by: G. Rees Cosgrove, MD, FRCS (C), Emad Eskandar, MD
Neurosurgical Service, Massachusetts General Hospital,
Harvard Medical School, Boston, Massachusetts

Address for Correspondence:
Emad N. Eskandar, M.D.
Massachusetts General Hospital
15 Parkman St. ACC # 331
Boston, MA 02114

E-mail: eeskandar@partners.org
Patient Appointments: 617.724.6590
FAX: 617.724.0339

Referrals | Stereotactic Surgery | Parkinson's Disease | Intractable Epilepsy | Movement Disorder Surgery
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Introduction

Surgery for Parkinson's Disease (PD) was introduced by Meyers in the late 1930s with resection of the head of the caudate nucleus and other selected lesions within the basal ganglia.(35) Improvement in tremor and rigidity occurred in many patients when lesions involved the pallidothalamic fibers although mortality was high. Fenelon used a specially designed leukotome to perform free-hand electrocautery of the ansa lenticularis at open craniotomy also with good results.(12) In 1952, Cooper, in the course of attempting to perform a pedunculotomy, inadvertently tore and then ligated the anterior choroidal artery. The patient recovered and was found to be free of tremor and rigidity. Subsequently, ligation of the anterior choroidal artery, which supplies the globus pallidus among other structures, was used in over 50 patients with good results although mortality was 10%.(9) The work of these early pioneers revealed that lesions of the globus pallidus and the ansa lenticularis could provide relief from some of the disabling symptoms of Parkinson's disease.

With the advent of human stereotactic frames, more accurate and reproducible lesioning of the basal ganglia was possible. Narabayashi began using chemopallidotomy for the treatment of Parkinson's Disease in the early 1950s while Guiot and Brion reported their success with thermocoagulation lesions of the pallidum in 1953.(16, 38) Cooper subsequently popularized the procedure in the United States using a guidance device of his own design that utilized craniocerebral landmarks.(9, 10)

The initial surgical target in the pallidum was in the anterodorsal portion of the globus pallidus, however Leksell reported less favorable outcomes with this target and moved to a more posterior and ventral location. The results of this "posteroventral pallidotomy" were reviewed in a study by Svennilson in 1960 which revealed that the majority of patients had improvement in all three cardinal symptoms of Parkinson's disease - tremor, rigidity and bradykinesia.(43)

In 1954, thalamatomy for Parkinson's disease was introduced by Hassler and Riechert.(18) Lesions in the ventrolateral thalamus were found to relieve tremor and improve rigidity although bradykinesia remained mostly unaffected. Largely because of the dramatic effect on tremor, thalamotomy became the operation of choice for the treatment of movement disorders and stereotactic surgery for PD became one of the most common neurosurgical interventions of the day. However, with the introduction of dopamine [L-dopa] replacement therapy in the late 1960s, the surgical treatment for Parkinson's disease decreased precipitously.

As experience with the use of dopamine replacement therapy accumulated, it became clear that it was not a cure for Parkinson's disease. The drugs become progressively less effective over time and require increasing dosages to maintain a beneficial effect. After 5 - 10 years of treatment, patients often begin to react unfavorably to l-dopa with severe drug induced dyskinesias during "ON-periods" and profound tremor, rigidity and akinesia during the "OFF-periods".

Laitinen rekindled interest in the posteroventral pallidotomy in 1992 by reporting his successful experience in 38 patients with medically refractory Parkinson's disease.(26, 27) Since then, numerous centers have reported similarly good results with pallidotomy for selected PD patients.(5, 11, 19, 21, 31, 32, 42) With the advent of improved stereotactic imaging techniques, along with micro-electrode recording and macrostimulation for intraoperative localization of lesions, pallidotomy has become a safe and reproducible procedure. For similar reasons, thalamatomy has also generated renewed interest and remains a valuable surgical option for selected PD patients in whom tremor is the predominant complaint or in patients who suffer from other forms of disabling treatment-refractory tremor.

The neural substrates related to movement have classically been divided into two broad but interrelated systems, the pyramidal and the extrapyramidal. The pyramidal system begins in the primary motor cortex, descends through the corticospinal and corticobulbar tracts, and ultimately affects lower motor neurons in the brainstem and spinal cord. The extrapyramidal system commonly refers to the basal ganglia and their cortical connections. The term basal ganglia as used here refers to the caudate nucleus and the putamen (the striatum), the globus pallidus interna and externa (Gpi and Gpe), the subthalamic nucleus, and the substantia nigra. The ventrolateral thalamus while not classically described as belonging to the basal ganglia also plays a critical role. A strict dichotomy between pyramidal and extrapyramidal systems is unwarranted. For example, collaterals of some corticospinal fibers project to the basal ganglia while the basal ganglia ultimately exert their effect by way of the corticospinal tracts. Nevertheless, lesions of the pyramidal system predictably result in paresis and spasticity, whereas lesions in the extrapyramidal system cause a distinct pattern of abnormalities in the initiation and maintenance of movement. These abnormalities have been classified as negative and positive symptoms. Negative symptoms include bradykinesia (abnormal slowness of movement), akinesia (absence of movement) and loss of postural reflexes. Positive symptoms include findings such as tremor, rigidity and involuntary movements (chorea, athetosis, ballismus, and dystonia). An understanding of the etiology of these disorders and the rationale for their surgical treatment requires some familiarity with the relevant anatomy.

The principal circuit of the basal ganglia is a loop which connects multiple areas of the cortex with the striatum which in turn projects to the globus pallidus which projects to the thalamus which projects back to the cortex (Figure 1). In addition to the primary loop, there are two relevant secondary loops. One such loop connects the striatum with the substantia nigra while the other loop connects the globus pallidus with the subthalamic nucleus.

The substantia nigra (SN) plays a crucial role in one of the side loops of the basal ganglia by way of reciprocal connections with the striatum (Figure 1). The pars compacta of the substantia nigra contains closely packed dopamine containing neurons which project to the caudate and putamen. Loss of these dopamine containing neurons leads to the dysregulation of movement seen in Parkinson's disease.

The other important side-loop of the basal ganglia involves the subthalamic nucleus (STN). The STN receives input from the Gpe and projects to Gpi. Lesions of the subthalamic nucleus classically give rise to hemiballismus. However, dysfunction of the subthalamic nucleus has also been implicated in the pathophysiology of Parkinson's disease.(6)

There are two pathways through the basal ganglia both of which converge on the internal segment of the globus pallidus (Gpi) which in turn comprises the primary output of the basal ganglia to the thalamus. Both pathways begin with projections from the cortex to the striatum. The caudate nucleus receives afferents from the prefrontal cortex while the putamen receives somatotopic input from sensorimotor cortex. The striatum also receives projections from the dopamine containing neurons of the substantia nigra. At this point the two pathways diverge. Some striatal neurons project directly to Gpi thus creating the direct pathway through the basal ganglia (Figure 2A). In the indirect pathway a separate population of striatal neurons first projects to the external segment of the globus pallidus (Figure 2B). Neurons in Gpe then project to the subthalamic nucleus which then projects to Gpi. Thus, both pathways ultimately affect the internal segment of the globus pallidus. The globus pallidus interna then gives rise to two fiber bundles, the lenticular fasciculus (LF) and the ansa lenticularis (AL) which project to the ventrolateral nuclei of the thalamus. The ventrolateral nuclei of the thalamus then project back to motor areas of the cortex completing the loop.

