1. The document outlines various technological innovations used in neurology, including deep brain stimulation (DBS), vagus nerve stimulation (VNS), radiofrequency ablation, high-intensity focused ultrasound (HIFU), transcranial magnetic stimulation (TMS), and other devices. 2. DBS involves surgically implanting electrodes into the brain which are connected to a pulse generator to electrically stimulate areas of the brain involved in movement disorders. TMS uses magnetic fields to non-invasively stimulate areas of the brain from outside the skull. 3. HIFU is a non-invasive technique that uses focused ultrasound to heat and destroy targeted brain tissue, avoiding the risks of surgery. These technologies are used

1. Technological innovations
in Neurology – 1
Dr Sanjoy Sanyal sanyal.sanjoy8@gmail.com
Professor – Neuroscience
An outline of techno-gadgets used in Neurological disorders
Med 3 Neuroscience students from Summer 2009 to Summer 2010 semesters of
Medical University of Americas (MUA), Nevis, St. Kitts-Nevis, W.I., contributed partly to
the material for this presentation
Updated June 2013

2. • Deep brain stimulation (DBS) (Slides 3 – 23)
• Vagus nerve stimulation (VNS) (Slides 23 – 24)
• Radiofrequency (RF) ablation – obsolete (Slide 25)
• High-intensity focused ultrasound (HIFU) –
ExAblate 4000 (Slides 26 – 37)
• Transcranial magnetic stimulation (TMS) –
Neurostar (Slides 38 – 49)
• Functional electrical stimulation (FES) (Slide 50)
• FES in UL palsy – NESS H200 (Slide 51)
• FES in Foot drop – NESS L300 (Slides 52 – 58)
• Auditory (Cochlear, Brainstem) implants (59 – 65)
• Tinnitus masker – obsolete (Slide 66 – 67)
• Wearable sound generator (WSG) (Slides 68 – 69)
Contents

3. Deep brain
stimulation (DBS)
Definition: Electrical
stimulation of specific
deep brain (basal
ganglia) structures
with implanted
electrodes, with the
aim of evoking a
therapeutic response
in motor (and other)
dysfunctions.

4. • DBS is an experimental neurosurgical treatment in
which the brain is stimulated with electrical
impulses
• Recently out of clinical trials, Medtronics made an
electronic stimulation device that stimulates the
Globus pallidus (GP) / Subthalamic nucleus (STN)
• DBS uses Activa® Therapy, a brain stimulation
technology developed by Medtronic Neurological
Therapy Development Group, to deliver carefully
controlled electrical pulses to precisely targeted
areas of the brain involved in movement control
• The procedure involves placing electrodes, thin
flexible wires, through the skull into deep portions
of the brain
Deep brain stimulation (DBS)

5. DBScomponents

6. Implanted pulse generator (IPG)

7. DBS components

8. • Invasive 8-10 hour surgery
• Target areas are located by
CT / MRI / Microelectrodes.
Latter are used to record the
electrical activity of brain
cells. When right pattern of
activity is noted, surgeon
decides on the best location
for the electrodes
• Lead is inserted via14mm
burr hole in skull, and
Electrodes are implanted in
Subthalamic nucleus (STN) /
Thalamus / Globus pallidus
DBS procedure

9. • Platinum-iridium Electrode has 4
metal contacts (3 cathodes, 1
anode) that can be used in many
different combinations
• Pulse generator (IPG; Neuro-
stimulator) in its titanium casing
is implanted subcutaneously
under left clavicle
• Insulated Extension from IPG is
tunneled under skin, runs behind
ear, up left side of neck and
connects IPG to Lead-Electrodes
DBS procedure

10. DBS in-
situ
>30,000
installed
Cost:
$40,000
Advantage:
No
destruction of
brain
Disadvantag
e: Increased
risk of
intracranial
infection

11. • Motor control structures – Basal ganglia
– Subthalamic nucleus
– Globus pallidus
– Thalamus
• Memory areas – Limbic
– Hippocampus
– Amygdala
– Hypothalamus
– Thalamus
• Motivation, emotion and cognition – Limbic
– Cingulate cortex
– Ventral striatum
DBS targets

12. • Experts are still not clear exactly how it works
• DBS works much like a pacemaker for the brain
• Battery-powered IPG (Neuro-stimulator) delivers
high-frequency, continuous electrical stimulation to
brain structures
• Pulses inactivate or modulate the brain’s impulses
which helps reduce motor symptoms (dyskinesias)
• The IPG creates electrical stimulation that stops
spasmodic contractions at the source
• Electrical impulses to the brain interfere with neural
activity of targeted site without destroying the brain
DBS mechanism of action

