Retrosigmoid transhorizontal fissure approach to lateral pontine cavernous malformation: comparison to transpetrosal presigmoid retrolabyrinthine approach.

OBJECTIVE: The retrosigmoid (RS) approach is a classic route used to access deep-seated brainstem cavernous malformation (CM). The angle of access is limited, so alternatives such as the transpetrosal presigmoid retrolabyrinthine (TPPR) approach have been used to overcome this limitation. Here, the authors evaluated a modification to the RS approach, horizontal fissure dissection by using the RS transhorizontal (RSTH) approach. METHODS: Relevant clinical parameters were evaluated in 9 patients who underwent resection of lateral pontine CM. Cadaveric dissection was performed to compare the TPPR approach and the RSTH approach. RESULTS: Five patients underwent the TPPR approach, and 4 underwent the RSTH approach. Dissection of the horizontal fissure allowed for access to the infratrigeminal safe entry zone, with a direct trajectory to the middle cerebellar peduncle similar to that used in TPPR exposure. Operative time was longer in the TPPR group. All patients had a modified Rankin Scale score ≤ 2 at the last follow-up. Cadaveric dissection confirmed increased anteroposterior working angle and middle cerebellar peduncle exposure with the addition of horizontal fissure dissection. CONCLUSIONS: The RSTH approach leads to a direct lateral path to lateral pontine CM, with similar efficacy and shorter operative time compared with more extensive skull base exposure. The RSTH approach could be considered a valid alternative for resection of selected pontine CM.

A Case of Dentatotomy for Pain and Spasticity and Systematic Review.

BACKGROUND: Surgical interventions for spasticity aim to improve motor function and pain in cases that are refractory to medical treatment. Ablation of the cerebellar dentate nucleus (dentatotomy) may be a useful alternative. CASE REPORT: A 55-year-old male patient with spasticity, secondary to a traumatic cervical spinal cord injury with quadriparesis, had bilateral lumbar DREZotomy with an improvement that lasted for 6 years. Ten years after the DREZotomy, a progressive increased spasticity manifested as spastic diplegia (Ashworth 4) and spontaneous muscle painful spasms (Penn 4), as well as spasticity in the upper extremities, predominantly on the right side (Ashworth 3). A right radio frequency dentatotomy was performed with intraoperative electrophysiological monitoring. Spasticity scales were applied at the following times: preoperative and at 1 and 8 months after surgery. During the first month, the patient presented a clear decrease in spasticity ipsilateral to the side of lesioning (Ashworth 1) and of painful spasms in the lower extremities (Penn 1). After 8 months, spasticity ipsilateral to the injury decreased even more to Ashworth (0), but a progressive increase in muscle spasms of lower extremities was observed (Penn 2). CONCLUSION: Stereotactic dentatotomy may be an effective surgical alternative for management of spasticity associated with painful spasms in selected patients.

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.

Distance between Active Electrode Contacts and Dentatorubrothalamic Tract in Patients with Habituation of Stimulation Effect of Deep Brain Stimulation in Essential Tremor.

Background Some patients under thalamic deep brain stimulation (DBS) for essential tremor (ET) experience habituation of tremor reduction. The nucleus ventralis intermedius (Vim) is the current main target side for ET in DBS. However, the dentatorubrothalamic tract (DRTT) is considered the relevant structure to stimulate. We investigated the distance between the active contact of the DBS electrode and the DRTT and compared this distance in patients with habituation of tremor reduction and good responders. Material and Methods In this retrospective study, we performed deterministic fiber tracking of the DRTT in 6 patients (12 hemispheres) with ET who underwent DBS in the Vim. We subsequently measured the distance between the active contact of the electrode and the ipsilateral DRTT in both hemispheres. The clinical tremor response of those 6 patients was analyzed accordingly. Results The distance between the active contact and the DRTT in patients with better and constant clinical tremor reduction was shorter (mean distance: 2.9 ± 2.2 mm standard deviation [SD]) than in patients who showed habituation of their response (mean distance: 6.1 ± 3.9 mm SD). After re-placement of a thalamic electrode inside the DRTT in one patient who experienced unsatisfying tremor reduction due to habituation of stimulation, the tremor alleviation was significant and persistent at a 13-month follow-up. Conclusion This retrospective analysis suggests that recurrence of ET tremor under chronic DBS might be associated with a larger distance between the DRTT and the active lead contact, in comparison with the smaller distances in patients with persistently good tremor control.