Several lines of evidence suggest that loss of dopamine in Parkinson's disease ultimately results in an increased inhibitory output from the internal segment of the globus pallidus to the thalamus.(4, 6, 50) The net action of dopamine appears to be different among the two subpopulations of striatal output neurons mentioned above, but in both cases the ultimate effect is increased activity of neurons in Gpi. Loss of striatal dopamine causes a decrease in the activity of the striatal neurons projecting directly to the internal division of the globus pallidus (Gpi) (Figure 2A).These neurons in the direct pathway are normally inhibitory to Gpi and therefore a decrease in their activity results in increased activity of Gpi and increased inhibition of the thalamus. In the indirect pathway, loss of striatal dopamine results in increased activity of the (inhibitory) striatal neurons projecting to the external segment of Gpe (Figure 2B). Neurons in Gpe have an inhibitory effect on the subthalamic nucleus and therefore increased inhibition of Gpe allows more activity in the subthalamic nucleus. The subthalamic nucleus has an excitatory effect on Gpi and therefore the increased activity in the subthalamic nucleus results in increased activity of Gpi. Thus in both pathways loss of striatal dopamine ultimately results in increased activity of Gpi and increased inhibition of the thalamus and thalamocortical neurons.

The ventrolateral nuclei of the thalamus are excitatory to the cortex and hence it follows that excessive inhibition of the thalamus by an overactive Gpi could result in clinical symptoms such as rigidity and bradykinesia. This model explains the rationale for pallidotomy, lesioning Gpi and the ansa lenticularis relieves the excessive inhibition of the thalamus which then presumably leads to the observed improvements in rigidity and bradykinesia. Undoubtedly this represents an overly simplified explanation of the mechanisms underlying Parkinson's disease but it is supported by a significant amount of experimental and clinical data. The etiology of tremor in Parkinson's disease is more difficult to elucidate and beyond the scope of this discussion. Nevertheless, the clinical observation that tremor is also frequently relieved by pallidotomy suggests that increased activity in Gpi contributes in some way to the genesis of tremor .

The ventro-lateral thalamus has also been a target for the surgical treatment of Parkinson's disease but its role in the pathology of movement disorders and the optimal location for therapeutic lesions have been the subject of much debate. Part of the difficulty lies in the fact that numerous anatomic classification schemes are in use. The most widely used schemes are the Anglo-American Terminology and the Hassler terminology. In the Anglo-American Terminology the ventro-lateral nuclei are divided from anterior to posterior into the ventralis anterior (VA), ventralis lateralis (VL), and ventralis posterior (VP) while in the Hassler terminology the same nuclei are divided into lateral polaris (LPO), ventralis oralis anterior (Voa), ventralis oralis posterior (Vop), Ventralis intermedius (Vim) and ventralis caudalis (VC) (Figure 3). The posterior portion of the VL nucleus in Anglo-American terminology corresponds to the Vop and Vim of the Hassler terminology while the VP nucleus is essentially the same as the VC nucleus. The Hassler nomenclature will be used in this discussion as it appears to correlate with the relevant anatomy and physiology.

As mentioned above the main pallidal output pathways terminate in the ventrolateral thalamus particularly the Voa nucleus which in turn projects back to the premotor cortex. In contrast the Vop and Vim nuclei receive multiple inputs including afferents from the contralateral cerebellum through the brachium conjunctivum. The Vop and Vim nuclei then project to the motor and premotor cortices. The VC nucleus is the primary thalamic relay for the medial lemniscal and spinothalamic tracts and projects to the somatosensory cortex. Microelectrode recordings in the area of Vim reveal neurons which respond to kinesthetic stimulation, i.e. movement of the joints and squeezing of muscle bellies, while neurons in VC respond to tactile stimulation.(8, 45) Furthermore, neurophysiological recordings have also revealed cells which fire synchronously with the observed tremor (tremor cells) further implicating the Vim in the pathology of tremor.(45) Whether the presence of these cells indicates that the genesis of tremor lies within Vim or that Vim is simply part of a larger loop mediating tremor is not clear. In either case, there is a considerable amount of clinical evidence that Vim lesions are quite effective in alleviating tremor. Lesions placed more anteriorly, in the Vop nucleus, or large lesions including both Vim and Vop lead to improvement in tremor and rigidity although bradykinesia is either unaffected or possibly worsened by such lesions.(23, 41, 46, 47) These findings support the contention that thalamotomy is best reserved for patients with Parkinson's disease in whom tremor is the predominant complaint or in patients with intractable essential or intention tremor.

The goal of both thalamotomy and pallidotomy is to impart functional improvement to the patient by placing a lesion in the appropriate target structure. This lesion should be large enough to provide long-term benefit but small enough to avoid irreversible neurological deficits. The procedure is not expected to change the natural history of the patient's underlying disease but rather to modify the physical manifestations of the illness. By relieving disabling involuntary movements, the patients' independence, functional capacity and ability to carry out normal activities of daily living is enhanced.

In thalamotomy, the goal is to permanently abolish tremor or other disabling involuntary movement disorder such as hemiballismus, chorea or dystonia by placing a small lesion in the Vim nucleus of the thalamus. In pallidotomy, the goal is to abolish drug-induced dyskinesias, tremor, rigidity and bradykinesia along with other motor manifestations of PD by placing a lesion in the ventral posterior globus pallidus.

Indications for Thalamotomy

The best candidates for thalamotomy are patients with tremor-predominant PD or those with incapacitating benign essential tremor. Tremor is defined as an involuntary rhythmical movement and is often categorized in three positions: hands in repose (rest ), hands held up with arms outstretched (postural ), and during movement (intention ). The amplitude, frequency and severity of the tremor varies from patient to patient, but at its worst, can cause severe functional disability.

Parkinsonian tremor is generally present at rest with a frequency of 3 - 5 Hz and is suppressed by movement. It can however be both postural and intentional and is often quite resistant to dopamine replacement therapy. Patients who receive the most benefit from thalamotomy are usually young with tremor predominant PD and unilateral or marked asymmetry in their symptoms. However, the effects of thalamotomy on the other cardinal symptoms of PD are much less predictable and may in some cases cause worsening of bradykinesia. Therefore, patients in whom the symptoms of dyskinesia, bradykinesia or rigidity predominate should be considered for other treatment modalities such as pallidotomy. In addition, since PD is a progressive disease, it is reasonable to expect that even patients with tremor-predominant PD will eventually develop the more disabling symptoms of akinesia and rigidity.

Essential tremor is characterized by disabling intentional tremor not secondary to PD and is one of the most common movement disorders.(30) It is an idiopathic disorder that involves a 4-12 Hz tremor of the extremities that is most prominent during purposeful movement. About half of the cases are familial and transmitted in an autosomal dominant mode with variable penetrance. This disorder has been termed "benign essential tremor" since tremor is the only major symptom but it can produce significant disability including inability to feed or drink, control hand movements or even talk on a telephone. The onset is insidious and can occur at any age with variable progression most often affecting the upper extremities. Recent studies support the observation that thalamotomy can be quite effective in controlling medically refractory essential tremor.(14, 20)

Other diagnoses which are amenable to treatment with thalamatomy include disabling intention tremor due to damage of the cerebellar tracts from cerebrovascular accidents, trauma or multiple sclerosis (3, 7, 15, 20, 25, 33). These conditions often imply more diffuse CNS pathology and therefore outcomes are less predictable and complication rates may be higher. Post-traumatic or post-CVA hemiballismus and chorieform movements have also been treated successfully with thalamotomy.(22, 29, 36) Finally, both primary and secondary dystonias may show improvement after thalamotomy.(2, 51)

Presurgical Evaluation of Thalamotomy Candidates

Patients being considered for thalamotomy should be evaluated by an experienced movement disorder team to ensure that they are good candidates for surgery and that all appropriate medical therapies have been tried. An essential element of this evaluation is to determine the major cause of the patients disability so that realistic goals and expectations can be agreed upon prior to surgery.

