Methods for microelectrode-guided posteroventral pallidotomy


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Methods for microelectrode-guided posteroventral pallidotomy
  ALLIDOTOMY was used as a surgical treatment forParkinson’s disease in the 1950s and 1960s. Varioustechniques were used to inactivate or ablate theglobus pallidus (GP) such as procaine in oil, occlusion of the blood supply, deposition of radioactive material, cryo-lesions, or electrocoagulation. 3,12,29 Pallidotomy was al-most entirely replaced by the thalamotomy procedure of Hassler and Riechert, 14 which was reported by these au-thors to be more effective for tremor reduction. The surgi-cal treatment of parkinsonism declined in general with theintroduction of L -Dopa pharmacotherapy. For several reasons, there is a renewed interest in ste-reotactic posteroventral pallidotomy for the treatment of Parkinson’s disease. First, current therapy is not totallysatisfactory, because certain patients do not tolerate avail-able drugs, they are inadequately treated, or they developmotor and nonmotor complications. Second, there havebeen significant improvements in neuroimaging and sur-gical techniques in the last 30 years, making the stereo-tactic procedure safer and more accurate. Third, the effec-tiveness of pallidotomy has been recently reconfirmed,which has prompted a reexamination of this surgical treat-ment. 19 Finally, advances in the understanding of the basalganglia and the pathophysiology of parkinsonism haveprovided a scientific rationale to proceed with neurosurgi-cal strategies to control the overactivity of the internalsegment of the GP. 24,34 Recently, several groups have initiated microelectroderecordings in the human pallidum and reported the iden-tification of cell types described in nonhuman pri-mates. 17,28,33 Our group has obtained extensive experiencewith thalamic recordings and localization techniques 20,30 and has now gained experience with pallidal functionalstereotactic localization. We examined the overall neu-ronal firing rates in the various segments of the GP andfound evidence of elevated activity in the internal seg-ments of the globus pallidus internus (GPi) that resemblesthe alterations reported in 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine–treated monkeys. 17 We have alsoidentified “tremor cells” in the GPi by means of spectraland autocorrelogram analyses. 16 In this study, we report using microelectrode recordingand stimulation techniques to determine the optimum sitefor radiofrequency lesions. To a large extent the target de-pends on the location of the optic tract and internal cap-sule, which are in intimate relation to the lesion site andfor which there is a risk of injury during pallidotomy. Clinical Material and Methods Patient Population We have currently performed microelectrode-guidedpallidotomy in 70 patients for refractory Parkinson’s dis- J Neurosurg 84 :194–202, 1996 194 Methods for microelectrode-guided posteroventralpallidotomy A NDRES L OZANO , M.D., P H .D., W ILLIAM H UTCHISON , P H .D., Z ELMA K ISS , M.D.,R ONALD T ASKER , M.D., K AREN D AVIS , P H .D., AND J ONATHAN D OSTROVSKY , P H .D.  Division of Neurosurgery and Playfair Neuroscience Unit, The Toronto Hospital (Western Division),Toronto, Ontario, Canada; and Department of Physiology, Faculty of Medicine, University of Toronto,Toronto, Ontario, Canada  Methods for localizing the posteroventral globus pallidus internus are described. The authors’ techniques include theuse of microelectrodes to record single-unit activity and to microstimulate in human pallidum and its surrounding struc-tures. This technique allows a precise determination of the locations of characteristic cell types in sequential trajectoriesthrough the external and internal segments of the pallidum. The location of the optic tract can be determined from micro-stimulation-evoked visual sensations and recordings of flash-evoked potentials. In addition, microstimulation-evokedmotor and sensory responses allow the internal capsule to be identified. The data collected using this technique are animportant adjunct to selecting optimum sites to place electrocoagulation lesions for stereotactic posteroventral pallidoto-my for refractory Parkinson’s disease. K EY W ORDS •stereotaxy•microelectrode•visual evoked potentials•pallidum•microstimulation P  J. Neurosurg. / Volume 84 / February, 1996   ease, and in four for striatonigral degeneration. The mainsymptoms were rigidity and bradykinesia/akinesia, withsome patients presenting with tremor of varying degree,and