Parkinson’s disease Surgery can be typically classified in three stages. Stage 1 is the stage when the medical treatment makes you almost forget the disease, i.e. you become quite normal after taking the pills. Over a period of time the duration for the normal phase shrink and you end up taking more pills. Newer drugs like dopamine agonists, MAO inhibitiors, etc. are added to manage the disease.

In stage II the duration of the ON periods i.e. good time shrink further. The OFF periods become longer and disabling, associated with pain, dystonia, gait difficulty etc. Increasing pills do not work as they give side effects like dyskinesias and hallucinations. This is the time when people decrease their work and start living at home.

It is at this time other interventions, mainly surgery, should be considered. The various interventions that are currently available include lesional surgeries and deep brain stimulation. Stem cell therapy is not available at this stage as there is no scientific proof for it to be used.

Thalamotomy has very limited role in the present scenario for PD surgery. It is only useful in relieving Parkinsonian tremor. This tremor is typically described as “Pill rolling” tremor. In advanced cases postural and intentional components also become apparent. Tremor is a presenting symptom in majority of PD patients. In eight out of ten patients it is well controlled with drug therapy. Surgery is indicated only in resistant cases. Thalamotomy is not effective in alleviating other symptoms, like rigidity, bradykinesia and postural instability seen in PD patients. For the treatment of these symptoms we need to use other surgical targets. When undertaking thalamotomy or thalamic stimulation, it is important to realize this and educate the patient and physician about the need for continuous medical management of other Parkinsonian symptoms following surgery.

axial map of the thalamusThe most preferred thalamic target is Vim (Ventrointermedius) nucleus of thalamus as defined by Hassler (Fig.1). Vim is a strip of thalamic nucleus located just anterior to the sensory thalamus. The dimensions of the Vim nucleus are 3 to 4 mm rostrocaudally, about 10 mm in width, and about 10 mm in height.

The axial map of the thalamus showing the location of thalamic target (marked in red).

Surgical Protocol

Patients being considered for thalamic surgery should be evaluated by an experienced movement disorders team to ensure that they are good candidates for surgery and that all appropriate medical therapies have been tried. Medical therapy for patient with essential tremor should include adequate trials of Propranolol, Wysolone and Clonazepam while therapy for Parkinson’s disease should include Sinemet, Dopamine agonist etc.

All patients undergoing surgery for PD go through a standard pre and post surgical protocols. The patient is jointly evaluated by the Neurologist, Neurosurgeon and Occupational therapist. Preoperative video, Unified Parkinson’s DiseaseScale (UPDRS), Schwab and England Activities of daily living (ADL) and Hoehn and Yahr scores are documented in “on” and “off” phase. Similar postoperative evaluations are performed at 1, 3, 6 and 12 months intervals.

Surgical techtechnique

We perform thalamotomy using CRW Stereotactic apparatus and macrostimulation. The stereotactic frame is fixed to the patient’s head with the help of four pins. The area of fixation is numbed with the help of local anesthetic. The stereotactic frame is placed in a plane parallel to the orbitomeatal line. Following this the patient is taken to the CT scan department where an axial CT scan is performed. The scanner gantry is angled in a plane to include the anterior commisure (AC) and posterior commisure (PC) in one plane.

These are fixed landmarks in the brain to which the target can be related. For high degree of accuracy the CT slices are 2mm thick and contiguous. The length of the AC-PC is measured and the thalamic target is chosen as a proportion of this length. It is ½ lateral and 2/10th to 3/10th anterior to the posterior commisure, of the AC-PC length. The relation of the target point to the medial border of the internal capsule is checked and if it is too close or encroaching the medial border than the laterality is adjusted. Once the target is defined the patient is taken back to the operation theatre and made to comfortably lie down on the operation table. A small opening (burr hole) is made in the skull after infiltrating local anesthetic at the operative site. The target is reached with the help of stereotactic arc system.