Case Study of Image-Guided Deep Brain Stimulation: Magnetic Resonance Imaging-Based White Matter Tractography Shows Differences in Responders and Nonresponders.

BACKGROUND: The caudal zona incerta (cZI) is an increasingly popular deep brain stimulation (DBS) target for the treatment of tremor-predominant disease. The dentatorubrothalamic tract (DRTT) is a white matter fiber bundle that traverses the cZI and can be identified using diffusion-weighted magnetic resonance imaging fiber tractography to ascertain its precise course. In this report, we compare 2 patient cases of cZI DBS, a responder and a nonresponder. CASE DESCRIPTION: Patient 1 (responder) is a 65-year-old man with medically refractory Parkinson disease who underwent bilateral DBS lead placement in the cZI. Postoperatively he demonstrated >90% reduction in baseline tremor and was not limited by stimulation side effects. Postoperative imaging showed correct lead placement in the cZI. Tractography revealed a DRTT within the field of stimulation, bilaterally. Patient 2 (nonresponder) is a 61-year-old man with medically refractory Parkinson disease who also underwent bilateral DBS lead placement in the cZI. He initially demonstrated >90% reduction in baseline tremor but developed disabling dystonia of his left leg and significant slurring of his speech in the months after surgery. Postoperative imaging showed bilateral lead placement in the cZI. Right-sided electrode revision was recommended and resulted in relief of tremor and reduced dystonic side effects. Tractography analysis of the original leads revealed a DRTT with an atypical anterior trajectory and a location outside the field of stimulation. Tractography analysis of the revised lead showed a DRTT within the field of stimulation. CONCLUSIONS: Preoperative diffusion-weighted magnetic resonance imaging fiber tractography imaging of the DRTT has the potential to improve and individualize DBS planning.

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.

Three-dimensional microsurgical anatomy of cerebellar peduncles.

The microsurgical anatomy of cerebellar peduncles and their relationships with neighbouring fasciculi were investigated by using a fibre dissection technique. As the dissection progressed, photographs of each progressive layer were obtained and stereoscopic images were created using the 3D anaglyphic method. These findings provided the anatomical basis for a conceptual division of cerebellar peduncles into segments. The middle cerebellar peduncle (MCP) was divided into two segments: cisternal and intracerebellar segments. The inferior cerebellar peduncle (ICP) was divided into three segments: cisternal, ventricular and intracerebellar segments. The superior cerebellar peduncle (SCP) was divided into three segments: intracerebellar, intermediate and intrategmental segments. The fibre dissection technique disclosed a constant course of peduncular fibres inside the white core of the cerebellum. The pontocerebellar fibres of the MCP pass over and laterally to the bundles of the ICP and SCP. The centripetal fibres of the ICP wrap around the radiation of the SCP and the dentate nucleus, directed towards the cortex of the vermis. The centrifugal bundle of the SCP ascends towards the mesencephalon where it sinks passing below the fibres the lateral lemniscus. The knowledge gained by studying the intrinsic anatomy of the cerebellum is useful to accomplish appropriate surgical planning and, ultimately, to understand the repercussions of surgical procedures on the white matter tracts in this region.

Cerebellar anatomy as applied to cerebellar microsurgical resections / Anatomia cerebelar aplicada à microcirurgia cerebelar ablativa

OBJECTIVE: To define the anatomy of dentate nucleus and cerebellar peduncles, demonstrating the surgical application of anatomic landmarks in cerebellar resections. METHODS: Twenty cerebellar hemispheres were studied. RESULTS: The majority of dentate nucleus and cerebellar peduncles had demonstrated constant relationship to other cerebellar structures, which provided landmarks for surgical approaching. The lateral border is separated from the midline by 19.5 mm in both hemispheres. The posterior border of the cortex is separated 23.3 mm from the posterior segment of the dentate nucleus; the lateral one is separated 26 mm from the lateral border of the nucleus; and the posterior segment of the dentate nucleus is separated 25.4 mm from the posterolateral angle formed by the junction of lateral and posterior borders of cerebellar hemisphere. CONCLUSIONS: Microsurgical anatomy has provided important landmarks that could be applied to cerebellar surgical resections.

