Delivery of electrical current to a specific subcortical grey matter target to stimulate a desired group of nerve cells which results in specific modulation the output of the involved neurocirciut.

1. DEEP BRAIN STIMULATION(DBS)
BY
DR PARTHA SARATHI MONDAL

2. INTRODUCTION
• Delivery of electrical current to a specific subcortical
grey matter target to stimulate a desired group of
nerve cells which results in specific modulation the
output of the involved neurocirciut.
• Targets are predefined, stimulated by predefined
dosage of electric current through implanted
electrodes.
• Collateral stimulation is minimal.
• Electric current delivery can be adjusted depending
upon response.
• Treats a variety of neurological disorders but
movement disorders remain the main targets.

3. HISTORY OF DBS
• Wilder Penfield may be considered as the pioneer of electrical
stimulation of brain (while performing epilepsy surgery)- surface
stimulation.
• In1948,J. Lawrence Pool, attempted to treat an elderly woman with
anorexia &depression by implanting an electrode in the patient’s
caudate nucleus-first deep stimulation. It lacked target specificity.
• In 1954, Robert Heath attempted to stimulate limbic system to
examine the emotional response using Spigel’s system.
• In 1960,Mazars reported a series of 14 patients treated with
intermittent hypothalamic stimulation for painful syndromes.
• From 1960-1970, main application of DBS was pain.
YEAR PERSON TARGET FOR PAIN
1952 HEATH LIMBIC SYSTEM
1962 MAZARS HYPOTHALAMUS
1967 SHEALY DORSAL COLUMN
1973 HOSOBUCHI THALAMUS

4. Modern era of DBS(after 1975)
YEAR PERSON TARGET DISEASE
1975 Bechtereva Basal ganglia Movement disorders
1979 Cooper Anterior thalamus Epilepsy
1987 Benabid Vim thalamus Tremor
1994 Benabid Subthalamic nucleus Parkinson’s disease
1994 Siegfried GPi Parkinson’s disease
1999 Nuttin Internal capsule OCD
1999 Vandewalle Thalamus Tourette’s syndrome
2003 Broggi Hypothalamus Cluster headache
2005 Mayberg Brodmann area 25 Dpression

5. Principles of neurostimulation
• DBS is essentially an extracellular stimulation.
• Cathodal(-) stimulation results in depolarization-if suprathreshold,
can evoke an action potential
• Anodic(+) stimuli cause hyperpolarization and depolarization of
nearby areas which is called virtual cathod-if suprathreshold, can also
evoke action potential.
• Stimulation can be monophasic/biphasic or polyphasic.
• Electrodes may be monopolar or bipolar.
• Stimulatory parameters-
PARAMETERS EFFECT
1)Amplitude Expressed in voltage or miliApm-controls the intensity of stimulus
2)Pulse width(mS) Duration of each pulse delivered.
3)Frequency(Hz) Rate of pulse delivered.

6. Stimulation can be along the nerve fiber or across it.
Longitudinal stimulation requires less intense stimuli
to evoke action potential.

7. When applied to axon, a stimulus evokes two action potentials which
propagate in opposite direction. Where orthodromic potential brings
the clinical effect, Antidromic (towards cell body) is of littleclinical
significance in most of the times.

8. step1
• Patient selection-Confirm diagnosis, selection of patients from
diagnosed patient pools, rule out unexpected pathologies by preop
imaging.
step2
• Planning of DBS-selection of target , electrode types, pulse
generator setting
step3
• Target localization:-U/L vs B/L, stereotactic image based
localization of electrode site, trajectory.
step4
• Intraop monitoring -for proper electrode placement
Microelectrode recordings(MER)
• Confirmation -stimulation induced improvement of symptoms
• Assessment of Stimulation Induced Side Effects
step5
• Lead placement and Implantable Pulse Generator (IPG) fixation.
step6
• Postoperative imaging- to confirm desired lead location and
trajectory , to detect complications (eg hematoma) .