13. • After the surgery adjustment has to be made to the
frequency and power of the electrical stimulus
being presented to the nerve cells through the
device
• If the right adjustment is made as to the rate and
strength of delivery, remarkable improvement can
be seen
• As patient’s response to stimulation changes over
time, the impulses can be adjusted from outside by
means of an external programming system,
w/out the necessity for repeat operation
• Several RCT’s are still going on to provide more
evidence of the effectiveness of DBS
DBS mechanism of action

14. • Apathy; Hallucination
• Compulsive gambling
• Hyper-sexuality
• Cognitive dysfunction
• Depression; Déjà vu episodes
• Parkinson's patients showed decline in
executive functions, and problems with word
generation, attention and learning
• Because brain can shift slightly during surgery, there
is possibility of electrodes becoming displaced or
dislodged. This may cause complications like
personality changes, but electrode displacement is
relatively easy to identify using CT or MRI
DBS side-effects / complications

15. • Parkinson’s disease (PD): Reduces
tremor, rigidity, stiffness (70% patients);
Improves speed, dexterity of arm; Blocks
involuntary movements, Reduces medication; FDA
approved for Rx of Essential tremor and PD
• Dystonias: Chronic, intractable (drug refractory)
Primary dystonia, including Generalized and/or
Segmental dystonia, Hemi-dystonia and Cervical
dystonia (Spasmodic torticollis) in patients >7
years; received FDA approval via Humanitarian
Device Exemption process in April 2005
• L-dopa-induced dyskinesia in PD
DBS applications

16. DBS applications
• Tourette’s syndrome
• Intractable epilepsy: Stimulation of the anterior
nuclei of thalamus for epilepsy (SANTE);
Modulates impulses in Papez circuit
• Obsessive compulsive disorder (OCD): 40%
decrease in symptoms
• Learning / Memory-associated disorders
• Major depression
• Multiple sclerosis: DBS controls tremor
• Stroke patients: For rehabilitation, neuropathic pain
and seizure control
• Lesch-Nyhan syndrome
• Phantom limb pain

17. DBSinCervicaldystonia

18. T1 weighted MRI shows
position of contacts; 0,1
are w/in STN; 2, 3 are
just above STN, where
GPi is located.
Table summarizes
results; Stimulation of
STN by cathode 0,1
resulted in decrease in
rigidity, tremor and
akinesia of PD, but no
change in L-dopa-
induced dyskinesia;
Stimulation of GPi by
cathode 2, showed same
results, and also a
marked decrease in L-
dopa induced Dyskinesia
DBS in L-dopa-induced
dyskinesia in PD

19. DBS in Tourette’s syndrome
Left: Plain X-ray of skull AP view, showing position of
intracranial lead and electrodes; Right: Axial T1 MRI
of brain showing DBS-induced lesion in both
thalamus (arrows) in Tourette’s syndrome

20. • Definition: DBS in conjunction with medications to
treat chronic symptoms of Obsessive compulsive
disorder (OCD) that are unresponsive to medical
and other therapies alone
• OCD: Ventral striatum is involved in the processing
of emotional and motivational behavior; These are
altered in OCD, due to potential impairment of
ventral striatum in these patients
• DBS sites: IPG (under abdomen skin or
infraclavicular) sends impulses to (in next slide)
– Ventromedial caudate nucleus (bilateral)
– Nucleus accumbens (bilateral)
– Anterior limb of internal capsule
Reclaim DBS in OCD

21. DBStargetOCD
Left: Most ventral axial MRI slice demonstrates Nucleus accumbens (acc)
and ventral portion of Putamen (P), which was used to determine ventral
striatum targets and trajectories. Targets were defined based on position of
the middle of Accumbens. Right: Coronal MRI slice passing through the
targets of Caudate nucleus head (C) and Anterior capsule (AC). Dark
lines represent trajectories passing through both ventromedial Caudate
nucleus head and Accumbens

22. • High frequency micro-stimulation rather than
low frequency result in sustained dopamine
release in the striatum
• Animal trials proved performance was
significantly better with high frequency rather
than low frequency
• Elicits specific autobiographical recollection of
precise episodes, TV advertisements,
Life events etc
• In some individuals semantic memory
is improved as opposed to episodic;
This is controlled by Broadmann Area 20
(object recognition)
DBS for learning – memory