three with severe tremor. Patients gave informed con-sent prior to the procedure, and the protocol was reviewedand approved by The Toronto Hospital Committee for Re-search on Human Subjects. Stereotactic Procedure A Leksell model (D or G) stereotactic frame was ap-plied after local anesthetic. Patients underwent magneticresonance (MR) imaging to localize the anterior commis-sure (AC) and posterior commissure (PC). A Sigma 1.5-tesla magnet (General Electric, Milwaukee, WI) was usedto produce 1-mm thick nonoverlapping slices in axial,sagittal, and coronal planes. Images were acquired usingthe “spoiled grass” sequence with a relaxation time of 43msec and an excitation time of 13 msec. The stereotacticcoordinates of AC and PC were calculated using the MRimaging console software. The calculated intercommis-sural line was transcribed onto a digitized sagittal stereo-tactic map from the Schaltenbrand and Wahren atlas. 27 The atlas map was stretched or shrunk as a function of the relative length of the patient’s intercommissural line.The tentative target was chosen at a point 1 mm abovethe most ventral portion of the GPi in a plane 20 mm fromthe midline and in the center of the GPi in the anteropos-terior plane.The patient received local anesthetic, and a single 3-mmtwist-drill hole was made in the skull anterior to the coro-nal suture approximately 2 cm from the midline corre-sponding to the parasagittal plane of the intended series of electrode trajectories. The dura was penetrated with asharp probe and the microelectrode guide tube, with anouter diameter of 1.1 mm, was stereotactically placed intothe cerebrum so that the tip was 1.5 to 2.0 cm from theintended target location. A sterile microelectrode in a pro-tective carrier tube was inserted into the guide tube so thatthe tip of the microelectrode was flush with the tip of thestereotactically placed guide tube. The microelectrodewas fastened to the hydraulic microdrive that was carriedon the arc car adaptor (or guide tube adaptor) of thestereotactic frame so that the tip could be advanced up toand beyond the intended target while recording neuronalactivity. The initial target was approached in a parasagittalplane at an angle of 47˚ to 81˚ from the horizontal axis of the stereotactic frame (approximately 50˚–60˚ from theAC–PC line). Usually three to six electrode trajectorieswere explored in each patient.  Microelectrodes and Signal Amplification Electrodes were constructed using commercially avail-able parylene-C–coated microelectrodes. The insulationof the parylene-C–coated electrodes is deposited by a“sputter” technique from a vapor phase, and the tips areexposed with a high-voltage arc pulse, techniques not per-formed in our laboratory. 21 The length of exposed tipranged from 15 to 40  m and initial impedance from 1 to2 Mohm. The shank of the electrode was stripped of insu-lation, crimped, and inserted into long thin 25-gauge stain-less steel tubing insulated with a covering of 23-gaugepolyimide tubing (Micro ML; Niemand Industries, NewYork, NY). Under microscopic control, the insulating tubewas slid down toward the electrode to overlap and coverthe insulated shank of the electrode, and epoxy resin gluewas used to join the two insulators to make a contiguousseal. The impedance of electrodes was monitored beforeand after electrolytic plating of the exposed tip with goldand platinum black, 23 which increases the microscopicsurface area and results in a drop in impedance measure-ment to one-fifth to 1/20 the srcinal measurements (fromapproximately 1 Mohm to  0.2 Mohm). The plating atthe electrode tip attracts free chloride ions when it comesinto contact with saline to form a nonpolarizable Pt–PtCl 2  junction. This reduces the impedance at the electrode tipsurface and decreases electrical noise at low frequencies.The patency of the insulation at the junction of the elec-trode shaft and polyimide tubing was tested by: immer-sion of the junction in 0.9% saline and observation of animpedance reading identical to that obtained with only thetip immersed; and/or application of a low DC voltage (5V) to the electrode and observation of bubble formationonly at the tip. 15 Completed electrodes were inserted into labeled protec-tive carrier tubes and placed in a perforated container forgas sterilization, along with leads for their attachment tothe preamplifier. The electrode leads were shielded co-axial cable that was kept to the shortest length possible(approximately 10 cm) to reduce noise from stray capaci-tance. The hydraulic microdrive was sterilized by immer-sion in a 2% glutaraldehyde solution for at least 20 min-utes, followed by a rinse in sterile water. In addition, alarger tipped electrode was constructed by insulating the25-gauge stainless steel tubing to within 1.5 mm of the tipwith polyimide tubing and beveling and polishing the tipto remove any sharp edges. This could be used for mac-rostimulation and for microinjection of lidocaine into theGP, as has been previously described for the thalamus. 