Deep Brain Stimulation Surgery Experience at Apollo Hospitals, New Delhi

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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

E-mail address: sudheerktyagi@gmail.com0976-0016/$ e see front matter Copyright ªhttp://dx.doi.org/10.1016/j.apme.2013.08.012

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 brain, rather than the skull. Locating brain targets with

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

.2013, Indraprastha Medic

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.

al Corporation Ltd. All rights reserved.

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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.

Microelectrode recording showing tracings of neuronal discharge from subthalamic nucleus.

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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).

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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.

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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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