9. INDICATIONS TARGETS EFFECT
1.Idiopathic Parkinson’s
disease
•STN
•GPi
•Vim of Thalamus
•tremor, rigidity, dyskinesia
•same as above
•Tremor
2. Primary dystonias •GPi •dystonia
3.Essential tremor •Vim of Thalamus •tremor
4. OCD •Medial Thalamus
•Anterior limb of Int capsule
•Medial Thalamus
•Improvement in compulsive
behavior.
•Improvement in depression
5.Epilepsy •Hippocampus
•Anterior Nucleus of the Thalamus
•Decreased seizure frequency
6.Major depression •Nucleus Accumbens
7.Cluster headache •Posterior hypothalamus
8.Anorexia nervosa •Nucleus Accumbens
•Subgenual Cortex (Brodmann area
25)
•Improved BMI and restoration
of menstruation
9.Tardive syndrome •Thalamus
•Posteroventral gpi
•Internal capsule(ic) & nucleus
accumbens
•reduction in tic
•reduction in tic and ocd
•reduction of ocd>tic
10. Alzheimer’s Disease
(AD)
•Ant fornix

10. DBS In Idiopathic Parkinson’s Disease(IPD)
• DBS is preferred over pallidotomy or thalamotomy because of
adjustability & reversibility of DBS with lower complication rate.
• Diagnosis-bradykinesia + atleast one of these(resting
tremor/rigidity/postural instability). Exclude atypical IPDs(MSA,PSP,
Lewy body dementia)
• Patient selection-duration >5yrs, severe disability (UPDRS score at
least 30/108), good(but may be fluctuating) response to levodopa,
absence of severe preexisting dementia or psychiatric illness.
• Expected outcome-
Symptoms responsive to DBS-rigidity, tremor, bradykinesia, levodopa
induced dyskinesia.
Symptoms not responsive to DBS-cognitive decline, hypophonia,
postural instability and “on” period gait freezing, autonomic
dysfunction.

11. The “Ideal Candidate”
• Excellent levodopa responder. However
response interrupted by troublesome motor
fluctuation and dyskinesia.
• No medication-refractory gait symptoms,
mood disorder or cognitive decline-none of
these can be improved by DBS.
• Not too early, nor too late.

12. Mechanism of DBS in IPD
• Inhibition Hypothesis-1)depolarization block
(2) inactivation of voltage-gated currents and
(3) activation of inhibitory afferents (GABAergic).
• Excitation Hypothesis-by altering abnormal firing
pattern of affected necleus.
• Disruption hypothesis-DBS activates axon terminals in
the stimulated nucleus, inducing extensive release of
different neurotransmitters from different axon
terminals, such as GABA and glutamate (Glu), and
dissociates inputs and outputs in the stimulated
nucleus, jamming the terminals in effect.

13. TARGETS ADVANTAGE DISADVANTAGE INDICATION
SUBTHALAMIC
nucleus(STN)
•Easier surgical target.
•Treats bradykinesia, tremor
and rigidity.
•Helps in levodopa dose
reduction.
•More chance of
cognitive decline.
•May be more chance
of weight gain
•Most common
target for IPD.
GLOBUS
PALLIDUS
internus(GPi)
•Treats bradykinesia, tremor
and rigidity.
•Lower chance of cognitive
decline.
•Difficult surgical target
than STN.
•Doesn’t help in
levodopa dose
reduction.
•May be preferred in
cases with drug
induced dyskinesia,
IPD with cognitive
decline or mood
disorder.
Ventral
intermediate
nucleus of
Thalamus
•Treats only tremor. •Other component of
IPD are unaffected.
•Difficult surgical target.
•May be tried in
tremor only IPD.
Caudal zona
incerta
•Controls tremor very well. •Recently described
target. Limited exp.
•Treats mainly tremor.
•May br tried in
tremor predominant
IPD.
Targets for DBS in IPD

14. STN DBS in IPD
• STN-small, obliquely oriented, biconvex, lens-shaped mass of gray
matter, difficult to visualize with conventional clinical 1.5 T and 3.0 T
MRI Dimension- 5.9 mm, 3.7 mm, and 5.0 mm in the AP,
mediolateral, and dorsoventral dimensions respectively.
• Dorsolateral STN is associated with sensorimotor functioning while
the anteromedial STN is associated with limbic function. Damage to
anteromedial part may give rise to mood and cognitive disturbances.