7 A preamplifier (model DAM 80; World Precision In-struments, Sarasota, FL) was used with the gold-platedheadstage mounted on the arc car adaptor along with thehydraulic drive attached to the microelectrode assembly.Signals from the preamplifier were amplified and elec-trically isolated (brush model 11414310; Gould Inc.,Valleyview, OH), filtered (model 3700; Krohn-Hite,Avon, MA), and led to oscilloscopes, a window discrimi-nator (Winston Electronics, Millbrae, CA), and an audiomonitor (Grass AM 8; Grass Instruments, Quincy, MA).The window discriminator used in the operating room hastwo variable voltage levels that can be set so that spikes of an intermediate voltage amplitude will trigger a logicpulse that is used to count and display firing frequencies.To better identify single-unit neuronal responses to activeor passive somatic movements, this pulse was monitoredon the audio amplifier. The audio monitor has a noise clip-ping circuit to remove the low-amplitude portion of thespike signal so that the various spike signals can be aural-ly discriminated without interference from background“hiss.” A digital recording device (VR-100-B; InstrutechCorp, Great Neck, NY) was combined with a high-fideli-ty video cassette recorder for storage of up to eight chan-nels of data (microelectrode recording, 4 electromyo-graphic (EMG) signals, accelerometer output, slow-wave)on individual video tapes. Another high-fidelity video cas-  J. Neurosurg. / Volume 84 / February, 1996 Microelectrode method for pallidotomy 195  sette recorder was used to film the patient’s movementssimultaneously with the neuronal data (recorded on one of the two audio channels).  Microstimulation and Photic Stimulation Electrical stimulation through the electrode tip was per-formed using a stimulus generator with a constant-currentstimulus isolation unit (models A310 and A360; WorldPrecision Instruments). A separate lead was manuallyclipped to the top of the electrode’s stainless steel shank.Stimulation was usually a 1-second train consisting of 0.2-msec negative-going monopolar pulses at 300 Hz. A. Lozano, et al . 196  J. Neurosurg. / Volume 84 / February, 1996  F IG . 1.A reconstruction of a microelectrode trajectory that traversed external globus pallidus (GPe), internal globuspallidus (GPi), and optic tract (OT).A: The trajectory through the pallidum is demonstrated on the sagittal brain map(from Schaltenbrand and Wahren atlas 27 ) 20 mm lateral to midline. The trajectory has been adjusted to approximate thephysiological data as shown in B; however, note that the physiological data still do not completely match the 20-mm lat-eral map.B: Reconstruction of the trajectory in A is shown with results of microelectrode recordings and stimulation.Thick lines represent the cellular areas and thin lines represent the acellular (quiet) regions. Receptive fields (RFs) areshown to the left of the line along with the depth of the recordings along the trajectory. Receptive fields are shown onfigurines. The joints around which movement elicited modulation of cellular activity are circled  . Projected fields (PFs),or the effects of microstimulation, are shown to the right of the line along with the current used. Stimulation was per-formed only at the bottom of the trajectory to help identify the OT (Vi = visual sensations). This example is somewhatunusual in that the patient did not have visual sensations with microstimulation at the depths at which recordings sug-gested the OT was present.C: Examples of typical cells recorded along this trajectory at each level of pallidum. Onesecond of recording is shown for all except the OT recording that shows 0.1 second. For the OT, a single-pass recordingis shown above the multisweep potential response to strobe light stimulation. The evoked potential is shown in the stan-dard format of negative upward used for visual evoked potentials (VEPs). The stimulus artifact is the large vertical deflec-tion at the beginning of the single-pass sweep. When this single-pass recording is amplified into an audible signal, theincrease in baseline noise occurring at the 40-msec deflection of the VEPs can easily be heard. Note that the gain hasbeen reduced in the lower GPe trace. AC = anterior commissure; PC = posterior commissure.  