SURGICAL ASPECTS OF DEEP BRAIN STIMULATION

SURGICAL ASPECTS OF DEEP BRAIN STIMULATION

Friehs, Gerhard M

In 1817 James Parkinson described a condition in several patients who had tremors and gait abnormalities. At the time, little was known about movement disorders or about the brains functions in general. It was not until the 1940s that the first attempts were made to try to treat movement disorders, especially Parkinson’s disease (PD). Since an effective pharmacological treatment had not yet been discovered for PD, the first attempts of treatment were of surgical nature. With the introduction of stereotactic equipment in 1947 by Spiegel and Wycis, treatment became more precise and in the 1950s and 1960s, tens of thousands of patients with movement disorders were treated successfully (and unsuccessfully) with lesioning procedures such as thalamotomy and pallidotomy. With the introduction and widespread use of L-Dopa around 1965, however, surgery for Parkinson’s disease and other movement disorders almost disappeared. Only when side effects from long-term use of L-Dopa medication were discovered did a resurgence of interest in neurosurgical treatment options ensue. Neurosurgeons had always used electrical stimulation during the course of lesioning surgery in order to guide the lesion placement and had found that stimulation using high- frequency electrical signals could abolish tremor. Since deep brain stimulation is a reversible and adjustable technique, it has become increasingly popular as opposed to the irreversible lesioning procedures. The introduction of deep brain stimulation electrodes makes it now possible to avoid lesioning procedures. The first successful DBS surgery attempts were reported in the 1970s but it took until 1987 until the first successful surgery with a fully implantable DBS system was reported in France by Benabid (1). Since then, about 50.000-100.000 DBS systems have been implanted worldwide.

PREOPERATIVE EVALUATION

DBS surgery today is not an experimental treatment for several conditions. It is approved for the treatment of essential tremor (FDA approval 1997), Parkinson’s disease and parkinsonism (FDA approval 2002) and dystonia (FDA approval 2002). For these conditions, electrodes are placed in the area of the basal ganglia. The originally recommended target was the ventro-lateral nucleus of the thalamus, pars intermedius (VIM) and later the globus pallidum internum (GPI) and subthalamic nucleus (STN) were introduced as even better targets for some patients2,4,7,8,10

The best surgical outcome is expected in patients who meet all inclusion criteria. The most important factors for patient selection are acceptable patient age (typically 70 years or younger) and lack of significant medical problems such as uncontrolled diabetes or hypertension. For Parkinson’s disease it is also important to document responsiveness to L-Dopa therapy. In our center, this is done by comparing the Unified Parkinson’s Disease Rating Scale (UPDRS) scores in the ON and OFF phase as part of the prospective patient’s preoperative full neurological evaluation. We also send these patients for psychiatric evaluation, as a small minority of PD patients can experience significant depression after surgery. One of the most important exclusion criteria for DBS surgery is the presence of dementia which has been associated not only with lack of responsiveness to DBS therapy but worsening of the patients’ overall brain function after surgery. Therefore, all of our potential DBS candidates undergo a full preoperative neuropsychological assessment.

In addition, DBS surgery is under intense investigation regarding its potential role for epilepsy or psychiatric diseases such as severe obsessive-compulsive disorder (OCD) and severe treatment-refractory depression. Several case reports show promising results with placement of the electrodes into the basal part of the anterior internal capsule, certain thalamic nuclei, subthalamic nucleus or around the cingulate cortex.3, 5, 9 At this stage this experimental treatment cannot be widely recommended to patients. It should be limited to dedicated research centers that have a history of collaboration between neurologists, psychiatrists, neurpsychologists and neurosurgeons.

SURGICAL PLANNING

Although the surgical procedure may differ slightly from center to center there are certain steps to every DBS surgery. The first step is the application of a stereotactic frame. This frame is a ring or rectangle, which is secured to the patient’s head under local anesthesia. It allows the surgeon to identify any point inside the frame in the X, Y and Z direction in terms of Cartesian coordinates. Therefore, any point inside the patients brain can also be identified and targeted using coordinates. These coordinates are obtained from the MRI scan that is performed as a next step in the procedure. Typically,the images produce a high contrast between gray and white matter. At our center, we rely on TIRM (turbo-inversion recovery) images in the axial and coronal planes with 2 mm thickness. In addition, a contrast-enhanced volumetric MP-rage study is obtained to outline vascular structures on the brain’s surface. Once all MRI studies are completed the images are transferred electronically to a stereotactic planning computer. On this workstation the images are reconstructed and aligned according to internal landmarks (AC – anterior commissure and PC – posterior commissure). The location of these landmarks in the brain is used as a reference to determine the location of the target area. The STN, for example, is typically located 11 mm lateral to midline, 8 mm anterior to PC and 4 mm inferior to the AC-PC plane. Although the STN can be visualized directly on MRI the coordinate system is used as a reference to verify the anatomical location. Other targets such as the VIM region are not directly seen on MRI and the anatomical location must therefore be determined using the internal landmark reference system alone. Once the target has been selected it is identified in terms of laterality (X-coordinate), anterior-posterior location (Y-coordinate) and superior-inferior location (Z-coordinate).