The physiological exploration is performed using an electrode with an exposed tip of 2 x 2 mm. This is introduced through a precoronal burr hole. The exploration starts 4 mm above the target and the electrode is advanced in increment of 2 mm using micro drive. At each level stimulation is performed using 5 Hz. and 100 Hz. frequencies. Motor evaluation to check for weakness, dysarthria and fasciculation’s in tongue is performed at 5 Hz. Sensory evaluations is performed at 100Hz. frequency. During sensory stimulation there is arrest of tremor. The sensory stimulation also guides the laterality of the electrode placement. The topography of the Vim nucleus is corresponding to that of the sensory thalamic nucleus located posterior to it.

The exploration of the final target is continued until one obtains complete arrest of tremors without any side effects. Initially a test lesion of 42 C for 60 seconds is made at this point, and if there is no deficits than a final lesion of 70C for 60 seconds is made. It is important to note that the lesion should not go beyond the AC-PC plane. Thalamic stimulation is performed using similar technique. The advantage of stimulation over lesioning is that it can be performed bilaterally or it can also be offered to a patient with contralateral thalamotomy. It is a useful alternative to thalamotomy in elderly patients.

The morbidity and mortality of thalamic stimulation is less than that of thalamotomy. The side effects are minimal. There are four contact points and innumerable programmable parameters available for programming the electrode. This offers greater flexibility over lesioning in achieving complete tremor control. However, we do not see a role of bilateral thalamic stimulation for PD treatment, as better surgical targets are available. Following the surgery the patient is observed in intensive care unit for 24 hours. In case of thalamic stimulation the IPG (Implantable pulse generator) is implanted on the next day and the programming of the electrode is commenced the day after. The usual hospital stay for thalamotomy is four days, whereas that for the thalamic stimulation is 10 days.

50_ParaS_Surgery_Thalamotomy4Untoward side effects resulting from a physiologically guided selective Vim thalamotomy are minimal. The most common complications of thalamotomy are pyramidal weakness, dysesthesia, cognitive and speech deficits. The cognitive and speech deficits are more commonly seen in left sided and bilateral thalamotomy. Due to increased incidence of morbidity, bilateral thalamotomy is not performed any more. The risk of intracerebral haemorrhage and infection is less than one per cent.

We have performed thalamotomy/thalamic stimulation for various diseases including rubral tremor, cerebellar tremors, tremor from multiple sclerosis, Parkinsonian tremors, post stroke tremors etc. The success rate is nearly 100% in controlling the tremors. (Fig. 2)There has not been any mortality.

In the early 1900′s before the advent of modern anti parkinsonian drugs, surgical treatment of Parkinson’s disease was most common. A variety of operations aimed at destroying certain areas of the brain were carried out in an attempt to relieve severe tremor and rigidity. In 1952, Dr. Lars Leksell performed pallidotomy and showed that it was effective in relieving parkinsonian symptoms. At that time, the preferred surgical target for Parkinson’s disease surgery was thalamus. However, after the introduction of Levodopa, pallidotomy took the back seat. Uncontrolled dyskinesias appeared as a side effect of prolonged levodopa treatment. Alternative drugs provided only temporary relief for this disabling side effect. This forced the surgeons to rethink about the surgical treatment for Parkinson’s disease. In 1985 Dr. Lauri Laitinen from Sweden demonstrated that the pallidotomy described by Dr. Leksell could be effective in treating advanced Parkinson’s disease patients. He modified the surgical target within the pallidum and achieved the better control of the symptoms. Many of his patients suffered from severe bradykinesia, rigidity, tremors and other unusual involuntary movements. These patients had long standing severe Parkinson’s disease and suffered from drug-induced dyskinesias. He reported his first pallidotomy series of 38 patients in January 1992 and claimed that 80% to 90% of the patients had a long lasting relief of symptoms. This encouraging experience prompted other specialists to re-examine the role of pallidotomy in Parkinson’s disease. Pallidotomy has been found to be most effective in controlling drug induced dyskinesias, dystonia and other associated with off phase symptoms.

53_ParaS_Surgery_Pallidotomy1The surgical target for pallidotomy is the most vetro-medial part of the globus pallidum known as Globus pallidum internus (Gpi). This part of the Gpi is located in close relationship to the internal capsule and optic tract. Internal capsule carries nerve fibers that are responsible for motor function and any damage to these fibers can cause weakness on the opposite side of the body whereas the optic tract carries the fibers for the vision and any damage to these fibers can cause visual field defect. These side effects can be avoided by using the expertise and experience of a functional neurosurgeon.