It is important to confirm the clinical diagnosis of idiopathic PD or benign essential tremor since a variety of neurodegenerative diseases such as striatonigral degeneration, Shy-Drager syndrome, and progressive supranuclear palsy can mimic PD in their early stages. Patients with these diseases appear to have a much poorer prognosis after thalamotomy. Evidence of dementia or other cognitive decline, speech disorders, serious systemic disease, and advanced age are also considered contraindications to surgery.

Patients whose tremor is caused by trauma, cerebrovascular accident or multiple sclerosis should undergo MR imaging to define the extent and location of intracranial pathology. This information can have important implications regarding the feasibility of thalamotomy in this group of patients. MR imaging is also useful in PD patients, especially older ones, to exclude co-existent intracranial pathology that might preclude surgery.

Standard preoperative blood tests are performed with special attention to platelets, bleeding time, PT and PTT. Patients are advised to discontinue aspirin and other non-steroidal anti-inflammatory agents at least 5 days prior to surgery.

Anesthetic Considerations

Patients are kept NPO on the evening before surgery and are generally advised to withhold their anti-parkinsonian and anti-tremor medication on the morning of surgery. Preoperative sedation with benzodiazepines or other anxyiolitics is avoided. These maneuvers ensure that the tremor will be evident throughout the surgery. If the tremor is pronounced enough to cause significant head movement that might degrade stereotactic image acquisition then a short-acting sedating agent such as propofol or midazolam can be used sparingly at this stage.

Thalamotomy is performed under local anesthesia and requires the full cooperation of the patient therefore the intraoperative use of sedating agents must be avoided. Intravenous access is established ipsilateral to the planned thalamotomy to allow complete freedom of movement in the extremity of interest and oxygen is supplied by nasal cannula. EKG, pulse oximetry and BP is monitored but an arterial line is not inserted. Blood pressure should be maintained in the normal range for the patient. Bladder catheterization is not routinely performed.

Operative Technique - Thalamotomy
Frame Placement

An MRI compatible stereotactic frame is affixed to the cranial vault after infiltration of the pin insertion sites with 1% lidocaine with 1/200,000 epinephrine. The pin insertion sites are chosen to avoid artifact through the planned axial imaging sections of interest. The frame should be placed as symmetrically as possible on the head to minimize rotation and lateral tilt. This ensures that any changes made in electrode position intraoperatively are entirely in the planned direction. We have utilized the CRW frame (Radionics, Burlington, MA) but any MR compatible frame can be used.

Stereotactic Imaging

Following frame placement, the patient is taken to the MRI scanner where sagittal T1-weighted images are obtained first. These images are used to identify the anterior commisure (AC) and the posterior commisure (PC) and measure the AC-PC length. Next T1-weighted (TR 400, TE 12/Fr, FOV 30x30, 2 NEX, 3mm thickness) axial images are obtained through the basal ganglia so that these images are 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 utilized depending on the experience of the center. Alternatively, 3-dimensional volumetric acquisition series can be acquired which allow thinner sections and reconstructions in any plane but these series generally require 10 - 11 minutes and are thus subject to movement artifacts. While a variety of MR sequences can be used for targeting, it is imperative that each center verify the spatial accuracy of their stereotactic frame in their scanner with phantoms. Some inaccuracies can exist with stereotactic MR imaging due to field inhomogeneity and chemical shift artifact therefore we have also performed stereotactic CT imaging to enhance our targeting accuracy. Alternative techniques that employ image fusion software to combine stereotactic CT images with non-stereotactic MR images have also been used to successfully overcome these inaccuracies.

After MR imaging, the patient is taken to the CT scanner and after the appropriate localizer is placed, axial CT images (DFOV, 1.0 - 1.5 mm thickness) roughly parallel to the intercommissural line and through the area of interest are obtained. CT images, although geometrically accurate, do not provide the intrinsic anatomical details that MR images provide and should not be used alone for targeting purposes. In most cases however, the AC/PC line can be identified and used for initial target identification.

Some centers have continued to use the classical 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.(1, 17, 44) We do not routinely perform ventriculography but ultimately each surgeon must choose a technique that in their own hands and experience is consistently accurate and safe.

Target Selection

A variety of stereotactic atlases are available with detailed anatomic representations of thalamic and basal ganglia anatomy. Although there is some controversy regarding optimal target location, the following parameters are generally agreed upon. The initial target is located at a point about 4 - 5 mm posterior to the mid AC-PC plane, 13.5 - 15 mm lateral to the midline, and 0 - 1 mm above the level of the intercommisural plane. When the third ventricle is dilated, it is wise to add 1 - 2 mm to the lateral dimension. (Table I)

Although the spatial resolution of modern MRI and CT scanners continue to improve, the detailed nuclear anatomy of the thalamus is still impossible to discern. Intraoperative physiologic confirmation of the lesion location through stimulation or a combination of stimulation and microelectrode recording remains essential.

Surgical Technique

Once the target point has been calculated, the patient is brought to the operating room. A single dose of an appropriate prophylactic antibiotic is given. The patient is placed in a comfortable position and the frame is fixed to the operating table with the head only slightly elevated above the chest to avoid air embolism. A small patch of hair is shaved over the appropriate frontal region and the area is then prepared and draped. After infiltration of the scalp with 1% lidocaine with 1/200,000 epinephrine, a 2.5 cm parasagittal incision is made and a burr hole placed 2.0 cm from the midline at the level of the coronal suture. The dura is coagulated and opened and a small pial incision is made avoiding any cortical veins to allow for atraumatic introduction of the electrode. At this point the stereotactic arc is brought into the target position and the electrode guide tube is lowered into the burr hole directly over the pial incision. The skin is then temporarily closed around the guide tube with nylon sutures to prevent excessive loss of CSF and brain settling.

Since there are individual differences in thalamic anatomy, initial target selection is only approximate and final targeting must be performed using micro-electrode recordings, macrostimulation or a combination of the two techniques. In general, the initial pass is performed with a micro-electrode to obtain spontaneous neurophysiologic data and then this is followed by the macrostimulation/lesioning electrode.

Microelectrode Recording

There are two techniques available for microelectrode recording in the thalamus. Some centers use true microelectrodes, usually made of tungsten, which allow for the discrimination of single neurons. Other centers use semi-microelectrodes, which are less delicate and easier to use in the electrically hostile environment of the operating theater, but cannot record from single units. These concentric bipolar electrodes have low impedance but can record useful subcortical electrical activity. Both kinds of electrodes are then connected via short leads to a preamplifier. The signal from the preamplifier is then filtered, amplified, and passed through a window discriminator.

Microelectrode recordings in the ventrolateral thalamus reflect the connectivity of the various nuclei as reviewed by Tasker.(45) 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.(39) Some cells may increase their firing shortly before the movement while 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 which 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. Microelectrode recordings in VC reveal very noisy spontaneous activity and many high voltage cells. These cells generally respond to superficial light tough 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 which is often difficult to discern 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

Macrostimulation can also be used to delineate the optimal lesion location. A commercially available lesion generator (Radionics, Burlington, MA) is used for impedance monitoring, stimulation and lesioning. Based on the stereotactic coordinates, a side-seeking (SSE) macroelectrode (Radionics, Burlington, MA) with a 4 mm X 1.8 mm uninsulated tip is introduced under impedance monitoring. The impedance is often seen to drop by about 100? when the gray matter of the basal ganglia/thalamus is reached. Within the electrode tip is a much smaller electrode ( 2 mm X 0.5 mm) that can be extruded in small increments so that without moving the parent electrode shaft, one can explore medially, laterally and posteriorly at any angle. It is through this smaller electrode that stimulation and lesioning is generally performed. Others prefer a standard electrode with any positional adjustments made by withdrawing the electrode and reintroducing it after appropriate change in the target coordinates. Stimulation is performed with square wave pulses at 0.5 - 2.0 volts with a frequency of 2 Hz to obtain motor thresholds and at 50 - 75 Hz to assess for amelioration of symptoms or sensory responses. (Table II)

The typical thalamotomy target is the Vim nucleus and occasionally, the mere introduction of the electrode reduces the tremor indicating that the electrode is in good position. More often, due to individual variation and the small size of Vim, the electrode may be in a suboptimal position and require adjustment. The goal is to place a lesion within Vim, directly anterior to the appropriate somatotopic area in VC and medial to the internal capsule without encroaching on either structure. Fortunately, intraoperative stimulation and microelectrode recording allows for differentiation of the internal capsule, Vop, Vim and VC nuclei based on their physiologic responses.

