Functional Neurosurgery

Parkinson disease is a brain disorder.  It occurs when certain nerve cells (neurons) in a part of the brain called the substantia nigra die or become impaired. Normally, these cells produce a vital chemical known as dopamine. Dopamine allows smooth, coordinated function of the body's muscles and movement.  When approximately 80% of the dopamine-producing cells are damaged, the symptoms of Parkinson disease appear.

Signs and symptoms of Parkinson disease

The loss of dopamine production in the brain causes the primary symptoms of Parkinson disease.  The key signs of Parkinson disease are:

Other signs of Parkinson disease may include:

Parkinson disease affects both men and women in almost equal numbers.  It shows no social, ethnic, economic or geographic boundaries.  In the United States, it is estimated that 60,000 new cases are diagnosed each year.  While the condition usually develops after the age of 65, 15% of those diagnosed are under 50.

The process of making a Parkinson disease diagnosis can be difficult. There is no X-ray or blood test that can confirm Parkinson disease.  A physician arrives at the diagnosis only after a thorough examination.  Blood tests and brain scans known as magnetic resonance imaging (MRI) may be performed to rule out other conditions that have similar symptoms.  People suspected of having Parkinson disease should consider seeking the care of a neurosurgeon /neurologist   who specializes in Parkinson disease

Indications for treatment :

• Prevention of disease progression
• Symptomatic control of parkinsonism
• Prevention of motor complications
• Control of motor complications
• Control of non-motor complications

Type of intervention

Drug treatment

Levodopa ,Amantadine , Anticholinergics , MAO-B inhibitors , COMT inhibitors , DA agonists
Ergot compounds :Bromocriptine , Cabergoline , Lisuride ,Pergolide
Non-Ergot Compounds: Apomorphine , Piripedil , Pramipexole ,Ropinirole

Surgical treatment
                                           
• Deep brain surgery                                          
• Neural transplantation

The purpose of drug therapy is to relieve symptoms and improve your quality of life . Drugs will not stop the progression of the disease . Drugs will help you function better but they are not perfect and may cause side effects . You may have to take your medication several times a day . these drugs work on the brain’s complex chemistry – use them only as prescribed and never alter dosages without first consulting your doctor .

After three to six years of drug treatment, many patients begin to lose sustained treatment
benefit. The result is increasing time spent "off," or without relief from symptoms. Increasing the amount of medication can usually minimize off time to acceptable levels for several years. After three to six years, patients often also develop uncontrolled movements called dyskinesias  that occur when their drug treatment is working. For patients on levodopa, a COMT inhibitor may be added to help increase the effectiveness of levodopa. These include tolcapone   and entacapone . A special combination pill contains levodopa and entacapone . In addition, a medication such as apomorphine injectable   may then be used as a rescue therapy, with a rapid return to the on state.  
Brain surgery is an option for advanced PD patients whose symptoms can no longer be adequately managed with medications. The best surgical candidate is someone who:

Advanced age is not necessarily a barrier to surgery, but impaired cognition, including forgetfulness, diminished decision-making ability, and language difficulties, along with gradual loss of brain matter (brain atrophy or shrinkage), make the surgery more risky and decreases the likelihood of an optimal outcome.
Depending on the patient, procedure, and skill of the operating team, cognition may be mildly impaired or largely unaffected by the surgery itself. The most commonly reported adverse cognitive effects are reduced decision-making abilities and language impairments.
It is impossible to predict the benefit any individual patient can expect from surgery. The general rule of thumb is that the maximum benefit is equal to the best response from a dose of levodopa (minus the effect on dyskinesias). Therefore, if a patient's symptoms are 50% better at the peak of a levodopa dose, the surgery is not likely to improve the patient's symptoms more than that amount. Importantly though, improvements from surgery are most dramatic during the times the patient is not experiencing the effects of medications ("off" time). Therefore, surgery may greatly improve the amount of the day during which symptoms are reduced.

Types of Surgery

There are two surgical procedures—lesioning and deep brain stimulation—and three target locations in PD surgery: thalamus, Globus pallidum internus (GPi), and subthalamic nucleus (STN). Other surgery-based procedures—cell transplants, gene therapy, and neurotrophic factor delivery—remain experimental procedures for the treatment of PD.
Lesion procedures (i.e., pallidotomy, thalamotomy) deliver radio-frequency energy to heat and ablate (destroy) a pea-sized region within the target, where there is abnormal activity related to the movement problems.