Fig. 1. Drawing showing the relationship of the pallidal target to the internal capsule and optic tract

Candidates for Pallidotomy

We currently advocate pallidotomy for the following group of patients

  • Patients who have predominantly unilateral Parkinson’s disease with drug-induced dyskinesias.
  • The patients who have marked motor fluctuations such that the significant portion of the day is spent in functionally impaired state. This includes dyskinesia and off period symptoms.
  • Patients suffering from severe pain related to off medication period which cannot be improved upon by drug adjustments. Severe painful off phase dystonia is also an indication for surgery.
  • The patients who have unpredictable symptomatic relief that prevent establishment of a consistent medical regime.
  • Patients suffering from primary idiopathic dystonia.

Surgical protocol

The patient is evaluated by the movement disorder neurologist prior to surgery. The patient is admitted two days prior to surgery. On the preoperative day the patient undergoes UPDRS, H&Y and Schwab and England activities of daily living assessment in “off” medication condition. A video recording is also performed at this stage. The same protocol of assessment and video recording is performed in “on” condition. Patient is observed in neurosurgical intensive care for one day after surgery and discharged on the third postoperative day. Follow up visits are scheduled at 1, 3, 6 and 12 months after surgery.

Surgical technique of Pallidotomy

We perform pallidotomy using CRW Stereotactic apparatus and macrostimulation. The stereotactic frame is fixed to the patient’s head with the help of four pins. The area of fixation is numbed with the help of local anesthetic. The stereotactic frame is placed in a plane parallel to the orbitomeatal line. Following this the patient is taken to the CT scan department where an axial CT scan is performed. The scanner gantry is angled in a plane to include the anterior commissure (AC) and posterior commissure (PC) in one plane. These are fixed landmarks in the brain to which the target can be related. For high degree of accuracy the CT slices are 2mm thick and contiguous. The length of the AC-PC is measured. The pallidal target is 2mm in front of the mid point of AC-PC line at a laterality of 21-22mm and a depth of 4-6 mm. A inversion recovery, coronal, MRI scan is performed perpendicular to the AC-PC plane. The pallidal target is on a slice that passes through the mamillary body. The correct laterality and depth of the pallidal target is confirmed on this MRI and the CT target refined accordingly. Once the target is defined the patient is taken back to the operation theatre and made to comfortably lie down on the operation table. A small opening (burr hole) is made in the skull after infiltrating local anesthetic at the operative site. The target is reached with the help of stereotactic arc system.

The physiological exploration is performed using an electrode with an exposed tip of 2 x 2 mm. This is introduced through a precoronal burr hole. The exploration starts 6 mm above the target and the electrode is advanced in increment of 2 mm using micro drive. At each level stimulation is performed using 5 Hz. and 100 Hz. frequencies. Impedance, which is a measure of resistance of various tissues, is also noted at each level to discriminate between nuclei and fiber tracts. Motor evaluation to check for weakness, dysarthria and fasciculation’s in tongue is performed at 5 Hz. Sensory evaluations is performed at 100Hz. frequency. During sensory stimulation there are some dyskinetic movements and decrease in rigidity. Patient is also asked to report any flashes of light or visual disturbances, indicating close proximity to the optic tract. If there are any motor or sensory side effects the electrode position is adjusted. If there are no side effects than a test lesion of 42 C for 60 seconds is made at this point, and if there is no deficits than a final lesion of 70C for 60 seconds is made. Similar procedure is repeated at a level 4mm, 2mm and at 0 target level.(Fig.2)

55_ParaS_Surgery_Pallidotomy2Fig. 2. Postoperative MRI a: Axial and b: Coronal, following pallidotomy. Note the relationship of the lesion to internal capsule and the optic tract

Pallidal stimulation is performed using similar technique. We mainly restrict the use of pallidal stimulation for the treatment of dystonia. We feel that STN stimulation is better than pallidal stimulation in the treatment of advanced Parkinson’s disease. Following the surgery the patient is observed in intensive care unit for 24 hours. In case of thalamic stimulation the IPG (Implantable pulse generator) is implanted on the next day and the programming of the electrode is commenced the day after. The usual hospital stay forthalamotomy is four days, whereas that for the thalamic stimulation is 10 days.

