DEEP BRAIN

STIMULATION

A BRAIN PACEMAKER

DR MAHESH KUMAR
CONTENTS

 INTRODUCTION
 HISTORY
 ANATOMY AND PATHOPHYSIOLOGY
 INDICATION
 SELECTION CRITERIA
 SPECIFICATION
 TARGET SELECTION
 SURGICAL TECHNIQUE
 COMPLICATION
INTRODUCTION-DBS

 What is DBS-
 Implanting electrodes in regions of the brain that exhibit
abnormal activity contributing to the disorder and then
stimulating those regions to change or interrupt the
pathologic activity
 Safe and effective surgical therapy for various neurological
and psychiatric disorders.
 Therapy is similar in principle to cardiac pacemaker.
DBS

 Offers hope to severely impaired patients when symptoms are

intractable despite optimal medication and other available therapies.

 One of the main advantages of DBS is that most of its side effects
are reversible and can be managed by adjusting stimulation
parameters.
 This enables the modulation of disease states without irreversibly
destroying neural tissue, as occurs with ablative procedures.
HISTORY
INDICATION-FDA

 Essential Tremor
 FDA approved in 1997
 Parkinson’s disease
 FDA approved in 2002
 Primary Dystonia
 FDA approved in 2003
 Obsessive Compulsive
Disorder
 FDA approved in 2009
POSSIBLY RESPONSIVE TO DBS POORLY RESPONSIVE TO DBS
 Tourette Syndrome  Multiple system atrophy
 Tardive dystonia  Progressive supranuclear palsy
 Huntington's chorea  Corticobasal degeneration
 Tics  Vascular parkinsonism
 Cerebellar tremor  Secondary Dystonia
OTHER INDICATION

 Chronic pain
 Psychiatric disordersOCD and major depression
 Intractable epilepsy
 Minimally conscious states
 Aggressiveness
 Cluster headaches
 Obesity
 Memory modulation
CONTRAINDICATION

 Absolute contra indications:

Uncorrected bleeding tendencies and unstable
cardiopulmonary status
 Relative contra indications:
 “Parkinson-plus” syndromes and dopamine-resistant
Parkinson disease.
 Previous ablative procedure done at same target
 Pregnancy
 Age<18 or >75 years
ANATOMY OF THE BASAL
GANGLIA

• Caudate
• Putamen (neostriatum)
DORSAL •
•
Globus pallidus
Associated are SN&STN

• Substantia innominata,
VENTRA •
•
Nucleus basalis of Meynert
Nucleus accumbens
L • Associated are amygdla,limbic
system
ANATOMY
 NUCLEI OF THE BASAL GANGLIA

 Input Nuclei
 Corpus Striatum (aka Striatum)
 Caudate
 Putamen
 Output Nuclei
 Globus Pallidus Interna
 Substantia Nigra Pars Reticulata
 Intermediate Nuclei
 Globus Pallidus Externa
 Subthalamic Nucleus
 Substantia Nigra Pars Compacta
 PATHOPHYSIOLOGY

Normal physiologic state with balance between the

direct and the indirect pathways
Loss of dopaminergic input from the SNc leads to
increased activity along the indirect pathway and
decreased activity along The direct pathway,
resulting in increased inhibitory input to the ventral
lateral thalamic nucleus (VL)
Effects of an STN lesion in parkinsonism,
decreasing inhibitory input to the VL
 Effects of a GPi stimulation in
parkinsonism, decreasing inhibitory
input to the VL
DYSTONIA

Increased activity
along the direct
pathway, leading to
excessive inhibition
of the GPi and
decreased inhibitory
input to the thalamus
THALAMUS

 Thalamus has four basic functional roles:

 Sensory
 All sensory information (except olfaction) is relayed to the cortex
via the thalamus
 Motor
 Motor system outputs from the basal ganglia and cerebellum are
relayed by the thalamus
 Emotion/memory
 The thalamus is part of the Papez circuit.
 Alertness and arousal.
 ANATOMICAL DIVISIONS

 Anterior Division
 Anterior nucleus
 Medial Division
 Dorsomedial Nucleus (DM)
 Lateral Division
 Dorsal Tier
 Lateral dorsal (LD)
 Lateral Posterior (LP)
 Pulvinar
 Ventral Tier
 Ventral Anterior (VA)
 Ventral Lateral (VL)
 Ventral Posterior (VP)
 SELECTION CRITERIA -
PARKINSON'S DISEASE
Diagnosis
 Presence of bradykinesia associated with
at least one of the three following
conditions: rigidity, resting tremor, and
postural instability
 A diagnosis of idiopathic PD should be
carefully established.
Disease severity
 Marked motor fluctuations in the
response to dopaminergic therapy.
 UPDRS-III scores of 30 (on period)
 UPDRS-III - 40 or 50 (off period)
 Disabling tremor unresponsive to
levodopa
 Disease duration of 5 yr or more.
SELECTION CRITERIA -
PARKINSON'S DISEASE

