Modern Concepts in Functional Stereotactic Neurosurgery

Neurosurgical interventions have been used for over a century to treat various diseases of the nervous system, primarily movement disorders. During this time, more than 8000 publications related to stereotactic surgery of extrapyramidal diseases have been released, the overwhelming majority of which concern PD. More than half of the publications are dedicated to DBS, which gradually took a dominant position among all types of functional stereotactic interventions. At the same time, traditional destructive operations on the basal ganglia have not lost their significance, with a renaissance of interest linked to the emergence of new non-invasive treatment methods such as MRgFUS.

Familiarity with this rapidly developing field of neurology and neurosurgery involves understanding the basic principles of the neural network organization of subcortical brain structures and related structures in both normal and pathological conditions.

Fundamental Principles of Functional Stereotactic Neurosurgery for Extrapyramidal Movement Disorders

The concept of stereotactic neurosurgery is based on the functional topography of the brain, which began to develop as far back as the time of Hippocrates, who described in IV century BC, motor deficit with damage to the opposite hemisphere of the brain. Later, the Roman physician Claudius Galen in the II expanded the understanding of the brain and the foundations of some movement disorders (tremor) in our era. After Galen, there was a 1000-year hiatus in the study of anatomy due to religious prohibitions on dissection of the deceased. The first information about the structure of the brain’s subcortical formations is found in the works of K.F. Burdach (1819) and I.P. Lebedeva (1873), and in the upcoming XX the century saw a rapid development of neuromorphology, complemented by the intensive advancement of brain imaging methods (computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)) and achievements in experimental neurobiology and neuropharmacology in recent years, allowing for the creation of a coherent picture of modern concepts of the structural-functional organization of the basal nuclei

The primary function of the basal ganglia is the organization of the involuntary component of motor acts, the formation and implementation of automated motor programs, including ensuring the synchronous activity of various muscle groups and regulating mechanisms for maintaining adequate muscle tone. This function is carried out in close interaction with the cerebellum. In addition to motor control, the basal ganglia also play a role in organizing cognitive activity, learning, and emotional behavior (Illarioshkin, Ivanova-Smolenskaya, 2011)

To perform such complex functions, the basal ganglia receive information from various cortical areas and, in turn, project it to the thalamus, as well as to the prefrontal, premotor, and motor cortex (Fig. 1.1). Afferentation to the striatum mainly comes from the hemispheric cortex (motor, sensory, associative, limbic) and the thalamus. Corticostriatal fibers are excitatory and use glutamatergic transmission. Their projections have a clear topographic organization: the putamen is mainly involved in general motor control, the caudate nucleus in the control of oculomotor functions and some cognitive operations, and the ventral part of the striatum is related to the organization of limbic system functions (emotional-volitional sphere). Further, the motor control pathways reach the globus pallidus and the reticular part of the substantia nigra—two main efferent structures of the basal ganglia. Fibers from the globus pallidus and the reticular part of the substantia nigra go to the thalamic nuclei—ventrolateral, ventral anterior, mediodorsal, and centromedian, after which the considered loop closes again on the prefrontal, premotor, primary, and supplementary motor cortex.

Thus, the basal ganglia have bilateral connections with both the cortical areas of the cerebral hemispheres and (through the thalamus) with sensory input structures. The projections of the basal ganglia influence descending motor pathways and, through connections with the superior colliculi, affect oculomotor functions. These numerous, well-branched connections of the basal ganglia provide them with direct involvement in the planning and execution of complex motor strategies.

In the functioning of the entire extrapyramidal system and, in particular, in the pathophysiological mechanisms of movement disorders, the subtle interaction of the direct and indirect pathways is of great importance ( Albin et al., 1989). Direct pathway (see Fig. 1.1) includes direct fiber projections from the striatum to the internal segment of the globus pallidus ( GPi) (and further to the reticular part of the substantia nigra and thalamus). The indirect pathway from the striatum leads to the external segment of the globus pallidus ( GPe) both the subthalamic nucleus, and only after that do the fibers of the indirect pathway reach GPi.

It is believed that the direct pathway ensures the execution of the current motor program, while the indirect pathway simultaneously suppresses competing motor programs (Bril et al., 2022). Based on these concepts, it is not surprising that the direct and indirect striopallidal pathways have different neurotransmitter organizations. The direct pathway uses inhibitory mediators – g-gamma-aminobutyric acid (GABA) and substance P, therefore cortical stimulation of the striatum leads to the suppression of activity in the globus pallidus and the reticular part of the substantia nigra. Since these last two structures have an inhibitory effect on the thalamus, ultimately this action is accompanied by the release of the thalamus from tonic inhibition and the execution of a motor act. In turn, thalamocortical activation induces the premotor and supplementary motor areas, projecting impulses to the motor cortex, brainstem, and spinal cord. The indirect pathway has the opposite effect and reduces the activation of cortical motor neurons. The hyperdirect cortico-subthalamic pathway plays a significant role in the dynamic organization of the functions of the basal ganglia, providing the possibility of direct modulating influences of the cortex on any voluntary movements Nambu et al., 2023). Additional effects within these functional “circuits” are exerted by dopaminergic projections of the compact part of the substantia nigra: they facilitate movements by exciting the direct and inhibiting the indirect pathway ( Albin et al., 1989). From the above, it is evident that the thalamus plays a key role as a synaptic relay for afferent and efferent flows in the subcortical structures of the brain. Thalamic nuclei relay motor signals generated in the cerebellar pathways and basal ganglia directly to the motor areas of the frontal cortex. Moreover, the thalamus is also involved in maintaining wakefulness and central regulation of autonomic functions. Thalamic nuclei can be divided into relay and projection nuclei.

There are 6 groups of thalamic nuclei (Fig. 1.2)

1. Lateral nuclei (their ventral and dorsal parts) are relay nuclei, receiving a limited number of afferents and projecting to specific sensory, motor, and associative cortical areas. They include: the ventral anterior and ventrolateral nuclei involved in motor control; the ventral posterior nucleus, important for somatosensory functions; the medial and lateral geniculate nuclei, mediating auditory and visual afferentation, respectively; the lateral dorsal and lateral posterior nuclei (function unclear); the pulvinar nucleus—the largest in the thalamus, responsible for integrating diverse sensory information.
2. Medial nuclei (the most studied being the mediodorsal) are relay nuclei, also related to motor control.
3. Anterior nuclei – relay, involved in emotion control
4. Intralaminar nuclei are projection nuclei. The largest of them is the centromedian nucleus, projecting to the frontal cortex and the striatum.
5. Midline nuclei – projection, located in the dorsal part of the wall III ventricle
6. Reticular nucleus – located in the lateral part of the thalamus. It is intensely interconnected with specific relay nuclei and is the only thalamic nucleus with an inhibitory function that does not project to the cerebral cortex.   

All the mentioned structures have close bilateral connections with the most important part of the CNS involved in the organization of movements—the cerebellum. Special attention should be given to the dentate-thalamo-cortical and dentate-rubro-olivary-cerebellar projections, which form the characteristic closed internal “loops” of cerebellar connections. The pathways that are part of the superior cerebellar peduncle, central tegmental tract, and inferior cerebellar peduncle form the so-called Guillain-Mollaret triangle, which is considered key in the genesis of certain types of tremor (ET, Holmes tremor, etc.) Berendse, van Laar, 2007).