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.(45)

Since Vim is thought to be the relay nucleus for kinesthetic sensation and VC the relay nucleus for superficial tactile sensation, high frequency stimulation can generally reflect this difference. Stimulation of the Vim usually elicits contralateral parasthesias at higher thresholds than those obtained in the VC nucleus. Vim stimulation may also induce a proprioceptive sensation that a contralateral limb is moving without any actual movement having taken place and may also induce peculiar sensations of vertigo, fainting, or dread but this is generally seen when the electrode is too inferior.

It is important to distinguish Vim from VC for optimal lesion positioning. High frequency stimulation of the VC nucleus always causes contralateral parasthesias. However, the threshold (0.25 - 0.5 volts) for inducing parasthesias is usually much lower than that of the Vim nucleus. Consequently, low threshold parasthesias of the fingertips or mouth indicate that the electrode is too posterior and needs to be moved anteriorly. Sustained suprathreshold stimulation within VC may cause parasthesias that are unbearably intense. There is a clear medial-to-lateral somatotopy within VC with neurons representing the face most medial, those representing the lower limbs more lateral and those representing the upper extremity and hand intermediate (Figure 3). The definition of this somatotopic distribution is important as the lesion in Vim should be made directly anterior to the appropriate site in the VC nucleus.(8, 23)

Another indication that the electrode is in good position relates to tremor response. Low frequency (2 Hz) stimulation within Vim usually causes driving of the tremor whereas high frequency (50 Hz) stimulation causes amelioration of the tremor. Suppression of tremor with 0.5 - 2.0 volts is the goal and indicates accurate targeting. In addition to the anterior-posterior differences between the nuclei, there is also a medial-to-lateral somatotopy within Vim. The face and mouth are represented most medially while the lower extremities are represented more laterally near the internal capsule. Lesions should be directed at the site corresponding to the most severe tremor. Thus lesions for tremor involving the upper extremity should be placed slightly more medial than lesions for tremor involving the lower extremities. Use of the side exploring electrode allows for simplified exploration of this somatotopic organization because the electrode can be partially withdrawn, rotated, and reinserted thereby eliminating the need for complete repositioning.

If the electrode is correctly positioned at the physiologic target site, the mere presence of the electrode in Vim, or more typically, high frequency stimulation causes a reduction in the tremor. In addition, stimulation should be used to ensure that there is no evidence or neurologic impairment with particular attention being paid to speech and motor difficulties.

Lesion Parameters

Once the target has been confirmed, a test lesion is made at 46 oC 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 neurologic problems then a permanent lesion is made at 75 oC 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 physiologic responses and recordings.

After lesioning, the electrode is withdrawn, and the incision is irrigated. The burr hole is filled with Gelfoam and bone dust and the scalp is closed using a layer of inverted 3.0 Vicryl sutures for the galea and 4.0 nylon for the skin. The frame is removed and a dry sterile dressing is placed.

Special Considerations

Bilateral thalamotomies are generally associated with a high complication rate and should not be undertaken lightly. The risks of dysarthria and intellectual or cognitive impairment have been estimated to be as high as 30 - 60 % in the acute postoperative setting. Bilateral procedures, if they must be undertaken, should be staged with at least 3-6 months between procedures and slight variation in the target coordinates from one side to the other may be useful in reducing major side effects.

Postoperative Care
After a brief period of observation patients are usually returned directly to their room. The patients continue with their preoperative medications and outside of mild analgesics, no other medications are usually necessary. Given that hemorrhage is an important cause of serious morbidity, good control of blood pressure in the perioperative period is essential. An MRI scan is obtained within the first 24 hours to assess the lesion location and to exclude perioperative complications.(Figure 5) If neurologically stable, the patient is discharged on the first postoperative day. Sutures are removed one week after surgery. A short course of outpatient rehabilitation therapy may be indicated for some patients to optimize functional recovery of the affected limb.
Complications of Thalamotomy

Thalamotomy shares the same general risks associated with stereotactic procedures namely hemorrhage and infection which occur in about 2-5% of patients. The mortality rate is between 0.5-1%. More specific complications of thalamotomy are due to inaccurate lesion placement or overly large lesions. Lesions placed too laterally may result in contralateral weakness due to injury of the posterior limb of the internal capsule. Many patients, about 25%, have transient contralateral facial weakness presumably secondary to edema involving the internal capsule.(13) The percentage of patients suffering from transient contralateral arm weakness ranges from 3-30% and 1-15% of patients go on to suffer mild but persistent contralateral weakness.(13, 20, 41, 49) Another major source of morbidity, particularly in bilateral lesions, relates to difficulties with speech. About 30% of patients have transient dysarthria or dysphasia while about 10% go on to have persistent deficits.(13, 20) Lesions placed too posterior may cause contralateral hemisensory deficits due to injury of the VC nucleus. Correspondingly, there may be numbness or parasthesias of the mouth or fingers in 1-5% of patients.(8, 46, 49) Transient confusion occurs in about 10-20% of patients and mild cognitive and memory deficits may persist in about 1-5% of patients.(20, 46, 49) Older patients and patients with preexisting cognitive deficits or evidence of tissue loss on CT scan appear to be at a higher risk for impaired postoperative cognition.(8) Left thalamic lesions are associated with an increased risk for deficits in learning, verbal memory and dysarthria while right thalamic lesions are associated with impaired visuospatial memory and nonverbal performance abilities.(28, 48) Bilateral thalamotomies are associated with deficits in memory and cognition in up to 60% of patients along with increased risk of hypophonia (decreased speech volume), dysarthria, dysphasia, and abulia.(8, 28)

Results and Prognosis of Thalamotomy

The observation that thalamotomy is an effective treatment for tremor in patients with PD but that it is ineffective for bradykinesia has been known for some time (23, 24, 34, 37, 41, 46, 47). In a study of the long term effects of thalamotomy on sixty patients, Kelly and Gillingham found that contralateral tremor was abolished in 90% of patients undergoing unilateral thalamotomy at the first postoperative evaluation.(24) Subsequent evaluations revealed that the effect diminished somewhat over time so that at 4 years 86% of patients remained tremor free while 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.(20) Of these patients, 72 percent had complete abolition of tremor while 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 out of 36 (94%) PD patients had complete abolition of contralateral tremor while 29 out of 34 (85%) remained tremor free at one year.(13) Similar results are obtained in patients with intractable essential tremor with 80-90% of patients having marked or moderate improvement.(14, 20) Patients with intractable cerebellar intention tremor respond at somewhat lower rates with 60-80% of patients having significant improvement in tremor.(15, 20, 33)

Indications for Pallidotomy

Only patients with treatment-resistant idiopathic Parkinson's disease that have clearly responded to dopamine replacement therapy in the past should be considered candidates for pallidotomy. While many of the cardinal symptoms of PD will respond to pallidotomy, the features of the disease which respond best are drug induced dyskinesias, painful dystonias, marked ON/OFF fluctuations, severe bradykinesia, and rigidity. Symptoms that may improve but do so less reliably are tremor, speech dysfunction and gait disturbance. Postural instabilitiy is rarely if ever helped. The ideal patient is young (< 50 years of age), suffers from asymmetric idiopathic PD and has severe ON/OFF fluctuations with drug induced dyskinesias. Hemidystonia is another indication for pallidotomy which appears to hold promise although the available data is limited.