Age at surgery Response to Levodopa

 Older age is not a specific
exclusion criterion(70yrs)
 >70 yearsCognitive and general
health status should be evaluated.
 Duration of illness is 10 to 15
years at the time of surgery
 Good response to levodopa is
positively correlated .
 A levodopa challenge test (30%
improvement or better)

• Cognitive status: No dementia

• Psychiatric disease:
Untreated psychiatric disease
Depression
 TARGET SELECTION -
PARKINSON'S DISEASE

VENTRAL INTERMEDIATE
THALAMUS
 First reports of DBS for the treatment
of PD .
 88% achieved relief of tremor.
 Currently the role limited to patients
with tremor-predominant symptoms.
 Rigidity, bradykinesia, or drug-
induced dyskinesias effects short
lasting
 Pure anti-tremoric target
 TARGET SELECTION -
PARKINSON'S DISEASE

GLOBUS PALLIDUS INTERNA

 Ideal target ->ventral-posterolateral
area of the pallidum.
 Improves tremor, rigidity, and
bradykinesia .
 Drug-induced dyskinesia
 Good candidates -motor
fluctuations and dyskinesias
 TARGET SELECTION -
PARKINSON'S DISEASE

SUBTHALAMIC NUCLEUS
 STN-stimulation provides a 60-
90% improvement
• Parkinsonian motor disability
• Drug complications
• Reduction in antiparkinsonian
drugs .
 Transient or major levodopa
response: excellent improvement in
motor score .
 DYSTONIA - SELECTION
CRITERIA

Diagnosis Disease severity

 Patients with primary generalized
dystonia (with or without a positive
DYT1 mutation) are the best
candidates.
 Some forms of secondary dystonia
(e.g., tardive) may also respond well
to DBS
 Dystonic symptoms should be either
generalized or disabling (e.g., severe
cervical dystonia)
Disease duration
 Patients with dystonia for less than 15
yrs may improve the most
 Negative correlation

Age at surgery-Younger the patient improve better

DYSTONIA – TARGET
SELECTION

 Globus pallidum-safe and effective .

 VIM nucleus or VOA nucleus of thalamus-
secondary dystonia.
 Subthalamic nucleus-on and off dystonia.
ESSENTIAL TREMOR-
SELECTION CRITERIA

Disease severity No Dementia.

 Tremor must significantly Absence of active psychiatric
interfere with the patient's quality disease.
of life.
Distal tremors better respond than
Response to medications proximal.
 Failed response inspite of all
combinations of a beta blocker,
primidone, and possibly a
benzodiazepine.
ESSENTIAL TREMOR-TARGET
SELECTION

 VIM nucleus of the thalamus -

most commonly targeted site.
 Stimulation of the STN can also
produce satisfactory tremor
control .
COMPLEX TREMOR SYNDROMES
TARGET SELECTION

 Cerebellar Tremor -VIM nucleus of thalamus

 Holmes' Tremor (rubral tremor” or midbrain tremor)-
VIM nucleus of thalamus
 Thalamic Tremor - VIM nucleus of thalamus
 Orthostatic Tremor - VIM nucleus of
thalamus/Subthalamic nucleus
TOURETTE'S SYNDROME
SELECTION CRITERIA

 1)Definite diagnosis  4)Trial of atleast 10 sessions of

behavioural therapy
Established by two
independent clinicians, preferably a  5)Age more than 25 years.
psychiatrist and a neurologist.
 2) Severe and incapacitating tics
as the primary problem.
 3)Refractory disease ,tried 3
different drugs for 12 weeks
atleast.
TOURETTE'S SYNDROME
TARGET SELECTION

 (1) The medial portion of the thalamus at the cross point of the
Centromedian nucleus/Substantia periventricularis/VOA
nucleus.
 (2) The medial portion of the thalamus at the centromedian
nucleus and parafascicular nucleus.
 (3) Posteroventrolateral GPi
 (4) Anteromedial GPi.
 (5) Nucleus accumbens and anterior limb of the internal
capsule
OTHER TARGET SELECTION