Thus, the implementation of motor functions is carried out within the activity of somatotopically organized thalamocortical circuits, including

a) cortical efferents to the striatum, globus pallidus (through direct, indirect, and hyperdirect pathways, affecting differently on GPi), to the subthalamic nucleus and thalamus;
b) afferent thalamocortical projections;
c) cerebellar efferent flows relayed by the thalamus to the motor cortex

In turn, activity GPi and the subthalamic nucleus is controlled by the nigrostriatal dopaminergic pathway. As a result, a clear coordination of various components of a single motor “ensemble” is established, carrying out reciprocal balanced interactions involving the main CNS mediators (GABA, dopamine, acetylcholine, glutamate). The main converging structures within the overall neurocybernetic organization of the cortico-subcortical motor loop are the thalamus (primarily its lateral nuclei) and GPi, as well as the subthalamic nucleus located ventrally between them and zona incerta (ZI) (fig. 1.3)

The essence of stereotactic surgery for movement disorders lies in the targeted impact on key relay structures of the brain that modulate the activity of the extrapyramidal system and facilitate the convergence of its connections with various levels of the CNS (Kandel, 1981)

From a pathophysiological perspective, in parkinsonism and other movement disorders, there is an imbalanced activity in the motor pathways, a kind of “brain arrhythmia,” which can be mitigated by the destruction of these relay structures or by inducing the work of their neurons in a specified rhythm through direct electrical stimulation (Illarioshkin, Ivanova-Smolenskaya, 2011 Tarsy et al., 2008). The most significant targets for such interventions aimed at treating tremor and other extrapyramidal movement disorders are the ventral intermediate nucleus of the thalamus ( VIM) (it modulates any rhythmic hypersynchronous discharges in the motor pathways of the CNS passing through the thalamus, regardless of their primary genesis), other motor nuclei of the thalamus, posterior ventral sections GPi, subthalamic nucleus ZI, dentate nucleus and other structures, as well as their connections (Illarioshkin, Ivanova-Smolenskaya, 2011; Lyons, Pahwa, 2005). It is also assumed that the destruction or electrical stimulation of certain structures disrupts the oscillators formed in the brain (groups of “pacemaker” neurons) that generate tremor (Illarioshkin, Ivanova-Smolenskaya, 2011). Recently, it was discovered that targeting the subthalamic nucleus during stereotactic interventions blocks signal transmission through it and restores cortically-induced inhibition GPi via the direct path (see Fig. 1.1), which ensures you crelease of planned movement by disinhibition of thalamocortical activity ( Nambu et al., 2023).

History of Stereotaxis

The name of the stereotactic method (abbreviated as stereotaxis) comes from the Greek words stereos – «volumetric, spatial» and taxis – «movement” (collectively – moving in space). The method is a combination of techniques and manipulations that allow, with the help of special devices, to precisely target a predetermined brain structure for therapeutic purposes. Currently, such an effect can be achieved using an electrode (radiofrequency thermodestruction DBS), Cannulas for cryoablation or chemical ablation, gamma knife (radiation ablation, radiosurgery) or MRgFUS (ultrasound ablation)

In Russia, interest in stereotactic surgery was documented as early as in XIX century. Thus, in 1889, Professor of Anatomy at Moscow University, D.N. Zernov, demonstrated the encephalometer he created at a meeting of the university’s Physical and Mathematical Society. It was designed for anatomical measurements and stereotactic operations on the brain’s surface structures (Zernov, 1892). In the same year, a patient with Jacksonian epilepsy underwent local trepanation of the skull in the area of the left Rolandic sulcus at a Moscow surgical clinic, and a brain abscess was drained. D.N. Zernov determined the localization of the Rolandic sulcus using his encephalometer. Several similar operations were conducted, all on the surface, in the cerebral cortex area, not in the subcortical brain structures. Subsequently, the encephalometer was successfully used in other Moscow clinics. Professor D.N. Zernov, together with his stu-
with N.V. Altukhov using an encephalometer, detailed encephalometric maps were created for men, women, and children, as well as tables of the average location of the basal ganglia (Altukhov, 1891). At the beginning of the 20th century, the outstanding domestic neurologist Professor G.I. Rossolimo used the D.N. Zernov encephalometer
during brain surgeries, he subsequently improved the encephalometer and in 1907 called it the “brain topograph”

Only 20 years after D.N. Zernov, a neurosurgeon V. Horsley and engineer R.H. С larke the first stereotactic frame was created, described by them in the journal ” Brain» (Horsley, Clarke, 1908). These researchers were the first to introduce the term “stereotaxis.” The stereotactic apparatus they created was used only on animals, and the first stereotactic brain atlases of experimental animals were released. Unfortunately, after the initial success, the authors ceased collaboration due to arising disagreements, and work with the stereotactic frame was halted. In the 1920s E. Saks used the device V. Horsley и R.H. S larke for animal experiments. Student R.H. S larke O. Mussen proposed using this device in people for galvanic heating of brain tumors through a 5 mm burr hole, but no operations were performed by him. Many years later, this device was found by relatives O. Mussen and transferred to the Montreal Neurological Hospital Museum. One of the first cases of using the stereotactic method dates back to 1918: Captain N. Ferguson extracted a bullet fragment from the depth of the brain using a guiding device, with the bullet localized using X-rays, and the extraction was performed with forceps mounted on a supporting arc

Despite certain successes, the pioneering works of all the aforementioned authors did not receive further development and remained unnoticed for a long time. Only in 1950, a neurologist E.A. Spiegel and neurosurgeon H.T. Wycis conducted the first stereotactic surgeries on the subcortical structures of the brain using their stereotactic apparatus and stereotactic atlas of the human brain ( Spiegel, Wysis, 1952). Stereotactic apparatus E.A. Spiegel и H.T. Wycis had high accuracy. According to the creators, in control experiments, in 12 out of 20 cases, the error in hitting the target point did not exceed 1 mm. By 1962, these scientists performed about 100 operations (dorsomedial thalamotomies and pallidoanzotomies) on more than 70 patients with Parkinson’s disease and achieved tremor reduction in 77% of cases with 2% mortality.

During the same period, other neurosurgeons were also working on similar projects, particularly a group led by J. Talairach in Paris. Their first stereotactic surgery J. Talairach conducted on December 7, 1948, on a 72-year-old patient – it was a thalamotomy for the treatment of severe trigeminal neuralgia. In 1949 J. Talairach et al. published the first work on stereotaxis ( Talairach et al., 1949), later they developed a coordinate system of the human brain. In 1950 J. Talairach performed my first stereotactic intervention (thermocoagulation of several brain areas, including the globus pallidus, etc.) for movement disorders in a patient suffering from hemiballismus

In Japan H. Narabayashi in 1949, he designed an original stereotactic apparatus, and in 1951, he performed the first stereotactic surgery on a patient with Parkinson’s disease ( Narabayashi, 1953). In 1957, he founded a private clinic where hundreds of stereotactic surgeries were successfully performed on patients from various countries around the world.

It may seem that stereotaxis was developed for the treatment of movement disorders (primarily Parkinson’s disease) and only later began to be used for psychiatric indications. However, already in the first lectures E.A. Spiegel и H.T. Wycis about the method they called “stereoencephalotomy,” it was stated that the basis for developing this procedure was the need to improve leucotomy, which was then used by them and other doctors in the USA in cases of schizophrenia, depression, obsessive states, etc. Studies of the dissected lobotomized brain ( Freeman, Watts, 1947) showed that retrograde Wallerian degeneration, developing after leukotomy, mainly affected the thalamus, particularly its dorsomedial nucleus. Based on this, E.A. Spiegel и H.T. Wycis concluded that the favorable effect of lobotomy on emotional reactivity was due to the induction of degeneration of the dorsomedial nucleus of the thalamus; this served as the basis for targeting this area during their first stereotactic procedure. According to the assumption E.A. Spiegel и H.T. Wycis, damage directly at the thalamic level could achieve the same result as a lobotomy but without the side effects caused by the destruction of large areas of the frontal lobes. The first targets of destructive operations were the dorsomedial parts of the thalamus in patients with obsessive-compulsive disorder, schizophrenia, and other mental illnesses. Later E.A. Spiegel и H.T. Wycis extended the stereotactic method to the treatment of pain, epilepsy, and only after that to movement disorders (Huntington’s disease, Parkinson’s disease, dystonia)