15. STN targeting-direct
• Ideal as location and morphology of STN may not be symmetrical and
may vary from patient to patient.
• Best done on 7T MRI. Atleast 1.5T MRI is required.
• SWI and T2 images-better delineation of grey matters.
• Target should be dorsolateral part of the STN.

16. Red nucleus, particularly anterior border,can be a radiological
reference point for indirect targeting. Red nucleus cut taken
4mm below and parallel to commisural plane.A transverse
line passed through its anterior border. Target is picked on
this line 2mm lateral to medial border of STN(if visible) or
atleast 3 mm lateral to lateral border of Red nucleus.
AC-PC line as standard reference-fixing target after
superimposition on standard radiological atlas (eg
Schaltenbrand Bailey atlas). Target point is picked 3mm
posterior, 4mm inferior and 12mm lateral to midcommisural
point.
STN targeting-Indirect

17. GPi as a target for DBS in IPD
• Indirect Targeting with AC-PC line=2 mm anterior, 5 mm inferior, and
21 mm lateral to the midcommissural point.
• Indirect targetting fromPallidocapsular border- on the axial cut
through intercommisural plane, target is chosen by drawing a 3- to 4-
mm line perpendicular to the pallidocapsular border at the junction
of its posterior 1/3rd and anterior 2/3rd.

18. Trajectory of electrodes and MER
• 60 degrees from the AC-PC line in the sagittal plane and 0 to
15 degrees from the vertical in the coronal plane.
• Avoid cortical veins and entry into ventricular system.
• Navigation can be used to place the burrhole .
• Recordings typically begin 10 mm dorsal to the anatomic
target in case of STN and from striatum in case of Gpi.

19. • ZI-zona incerta
• H1-H1 field of
Forel(thalamic
fasciculus)
• H2-H2 field of
Forel(lenticular
fasciculus)
• IC-internal capsule
• OT-optic tract
H1

20. Microstimulation (STN) -assesment of collateral stimulation
Tip location Effect
1.Corticospinal
-corticobulbar
tract (anterior/
lateral to STN)
Tonic muscle contraction,
dysarthria-reposition lead or
reduce amplitude
2. Medial
lemniscus
(posteromedial to
STN)
Paresthesia-reposition the tip
or decrease amplitude
3. Fascicles of
3rd nerve
(inferomedial to
STN)
Diplopia-use upper electrode
or change to bipolar
electrode.
4.Hypothalamus Flushing, perspiration- usually
get habituated.
5. SNr Levodopa blocking effect,
depression,worsened akinesia
6.Red nucleus Dysequilibrium and gait ataxia
without limb ataxia

21. Microstimulation(GPi) -assesment of collateral stimulation
1. Optimum
location
Usually tremor and dyskinesia
Disappear stat. Rigidity also
diminishes.
2.Medial shift contractions of the
contralateral hand and leg-
corticospinal tract ( CST ).
3.Anteromedi
al shift
dysarthria, conjugate eye
movement, or tonic facial
contraction-corticobulbar tract
4. Posterior
shift
Numbness on the contralateral
face and hand
5. Lateral shift No evoked responses are
shown
during a high-intensity
stimulation.

