snu open courseware - deep brain stimulation · 2018. 4. 19. · medtronic inc. activa® tremor...
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Neural Prosthetic Engineering
Deep Brain Stimulation
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Neural Prosthetic EngineeringSeoul National University Nano Bioelectronics & Systems Laboratory
DBS Video
Medtronic Inc. Activa® Tremor Control Therapy
Deep Brain Stimulation
Neural Prosthetic Engineering
Neurological Movement Disorder
Cause
Overactivity in the neighboring neural
network due to loss of the inhibitory
neuron present in the substantia nigra
responsible for movement functions
Kinds and symptoms
• Parkinson’s disease
Tremore at rest state
lower shaking frequency
Ceases during purposeful movement
• Essential Tremor
Tremore during movement
Higher shaking frequency
• Dyskinesia
Power Impairment of voluntary movement
• Dystonia
Disordered tonicity of muscles
substantia nigra
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Treatments for Movement Disorders
Ablative Surgery•Classical method used since 1950’s
•Removal of the deep brain area (thalamotomy)
showing over activities
•Irreversible Process
•Can cause damage of the brain near to the
lesion
Drug Medication
•Drugs based on neural transmitter (dopamine)
•Effects may be reduced in time
Deep Brain Stimulation
•Electrical stimulation of the target cells
•Reversible Process
•Diverse applications
Three Stimulating Targets of DBS
• Thalamic nucleus (시상핵)
• Subthalamic nucleus (시상하핵)
• Globus pallidus (창백핵)
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INTRODUCTION
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What is Deep Brain Stimulaion?
• Deep brain stimulation
(DBS) is surgical treatment
involving the implantation
of a medical device called
“brain pacemaker”, which
sends electrical impulses to
specific parts of the brain.
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https://commons.wikimedia.org/wiki/File:Typi
cal_deep_brain_stimulation_setup.jpg
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• A.D. 46 - Ancient medicine Scribonius Largus suggested applying the live ray to the head of a patient suffering from a headache. This remedy was later used for hemorrhoids, gout, depression, and epilepsy.
• 1786 – Luigi Galvani discovered that nerves and muscles are excited by electricity.
• 1809 – Luigi Rolando showed that brain is electrically excitable.
• 1870 - G. Fritsch and E. Hitzig verified body movements by electrical currents on cerebral tissue (motor cortex) possibility that neurological disorders affecting volitional movement could be treated with electrical stimulation.
Electric Ray
Experiment of Luigi Galvani at 1786
History of Deep Brain Stimulation
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History of Deep Brain Stimulation
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• 1875 – David Ferrier produced an analogous
map of functional localization of human brain
by transposition of monkey brain map with
lesion and stimulation technique.
• 1960s – Cardiac pacemaker was introduced Technological advances made possible the implantation of a comparable device for the focal stimulation of brain.
• 1960 – Hassler et al., stimulation of the ventrolateral thalamus for tremor
• 1973 – Hosobuuchi et al., for pain
http://www.parkinsonsappeal.com/pdfs/The%20History%20of%20Dee
p%20Brain%20Stimulation.pdf
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History of Deep Brain Stimulation
• 1983~1990 – Recordings in the basal ganglia of both normal and MPTP-treated monkeys helped to define the operational principles of basal ganglia-thalamocortical loops, and showed for the first time pronounced over-activity in a part of the basal ganglia called the sub thalamic nucleus (STN)
• 1990 – Lesions of STN in monkeys were shown to completely and permanently reverse the effects of MPTP
• 1993 – The first report from Benabid’s clinic of the use of DBS in the STN to treat Parkinson’s Disease. Benabid’s group had first used DBS in the thalamus as early 1987. This was carried out in three patients, with DBS electrodes implanted on both sides of the brain, which is now the standard approach in PD patients
• 1997 - FDA approved DBS of the thalamus for PD and essential tremor
• 2002 – FDA approved DBS STN and GPi for symptoms of PD
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https://commons.wikimedia.org/wiki/Fi
le:Parkinson_surgery.jpg
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The father of DBS – Alim-Louis Benabid
• Before DBS was developed, the main surgical treatment for Parkinson’s disease was lesioning.
