Advanced Imaging and Direct Targeting of the Motor Thalamus and Dentato-Rubro-Thalamic Tract for Tremor: A Systematic Review.

Direct targeting methods for stereotactic neurosurgery in the treatment of essential tremor have been the subject of active research over the past decade but have not yet been systematically reviewed. We present a clinically oriented topic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses Group guidelines. Our focus is studies using advanced magnetic resonance imaging (MRI) techniques (ultrahigh-field structural MRI, diffusion-weighted imaging, diffusion-tensor tractography, and functional MRI) for patient specific, in vivo identification of the ventral intermediate nucleus and the dentato-rubro-thalamic tract.

Deep Brain Stimulation of the Dentato-Rubro-Thalamic Tract: Outcomes of Direct Targeting for Tremor.

OBJECTIVES: Targeting the dentato-rubro-thalamic tract (DRTt) has been suggested to be efficacious in deep brain stimulation (DBS) for tremor suppression, both in case reports and post-hoc analyses. This prospective observational study sought to analyze outcomes after directly targeting the DRTt in tremor patients. METHODS: 20 consecutively enrolled intention tremor patients obtained pre-operative MRI with diffusion tensor (dTi) sequences. Mean baseline tremor amplitude based on The Essential Tremor Rating Assessment Scale was recorded. The DRTt was drawn for each individual on StealthViz software (Medtronic) using the dentate nucleus as the seed region and the ipsilateral pre-central gyrus as the end region and then directly targeted during surgery. Intraoperative testing confirmed successful tremor control. Post-operative analysis of electrode position relative to the DRTt was performed, as was post-operative assessment of tremor improvement. RESULTS: The mean age of patients was 66.8 years; mean duration of tremor was 16 years. Mean voltage for the L electrode = 3.4 V; R = 2.6 V. Mean distance from the center of the active electrode contact to the DRTt was 0.9 mm on the L, and 0.8 mm on the R. Improvement in arm tremor amplitude from baseline after DBS was significant (P < 0.001). CONCLUSION: Direct targeting of the DRTt in DBS is an effective strategy for tremor suppression. Accounting for hardware, software, and model limitations, depiction of the DRTt allows for placement of electrode contacts directly within the fiber tract for modulation despite any anatomical variation, which reproducibly resulted in good tremor control.

The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation.

OBJECT The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans. METHODS The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1-Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler's method. RESULTS The authors identified the "classic" decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle. CONCLUSIONS The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles.

The cerebellum is necessary for rabbit classical eyeblink conditioning with a non-somatosensory (photic) unconditioned stimulus.

The present research investigated the acquisition of classically conditioned eyeblinks in rabbits using a light flash unconditioned stimulus (US), as well as the contribution of deep cerebellar nuclei to such an association. Two independent groups of animals experienced three phases of training: (1) pre-lesion delay conditioning using either a light- (Group 1) or an air puff-US (Group 2), (2) post-lesion testing of response performance, and (3) post-lesion acquisition to the opposite US. During the initial acquisition (720 trials), the groups did not differ with regard to their rate of learning or their overall level of responding. To assess the contribution of the cerebellum to the maintenance of responding, the interpositus nucleus was electrolytically lesioned and animals were given 8 days of additional training. Both groups exhibited a profound reduction in conditioned responding (CR) and showed no signs of recovery over the remainder of this phase (480 trials). Animals were then shifted to the opposite US (same eye) and given 12 days of training to assess the effect of interpositus lesions on the acquisition of CRs to a novel US. No learning was observed during this phase, regardless of whether animals experienced the light- or air puff-US. These results demonstrate: (1) the ability of a non-somatosensory stimulus to serve as a US during classical eyeblink conditioning; and (2) a common reliance on deep cerebellar nuclei for both somatosensory- and non-somatosensory-based reflexive motor learning. The findings are discussed in reference to the processing of conditioning stimuli within the brainstem-cerebellar circuitry that underlies eyeblink conditioning.

[The effect of damage to the cerebellar nuclei on acquired motor coordination in dogs]. / Vliianie povrezhdeniia iader mozzhechka na vyrabotannuiu dvigatel'nuiu koordinatsiiu u sobak.

In the experiments was studied the role of the cerebellar nuclei (n. dentatus and n. interpositus) in the realization of a conditioned motor coordination in dogs. Destruction of the cerebellar nuclei leads to disturbances of the conditioned precision movement of a forelimb and of the conditioned coordination of movements of a head decline to a feeding cap and a forelimb flexion. All the disturbances are of a reversible character. Elaboration of a new coordination is connected with the reorganization of the initial motor coordination. During the first experiments after the destruction of the cerebellar nuclei the reorganized coordination relations return to the initial ones. The cerebellum was suggested to participate in the formation and realization of the motor coordination under study.

