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Functional neurosurgery is concerned with the treatment of conditions where central nervous system (brain and spinal cord) function is abnormal although the structure or anatomy is normal. Eighty-seven Deep Brain Stimulation surgeries were done at Indraprastha Apollo Hospital, New Delhi since year 2000. This included 81 cases of Parkinson’s disease (STN stimulation), 4 cases of Essential Tremors (VIM thalamic nucleus stimulation) and three cases of Dystonia (Globus Pallidus stimulation). All the patients showed good response and one patient developed small thalamic hemorrhage which improved over a period of six weeks.
Citation preview
Deep Brain Stimulation surgery experience at Apollo Hospital, New Delhi
Research Article
Deep Brain Stimulation surgery experienceat Apollo Hospital, New Delhi
Sudheer Tyagi
Sr. Consultant Neurosurgeon, Indraprastha Apollo Hospital, New Delhi, India
a r t i c l e i n f o
Article history:
Received 23 July 2013
Accepted 8 August 2013
Keywords:
Parkinson’s disease
Dystonia
Essential Tremors
a b s t r a c t
Eighty-seven Deep Brain Stimulation surgeries were done at Indraprastha Apollo Hospital,
New Delhi since year 2000. This included 81 cases of Parkinson’s disease (STN stimulation),
4 cases of Essential Tremors (VIM thalamic nucleus stimulation) and three cases of Dys-
tonia (Globus Pallidus stimulation). All the patients showed good response and one patient
developed small thalamic hemorrhage which improved over a period of six weeks.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction
Functional neurosurgery is concerned with the treatment of
conditions where central nervous system (brain and spinal
cord) function is abnormal although the structure or anatomy
is normal.
Horsley and Clarke1 were the first to put stereotactic
principles into practice: they designed a stereotactic frame
for laboratory experiments that directed a probe to a pre-
determined target located in the brain within a three
dimensional reference grid. The lateral was based on the
location of the midsagittal plane, the external auditory
meatus and the orbital meatus plane. The principles could
not unfortunately be applied to the human brain because of
the variability of the skull dimensions. The breakthrough in
the development of human stereotactic surgery came in
1947 when Spiegel and Wycis2 used landmarks within the
brain, rather than the skull. Locating brain targets with
reference to the ventricular system, outlined by contrast
medium. Sweet and Mark3 introduced the use of radio fre-
quency current in 1960, and this was a major factor in
bringing stereotactic functional neurosurgery to its present
sophistication.
Further development of functional neurosurgery occurred
hand-in-hand with the development of computer techniques
for complicated calculations and display online graphics of
themass of data collected during surgery. The development of
imaging techniques gave another boost in 3-dimensional
radiological localization of ventricular landmarks and
different brain targets with reference to a suitable brain atlas.
Image fusion technique was used at Apollo Hospital, New
Delhi, to utilize CT scans as well asMRI data to use collectively
for target localization in cases of Deep Brain Stimulation
surgery.
E-mail address: [email protected].
Available online at www.sciencedirect.com
journal homepage: www.elsevier .com/locate /apme
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8e1 9 2
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.http://dx.doi.org/10.1016/j.apme.2013.08.012
2. Indications of Deep Brain Stimulationsurgery
The Functional Stereotactic Neurosurgery was first used by
Spiegel et al4 in a case of Huntington’s Chorea. They made a
pallidal lesion in this case followed by many cases of
Parkinsonism. After successful outcome of Functional Ste-
reotactic Neurosurgery in movement disorders it was fol-
lowed by its use in psychiatric illnesses, intractable pain,
epilepsy and cerebral palsy. With the advent of Levodopa in
1968 interest in stereotactic surgery for Parkinson disease
waned but over the next 15 years an increasing number of
Parkinson’s patients with dopa dyskinesias and motor
fluctuations led to a resurgence in Functional Stereotactic
surgery. Adrenal medullary grafts and transplantation
of fetal dopamine cells into the striatum has remained
mostly an experimental procedure. In the late 1980s
pallidotomy was revisited and by the mid 1990s many
groups had confirmed its efficacy, particularly for alleviating
levodopa-induced dyskinesias. Expertise and confidence
in these techniques were rekindled but concern remained
regarding high complication rates, particularly when bilat-
eral lesions were required.5,6,7 Next revolution came
with the invention of Deep Brain Stimulation Technique.
