1. Deep brain stimulation for PD
DR AMIT KUMAR GHOSH
Consultant neurosurgeon
NATIONAL NEUROSCIENCES CENTER,CALCUTTA
PEERLESS HOSPITAL AND B. K. ROY RESEARCH CENTER
2ND FLOOR, DEPARTMENT OF NEUROSURGERY
360,PANCHASAYAR
EM BYPASS, GARIA
KOLKATA—700094, INDIA

2. NEUROMODULATION
Neuromodulation is a technology that acts directly on nerves altering or modulating nerve activity by delivering electrical stimulation or pharmaceutical agents directly to a target area
Applications--- Deep brain stimulation
Spinal cord stimulation
Occipital nerve stimulation
Sacral nerve stimulation
Peripheral nerve stimulation
Baclofen pump
Morphine pump

3. Deep brain stimulation for PD
What is Deep Brain Stimulation ?
Electrical stimulation of deep cerebral nuclei by surgically implanted medical device called a Brain Pacemaker (IPG—Implantable pulse generator)
IPG sends electrical impulse to specific nuclei of brain which need to be stimulated .
10/01/2017
NNC

4. PATIENT SELECTION for PD-DBS
Idiopathic Levodopa responsive PD with UPDRS>25(off-medication) with age<75 years
Complaining---
Significantly disabling motor fluctuations
2) On /Off-medication rigidity, freezing and
Bradykinesia
3) On-medication-related dyskinesias
The best indication of a patient’s suitability for DBS surgery is Levodopa challenge test---at least a 30% improvement in the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS) following a 12-hour medication withdrawal
Neuropsychology--- MMSE>24
Lack of co-morbidities and no long-term anticoagulation

6. Physiological justification Must be identified in high quality image
TARGET SELECTION
( STN,Gpi,ViM)
Physiological justification
Must be identified in high quality image
Safe access

7. TARGET SELECTION
The two main targets considered for DBS in PD are the STN and the GPi.
Current tendency is to prefer targeting the STN because of
Greater improvement in the OFF phase motor symptoms
Higher chance to decrease the medication dosage
3) Lower battery consumption linked to the use of lower voltage in the STN compared to the GPi DBS.
GPi can be the preferred target if LID(Levodopa induced dyskinesia) is the main complaint.
GPi DBS might be preferred for patients with mild cognitive impairment and psychiatric symptoms. Because STN DBS might have a higher rate of cognitive decline and/or depression and worsening of verbal fluency in some studies.

8. The STN( SUB-THALAMIC NUCLEUS) Target
Targeting the STN has been demonstrated to effectively treat the entire spectrum of advanced PD symptoms –
Tremor
Rigidity
Bradykinesia
Motor fluctuations
Drug-induced dyskinesias with consistent reduction the need for dopaminergic medication postoperatively.

10. Neighbours of STN

11. Effect of stimulation of different part of STN
Somatotopic organization of the STN
STN is organized into motor, limbic, and associative regions.
The limbic region lies in the anteromedial portion, the motor region of STN lies in the dorsal 2/3rd region
Lower extremity neurones tend to be found more medially to upper extremity neurones and slightly more posteriorly
Effect of stimulation of different part of STN
Orofacial-related neurones were evenly distributed throughout the dorsal two-thirds
STN trajectories

12. DBS procedure Pre-operative MRI 2-Steps surgery
DBS electrode placement
(i) Planning step– through software work station (anatomical targeting)
MRI/CT fusion ,target selection, AC/PC localisation, entry point selection,trajectory selection and finally to get frame setting
(ii) Insertion of leads ---accomplished by stereotactic apparatus Physiological targeting by MER followed by insertion of DBS electrode
2. DBS battery placement:
> Battery is placed below the clavicle or in some cases the abdomen.

13. Procedure MRI-------------- DBS protocol
STN definition -- T2-weighted images
(TR 2800, TE 90, flip angle 90˚, slice thickness 2.0 mm)
Magnetisation prepared rapid acquisition gradient echo (MPRAGE) sequences were obtained (slab thickness 240 mm (effective thickness 2.0 mm), matrix , TR 9.7) and the scanning time was six minutes and 30 seconds.

14. Planning

15. Attachment of stereotactic frame
The frame should be placed parallel to orbito-meatal line in order to approximate the AC-PC plane

16. Frame Application Checklist
Patient review
☐ Prior shunt
   ☐ Side of shunt and location of catheter
☐ Prior craniotomy
   ☐ Date of craniotomy
   ☐ Side of craniotomy (left/right/midline)
   ☐ Type of craniotomy (frontal/parietal/occipital/pterional)
☐ History of local anesthesia experience
   ☐ Need for more than normal amounts
   ☐ Medication allergies
Imaging review
☐ Plain XR
☐ CT head/brain
☐ MRI head/brain
Equipment review
☐ IV access
☐ Frame components complete
☐ Pin and post sets available
☐ Topical and local anesthesia available
☐ Torque wrenches available

17. CT SCAN WITH FRAME
Thin cut CT (2 mm slices with no gap and no gantry tilt)

18. CT and MRI fusion and Frame setting
The advantage of fusing the CT with MRI is the ability to avoid image-distortions inherent to MR imaging adding to the stereotactic accuracy

19. Burr hole and the StimLoc base fixed over the burr hole before beginning of MER

20. Micro-electrode recording
Platinum-iridium glass coated microelectrodes dipped in platinum black with an impedance of around 0.3–0.5 Mo.
Micro-electrode drive
These platinum-iridium microelectrodes are capable of recording single unit activity
Also be used for micro-stimulation up to 100 MA without significant breakdown in their recording qualities