We recorded the axonal activity in the optic tractevoked by repetitive flashes of a strobe light with theroom darkened. Photic stimulation was performed with astrobe light (Grass Instruments) normally at 1 Hz repeti-tion. The filter was set for a wide-frequency bandpassfrom 0.1 Hz to 10 kHz, and signal averaging was per-formed with a digital oscilloscope (model DS6411-40MHz; Iwatsu, Japan) with at least 16 sweeps per average.Offline analog filtering was performed with a low-fre-quency bandpass filter set at 0.2 Hz to 100 Hz and a gainof 20 dB and digitized at a rate of 200 Hz. Sampled laten-cies of biphasic peaks were calculated with a field poten-tial computer program (see bottom trace in Fig. 1). Testing for Movement-Related Activity of Pallidal Neurons Single units were tested for responses to active and pas-sive movements about various joints. Stable units weretested with a comprehensive battery of passive and activemovements of digits, wrist, elbow, shoulder, ankle, knee,and hip both ipsi- and contralateral to the operative side.In addition voluntary orofacial movements were request-ed: jaw opening and closing, tongue protrusion, and ocu-lar movements. In cases of neurons with rhythmic dis-charges, irregular repetitions of the passive movementswere tested to better distinguish movement-related ac-tivity. For research purposes, surface EMG activity wasrecorded from contralateral wrist flexors and wrist exten-sor muscles, ipsilateral wrist flexors as well as foot dorsi-flexors (tibialis anterior). An EMG signal conditioner(model 2004-F; Intronix Technologies, Concord, Canada)was used to amplify and filter EMG signals using a low-pass filter (1 Hz–500 Hz) to avoid signal aliases duringsubsequent off-line digitization. An accelerometer (EntranDevices, Fairfield, NJ) was attached to the patient’s dorsalindex finger (or sometimes under the chin to monitor jawmovements), and the output was amplified and recordedon tape for off-line analysis. Typical Findings and Strategy In most cases, penetrations passed successively throughthe external GP (GPe), the external and internal segmentsof the GPi, and the optic tract. Anteriorly, the external andinternal segments of the GPi are separated by a lamina of white matter (approximately 1 mm wide from the stereo-tactic atlas), which can often be recognized as an area of diminished neuronal activity (Fig. 1B). Border cells werefrequently recorded in the vicinity of this lamina. Theseregions could be identified on the basis of their differingneuronal characteristics as described below. In general thetypes of cells encountered in human pallidum are similarto those described in nonhuman primates. 4,8,9  External Globus Pallidus. Two distinct patterns of spon-taneous ongoing activity were usually observed. Someunits had a slow-frequency discharge (10 Hz–20 Hz)punctuated by rapid bursts (Fig. 1C, GPe top trace). Otherunits discharged with an irregular pattern at a higher fre-quency (30 Hz–60 Hz) also with intervening brief pauses(Fig. 1C, GPe lower trace ). However, we occasionallyfound neurons with high irregular firing rates localizedto this region as well. Many of the GPe units fired inresponse to repetitive movements. Some units showed aninhibition of the baseline rate of discharge (see Fig. 2 upper  ), whereas the majority showed an increase in thedischarge frequency with passive or active contralateralmovements.  Internal Globus Pallidus. In patients with Parkinson’sdisease, neurons in the internal segment of GPi generallyhad a baseline rate of firing that was higher than thatfound in GPe (82  32 Hz vs. 60  36 Hz, mean  stan-dard deviation). 17 The range of discharge rates in GPi as awhole was 20 to 200 Hz with few of the brief pause peri-ods described above for neurons in GPe. Typical GPi unitsare shown in Fig. 1C. Some GPi units responded to move-ments, and the majority of units responded exclusively tocontralateral movements, although some units could beactivated by movements of both right and left limbs, witha preference to either voluntary or passive movements.The most common finding with movement was an in-crease in the discharge rate of the GPi neuron, as illustrat-ed in Fig. 2 lower  . In addition some of the units fired insynchrony with tremor (Fig. 3). Microstimulation in the  J. Neurosurg. / Volume 84 / February, 1996 Microelectrode method for pallidotomy 197 F IG . 