epileptogenic zone is cri0cal in surgical treatment of refractory focal epilepsy Ictal EEG is very useful for diagnosing and classifying seizures and epilepsy Epilep0form discharges are highly specific for the epilep0c brain, but Not always concordant with ictal onset zone Only loosely related to disease ac0vity HFOs may be a new biomarker for epilepsy 4

5 EEG frequency bands Ripples ( Hz) Fast ripples ( Hz) 5

6 High frequency oscilla0ons (HFOs) Defini&on: Events with at least 4 consecu0ve oscilla0ons between Hz that clearly rise above baseline. Recorded in humans and animals Most studies recorded HFOs from mesial temporal structures Best seen during slow- wave sleep Seen with interictal discharges, seizures, and in between 6

7 Zijlimans et al. Ann Neurol 2012; 71:169. 7

8 Mechanisms underlying epilep0c HFOs Co- firing of small groups of pathologically- interconnected principal cells Ephap0c interac0ons Gap junc0ons Fast synap0c transmission Out- of- phase firing of neuronal popula0ons Structural, molecular, func0onal changes Increased synap0c noise Acquired channelopathy Synap0c inhibi0on limits spa0al extent of HFOs 8

9 Physiological HFOs Ripples ( 200 Hz) first described in area CA1 and entorhinal cortex of freely behaving rats Memory forma0on and reac0va0on of previous experiences Extratemporal neocortex Related to informa0on processing func0ons 9

10 Pathological HFOs animal model Fast ripples (> 250 Hz) first recorded in the hippocampus in a rat model of epilepsy, but not control animals (Bragin et al. Epilepsia 1999;40:127) Physiological ripples decreased in epilep0c hippocampus 10

11 HFOs & Suscep0bility Kainic acid model of status epilep0cus in rats Post- status, all animals that exhibited HFOs (in DG) went on to develop spontaneous seizures The sooner HFOs appeared the sooner the spontaneous seizures appeared Bragin et al. Epilepsia 2004; 45:

12 Fast ripples in rat Bragin et al. Epilepsia 1999; 40:

13 HFOs in humans Photo of microelectrode Bragin et al. Hippocampus 1999; 9: Bragin et al. Ann Neurol 2002; 52:407.

14 HFOs and the seizure onset zone HFOs are reliable markers of the seizure onset zone Occur in regions of spontaneous seizures, more reliably than interictal discharges Occur in regions where the aeerdischarge threshold is low for cor0cal s0mula0on HFOs increase prior to seizures and AED withdrawal HFOs occur independently of the loca0on and type of lesion HFOs can be found in non- lesional epilepsy 14

15 Iden0fying the Epileptogenic Zone Pathological HFOs may be useful for pre- surgical evalua0on Ripples and fast ripples more abundant at seizure onset zone. Worrell et al. Brain 2008; 131:

16 Zijlmans et al. Ann Neurol 2012; 71:

17 HFOs & post- surgical outcome Beger post surgical outcome has been related more with the amount of fast ripples removed from brain 0ssue Jacobs et al. Ann Neurol 2010; 67:

18 Interictal to ictal transi0on N = 7 animals, N = 14 slices Wistar rats p successive pre- seizure to seizure transi0ons were recorded for 7 animals, N = 35 Khosravani et al. Epilepsia 2005; 46:

19 Pre- ictal HFO power changes Hz Hz * Hz * Hz p < 0.01 n = 35 pre- seizure epochs Khosravani et al. Epilepsia 2005; 46:

20 Pre- ictal HFO changes in humans Khosravani et al. Epilepsia 2009; 50:

21 Seizure onset Khosravani et al. Epilepsia 2009; 50:

22 Electrodes used to record HFOs in humans Depth electrode microelectrode (UCLA) 1.25 mm & 0.04 mm diameter Custom made depth macroelectrode (MNI) 0.85 mm 2 surface area Commercial subdural grid/strip and depth electrodes (Ad- tech, U of Calgary, Toronto Sick Kids) 50 mm 2 surface area (grid/strip) 16 mm 2 surface area(depth) 22

23 Detec0on of HFOs Fast sampling rate, at least 4 x upper frequency of interest (2000 Hz) High pass filter may not be available in all commercial EEG systems Increase EEG amplitude and 0me base Beware of filtering artefact 23

24 Prac0cal considera0ons High sampling rates produce large volumes of data 10 min recording is all that is needed Bipolar montages have less artefact Beware of artefacts electrical (60 or 50 Hz) muscle artefact looks less smooth than HFOs Do not over- interpret very sporadic HFOs 24

25 Zijlmans et al. Ann Neurol 2012; 71:

26 Other methods of detec0ng HFOs Frequency power spectrum, using a Fourier or wavelet transform 26

27 HFOs in scalp EEG and MEG HFOs been recorded in rela0on to epilep0form discharges in scalp EEG & MEG This may represent a new biomarker Epileptogenesis (e.g., following CNS insult) AED effec0veness 27

28 Muscle artefact and ripple oscilla0ons Andrade- Valenca et al. Neurology 2011; 77:

29 Summary HFOs (> 80 Hz) can be recorded with commercially available intracranial electrodes and scalp electrodes HFOs may be a biomarker of the epileptogenic zone Fast ripples more localized to the ictal onset zone Beger post surgical outcome is associated with removal of 0ssue producing fast ripples Recording HFOs is possible with most clinical EEG systems, However, fast sampling rate (> 2000 Hz), ample data storage, and exper0se in iden0fying HFOs (in seqng of artefact) is required Automated detec0on of HFOs is a currently ac0ve field of inves0ga0on 29

30 Thank you 30