Hertel Unigr Workshop Febr 2015

Deep Brain Stimulation
(DBS) –
State of the art
Frank Hertel
Service National de Neurochirurgie
CH – Luxembourg
1st Uni GR Workshop on DBS for Eating Disorders, Esch / Lux 27.02.2015
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disclosures
DBS cooperation project CHL-LCSB-TUAS
funded by Luxemburg Research Fund (FNR), Luxemburg
CNM-DBS project funded by Stiftung Rheinland-Pfalz,Germany
DTI-fibretracking project funded by Luxemburg Cancer Society
private donation for DBS/navigation research Mr Dalm, Germany
speaker got travel grants in the past from following companies:

Medtronic-Europe, Inomed-Germany, St Jude-Europe
Esch, 2015
DBS, an established therapy !
Deep brain stimulation
From Wikipedia, the free encyclopedia (March 2011)
Deep brain stimulation (DBS) is a surgical treatment …for otherwise-treatment-resistant
movement and affective disorders such as Parkinson's disease, essential tremor, dystonia,
and chronic pain.[1] Despite the long history of DBS,[2] its underlying principles and
mechanisms are still not clear.[3][4] …it is one of only a few neurosurgical methods that allow
blinded studies.[citation needed]
The Food and Drug Administration (FDA) approved DBS as a treatment for essential tremor in
1997,[citation needed] for Parkinson's disease in 2002,[5] and dystonia in 2003.[6]
> 4 Mio hits @ > 8000 hits @ > 27000 hits @
HIRNSTIMULATIONStromschläge lindern Hirnschrittmacher: Für viele

schwerste Depressionen anhaltend PATIENTEN-SCHICKSAL Parkinsonpatienten gibt es neue
Erstmals haben Mediziner Schwerstdepressive
rasch und langfristig heilen können. 8. April
Zwei Elektroden tief im Gehirn Hoffnung: Der sogenannte
2013 16:48 Uhr bremsen das Zittern Hirnschrittmacher kann ihre
Lebensqualität teils dramatisch
verbessern.
Esch, 2015
publications DBS form 1989 – 2013; pubmed 2014
Esch, 2015
stereotactic DBS
since > 25 years DBS
currently 4 ( plus 1) companies with
commercially available systems with
CE and / or FDA mark
Parkinson / Dystonia / Epilepsy (OCD)
about 700 new implantations / year in
Germany
3000 new implantations DBS / year in EU
increasing frequency !
ww >> 100 000 implanted patients
lesioning still present (VIM, GPI)
Esch, 2015 pers Komm
DBS / SL spectrum (… plus X !)
Parkinson´s Disease
Tremor (ET, Holmes…)
Dystonia
OCD
Epilepsy
Clusterheadache
Depression ?
Alzheimer´s ?
Addiction ?
Eating disorders ?
Aggression ?
Loss of consciousness ?
Arterial Hypertension ?
Neuroreport, 2010, Laureys, 2009
Esch, 2015
?
… Spiegel online 2012 about
DBS: „They don‘t know, what
they are doing…“
Esch, 2015
targets
Esch, 2015
DBS / SL - targets
VIM (mot thalamus,PD,tremor)
VOA (anter thalamus,epilepsy)
VOP (poster thalamus,pain)
STN (PD, tremor,epilepsy)
GPI (Dystonia, Tourette´s,PD)
N.acc (OCD, depression)
capsula interna (OCD)
posteriorer hypothalamus
(Cluster, eating diseases)
PPN (REM sleep dist ?)
hippocampus (epilepsy)
… !!! Esch, 2015
fundamentals of Deep Brain
Stimulation / SL
- imaging
- microrecording
- teststimulation
Esch, 2015
imaging
Esch, 2015
direct vs indirect targeting
indirect targeting via ACPC determination
eg VIM not visible even in 3T MRI, Guiot scheme
Optic Tract as orientation for GPI
direct targeting eg for STN
CHL/IO, IKNTec, Hertel et al 2006-14
Esch, 2015
MRI sequences
3D T1 with Gd (double GD?)
(trajectory planning, vessels)
T2 (direct visualisation of STN, optic tract)
inversion recovery (delineation of GPI)
SWAN ® sequence ? (better visualisation of STN)
T1, Gd
SWAN T2
CHL/IO, Bernard, Husch, Dooms,
Gunness, Hertel, 2012, 2014 Esch, 2015
DTI – fibre tracking
Stealth-Viz®
for Navigation and stereotaxy
V Coenen, A Hana, A Husch, G Dooms, F Hertel
CT / MRI matching
1,5 T / 3 T
special interest in
susceptibility weighted MRI
CHL 2014
philosophy : approximation (determination?)
of targets with imaging
variability, not trivial,