From the very beginning, the leading approach to stereotactic treatment of Parkinson’s disease was pallidotomy. The history of this operation dates back to the 1950s, when I.S. Cooper accidentally ligated the anterior choroidal artery to stop bleeding during an attempt at pedunculotomy in a patient with PD, leading to an unintended infarction of the globus pallidus and related structures. The pedunculotomy operation was canceled, but, surprisingly I.S. Cooper, tremor and rigidity in the patient’s limbs contralateral to the infarct significantly decreased ( Cooper, 1953). In the future I.S. Cooper began intentionally ligating the choroidal artery and operated on 50 patients in this way, which allowed for the elimination of tremor in 65% of patients with Parkinson’s disease. Although the technique of ligating the choroidal artery to create a pallidal infarction did not gain widespread acceptance due to its contradictory benefits and high complication rate (including hemiparesis), in the 1950s, stereotactic pallidotomy began to be performed for Parkinson’s disease. The Swedish neurosurgeon working in those years L. Leksell moved the destruction zone to the posteroventral parts of the globus pallidus and achieved a reduction in the severity of all major parkinsonian symptoms ( Leksell, 1966), however, his observations went unnoticed for a long time

When analyzing the results of pallidotomy, it gradually became clear that this operation for Parkinson’s disease has a greater impact on rigidity and less effectively suppresses tremor (and it was the tremor that primarily attracted the attention of neurologists and neurosurgeons at that time) R. Hassler suggested that the ventro-oral group of thalamic nuclei converges pallidothalamic, cerebellothalamic, and vestibulothalamic pathways directed to the premotor cortex, after which in 1951 R. Hassler и T. Reichert performed stereotactic destruction of the ventro-oral posterior nucleus of the thalamus ( VOP) c to suppress tremor ( Hassler, 1953). After the publication of the first works R. Hassler many neurosurgeons with Parkinson’s disease began to try targeting the thalamus (mainly the ventrolateral sections) instead of the globus pallidus. This was also facilitated by another coincidence: in 1957 I.S. Cooper began using chemopallidectomy with novocaine injection into the medial parts of the globus pallidus, and in a patient with significant tremor suppression after the presumed pallidotomy, years later, an autopsy revealed that the lesion was located not in the globus pallidus but in the thalamus. After 1961 I.S. Cooper performed about 3000 stereotactic cryothalamotomies, resulting in tremor suppression in 89% of patients and reduction of rigidity in 66% of patients, with the development of various complications in 10% of operated patients and a mortality rate of 1.3% ( Cooper, 1969). Surgeons performing thalamotomies gradually reduced the size of the destruction focus and shifted it posteriorly – to the area VOP и VIM. As a result, the number of thalamotomies for PD began to increase exponentially.

Thus, the development of stereotaxis occurred mainly through empirical methods. The well-known American neurosurgeon R. Kelly wrote: “Throughout the history of functional neurosurgery, theories have been developed to justify empirical observations” ( Kelly, 1995).

Since the 1950s and until the second half of the 1960s, stereotactic surgeries (thalamotomy and pallidotomy) were the main method of treating Parkinson’s disease. By that time, the global literature had reported on the experience of more than 38,000 such interventions. In reality, the number of surgeries conducted was significantly higher, as not all neurosurgeons reported their work and summarized their experiences. Neurosurgeons attempted to improve results by performing destructions in other parts of the thalamus (reticular nucleus, posterior ventral and dorsomedial nuclei, centromedian nucleus). In 1963 E.A. Spiegel и H.T. Wycis proposed a campotomy (subthalamotomy) surgery c focus of destruction in ZI, the Forel fields and prerubral area. During this period of rapid stereotaxis development, a large number of stereotactic devices were proposed L. Leksell, J. Gillingham, T. Riechert, F. Mundinger, J. Talairach, T. Wells, L.V. Laitinen. All of them gradually improved; for example, E.A. Spiegel и H.T. Wycis in a short time, created 5 modifications of their own design of the stereotactic apparatus

The introduction of levodopa medications into clinical practice led to a sharp decrease in the number of neurosurgical operations performed on patients with Parkinson’s disease—the pendulum swung towards pharmacological treatment. However, the predictable development of levodopa-induced complications (fluctuations, dyskinesias) and the weaker effect of levodopa on tremor compared to its effect on rigidity and hypokinesia showed that there is no pharmacological “panacea” for Parkinson’s disease. Renewed interest in surgical treatment for Parkinson’s disease began in the mid-1980s after reports L.V. Laitinen on the beneficial effect of destructive interventions on the medial segment of the globus pallidus ( Laitinen et al., 1992). Around the same time, more advanced neuronavigation systems and ablation techniques emerged, solidifying the place of stereotaxis in the arsenal of doctors treating patients with extrapyramidal movement disorders.

Compared to patients with Parkinson’s disease, the number of patients with other extrapyramidal movement disorders, for which ablative stereotactic interventions have been successfully performed, is relatively small. Among them, dystonia, essential tremor, and some symptomatic forms of tremor, double athetosis, and tics should be mentioned first.

The role of stereotactic ablations of subcortical nuclei in the history of dystonia treatment is extremely significant: for 40 years (until the advent of botulinum therapy and DBS) these surgeries were practically the only effective method to reduce the severity of severe, often extremely painful muscle spasms and pathological postures (Kandel, Voitina, 1971; Kandel, 1981; Shabalov, 2002). According to E.I. Kandel, the diagnosis of dystonia itself was already a direct indication for surgery.

The use of stereotactic destructions of subcortical structures in dystonias was initiated in the mid-20th century by the pioneers of this neurosurgical method E.A. Spiegel и H.T. Wycis, as well as I.S. Cooper. The largest generalized experience of ablative surgeries in patients with various forms of dystonia was presented in the early 1980s by E.I. Kandel (1981) and I.S. Cooper et al. (1982). As the main target structure, depending cdepending on the form of the disease, various nuclei of the ventrooral thalamic group, structures of the subthalamic area (Fields of Forel) were most often selected H1 и H2) and their combinations (Shabalov, 2002) R.R. Tasker et al. (1982) upon careful analysis of the results of nearly 200 stereotactic ablations in patients with dystonias, it was found that the most effective was the destruction in the basal parts of the ventrooral group of thalamic nuclei

According to various authors, the effectiveness of stereotactic interventions with significant regression of symptoms occurred in 66–85% of dystonia cases (up to 30 years of observation). A good result was considered either almost complete disappearance of hyperkinesias and dystonia of the axial muscles and limbs, or a reduction in symptom severity by 60–70%. Higher effectiveness of stereotactic interventions was noted in primary dystonia compared to secondary forms (Kandel, 1981). According to E.B. Sungurov (1997), who conducted a follow-up study (up to 23 years) on patients operated on at the Research Institute of Neurology, long-term results were somewhat better in patients with focal forms of dystonia (symptom regression 74%) than in patients with generalized form (67%). It should be noted that the complication rate in the described series of observations was quite high—ranging from 10.0 to 21.4%

In focal forms of dystonia, especially in cervical dystonia (CD) (one of the most frequently operated), E.I. Kandel and other authors successfully applied the destruction of the Cajal nucleus (Kandel, Voitina, 1971; Kandel, 1981). This nucleus is part of the medial longitudinal fasciculus system and has extensive connections with the ventrooral group of thalamic nuclei and the system responsible for turning the head and eyes toward the source of stimulation. Destructions are performed both on the Cajal nucleus itself and on the interstitial-thalamic pathways in the subthalamic area or in the medial parts of the ventrooral group of thalamic nuclei (ventrooral internal nucleus, ventrooral medial nucleus). During the operation, to avoid the risk of damaging the medial longitudinal fasciculus and oculomotor nuclei, the use of microelectrode recording (MER) techniques and more precise targeting of structures involved in dystonia is mandatory (Shabalov, 2002). A positive effect after ablation of the Cajal nucleus was observed in more than 65% of CD cases, often developing only several months after the operation (Vasin et al., 1985)