21. Micro-electrode recording

22. Electrophysiological Mapping
Sedation was discontinued at least 20 min before microelectrode mapping to ensure patient is alert
Microelectrode recording was used to confirm STN location, and to overcome any intraoperative shift in target position due to gravity, cerebrospinal loss or edema.
After the MER mapping, stimulation mapping along the extent of electrophysiologically identified STN was then performed for all tracts under the supervision of a movement disorders neurologist to characterize
the stimulation thresholds for reduction in symptoms (efficacy) and
Stimulation threshold for side effects (such as paresthesias, muscular contraction, or eye deviation).
Rigidity and tremor were rated in a combined rating from 0 to 100%.
Stimulation side effects (e.g., paresthesias and contraction) and affected body part (e.g., eyes and hand) were recorded
The range of current used for the efficacy and side effect mapping was approximately 0–5 mA, stepped by 0.5 mA

23. Final electrode placement and fixation
Point of best MER activity was selected as the final target. The microelectrode was replaced with a permanent quadripolar macroelectrode
The proximal part of this electrode consists of four nickel conductor wires insulated with a polytetrafluoroethylene jacket tubing. The distal part has four metallic noninsulated contacts of 1.5 mm spaced at 0.5 mm intervals. The diameter of the distal electrode is 1.27 mm

24. DBS system Components of the Medtronic DBS system3
Neurostimulator 1
Lead and Electrodes 1 2
Extension
So, lets look at the medical device in more detail.
Deep Brain Stimulation involves the surgical implantation of three components. The first is a neurostimulator, which is a small, robust electronic device similar to a cardiac pacemaker. It is slim, sleek and no larger than a small pocket calculator. The device is implanted in the upper chest near the clavicle. An extension wire connects the neurostimulator to the third parts of the device, which are the lead and electrodes. The lead is a specially insulated wire with 4 electrodes at the tip. Once programmed, the neurostimulator sends mild electrical pulses via the insulated leads to targeted areas of the brain - different brain structures are targeted for different motor disorders 2 4 3
Patient programmer
Long-term Management

25. Components of DBS DBS system consists of 3 parts,
(i)The IPG : is a battery-powered neurostimulator encased in a titanium housing, which sends electrical pulses to the brain to interfere with neural activity at the target site.
(ii)The lead: is a coiled wire insulated in polyurethane with four platinum iridium electrodes .
(iii)The Extension: it is an insulated wire. The lead is connected to the IPG by the extension.
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NNC

26. Programming parameters
Initial programming is always refined by using intra-operative macrostimulation
data
Four variables that are used in programming are
1. Choice of contacts (0, 1, 2 or 3 used either as the cathode or anode)
2. Frequency of stimulation (hertz),
3. Pulse-width
(ms)
4.Amplitude (voltage).

27. Therapy Specifications of IPG
Longevity
Depends on rechargibility
Amplitude
V (voltage mode) mA (current mode)
Rate
Hz (voltage mode) Hz (current mode)
Pulse Width
60 to 450 µs
* For typical PD patients , the device longevity depends on the programmed settings.
10/02/17
NNC

28. Basal ganglia consists of neostriatum (putamen and caudate nucleus),ventral striatum,globus pallidus externus and internus, STN and SNr pars compacta and reticulata. (Youman’s Text book)

29. Sensory feedback

30. Sensory feedback

31. Frontal cortex includes the supplementary motor area (SMA), the motor cortex (MC) and pre-motor cortical areas (PMC).
(1) skeletomotor,(2) oculomotor, (3) associative, and (4) limbic modalities. Of these the skeletomotor or ‘‘motor’’ circuit, has been considered most important in the pathogenesis of hypokinetic movement disorders such as Parkinson’s disease and
hyperkinetic movement disorders including dystonia, hemiballismus, and dyskinesia.
Striatum is the principal input structure of the basal ganglia, while the Gpi and the substantia nigra pars reticulata (SNr) are the main output structures.

32. Input and output structures are connected by a ‘‘direct’’ pathway that consists of a monosynaptic striato-pallidal (GPi) projection and an ‘‘indirect’’ pathway that is polysynaptic and passes from the striatum to the globus pallidus externus (GPe) and the
subthalamic nucleus (STN) before terminating in GPi and SNr.

33. In addition to thalamic projection GPi also projects to the brainstem pedunculopontine nucleus (PPN) and midbrain extrapyramidal area (MEA).
These regions in turn send projections to the thalamus and spinal cord and likely also play a significant role in mediating the development of parkinsonian motor signs, in particular have been implicated in the development of the postural and gait disorders associated with PD.
In PD the loss of dopaminergic neurons in SNc results in a reduction in striatal and extra-striatal DA. The reduced DAergic input in striatum leads to reduced activity in the direct pathway and increased activity over the indirect pathway.
reduction of neuronal activity of GPe
hyperactivity of the STN
Reduced activity in the direct pathway and increased activity in the indirect pathway lead to increased mean discharge rates of neurons in GPi, and SNr
Increased inhibition of thalamocortical pathways, a reduction in cortical activity and the classic motor symptoms associated with PD

34. Complications of DBS surgery
Wound infection, postoperative headache and worsening/irritable mood and increased suicidality.
Intracerebral haemorrhage
It is expensive.

35. NNC –Centre for Neuromodulation
Deep brain stimulation
Spinal cord stimulation
Change of battery
Programming
Baclofen pump insertion and re-filling

36. 10/02/17
NNC