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r TMS workshop RNCM 2


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r TMS workshop RNCM 2

  1. 1. The talk will propose an historical point of view Specifically for the case of Major Depressive Episode, the first major therapeutic goal set for TMS With 3 historical steps FromStep 1 18th Century: Historical Background Electrical Brain “Stimulation” in Psychiatry P L A NStep 2 End of the 20th Century : Validation of rTMS treatment as a focal brain stimulation ToStep 3 21-22th Century: Future Proposition Electrical Brain “Interaction” in Psychiatry
  2. 2. In 1993, first use of TMS in patient with Depression Two cases reports of a single pulse TMS (not repetitive) applied overthe whole cortex with a circular coil 250 single pulses / day 10 days 5-30 % motor threshold S T Depression intensity E PPossible antidepressant effect for one patient 2 50% efficacy! Encouraging result! But did not stimulate a specific focal brain region Höflich et al. 1993
  3. 3. Why to stimulate a focal brain region in depression ? Sadness Happiness More happyTMS may affect mood states Less sad ☐ DLPFC Right ☐ DLPFC RightStudies of rTMS to prefrontal structureshave shown a lateralized effect on mood innormal (healthy) volunteers Less happyGeorge et al. 1996, Pascual Leone et al. 1996. More sad  DLPFC Left  DLPFC Left S T E PLeft frontal lobe is involved in the L R L R 2pathogenesis of depressionLesion and imaging studies suggest that leftprefrontal lobe dysfunction is linked todepressionGeorge et al. 1994. Healthy Depressed Martinot et al. 1990
  4. 4. In 1995, first proof of efficacy of rTMS in depression The “George Team” Open study of 6 patientsrTMS applied over the left DLPFC 20 2s trains of rTMS at 20 Hz 800 pulses / day S T Continued if response after 5 days E P 80 % motor threshold Depression intensity 2 Significant improvement One complete improvement : Encouraging result! George et al. 1995
  5. 5. In 1996, first controlled study of rTMS in depression The “Pascual Leone Team”Multiple cross-over, randomized,placebo-controlled trial with 17 patientsrTMS applied over the left DLPFC Depressed 20 10s trains of rTMS at 10 Hz S  2000 pulses / day T E P 5 days (5 conditions) 2 90 % motor threshols Significant improvement Less depressed6 non responders patients (35 %) Pascual-Leone et al. 1996
  6. 6. Many controlled studies and 11 Meta analysis since 1996 Pascual-Leone trial 2007rTMS is an efficacy and sure focal brain stimulation treatmentThe U.S. Food and Drug Administration (FDA) has approved rTMS for patientswho have not responded to one adequate trial of 2010 antidepressant medication (2007) S T Thus 2007 E P The question is not 2Is rTMS effective for the treatment of depression ? 2008 But Why rTMS is not effective for all patients with depression ? 2011
  7. 7. Why rTMS is not effective for some patients with depression ? There are two classical But we will focus on two less factors of variability classical factors of variability a c   Clinical Stimulation Neuro-anatomical Neuro-functional variability Parameters variability variability S variability T Age  E  P Motor threshold Treatmentrefractoriness Number of pulse Anatomical … 2 precision on the Step 3 Duration of Frequency EDM left DLPFC ?  MRI guided rTMSMicoulaud-Franchi et al., submittedMicoulaud-Franchi and Vion-Dury, 2011
  8. 8. Neuro-anatomical variability: the 5 cm standard method5 cm method 5 cm anterior on a parasagital line 5cm Optimal surface site for activation of the controlateral Abductor Policis Brevis (APB) S TrTMS is supposed to be E Papplied to the left DLPFC 2according to a methodbased on a presumedcoordinates (Talairach 45°Atlas)George et al. 1995Pascual Leone et al. 1996
  9. 9. 5 cm standard method  Neuro-anatomical variabilityThe small black dots indicate the optimal sites for abductor pollicis brevis muscle stimulation over the motor cortex The larger dots indicate the rostral coil positions S T E P 2 Herwig et al., 2001 A considerable variability occurs with the 5cm standard method
  10. 10. Neuro anatomical variability  MRI guided rTMS (Neuronavigated rTMS) Camera Spatial mark Personal MRI of the patient with the dorso prefrontal targetedSzekely© Note that subject can see in real time if the coil stimulates the target and Szekely© Szekely© Szekely© move his head to the right position (beginning of the rTMS interaction…) From David Szekely « Club rTMS et Psychiatrie »
  11. 11. Future rTMS should probably use MRI guided rTMS in order to limit neuro anatomical variability The “Fitzgerald Team” Randomized trial of 51 patientsrTMS applied over the left DLPFCwith either standard 5cm method or using a neuronavigational method (BA9 and 46) S30 5s trains of rTMS at 10 Hz T  1500 pulses / day Depression intenstity E Standar d rTMS P 3 weeks 2 100 % motor threshold MR I gu ided rTM SSignificantly better improvement for the MRI guided rTMS groupFitzgerald et al. 2009
  12. 12. Second step : Neuro-anatomical MRI guided rTMS Electrical Brain Focal Electrical Brain More Stimulation in Focal Stimulation in psychiatry psychiatry S T E P 2 Electrical Brain GlobalCamphor Stimulation inMetrazole psychiatry