Untoward side effects resulting from a physiologically guided selective Vim thalamotomy are minimal. The most common complications of thalamotomy are pyramidal weakness, dysesthesia, cognitive and speech deficits. The cognitive and speech deficits are more commonly seen in left sided and bilateral thalamotomy. Due to increased incidence of morbidity, bilateral thalamotomy is not performed any more. The risk of intracerebral hemorrhage and infection is less than one per cent.

Results

Pallidotomy is a useful surgery in the armamentarium of Parkinson’s disease treatment. When performed in a carefully selected group of patients it provides a significant improvement in the quality of life. The risk of major complications and mortality is less than 2%. It is at present the most acceptable form of surgical treatment for the idiopathic dystonia. Pallidal stimulation has proven to be superior than any other treatment in primary dystonia.

Guidance

Subthalamotomy surgery was developed following extensive experience of performing Subthalamic nucleus deep brain stimulation surgery. The STN target is very small and deeply located in the brain making it a challenge for average neurosurgeon to access it easily. Presently there are only two to three surgical units in the world who have developed the expertise to perform this surgery. In our experience we provide this surgical option to patients who cannot afford the cost of DBS. We also offer this surgery to patients who do not have easy access to postoperative programming which is required for DBS procedures. We offer this procedures to patients less than 65 years of age as we are still in the process of evaluating its efficacy in the elderly patients.

The Procedure

The targeting for the subthalamtomy is similar to that of STN DBS (provide with an hyperlink with the DBS section). The difference is only at the end of therapy. In case of subthalamotomy, three discreet lesions are made on each side instead implanting a DBS lead. The lesions are made using a special electrode (having exposed tip of 0.75 X 1mm) and a radiofrequency lesion generator.

Subthalamotomy involves inserting very fine needles into the brain through small holes made in the skull, to destroy a part of the subthalamic nucleus using heat or radiofrequency. The exact points of needle insertion may be different in each patient.The procedure is usually carried out under local anaesthetia. Patients remain awake during the procedure so that the effects on movements can be monitored.

Efficacy

Subthalamotomy is a very effective alternative therapy in place of DBS. The only disadvantage of this therapy is the lack of titrability offered in DBS procedures. The surgery is very effective in alleviating tremors and rigidity.

Parkinson’s Disease is a degenerative disease caused by loss of dopamine-producing cells in the substantianigra. So replacement of the cell that are capable of producing dopamine remains a possible treatment for Parkinson’s disease. The best way to achieve this is through neural transplantation. One of the forms of neural transplantation, include stem cell transplants.

Stem cells have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that renew themselves for long periods through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.

Stem cells can be of two types Embryonic and adult. Embryonic stem cells (ESC) represent the classic manifestation of a stem cell population, showing great capacity of self-renewal and differentiation. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, in recent years a large body of evidence indicated that some subpopulations of adult stem cells are capable of differentiating into mature cells different from their original lineage, a phenomenon termed trans differentiation. These multipotent adult stem cells reside in various compartments in the mature organism and display plasticity initially thought to belong exclusively to ESCs. Those cells have been isolated from brain, bone marrow, skin, fat, skeletal muscle and other visceral organs.

Adult stem cells appear to be the ideal candidates to serve as the cellular reservoir. In comparison to embryonic stem cells, adult stem cell harvesting does not involve the controversial use of embryos or eggs.

Current therapies in Parkinson’s disease are mostly symptomatic. The tireless efforts being invested in developing new technologies in stem cell research will hopefully yield the knowledge that will enable doctors to present patients with a cure.

Autologus Mesenchymal Stem Cell Transplant Research Project- Jaslok Hospital:

Jaslok Hospital and Reliance Life Sciences  carried out  autologus MSC transplantation in four Parkinson’s disease patients. These cells were implanted bilaterally in the basal ganglia using stereotactic technique. A two year follow up of these patients have confirmed that this procedure can be safely performed. Further studies will be required to confirm the role of stem cells in the treatment of PD. Till further scientific data becomes available stem cell therapy will remain a mater of research.

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