23. DBS in PD
DBS of STN
is accepted
form of
therapy in
intractable
Parkinson’s
disease
(PD); It is
most
commonly
performed
DBS
procedure

24. Vagus nerve stimulation (VNS)
Implanted pulse generator (IPG) is
similar to that in DBS; but electrode
stimulates left vagus nerve in neck;
Uses: Intractable epilepsy, Major
depression; MOA is unclear

25. Radiofrequency ablation
Invasive and destructive procedure; Replaced by HIFU (next)

26. • Focuses a large number of ultrasound beams
onto a small target of a few millimeters inside
the body
• Uses high intensity ultrasound beams that are
focused into a hotspot where the heating is high
enough to induce thermal tissue destruction
• A focal temperature increase can be produced
which is sufficient to ablate (surgically remove)
the tissue through coagulation
High-intensity focused ultrasound
(HIFU) principle

27. HIFUinpelvis

28. Magnetic resonance
guided high-intensity
focused ultrasound (MR-
Guided HIFU) has been
successfully used in non-
invasive surgery in
Gynecology and Urology
HIFU in body

29. Focuses high intensity US
waves thro a transducer (like
a magnifying glass focusing
sunlight) on a deep lesion;
Raises local temperature
w/out damaging surrounding
tissue

31. • Ultrasound (US) does not go through skull
because bone absorbs US waves;
• Transducers: 1,024 (210) Transducers create a
helmet-like atmosphere; individually set to beam
separately into skull, and calculated to individually
meet the targeted focus
• The HIFU beams produced by transducers are
transferred through the intact skull into the brain
and concentrated on a 3-5 mm focus (‘Hot Spot’)
• This coagulates sharply defined targets deep
inside the brain by heating them up to a focal
temperature of 60 degrees Celsius
• This non-invasive procedure lasts several hours
and is performed without anesthesia; Patients are
awake and fully conscious during the intervention
HIFU in brain

32. • The whole procedure is planned and monitored in
real-time by MRI
• The temperature increase during the sequential
sonifications, each lasting 10-20 seconds, is
continuously displayed and controlled on precise
MR temperature distribution maps
• The combination of HIFU and MR imaging allows
– Exact planning of the target area
– Visualization of the whole procedure
– Precise monitoring of temperature development
throughout the procedure
• Despite its great potential, MRI exhibits limitations
when information with very high spatial and / or
temporal resolution is needed
MR-guided HIFU

33. MR-guided ExAblate® 4000

34. • ExAblate is the 1st
MR-guided focused
ultrasound technology
that uses MRI to
visualize body
anatomy, plan
treatment and monitor
outcomes in real time;
and deliver HIFU to
brain tissue non-
invasively
ExAblate® 4000

35. • Benefits: Main advantage is non-invasiveness;
Safer than conventional surgery; Avoids risk of
complications – infection, hemorrhage and
collateral damage to normal brain structures
– The whole procedure is performed without
anaesthesia (patient is awake and conscious)
– Procedure can be performed on out-patient
basis
– Extreme precision and accuracy deep in brain
• Side effects: Vertigo, light headedness, and
stinging sensation during procedure
HIFU advantages / side-effects

36. Patients treated
• Neuropathic pain due to functional brain disorders
• Post-amputation phantom limb syndrome, Nerve
injury, Stroke, Trigeminal neuralgia, Post-herpetic
neuralgia from shingles
Future
• Long term effects such as heat-related swelling
and what happens when brain tissue is heated
• Paves the way for further research and other
potential clinical applications of treatment;
Alzheimer's; Parkinson's disease; Essential tremor;
Epilepsy; Brain tumors
HIFU applications present / future

37. HIFU result
• Axial T2 MRI
(with fluid
attenuation) of
brain
• Showing
HIFU-induced
lesions in
pulvinar region
of both
thalamus

38. Transcranial magnetic
stimulation (TMS)

39. TMS principle

40. TMSprinciple
(1) Electric current applied to external coil in anti-clockwise direction; (2)
Magnetic field generated around coil (according to Right-hand rule of
Physics), with high concentration of magnetic field in center of coil; (3)
This induces electric current in brain substance in clockwise direction;
(4) Which stimulates nerve cells in the field of induced current

41. • Electromagnetic coil on the scalp creates very
rapid bursts of magnetic energy on the brain
surface, which penetrates 2-3 cm deep
• Once inside the brain, the dynamic (rapidly
changing) nature of the magnetic pulses
induces electrical charges to flow, which
activates or inhibits neural activity
• The amount of electricity created in the brain is
very small and cannot be felt by the patient
• When in the correct orientation relative to brain
neurons, these very small electric charges can
cause the neurons to fire or become active
TMS principle

