snu open courseware - deep brain stimulation · 2018. 4. 19. · medtronic inc. activa® tremor...

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



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


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


•Electrical stimulation of the target cells

•Reversible Process

•Diverse applications

Three Stimulating Targets of DBS

• Thalamic nucleus (시상핵)

• Subthalamic nucleus (시상하핵)

• Globus pallidus (창백핵)


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


• 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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• 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



• 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


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


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


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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Edited from youtube video - https://www.youtube.com/watch?v=47anvWA3an4


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


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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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


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



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


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/


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


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

Neural Prosthetic Engineering32

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


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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https://www.neuropace.com/the-rns-system/#how-it-works


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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snu open courseware - deep brain stimulation · 2018. 4. 19. · medtronic inc. activa® tremor...

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