targets not as clear, as published ?
CHL / IO, IKNTec, 2013, Bernard, Husch, Hertel
Esch, 2015
target`s visibility in MRI
target visibilty sequence
STN ++ T2, Swan
GPI + INR, T1
VIM - (SWAN ?)
VOA,VPO - (SWAN ?)
internal capsule ++ T2,T1
N. accumbens ? T1,T2
even STN limits not completely clear

limited improvement with 3T
probably sigificant improvements with 7T
Esch, 2015
intraoperative
electrophysiology
Esch, 2015
electrophysiology for
definitive placement
testimulation (macro)
field potentials (macro)
microrecording (micro)
real time functional information
Esch, 2015
surgical strategy due to MER
simultaneous MER tracts (up to 5)
determining stimulation sites depending on best MER

signals
looking mainly for side effects
average time for MER STN: 10 - 15 min / side
average procedure time STN bilateral: 2,75 hs
Hertel 2005
Burchiel, 2004
4 mm
Esch, 2015
simultaneous multitract
exploration makes sense !
Hertel 2013
Rodriguez-Oroz, 2004
personal experience in > 400 MER guided DBS

procedures: 35 % of definitive electrodes not in
central trajectory
Esch, 2015
procedure Luxemburg - IO
preop multimodal MRI
intraop CT (frame / fiducials)
planning
intraop electrophysiology
postop CT / matching
Esch, 2015
frame – based or frameless ?
different systems
493 with / 22 without frame
pitfalls
bias, but that far no real advantage CHL - IO
Cheng 2013, Khan 2013, (Burchiel 2014 ?)

Esch, 2015
current strategies Lux - IO
STN GPI VIM
MRI (T1-Gd, T2) T1-Gd, INR T1-Gd
SWAN (SWAN?) (SWAN?)
Anesthesia local general local
(general)
IPG non-RC RC non-RC
IPG same day (except multiple sclerosis),

mean OR time: 3 hours
Esch, 2015
Parkinson´s disease
Esch, 2015
Leitlinien - THS - Parkinson
THS verbessert QOL, wenn dies mit Med nicht mehr
geht. THS bei IPS mit med nicht behandelbaren hyper-
oder hypokinetischen Fluktuationen. In
Ausnahmefällen Pat, die wegen Dopamin induzierten
Psychosen nicht ausreichend dopaminerg behandelt
werden können. Bei med induzierten
Impulskontrollstörungen…
Vorraussetzungen: Symptome dopasensitiv, schwere
Beeinträchtigung, keine KI.
Dopamin induzierte Psychosen ohne Demenz keine KI.
Esch, 2015
targets Parkinson
VIM GPIi
STN
effective for all cardinal symptoms
(CMPf) (ZI) (VOA/VP) (PPN)

Bergmann 1990, Aziz 1991, Aebischer 1991, Okun 2010, Bernard, Husch, Hertel, 2013
Esch, 2015
tremor dominant Parkinson´s
• STN, VIM, ZI, combinations ?
Lux - IO, 2014
Esch, 2015
MER permits STN surgery
under GA
STN DBS under GA is possible with
reasonable clinical results
50
45 off medication
without
40
stimulation
35 (preop)
30 off medication with
25 stimulation
20
15
10 on medication with
5 stimulation
0
UPDRS III
STN MER in LA STN MER in GA clinical results
special anesthesia protocol

(propofol / remifentanyl / BIS)
Hertel et al, Neurosurgery, 2006
Esch, 2015
Dystonia
Esch, 2015
GPI targeting
• posteroventral GPI
• somatotopy
Hutchison 2003, Rozanski 2013
Esch, 2015
GPI strategy
imaging / optic tract
general anesthesia (in our center)
MER (determination of borders)
teststimulation for side effects
CHL 2013 - 14
Esch, 2015
stable long time effects
• 10 y, n = 47, GPI, DYT1
(Panov)
• 5 y, n = 40, GPI, gen or
segmental D (Volkmann)
DBS is a safe 1st line therapy

for gen and segm Dystonia !
Volkmann 2012, Panov 2013
Esch, 2015
Leitlinien
EFNS guidelines on diagnosis and treatment of primary dystonias.
Albanese A1, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss
JK, Nardocci N, Newton A, Valls-Solé J.
TREATMENT:
…Pallidal deep brain stimulation (DBS) is considered a good option, particularly
for primary generalized or cervical dystonia, after medication or BoNT have
failed. DBS is less effective in secondary dystonia. This treatment requires a
specialized expertise and a multidisciplinary team.
THS empfohlen bei schweren therapierefraktären primär generalisierten und