22. Chronic stimulation
• Should start after approx 3-4 weeks post surgery to
avoid initial lesional improvement.
• Attempt dose adjustment of levodopa depending on
response.
• Select the electrode with widest stimulation window.
• Start with lowest possible stimulation to bring desired
effect , readjustment can be done depending on
response.
Stimulation
Parameters
Values
1.Amplitude 2.4 to 4.4 V
2.Frequency 143 to 173 Hz
3.Pulse 67 to 138 μs

23. Deep Brain Stimulation for Dystonia
• More effective for primary dystonias. Persistent
hypertonia at rest has negative impact on outcome.
• Patient Selection –correct diagnosis, medically resistant or
primary generalized dystonia.
• Target selection- Gpi which lies 19 to 22 mm lateral, 2 to 3
mm anterior, and 4 to 5 mm inferior to the
midcommissural point.
• Trajectory- 60 to 65 degrees anterior & superior to the
intercommissural plane & 0 to 10 degrees lateral to the
vertical axis. Electrode should have 3- to 4-mm span of
GPe and at least 6 mm of GPi.

24. How does GPi DBS differ in Dystonia from IPD?
• Usually done B/L in case of dystonias.
• GA is preferred in dystonias .
• Stimulation parameters of pallidal DBS higher in
dystonias(130–185 Hz, 210–450 μs pulse width,
1.5–5 V) than in PD.
• Rebound dystonic episodes are common after
sudden withdrawal from DBS(eg infected).

25. DBS in secondary dystonia
• Heterogenous group of disorders.
• Course of the dystonia dictated by the primary
disease.
• Usually don’t respond consistently and as
effectively to DBS as in primary except
few(such as tardive dyskinesia).
• Alternative targets(STN) than GPi may be
utilized who fails to respond to GPi
stimulation.

26. DBS for Essential tremor(ET)
• Patient selection-younger pt, refractory tremor, good cognitive
reserve.
• Targets-usually a B/L procedure.
1)Vim-Most commonly used target. 15 mm lateral to the midline at the
level of the intercommissural line (ICL) and 6 mm anterior to the PC.
2)Posterior subthalamic area(PostSTA) –usually direct targeting
3)STN-12 mm lateral to the midline, 16 mm
posterior to the AC, and 4 mm below the ICL.
• Stimulation parameters
TARGET AMPLITUDE WIDTH FREQUENCY Complication of DBS
Vim 145–185 Hz 60–117 μs 2.0–3.7 V Paresthesia, dysarthria, headache
disequilibrium & paresis
Post STA 130–170 Hz 60–112.5 μs 1.9–2.5 V Transient dysphasia ,clumsiness,
Hemiparesis, persistent dizziness
STN 130–180 Hz 60–90 μs 1.5–3 V arm dystonia, dysarthria,
dizziness, balance disturbances

27. Optimal Target in the Treatment for ET?
• Post STA DBS showed better tremor control and hand function with the use of
lower voltages, which resulted in a reduction of side effects, such as dysarthria
and disequilibrium and longer battery life.
• Tolerance (Habituation)-is a notorious phenomena peculiar to Essential tremor
which is not seen in Parkinson’s tremor.May be seen upto 40% cases treated with
Vim-DBS. Tolerance doesn’t develop if target is PostSTA.
• Considering the above, PostSTA DBS probably the optimal target in essential
tremor.
Axial Coronal Saggital

28. DBS in Epilepsy
Target Indication
1)MTLE Head of the hippocampus or the
amygdalohippocampal junction.
May be tried in dominant lobe epilepsy
2)Myoclonic and
focal seizure
STN& Substantia Nigra May be tried as a palliative option,
particularly in patients with myoclonic
epilepsy
3)Lennox-
Gastaut
syndrome
Centromedian Nucleus of the
Thalamus
May be indicated in other generalized
seizures.
4) Medically
refractory
partial seizures
+/-secondary
generalization
Anterior Nucleus of the
Thalamus
Decreases seizure frequency and AED
requirement. But cant completely
abolish seizures without drugs.