Contraindications to pallidotomy include disorders which may mimic idiopathic Parkinson's disease such as progressive supranuclear palsy, Shy-Drager syndrome, or striatonigral degeneration. Dementia or other evidence of a serious cognitive decline are also contraindications. Patients with severe ataxia or other serious gait problems are usually not good candidates for pallidotomy. Advanced age (greater than 75 years) or serious systemic illnesses constitute relative contraindications. Structural abnormalities on MRI may also represent a relative contraindication to pallidotomy.

Presurgical Evaluation of Pallidotomy candidates

Patients being evaluated for pallidotomy at our institution receive an extensive preoperative assessment administered by a team of neurologists and the attending neurosurgeon. An initial screening is performed by review of the medical records and videotapes of the patient in their best ON and worst OFF states. If a patient is felt to be a good candidate then a more thorough clionical evaluation is undertaken. The evaluation begins with a detailed history and physical examination and includes the use of four clinical rating scales. The first is the Unified Parkinson's Disease Rating Scale (UPDRS) which includes assessment of motor function, mentation, and activities of daily living. In addition patients are evaluated using the Schwab and England scale, and the Hoehn and Yahr scale. The SF - 36 Health survey, which is a self assessment of symptoms and level of function is also administered. These test are used to quantify the severity of the patients' symptoms before and after surgery in an effort to determine which patients are best suited for surgery and to assess the overall benefits of surgery. Neuropsychological testing and ophthalmologic consultations are obtained as clinically indicated. All candidates for pallidotomy undergo a routine preoperative brain MRI to rule out gross abnormalities. Once the evaluation is complete, the case is reviewed by the movement disorders team and a decision regarding the appropriateness of the procedure is made.

Operative Technique - Pallidotomy
Anesthetic Considerations

Before surgery, patients are kept without medications for 12 hours. This is done to ensure that patients are in their OFF state in order to minimize involuntary movements during imaging and to more readily assess the effects of surgery. Prior to placement of the frame the patient is mildly sedated with a short acting sedative, such as midazolam or propofol.

Pallidotomy is performed under local anesthesia and requires the full cooperation of the patient therefore the intraoperative use of sedating agents must be avoided. Intravenous access is established ipsilateral to the planned pallidotomy to allow complete freedom of movement in the extremity of interest and oxygen is supplied by nasal cannula. EKG, pulse oximetry and BP is monitored but an arterial line is not inserted. Blood pressure should be maintained in the normal range for the patient. Bladder catheterization is not routinely performed.

Frame placement

An MRI compatible CRW stereotactic frame is then affixed to the cranial vault after infiltration of the pin insertion sites with 1% lidocaine with 1/200,000 epinephrine. Attention is directed to insure that the frame is not tilted or skewed for optimal imaging and target localization. The patient is then brought to the MRI scanner.

Stereotactic Imaging

In our institution, we first obtain a mid-sagittal T1 weighted scout. This image is used to align the gantry of the scanner so that axial images are parallel to the AC-PC (anterior commisure - posterior commisure) plane. Next T1 weighted (TR 400, TE 12/Fr, FOV 30x30, 2 NEX, 3mm thickness) axial images are obtained through the basal ganglia. The patient is then taken to the CT scanner and after the appropriate localizer is placed, axial CT images (DFOV, 1.5 mm thickness) through the area of interest are obtained. An alternative imaging strategy involves first obtaining T1 weighted sagittal images followed by fast spin echo inversion recovery axial and coronal images. This sequence is reported to better delineate gray/white matter differences and allows for better visualization of the internal capsule and optic tract. Another imaging strategy is to use a 3 dimensional SPGR volumetric sequence but these series generally require 10 - 11 minutes and are thus subject to movement artifacts. However, they do allow for reconstruction of the images in sagittal, coronal and axial planes with 0.75 - 1.5 mm slice thickness.

Target Selection

The standard pallidal target lies 2-3 mm in front of the midcommisural point, 5-6 mm below the intercommisural line, and 19-22 mm lateral to the midline of the third ventricle.(Table I) The appropriate coordinates are obtained from both the MRI and CT images and are compared for accuracy. A correctly placed lesion will lie just behind the posterior margin of the mammilary bodies and just superior and lateral to the optic tract on the appropriate images. (Figure 4).

Surgical Technique

Once the imaging is complete, the patient is brought to the operating room. A single dose of an appropriate prophylactic antibiotic (typically cefazolin) is given. The patient is placed in a supine semi-sitting position, with the head slightly raised above the horizontal, and the frame is affixed to the table. The head of the table should not be excessively elevated to prevent air embolism. Great care must be taken to insure that the patients are comfortable since their cooperation is necessary for a successful procedure. A grounding patch is attached to the patient to allow for stimulation and lesioning. A small patch of hair is shaved over the appropriate frontal region and the area is then prepared and draped. Draping should be kept to a reasonable minimum to allow for intra-operative assessment of the patient. We typically use only a single clear plastic drape over the patient's head.

The skin is infiltrated with 1% lidocaine with 1/200,000 epinephrine. A 2.5 cm parasagittal incision is made centered at a point about 3 cm lateral to the midline, in the midpupillary line, and 1-2 cm anterior to the coronal suture. A Hudson brace is used to make a 1 cm burr hole and the bone edges are waxed. The dura is coagulated and opened. Next, the pia of the underlying cortex is coagulated with the bipolar, and a small pial incision is made to allow for atraumatic introduction of the electrode. At this point the stereotactic frame is brought into position and the electrode guide is lowered into the burr hole. The trajectory of the electrode should subtend an angle of 65-70 degrees from the horizontal and 5-10 degrees from the sagittal planes. A piece of Gelfoam is placed around the guide tube and the skin is temporarily closed over the hole with nylon sutures to prevent excessive loss of CSF and brain settling.

Microelectrode Recording

Microelectrode recordings have been used by many centers in an effort to better identify the optimal lesion location and to minimize the risk of injury to the internal capsule or the optic tract. There is as yet insufficient evidence as to whether such recordings offer an advantage over macrostimulation alone and whether such an advantage outweighs the potential increased risks of intracerebral hemorrhage or of prolonged surgery.

The techniques for microelectrode recording in the globus pallidus have been well described by Lozano et al and Sterio et al.(32, 40) Typically, tungsten microelectrodes with an impedance of 1-2 M Ohm at 1 khz are used. Other electrode configurations such as tungsten semi-microelectrodes have also been used successfully.

Usually, the electrodes are clamped to the stereotactic frame and advanced through a guide tube with a microdrive. In all cases, the microelectrode is connected via short leads to a preamplifier which increases the signal to noise ratio. It is important that leads from the electrode to the preamplifier be kept short to minimize the introduction of background electrical noise. The signal from the preamplifier is then filtered, amplified, and passed through a window discriminator. The window discriminator is an electronic device which converts action potentials to digital pulses. These digital pulses can then be stored and analyzed off-line. In addition, these pulses can be converted to an audio signal which is useful for listening to the activity of cells without interference from background neuronal noise.

During pallidotomy, recordings usually proceed from the putamen and Gpe through the Gpi and then near the optic tract. Recent studies have revealed that there are consistent and relatively unique patterns of activity in the Gpe as compared to Gpi.(32, 40) Neurons in Gpe have two distinct patterns of activity. Some units have a slow frequency discharge (10-20 Hz) punctuated by rapid bursts. Other units discharge with an irregular pattern at higher frequencies (30-60 Hz) but also have a bursting pattern with intervening periods of low activity. Many neurons in Gpe respond to repetitive movements with the majority of cells showing an increase in activity to passive or active movements of the contralateral limbs. In contrast, neurons in the Gpi of Parkinson's patients have a higher baseline firing rate than neurons in Gpe (mean 80 Hz) . Furthermore, neurons in Gpi have few of the pauses in activity observed in Gpe. Most commonly, Gpi neurons respond to contralateral movements with an increase in firing rate. In addition, some neurons have been found that respond in synchrony with the patients' tremor.