SURGERY

After this planning procedure, the patient is brought to the surgical suite, where s/he is positioned on the operating table in the supine position. After shaving, prepping and draping, the patient receives anesthetic medication for sedation. Some of the surgical procedure is performed with the patient asleep in monitored anesthesia care (MAC); at other parts of the surgery the patient must be awake and able to cooperate. For the initial parts of surgery the patient is asleep. During this time, the coordinates are adjusted on the stereotactic frame system and the entry locations through the skull are determined. Local anesthetic is infiltrated and a 3 cm skin incision is made in the patients forehead behind the hairline. Self-retaining retractors are applied and the skull is identified. Using a surgical drill, a burr-hole is placed at the appropriate location and the dura is exposed through the hole. The dura is opened in a cruciate fashion to expose the actual cerebral cortex covered with arachnoid and pia mater. A C-arm X-ray machine is positioned which allows us to visualize the electrode probe located inside the patient’s skull.

For most DBS surgeries micro-electrode recording (MER) is performed as the next step. One to five microelectrodes record signals from the target area and surrounding structures. These electrodes allow for extracellular single-cell recording. Since most brain structures have unique cell assemblies with unique cell firing patterns it is possible to characterize brain structures by their electrical discharge signature. This method gives electro-physiological confirmation of the presumed location of the ideal target as determined by anatomical landmarks. Although MER is the most time-consuming part of DBS surgery, it is believed to be extremely useful in determining the ideal target location. Only in certain circumstances where a short surgery time is essential for patient safety is DBS surgery performed without MER.

Once the ideal target has been confirmed, the DBS electrode array is introduced. It is a shielded wire bundle with 4 exposed contacts at the tip. For the first time, the electrode array is activated in the operating room. For that, an external stimulator-box is temporarily connected to the electrode array and intraoperative stimulation is commenced. It is also the time when the beneficial effect of DBS surgery may become quite obvious. This is especially dramatic in patients who suffer from tremor where the tremor comes to a sudden arrest as soon as the electrode array is activated. When the temporary stimulator is turned off the tremor sometimes returns seconds later only to disappear again with the stimulator being turned back on. During this time the patient has to be awake and cooperative since stimulation-related side effects can be detected. It is then possible to change the final position of the electrode slightly to avoid or minimize these side effects.

Once the optimal location of the DBS electrode has been determined the electrode is fixated to the skull to prevent further dislodgement. The burr holes are then also covered mainly to give a pleasing cosmetic result. The last step for surgery is implantation of the implantable pulse generators which are basically the implantable battery units that also contain the electronics to provide chronic pulsed stimulation. These battery packs are placed subcutaneously in the sub-clavicular area or abdominal area. Many centers recommend having these stimulators implanted in a second surgical procedure 2-3 weeks after the electrode implantation. Since surgical planning, MER and electrode implantation can take 8 hours or more patients commonly agree with this two-stage approach.

POSTOPERATIVE FOLLOW UP

Most patients tolerate the often lengthy surgical procedure well despite being off their routine medications for almost the entire day. The majority of patients feel well enough to leave the hospital the day after surgery. Elderly patients may take extra days to recover but only rarely is inpatient rehabilitation necessary. Once the DBS system is implanted, patients follow up with their movement disorder neurologist, who then starts programming their DBS stimulators. The initial programming session in our center occurs at least two weeks after surgery. Multiple clinic visits are subsequently needed to optimize stimulator settings. This process can take several weeks or months since with every programming step and fine-tuning a change in medication may also be advisable. Patients are now given handheld programmers which allow them to interrogate the DBS system. Patients therefore are able to identify if the stimulator is turned on or off, they can turn the system on or off themselves if so desired.

