By: Hadas Goshen with Prof. Menashe Zaaroor, Director of the Department of Neurosurgery, Rambam Health Care Campus and
Dr. Ilana Schlesinger, Head of the Center for Movement Disorders and Parkinson's Disease, Rambam Health Care Campus

Mrs. R.P., a 72-year-old patient, could not lift a glass of water to her lips for 12 years. She suffered from severe uncontrolled tremor, which precluded any independent functioning ability, even the simplest activity such as eating and drinking independently. These actions were a "mission impossible" for her.
Mrs. R.P. was referred for consultation with Dr. Ilana Schlesinger, Head of the Center for Movement Disorders and Parkinson's disease at Rambam.
"There is no medication that we didn't try during the three years we treated this patient, but without any effect," Dr. Schlesinger recalls. Finally, we decided she needed an operation, using a novel surgical technique involving implantation of a brain pacemaker, which significantly improves tremor.
Mrs. R.P. was among the first patients who underwent surgery with implantation of a brain pacemaker at the Department of Neurosurgery at Rambam. During the surgery, when the electrode, guided by the experienced hands of Prof. Menashe Zaaroor, reached its precise position in the brain – the tremor stopped immediately. In order to ensure that the electrode had indeed reached its precise position in the brain, R.P. was given a glass and was asked to bring it to her lips. For the first time in 12 years, she succeeded in bringing the glass to her mouth. R.P., with tears of excitement in her eyes, murmured "Shema Israel," and gently released the glass.
Dr. Schlesinger described the scene: "This was one of the most exciting moments of my life." After a few weeks, R.P. returned to the Center for Movement Disorders to have the pacemaker adjusted. Today, she is free of tremor.
A new team has been set up at the Rambam Health Care Campus, for treatment of patients with severe movement disorders, using a method involving implantation of an electrical stimulation electrode in the brain connected to a pacemaker (Deep Brain Stimulation ─ DBS). The team includes the staff of the Center for Movement Disorders, headed by Dr. Ilana Schlesinger, a specialist in neurology and movement disorders, who identifies suitable patients, Prof. Menashe Zaaroor, Director of the Department of Neurosurgery, who operates on the patients and implants the electrodes and the pacemaker, the neurophysiologist Dr. Alon Sinai, an EEG specialist responsible for EEG recording during surgery, Prof. Judith Aharon-Peretz, a specialist in neurology and neuropsychological who performs the cognitive evaluation. The team also includes nurses, physiotherapists and social workers, while the comprehensive treatment provided to the patients is coordinated by Ilana Erikh, a nurse specially trained for this purpose. The entire team accompanies the patient throughout treatment: from diagnosis and the decision to carry out surgery, through surgery planning and performance, followed by adjustment of the stimulation and patient follow-up. 

What is Parkinson's disease (PD)?
PD is manifested by limb tremor at rest, slow movement, muscle rigidity, and, following years of gradual disease progression, the appearance of gait imbalance. The symptoms are caused by reduced secretion of a substance called dopamine, due to damage caused by the disease, to a brain region called "the black matter" (substantia nigra). The prevalence of PD in the population of people above the age of 65 is 1%.
The treatment of choice for PD is medication, designed to restore the balance that has been impaired by reduced dopamine secretion. In patients suffering from significantly reduced quality of life despite optimal medication therapy, a surgical option should be considered.
"Surgical treatment of PD has been known since the 1940s; it was based mainly on destruction of brain regions involved in movement control," explains Prof. Zaaroor, "Following these surgeries, significant improvement was observed in the symptoms of movement disorders, mainly tremor and rigidity, but the surgeries were sometimes associated with irreversible side effects. In the late 1960s, a drug called L-DOPA, a molecule that is converted into dopamine in the brain, was discovered, and surgical treatment was nearly abandoned. However, following years of experience, it was found that the efficacy of L-DOPA therapy declines over the years, and the dose and administration frequency must be increased. In addition, severe side effects develop as a result of this treatment:
1. ON-OFF situation. The patient functions well while the drug is effective (ON), and then a condition of "freezing" develops (OFF).
2. Involuntary movements occur (dyskinesia).
These limitations of treatment with anti PD medications revived the interest in development of novel surgical techniques.
In 1992, the French neurosurgeon Dr. Alim-Louis Benabid discovered that electrical stimulation of basal nuclei in the brain (groups of brain cells involved in movement control) improves the symptoms of movement disorders, without causing damage to the tissues of these areas.
"Currently, there is a consensus that the hypothalamic nucleus (a tiny nucleus of 5 6 mm in diameter) is the brain region most suitable for the treatment of PD," says Prof. Zaaroor. "Implanting an electrode in the hypothalamic nucleus may significantly improve the symptoms of the disease and alleviate the severe side effects caused by the drug treatment. Stimulation of the hypothalamic nucleus by an electrode reduces its activity, thus breaking the circuit of overactivity of the neural pathways in the brain, characteristic of this disease."

