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Neurophysiological monitoring during neurosurgery for movement disorders


34.1

Introduction

The full potential of intraoperative neurophysiology is realized during the performance of so-called functional neurosurgical procedures. During these interventions, therapeutic lesions or stimulating electrodes are stereotactically placed within deep brain structures to treat movement disorders, such as Parkinson’s disease (PD), essential tremor (ET) and dystonia, mood and affective disorders, or chronic neuropathic pain.

The deep location of these structures precludes direct surgical approaches. Instead, surgeons rely on a combination of image-guided stereotactic techniques and intraoperative neurophysiology to place the therapeutic lesions or stimulating electrodes with acceptable accuracy and safety. Although imaging techniques, including the increased use of fiber tractography and quantitative susceptibility mapping (QSM) sequences, have enhanced direct visualization of the desired deep nuclei , the target remains physiological. Because these are physiologic as much as anatomic targets (ATs), image-based targeting may incompletely identify the desired location. Consequently, intraoperative recording and stimulation techniques have been developed to aid during target localization. These techniques complement anatomical targeting by providing real-time electrophysiological data concerning the probe position and the surgical target. The surgeon and physiologist use this data to “fine-tune” their anatomic targeting before completing the therapeutic intervention. Thus employed, intraoperative neurophysiology does not simply monitor surgical activity, it guides it.

In this chapter, we provide historical overview of intraoperative monitoring for movement disorder surgery and a detailed account of our approach to these surgeries, which has evolved over the course of more than 200 interventions.

34.2

History and theory

34.2.1

Historical notes

34.2.1.1

Surgery for movement disorders

Sir Victor Horsley is reported to have performed the first neurosurgical procedure for a movement disorder when, in the late 1800s, he resected part of the precentral gyrus in a patient with athetoid movements. The surgery halted the abnormal movements but caused dyspraxia and paralysis of the limb . The first successful basal ganglia surgery is credited to Meyers who reported improvement in a patient with postencephalitic parkinsonism in 1939. Prior to this landmark report, surgery within the basal ganglia was avoided, as it was believed that human consciousness resided in these structures. Despite the high mortality rates (10%–12%), which plagued these “open” procedures (i.e., via craniotomy) , Meyers demonstrated the potential benefits of basal ganglia surgery and opened the door for the application of less invasive stereotactic approaches to these deep brain structures. Meyers also provided the first accounts of human basal ganglia physiology, describing the frequency, phase, and amplitude of neuronal signals from the striatum, pallidum, corpus callosum, internal capsule, subcallosal bundle, and dorsal thalamus in patients with and without movement disorders . Meyers quickly realized the potential value of the accumulated data, which he ultimately employed to help localize specific deep brain structures during movement disorder surgery.

Robert Clarke designed the first stereotactic frame in 1908 . His frame employed skull landmarks to target deep brain structures in small animals, a technique that could not be translated to clinical use due to the more varied and complex shape of the human skull and brain. Consequently, it was not until 1947, after the introduction of ventriculography, that Spiegel et al. performed the first human stereotactic surgeries, for psychiatric illness and Huntington’s chorea . In the following years a number of human stereotactic atlases were published, and standard meridia (e.g., the intercommissural line) from which stereotactic coordinates could be determined were established.

Effective targets for stereotactically guided neuroablation were discovered empirically. For example, Cooper stumbled upon the beneficial effects of globus pallidus (GPi) lesioning by accidentally ligating the anterior choroidal artery of a PD patient while performing a pedunculotomy. He later adopted stereotactic approaches to pallidal lesioning, reporting favorable results and reduced surgical mortality rates (~3%) as compared to open procedures . Leksell further improved the results of pallidotomy by placing the lesion more posteriorly and ventrally within the internal segment of the GPi, that portion of the nucleus that we now know is responsible for sensorimotor processing . In 1963 Spiegel et al. described campotomy, in which the fibers of the pallidofugal, rubrothalamic, corticofugal, and hypothalamofugal pathways are interrupted within the H fields of Forel. They reported promising results in 25 patients with tremor and 25 with rigidity. In the end, however, thalamotomy emerged as the most commonly performed movement disorder procedure in the pre-levodopa ( l -DOPA) era due to the consistent tremor control it provided. Though most surgeries for PD ceased after the introduction of l -DOPA in 1967, small numbers of thalamotomies were performed for medically refractory tremor during the next 25 years, until the reintroduction of Leksell’s pallidotomy by Laitinen et al. in 1992 .

