Aplicación ARToolKit nativa

The   clinical   value   and   contribution   of   scalp   EEG-­‐fMRI   in   the   localisation   of   the   EZ   in   patients  with  focal  epilepsy  has  been  assessed  by  comparing  the  IED-­‐related  BOLD  maps   to   non-­‐invasive   methods   used   during   presurgical   evaluation   (Zijlmans   et   al.,   2007,   Moeller  et  al.,  2009,  Pittau  et  al.,  2012),  as  well  as  the  invasively  defined  SOZ  (Thornton   et  al.,  2011,  Khoo  et  al.,  2017)  and  in  some  studies  the  area  of  resection  (Thornton  et  al.,   2010,  An  et  al.,  2013,  Coan  et  al.,  2016).  

2.3.3.1.1  Comparison  with  non-­‐invasive  studies  

Zijlmans   et   al.   (2007)   carried   out   an   EEG-­‐fMRI   study   on   patients   that   were   initially   rejected   for   surgical   resection   due   to   an   unclear   focus   or   if   focus   was   presumed   to   be   multifocal.  Eight  out  of  fifteen  patients  showed  an  IED-­‐related  BOLD  cluster  concordant   to   the   field   of   the   IED   and   in   four   of   these   patients,   EEG-­‐fMRI   results   were   shown   to   improve   the   localisation   of   the   EZ.   In   these   four   patients,   non-­‐invasive   presurgical   evaluation   tools   indicated   an   unclear   focus   in   three   and   presumed   multifocality   in   the   other.  However,  EEG-­‐fMRI  results  showed  a  circumscribed  focus  in  all  four  patients  and   these   patients   were   reconsidered   for   surgery.   Two   out   of   these   four   patients   subsequently  underwent  icEEG  and  the  invasively  defined  SOZ  validated  the  findings  of   the  EEG-­‐fMRI  results  (Zijlmans  et  al.,  2007).  These  findings  suggest  that  scalp  EEG-­‐fMRI   can   improve   the   localisation   of   the   presumed   EZ   in   patients   considered   for   surgery.   Moeller  et  al.  (2009)  also  investigated  a  cohort  of  nine  patients  that  had  an  unclear  focus   (non-­‐lesional   FLE).   In   eight   out   of   nine   patients,   they   found   the   most   statistically   significant  BOLD  cluster  (the  global  maximum  (GM))  to  be  concordant  to  the  field  of  the   IED   and   to   the   corresponding   PET   and   SPECT   results.   Furthermore,   two   of   these   patients   underwent   postoperative   histological   analysis   revealing   FCD   and   microdygenesis;   the   GM   IED-­‐related   BOLD   clusters   were   found   to   be   adjacent   or   overlapping  these  regions  (Moeller  et  al.,  2009).  A  larger  study  by  Pittau  et  al.  (2012),   determined   whether   the   IED-­‐related   BOLD   maps   added   any   further   information   than   scalp   EEG   to   the   presumed   region   of   the   EZ.   Similar   to   Moeller   et   al.   (2009),   they   discovered  that  in  the  majority  of  patients  (29  out  of  33  patients;  88%),  the  GM  BOLD   cluster  was  concordant  to  the  field  of  the  IED.  Furthermore,  the  GM  BOLD  cluster  for  21   of  the  33  patients  was  found  to  be  more  contributory  in  the  localisation  of  the  presumed   region   of   the   EZ   compared   to   scalp   EEG   alone   (the   GM   BOLD   cluster   was   deemed   contributory   if   it   more   accurately   localizes   the   region   responsible   for   generating   the   spike  (i.e.  anterior  or  posterior  region  of  a  lobe)  or  if  it  identified  a  deep  brain  structure   such   as   the   hippocampus)   (Pittau   et   al.,   2012).   In   12/14   patients   the   GM   BOLD   was   validated  in  as  the  region  of  the  EZ  using  the  information  obtained  from  icEEG  and/or   lesions  detected  on  MRI  (Pittau  et  al.,  2012).  