The experience of stereotactic ablations in patients with ET, symptomatic tremor, tics, athetosis, chorea, and ballism is significantly less (Kandel, 1981; Shabalov, 2002; K andel, 1989). In ET, the intervention strategy is fundamentally similar to that for tremor variants of PD, and the long-term results of the intervention can be quite favorable (Shabalov, 2002). However, due to the relative benignity of this condition, patients less frequently “reached” destructive surgeries. Today, the leading role in the treatment of these pathologies is held by DBS, but recently the situation has gradually started to change with the emergence of the MRgFUS method (see chapter 6)

Human Brain Atlases

During a stereotactic surgery, a neurosurgeon cannot do without a human brain atlas. The first stereotactic atlas of the human brain, as mentioned above, was created E.A. Spiegel и H.T. Wycis in 1952. It consisted of photographs of brain slices every 5 mm in three planes.

Atlas of the Brain of Experimental Animals, Created by V. Horsley и R.H. С larke in 1908, as well as the stereotactic technique used in animal experiments, are not applicable to humans. In experimental animals, this technique is based on relatively constant relationships of brain structures with external bony landmarks, whereas in humans, such constancy does not exist. Therefore, in humans, during stereotactic brain operations, only intracerebral points can be used as landmarks, relative to which the localization of other desired intracerebral structures can be established.

In 1959, an atlas was published G. Schaltenbrand и P. Bailey. The coordinate system in this atlas is tied to the intercommissural line. The atlas contains many diagrams based on a large number of studied specimens; these diagrams standardize the coordinates of the main subcortical nuclei used as target points in stereotactic operations. In 1977, the 2nd edition of this atlas was published in 3 volumes under the editorship of G. Schaltenbrand, W. Wahren (1977). This atlas turned out to be very successful and is widely used by neurosurgeons to this day.

There are 4 generations of atlases: early brain cortex maps, printed stereotactic atlases, early digital atlases, and the most advanced digital brain atlas platforms, as well as 5 directions in electronic atlases covering the last 2 generations. In terms of content, new electronic atlases are divided into 8 groups considering their application, parcellation, modality, multiplicity, scale, ethnicity, anomalies, and their combinations. The development of atlas content in these groups is conducted in 23 different directions.

Ablation Methods

The final stage of each stereotactic surgery, except DBS, is ablation (destruction) in the рас cread by the neurosurgeon at the target point. The primary requirement for a destructive method of impact is controllability—the ability to regulate the volume of destruction during the operation and immediately stop the destruction if undesirable side effects occur. Another significant condition is the ability to destroy a predetermined volume of brain tissue, ensuring the stability of the lesion size. The perifocal reaction of brain tissue to the destruction site is important. Among all possible methods of contact (invasive) ablation of brain substance that have been tested over decades, currently, only radiofrequency thermodestruction is mainly used in neurosurgery. Lesions caused by thermal destruction methods induce relatively minimal perifocal reactions, allowing them to be considered biologically inert.

Destructive methods also include radiosurgery (gamma knife) and MRgFUS, which do not require trepanation of the skull and direct invasive contact with brain tissue. A feature of the radiosurgical destruction method is that the effect of the operation does not appear immediately but after a certain latent period following the focused gamma radiation, lasting several months ( Duma et al., 1998; Young et al., 2010; Niranjan et al., 2017). The maximum effect in 80% of patients develops approximately 1 year after the intervention, which is a major drawback of this technology. Despite the non-invasive nature of the procedure, the radiosurgical method is not safe, and complications (such as radiation necrosis of brain tissue, etc.) can also be delayed ( Young et al., 2010).

Advantages and disadvantages of the new MRgFUS technology, providing non-invasive ablation of specific targets in brain matter through the impact of a focused beam of ultrasound waves, are presented in the following chapters of the monograph.

Origins of the Domestic School of Stereotactic Neurosurgery

The pioneer of domestic stereotaxis is Professor Eduard Izrailevich Kandel, an outstanding neurosurgeon, to whose 100th birthday this monograph is dedicated. A brief biographical sketch of Professor E.I. Kandel is presented in Appendix 1.

Since the early 1950s, E.I. Kandel began developing stereotactic surgery for movement disorders (primarily for Parkinson’s disease, essential tremor, and dystonia) initially at the N.N. Burdenko Neurosurgery Research Institute, and later at the Institute of Neurology. He created a stereotactic apparatus of original design, developed a system for calculating the target point based on ventriculograms, and also implemented and advanced the method of cryodestruction using liquid nitrogen Kandel, 1965). A cryocannula of their own design was created by Professor E.I. Kandel in collaboration with Academician A.I. Shalnikov, which underwent 7 modifications and was widely used in operations for patients with extrapyramidal pathology.

In subsequent years, E.I. Kandel began using the stereotactic method for the removal of intracerebral hematomas, stereotactic clipping of cerebral aneurysms, cryodestruction of brain tumors, pain relief surgeries, and more. The list of diseases for which E.I. Kandel and his students successfully applied stereotactic cryodestruction is quite impressive: Parkinson’s disease, essential tremor, dystonia, cerebral palsy, Tourette syndrome, post-traumatic hyperkinesias, and others.

The unique experience of E.I. Kandel, the research school he established, and the classic monographs and guides he wrote have significantly contributed to the development of this field in Russia and all the countries of the former Soviet Union, as well as attracting many talented young doctors to the world of stereotactic neurosurgery. Such operations were performed in clinics in Moscow, St. Petersburg, Ryazan, Yekaterinburg, Samara, and others. These works laid the foundation for the further development of stereotaxis and the emergence of new effective technologies for the functional treatment of extrapyramidal disorders in our country.

From Destructive Stereotaxis to Electrical Brain Stimulation

Method of stimulating subcortical structures with electrical impulses of different frequencies ( DBS), in its modern form, which appeared just over 30 years ago, it represents a logical continuation of the long history of the development of functional and stereotactic neurosurgery (Illarioshkin, 2013a)

As early as 1954, the American neurosurgeon R. Heath performed pioneering operations for electrode implantation in the brain using stereotactic techniques. The targets R. Heath there were limbic and other nonspecific brain systems, but his experiments on inducing emotional reactions and other “social” responses through deep electrical stimulation were ethically controversial and did not develop further Moan, Heath, 1972). Over the next two decades, the main indication for brain electrostimulation was chronic central pain syndromes (stimulation of the hypothalamus, thalamus, dorsal columns of the spinal cord). One of the first works in which brain electrical stimulation was proposed for the treatment of tremor was a publication by the team of the Institute of Experimental Medicine of the USSR Academy of Medical Sciences led by Academician N.P. Bekhterev Bechtereva et al., 1975). Another milestone in the surgical treatment of tremor was an article by American neurosurgeons, who in 1980 described the moderate effect of electrical stimulation of the midbrain and basal ganglia in 5 patients with intention tremor against the background of multiple sclerosis Brice, McLellan, 1980).