 Bilateral GPi DBS –Huntingtons disease

 VOP nucleus of the thalamus – neuroacanthocytosis (NA).
 Subgenual cingulum , inferior thalamic peduncle, and nucleus
accumbens–anterior limb of the internal capsule-Targets in
depression.
 VC/VS of Thalamus –target in OCD
 PHYSIOLOGIC EFFECTS OF
STIMULATION
S
y
n
a
p
D t
e
p i
o
larizt c
o
n

b
i
l
o
n
c
k
h
a
d
i
e b
i
t
i
o
n

4 THEORIES

S
y
n
a
p
t
i
c

d
e
p
l
e
t
i
o
n
 NEUROIMAGING

 PREOP
 High-resolution, T2-weighted, fast
spin echo-inversion recovery
sequence( 3-tesla MRI)
 T2 sequences are particularly
important in GPi and STN
targeting

 WITH FRAME IN PLACE

T1-weighted (spoiled
gradient recalled
acquisition in the steady
state sequence) SPGR
 STN IMAGING

 1)T1-weighted volumetric acquisition of the whole brain with

gadolinium enhancement
 2)T2-weighted axial acquisition through the region of the
subthalamus parallel to the AC-PC plane.
 3)T2-weighted coronal acquisition through the region of the
subthalamus orthogonal to the AC-PC plane.
 The T2-weighted images are acquired in 2 mm intervals with
no-gap.
PAC

 Preoperative blood tests

 ECG,CHEST X RAY,(2D Echo)
 Discontinue vitamin E, aspirin, and other medications
interfering with coagulation for at least 2 weeks before
surgery .
 COMPONENTS OF DBS

IMPLANTABLE EXTENSION
ELECTRODES
PULSE GENERATOR CABLES
COMPONENTS OF DBS

IPG-IMPLANTABLE PULSE
GENERATOR
 Battery encased in titanium cage
 Battery -hybrid combined silver vanadium
oxide battery
 Sends continues impulse to target site
 Size: 65 x 49 x 15 mm (2.6 x 1.9 x 0.6 in)
 Weight: 67 g (2.4 oz)
 Longevity 4–6 years*
(Device longevity depends upon program
settings)
 Channels-2
 Amplitude range
0 - 10.5 V (voltage mode)
0 - 25.5 mA (current mode)
 Frequency Rate
2 - 250 Hz (voltage mode) 30 -
250 Hz (current mode)
 Pulse Width 60 to 450 µs
COMPONENTS OF DBS

ELECTRODES
 Model 3387 &Model 3391
(Approved by FDA )
 Four cylindrical electrode contacts
(1.5 mm high, 1.27 mm in diameter)
spaced either 1.5 mm /0.5mm.
 Platinum–iridium electrode contacts
 Firm tungsten stylet for accurate
targeting and placement
 Soft, blunt tip for passage through
brain tissue
COMPONENTS OF DBS

EXTENSION CABLE
 Leads are connected to IPG
 Model 7483 ( PD)= >Lengths :
40, 60, 95 cm
 Model 7086 (OCD) >Lengths :
40 to 110 cm) 
PROCEDURE

 2 stages  Local anesthesia except severe

movement disorder where proper
 A)Placement of DBS
positioning difficult GA given.
electrodes
 Medication withheld for at least
 B) Placement of a DBS
12 hours
generator and connection to
the electrodes.
PLANNING AND WORK STATION
 FRAME PLACEMENT

 Local anesthesia.
 Frame orientation on the
patient’s head.
 Accurate placement is
parallel to the AC-PC line.
PLANNING AND WORK STATION

 MRI with framespoiled

gradient recalled acquisition in
the steady state sequence(SPGR).
 CT scan/ventriculography can
also done .
 Images transferred to work
station.
 Fusion of preop fast spin echo
and SPGR Images done
PLANNING AND WORK STATION

 Targets-system’s Frame Link

software.
 The AC and PC are identified on
axial images.
 The target coordinates are then
calculated based on fixed
relationships to these structures.
 Software –axial ,coronal and
sagittal coordinates.
 Corrections
 WORK STATION

Posterior edge of AC Anterior edge of PC

WORK STATION

Junction of septum pellucidum with

Aqueduct of Sylvius
splenium of corpus callosum
REGIONAL VIM ANATOMY

 Internal Capsule – ventral and lateral

 Stimulation can cause tonic
contracture
 Ventral Caudal (Vc) thalamus (sensory
relay) – posterior
 Stimulation can cause intolerable
paresthesia
 Ventral Oralis Posterior (Vop)
thalamus – anterior
 Stimulation may cause no effect on
tremor
VIM STIMULATION

 Used in ET and parkinsonian tremor.