These  results  indicate  that  IED-­‐related  BOLD  clusters  show  good  concordance  with  the   field   of   the   IED   and   can   contribute   more   to   the   localisation   of   the   EZ   compared   to   current  non-­‐invasive  presurgical  studies  (Zijlmans  et  al.,  2007)  and  scalp  EEG  (Moeller   et  al.,  2009,  Pittau  et  al.,  2012)  during  presurgical  evaluation.  However,  as  mentioned  in   Chapter  1,  most  centres  use  the  invasively  defined  SOZ  as  the  gold  standard  in  localising   the   EZ.   Two   of   the   three   studies   discussed   above   used   the   invasively   defined   SOZ   to   validate  their  findings  however,  this  was  in  a  few  patients  within  a  cohort  (Zijlmans  et   al.,  2007,  Pittau  et  al.,  2012).    

2.3.3.1.2  Comparison  with  invasive  studies  

Two  studies  have  compared  scalp  IED  related  BOLD  maps  only  to  the  invasively  defined   SOZ  (Thornton  et  al.,  2011,  Khoo  et  al.,  2017).

Thornton  et  al.  (2011)  carried  out  a  study  in  patients  with  FCD  and  discovered  that  in  9   out   of   11   patients,   there   was   at   least   one   IED-­‐related   BOLD   cluster   concordant   to   the   same  region  as  the  invasively  defined  SOZ.  This  study  also  showed  that  scalp  EEG-­‐fMRI   is   good   at   delineating   the   area   of   resection   in   FCD   patients.   For   example,   in   those   patients   in   whom   all   the   IED-­‐related   BOLD   clusters   were   in   the   same   lobe   as   the   invasively  defined  SOZ,  they  had  a  good  postsurgical  outcome.  In  those  patients  in  whom   the  IED-­‐related  BOLD  clusters  were  more  widespread  (in  other  lobes  to  the  invasively   defined   SOZ)   they   were   likely   to   have   a   poor   postsurgical   outcome   or   a   SOZ   that   was   widespread  (Thornton  et  al.,  2011).  Khoo  et  al.  (2017)  carried  out  a  larger  study  in  37   patients  with  mixed  aetiology  and  hypothesised  that  the  GM  IED-­‐related  BOLD  cluster  is   the  region  of  the  IZ  that  also  delineates  the  invasively  defined  SOZ.  They  discovered  that   the  GM  BOLD  cluster  could  predict  the  invasively  defined  SOZ  with  high  confidence  in   68%  of  the  IED-­‐related  BOLD  maps  (Khoo  et  al.,  2017)  and  concluded  that  the  GM  BOLD   clusters  could  contribute  and  guide  icEEG  electrode  placement.  However,  in  contrast  to   Thornton   et   al.   (2011),   Khoo   and   her   colleagues   did   not   include   details   as   to   whether   these   patients   had   surgical   resection   and   their   postsurgical   outcome.   Therefore,   they   were  unable  to  determine  whether  the  location  of  the  GM  BOLD  cluster  is  also  indicative   of  the  EZ  as  the  EZ  can  only  reliably  determined  once  the  patient  has  had  surgery  since  it   is   ‘the   minimum   amount   of   cortical   tissue   that   must   be   resected   to   produce   seizure  

freedom’  (Lüders  et  al.,  2006).  There  are  only  three  studies  that  use  the  area  of  resection  

to   determine   how   well   scalp   EEG-­‐fMRI   localises   the   EZ   and   potentially   predict   postsurgical  outcome  (Thornton  et  al.,  2010,  An  et  al.,  2013,  Coan  et  al.,  2016).    