Initially two patients of multiple sclerosis induced tremors
were treated by fully implantable thalamic stimulators.
Experience increased and technology improved. In
1993 Benebid reported stimulation of the subthalamic nu-
cleus (STN), which improved almost all parkinsonian
symptoms allowing substantial reduction of dopaminergic
medication.8
3. DBS in Parkinson’s disease
3.1. Patient selection
Surgical intervention is usually reserved for patients with
advanced Parkinson’s disease when medical treatment has
been exhausted. Apart from tremor response, the outcome
of surgery for Parkinson’s disease is dependent upon the
presence of dopaminergic responsive symptoms to be
effective but at the same time non-dopa responsive Par-
kinson diseases, such as multiple system atrophy, will not
significantly benefit from surgery. The criteria of patients
for surgery are listed. It is important that patients with
significant cognitive or psychiatric difficulties are not
considered for surgery. Patients with drug-induced hallu-
cinosis, postural instability and dysphonia are usually not
good candidates. The temptation to offer surgery because
nothing more can be done, has often lead to disaster. Some
patients prefer to surgery without a trial of medication,
despite a thorough counseling. Early surgery may be
appropriate for tremor predominant disease (particularly
“benign tremulous” Parkinson’s disease), but for other
types, the balance between side effects and efficacy is not
adequate to recommend surgery early in the course of the
disease.6
3.2. Surgical technique
The outcome of functional stereotactic surgery is dependent
upon the precise localization of correct target that is
why different imaging techniques are used to locate
the target and with neurophysiological reconfirmation
intraoperatively is usually fitted under local anesthesia and
patient remains conscious throughout the surgical proce-
dure to allow clinical confirmation of symptom effective-
ness and side effects. Patients without significant tremor or
rigidity in the “off” state are difficult to assess intra-
operatively. Bradykinesia seldom responds to stimulation
and therefore cannot be reliably used. Microelectrode
recording has been used to map out the various nuclei
neurophysiologically.9 This can add to the length of the
surgical procedure, which in some centers with the best-
published outcomes often take more than 12 h! On stimu-
lation or lesioning of the pallidum or STN, transient dyski-
nesias may occur, which usually indicate successful
outcome. All in all the procedure is remarkably well
tolerated.
3.3. Intraoperative neuro stimulation
Stimulation is probably still the most widely used method
of physiological localization.10 However, the problem of
current spread must be kept in mind. Only threshold
responses are meaningful; suprathreshold responses
result in indiscriminate current spread. Stimulation map-
ping is most productive if performed methodically at in-
tervals of say, 2e3 mm. Interpretation is facilitated if
trajectories are arranged in a single sagittal plane by placing
the access burr hole in the same sagittal plane as the
intended target. Electrode with 1.9 � 4.0 mm uninsulated tip
is preferred and frequency of 2 Hze130 Hz is used
for stimulation in 2 mm steps starting 6 mm above the
target.
3.4. Micro electro recording
The use of microelectrodes in stereotactic surgery allows
assessment of both the spontaneous and evoked activity of
neurons. One may recognize a desired target outright by
virtue of a distinctive spontaneous firing pattern such as
that of the “tremor cells” in the thalamic target for ablative
lesions in Parkinson’s disease, or else evoked activity may
be distinctive, as in nociceptive neurons in the medial
thalamus. On the other hand, as Guiot observed, a target
may be located by the identification of structures immedi-
ately adjacent, such as, during a procedure for relief ;of
dyskinesia, somatosensory neurons that lie immediately
caudal to the target.11 Microelectrodes may also be used to
serially record spontaneous activity as an electrode is
advanced through the brain; this activity is distinctive and
can be used to identify each nuclear structure through
which the electrode passes.