In the late 1970s to early 1980s, studies appear I.S. Cooper on the use of electrical stimulation of various parts of the brain (with a focus on the cerebellar cortex and thalamus) in dystonia, epilepsy, and spasticity ( Cooper, Upton, 1985). And although most of the positive results he presented were not confirmed by other authors, an important outcome of these works was the creation of the first direct current generators for cerebral stimulation. It is precisely I.S. Cooper first indicated that the reversible nature of chronic electrical stimulation can help avoid complications typical of bilateral thalamotomy

Modern Era of Application DBS began in 1987–1991 after the pioneering publications of the French neurosurgeon A.-L. Be­ nabid, demonstrating extremely favorable results of high-frequency electrical stimulation VIM and the subthalamic nucleus in patients with PD ( Benabid et al., 1987, 2000). Shortly after that, many researchers noted the high effectiveness DBS in the treatment of PD, ET, dystonia, and other diseases. To date, the method DBS has firmly gained widespread recognition due to its significant “flexibility” in target selection, reversibility of the achieved effect, and the possibility of non-invasive modification of the effects of electrical stimulation, as well as safety and, in particular, a substantially lower risk of pseudobulbar syndrome in bilateral interventions compared to traditional destructive surgeries (Illarioshkin, 2013a; Wårdell et al., 2022).

In our country, the pioneer in the field of brain electrical stimulation was Professor V.A. Shabalov, who worked at the N.N. Burdenko Research Institute of Neurosurgery. Since 1993, he actively developed surgical neuromodulation for extrapyramidal movement disorders and pain syndromes (Shabalov, 2002; Shabalov, Tomsky, 2003; Shabalov, Isagulyan, 2010). A few years later DBS for movement disorders was implemented at the Research Center of Neurology and later in other institutions. As of early 2024, the method DBS are actively used by 11 specialized neurosurgical clinics in various cities of the Russian Federation

Microelectrode Recording

Microelectrode recording in stereotactic surgeries has been the “gold standard” in developed countries for 25 years. Signal recording is conducted by inserting ultra-thin electrodes into the area of interest, allowing for the registration of brain cell activity and differentiation based on the obtained signals. Mapping zones during microelectrode recording determines the optimal area for electrode implantation, and the ability to perform trial stimulation helps avoid undesirable side effects. Registration is carried out using an electric current (from 5 to 100 µA) at a very high frequency (Nizametdinova et al., 2016)

Stereotactic surgery involves precise localization of targets
areas; however, deep functional structures in different people have their individual characteristics. The MER technique eliminates possible errors during destructive operations, as well as at the stage of final electrode implantation for DBS. Microelectrode recording not only allows for the visualization of unique neuronal activity based on real-time diagrams, but also
«listen to sound signals corresponding to specific physiological structures (Fig. 1.4)

The MER procedure is performed intraoperatively during stereotactic interventions under local anesthesia, allowing contact with the patient during the procedure. By performing active or passive movements, it is possible to modulate the activity of neurons in the corresponding sensorimotor zone involved in the execution of the movement, and recording neuronal activity using MER allows the surgeon to select the most significant functional area for further destruction or stimulation.

Modern Stage of Functional and Stereotactic Neurosurgery

Nowadays, methods of stereotactic interventions on the brain continue to improve, and the range of indications is constantly expanding. The stereotactic method is widely used for electrode implantation, delivering a beam of radiation to the desired area of the brain, performing targeted ablations for movement disorders, brain tumors, epilepsy, vascular malformations, pain syndromes, and other conditions.

Destructive procedures

The modern approach to destructive stereotactic operations on the brain has been formed based mainly on the use of radiofrequency thermodestruction, which for improved navigation can be performed using MER techniques. This section of the chapter is dedicated to a brief overview of invasive (contact) stereotactic destruction of the basal ganglia. In XXI century, non-invasive technologies for ablative stereotaxis also emerged – gamma knife (radiosurgery) and MRgFUS. The gamma knife is rarely used today in the treatment of PD, ET, and other movement disorders, whereas the following chapters of the monograph are dedicated to a detailed examination of the increasingly popular MRgFUS method worldwide.

The main targets for destruction in extrapyramidal pathology are the ventrolateral nuclei of the thalamus (thalamotomy) and the globus pallidus (pallidotomy).

Pallidotomy

Played a significant role in improving this intervention and expanding its application in PD L.V. Laitinen, who “rediscovered” the outcomes of surgeries L. Leksell and moved the target point to the posteroventral sections GPi. The operation was named posteroventral pallidotomy (PVP). In its foundational work L.V. Laitinen et al. (1992) analyzed the results of surgical treatment of patients with Parkinson’s disease operated on from 1985 to 1990: it was found that the posteroventral pallidotomy effectively suppresses tremor, rigidity, and bradykinesia. The mechanism of action of the posteroventral pallidotomy is that the destruction of the posteroventral sensorimotor area GPi contributes to the elimination of the pathological model of neuronal activity GPi and releases or “normalizes” thalamocortical activity, causing a reduction in PD symptoms

Indications for MRI-guideded focused ultrasound include preserved cognitive functions without significant brain atrophy in patients with Parkinson’s disease who have motor fluctuations, medication-induced dyskinesias, dystonias, and muscle cramps during the “off” period, as well as tremor. Ideally, the patient should have asymmetrical symptoms. Unilateral MRI-guideded focused ultrasound in elderly patients is preferable to bilateral DBS to the area of the subthalamic nucleus Hariz, Bergenheim, 2001).

A.E. Lang et al. (1997) conducted an analysis of DBS outcomes presented in 11 studies. The immediate results were assessed using the Unified Parkinson’s Disease Rating Scale ( Unified Parkinson’s Disease Rating Scale, UPDRS) 3–6 months after surgery: on average, motor functions improved by 28% during the “off” period, while the “on” period showed almost no change; daily activity in part II UPDRS improved both during the “on” period (by 28%) and the “off” period (by 25%). The most dramatic effect was observed in relation to drug-induced dyskinesias: they decreased by 77% on the contralateral side of the operation and by 43% on the side of the operation. In addition to hypokinesia and rigidity, PVP was also effective for tremor. It was noted that unilateral PVP does not allow for a reduction in the daily dose of levodopa and does not affect speech, gait, or freezing.

There is a limited number of studies analyzing the long-term results of MRI-guideded focused ultrasound in patients with Parkinson’s disease. It has been noted that the regression of contralateral dyskinesias from the operation persists for a long time, whereas ipsilateral dyskinesias may recur as early as 1 year after the operation ( Goodman et al., 1998). A number of authors confirm a sustained improvement on the side contralateral to the intervention (especially regarding dyskinesia and tremor, to a lesser extent regarding bradykinesia) after unilateral MRgFUS ( Lang et al., 1997; Kimber et al., 1999). When observing 10 patients over 4 years, a decrease in the effect of focused ultrasound was noted: for instance, improvement in motor functions decreased from 27% during the first year of observation to 7% after 4 years ( Kelly, 1995).

Until now, certain discussions continue in the literature regarding the optimal location of the lesion during pallidotomy ( Laitinen, 1998).

The risks of side effects after MRI-guideded focused ultrasound in patients with Parkinson’s disease are lower than after thalamotomy; it is no coincidence that elderly patients tolerate MRI-guideded focused ultrasound better Kimber et al., 1999). Posteroventral pallidotomy in any hemisphere can lead to frontal-type mental changes (in 25-30% of patients), memory impairments, damage to the optic tract, paresis, depression, and PVP in the dominant hemisphere can cause dysarthria. Some side effects may become apparent only days or weeks after PVP (especially concerning dysarthria and memory impairments). Observations show that adverse effects correlate with more anterior and posterior damage GPi. As a rule, cognitive impairments after MRgFUS are minimal in patients without signs of dementia, so a thorough neuropsychological examination is recommended before surgery.

Serious complications include hemorrhage (most often associated with the destruction site) and brain infarctions. The risk of hemorrhage is somewhat higher in patients operated on using MER to confirm the target point (2.7% after MER vs 0,5% без МЭР) ( Palur et al., 2002).

In the conducted meta-analysis of MRgFUS results performed in 7 neurosurgical centers (170 patients with Parkinson’s disease), the mortality rate averaged 1.8% ( Palur et al., 2002).