34.2.2

Neurophysiology and movement disorder surgery

Most early electrophysiologic studies of the human thalamus and basal ganglia were performed with macroelectrode techniques that yielded relatively crude, electroencephalogram (EEG)-like responses . Electrodes and recording techniques were refined over subsequent decades, culminating in the development of single-cell microelectrode recording (MER). Of note is the work of Albe-Fessard, who refined microelectrode techniques for experimental purposes and paved the way for their intraoperative use . It was her belief that MER would “ …provide a powerful tool in improving stereotactic localization and that it would furthermore reduce the risk due to anatomical variability ” . In recent years, Madame Albe-Fessard’s vision has been realized as MER has gained popularity and ready-to-use recording systems are commercially available.

The history of electrical brain stimulation begins with Fritsch and Hitzig, who in 1870 elicited limb movement in dogs by stimulating the frontal cortex and then defined the limits of the motor area electrophysiologically. Intraoperative cortical stimulation studies by Penfield et al. from the late 1920s through the late 1940s contributed seminal information concerning the somatotopical organization of the cerebral cortex by defining the motor and sensory “homunculi.” In 1950, Spiegel et al. described the use of stimulation during surgery at the H fields of Forel to both “ …test the position of the electrode and to avoid proximity to the corticospinal pathways ventrally, the sensory thalamic-relay nuclei dorsally, and the third nucleus posteriorly” .

Other neurophysiological techniques, such as impedance monitoring , evoked potential recordings also have been employed as localization tools; however, these techniques serve predominantly as adjuncts to recording and stimulation.

Oscillatory activity within the basal ganglia has been shown to be unique in various disease states such as PD . Recently, the use of local field potentials (LFP) has been utilized for target confirmation and deep brain stimulation (DBS) parameter programming optimization following surgery . Furthermore, analysis of specific frequency bands, such as beta (13–35 Hz) and gamma (35–100 Hz), have been shown to potentially represent disease-specific phenotypic markers that are being exploited for the use in closed-loop stimulation systems . Perhaps the most significant advancement in functional neurosurgery in the last three decades has been the introduction of chronic electrical stimulation (termed DBS) as a therapeutic alternative to neuroablation. DBS provides three potential advantages when compared to neuroablation:

  • 1.

    DBS is reversible. If stimulation induces an unwanted side effect, one simply turns the stimulator off or adjusts parameters. Thus the risk of permanent adverse neurological events is reduced.

  • 2.

    Stimulation parameters may be customized to each patient, potentially enhancing therapeutic efficacy.

  • 3.

    Access to the surgical target is maintained via the implanted electrode and programmable pulse generator. Therefore therapy may be modified over time through simple stimulation adjustments, potentially increasing the longevity of response.

The superiority of DBS to best medical treatment has been studied in randomized controlled trials along with long-term data on its safety profile . For all of these reasons, DBS has become the “go to” surgical procedure for refractory movement disorders.

Presently, movement disorder surgery is focused on three structures: the ventrolateral (VL) nucleus of the thalamus, the GPi pars internus, and the subthalamic nucleus (STN) ( Fig. 34.1 ). Each of these structures can be targeted for ablative lesioning, procedures that are respectively termed thalamotomy , pallidotomy , and subthalamotomy . In contemporary practice, these targets are commonly used for chronic stimulation by DBS . The choice of target is based largely on clinical diagnosis and the symptoms to be treated.

Figure 34.1, A three-dimensional, artist’s rendition of the structures involved in the surgery for movement disorders. The light greenish blue structure on the left is the globus pallidus (GPi and GPe). The large gray structure on the right is the thalamus, and the small dark green structure is the STN. The medial edge of the STN is only 6.0 mm from the midline of the brain. With the trajectories that our group uses in the operating room we encounter around 10.0 mm of GPi, 11.0 mm of VIM, and 5.0 mm of STN [48] . GPe , External segment of the GPi; STN , subthalamic nucleus; VIM , ventral intermediate.