2.Neurons in the globus pallidus (GP) respond to limbmovements. Upper: The firing rate histogram illustrates themodulation of activity of a neuron in the external GP (GPe) to wristflexion and extension.  Lower: Histogram of discharge rate of asingle unit in the internal GP (GPi) showing responses to wristextension and flexion. In each case the upper two traces show elec-tromyographic (EMG) activity of the wrist flexors and extensors.Bin widths are 100 msec.  GPi rarely evoked sensations or motor effects, but tremorreduction from microstimulation in GPi has been ob-served in some patients.  Border Cells. Border cells in nonhuman primates havebeen found at the borders of the internal and external pal-lidal segments 4,8,10 and are thought to have neurophysio-logical properties similar to cells of the substantia innom-inata found at the ventral border of the GP. 4 Recent reportsfrom several groups have confirmed the existence of bor-der cells in comparable locations in human pallidum. 17,28 In 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine–treatedmonkeys showing Parkinson-like symptoms, border cellstake on a slightly more irregular firing pattern than isfound in untreated control animals. 8,9 In humans withParkinson’s disease, border cells (Fig. 1C) are distinguish-able from GP units by their regular firing pattern of 30 to40 Hz. In contrast to neurons in the GPi and GPe, no bor-der cells have been found to respond to repetitive limbmovements. Optic Tract. It is very important to identify the optictract to localize the target and avoid possible visual com-plications of lesion making. It is usually quite apparentwhen the electrode emerges from the ventral and posteri-or border of the GP, because no further cellular activity isdetected and the background noise in recordings dimin-ishes. Action potentials arising from axons in the optictract or capsule are not usually recorded by the electrodeused; however, in some cases axonal spikes can be detect-ed. Axons were tentatively identified by narrow (  0.5msec) monophasic spikes that were transiently recordedby the electrode tip. We have found that the most reliableway of detecting whether the electrode tip is in or near theoptic tract is to use microstimulation. Stimulation in theoptic tract should evoke visual sensations at currents of less than 20  A, and thresholds can be as low as 2  A.Patients report seeing lights or “stars” of various colors(most often blue, yellow, or white) or scotomata (clouds)in the contralateral visual field, and increasing the stimu-lation current produces a larger and brighter visual sensa-tion. Some patients detect the stimulation-evoked visualsensations more readily if the ambient lighting is dimmed.With increasing distance away from the optic tract, thestimulation threshold increases. We do not use currentsabove 100  A. The mean distance between the most ven-tral GPi unit and the visual responses evoked by stimula-tion of the optic tract was 1.6 mm  0.9 mm (23 cases).For further confirmation of the location of the optictract, we recorded strobe-evoked optic tract potentialsfrom the appropriate portion of the trajectory. In mostcases, optic tract potentials (see lower portion of Fig. 1C)could be obtained over the region corresponding to thelowest threshold for microstimulation-evoked visual re-ports. However this was not seen in all cases, and occa-sionally optic tract potentials were recorded where thepatient did not report visual sensation from microstimu-lation.  Internal Capsule. The internal capsule lying medial andposterior to the GP is identified by the relative absence of somatodendritic action potentials and the occasionalrecording of axonal spikes. Stimulation in the capsule usu-ally resulted in tetanic contractions due to activation of corticospinal tract fibers and/or sensations of paresthesia(pulling, tugging, or tingling sensation). In eight of 23cases sensorimotor responses (internal capsule) werefound in tracks posterior to the GPi approximately 3 to 6mm posterior to the evoked visual responses (optic tract).  Lesion Making We did not perform lesioning until the ventral and pos-terior borders of the GPi were identified by recording andstimulation findings characteristic of the optic tract andinternal capsule. Lesions, made in areas containing neu- A. Lozano, et al . 198  J. Neurosurg. / Volume 84 / February, 1996  F IG . 3.An example of the firing of a “tremor-cell” in the internal globus pallidus (GPi). Note that the discharge rate (lower trace) is responding to rest tremor in the arm.
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