2.3.3.1.3  Comparison  with  area  of  resection  

The  three  studies  that  have  aimed  to  determine  whether  IED-­‐related  BOLD  maps  can  be   predictive  of  good  postsurgical  outcome  have  compared  the  BOLD  maps  to  the  area  of  

resection  between  good  and  poor  postsurgical  outcome  patients  (Thornton  et  al.,  2010,   An  et  al.,  2013,  Coan  et  al.,  2016).  Thornton  et  al.  (2010)  showed  that  in  the  7  out  of  10   patients   that   were   seizure   free   after   surgery,   six   patients   had   the   GM   BOLD   cluster   present  in  the  area  of  resection.  In  the  other  poor  postsurgical  outcome  patients,  BOLD   clusters  were  found  remote  from  the  area  of  resection.  A  larger  study  by  An  et  al.  (2013)   showed   that   70%   of   the   patients   that   had   the   GM   BOLD   cluster   resected   had   a   good   postsurgical  outcome  whereas  90%  of  the  patients  that  had  no  BOLD  cluster  in  the  area   of  resection  had  a  poor  postsurgical  outcome.  Therefore,  similar  to  some  of  the  previous   studies  mentioned  (Moeller  et  al.,  2009,  Pittau  et  al.,  2012,  Khoo  et  al.,  2017),  these  two   studies  also  indicate  that  the  GM  BOLD  cluster  is  a  good  indicator  of  the  EZ.  However,  it   is  important  to  note  that  although  An  et  al.  (2013)  showed  that  the  resection  of  the  GM   BOLD  cluster  increases  the  likelihood  of  a  good  postsurgical  outcome,  the  sensitivity  of  a   BOLD  cluster  being  in  the  area  of  resection  for  a  good  postsurgical  outcome  patient  was   47%   (An   et   al.,   2013).   Indeed   an   investigation   carried   out   by   Coan   et   al.   (2016)   concluded  that  any  significant  BOLD  cluster  in  the  area  of  resection  is  a  good  predictor   of  postsurgical  outcome  whereas,  the  absence  of  a  significant  BOLD  cluster  in  the  area  of   resection  is  good  predictor  of  poor  post  surgical  outcome  (Coan  et  al.,  2016).    

The   studies   described   in   this   section   show   that   the   IZ   mapped   using   scalp   EEG-­‐fMRI   show  good  concordance  to  the  field  of  the  scalp  IED  (Zijlmans  et  al.,  2007,  Moeller  et  al.,   2009,  Pittau  et  al.,  2012)  and  has  been  able  to  contribute  more  to  the  localisation  of  the   EZ  compared  to  scalp  EEG  alone  (Pittau  et  al.,  2012).  IED-­‐related  BOLD  maps  have  also   shown  good  concordance  to  the  invasively  defined  SOZ  (Thornton  et  al.,  2011,  Khoo  et   al.,  2017)  and  have  the  potential  to  predict  good  postsurgical  outcome  (Thornton  et  al.,   2010,  An  et  al.,  2013,  Coan  et  al.,  2016).  A  common  feature  amongst  these  maps  is  that   they  show  BOLD  clusters  in  multiple  regions  indicating  that  the  region  responsible  for   generating   IEDs   are   widespread,   further   reinforcing   the   epilepsy   network   hypothesis   (Laufs,  2012b).  Some  of  the  studies  above  have  described  the  GM  BOLD  cluster  as  the   marker  of  the  IZ  that  best  represents  the  EZ  (Moeller  et  al.,  2009,  Thornton  et  al.,  2010,   Pittau   et   al.,   2012,   Khoo   et   al.,   2017)   whereas   other   studies   have   shown   the   GM   to   be   remote  from  the  EZ  (Thornton  et  al.,  2011,  An  et  al.,  2013).  This  indicates  that  the  GM  as   a   marker   of   the   EZ   is   still   controversial   however,   a   common   finding   amongst   these   studies   is   that   the   absence   of   BOLD   clusters   in   the   area   of   resection   predicts   poor   postsurgical  outcome  (Thornton  et  al.,  2010,  An  et  al.,  2013,  Coan  et  al.,  2016).