segmentalen Dystonien. Ergebnisse eher schlecht bei choreoathetoiden
Bewegungsstörungen durch IP oder sekundären Dystonien
2012
Esch, 2015
DBS for children
general anesthesia
BIS monitoring !
subfascial (RC) IPG
inzision
electrode fixation
wound closure
CHL/IO, 2000-14 Esch, 2015
Tremor
Esch, 2015
VIM (Ncl ventrointermedius)
tremor
different cell types
(tremor cells,
somatosensory cells …)
(clinically MER
relevant for DBS ?)
El-Tahawy 2004
Esch, 2015
special tremors
multiple sclerosis: stable disease necessary,
worse results, ataxia, always externalisation
for test
midbrain tremor: good results, mostly VIM,

ev VIM plus GPI
Hertel, J Neurosurg, 2005

Esch, 2015
paradigm shift in DBS for
movement disorders
Esch, 2015
Esch, 2015
early(ier) stim in Parkinson’s
Esch, 2015
41 |
BASELINE
DBS vs best medical treatment
earlier in the disease!
Baseline EARLYSTIM in comp to other studies
Patients Disease Duration

Randomized Trials (n=) Age at Surgery (years)
Deuschl G, et al. 2006 156 61 13.4*
Williams A, et al. 2012 366 59 11.4
Follet K, et al. 2010 299 62 11.7*
Okun M, et al. 2012 136 60 12
EARLYSTIM 251 52.6 7.5
• Duration of dopaminergic treatment Baseline: patients younger

• Between group statistically
significant differences noted and earlier in the disease
• Within-group percent changes with
statistical significance noted
Esch, 2015
42 |
PDQ-39 summary index
Medication
35
PDQ Summary index

significant improvement in 30
QOL in operated patients 25
20
15
0 5 12 24
Time after randomization (months)
60 PDQ-39 subscales
50 p<0.001
40
Change of sub score (% of baseline)
p=0.002 p<0.001 p<0.001 p<0.001 P=0.044 n.s. p<0.009 n.s.

30
20
10
-10
-20
Neurostimulation
Medication
Esch, 2015
shorter disease duration
correlates with better results
in primary and secondary Dystonia

Markun 2012, Lumsden 2013
Esch, 2015
others …
Esch, 2015
Tourette´s
different targets
100 patients published
RCT necessary
option for difficult cases
spont improvement possible for childs
Esch, 2015
TICs / Tourette - Leitlinien
…bei Erwachsenen, schwer betroffenen
Patienten sollte an die Möglichkeit der
Tiefen Hirnstimulation gedacht werden…
Esch, 2015
Pain / OCD
Esch, 2015
Pain / OCD
cluster atypical facial poststroke pain OCD
pain
target posterior PVG plus PVG plus NCL
Hypothalamus sensory sensory accumbens
Thalamus Thalamus
permanent 2/2 2/5 2/4 6/6
implants
result very good fair good very good
Hertel, 2009
Esch, 2015
surgical complications are low !
• 4961 DBS patients in 14 y
• mortality 0,26 % (0,15 % surgical)
• complications correlated with age and
comorbidity
chirurgisch bed Mortalität 0 /515
Intracerebral bleeding 1 / 515 (0,2%)
(with perm deficit)
acute subdural bleedings 2/515 (0,4%)
(OP without deficit)
late infections 35/515 (7%)
(IPG, connectors)
personal series
Rughani 2013
Esch, 2015
DBS network
Luxemburg – SW - Germany
surgeon1 515 DBS
surgeon 2 160 DBS
Institutional 675 DBS
Clinics
CH Luxemburg
SHG Idar Oberstein
SHG Merzig
Westpfalz Kaiserslautern
KINZ Mainz, SPZ Trier
Research
Hochschule Trier, CRP, LCSB (Uni Lux)
psychhiatry,
metabolic disorders
Esch, 2015
DBS for psychiatric diseases
history ethics future

Esch, 2015
DBS for metabolic disorders ?
Brainstorming workshop UNI-GR

Luxemburg
27th febr 2015
J Schneider
K Voegele
F Hertel
Invited speakers:
Prof Bomin Sun – Shanghai
Prof Bart Nuttin - Leuwen
technology, future,
research in Luxemburg
Esch, 2015
Computer assistierte Neuromodulation
Forschungsleistungen im Bereich tiefe
Hirnstimulation wurden vom DAAD und der HRK
als eine von 73 bahnbrechenden Entwicklungen
deutscher Universitäten und Fachhochschulen
ausgewählt.
Forschungsprojekt CNM
Stiftung Rheinland-Pfalz für Innovation fördert
Forschungsvorhaben Computerunterstützte
Neuromodulation.
Das Kooperationsprojekt mit Prof. Dr. K.P.
Koch und Dr. F. Hertel hat zum Ziel, Planung
und Navigation des chirurgischen Eingriffs zur
tiefen Hirnstimulation durch 3D-Volumen- und
Stimulationsmodelle effektiv zu unterstützen und
Arzt und Patient nachhaltig zu entlasten.
Projektlaufzeit: 1.1.12 -31.12.14
Ausgewählt bei "100 Produkte der Zukunft"
PhD students (CHL-TUAS-LCSB)
procedure analysis
automated image
segmentation
A Husch
F Bernard
P Gemmar
N Vlassis
J Thunberg
electrical field modelling
Volume of Tissue activated concept
integration of imaging and electrical