• While the lesioning surgery, the spot was ensured by observing response of patient when electric stimulation with 20-50 Hz freqeuncy was applied.E.g.) posterior – sense of tingling,
lateral – contraction of hand or face
• In 1987, a French neurosurgeon, Benabidexperimented the effect of pulses withfrom 1 to 100 Hz, and found that tremorwas suppressed at 100 Hz.
• Initial target was the thalamus, and later studieson animal have found the subthalamic nucleusis more effective target.
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Wiliams, R., 2010, “Alim-Louis Benabid: stimulation and serendipity”, The Lancet Neurology., Vol.9, Issue 12, 1152, doi:http://dx.doi.org/10.1016/S1474-
4422(10)70291-X
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Timeline
11http://www.medtronicdiabetes.com/
1800 1900
1786: Luigi Galvani’s
experiment of nerve and
muscle excitement by
electricity
1990
1870: Fritsch and Hitzig verified movement induced by cortical stimulation
1875: The first analogous
map of functional
localization of human
brain by David Ferrier
2000
1992: DBS on GPi for Dyskinesia is suggested
1993: DBS on STN for Parkinson’s disease is suggested
2005: DBS on PPN for falls and freezing of gait
1960’s : L-Dopa therapy for Parkinson’s disease is introduced
1997: FDA approved DBS on thalamus for tremor
1950’s: Lesioning on the thalamus was introduced as treatment for Parkinson’s disease
1987: DBS on thalamus for tremor was suggested by A.-L. Benabid and P. Pollak
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Target Applications
• Validated for movement disorders– Parkinson’s disease, essential tremor, dystonia…
• Under validation for affective disorders– Obsessive-compulsive disorder, depression, Tourette’s
syndrome…
• Other various disorders– Chronic pain, anorexia, dementia…
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Parkinson’s Disease
• Parkinson’s Disease (PD) is a neurodegenerative disorder of unknown cause which belongs to a group of conditions called motor-system disorders.
• PD and its related disorders occur when certain neuron become impaired. These are the result of the loss of dopaminergic neurons.
• Loss of dopamine causes the nerve cells to fire out of control, leaving patients unable to direct or control their movement normally.
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Parkinson’s Disease
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Parkinson’s Disease
Edited from youtube video - https://www.youtube.com/watch?v=47anvWA3an4
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Dystonia
• Dystonia is a neurological movement disorder in which sustained muscles contractions causes twisting and repetitive movements or abnormal postures.
• It is often initiated or worsened by voluntary movements, and symptoms may overflow into adjacent muscles.
• Dystonia does not have a specific cause. It seems to be related to a problem in the basal ganglia.
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Dystonia
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Dystonia
Kringelbach, M. L., et al., 2007, “Translational principles of deep brain stimulation”, Nat. Rev. Neurosci., AOP, 623-35, doi:10.1038/nrn2196
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Chronic Pain
• Chronic pain is literally, pain that lasts a long time. It is often defined as any pain lasting more than 12 weeks.
• It is not clear what is exact cause of chronic pain. It may arise from an initial injury such as a back sprain, or there may be an ongoing cause such as illness.
• Consisting of pain may induce sleep disturbance, decrease appetite, and mood change. These difficulties make hard to carry out daily activities.
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Chronic Pain
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Kringelbach, M. L., et al., 2007, “Translational principles of deep brain stimulation”, Nat. Rev. Neurosci., AOP, 623-35, doi:10.1038/nrn2196
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THEORETICAL BACKGROUND
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Then, how does DBS work?
• DBS is suggested as alternative to ablating target structures in the thalamus or basal ganglia, and shows similar therapeutic outcomes with it.
• But the mechanisms of the therapeutic action of DBS remains still uncertain, even though it works.
• DBS works by inhibiting or activating target neurons in thalamus and in basal ganglia.
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Target Area
• Most main target structures of DBS for treatment of movement disorders are in the basal ganglia. But specific location varies depending on the target application.
– For PD, globus pallidus interna (GPi) and subthalamic nucelus (STN) have been found as safe and efficacious targets, and recent study has identified the pedunculopontine nucleus (PPN) as potential target for PD.
– For dystonia, GPi is preferred. And commonly used parameter differs from those of PD with a broader pulse width (200-400 μs) and higher voltage (2.2-7 V)
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Leisman, G., et al., 2013, “Clinical Motor and Cognitive Neurobehavioral Relationships in the Basal Ganglia”, Basal Ganglia – An Integrated View, ISBN
978-953-51-0918-1, Publisher: InTech, doi:10.5772/55227
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Neural Network Involving Motor Circuits
When the decision of movement is made, the information from the frontal cortex passes through the complex loop of basal ganglia, then returns to the supplementary motor area via the thalamus.