29. DBS in psychiatric disorders
TARGET OUTCOME
1) TARDIVE
SYNDROME
•THALAMUS
•POSTEROVENTRAL Gpi
•Internal Capsule(IC) & Nucleus
Accumbens
•Reduction in tic
•Reduction in tic and OCD
•Reduction of OCD>tic
2) OCD •Anterior limb of IC.
•Ventral Capsule and Ventral Striatum
•Ventral Capsule and Ventral Striatum.
•Nucleus Accumbens
•STN
•Inferior thalamic peduncle
•Improvement in compulsive
behavior.
•Improvement in depression as well
3) MAJOR
DEPRESSION
•Subgenual cingulate gyrus
•Nucleus accumbens
•Anterior Limb of the Internal Capsule
•Medial Forebrain Bundle
•Most common target.
•Treats depression as well as OCD
•Augments reward effects
3) ANOREXIA
NERVOSA
•Nucleus accumbens. •Improvement of BMI & restoration
of menstruation

30. DBS in obesity
TARGETS FUNCTIONS EFFECT OF DBS
1) Lateral Hypothalamus (LH) Controls feeding behaviour. B/L high-frequency (180- to
200-Hz) LH stimulation results
in inhibition of LH
>deacreased food intake
&increased energy
expenditure
2) Ventromedial
Hypothalamus
Satiety center Continuous low-frequency
stimulation at 60 -80Hz results
in early satiety and thus
decreased wt gain
3) Nucleus Accumbens Reward centre for feeding Reduce binge eating
DBS for other diseases
DISEASES TARGET OUTCOME
1) Alzheimer’s Disease (AD) •Ant Fornix
•Nucleus basalis of meynert
Improved memory
Transient improvement of
neuropsychological status

31. Complications of DBS and avoidance
• Related to the surgical procedure- hemorrhages,
infections, epilepsy, and air embolisms
• Related to machinery failure- electrode breakage,
skin erosion over the IPG or wirings.
• Related to stimulation itself- psychiatric or cognitive
malfunctions and the increased risks for suicide.

32. Related to the surgical procedure or machinery failure
COMPLICATION RISK FACTORS AVOIDANCE
1) Intracranial
Hemorrhage-
incidence 0to 5 %
•Old age, HTN,
•Ventricular entry or gyrus breach
•Multiple electrode passage
•? Intraop MER(questionable)
•Navigation guided entry /passage
& avoid cortical vessels.
•Limit electrode passage to
minimum.
2)Mechanical
failure
(4 to 9.7 %)
•Acute angulation and/or Lack of
fixation at burrhole exit.
•Subcutaneous placement of wires
•Avoid sharp angling.
•Fix electrodes with miniplates at
exit point near burr holes.
•Submuscular implantation
•of the IPG(except in dystonia)
3) Infections, Skin
Erosions
(2.9 to 7.7 %)
•Frontal subcutaneous connector bulk
Straight frontal skin incision.
•Thin scalp skin
•Age < 58 years or >65yr(*Bhatia et all)
•Maintance of thorough asepsis
•Hockey-stick or crescent incisions.
•Partial drilling of outer table.
4) Epilepsy and
Air Embolisms
(0 to 13 %.)
•Abnormal postop imaging
(hemorrhages, edema, ischemia)
•Age over 60
•Transventricular electrode trajectories
•Avoid hemorrhagic risks/
venricular penetration.
•Minimize electrode passage

34. Psychiatric and cognitive disturbance
COMPLICATION RISK FACTORS AVOIDANCE
1)Cognitive decline in IPD •DBS target is GPi •Use STN as target in patients with
already impaired cognitive
functions
2)Mood changes/depression
in IPD
•Increased incidence when target is
STN (microlesioning of the outer part
of the SNr)
•Proper lead placement
3) Suicidal tendency •Relatively younger age
•Early onset of IPD.
•Preoperative major depression or
suicide attempt
•Precise lead placement into
dorsolateral part of STN

35. THANK YOU