A small number of clinics have experience performing bilateral MRI-guideded focused ultrasound in patients with Parkinson’s disease ( Scott et al., 1998). More significant regression of PD symptoms after such surgeries, unfortunately, is often outweighed by an increased frequency of dysarthria, hypophonia, dysphagia, hypersalivation, and cognitive impairments.

Thus, the effectiveness of MRgFUS for Parkinson’s disease is beyond doubt: it is one of the few procedures with a class A evidence level. Unilateral pallidotomy is comparable in effectiveness to unilateral DBS GPi и DBS subthalamic nucleus, but is inferior to bilateral DBS subthalamic nucleus ( Intemann et al., 2001).

In the Neurology Research Center, the results of unilateral MRgFUS procedures were studied in 14 patients with Parkinson’s disease complicated by drug-induced dyskinesias. Among them, 11 patients had the akinetic-rigid form of the disease, and 3 had the mixed form. The patients included 6 men and 8 women, aged 56 to 69 years (average age 65.4 years), with a disease duration of 5–11 years (average 7.2 years), and stage 3–4 according to the Hoehn and Yahr functional scale. The severity of drug-induced dyskinesias, assessed by part IV UPDRS, averaged 3.7 points. No significant cognitive and somatic disorders were identified in the patients. In 9 patients, the procedure was performed on the left side and in 5 patients on the right; ablations were conducted using the method of radiofrequency thermodestruction with the use of a planning station Radionics. Patients were examined during the “on” and “off” periods 1 week and 6 months after surgery using UPDRS (parts II, III, IV), Schwab and England scales, the 39-item Parkinson’s Disease Questionnaire ( The 39-Item Parkinson’s Disease Questionnaire, PDQ-39).

One week after pallidotomy, regression of drug-induced dyskinesias on the contralateral side was observed in 100% of patients, ranging (according to the severity of dyskinesias in points) from 44 to 82% (average 68%), and on the ipsilateral side in 50% of patients (average reduction in severity by 43%). In pallidotomy, a positive effect was achieved in 100% of patients in the form of reduced rigidity and bradykinesia, and in 50% of cases, a reduction in the dose of levodopa was achieved (average of 15%). Six months after the operation, a reduction in drug-induced dyskinesias was observed contralaterally by 32–64% (average 52%), but ipsilaterally, the severity of dyskinesias returned to preoperative levels. Improvement in UPDRS (parts II, III) amounted to 49% during the “off” period and 45% during the “on” period. The use of pallidotomy significantly improved daily activity and quality of life indicators: by 30% on the Schwab and England scale, by PDQ-39 – at 31%. Overall, the most positive impact of MRgFUS on motor functions (including tremor) was observed on the contralateral side of the operation, while improvements on the ipsilateral side were less significant and diminished within the next 6 months. The dose of levodopa returned to previous levels in all patients 6 months after the operation. No significant postoperative complications were observed: 3 patients experienced mild speech disturbances of the dysarthria type, which regressed 2–3 weeks after the operation.

As stated above, historically, pallidotomy played a significant role in treating patients with dystonias. However, nowadays, the number of pallidotomies for dystonic disorders has practically diminished due to the advancement of technology DBS, since it is chronic electrical stimulation that provides the possibility of safe bilateral impact (which is usually required in most forms of dystonia). Classical unilateral pallidotomy is occasionally used in patients with lateralization of dystonic hyperkinesis in the clinical picture, especially in the absence of signs of generalized motor disorders. However, the introduction of the MRgFUS method into clinical practice has revived interest in pallidotomy for patients with dystonia at a new technological level (see chapter 8)

Thalamotomy

Leading neurosurgical centers worldwide for the treatment of tremor most commonly use ablation of the ventrolateral group of thalamic nuclei. At the same time, there is data on the use of other target points (pallidum ZI, Forel’s fields, subthalamic nucleus, dentate nucleus of the cerebellum)

According to E.I. Kandel (1981), the ideal candidate for stereotactic thalamotomy is a patient under 65 years of age, with ineffective or intolerable conservative treatment, preserved intelligence, no significant organic brain changes, and predominant tremor on one side. The list of diseases with various types of tremor for which thalamotomy is performed is diverse: these include Parkinson’s disease, essential tremor, dystonic, kinesia-specific, post-traumatic and post-stroke tremor (including rubral), intention tremor with cerebellar lesions, and others.

The most effective targets are considered to be the ventro-oral group of thalamic nuclei ( VOA (ventro-oral anterior nucleus), VOP) и VIM. Destruction of these nuclei is accompanied by persistent suppression of tremor and reduction of rigidity in the contralateral limbs. Currently VIM is considered the main target point in such interventions. Before conducting VIM-thalamotomies for the purpose of neurophysiological mapping of boundaries and assessment of individual extent VIM, as well as the identification of “tremor” neurons, the MER procedure can be performed using special intraoperative neuromonitoring systems

In the Scientific Center of Neurology, from 1965 to 2023, 2800 thalamotomies were performed for tremor and mixed (tremor-rigid) forms of Parkinson’s disease and essential tremor. Significant reduction of tremor in contralateral limbs was observed in 92% of patients, and reduction of rigidity in 90%. It is important to note that in the long-term postoperative period, 65% of patients maintained the effect of the operation for more than 5 years, and half of the patients for more than 10 years. Functional improvement was assessed at 1–2 points on the Hen-Yahr scale in 70% of patients. Complications of the operations included contralateral hemiparesis (0.8%), pseudobulbar speech and swallowing disorders (4%), psychopathological changes (5.8%), hemiballism (0.5%), hemorrhage in the destruction area (2.5%). Postoperative mortality was 0.8%

Early results from the Research Center of Neurology and numerous literature data indicate that after the second surgery (thalamotomy on the other side), the complication rate in patients with Parkinson’s disease sharply increases: for instance, pseudobulbar disorders develop in 25–36% of cases. Therefore, the need for bilateral destructions is currently a contraindication for surgery.

It has been noted that patients with generalized or segmental dystonia who have previously undergone thalamotomy show a lesser degree of clinical improvement after stimulation GPi (Levin et al., 2022). Therefore, performing thalamotomy for primary dystonia is currently not recommended.

Due to the widespread adoption of the technology DBS over the past 30 years, the frequency of thalamotomies in patients with tremor has steadily declined. The renaissance of ablative stereotaxis for tremor (parkinsonian, essential, dystonic) is associated with the emergence of the non-invasive MRgFUS method (see chapters 6–8)

Deep Brain Stimulation

Chronic electrical stimulation of deep brain structures using implanted electrodes is part of the group of surgical neuromodulation methods. The essence of the technology is that an electrode is stereotactically implanted into a specified target using a special CT/MRI-guided program, fixed in the skull bones, and connected via a connector to a neurostimulator implanted subcutaneously (Shabalov, 2002; Tarsy et al., 2008). Modern systems for DBS allow programming, modifying, saving specified stimulation parameters (amplitude, frequency, pulse duration, etc.) or pausing it using a magnetic switch. The standard stimulation frequency is 110–150 Hz, pulse duration is approximately 60 μs. A fundamental feature DВ S is minimal damage to brain tissue and the possibility of non-invasive correction of the effects of electrical exposure, as well as fewer complications in bilateral operations on the subcortical structures of the brain (Shabalov, 2002; Levin et al., 2022)

Traditionally, it is believed that DBS neutralizes the pathological hyperactivity of neurons in the stimulation zone, forming a depolarization block (Illarioshkin, 2013a). Available data from fundamental and clinical research indicate additional mechanisms of impact DBS, related to synaptic modulation in the basal ganglia area and activation of a specific set of both afferent and efferent axons, which alters the overall synaptic response in target neurons (Bril et al., 2022). In DBS intervention is carried out in spontaneous pathological patterns by “imposing” new activity at the nodal points of the neural network (Illarioshkin, Ivanova-Smolenskaya, 2011; Tarsy et al., 2008). Influence shown DBS on synaptic plasticity through activation of glial cells ( Fenoy et al., 2014). Certain neuroprotective (including long-term) effects of this intervention are also suggested (Brill et al., 2022)