Deep brain stimulation (DBS) uses implanted electrodes to stimulate one or another of these same regions. The electrical stimulation interferes with the abnormal activity, creating the same effect as a lesion. The effect lasts as long as the stimulation continues, but ceases when it is shut off.

During needle-guided (stereotaxic) brain surgery, the patient remains awake. This is for two reasons. The first is that the brain itself has no pain sensors, and once the initial incision is made (using a local anesthetic like Novocain), there is no pain. The second is that patients must be able to respond to the surgical team's questions about what they are experiencing during the surgical procedure. The pathway to the target lies close to several other important structures in the brain that may be inadvertently stimulated during the procedure. This may cause unusual sensations such as flashing lights, tingling, or experience of emotions. Patients then report these sensations to the surgeon during the procedure. Avoiding these areas is crucial for successful surgery.
Because surgery requires very precise placement of surgical instruments, a three-dimensional frame is attached to the patient's head to guide the surgeon. The frame may be uncomfortable and local anesthetic is used to ease the discomfort. Before surgery, patients will also undergo several imaging procedures, in order to identify the target and other landmarks within the brain. Depending on the center, the procedures may include magnetic resonance imaging (MRI) scans, computerized tomography (CT), or ventriculography.

Neurostimulators:

A pacemaker-like device that contains a battery and microelectronic circuitry for controlled electrical pulse generation. The neurostimulator is implanted subcutaneously near the clavicle, and generates electrical signals that are delivered by the extension and lead(s) to the targeted structures deep within the brain.

Kinetra Dual channel Neurostimulator
The Kinetra® dual-channel neurostimulator accommodates two extensions/leads, and thus provides bilateral neurostimulation from a single neurostimulator. The Kinetra neurostimulator is 61 mm x 76 mm x 13 mm and weighs 83 grams.

DBS Lead:

Four thin, insulated, coiled wires bundled within polyurethane insulation. Each wire ends in a 1.5 mm electrode, resulting in four electrodes at the tip of the lead. The DBS Lead delivers stimulation using either one electrode or a combination of electrodes.

Therapy Controllers:

A patient places the compact, handheld therapy controller over the neurostimulator and presses buttons to turn one or both of the neurostimulators ON and OFF, to view the system's ON/OFF status, and to check the system's battery status.
Patients with a Kinetra® neurostimulator may use the Access® Therapy Controller, which allows them limited control of stimulation parameters within a physician’s prescribed limits

Experimental Therapies

Cell Transplant Therapy
Transplant of fetal substantia nigra cells has been performed in several hundred patients to date in multiple centers throughout the world. While results have been encouraging in some individual patients, two recent double-blind placebo-controlled studies showed that consistent benefit was only seen in young PD patients (age 60 or below), and side effects in some patients were significant. In particular, some patients developed off-medication dyskinesias (uncontrolled movements) even without any levodopa or other dopaminergic medication. The lack of consistently good results and the significant side effects encountered have been interpreted by the scientific and medical community to indicate that further research in animal models of PD is needed to improve upon what has been observed to date before more studies in PD patients are undertaken.
Another cell transplant technique that shows some promise is the use of retinal pigment epithelial cells. These cells are derived from tissue at the back of the eye, and they produce and release dopamine. An open-label trial in six advanced PD patients has shown promise, and a double-blind trial is underway.

Gene Therapy
As of 2006, gene therapy has been tried in only a few PD patients, and is still highly experimental. While experiments in animal models of PD have shown promise, further research is needed. The only publicized trial is of delivery of the gene for glutamic acid decarboxylase (GAD) to the subthalamic nucleus or STN. GAD is a key enzyme in the production of the inhibitory neurotransmitter GABA. Gene therapy with GAD is meant to increase GABA production, reducing STN activity in the manner of STN DBS. Monitoring is still in progress.

Growth Factor Delivery
Glial cell-derived neurotrophic factor (GDNF) stimulates sprouting of dopamine neurons in animal models. Direct delivery of GDNF to the brain has produced promising results in an open-label trial in a small number of patients, but by mid-2004 a larger, double-blind trial failed to show efficacy. Further research is needed, especially regarding how to improve delivery of growth factors to the correct targets in the brain.
If you have further queries regarding Surgical management of Parkinson’s disease or other movement disorders  email me :  radiosurgeon_9@yahoo.com .