 Contralateral tremor in decrease approximately 85% of
patients.
 High-frequency stimulation (more than 100 Hz ) suppress the
tremor.
 Low frequency stimulation exacerbates tremors.
VIM TARGETING AND LEAD
PLACEMENT

 At the level of the anterior commissure–posterior commissure

(AC-PC) line.
 25% the length of the AC-PC line anterior to the PC(3/4 and ¼
junction).
 55% of the AC-PC length laterally
 Target Corrections –wide 3rd ventricle/too close internal
capsule.
VIM TARGETING AND LEAD
PLACEMENT
VIM STIMULATION

 First Macrostimulation is carried  Finally stimulation at 180 Hz to

out to assess efficacy and side assess tremor suppression
effects.  Final position with middle two
 First less than 5 Hz-> see for contact with target.
motor deficits(indicates too close
to Int capsule).
 Next 50 Hz to assess the sensory
threshold.(paresthesia indicates
lead is too posterior)
THALAMIC MAPPING
OUTCOME
 REGIONAL STN ANATOMY

 Target is the dorsal-lateral portion of STN

 Medial lemniscus – posterior
 Stimulation can cause intolerable paresthesia
 Internal Capsule – anterior, lateral and ventral
 Stimulation can cause tonic contracture
 CN III – medial caudal
 Stimulation can cause diplopia
 Hypothalamus – medial rostral
 Stimulation can cause autonomic symptoms
 Ventral Medial STN
 Stimulation can cause mood changes
STN STIMULATION

 Improve motor symptoms in PD.

TARGETING AND LEAD PLACEMENT
INDIRECT
 4 mm below the level of the AC-PC line
 3 mm posterior to the midcommissural point
 12 mm lateral to the AC-PC line
 Corrections-too anterior within the cerebral peduncle / too medial
with respect to the red nucleus.
DIRECT
 visualization of the target structure borders on T2 images
STN STIMULATION
STN STIMULATION
MICROELECTRODE RECORDING OF STN

 Start 15 mm above the anatomic

target
 Reticular nucleus - brief bursts of
spontaneous of activity.
 The subthalamic white matter is
relatively electrically quiet.
 zona incerta-some increased
cellular activity.
 STN is identified by high-
frequency (30-70 Hz), irregularly
firing cells that may respond to
contralateral passive limb
movements.
 Final position with middle two
contact with target
ANGLE OF APPROACH

 By volumetric contrast enhanced  Trajectory avoid trans

T1 image. sulcal,transependymal,transventri
cular routes.
 Start with an AP angle that is
about 50–70 degrees with respect  Avoid damage to vessels.
to the ac-pc plane
 Lateral angle that is about 10–20
degrees from the parasagittal
plane
STN STIMULATION OUTCOME
REGIONAL GPI ANATOMY

 Internal Capsule - posterior

 Stimulation can cause tonic
contracture
 Optic Tract – ventral
 Stimulation can cause visual
disturbances
GPI STIMULATION

 Pallidotomy has been used to treat the akinesia and rigidity

associated with PD-Prelevodopa era.
 Siegfried and Lippitz to perform high-frequency bilateral GPi
stimulation for the treatment of PD.
 Both the motor symptoms and the dyskinesias of PD responds
well.
 Also used in Dystonia
GPI TARGET AND LEAD PLACEMENT

 4 mm below the level of the AC-PC line.

 2 mm anterior to the midcommissural point.
 21 mm lateral to the AC-PC line.
 Corrections -abut the optic tract.
GPI TARGET AND LEAD
PLACEMENT
 PATTERN OF
MICROELECTRODE
RECORDING IN GPI
• MER is performed to identify the external and
the internal segments of the globus pallidus, as
well as the subpallidal white matter.

• Gpe typically displays large-voltage

spontaneous activity at low frequency
interspersed with rapid bursts.

• Transitional zone between Gpe and Gpi-slow

discharge.

• GPi is marked by highly active, high-frequency

(80-90 Hz) neurons
GPI OUTCOME
SURGICAL
TECHNIQUE
 POSITIONING

Supine/Semisitting position
SKIN INCISION

 1 cm in front of the coronal

suture.
 Distance from the midline varies
according to the target and the
size of the ventricle.(1cm-3cm)
 Goal is to avoid entry into the
ventricle and ensure more or less
parallel electrode trajectories
 Preop antibiotic dose
 BURR HOLE PLACEMENT(14mm)

• Once dura opened care taken to prevent CSF loss,,,Target shift may occur
• Immediate pack with gelfoam
INSERTION OF MICROELECTRODES

 Microelectrode recording unit

assembly and attachment
 Special cannula (guide tube) is
inserted into the brain to harbor the
microelectrode and DBS electrode.
 Done under fluoroscopic guidance.
 Record two electrodes
simultaneously.
ELECTRODE INSERTION