Parkinson’s Disease

Bilateral stimulation of the subthalamic nucleus or GPi is used in the therapy of advanced stages of Parkinson’s disease in patients responding to levodopa-containing therapy, in cases where conservative treatment does not achieve adequate results ( Vingerhoets et al., 2002). Stimulation VIM used to suppress tremor (Parkinsonian, essential, dystonic, etc.) when conservative therapy is ineffective and there are significant functional and social limitations

More commonly used in PD DBS subthalamic nucleus, as targeting this area allows for influencing both tremor and other motor symptoms of the disease—hypokinesia, muscle rigidity, and drug-induced dyskinesias. The basis for targeting the subthalamic nucleus was the understanding of its hyperactivation’s role in the pathogenesis of movement disorders in PD. Suppression of excessive activity of the subthalamic nucleus against the background of DBS leads to enhancement (through GPi and nonspecific thalamic nuclei) activating influences on the premotor/supplementary motor cortex, as evidenced by PET and functional MRI data, accompanied by a reduction in hypokinesia (Levin et al., 2022)

A detailed analysis of the follow-up of bilateral subthalamic stimulation surgeries in patients with Parkinson’s disease revealed that the severity of tremor decreases by an average of 74%, rigidity by 66%, bradykinesia by 59%, postural instability by 17%, and gait disturbances by 37% ( Gervais-Bernard et al., 2009). Anti-tremor effect DBS the subthalamic nucleus in PD is quite stable for 5 years or more ( Tarsy et al., 2008). Stimulation of the subthalamic nucleus does not affect the pharmacodynamics of levodopa; however, its average daily dose can be reduced by about 50% after surgery (and in some patients, completely discontinued), which is explained by the decreased need for the drug due to the regression of the main clinical manifestations ( Fox et al., 2018). Severity of dyskinesias in DBS subthalamic nucleus decreases by 60–80% (mainly due to the reduction of the daily dose of levodopa), and the duration of the “off” period – by 33–90% ( Gervais-Bernard et al., 2009; Limousin, Foltynie, 2019). The economic efficiency has been proven in a number of studies DBS subthalamic nucleus: the overall treatment costs increased by 32% by the end of the first year of stimulation, but decreased by 54% by the end of the second year compared to pre-surgery expenses (Levin et al., 2022)

According to the experience of the Research Center of Neurology, in a large group of operated patients with a mixed form of Parkinson’s Disease, 92.8% of patients against the background of DBS complete suppression of tremor was achieved in the subthalamic nucleus, and partial suppression in the remaining patients. In a group of 50 patients with the akinetic-rigid form of PD, after 6 months of conducting DBS subthalamic nucleus noted a decrease in the average total score for UPDRS (parts II и III) during the “off” period from 88.2 to 44.3 and during the “on” period from 41.2 to 22.4, improvement in daily activity scores on the Schwab and England scale by 20% and quality of life by PDQ-39 – на 31%.

As experience accumulates in conducting DBS in patients with PD, it was suggested that earlier intervention, younger patient age at the time of surgery, and shorter disease duration are predictors of better postoperative outcomes (Brill, 2020; Suarez-Cedeno et al., 2017). In initiated research ( EARLYSTIM and others), which included working-age patients with PD under 60 years old with a disease duration of about 7 years and a recent onset of fluctuations, demonstrated the advantages of surgery in almost all parameters compared to medication therapy, with early DBS subthalamic nucleus alleviated neuropsychiatric non-motor fluctuations and allowed better control of hyperdopaminergic behavior without significant manifestations of apathy, depression, or anxiety ( Schuepbach et al., 2013; Lhommée et al., 2018). In 2020, the 5-year results were published DBS at the earliest stage of PD (stage 1–2 on the Hoehn and Yahr scale), showing that early stimulation of the subthalamic nucleus combined with medication provides better control of motor symptoms compared to medication alone, mainly by slowing the progression of tremor Hacker et al., 2020). Simultaneously early DBS subthalamic nucleus allows for simplifying the therapeutic regimen for patients whose disease progresses from early to mid-stage, significantly reducing the proportion of patients requiring polypharmacy over 5 years; possibly due to reduced pharmacological load early DBS the subthalamic nucleus may reduce the risk of developing or worsening dyskinesia in PD ( Hacker et al., 2020). Long-term safety of early intervention demonstrated DBS subthalamic nucleus (Levin et al., 2022; Hacker et al., 2020). It should be emphasized that the issue of earlier patient selection c BP for conducting DBS the subthalamic nucleus remains controversial due to the high likelihood of misdiagnosis (which occurs in at least 25-30% of early-stage PD cases), the risk of various surgical complications, etc., therefore further research is needed to determine the role of stimulation surgery in this category of patients

In patients with PD who predominantly have tremor, chronic stimulation is successfully used VIM. Immediate and Long-term Results DBS VIM were comparable to the effect of thalamotomy with fewer persistent neurological complications, due to being less invasive DBS and the reversibility of the effect of electrical stimulation ( Benabid et al., 1991, 1993).

Another target for DBS in patients with PD is GPi. In PD, pallidal stimulation is particularly effective for controlling contralateral levodopa-induced dyskinesias, although it also improves tremor, muscle rigidity, and hypokinesia. Chronic electrical stimulation of this structure is characterized by a significantly lower frequency of postoperative complications compared to pallidotomy. It has been noted that with pallidal stimulation, the effect is more variable than with subthalamic stimulation (possibly due to the larger size of this structure), and some patients with initially good tremor control may lose it within 1–3 years after surgery ( Durif et al., 2002). Bilateral DBS GPi affects symptoms on both sides, which increases its effectiveness compared to unilateral pallidotomy (Shabalov, 2002; Shabalov, Tomsky, 2003)

Essential tremor

No less effective VIM-stimulation in the treatment of patients with ET, as reflected in numerous publications ( Benabid et al., 1993; Pahwa et al., 2006; Altinel et al., 2019). In a number of prospective studies with an average follow-up duration of 1 to 7 years, it was found that against the background of DBS VIM the severity of hand tremor can decrease by 50–91%, and head and voice tremor by 15–100% (Levin et al., 2022). For head and voice tremor, the results of bilateral surgeries were significantly better, which are quite safe for this category of patients ( Tarsy et al., 2008). Although the improvement achieved with ET is long-lasting, in some cases the effect of the surgery may decrease over time, requiring periodic adjustment of the neurostimulation regimen

In some patients c Is good control of tremor in the dominant hand sufficient in terms of improving overall functioning, and can they be offered unilateral DBS. In such cases, there is no need for the additional surgical risk associated with implanting a second electrode in the contralateral hemisphere of the brain

Positive effect DBS VIM in patients with ET is confirmed by the experience of the Neurology Research Center: favorable treatment outcomes in our cohort of patients were objectified using tremorography and other physiological tests (Fig. 1.5, 1.6)

Dystonia

Unilateral or bilateral stimulation GPi is currently considered the treatment of choice for severe pharmacoresistant primary dystonia (various forms) in adults and children over 7 years old (Shabalov, 2002; Levin et al., 2022). Bilateral pallidal DBS leads to a reduction in the severity of dystonic hyperkinesia by 33–90% with minimal side effects ( Krause et al., 2020; Kamel et al., 2021). A criterion for a favorable prognosis is the reduction in the severity of movement disorders in the first days of neurostimulation; subsequently, the reduction of hyperkinesis continues and reaches a maximum 9–12 months after the surgery. The effectiveness of bilateral pallidal electrical stimulation in primary generalized dystonia is evidenced by the results of all conducted prospective randomized studies Vidailhet et al., 2005; Alterman, Snyder, 2007), indication for DBS the appearance of the first signs of disability is considered. It should be noted that during pallidal DBS in patients with dystonia, a rather intensive stimulation mode is used, which contributes to the faster depletion (within 2–3 years) of the impulse generator battery and the need for replacement or recharging of the device