34.2.3

Theoretical basis for surgery in the basal ganglia

Our current understanding of the functional organization of the basal ganglia and PD pathophysiology is based predominantly on data derived from the study of primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism . Microelectrode techniques also have contributed greatly to this body of knowledge. Though incomplete, the current model of basal ganglia function is partly responsible for the rebirth of movement disorder surgery, providing a scientific basis for selecting those deep brain structures that are currently targeted for therapeutic interventions.

The model is depicted in Fig. 34.2 . The basal ganglia are composed of two principal input structures (the corpus striatum and STN), two output structures [GPi and substantia nigra pars reticulata (SNr)], and two intrinsic nuclei [external segment of the GPi and substantia nigra pars compacta (SNc)] . Five parallel basal ganglia-thalamocortical circuits (motor, oculomotor, two prefrontal, and limbic) have been described . While surgical interventions target the motor circuit, it is likely that lesioning and stimulation also impact other circuits.

Figure 34.2, Diagrammatic representation of the basal ganglia circuit, showing the direct and indirect pathways proposed by DeLong et al. [133 134] . The green lines represent excitatory pathways while the red lines show inhibitory pathways.

The corpus striatum, which is composed of the caudate and putamen, is the largest nuclear complex of the basal ganglia. The striatum receives excitatory (glutamatergic) input from several areas of the cerebral cortex as well as inhibitory input from the dopaminergic cells of the SNc. Cortical and nigral inputs are received via the “spiny” neurons. One subset of these cells projects directly to the GPi forming the “direct pathway,” while another subset projects to the GPe, the first relay station of a complementary “indirect pathway,” which passes through the STN before terminating at GPi. The antagonistic actions of the direct and indirect pathways regulate the neuronal activity of GPi, which, in turn, provides inhibitory input to the pedunculopontine nucleus and the VL nucleus of the thalamus. The VL nucleus projects back to the primary and supplementary motor areas , completing the cortico-ganglia-thalamocortical loop. The direct pathway inhibits GPi, resulting in a net disinhibition of the motor thalamus and facilitation of the thalamocortical projections. The indirect pathway, via its serial connections, provides excitatory input to the GPi, inhibiting the thalamocortical motor pathway. More recently, the hyperdirect pathway has been characterized as a cortico-subthalamo-pallidal that bypasses the striatum and therefore has a shorter conduction time in comparison to the above pathways that require processing through the striatum .

In PD, loss of dopaminergic input to the striatum leads to a functional reduction of direct pathway activity and a facilitation of the indirect pathway. These changes result in a net increase in GPi excitation and a concomitant hyperinhibition of the motor thalamus. The excessive inhibitory outflow from GPi reduces the thalamic output to supplementary motor areas that are critical to the normal execution of movement.

This model accounts well for the negative symptoms of PD (i.e., rigidity and bradykinesia) and supports both GPi and STN as rational targets for surgically treating PD. The model is incomplete, however, as it does not fully account for hyperkinetic features of PD such as tremor and l -DOPA-induced dyskinesias (LID), physiological phenomena that are poorly understood.

Tremor activity is consistently detected in the VL nucleus of patients with parkinsonian or ET, and VL continues to be the primary surgical target for treating medically refractory tremor. However, it is unclear if the motor thalamus is the primary generator of tremor activity or merely participates in the transmission of tremor-generating signals. Moreover, the evidence that both pallidotomy and STN DBS also control parkinsonian tremor suggests that intervention at many points within the tremor generating loop may suppress this symptom.

LID are involuntary movements of the limbs or trunk that are temporally associated with l -DOPA administration . These movements are typically choreiform or dystonic in nature and are easily distinguished from the tremor of PD. Pharmacodynamic factors related to chronic exogenous dopaminergic stimulation probably play a fundamental role in l -DOPA-induced dyskinesia. According to the model, pallidotomy should worsen LID by reducing pallidal inhibition of VL, a hypothesis that is supported by the experimental observation that STN lesions, which reduce the excitatory output from STN to GPi, cause dyskinesia in primates that are indistinguishable from LID . On the contrary, LID is the most responsive symptom to pallidotomy, a consistently observed phenomenon . It has been hypothesized that the sensitization of dopamine receptors by exogenously administered l -DOPA may cause aberrant neuronal firing patterns with consequent disruption of the normal flow of information to the thalamus and the cortical motor areas . It follows that pallidotomy may improve LID by disrupting this aberrant flow.