Also, GPi and STN are found out as safe and efficacious targets of DBS for Parkinson’s disease from animal model.
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-Blue lines : excitatory connections
-Red lines : inhibitory connections
-GPi : Globus Pallidus interna
-GPe : Globus Pallidus externa
-STN : Subthalamic Nucleus
-SMA : Supplementary Motor Area
-VL : Ventrolateral Nucleus of the thalamus
Kringelbach, M. L., et al., 2007, “Translational principles of deep brain stimulation”, Nat. Rev. Neurosci., AOP, 623-35, doi:10.1038/nrn2196
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Dopaminergic Pathway
• The motor symptoms of Parkinson’s disease is caused by cell death of dopaminergic neurons of the SNc.
• Fundamental of DBS is applying stimulation to a node in the pathway to suppress its activity. Usually, its STN.
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-Blue lines : Excitatory connections
-Red lines : Inhibitory connections
-M1: Primary motor cortex
-PMC : Pre-Motor Cortex
-CMA : Cingulate Motor Area
-SMA : Supplementary Motor Area
-GPe : Globus Pallidus externa
-GPi : Globus Pallidus interna
-STN : Sub-Thalamic Nucleus
-SNc : Substantia Nigra pars
compacta
-SNr : Substantia Nigra pars
recticularis
-VA : Ventroanterior nucleus of the
thalamus
-VL : Ventrolateral nucleus of the
thalamus
PPN : Pedunculopontine Nucleus
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Summary
• Deep Brain Stimulation
– History
– Applications
– Theory
– Practical devices
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PRACTICAL DEVICES
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Medtronic
• Founded in 1949 at Minneapolis, Minnesota.
• Developed implantable battery-powered cardiac pacemaker in 1960s.
• The system of DBS is based on the cardiac pacemaker.
→ Therefore, package located at chest and long leads are needed for connect to brain.
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Cardiac Pacemaker
• The first field of Medtronic was battery operated cardiac pacemaker. It regulates the rhythm of heartbeat.
• Cardiac pacemakers before Medtronic had to be plugged into a wall outlet to operate. It was very dangerous while situations like power outage.
• Now, cardiac rhythm disease management division brings about $ 5 billion revenue to Medtronic.
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Cardiac Pacemaker vs. Deep Brain Stimulator
• Fundamental system of cardiac pacemaker and DBS are almost the same.
• Also, location of surgery for stimulation package is the same, too.
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Products
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• Areas– Implantable Cardiac Pacemakers
– Deep Brain Stimulator for Dystonia, Essential Tremor, Parkinson’s Disease
– Implantable Cardioverter Defibrillator
– Low-Pressure Pulse Generator for Meniere's Disease Management
– Implantable Neurostimulator for Chronic Pain/Neuropathy
– Other Surgery Related Products
http://www.medtronic.com/
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DBS Products
30http://www.medtronic.com/
Power Supply Primary Cell
Rechargeable Battery(9 years)
Primary Cell (4-6 years)
Weight 67 g 40 g 44 – 45 g
Size 65 × 49 × 15 mm3 54 × 54 × 9 mm3 55 × 60 × 11 mm3
Channel Bilateral Bilateral Unilateral
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DBS patient programmer
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• Turn the neurostimulator on and off
• Control amplitude, pulse width, and rate
within physician-prescribed limits
• Change therapy group that is active
• Monitor neurostimulator battery life
• Simple Mode — Simple mode allows the
patient to check the status of his or her deep
brain stimulation device without making any
therapy changes.
• Advanced Mode — Advanced mode gives
the physician the ability to set up four
therapy groups with different stimulation
parameters. The patient can toggle between
groups and adjust therapy within physician-
defined limits. If permitted to do so, the
patient can adjust rate, amplitude, and pulse
width.
http://professional.medtronic.com/pt/neuro/dbs-
md/prod/dbs-patient-programmer-model-
37642/#.WCpF5fmLS71
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MRI and Medtronic DBS Therapy
MR Conditional – Non-clinical testing has demonstrated that Medtronic DBS Systems have been found to be MR Conditional. If this patient
is implanted with a Medtronic DBS System, MRI examinations of the head only or the entire body may be safely performed depending on the
DBS system components implanted.
