The indications for thalamotomy or thalamic stimulation are similar. Patients should have tremor that is refractory to medical therapy and represents the predominant form of disability. The best candidates for thalamic surgery are patients with incapacitating benign essential tremor and those with tremor-predominant PD that is unilateral or asymmetric. Patients with PD who have other motor signs should be considered for surgery aimed at other targets, such as the globus pallidus internus (Gpi) or the subthalamic nucleus (STN). Thalamic surgery may also be useful in patients with tremor secondary to multiple sclerosis or trauma, although the results are less predictable because of the associated injury to other brain structures inherent in these afflictions.
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 patients with ET should include adequate trials of pro-panolol, mysoline, and clonazepam, whereas therapy for patients with PD should include Sinemet, dopamine agonists, and anticholinergics. An essential element of this evaluation is to determine the major cause of the patient's disability so that realistic goals and expectations can be agreed on before surgery.
It is important to confirm the clinical diagnosis of benign essential tremor or idiopathic PD, as a variety of neurodegenerative diseases can present with tremor in their early stages. Patients with these other neuro-degenerative diseases appear to have a much poorer prognosis after thala-motomy. Evidence of dementia or other cognitive decline, speech disorders, serious systemic disease, and advanced age are also considered contraindications to surgery. As a final point, bilateral thalamotomies are generally associated with a prohibitively high complication rate and should not be undertaken.
4 OPERATIVE TECHNIQUE—THALAMOTOMY AND THALAMIC STIMULATION
Patients are kept NPO on the evening before surgery and are generally advised to withhold their antiparkinsonian and antitremor medication on the morning of surgery to ensure that the tremor will be evident throughout the surgery. Surgery is performed under local anesthesia and requires the full cooperation of the patient; therefore, the intraoperative use of sedating agents should be avoided.
A magnetic resonance imaging (MRI) compatible stereotactic frame is affixed to the cranial vault after infiltration of the pin insertion sites with local anaesthetic. Stereotactic sagittal T1-weighted MR images are obtained first to identify the anterior commissure (AC) and the posterior commissure (PC) and measure the AC-PC length. Text T1-weighted axial images are obtained through the basal ganglia and thalamus parallel to the AC-PC plane. Additional images in the coronal plane with fast spin echo inversion (FSE IR) recovery sequences to accentuate the gray-white matter borders of the thalamus and internal capsule can be used, depending on the experience of the center. Alternatively, three-dimensional volumetric acquisition series can be acquired that allow thinner sections and reconstruction in any plane, but these series generally require 10 to 12 minutes and are thus subject to movement artifacts.
A variety of MR sequences can be used for targeting, but it is imperative that each center verify the spatial accuracy of their stereotactic frame in their scanner with phantoms. At our center, we prefer to complement the MRI targeting with computed tomographic (CT) images parallel to the in-
tercommissural line and through the area of interest. Computed tomographic images, although geometrically accurate, do not provide the intrinsic anatomical detail that MR images provide and should not be used alone for targeting purposes. The target coordinates from both the MRI and CT images are then compared for accuracy. Some centers have continued to use the classic method of ventriculography to localize the target; however, recent studies have shown that surgery guided by CT/MRI alone is just as effective and may have a lower complication rate [8,11].
A variety of stereotactic atlases provide detailed anatomical representations of thalamic and basal ganglia anatomy. There is some controversy regarding optimal target location in the thalamus, but the following parameters are generally agreed on. The initial target is located at a point about 5 mm posterior to the mid AC-PC plane, 13.5 to 15 mm lateral to the midline, and 0 to 1 mm above the level of the intercommissural plane. When the third ventricle is dilated, it is wise to add 1 to 2 mm to the lateral dimension. Alternatively, one can measure 11 mm lateral to the wall of the third ventricle. The spatial resolution of modern MRI scanners continues to improve, but the detailed nuclear anatomy of the thalamus is still impossible to discern. Therefore, intraoperative physiological confirmation of the lesion location through stimulation or a combination of stimulation and microelec-trode recording remains essential.
With the patient in a comfortable position, the scalp is infiltrated with local anaesthetic and a parasagittal incision is made for a burr hole placed 2.5 cm from the midline at the level of the coronal suture. The dura and pia is coagulated, avoiding any cortical veins to allow for atraumatic introduction of the electrode. At this point, the stereotactic arc is brought into position and the electrode guide tube is lowered into the burr hole directly over the pial incision. The burr hole is filled with fibrin glue or the skin is temporarily closed around the guide tube with nylon sutures to prevent excessive loss of cerebrospinal fluid (CSF) and brain settling.
Microelectrode recordings in the ventrolateral thalamus reflect the connectivity of the various nuclei as reviewed by Tasker . Recordings in the Vop nucleus frequently reveal voluntary cells that are less noisy than those in Vim or VC. These cells change their firing rate in advance or at the beginning of their related movements . Some cells may increase their firing shortly before the movement, whereas others may show a decreased rate or become rhythmic at the onset or completion of a movement. Recordings in Vim reveal moderately noisy high voltage neurons that respond to contralateral passive joint movement, squeezing of muscle bellies, or pressure on deep structures such as tendons. In patients with tremor, kinesthetic cells fire rhythmically at tremor frequency. Recordings in VC reveal very noisy spontaneous activity and many high voltage cells. These cells generally respond to superficial light touch such as light brushing of the skin or a puff of air. These cells respond faithfully without fatigue. The largest volume of VC is occupied by tactile cells representing the face and manual digits. The floor of the thalamus can be identified by the sudden loss of spontaneous neuronal activity as the microelectrode leaves the gray matter of the thalamus and enters the white matter of the zona incerta. A careful analysis of the neuronal activity of these various cell types can confirm that the appropriate target in Vim thalamus is selected.