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8e1 9 2 189
3.5. Implantation of microelectrodes for deep brainstimulation
Parasagittal burr holes of 15mmdiameter aremade, 2 cm lateral
to midline just anterior to coronal suture. A plastic ring of cor-
responding size is fixedover the burrholes. Thedura is incised in
a way that CSF should not leak and a small cortical incision is
made. At a time only one microelectrode implantation can be
carried out, the microelectrode is guided into the brain through
the burr hole according to XYZ coordinates fixed on the frame.
Microelectrode implantation for deep brain stimulation is best
done with the help of micro guide along with microelectrode
recording (MER). Microelectrode recording helps in precise
localization of the tip of microelectrode especially in case of a
small target like the subthalamic nucleus. The tip of each elec-
trode has four microelectrodes of which at least three should
remainwithin the nucleus. Neuro stimulation procedure should
be carried out at this stage to see for change in rigidity and
tremors, which further confirms the correct target localization.
After the microelectrode is implanted it should be fixed at the
burr hole site with the help of a plastic cap which fits into the
already fixed plastic ring in the burr hole. In the same way the
opposite side microelectrode implantation is carried out and
confirmed by viewing with an image intensifier (C arm).
Microelectrode recording showing tracings of neuronal discharge from subthalamic nucleus.
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8e1 9 2190
3.6. Lesions or stimulation
After successful implantation microelectrodes are connected
to the neurological pacemaker through the leads, which are
passed through a subcutaneous tunnel from burr hole site to
the infraclavicular portion of chest where neurological pace-
maker is placed through a transverse incision.
High frequency electrical DBS provides an adjustable
inhibitory effect on the target site, but at increased cost. An
accurately placed lesion in the thalamus or pallidum provides
reliable long lasting suppression of tremor and dyskinesias
respectively, with no adverse effects. Bilateral RF lesions are
invariably associated with adverse cognitive and bulbar ef-
fects, even whenwell placed, and stimulation is consequently
preferable. Lesioning of the STN is technically demanding
because of its small size, and benefits appear to be temporary
and therefore stimulation of this target is now recommended.
Though effective, DBS requires careful postoperative adjust-
ment that often takes many hours, and the replacement of
equipmentwhen hardware failure occurs. In some series up to
20% ofwiresmove, break, or become infected. The stimulation
battery unit requires replacement every five years for STN
stimulation, and three years for pallidal stimulation.
3.7. Post operative programming
Programming is a very important part in cases of deep brain
stimulation and good programming makes considerable dif-
ference in the post op results. Programming for rigidity,
tremor, akinesia and freezing should be done in the off stage
and for dyskinesias in the on stage. Channel one in pro-
grammer indicates the microelectrode which is implanted in
the left side of brain which controls right half of body. Simi-
larly channel two is for microelectrode implanted in the right
side of brain which controls the left half of body. Usually the
amplitude for STN is kept between 1.5 and 4.0 V and pulse
with 60e90 ms. Frequency of current used for STN is usually
from 130 to 180 Hz. Electrode configuration can be either Bi-
polar or Unipolar. In Bipolar setting one electrode is positive
and another one is negative and this leads to stimulation of
focal region between two electrodes. In Unipolar setting one of
the electrode is negative and case of pulse generator is posi-
tive and this leads to stimulation of greater area. Repeated
programming is required to ensure optimal results.