In patients with primary diabetes mellitus, conducting DBS GPi accompanied by a reduction in the severity of hyperkinesis by 50–70% and a decrease in pain syndrome by 50–60% ( Krauss, 2007). If pallidal stimulation is insufficiently effective, it may be recommended DBS thalamic nuclei. The question of neurosurgical treatment in patients with CD should be considered when at least 3–5 consecutive injections of botulinum toxin preparations are ineffective

A relatively new target for dystonia is the subthalamic nucleus, the stimulation of which began to be used later than the stimulation GPi. One of the reasons researchers were searching for an alternative GPi targets, became the fact that some patients with dystonia against the background DBS GPi such an undesirable phenomenon as “Parkinson-like” hypokinesia may occur ( Tisch, 2018). In the meta-analysis of published results of chronic electrical stimulation GPi (16 studies, 30 patients) and the subthalamic nucleus (3 studies, 12 patients) in isolated dystonia showed a slight advantage DBS subthalamic nucleus in reducing the severity of hyperkinesis ( Wu et al., 2019). The results were better with a shorter duration of dystonia. Y. Liu et al. (2019) noted the same short-term effectiveness of stimulation of both nuclei ( GPi and subthalamic nucleus) in primary dystonia, with a slightly higher number of side effects during subthalamic stimulation. The effectiveness of subthalamic stimulation over at least 3 years of observation was confirmed in a large cohort of patients with severe medication-refractory primary dystonia ( Ostrem et al., 2017). According to B. Sun et al. (2007), the subthalamic nucleus may be a more attractive target for stimulation compared to GPi, since: 1) symptomatic improvement in DBS the subthalamic nucleus occurs immediately after surgery and allows for quicker selection of the necessary stimulation parameters; 2) the intensity of subthalamic stimulation is lower, which conserves battery life; 3) the results of subthalamic stimulation obtained by the authors in patients with primary and tardive dystonia were better compared to the results published in the literature DBS GPi. Positive effect DBS the subthalamic nucleus in various forms of dystonia can have a long-term effect – from 7 to 14 years ( Li H. et al., 2021; Wu et al., 2021).

Common side effect DBS subthalamic nucleus in dystonia is the development of dyskinesias, which can be controlled by careful reprogramming of the stimulation mode ( Tisch, 2018).

In cases where dystonic tremor predominates in the clinical picture, preference is given to stimulation VIM (Shabalov, 2002; Lyons, Pahwa, 2005). Effectiveness DBS VIM in dystonic tremor is generally comparable to that of tremor of other etiologies, however, in some cases, the tremor remains resistant and requires pallidal or combined VIM + GPi) stimulation.

One of the prognostic criteria for the effectiveness of subcortical nuclei electrostimulation in patients with primary dystonia is the presence of specific mutations. The best results DBS noted with DYT1-dystonia; a good effect of pallidal stimulation is also observed in myoclonic dystonia DYT-SGCE (DYT11) и при X-linked dystonia-parkinsonism ( DYT3) (Artusi et al., 2020; Tisch, Kumar, 2021). Less favorable response to DBS GPi described for the form of dystonia DYT-THAP1 (DYT6) (Levin et al., 2022)

In secondary dystonia, the results of pallidal stimulation are not as convincing: the degree of reduction in the severity of hyperkinesias ranges from 5 to 30%, which is attributed to differences in the pathogenesis of movement disorders in primary and secondary forms. In some cases of secondary dystonia, positive results can be obtained by stimulating other brain structures (thalamic nuclei, subthalamic nucleus GR e), however, such reports are rare. Exceptions include cases of late dystonia, where promising results have been noted with DBS pale globe ( Tisch, 2018).

Tics and Tourette Syndrome

Deep brain stimulation is an effective procedure for treating severe pharmacoresistant tics, including in patients with Tourette syndrome. During chronic brain electrostimulation in this category of patients, various neurosurgical centers worldwide targeted 9 different subcortical targets in GР e и GPi, dorsomedial thalamus, subthalamic nucleus, nucleus accumbens, anteromedial part of the internal capsule, etc. ( Hariz, Robertson, 2010). As a result of surgical treatment, tics were reduced by 25–85%, according to various authors. In our country, priority results for this pathology have been obtained at the Scientific Center of Neurology. From 2012 to 2023, we operated on 10 patients with Tourette syndrome who had disabling motor and vocal manifestations of the disease that were not controlled with standard pharmacotherapy (Tyurnikov, 2022). The condition of the patients before and after surgery was assessed using the Yale Global Tic Severity Scale ( Yale Global Tic Severity Scale, YGTSS). As a target DBS used GPi. In all cases, the results of stimulation were positive: the severity of tics according to YGTSS on average decreased by 41% (from 15 to 85%), and these results remained relatively stable when observing operated patients for up to 12 years. No significant complications from the surgery were recorded

It should be noted that many questions regarding the surgical treatment of Tourette syndrome remain unanswered, particularly the effectiveness DBS regarding various “non-tic” manifestations of the disease, predictors of a good response to stimulation, its parameters, the choice of the optimal target, and more. Even for the same target, such as the globus pallidus, there is no evidence base on which part of this structure needs to be stimulated for maximum suppression of tics – anteromedial or posteromedial. Therefore, until now DBS is considered an experimental treatment method for Tourette syndrome

Future Prospects DBS and a combination of stereotactic methods

Continuous development of the method DBS continues at present and is related both to the improvement of navigational and neurosurgical techniques and the stimulators themselves, as well as to the differentiated selection of new targets for electrode implantation depending on specific diseases ( Wårdell et al., 2022). Over the past few years in the field of DBS a number of important innovations were implemented Merola et al., 2021). Sensory electrodes have been developed to optimize settings using feedback from local brain potentials (algorithm “adaptive DBS» for personalized therapy), asynchronous high-frequency pulse sequences have been proposed for more effective retuning of dysfunctional brain neural networks, simpler programming algorithms have been developed, platforms for remote management of neurostimulation via telemedicine have been implemented, and tools for assessing the volume of tissue activated inside and outside the target have been introduced. Surgical precision has increased due to intraoperative MRI/CT and robotic surgery for submillimeter electrode placement. These and other new technologies significantly improve outcomes DBS (Levin et al., 2022)

At the same time DBS – this is just one of the tools in the broad arsenal of modern functional stereotactic neurosurgery. Our experience confirms the emerging trend in recent years in the surgical treatment of Parkinson’s disease and other extrapyramidal movement disorders—a more balanced approach to the possibility of using not only stimulation but also (when necessary and considering potential risks) destructive functional neurosurgery. For example, unilateral pallidotomy affecting the posteroventral sections GPi in patients with Parkinson’s disease can be considered an effective and safe surgical method for treating drug-induced dyskinesias, and unilateral VIM-thalamotomy – tremor. Unilateral destructive operations compared to the method DBS do not require the use of expensive stimulation systems and constant patient monitoring for stimulation parameter adjustment, no risk of infectious complications and hardware issues, this procedure is safe and suitable for elderly patients, and it is accessible for patients living far from specialized movement disorder centers

Currently, many authors agree that destructive surgeries for extrapyramidal pathology are quite viable, especially when it comes to unilateral interventions. It is evident that the further development of non-invasive MRgFUS technology (see below) significantly expands the potential of ablative surgery. Ultimately, the rational choice of surgical treatment method for a specific disease in a particular patient (considering the available conditions), the experience of the surgeon and the relevant center, as well as the possibility of combining different technologies, become crucial.