Deep Brain Stimulation for Movement Disorders

Basal Ganglia as a Surgical Target in Movement Disorders

Pathology within the basal ganglia was noted in patients with Parkinson disease (PD) and chorea in the latter half of the 19th century. Animal experimentation and clinical observations suggested a role for the basal ganglia in the physiology of movement. Several pioneers noted the potential of strategically placed basal ganglia lesions in the management of movement disorders. Irving Cooper abandoned a cerebral pedunculotomy in a patient with PD when accidental damage forced him to ligate the anterior choroidal artery. The patient's tremor was abolished without concomitant neurologic deficit, and this improvement was attributed to vascular damage of the globus pallidus and ansa lenticularis. Surgeons began to explore minimally invasive approaches with probes placed deep within the brain parenchyma via a burr hole under local anesthetic, initially guided solely by plain radiography and intuition for anatomic localization. Reversible lesions with local anesthetic or mild thermal manipulation allowed the effect of the intervention to be assessed before permanent ablation. Despite functional improvements in individual patients, ambiguity over anatomic location of the lesion interfered with the replication of clinical results.

Stereotactic Technique

Precise neurosurgical targeting relies on the stereotactic technique, the principles of which were established by Clarke and Horsley who first reported their findings in 1906. The term stereotactic , literally “three-dimensional touch,” conveys the philosophy behind this powerful navigational technique. In essence, it provides accurate localization of an intracranial target by ascertaining its triplanar coordinates with reference to fixed landmarks, and it affords surgical access to targets deep within the brain in a minimally invasive fashion.

Inability to visualize the desired intracranial target led to the development of stereotactic atlases depicting the spatial relations of neural anatomy with respect to landmarks that could be localized. Spiegel (a neurologist) and Wycis (a neurosurgeon) combined stereotactic principles with ventriculography to introduce the stereotactic technique to surgical practice in 1947 and described its use in the treatment of psychiatric conditions, pain, and involuntary movements. Frame-based stereotactic surgery involves the application of a frame providing fixed external reference points (fiducials) to the skull that can be localized with reference to intracranial coordinates. The coordinates of intracerebral structures are acquired by imaging the patient's brain with the frame in situ. The anterior and posterior commissures (ACs, PCs) could be readily visualized on ventriculography and were in close proximity to the target structures of interest, making them the most popular intracranial landmarks.

Stereotactic atlases were developed that provided a guide to anatomic localization. Once the ACs, PCs, and midcommissural points are defined in space, standard stereotactic coordinates or ratios derived from stereotactic atlases provide the surgeon with an estimated location of the target structure. However, this approach does not eliminate the problem of anatomic variability. Indeed, anatomic variability results in diverse coordinates being quoted for the same structures. Commonly employed coordinates from the midcommissural point for initial indirect localization of oft-employed surgical targets are presented in Table 57.1 . The AC-PC line still plays a central role in modern functional neurosurgical practice ( Fig. 57.1 ).

In the 1950s and 1960s, the combination of the stereotactic technique, stereotactic atlases, and ventriculography allowed safe targeting of deep-seated structures and the discipline of functional neurosurgery flourished. Tens of thousands of patients with psychiatric and neurologic indications underwent functional neurosurgical operations in the years that followed.

Refinement of Initial Surgical Targeting

The indirect nature of anatomic localization and the “exploratory” nature of surgery on clinical symptoms, combined with the finality of creating a brain lesion, dictated an additional process of intraoperative refinement. As a result, functional neurosurgical interventions were traditionally performed under local anesthesia. This allowed surgeons to assess the clinical effects of the surgical intervention in real time, in terms of both the positive effect on symptoms and the possible undesirable side effects. Diverse methods may be used to produce “reversible” lesions of the target area to assess the clinical effects, including thermal manipulation, injection of local anesthetic, and high frequency electrical stimulation. Intraoperative observations included the measurement of electrical impedance and recording of neural activity via macroelectrodes. This process often involves numerous tracks being made through the brain to the target region, especially when recording neural activity, a process referred to as brain mapping. Surgeons traditionally used a combination of these observations to guide them to the anatomic placement of the surgical intervention. Semimicroelectrode recording was first introduced to functional neurosurgery by a collaboration between French neurophysiologist Denise Albe-Fessard and neurosurgeon Gerard Guiot in 1961. The pattern of neural activity at the tip of the advancing microelectrode provides a surrogate marker of electrode location. Many functional neurosurgeons still employ similar techniques to “refine” anatomic targeting in routine clinical practice.

Surgical Intervention

In the early decades of functional neurosurgery, lesions were by far the most common interventions performed on the brain. Reversible lesions with local anesthetic, mild thermal manipulation, or high-frequency electrical current allow the effect of the intervention to be assessed in awake patients before permanent ablation. Lesions were made by diverse methods including alcohol injection, cryosurgery, and, most commonly, radiofrequency ablation.