OBJETIVO: Definir a anatomia do núcleo denteado e dos pedúnculos cerebelares, demonstrando a aplicação dos marcos anatômicos em cirurgias cerebelares. MÉTODOS: Foram estudados 20 hemisférios cerebelares. RESULTADOS: A maioria dos núcleos denteados e pedúnculos cerebelares demonstraram relação anatômica constante com outras estruturas cerebelares, fato que proporcionou o estabelecimento de marcos anatômicos específicos a serem utilizados em acessos cirúrgicos. O bordo lateral do núcleo denteado é separado da linha média em 19,5 mm em ambos os hemisférios cerebelares. O bordo posterior do córtex é separado do segmento posterior do núcleo denteado por 23,3 mm. O bordo lateral do córtex é separado do bordo lateral do núcleo por 26 mm e o segmento posterior do núcleo denteado é separado por 25,4 mm do ângulo posterolateral, que é formado pela junção dos bordos lateral e posterior do hemisfério cerebelar. CONCLUSÕES: O estudo da anatomia microcirúrgica proporcionou o estabelecimento de marcos anatômicos importantes que podem ser utilizados durante cirurgias cerebelares ablativas.

A role of diffusion tensor imaging fiber tracking in deep brain stimulation surgery: DBS of the dentato-rubro-thalamic tract (drt) for the treatment of therapy-refractory tremor.

INTRODUCTION: Deep brain stimulation (DBS) can alleviate tremor of various origins. A number of regions are targeted. In recent work our group was able to show the involvement of the dentato-rubro-thalamic tract (drt) in tremor control with fiber tracking techniques. Here we report for the first time the successful use of magnetic resonance tractography in combination with traditional landmark-based targeting techniques to perform the implantation of a bilateral DBS system in a patient with dystonic head tremor. METHODS: We report on a 37-year-old female with long-standing pure head tremor from myoclonus dystonia. She was identified as a candidate for thalamic DBS. The use of head fixation in a stereotactic frame would blur target symptoms (head tremor) during surgery and was therefore avoided. Her dentate-rubro-thalamic tracts were visualized with preoperative diffusion tensor imaging (DTI) and tractography, and then directly targeted stereotactically with DBS electrodes. RESULTS: Three months after implantation, tremor control was excellent (>90%). A close evaluation of the active electrode contact positions revealed clear involvement of the drt. CONCLUSION: This is the first time that direct visualization of fiber tracts has been employed for direct targeting and successful movement disorder tremor surgery. In the reported case, additional knowledge about the position of the drt, which previously has been shown to be a structure for modulation to achieve tremor control, led to a successful implantation of a DBS system, although there was a lack of intra-operatively testable tremor symptoms. In concordance with studies in optogenetic neuromodulation, fiber tracts are the emerging target structures for DBS. The routine integration of DTI tractography into surgical planning might be a leading path into the future of DBS surgery and will add to our understanding of the pathophysiology of movement disorders. Larger study populations will have to prove these concepts in future research.

Extracerebellar progenitors grafted to the neurogenic milieu of the postnatal rat cerebellum adapt to the host environment but fail to acquire cerebellar identities.

Stem or progenitor cells acquire specific regional identities during early ontogenesis. Nonetheless, there is evidence that cells heterotopically transplanted to neurogenic regions of the developing or mature central nervous system may switch their fate to adopt host-specific phenotypes. Here, we isolated progenitor cells from different germinative sites along the neuraxis where GABAergic interneurons are produced (telencephalic subventricular zone, medial ganglionic eminence, ventral mesencephalon and dorsal spinal cord), and grafted them to the prospective white matter of the postnatal rat cerebellum, at the time when local interneurons are generated. The phenotype acquired by transplanted cells was assessed by different criteria, including expression of region-specific transcription factors, acquisition of morphological and neurochemical traits, and integration in the cerebellar cytoarchitecture. Regardless of their origin, all the different types of donor cells engrafted in the cerebellar parenchyma and developed mature neurons that shared some morphological and neurochemical features with local inhibitory interneurons, particularly in the deep nuclei. Nevertheless, transplanted cells failed to activate cerebellar-specific regulatory genes. In addition, their major structural features, the expression profiles of type-specific markers and the laminar placement in the recipient cortex did not match those of endogenous interneurons generated during the same developmental period. Therefore, although exogenous cells are influenced by the cerebellar milieu and show remarkable capabilities for adapting to the foreign environment, they essentially fail to switch their fate, integrate in the host neurogenic mechanisms and adopt clear-cut cerebellar identities.