Medtronic DBS Systems that are eligible for MRI scans of the entire body (ie, full-body eligible) must be scanned under the
following conditions:
▪ 1.5-tesla (T) horizontal closed bore
▪ Maximum spatial gradient of 19 T/m (1900 gauss/cm)
▪ RF transmit/receive body coil (built-in) or RF transmit/receive head coil
▪ Maximum RF power of 2.0 µT B1+rms (B1+ root mean squared)
▪ If B1+rms is not available, a maximum RF power of 0.1 W/kg (0.05 W/lb) whole body and head SAR (specific absorption
rate). Using a SAR setting may result in a more restrictive MRI scan.
▪ Gradient slew rate limited to 200 T/m/s Medtronic DBS Systems that are eligible for MRI scans of the head only must be scanned under the following conditions:
▪ 1.5-tesla (T) horizontal closed bore
▪ RF transmit/receive head coil only
▪ Maximum RF power of 0.1 W/kg (0.05 W/lb) head SAR
▪ Gradient slew rate limited to 200 T/m/s
Follow these MRI guidelines and conditions for approved indications to determine whether and how to conduct an MRI scan safely on a patient
with a Medtronic DBS system. No claims of safety are made for MRI scans involving modified Medtronic DBS systems or components (eg,
custom devices to mitigate allergies) or for non-Medtronic components or accessories.
2015-12-01 MRI guidelines for Medtronic deep brain stimulation systems English 7Note: The MRI guidelines provided here may
significantly extend the MRI examination time or prevent some types of MRI examinations from being conducted on Medtronic
DBS patients.
Image artifacts and distortion
DBS leads have demonstrated image distortion for areas surrounding the implanted leads--
http://manuals.medtronic.com/wcm/groups/mdtcom_sg/@emanuals/@era/@neuro/documents/documents/contrib_228155.pdf
MRI GUIDELINES
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Surgical procedures
• Planning
• Surgery 1
• MER
• Lead insertion
• Confirm efficacy
• Surgery 2
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Potential problems
• Location of stimulator
• Surgery
• Suboptimal lead location
• Stimulation by voltage
• Batteries
• MRI compatibility
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Controller
Neural Stimulator
Electrode arrays
A new neuromodulation system
Prototype Developed within SNU-YUH team work
Head-mountable DBS
Rechargeable DBS
Optimal-sized, reliable Electrode
User friendly Controller
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M.i.Tech Corp. NMD Prototype II
Neural stimulator Hermetic feedthroughs (under 5.0×10-9 sccs @He gas)
Hermetic seal test
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Neuropace Inc.
• Founded in 2014, Mountain View, CA.
• Head-mountable neurostimulator for epilepsy• https://www.neuropace.com/the-rns-system/#how-it-works
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References
[1] Kringelbach, M. L., et al., 2007, “Translational principles of deep brain stimulation”, Nat. Rev. Neurosci., AOP, 623-35, doi:10.1038/nrn2196[2] McIntyre, C. C., et al., 2004, “Uncovering the mechanism(s) of action of deep
brain stimulation: activation, inhibition, or both”, Clin. Neurosphysiol., Vol. 115, 1239-48, doi:10.1016/j.clinph.2003.12.024[3] Leisman, G., et al., 2013, “Clinical Motor and Cognitive Neurobehavioral Relationships in the Basal Ganglia”, Basal Ganglia – An Integrated View, ISBN 978-953-51-0918-1, Publisher: InTech, doi:10.5772/55227[4] Wiliams, R., 2010, “Alim-Louis Benabid: stimulation and serendipity”, The
Lancet Neurology., Vol.9, Issue 12, 1152, doi:http://dx.doi.org/10.1016/S1474-4422(10)70291-X[5] Kotagel, V., et al., “Deep brain stimulation in movement disorder”, online article, url : http://www.medmerits.com/index.php/article/deep_brain_stimulation_in_movement_disorders/P1[6] http://www.cerebromente.org.br/n18/history/stimulation_i.htm[7] Melzack, R., et al., 1965, “Pain mechanisms: a new theory”, Science Vol.150,
No.3699, 971–9.
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