42. TMS principle
• Right-hand rule (Physics): When electric current
flows along a conductor in the direction of pointing
thumb of a semi-clenched fist, the resultant
magnetic field is generated in the direction of other
4 semi-clenched fingers of the hand
• If the electrical conductor is in form of a coil placed
over the brain, a high-intensity magnetic field is
generated in the center of the coil in the brain
substance, at right angles to the plane of the coil
• The magnetic field, in turn, induces electric current
in brain, whose direction of flow is opposite to the
original current in the coil
• This induced electric current in the brain stimulates
nerve cells, which is the basis of TMS therapy

43. • rTMS mechanism
– Electrostatic energy in a coil produces fast
oscillating magnetic fields
– High intensity, multiple impulses in high tempo
(trains) within a short interval produces
‘repetitive’ magnetic field (rTMS), which
influence neurons within reach of magnetic field
• >1Hz pulses produce neuronal excitation
• <1Hz pulses produce neuronal inhibition
–Exact mechanism is uncertain
• rTMS uses
– Examine brain behavior relationships
– Used on the Pre-frontal cortex (PFC) to treat
Resistant depression
Repetitive TMS (rTMS)

44. Effects of TMS
can be
recorded by:
EEG: Electro-
encephalogram
PET: Positron
Emission
Tomogram
fMRI:
Functional MRI
NIRS: Near
Infra-red
Spectroscopy
SPECT: Single
Photon
Emission
Computerized
Tomogram
EMG: Electro-
myogram

45. • Advantages
– Non- Invasive; Painless
– Anesthesia is not required
– Economical
– Quite effective
– Requires a significantly shorter amount of time
to implement
– Reduces dependence on medication; Important
for those who do not tolerate medications
• Side effects
– Headaches or scalp discomfort
– Nausea in some patients
TMS advantages / side-effects

46. TMSclinicalapplication

47. TMSapplication–Neurostar

48. rTMSofPFC
forDepression

49. • Resistant depression: rTMS excites neurons
especially in Prefrontal cortex (PFC) to improve
symptoms of major depression
• Tinnitus: PET scans look for excessive neuronal
activity with increased blood flow in the temporal
lobe; This area is then targeted with TMS to
decrease neuronal activity and tinnitus
• Stroke
• Parkinson’s disease
• Epilepsy
• Migraine
• Obsessive-compulsive disorder (OCD)
• Amyotrophic lateral sclerosis (Lou Gehrig’s)
• Fibromyalgia
TMS applications – present / future

50. • FES: Application of neuromuscular electrical
stimulation concurrently with training for specific
task or functional activity. This application is
termed as neuroprosthetics
• FES tries to benefit patients who had a low initial
volitional motor control, and who were not
expected to recover limb function after stroke
• FES + Exercise is likely to minimize motor loss,
but it may not significantly enhance the ability to
use the limb after ischemic stroke
• More patients may regain some functional ability
after training with FES compared with training
without FES. Patients with severe motor loss may
require prolonged task-specific FES training
Functional electrical stimulation (FES)

51. • Improves active
range of hand
motion and
function
• Improves
voluntary
movement
• Re-educates
muscles
• Prevents or retards
disuse atrophy
• Increases local blood
circulation
• Reduces muscle spasm
• Maintains or increases
range of motion
•Prevents contractures
FES – NESS H200

52. • Pathology: Injured Deep Fibular (Peroneal) nerve,
which supplies the anterior compartment of leg
(especially Tibialis anterior muscle)
• Manifestations: Inability to dorsiflex the foot; Foot
hangs inferiorly; hence the term ‘Foot drop’;
Patients catch their toes on the ground when
walking, making it difficult to walk normally
• Etiology: (Other than Common/Deep Fibular nerve
transection)
–Multiple Sclerosis (MS)
–Traumatic brain injuries
–Incomplete s. cord injury
–Cerebral palsy
–Stroke
Foot drop

53. • Functional Electrical
Stimulation (FES)
system to treat Foot drop
• Sends low-level electrical
impulses to Deep Fibular
nerve in the leg
• Stimulates lifting of foot
• FDA approved NESS
L300 in 2008
• By 2008, 7/10 major
rehabilitation centers in
US had implemented it
FES – NESS L300

