Tag: Thalamus

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Multinuclear thalamic targeting with human stereotactic electroencephalography

J Neurosurg 142:936–944, 2025

The study details a novel stereotactic electroencephalography (sEEG) approach targeting thalamic nuclei for personalized epilepsy treatment. It describes surgical techniques for sampling thalamic regions, aiming to improve neuromodulation strategies. The focus is on minimizing electrodes and maximizing cortical and subcortical coverage.

Multinuclear Thalamic Targeting with sEEG

• Novel sEEG approach identifies personalized seizure networks in the thalamus.

• Multilead orthogonal and trans-massa intermedia trajectories efficiently sample thalamic nuclei.

• Long-axis trajectory samples lateral PLV, MD, and ANT with a single electrode.

• Approaches resulted in no complications in 34 patients.

• Thalamic nuclei are crucial for neuromodulation in refractory epilepsy.

• DBS of thalamic nuclei shows heterogeneous patient responses.

Surgical Techniques and Trajectories

• Orthogonal trajectories maximize mediolateral thalamic coverage.

• Trans-massa intermedia approach samples bilateral MD nuclei with a single electrode.

• Long-axis trajectory samples ANT, MD, and PLV in a single plane.

• Extraventricular trajectories optimize thalamic coverage and safety.

Patient Selection and Outcomes

• 34 patients with drug-resistant epilepsy underwent sEEG implantation.

• Postoperative analysis showed millimetric accuracy in electrode placement.

• No thalamic hemorrhage or edema observed postoperatively.

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Microsurgical anatomy and approaches to thalamic gliomas. Part 2: Maximal safe resection of thalamic gliomas improves outcomes.

J Neurosurg 141:1472–1483, 2024

As presented in Part 1 of this series, thalamic gliomas (TGs) are deep-seated, difficult-to-access tumors surrounded by vital neurovascular structures. Given their high operative morbidity, TGs have historically been considered inoperable lesions. Although maximal safe resection (MSR) has become the treatment standard for lobar and even deep-seated mediobasal temporal and insular gliomas, the eloquent location of TGs has precluded this management strategy, with biopsy and adjuvant treatment being the mainstay. The authors hypothesized that MSR can be achieved with low morbidity and mortality for TGs, thus resulting in improved outcomes.

METHODS A retrospective single-center study was performed on all TG patients from 2006 to 2020. Clinical, imaging, and pathology reports were obtained. Univariate and multivariate analyses were performed to determine prognostic variables. Case examples illustrate various approaches and the rationale for staging resections of more complex TGs.

RESULTS A total of 42 patients (26 males, 16 females), among them 12 pediatric (29%) cases, were included. Their mean age was 36.0 ± 21.4 (median 30, range 3–73) years. The median maximal tumor diameter was 45 (range 19–70) mm. Eighteen patients (43%) had a prior stereotactic needle tumor biopsy, with the ultimate diagnosis changed for 7 patients (39%) following microsurgical resection. The most common surgical approaches were transtemporal (29%), anterior interhemispheric transcallosal (29%), and superior parietal lobule (25%). Overall, the combined subtotal and grosstotal resection rate was 95% (n = 40). Low-grade gliomas (LGGs; grades I and II) comprised one-third of the group, whereas half of the patients had glioblastoma multiforme. There were no operative mortalities. Although temporary postoperative motor deficits were observed in 12 patients (28.6%), all improved during the early postoperative period except 1 (2.4%), who had mild residual hemiparesis. Two patients required CSF diversion for hydrocephalus. The 2-year overall survival rate was 90% for LGG patients and 15% for high-grade glioma (HGG) patients. Multivariate analysis revealed that histological grade, age, and extent of resection were independent prognostic factors associated with survival.

CONCLUSIONS Management of TGs is challenging, with resection avoided by many, if not most, neurosurgeons, especially for HGGs. The results reported here demonstrate improved outcomes with resection, particularly in younger LGG patients. The authors therefore advocate for MSR for a select cohort of TG patients using carefully planned surgical approaches, contemporary intraoperative adjuncts, and meticulous microsurgical techniques.

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Microsurgical anatomy and approaches to thalamic gliomas. Part 1

J Neurosurg 141:1457–1471, 2024

The selection of appropriate microsurgical approaches to treat thalamic pathologies is currently largely subjective. The objective of this study was to provide a structured cartography map for surgical navigation to treat gliomas involving different surfaces of the thalamus.

METHODS Fifteen formalin-fixed, silicone-injected cadavers (30 sides) were dissected, and 10 adult brain specimens (20 sides) were used to illustrate thalamic microsurgical anatomy using the Klingler fiber dissection technique. Exposures and trajectories for the six most common microsurgical approaches were depicted using MR data from healthy subjects converted into surface-rendered 3D virtual brain models. Additionally, thalamic surfaces exposed with all six approaches were color mapped on the virtual 3D model and compared side-by-side in 360° views with previously reported microsurgical approaches. These 3D models were then used in conjunction with topographic data to guide cadaveric dissection steps.