Once the electrode emerges from the ventral border of the GP into the white matter of the ansa lenticularis, neuronal activity diminishes along with background activity. Deeper penetration of 1 - 2 mm places the electrode tip in close proximity to or within the optic tract. It is difficult to record directly from the optic tract because it contains only axons and the action potentials are correspondingly small. Photic stimulation with averaging of the evoked visual potential can be useful. The most reliable way to determine proximity to the optic tract is by either micro- or macrostimulation. The techniques for macrostimulation are described below. In microstimulation, a 1 sec train consisting of 2 msec square wave pulses at 300 Hz is used to elicit visual phenomenon. Visual thresholds at or near the optic tract are usually between 2-20 ćA. As with macrostimulation, patients report seeing flashing lights of various colors or scotomata in the contralateral visual field.

Macrostimulation

At our institution, we have relied primarily on macrostimulation to verify the location of the lesion. Impedance monitoring, stimulation and lesioning are handled by a Radionics RF lesion generator. A macroelecrode with a 2 X 1.6 mm uninsulated tip is introduced through the guide tube under impedance monitoring. The impedance is seen to drop about 100? when the gray matter of the basal ganglia is reached. The electrode is stopped at a point 6 mm above the target and macrostimulation is then used to further delineate the optimal target location. Low frequency stimulation is performed with square wave pulses at a frequency of 2 Hz at 0-5 Volts to obtain motor thresholds in order to insure that the lesion does not injure the internal capsule. High frequency stimulation using square wave pulses of 50-75 Hz at 0-5 Volts is used to assess for proximity to the optic tract, speech dysfunction, and amelioration of symptoms.(Table II) Stimulation is carried out at 6 mm, 4 mm, and 2 mm above the target and at the target. At each point both low and high frequency stimulation is performed. To obtain the motor thresholds, low frequency stimulation is used and the voltage is gradually increased until fine contractions can be seen in the contralateral hand and/or the tongue. The voltage at which definite contractions can be first seen is the motor threshold. As the electrode is lowered the thresholds are seen to decrease. Typically the motor thresholds are around 4-5 volts at the highest electrode position and decrease to about 2-3 volts at the target. When the electrode is near the target it is usually wise to perform high frequency stimulation first to insure that the electrode is not too close to the optic tract before proceeding with low frequency stimulation. Thresholds which are considerably lower than those outlined above suggest that the electrode is too close to the internal capsule and may need to be moved anteriorly or laterally. High frequency stimulation usually causes an improvement in contralateral rigidity and bradykinesia which may be readily appreciated intra-operatively by using tasks such as finger tapping, rapid pronation/supination of the forearm, and toe tapping. On occasion, high frequency stimulation may elicit dyskinesias, a finding which generally predicts a successful outcome. Potential problems in speech are also assessed during high frequency stimulation by asking the patient to repeat several complex phrases and noting any difficulties. Once the electrode is 2 mm above target, visual thresholds are obtained by turning off the room lights and asking the patient to report if he sees any flashing lights as the voltage as quickly increased and decreased with the high frequency stimulation. The classical response is a perception of flashing lights or phosphenes in the contralateral hemifield. The minimal voltage which elicits visual phenomenon constitutes the visual threshold. The electrode is then lowered to the target position and visual thresholds are again assessed. If the electrode is correctly placed, visual thresholds are usually between 2-3 volts. Higher values indicate that the electrode is too superior and the electrode is then advanced in 1 mm increments while testing the visual threshold at each point. Lower values indicate that the electrode is too inferior and should be raised.

If the stimulation parameters are not as expected, then the electrode is repositioned by 1-3 mm in an appropriate direction as indicated by the stimulation and the entire process is repeated with gradual lowering of the electrode and careful stimulation and assessment of neurologic function. If the stimulation parameters are still not satisfactory then the surgery should be aborted to avoid placing an inaccurate lesion. Obviously the specific stimulation values may differ and considerable experience on part of the surgeon is needed to correlate the thresholds with their location. At final target coordinates, the optimal motor thresholds should be 2-3 Volts while the visual thresholds should be greater than 2 Volts to avoid injury to the internal capsule or optic tract respectively.

Lesion Parameters

Once the target location is verified a test lesion is made at 46 oC for 60 seconds. The patient is then assessed for any evidence of motor, sensory, visual, or speech impairment. If there are no deficits, then a permanent lesion is made at 75-85 oC for 60 seconds. The electrode is then withdrawn to 2 mm and 4 mm above the target and a lesion is made at each site with the similar parameters (85 oC for 60 seconds).

The electrode is then withdrawn and the wound is copiously irrigated. The burr hole is closed with Gelfoam and the scalp is closed using a layer of inverted 3.0 Vicryl sutures for the galea and 4.0 nylon for the skin. The frame is removed and a dry sterile dressing is placed.

Lesion Results

With careful attention to detail the technique described above can be reliably used to create lesions in the posteroventral pallidum (Figure 6). Typically, these acute lesions are about 100 - 150 cu mm and shrink over time. Several studies using similar lesion parameters have reported good outcomes with lesions ranging in size from 50 to 180 cu mm based on postoperative MRI scans.(5, 21, 26, 32) Interestingly, with chronic lesions it is not unusual to obtain follow-up MRI scans and barely be able to see the lesion.

Postoperative Care

At the completion of surgery the patients are allowed to take their next scheduled medications. After a brief period of observation patients are usually returned directly to their room. An MRI scan is obtained within the first 24 hours to assess lesion location and to rule out unforeseen complications. Patients continue with their preoperative medications and outside of mild analgesics, no other medications are usually necessary. The hypokinesia, rigidity, and dyskinesia usually show some immediate improvement, while tremor may improve over several days to weeks. On the first postoperative day the patient is assessed by the neurologists and the neurosurgeon and if all is well, the patient is discharged that day. Sutures are removed one week after surgery.

Special Considerations

In contrast to bilateral thalamotomy, bilateral pallidotomy seems to be associated with fewer complications and is sometimes necessary for adequate control of severe bilateral symptoms. In Laitinen's original report four patients underwent bilateral pallidotomies without any apparent distress.(26) Iacono reported performing 68 bilateral pallidotomies, 49 of which were contemporaneous, also without an apparent increase in the complication rate.(19). Other centers have experienced major and devastating complications from bilateral pallidotomies and are extremely reluctant to recommend it. When necessary, we prefer to perform staged bilateral pallidotomies, operating contralateral to the more affected side first. This allows for an opportunity to determine the benefit of the operation. Furthermore, the functional improvement obtained after unilateral pallidotomy often negates the need for a second operation At our institution, we have performed 14 staged bilateral pallidotomies with only one patient having suffered an apparent complication which was a significant deterioration in her ability to walk. Many patients and their families may also complain of some mild increase in hypophonia. The reasons why some centers have had more complications with bilateral pallidotomies are not well understood.