55. FES – NESS L300
Gait sensor over ankle
detects attempted movement
during walking; Stimulator in
leg cuff sends impulses to
leg dorsiflexors during heel-
strike phase of gait

56. • While walking, the ankle Gait sensor detects
gait events and transmits wireless signals to
synchronize with electrical impulses emitted by
the Stimulator
• Electrical impulses from the leg cuff Stimulator
work on the common Fibular nerve and Tibialis
anterior at the appropriate time during walking
• The mini Control unit displays real-time
information regarding the system’s current
status, and allows fine-tuning of adjustments
• Monitoring unit for healthcare professionals
logs all information and monitors patient
compliance
FES – NESS L300

57. Benefits
• Normal natural walking gait
• Prevents muscle atrophy
• Increases range of joint motion
• Increases local blood flow
• Clinical research has shown
–17% immediate increase in mean walking speed
–34% increase in mean walking speed after 8 wks
–45% improvement in gait asymmetry index after
8 weeks
–92% decrease in fall frequency
• Note: NESS L300 cannot function if Common /
Deep Fibular nerve itself is cut and / or Tibialis
Anterior muscle is atrophied
FES – NESS L300

58. • The NESS L300 uses wireless communication
which eliminates the need for externally worn
cumbersome wires
• Stimulation of the Common Fibular nerve and
Tibialis Anterior causes dorsiflexion in individuals
with Foot drop
• Ness L300 can dramatically improve the lifestyle of
these patients by helping them to:
–Walk normally
–Enjoy everyday activities, which were previously
difficult or impossible to accomplish
NESS L300 summary

59. Newer generation cochlear implant

60. Newergeneration
cochlearimplant
Inset shows a post-
operative view

62. • Microphone: Positioned over external ear;
Receives the sound; transmits to Speech
processor
• Speech processor: (a) Behind ear; or (b)
Body-worn; Receives sound from microphone
and decides how the electrodes stimulating
cochlear nerve should be activated
• Transmitter coil: Attached by magnet to side
of skull; Receives info from Speech processor
and transmits radiofrequency (RF) waves to
Receiver-Stimulator inside skull; Lack of direct
connection thro skull reduces infection and pain
Cochlear implant

63. • Receiver-Stimulator: Embedded in skull bone
behind ear; Receives input from Speech
processor via the external Transmitter coil;
Receives its power by magnetic induction;
Transmits processed sound info, and controls
electric current to cochlear electrodes
• Electrode array: Drilled thro mastoid bone into
inner ear and implanted on cochlea; Stimulates
different areas of cochlea (and CN8c), based
on how sound is interpreted by Processor (~to
organ of Corti); Several weeks after insertion,
cochlear implant is fine-tuned
Cochlear implant

64. Brainstem implant

65. • In May 2013 a Brainstem implant was performed in the US
for the first time on a 3-year old child. An earlier attempt at
Cochlear implant failed because the Cochlear nerve was
congenitally absent.
• The components of Brainstem implant are similar to
Cochlear implant; but the technique is 4-5 times more
challenging because the cable has to go under the
Temporal lobe and the Electrode has to be positioned on
the Brainstem
• The composite image was created from screenshots of the
news video. The labels are self-explanatory. An
anatomical error has been highlighted.
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Brainstem implant

66. Tinnitus masker console

67. • Tinnitus masker: Tinnitus masking was once
thought to be useful because it blocked the sound
perceived by the patient
• It proved to be counter-productive because for
habituation (one of the effective modes of
treatment) to work, the sound needs to be audible
• Habituation cannot occur if perception of the sound
is not present; viz. one cannot cure acrophobia
simply by avoiding heights
• Tinnitus Retraining Therapy: Goal of this therapy
is to adjust the reaction of patient to the tinnitus
and the perception of the tinnitus sound itself. This
includes counseling and use of Noise generators
Tinnitus masker

68. • Sound generators: Electronic devices in ear that
amplifies hearing and masks tinnitus with ‘white
noise’ or static (different sounds at different
frequencies that block out the tinnitus sounds)
• Disadvantages: Long time period before patient
experiences benefits; High cost related to the
prosthesis, High dependence on counseling, Not
covered by health insurance
• Wearable sound generator (WSG): New WSGs
use many frequencies to stimulate all nerve cells in
the auditory pathway, to make allowances for
greater plasticity of the nerve cells
Sound generator

69. • Sound
generator
produces sound
at many
different
frequencies
(a.k.a. ‘white
noise’)
• This masks the
perception of
tinnitus by
impedance
Wearable sound generator