Field modelling
RP Bremm, KP Koch, CNM project
important for analysis of directional
deep brain stimulation …
Pollo, 2014
Esch, 2015
towards
adaptive (autoregulated)
stimulation ?
J Goncalvez
RP Bremm
mathematical modelling of
feedback control for tremor
Oscillator - based A B
linear (A) and non linear (B) Tremor modell

Rehan 2013
local field potentials in PD
pathology of PD and beta peak

in power spectrum
Little, Brown, Eusebio 2012
fast scan Voltametry (Redoxpotencial-
measurement of Neurotransmittershift)
different Neurotransmitters
measurable
Jang 2014
Voltametry
potential cooperation with

Mayo Clinic / Rochester / US,
K Lee
adaptive DBS with multiple feedback signals ?
LFP, MER, Neurotransmittershift

mathematical modelling and simulation
Grahn 2014
Network - hierarchy
Organism
Brain-global
Brain-local
intercellular
subcellular
excellent possibilities
together with Uni-Lux / LCSB !
Parkinsons Disease Map,
LCSB, Uni-Luxemburg
working on a DBS module ?

Pdmap.uni.lu
conclusions
DBS is established and effective for PD,
Dystonia, Tremor, OCD
emerging indications
procedure (including MER) is safe
earlier for Parkinson´s and Dystonia
possible under general anesthesia
that far, frameless systems do not seem to be
superior
upcoming psychiatric indications
DBS for metabolic disorders promising
DBS is a key future technology!
Esch, 2015
determining foci
creating working groups

multidisciplinary - multinational
many thanks to the
whole clinical and
research team N Vlassis
Jochen Schneider J Thunberg
Claus Voegele Christoph Berthold
Kristina Holindra Jorge Goncalvez
Rainer Rink Klaus P Koch
Robert Mandler Robert Strittmatter
Andreas Husch Hans Böcher-Schwarz
Florian Bernard Harald Standhardt
Peter Gemmar Leon Bofferding
Reijko Krüger Lutz Bindl
Jan Koy E Scalais
Nitish Gunness Rudi Balling
Ardian Hana Georges Dooms
The Family of Man, Clairvaux, Luxemburg
Thank You !
Vielen Dank ! Merci beauocoup !
hertel.frank@chl.lu
UNESCO World Heritage, Clairvaux, Luxemburg
Esch, 2015

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Deep Brain Stimulation

CNM-DBS project funded by Stiftung Rheinland-Pfalz,Germany

DTI-fibretracking project funded by Luxemburg Cancer Society

private donation for DBS/navigation research Mr Dalm, Germany

speaker got travel grants in the past from following companies:

> 4 Mio hits @ > 8000 hits @ > 27000 hits @

HIRNSTIMULATIONStromschläge lindern Hirnschrittmacher: Für viele

… !!! Esch, 2015

CHL/IO, IKNTec, Hertel et al 2006-14

variability, not trivial,

even STN limits not completely clear

real time functional information

determining stimulation sites depending on best MER

looking mainly for side effects

average time for MER STN: 10 - 15 min / side

average procedure time STN bilateral: 2,75 hs

personal experience in > 400 MER guided DBS

Cheng 2013, Khan 2013, (Burchiel 2014 ?)

IPG same day (except multiple sclerosis),

(CMPf) (ZI) (VOA/VP) (PPN)

Lux - IO, 2014

STN MER in LA STN MER in GA clinical results

special anesthesia protocol

Hutchison 2003, Rozanski 2013

DBS is a safe 1st line therapy

THS empfohlen bei schweren therapierefraktären primär generalisierten und

CHL/IO, 2000-14 Esch, 2015

midbrain tremor: good results, mostly VIM,

Hertel, J Neurosurg, 2005

Patients Disease Duration

• Duration of dopaminergic treatment Baseline: patients younger

PDQ Summary index

QOL in operated patients 25

p=0.002 p<0.001 p<0.001 p<0.001 P=0.044 n.s. p<0.009 n.s.

in primary and secondary Dystonia

surgeon 2 160 DBS

Institutional 675 DBS

history ethics future

Brainstorming workshop UNI-GR

integration of imaging and electrical

RP Bremm, KP Koch, CNM project

linear (A) and non linear (B) Tremor modell

pathology of PD and beta peak

potential cooperation with

LFP, MER, Neurotransmittershift

working on a DBS module ?

creating working groups

The Family of Man, Clairvaux, Luxemburg

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