 The DBS electrode is placed and ready for macrostimulation and

microelectrode monitoring.
MACROSTIMULATION
 For STN and GPi implants, MER
is performed using the
MicroGuide system.
 Recordings are begun using a
single-channel electrode system.
 Approximately 25 mm above the
presumed target.
 Initial recordings are taken in 0.5-
mm increments until the target
nucleus is encountered and then
are taken every 0.1 to 0.2 mm
 Recordings continue until either
the reticular portion of the SN
(for the STN) or the subpallidal
white matter (for the GPi) is
identified.
 Once the recordings and
macrostimulation are complete,
permanent lead is inserted so that
the maximal number of contacts
lies within the target nucleus.
LOCKING IN POSITION

 The DBS electrode is secured

using Stim loc
(Medrotonic cap)
VERIFICATION

 X-ray verification of the

electrode after being locked in
place to verify non migration.
SECOND STAGE OF DBS

• 1 week later/same time

• Under GA
• Tunneling s/c pocket in infra clavicular fossa
 PROGRAMMING

GOALS

Select a program that

Stimulation parameters Stimulation should provides maximal
must provide therapeutic produce minimal to no benefits for the patient
benefit for the patient side effects with minimal power
drain on the battery.
 Typical stimulation-
 Frequency of 130 to 185
Hz/sec
 Pulse width of 60 to 90 µs
 Amplitude of 1 to 3 V
PROGRAMMING

 Time consuming and labor intensive

 Concurrent adjustments in medications.
 Neurologists to conduct the majority of the programming.
 Approximately 2 weeks following implant
 Medication withheld for at least 12 hours.
 Baseline motor assessments.
 Electrode sequentially stimulated(mono polar)
PROGRAMMING

 Frequency and pulse width -kept at constant settings of 180 Hz

and 90 μsec.
 The amplitude is then steadily increased to the tolerance level
of the patient or until side effects occur.
 Repeat motor evaluation-to assess efficacy of stimulation.
 This process is carried out for each of the four electrode
contacts.
 Between trials gap of 10 to 15 minutes to allow washout of
any previous stimulation effects.
PROGRAMMING

 Once an effective program has

been established, patients are
given an appropriate dose of
levodopa and are observed for
dyskinesias.
 Further programming
adjustments –drug induced
dyskinesia.
COMPLICATIONS

(1) Procedure related

(2) Hardware
related

(3) Stimulation related

COMPLICATIONS

(1) PROCEDURE RELATED

 Overall incidence-approximately 30%.(Minor)
 Most common –
 Intracerebral hemorrhage (1-5%)
 Superficial Infection(3% to 13%)
 Mortality rates are less than 1%.(ICH )
(2) HARDWARE RELATED
 Lead fractures, lead migration, skin erosion, and hardware
malfunctions(5% to 13%)
 Fracture of the electrode is the most common cause of device failure(just
proximal to connection of extension cable)
COMPLICATIONS

(3) STIMULATION RELATED

 Related to activation of adjacent nuclei or fiber tracts.
 THALAMUS - paresthesia involving the face or limb,
dysarthria, dysmetria,and ataxia.
 STN -dysarthria, diplopia, apraxia of eyelid opening, and
depression.
 GLOBUS PALLIDUS -dyskinesia, dystonia, and ataxia
LONG TERM MAINTENANCE

 No MRI other than of the head with use of specific restrictions.

 Avoid activities that cause excessive torque on the neck
 Awareness of electromagnetic fields that can cause DBS devices to turn on/off.
 Battery drain – monitor battery status
 Watch for signs of skin breakdown or irritation around DBS hardware, and inspect for
signs of disconnections or lead wire migration
 Check and reset activations with each programming session, and check impedance
levels.
 If concern for device failure, check unit if on/off, number of activations, battery status,
hardware malfunction (imaging), and impedances
CONCLUSIONS

 Significant advance in treatment

 DBS is safe and efficacious
 With proper patient selection, there is improvement seen with:
 Quality of life measures
 Co-morbid conditions
 Medication intake
 Chronic care costs
 QUESTIONS
O
p
ti
m
al
tar
g
et
(
G
P
i
v
s.
S
T
N
)
t
o
trea
t
h
e
car
d
i
n
al
s
y
m
p
t
o
m
s
o
f
P
D
?

D
o
e
s

t
h
e

u
s
e

o
f

M
E
R

f
o
r

l
o
c
a
l
i
z
a
t
i
o
n
i
m
p
r
o
v
e

c
l
i
n
i
c
a
l

o
u
t
c
o
m
e
s
?
 .

.
THANK U