34.2.4

Modern movement disorder surgery: general overview

There is no one best method for performing movement disorders surgery. Rather, stereotactic surgeons modify general approaches to target localization to suit their personal preferences and to take advantage of their institution’s strengths. Currently accepted technique involves frame-based or frameless anatomical localization supported by intraoperative physiological confirmation of proper targeting. An overview of the various anatomic and physiologic techniques currently in use follows.

34.2.4.1

Anatomical targeting techniques

In the pre- l -DOPA era, positive contrast and air ventriculography were employed to localize the foramen of Monro and the anterior and posterior commissures. The stereotactic coordinates of therapeutic targets were then determined based on their relationship to these structures as described in various stereotactic atlases. Targeting accuracy was therefore limited by the inaccuracies of human stereotactic atlases that were typically generated from just one or a few specimens whose true dimensions were distorted by formalin fixation and by anatomical distortions created by the intraventricular injection of air or contrast. Today, computerized tomography (CT) and magnetic resonance imaging (MRI)-based techniques, which demonstrate the brain parenchyma noninvasively, have supplanted ventriculography as the primary means of anatomically localizing stereotactic targets. Nevertheless, ventriculography is still employed by some stereotactic surgeons and therefore remains an important technique.

The introduction of CT revolutionized the diagnosis and treatment of neurologic diseases and encouraged changes in stereotactic frame design, expanding the uses of frame-based stereotaxis to include tumor biopsy and resection . Soon after the introduction of MRI, T. Herner et al. demonstrated its applicability to stereotactic systems. MRI provides superior resolution as compared to CT, as well as multiplanar images with minimal frame-related artifact . Nonreformatted MRI beautifully demonstrates the commissures, thalamus, and most basal ganglia structures . Utilization of T2-weighted and susceptibility-weighted imaging provide enhanced resolutions of STN and GPi including anatomical borders . Recently identified sequences such as QSM are likely to even further increase the signal-to-noise ratio of identifying these structures. Recently, computational neuroimaging techniques have shown excellent visualization of surrounding fiber tracks using diffusion-weighted imaging, particularly in targeting the ventral intermediate (VIM) nucleus where nearby crossing pathways are not readily visualized on standard imaging . These features permit direct stereotactic localization of the surgical target in some instances, and recent efforts at direct targeting with intraoperative imaging under general anesthesia, so-called asleep DBS, have been published with acceptable safety profiles . However, long-term efficacy of pure direct anatomical targeting is not known . The most significant drawback to targeting with MRI is the potential for image distortion introduced by nonlinearities within the magnetic field . Distortions can be generated by number of factors, including the presence of ferromagnetic objects within the field, imperfections in the scanner’s magnets, and, most commonly, patient movement . Walton et al. demonstrated that targeting errors are greater in the periphery than in the center of the magnetic field and stereotactic space . MRI distortion may also be related to the pulse sequence(s) employed. For example, it has been suggested that fast spin echo inversion recovery sequences resist imaging distortions secondary to magnetic susceptibility better than other image acquisition methods .

In contrast to MRI, CT maintains linear accuracy, thereby reducing image-induced targeting errors . However, metallic artifact can impede visualization of the commissures, and CT tissue resolution is inferior to MRI. Commercially available targeting software packages nowadays readily fuse CT and MRI images with acceptable accuracy . This is also a particularly useful tool intraoperatively as it allows for merging of intraoperative CT with preoperative MRI sequences, allowing for visualization of the microelectrode or DBS trajectory. Targeting accuracy of MRI–CT based and intraoperative CT usage is generally in the 1–2 mm range as reported in the literature . Further refinements in image sequencing and merging techniques are likely to incrementally improve the targeting accuracy; however, it is worth noting that the ultimate limit of direct targeting is a single MRI 1 mm×1 mm voxel.

34.2.4.2

Physiological targeting: recording techniques

The five historically employed techniques for physiologic localization during movement disorder surgery are (1) impedance measurements, (2) macroelectrode recordings and stimulation, (3) semi-MER (and/or stimulation), (4) MER (with or without stimulation), and (5) LFP. Evoked potentials have also been employed at times . At the present time, MER with or without stimulation testing is the standard technique used by nearly all centers that employ recording during DBS surgery.

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