Complications of Pallidotomy

Any surgical procedure which involves creating a permanent lesion carries a risk of inadvertent injury to nearby structures. However it is possible to minimize that risk with a combination of careful stererotactic planning and intraoperative stimulation and/or microelectrode recording. A number of recent studies have shown that pallidotomy can be a relatively safe procedure with minimal risk of serious morbidity or mortality. Pallidotomy carries the same general risks of hemorrhage and infection associated with any stereotactic procedure. In general the risk of such complications ranges from 2-5 %. Pallidotomy carries the additional risks of injury to the optic tract or the internal capsule which are both near the optimal lesion location and hence prone to injury. In Laitinen's original report, 7 out of 38 patients (15%) suffered complications.(26) Six patients suffered from central homonymous visual field defects while one patient had transitory facial weakness and dysphasia. Later studies reported somewhat lower complication rates. Iacono et al. reported complications in 8 out of 126 patients for an overall complication rate of 6.3%.(19) Three patients suffered visual field defects and 5 patients suffered from hemiparesis due to hemorrhage or in one case an intracranial abscess. In a series of 70 patients reported by Lozano one patient suffered an intracortical hematoma requiring evacuation and in a series of 33 patients reported by Dogali et al. one patient suffered from transient sexual disinhibition and one patient suffered from a stroke 7 months after the procedure.(11, 32) In our institution, we have performed over 90 pallidotomies. To date, only 2 patients have suffered from small (< 2 cm) cortical hematomas that were cklinically silent and only detected on postoperative MRI and one patient suffered a visual field defect. Thus the reported risk for pallidotomy ranges from 3-15% but using the most current techniques a better estimate is probably between 3-6%.

Results and Prognosis

Given that pallidotomy has only recently enjoyed increased attention there are few studies evaluating its efficacy. Furthermore the long term benefits of pallidotomy are unknown. Nevertheless the existing studies seem to agree on several points. The primary benefit of pallidotomy during the ON state is a dramatic reduction in contralateral dyskinesias. Virtually all patients, 90-100%, with well-placed lesions have significant improvement or abolition of contralateral dyskinesias.(5, 19, 21, 26, 31) Pallidotomy also improves many of the OFF state symptoms. Most patients report a decrease in the number of hours per day that they are OFF along with a reduction in symptom severity during the OFF state.(5, 19, 21, 31) Rigidity and bradykinesia appear to be improved in about 90% of patients while tremor appears to improve in about 80% of patients. Other facets of Parkinson's disease which may show improvement with pallidotomy include gait and speech volume. Freezing episodes and postural instability do not appear to be improved with pallidotomy. Although long term studies are not available, it appears that the effects of pallidotomy are relatively long lasting with most patients retaining some benefit at 12 months postoperatively.(5, 11, 21, 26) The results at our own institution are largely in agreement with previous studies. We have found that most patients have good or excellent relief of l-dopa induced dyskinesias, rigidity, and bradykinesia, while the majority of patients have some improvement in tremor.

Conclusions

The management of patients with PD has evolved substantially over the past fifty years. Initial enthusiasm for stereotactic ablative surgical therapy was followed by its abandonment and an almost complete reliance on medical therapy. More recently, as the long term consequences of dopamine replacement therapy have become evident, there has been a resurgence of interest in stereotactic surgery. Both thalamotomy and pallidotomy can impart useful functional improvement in selected patients although neither intervention will change the course of the underlying disease. In the future, it appears that the optimal management of patients with movement disorders will require a combined approach with medical therapy providing the first line of treatment and surgery providing an option for selected patients who can no longer be adequately managed with medical therapy alone. Whether alternative surgical treatments such as chronic deep brain stimulation or neural transplantation can ultimately provide a long term solution for Parkinson's disease remains to be seen.