Impact of surgery and adjuvant therapy on balance function in children and adolescents with cerebellar tumors.

OBJECTIVES: This study examined the effects of posterior fossa tumor surgery and concomitant irradiation and/or chemotherapy on the long-term recovery of balance function in children and adolescent patients. SUBJECTS AND METHODS: 22 patients, treated during childhood for a benign (n = 14) or malignant cerebellar tumor (n = 8), were examined in chronic state (mean latency between surgery and testing: 7.7 years, range 3 - 17 years). Postural impairments were assessed with static and dynamic posturography. All cerebellar lesions were documented by standardized and normalized MRI data. Healthy age- and gender-matched subjects served as a control group. RESULTS: Comparing the balance function of (i) children with or without affected cerebellar nuclei and (ii) children with and without adjuvant chemotherapy and/or radiotherapy revealed that damage to the cerebellar nuclei had more impact on neurological impairment than concomitant tumor therapy. Balance abnormalities were most pronounced when a lesion affected the fastigial nucleus. Chemotherapy with its neurological side effect was associated with enhanced postural sway in only two children with malignant tumors. CONCLUSIONS: The study results indicate that the sparing of the deep cerebellar nuclei had the greatest impact on the recovery of balance function in pediatric patients treated for both a benign or malignant cerebellar tumor.

Palatal myoclonus induced by extirpation of a cerebellar astrocytoma. Case report.

A 45-year-old woman developed a rare case of palatal myoclonus with no other neurological signs after undergoing extirpation of a small cerebellar low-grade astrocytoma that was located in the right dentate nucleus. The palatal myoclonus has persisted for 4 years after the operation. Magnetic resonance T2-weighted imaging revealed a high-intensity lesion in the left inferior olive. Palatal myoclonus associated with the removal of cerebellar tumors is unusual but may easily be overlooked.

Cerebellorubral degeneration after resection of cerebellar dentate nucleus neoplasms: evaluation with MR imaging.

The authors describe the magnetic resonance (MR) findings in seven patients who developed severe cerebellar symptoms and atrophy of the contralateral red nucleus following removal of unilateral neoplasms in the deep nuclei of the cerebellum. For most patients, pre- and postoperative spin-echo MR images were obtained with long repetition times (TRs) at 1.5 T. The long TR images obtained before surgery demonstrated unilateral masses involving the dentate nucleus. Long TR images obtained after surgical resection of the dentate nucleus showed increased signal intensity in all of seven contralateral red nuclei, three of seven ipsilateral superior cerebellar peduncles, and two of seven contralateral inferior olivary nuclei. Three other patients who underwent surgery for cerebellar neoplasms without resection of the dentate nuclei showed no postoperative brain stem changes on MR images. The authors speculate that the changes in the contralateral red nuclei are due to cerebellorubral degeneration (since well-described neural tracts interconnect the dentate nucleus and the contralateral red nucleus). Injury of the dentate nucleus may result in degeneration of distant neural connections.

Stereotactic surgery for cerebral palsy.

The results of stereotactic surgery in 38 patients with cerebral palsy are reviewed. A total of 67 nuclei were approached and 109 stereotactic lesions performed. The motor disorders were spasticity, athetosis, dystonia and tremor. The targets were chosen according to the motor disorder, and included the pulvinar, ventrolateral (VL), sub-VL and cerebellar dentate, and a combination of 2 or 3 of these. The results of the surgery were evaluated on the basis of objective functional improvement using a scale for task achievement. Varying degrees of overall improvement were found in over 80% of the patients; these are discussed in detail.

[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.

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.

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.