[Stereotaxic surgery in infantile cerebral palsy]. / Stereotaksicheskie operatsii pri detskom tserebal'nom paraliche.

The article analyses the results of 439 stereotaxic operations performed on 326 patients with the spastic-hyperkinetic form of infantile cerebral paralysis (ICP). Differentiated destructions of the brain structures were conducted. Extended thalamotomy, sagittal thalamotomy, and combined (cross) thalamodentatotomy were the most frequent complexes of destructions. Essential diminution of hyperkineses and hypertonia was noted in 86 and 81% of patients, respectively, in the immediate postoperative periods; the condition of 70% of patients improved in the late-term periods as compared to that in the preoperative period. Combined (cross) thalamodentatomy was found to be the most effective operative intervention.

[Neurosurgical anatomy of Forel's field H as applied to campotomy]. / Neirokhirurgicheskaia anatomiia polia Forelia H primenitel'no k campotomii.

Based on a study of 100 specimens of the brain of adult humans, data are presented on the variability of the shape and size of Forel's H field and its position in relation to intercerebral orienting points depending on the length of the intercommissural line and the breadth of the cerebral hemisphere and third ventricle. The stereotaxic coordinates, the shape and size of the foci of destruction for campotomy are given with due consideration for the individual anatomical features of the H field.

Clinical, physiological and philosophical implications of innovative brain surgery in humans.

Abnormal states of motor behaviour can be reversed by interruption of facilitating mechanisms and augmentation of inhibitory mechanisms. Similarly, psychological and emotional behaviours which were abnormal due to disinhibition, such as screaming, repetitive speech and aggressive violent behaviour, have been favourably affected from a clinical and sociological standpoint. The mechanisms of the facilitatory and inhibitory systems which modulate motor behaviour also modify psychological and emotional behaviour. The findings of our studies in experimental neurosurgery may help to provide new insights into mechanisms of mental capacity and behaviour.

[Clinical physiological effects of electrostimulation and destruction of the ventrolateral portions of the cerebellar dentate nuclei in different forms of motor pathology]. / Kliniko-fiziologicheskie éffekty élektrostimuliatsii i destruktsii ventro-lateral'nykh otdelov zubchatykh iader mozzhechka pri razlichnykh formakh dvigatel'noi patologii.

The effect of electrostimulation and destruction of the ventrolateral parts of the cerebellar dentate nuclei is described on the basis of 27 dentotomies performed on patients with different forms of motor pathology. The dento-cortical connections were studied by advancing electrodes to the cerebral and cerebellar cortex through trephination openings made in the postero-frontal-parasagittal area for ventriculography and in the occipital area for the insertion of a stereotaxic cannula. It was found that the principal test for operative identification of the ventro-oral parts of the dentate nucleus in electrostimulation are motor reactions and changes in the muscular tonus in the homolateral limbs and reactions of the cortex of the central and precentral areas of the cerebral hemispheres revealed by electrocorticography. The main clinical effect produced by the destruction of these parts of the dentate nuclei is diminution of the spastic component of muscular hypertonus; hardly any effect is caused on the rigidity component. Redistribution of muscular tonus is among the factors inducing postoperative changes in hyperkinesia.

Neurosurgical treatment of the dyskinesias.

I have attempted to review what I consider to be the principal conclusions of a 25 year study of the neurosurgical treatment of the dyskinesias. The concept that the pathological disinhibition which is responsible for the production of these syndromes can be modified by destructive lesions within the thalamus or by prosthetic mobilization of inhibitory mechanisms of the cerebellum is supported by the results presented in this report. Neurosurgical treatment of the dyskinesias is potentially a relatively safe and efficacious means of alleviating incapacitation of a large group of patients. However, meticulous attention to patient selection as well as adherence to the general principles of surgical technique which have been reviewed are essential if the full potential of these approaches is to be realized.

Stereotaxic neurosurgery in the management of cerebral palsy.

Ten children with cerebral palsy are presented on whom stereotaxic operations on the central nervous system were performed with the aim of ameliorating athetosis and spasticity. Tere were seven alert and co-operative children with spastic hemiplegia or diplegia, of whom six received benefit from thalamotomy or dentatotomy. The seventh, a child with diplegia, had improvement of his left lower limb, but the right became worse. One child with spastic diplegia, in whom a thoracic meningocoele had been closed at birth, was not improved by bilateral dentatotomy. Two severely quadriplegic children each had bilateral dentatotomy; one was a child with dystonic and spastic quadriplegia. In both cases the resulting reduction in tone and extensor spasm rendered the nursing of these patients much easier. The place of stereotaxic surgery in the central nervous system in the management of children with cerebral palsy is discussed. We suggest that in selected cases the stereotaxic operation should be performed early in order to gain the greatest benefit. Stereotaxic surgery should be regarded as an integral part of the management which involves close co-operation of paediatrician, physiotherapist, neurosurgeon and orthopaedic surgeon.