4. Different targets used in movementdisorders according to predominant symptom
4.1. Thalamus
The thalamus is the final common outflow pathway for all
tremors. Contralateral tremor is reliably suppressed with a
lesion in the VIM nucleus and rigidity in the ventralis oralis
posterior (Vop) nucleus. There is no effect on bradykinesia and
although dyskinesia is occasionally helped, this is certainly not
a reliable observation. Even patients with tremor predominant
Parkinson’s disease will eventually develop bradykinesia in
time, so it is now recommended that such patients shouldhave
STNstimulation, rather thana thalamic lesionor stimulation.12
4.2. Globus Pallidus
Posteroventral pallidal lesion7 or stimulation will reliably
abolish contralateral dyskinesias. This includes biphasic and
peak dose, and “off” state dystonias. Following optimal
lesioning, the benefit can persist for at least five years. The
improvement in “off” state bradykinesia also persists, but any
improvement in “on” state dissipates after six months.
Contralateral tremor may also be improved but this is not a
reliable effect. Globus Pallidus stimulation was done in three
selected cases of dystonia at Apollo Hospital, New Delhi.
Coordinates for Globus Pallidus internus are 2e3 mm
anterior to mid commissural point, 6 mm inferior to ACePC
line and 18e22 mm lateral to midline.
4.3. Subthalamic nucleus (STN)
Bilateral subthalamic stimulation alleviates all the cardinal
symptoms of Parkinson’s disease and benefits are preserved
for as longasfiveyears.Unlikepallidal surgery,medication can
be reduced by at least half postoperatively, and this leads to a
reduction in drug-induced dyskinesias.12,13 Unilateral surgery
can be offered to patients with very asymmetric disease, but
most require bilateral surgery to avoid problems with variable
medication requirements on the two sides. Complications can
be transient or permanent and tolerancemay develop in some
patients. Dramatic rebound symptoms can be seen following
acute stimulator failure, sometimes necessitating emergency
admission. The current stimulator units are less sensitive to
electromagnetic interference, such as from light switches and
electricmotors. Patients are nowusually given control devices
that can be preset to alter the stimulation parameters at home.
Although the results in well-selected patients can be dramatic
and well maintained, SIN stimulation requires considerable
long-term commitment from the team looking after the pa-
tient. It has been estimated that each patient requires on
average 40 h of adjustment for optimum benefit and mainte-
nance of effect. For this reason, it is difficult to envisage this
procedure becoming widely available, unless there is a sub-
stantial increase in thenumberofexperiencedstaff in theunits
offering this service. There is also concern about the frequency
of psychiatric side effects, particularly depression that prob-
ably arises as a result of the inhibition of STN limbic areas. The
rate of suicide has been high in some series, which is rarely
seen with surgery to other targets. Patients with a history of
significant depression should not be offered STN surgery. Co-
ordinates for subthalamic nucleus are 2e7mm inferior to mid
point of ACePC line and 12.5 mm lateral to midline. STN
stimulation was done in 81 cases of Parkinson’s disease.
5. DBS in essential tremor
A thalamic VIM lesion will reliably suppress contralateral
tremor. Given the bilateral nature of the condition, bilateral
thalamic stimulation is now the preferred option. Side effects
are similar to those seen in ‘pallidal surgery’ wide. Four cases
of essential tremor underwent Deep Brain Stimulation surgery
and showed excellent response.
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 8 8e1 9 2 191
6. Summary
There is no doubt that functional neurosurgery can produce
dramatic benefits, with a relatively small risk of adverse ef-
fects in experienced hands. The last decade has witnessed the
rebirth of neurosurgery for movement disorders with the
introduction of Deep Brain Stimulation surgery at different
targets in the brain. Improvement in stimulator design should
eliminate the need for battery changes and may also permit
simultaneous stimulation at multiple targets further broad-
ening surgical option. Advances in frameless stereotaxy may
soon allow DBS implantation without the need for a stereo-
tactic frame. The long-term future, however, lies in therapies
aimed at altering the course of disease by possibly neural
grafting and in vivo gene therapy.
Conflicts of interest
The author has none to declare.
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