• 1. Alterman RL. Kall BA, Cohen H, and Kelly PJ. Stereotactic ventrolateral thalmatomy: Is ventriculography necessary? Neurosurgery 1995; 37(4):717-21.
• 2. Andrew J, Clare JF, Harrison MJG. Stereotaxic thalamatomy in 55 cases of dystonia. Brain 1983; 106:981-1000.
• 3. Arsalo A, Hanninen A. Laitinen L. Functional neurosurgery in the treatment of multiple sclerosis. Ann Clin Res 1973; 5:74-79.
• 4. Bakay RAE, DeLong MR, Vitek JL. Posteroventral pallidotomy for Parkinson's disease (letter). J Neurosurg 1992; 77:487-488.
• 5. Baron MS, Vitek JL, Bakay RAE, et al. Treatment of Advanced Parkinson's Disease by Posterior Gpi Pallidotomy: 1-Year results of a Pilot Study. Ann Neurol 1996; 40(3):355-366.
• 6. Bergman H. Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 1990; 249:1436-1438.
• 7. Bullard DE, Nashold BS. Stereotaxic thalamotomy for treatment of posttraumatic movement disorders. J Neurosurg 1984; 61:316-321.
• 8. Burchiel KJ. Thalamotomy for movement disorders. Neurosurg Clin North America 1995; 6(1):55-71.
• 9. Cooper IS. Parkinsonism: Its Medical and Surgical Therapy. 1961. Springfield IL. Charles C. Thomas.
• 10. Cooper IS, Bravo G: Chemopallidectomy and chemothalamectomy. J Neurosurg 1958; 15:244-250.
• 11. Dogali M, Sterio D, Fazzini E, et al. Effects of posteroventral pallidotomy on Parkinson's Disease. Adv Neurol 1996; 69:585-590.
• 12. Fenelon F. Essais de traitement neurochurgical du syndrome parkinsonien par intervetion directe sur les voies extrapyramidales immediatement soussstriopallidales. Rev Neurol 1950; 83:437.
• 13. Fox MW, Ahlskog E, Kelly PJ. Stererotactic ventrolateralis thalamotomy for medically refractory tremor in post-levodopa era Parkinson's disease patients. J Neurosurg. 1991; 75:723-730.
• 14. Goldman MS, Ahlskog E, Kelly P. The symptomatic and functional outcome of stereotactic thlamotomy for medically intractable essential tremor. J Neurosurg 1992; 76:924-928.
• 15. Goldman MS, Kelly PJ, Symptomatic and functional outcome of stereotactic ventralis lateralis thalamotomy for intention tremor. J Neurosurg. 1992; 77:223-229.
• 16. Guiot G, Brion S. Traitement des mouvements anormaux par la coagulation pallidale. Rev Neurol 1953; 89:578-580.
• 17. Hariz MI, Bergenhiem AT. Clinical evaluation of CT guided versus ventriculography guided thalamotomy for movement disorders. Acta Neurochir. 1993; 123:147.
• 18. Hassler R, Riechert T. Indikationen und Lokalisations methode der gezielten Hirnoperationen. Nervenarzt 1954; 25:441.
• 19. Iacono RP, Shima F, Lonser RR, Kuniyoshi S, Maeda G, Yamada S. The results, indications, and physiology of posteroventral pallidotomy for patients with Parkinson's disease. Neurosurgery 1995; 36:1118-1127.
• 20. Jankovic J, Cardoso F, Grossman R, et al. Outcome after stereotactic thalamatomy for Parkinsonian, essential, and other types of tremor. Neurosurgery 1995; 37:680-687.
• 21. Johansson F, Malm J, Nordh E, Hariz M. Usefulness of pallidotomy in advanced Parkinson's disease. J Neurol Neurosurg Psych 1997; 62:125-132.
• 22. Kawashima Y, Takahashi MH, Ohye C. Stereotactic Vim-Vo-Thalamotomy for choreatic movement disorder. Acta Neurochir Supp 1991; 52:103-106.
• 23. Kelly PJ, Ahlskog JE, Goerss SJ, Daube JR, Duffy JR, Kalls BA. Computer-assisted stererotactic ventralis lateralis thlamatomy with microelectrode recording control in patients with Parkinson's disease. Mayo Clin Proc 1987; 62:655-664.
• 24. Kelly PJ, Gillingham FJ. The long-term results of stereotaxic surgery and l-dopa therapy in patients with Parkinson's disease. J Neurosurg 1980; 53:332-337.
• 25. Krayenbuhl H, Ysargil MG. Relief of intention tremor due to multiple sclerosis by stereotaxic thalamotomy. Confin Neurol 1962; 22:368-374.
• 26. Laitinen LV, Bergenheim AT, Hariz MI. Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease. J Neurosurg 1992; 76:53-61.
• 27. Laitnen LV, Bergenheim AT, Hariz MI. Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stererotactic Funct Neurosurg 1992; 58:14-21.
• 28. Laitnen LV, Hariz MI. Movement Disorders. In Youman's Neurological Surgery. 4th Edition. Philadelphia PA. W.B. Saunders Company. 1996.
• 29. Levesque MF, Markham CH. Ventral intermediate thalamotomy for posttraumatic hemiballismus. Stereotact Funct Neurosurg 1992; 58:26-29.
• 30. Lou JS and Jankovic J. Essential tremor. Clinical correlates in 350 patients. Neurology 1991; 41:234-238.
• 31. Lozano AM, Lang AE, Galvez-Jimenez N, et al. Effect of Gpi Pallidotomy on motor function in Parkinson's disease. Lancet 1995; 346:1383-1387.
• 32. Lozano A, Hutchison W. Kiss Z, et al. Methods for microelectrode guided posteroventral pallidotomy. J Neurosurg 1996; 84:194-202.
• 33. Marks PV. Stereotactic surgery for post-traumatic cerebellar syndrome: An analysis of seven cases. Stereotact Funct Neurosurg 1993; 60:157-167.
• 34. Matsumoto K, Shichijo F, Fukami T. Long-term follow-up review of cases of Parkinson's disease after unilateral or bilateral thalamotomy. J Neurosurg 1984; 60:1033-1044.
• 35. Meyers R. The modification of alternating tremor, rigidity and festination by surgery of the basal ganglia. Res Publ Assoc Res Nerv Ment Dis 1942; 21:692-665,. v36. Mundinger F, Riechert T, Disselhoff J. Long term results of stereotaxic operations on extrapyramidal hyperkinesia (Excluding Parkinsonism). Confin Neurol 1970; 32:71-78.
• 37. Narabayashi H. Maeda T, Yokochi F. Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamtomy using a microelectrode technique in Parkinsonism. Appl Neurophysiol 1987; 50:330-337.
• 38. Narabayashi H, Okuma T. Procaine-oil blocking of the globus pallidus for the treatment of rigidity and tremor of parkinsonism. Proc Jpn Acad 1953; 29:134-137.
• 39. Raeva S. Localization in human thalamus of units tirggered during verbal commands, voluntary movements, and tremor. Electroenceph and Clin Neurophysiol 1986; 63:160-173.
• 40. Sterio D, Beric A, Dogali M, et al. Neurophysiological properties of pallidal neurons in Parkinson's disease. Ann Neurol 1994; 35:586-951.
• 41. Selby G. Stereotactic surgery for the relief of Parkinson's disease. Part 2. An Analysis of results in a series of 303 patients. J. Neurol Sci. 1967; 5:343-375.
• 42. Sutton JP, Couldwell W, Lew MF, Mallory L, Grafton S, DeGiorgio C, Welsh M, Apuzzo MLJ, Ahmadi J, Waters CH. Ventroposterior medial pallidotomy in patients with advanced Parkinson's disease. Neurosurgery 1995; 36:1112-1117,.
• 43. Svennilson E, Torvik A, Lowe R, Leksell L. Treatment of parkinsonism by stereotactic thermal lesions in the pallidal region. Acta Psychiatr Scand 1960; 35:358-377.
• 44. Tasker RR, Dostrovsky JO, Dolan EJ. Computerized tomography is just as accurate as ventriculography for functional stereotactic thalamotomy. Stereotact Funct Neurosurg 1991; 57:157-166.
• 45. Tasker RR, Kiss ZH. The role of the thalamus in functional neurosurgery. Neurosurg. Clin North America 1995; 6(1):73-104.
• 46. Tasker RR, Siqueira J, Hawrylyshyn P, Organ L. What Happened to VIM thalamotomy for Parkinson's disease? Appl Neurophysiol. 1983; 46:68-83.
• 47. Van Buren JM, Choh-Luh L, Shapiro DY et al. A qualitative evaluation of Parkinsonians three to six years following thalamotomy. Confin Neurol 1973; 35:202-235.
• 48. Vilkki J, Laitinen LV.Effects of pulvinotomy and ventrolateral thlamatomy on some cognitive functions. Neuropsychologia 1976; 14:67-78.
• 49. Waltz JM, Riklan M, Stellar S, Cooper I. Cryothalamectomy for Parkinson's disease. A statistical analysis. Neurology 1966; 16:994-1002.
• 50. Wichmann T, DeLong MR. Pathophysiology of Parkinsonian motor abnormalities. Adv Neurol 1993; 60:53-61.
• 51. Yamashiro K, Tasker RR, Stereotactic thalamotomy for dystonic patients. Stererotactic Funct Neurosurg 1993; 60:81-85.

• FIGURE 1. Connections between the cortex, basal ganglia and thalamus. Excitatory connections are indicated by a + sign while inhibitory connections are indicated by a - sign. Abbreviations are as follows: AL - ansa lenticularis, Gpe - Globus pallidus externa, Gpi - globus pallidus interna, LF - lenticular fasciculus, , LPO - lateralis polaris, SN - substantia nigra, STN - subthalamic nucleus, VC - ventralis caudalis, Vim - Ventralis intermedius, Voa - ventralis oralis anterior, Vop - ventralis oralis posterior.
• FIGURE 2. Abnormalities in Parkinson's disease. Gray lines indicate abnormally decreased activity while black lines indicate abnormally increased activity. A. In the direct pathway, loss of dopamine causes a decrease in the inhibitory activity of the striatum on Gpi leading to increased inhibition of the thalamus. B. In the indirect pathway loss of dopamine causes decreased inhibition of the striatum, increased inhibition of Gpe, decreased inhibition of the STN, increased activity in Gpi, and finally increased inhibition of the thalamus. Abbreviations are the same as Figure 1.
• FIGURE 3. Axial section through the thalamus at 1.5 mm above the AC-PC plane. Abbreviations are as follows: III V - third ventricle, Cd - caudate, Fx - fornix, Gpe - globus pallidus externa, Gpi - globus pallidus interna, IC - internal capsule, LPO - lateral polaris, LV - lateral ventricle, Put - putamen, Pv - pulvinar, VC - ventralis caudalis, Vim - Ventralis intermedius, Voa - ventralis oralis anterior, Vop - ventralis oralis posterior. L, H, and F refer to the somatotopic representation of the leg, hand, and face in the VC and Vim nuclei.
• FIGURE 4. Axial and sagittal diagrams showing the globus pallidus and relevant nearby structures. Note the proximity of the lesion target to the optic tract, internal capsule, and the ansa lenticularis. A. Axial section through the basal ganglia at 3.5 mm below the AC-PC plane. B. Coronal section through the basal ganglia at 2 mm anterior to the mid AC-PC line. Abbreviations are as follows: AC - anterior commisure, AL - ansa lenticularis, Amg - amygdala, CC - corpus callosum, Cd - Caudate, CR - corona radiata, Fx - fornix, Gpe - globus pallidus externa, Gpi - globus pallidus interna, IC - Internal capsule, OT - optic tract, Put - putamen, RN - red nucleus, Sth - subthalamic nucleus, and Th - thalamus. The + indicates center of initial lesion target.
• FIGURE 5. CT images taken within 24 hours after right thalamotomy (left). Axial proton density MR images at the intercommisural plane 4 months after surgery (right).
• FIGURE 6. Axial (left) and coronal (right) T2 weighted MR images obtained 1 day following macro-stimulation guided pallidotomy.