RISKS AND BENEFITS

In addition to the routine surgical risks related to bleeding, anesthesia, and possible infection, DBS presents a small risk of neurological complications. There is approximately a 2-3% chance of brain hemorrhage that may be of no significance, or may cause paralysis, stroke, speech impairment or other major problems. This means that for every 100 patients who undergo surgery, two or three will experience a permanent or severe complication. However, most patients will have no complications. Infection is a problem associated with any implantable device including DBS systems. While treatment of infection may require removal of the electrode, the infections themselves usually do not cause lasting damage. The electrode that is implanted in the brain and the electrical systems that provide stimulation is subject to failure as well.6 However, they are generally well tolerated with no significant changes in brain tissue around the electrodes even decades after implantation.

Stimulation-related side effects are possible but can usually be minimized by changing the stimulation parameters of the DBS system (re-programming). Dependent on the location of the electrode stimulation may cause unwanted paresthesias in the face or hand (typically seen with the electrode in the VIM region), blurry vision or light flashes (with the electrode in the GPi region) or problems with eye coordination (location of electrode in the STN region). Also, if the electrode is close to but not in the ideal target location it may be impossible to evoke a beneficial response even with high energy output. An electrode misplacement of 2-3 mm in any direction can be enough to cause failure of DBS treatment.

Beneficial effects have been demonstrated to last for several years for patients with PD. Patients who initially responded well to medications, but over time have developed side effects, can experience between 60 to 80% improvement in such symptoms as tremor and slowness of movement. In addition, the majority of patients report significant improvement in their walking and balance. Similarly, patients with involuntary movements (dyskinesias) due to their medications, experience over 80 percent reduction in their involuntary movements. Most patients are able to reduce their medications by 50% or more following DBS of the STN.

DISCUSSION AND SUMMARY

In properly selected patients, DBS is safe and effective. It has become standard of care for PD patients with refractory medication-induced motor problems and it is highly effective for patients suffering from essential tremor and dystonia. The promising results reported in the medical literature lead us to believe that DBS surgery will be offered in the near future to many more patients, including those suffering from epilepsy or certain psychiatric diseases.

REFERENCES

1. Benabid AL, Pollak P, et al. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 1987; 50: 344-6.

2. Goetz CG, Poewe W, et al. Evidence-based medical review update. Mov Disord 2005, 20: 523-39.

3. Greenberg BD, Price LH, et al., Neurosurgery for intractable obsessive-compulsive disorder and depression. Neurosurg Clin N Am 2003; 14:199-212.

4. Lagrange E, Krack P, et al. Bilateral subthalamic nucleus stimulation improves health-related quality of life in PD. Neurol 2002 59:1976-8.

5. Mayberg HS, Lozano AM, et al. Deep brain stimulation for treatment-resistant depression. Neuron 2005;45:651-60.

6. Oh MY, Abosch A, et al. Long-term hardware-related complications of deep brain stimulation. Neurosurg 2002 50:1268-74;

7. Rodriguez-Oroz MC, et al, Bilateral deep brain stimulation in Parkinson’s disease. Brain 2005 (Epub ahead of print).

8. Vitek JL, Bakay RA, et al. Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol 2003 53:558-69.

9. Vonck K, Boon P, et al., Neurostimulation for refractory epilepsy. Aaa Neurol Belg. 2003 Dec; 103:213-7.

10. Walter BL, Vitek JL, Surgical treatment for Parkinson’s disease. Lancet Neurol 2004; 3: 719-28.

GERHARD M. FRIEHS, MD, PHD, CATHERINE OJAKANGAS, PHD, LINDA L. CARPENTER, MD, BENJAMIN GREENBERG, MD, PHD, KELVIN L. CHOU, MD

CORRESPONDENCE:

Gerhard M. Friehs, M.D.

2 Dudley Street

Providence, RI 02905

phone: (401) 273-8822

e-mail: Gfriehs@yahoo.com

Gerhard M. Friehs, MD, is Associate Professor, Clinical Neurosciences (Neurosurgery), Brown Medical School.

Catherine Ojakangas, PhD, is Assistant Professor, Department of Neuroscience, Brown Medical School and University of Chicago.

Linda L. Carpenter, MD, is Associate Professor, Department of Psychiatry and Human Behavior, Brown Medical School; and Chief, Mood Disorders Program, Butler Hospital.

Benjamin D. Greenberg, MD, PhD, is Associate Professor, Department of Psychiatry and Human Behavior, Brown Medical School; and Chief of Outpatient Services, Butler Hospital.

Kelvin L. Chou, MD, Affiliation previously cited.

Copyright Rhode Island Medical Society Apr 2006

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