Lesions were placed in a variety of basal ganglia targets for numerous indications. The pallidum and its outflow fibers were early targets for lesional surgery in the management of movement disorders. The thalamus gained increasing popularity as a basal ganglia target during this first wave of functional neurosurgery such that the number of publications on thalamotomy vastly outnumbered those on pallidotomy by the late 1960s and throughout the 1980s.

Intraoperative electrical stimulation was used from the very first stereotactic functional procedure as a mean of exploring the brain target prior to lesioning. Although often considered a modern technique, numerous authors in the 1950s and 1960s reported early forays into chronic electrical stimulation of the brain.

Demise and Resurgence of Functional Neurosurgery

Functional surgery for motor disorders had become well established by the mid-1960s, but the number of procedures performed plummeted after the introduction of l -dopa for the treatment of PD in the late 1960s.

During the last few decades of the 20th century it became increasingly clear that, although medication had a dramatic beneficial effect in many patients, there were others whose symptoms were refractory to medication or in whom significant side effects developed. In patients with PD, tremor could be particularly difficult to control, and dyskinesias appeared as a side effect of medication. Laitinen's seminal paper in 1992 revisiting Leksell's posteroventral radiofrequency pallidotomy was an important factor in the resurgence of neurosurgery for movement disorders. Radiofrequency thermal lesions remain an excellent surgical technique offering an inexpensive and effective means of controlling symptoms of various movement disorders at numerous brain targets.

Subthalamic Nucleus in Functional Neurosurgery

Primate studies in the 1980s provided substantial evidence for the role of the subthalamic nucleus in the pathology of parkinsonian symptoms. Subthalamic nucleus lesions in primate models of PD suggested that parkinsonian symptoms could be reversed. However, there were concerns of inducing permanent ballistic movements when lesioning the subthalamic nucleus as well as the added risk of bilateral lesional procedures. It was then demonstrated that high-frequency subthalamic nucleus deep brain stimulation (STN DBS) in primate models of PD improved motor control without inducing hemiballismus. This led the pioneering Grenoble group to proceed with bilateral subthalamic nucleus DBS in humans. The positive results were widely replicated in numerous centers and eventually confirmed in several randomized controlled trials. Together with its potential to reduce the dose of dopaminergic medication in patients, STN DBS superseded posteroventral pallidotomy, the preferred surgical procedure for Parkinson disease in the 1990s.

Dominance of Deep Brain Stimulation

DBS has a number of advantages over lesional surgery in movement disorder surgery: the ability to perform simultaneous bilateral procedures with a lower risk of axial complications, its early reversibility, and the fact that DBS is socially more acceptable than stereotactic ablation. In addition, DBS provides a unique opportunity to conduct scientific studies on brain function. Despite the drawbacks of high cost, a potential for hardware-related complications, and the requirement of programming expertise, DBS has virtually replaced lesions in contemporary neurosurgical practice.

Role of Imaging in Functional Neurosurgery

Leksell, with characteristic insight, recognized the fundamental importance of MRI in the practice of functional neurosurgery:

In clinical practice, brain imaging can now be divided in two parts: the diagnostic neuroradiology and the preoperative stereotactic localization procedure. The latter is part of the therapeutic procedure. It is the surgeon's responsibility and should be closely integrated with the operation.

Advances in imaging mean that most anatomic targets relevant to functional neurosurgery can be visualized and localized on stereotactic MR images in individual patients. The ability to visualize the anatomic structure being targeted raises the possibility of acquiring the target on the first pass through the brain in the majority of cases, further reducing the morbidity and mortality of the procedure. Stereotactic MRI also provides a means of accurately assessing the anatomic location of the intervention after the procedure, in vivo. Furthermore, stereotactic MRI permits verification of lead location and directs lead relocation when necessary. Such an approach removes reliance on other surrogate markers and allows the DBS procedures to be performed under general anaesthesia. A meticulous approach to MRI-guided and MRI-verified DBS surgery is beyond the scope of this chapter. However, it is a technique that is gaining popularity due to benefits in surgical time, comfort, cost, and safety.

Overview

Motor control depends on the integrated function of virtually all of the major divisions of the central nervous system ( Fig. 57.2 ). Cortical centers include the premotor cortex, supplementary motor area, and primary motor area that are implicated in the genesis, preparation, and execution of motor commands. The cerebellum is implicated in learning and coordination of motor tasks. Processing of sensorimotor information occurs at spinal and brainstem levels as well as in cortical-basal ganglia-thalamic-cortical loops and cerebellar-cortical-subcortical pathways.

Descending motor pathways from cortical and brainstem areas allow interaction with spinal cord motor systems. The “final common pathway” is the motor unit comprising motor neuron and innervated muscle fibers. Input from sensory mechanisms at every level is of paramount importance in regulating these motor systems.