Macrostimulation using an electrode with a 2-mm exposed tip can also be used to delineate the optimal lesion location. Stimulation is performed with square wave pulses at 0.5 to 2.0 volts at a frequency of 2 Hz to obtain motor thresholds and at 50 to 75 Hz to assess for amelioration of symptoms or sensory responses.
The typical thalamotomy target (Vim) is directly anterior to the appropriate somatotopic area in VC and just medial to the internal capsule. Occasionally, the mere introduction of the electrode reduces the tremor, indicating that the electrode is in good position. More often, because of individual variation, targeting error, and the small size of Vim, the electrode may be in a suboptimal position and require adjustment. If the electrode is placed too anteriorly in the Vop nucleus, low frequency stimulation may induce movement in the contralateral limbs. This movement is focal at threshold, beginning at one joint and involving greater parts of the contralateral limbs as stimulation intensity is increased . Because VC is the relay nucleus for superficial tactile sensation, high frequency stimulation can induce parasthesias at much lower thresholds than that of the Vim nucleus. Therefore, low threshold (0.25 to 0.5 volts) parasthesias of the fingertips or mouth indicate that the electrode is too posterior and needs to be moved anteriorly.
In addition to the anterior-posterior differences between the thalamic nuclei, there is also a clear medial-to-lateral somatotopy within both Vim and VC. Neurons in VC representing the face are found more medial; those representing the lower limbs more lateral near the internal capsule; and those representing the upper extremity and hand intermediate (Fig. 3). The definition of this somatotopic distribution is important as the lesion or the stimulating electrode in Vim should be placed directly anterior to the appropriate site in the VC nucleus [7,15]. Thus lesions for tremor involving the upper extremity should be placed more medial than lesions for tremor involving the lower extremities.
If the electrode is in good position, low frequency (2 Hz) stimulation within Vim usually drives the tremor, whereas high frequency (75 Hz) stimulation suppresses it. Suppression of tremor with 0.5 to 2.0 volts is the goal and indicates accurate targeting. In addition, high frequency stimulation should be used to ensure that there is no evidence of neurological impairment such as motor, speech, or cognitive difficulties.
Once the target has been confirmed, a test lesion is made at 46° to 48° C for 60 seconds. During this time, the patient is tested neurologically for
contralateral motor dexterity and sensation along with verbal skills. If there is improvement in tremor and no neurological deficits, then a permanent lesion is made at 75° C for 60 seconds. During the lesioning, the neurological status of the patient is continuously monitored and lesioning is halted if any impairment or change is noted. If complete abolition of the tremor has not been accomplished, then the lesion may be enlarged as guided by the intraoperative physiological responses and recordings.
Once the optimal target coordinates have been obtained, the deep brain stimulating (DBS) electrode is introduced to the appropriate depth. By temporarily connecting the lead to an external stimulator, the inhibitory effect on tremor can be assessed along with the presence of any side effects. If tremor suppression is obtained, the probe is secured in place using the burr hole cap or bone cement. The primary incision is closed and the patient is then placed under general anesthesia. The infraclavicular pocket for the stimulator is made and the leads are tunneled and connected. Some groups use fluo-roscopic guidance to ensure that the electrode has not migrated during the procedure.
The general finding that thalamotomy is an effective treatment for tremor in patients with tremor-predominant Parkinson's disease has been known for some time (Table 1) [8,14-16,24,26,30,36,39]. In a study of the long-term effects of thalamotomy on 60 patients, Kelly and Gillingham found that contralateral tremor was abolished in 90% of patients undergoing unilateral thalamotomy at the first postoperative evaluation . Subsequent evaluations revealed that the effect diminished somewhat over time so that at 4 years, 86% of patients remained tremor free, whereas at 10 years, 57% of surviving patients remained tremor free. Rigidity was also improved by thalamotomy in 88% of patients initially and in 55% of patients at 10 years. There was no effect of thalamotomy on bradykinesia or other manifestations of Parkinson's disease, such as mental deterioration or gait disturbance. More recent series reflect a similar distribution. Jankovic et al reported a series of 42 patients who underwent thalamotomy for intractable tremor . Of these patients, 72% had complete abolition of tremor, whereas an additional 14% had significant improvement in tremor. There was a small but statistically insignificant effect on rigidity and no effect on bradykinesia. In another series reported by Fox et al, 34 of 36 (94%) PD patients had com-
Table 1 Summary of Thalamotomy and Thalamic Stimulation Studies
PD patients number
ET patients number
Fox etal, 1991 36 86% Goldman et al, 1992
Jankovic et al, 1995 42 86%
Kelly et al, 1987 12 100%
Kelly et al, 1980 60 90%
Linhares et al, 2000 40 75%
Nagaseki et al, 1986 27 96%
Wester et al, 1990 33 79% Thalamic stimulation
Benabid et al, 1996 80 86%
Blond et al, 1992 10 80% Huble et al, 1996
Koller et al, 1997 29 71%
Limousin et al, 1999 73 85%
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