The surgery
In the 2000s, the surgical technique for implantation of stimulating electrodes into the brain developed into a very sophisticated high-technology procedure, requiring performance precision at the level of millimeter fractions, using a computer and a unique imaging method, based on the combination of images obtained by CT and MRI. The MRI scan is performed using a unique sequence of cross-sections, enabling identification of the specific regions reached during the surgery. This combination enables high precision while navigating the electrode to its target region, which is only a few millimeters in size. Similar to navigation using a state-of-the-art GPS device, the method guides the surgeon to the target by the shortest and safest way. A system that records and analyzes brain cells assists the team in the navigation process. "We confirm the correct position by identifying the electrical activity characteristic of the hypothalamic nucleus," explains the neurophysiologist, Dr. Alon Sinai. "We identify the electrical activity characteristic of this region, thus determining the precise position of the electrode," explains Prof. Zaaroor. "We also confirm the position by examining the patient and observing significant symptom reduction, even at this early stage. This requires the patient's cooperation; therefore, the operation is performed under local anesthesia, where the patient stays awake."
About a week after the electrode implantation surgery, the second stage procedure, the pacemaker implantation, is carried out. The pacemaker is implanted in the chest region beneath the collarbone, similarly to a cardiac pacemaker. The wire connecting the electrode to the pacemaker is inserted subcutaneously along the back of the neck, behind the ear and under the skin of the scalp. Implantation of the pacemaker is performed under general anesthesia by Prof. Zaaroor.

After the surgery, the patient comes to Dr. Schlesinger, who programs the pacemaker. Dr. Schlesinger emphasizes that: "An adjustment period ranging between days and weeks is required, until the maximum therapeutic effect is achieved. This adjustment procedure requires patience on the part of both the patient and the physician, skill on the part of the physician, as well as close follow-up.

In 1997, the US Food and Drug Administration (FDA) approved the surgery as a treatment for uncontrolled tremor, and in 2002 – as treatment for PD. Since then, thousands of people treated with this method have experienced significant relief in the symptoms of their disease, and their drug doses have been significantly reduced. This surgery is also included in the Israeli Basket of Health services.

Who is eligible, who is not, and who may be eligible in the future?
"The success of the surgery is highly dependent on the patient's eligibility for the surgery," as indicated by Prof. Zaaroor and Dr. Schlesinger. "The most suitable are patients with severe PD, who were treated with L-DOPA for several years, and developed side effects due to the treatment, such as fluctuating symptoms between being able to function and freezing and involuntary movements."
Additional patients who may benefit from Deep Brain Stimulation are patients with severe essential tremor, like Mrs. R.P. The surgery is also applicable to dystonia patients suffering from uncontrolled spasms.
Patients suffering from cognitive deterioration, Parkinson-like diseases, imbalance and falls are not eligible for this surgery.
Prof. Zaaroor indicates that according to the reports published in the professional literature, implantation of a brain pacemaker assists in the treatment of endogenous depression, chronic pain, Tourette's (motor and vocal tics), and even in patients who are unconscious as a result of head trauma.