RESULTS There are two general surgical routes to thalamic lesions: the subarachnoid transcisternal and transcortical routes. The transcisternal route consists of the following three approaches: 1) anterior interhemispheric transcallosal approach, which exposes the anterior and superior thalamus; 2) posterior interhemispheric transcallosal approach, which exposes the posterosuperior thalamus; and 3) supracerebellar infratentorial approach, which exposes the posteromedial cisternal thalamus and can be extended laterally to approach the posterolateral thalamus by cutting the tentorium. The three transcortical approaches are the 1) superior parietal lobule approach, which exposes the posterosuperior thalamus and is particularly advantageous in the setting of hydrocephalus; 2) transtemporal gyrus approach, which exposes the inferolateral thalamus; and 3) transsylvian transinsular approach, which exposes the lateral thalamus (slightly more superiorly and posteriorly) and is advantageous for pathologies extending laterally into the peduncle, lenticular nucleus, or insula.

CONCLUSIONS Microsurgical approaches to thalamic gliomas continue to be challenging. Nonetheless, safe and effective cisternal, ventricular, and cortical corridors can be developed with thoughtful planning, anatomical understanding, and knowledge of the advantages, risks, and limitations of each approach. In some cases, it is wise to combine these approaches with staged procedures, as the authors demonstrate in Part 2. In Part 1 of this two-part series, they discuss thalamic microsurgical anatomy and illustrate the trajectory and exposures of all six approaches to guide decision-making. Part 2 discusses their thalamic glioma microsurgical case series, which utilizes these microsurgical approaches.

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A taxonomy for deep cerebral cavernous malformations: subtypes of thalamic lesions

J Neurosurg 139:1681–1696, 2023

Anatomical taxonomy is a practical tool to successfully guide clinical decision-making for patients with brain arteriovenous malformations and brainstem cavernous malformations (CMs). Deep cerebral CMs are complex, difficult to access, and highly variable in size, shape, and position. The authors propose a novel taxonomic system for deep CMs in the thalamus based on clinical presentation (syndromes) and anatomical location (identified on MRI).

METHODS The taxonomic system was developed and applied to an extensive 2-surgeon experience from 2001 through 2019. Deep CMs involving the thalamus were identified. These CMs were subtyped on the basis of the predominant surface presentation identified on preoperative MRI. Six subtypes among 75 thalamic CMs were defined: anterior (7/75, 9%), medial (22/75, 29%), lateral (10/75, 13%), choroidal (9/75, 12%), pulvinar (19/75, 25%), and geniculate (8/75, 11%). Neurological outcomes were assessed using modified Rankin Scale (mRS) scores. A postoperative score ≤ 2 was defined as a favorable outcome and > 2 as a poor outcome. Clinical and surgical characteristics and neurological outcomes were compared among subtypes.

RESULTS Seventy-five patients underwent resection of thalamic CMs and had clinical and radiological data available. Their mean age was 40.9 (SD 15.2) years. Each thalamic CM subtype was associated with a recognizable constellation of neurological symptoms. The common symptoms were severe or worsening headaches (30/75, 40%), hemiparesis (27/75, 36%), hemianesthesia (21/75, 28%), blurred vision (14/75, 19%), and hydrocephalus (9/75, 12%). The thalamic CM subtype determined the selection of surgical approach. A single approach was associated with each subtype for most patients. The main exception to this paradigm was that in the surgeons’ early experience, pulvinar CMs were resected through a superior parietal lobule–transatrial approach (4/19, 21%), which later evolved to the paramedian supracerebellar-infratentorial approach (12/19, 63%). Relative outcomes implied by mRS scores were unchanged or improved in most patients (61/66, 92%) postoperatively.

CONCLUSIONS This study confirms the authors’ hypothesis that this taxonomy for thalamic CMs can meaningfully guide the selection of surgical approach and resection strategy. The proposed taxonomy can increase diagnostic acumen at the patient bedside, help identify optimal surgical approaches, enhance the clarity of clinical communications and publications, and improve patient outcomes.

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Parietal trans‑sulcal para‑fascicular approach to lateral thalamic/internal capsule cavernous malformation

Acta Neurochirurgica (2021) 163:2497–2501

The surgical management of deep brain lesions is challenging, with significant morbidity. Advances in surgical technology have presented the opportunity to tackle these lesions.

Methods We performed a complete resection of a thalamic/internal capsule CM using a tubular retractor system via a parietal trans-sulcal para-fascicular (PTPF) approach without collateral injury to the nearby white matter tracts.

Conclusion PTPF approach to lateral thalamic/internal capsule lesions can be safely performed without injury to eloquent white matter fibres. The paucity of major vessels along this trajectory and the preservation of lateral ventricle integrity make this approach a feasible alternative to traditional approaches.

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What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center

J Neurosurg 135:619–628, 2021

In the absence of a standard or guideline for the treatment of epilepsy patients with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT), systematic single-center investigations are essential to establish effective approaches. Here, the authors report on the long-term results of one of the largest single-center ANT DBS cohorts.

METHODS The outcome data of 23 consecutive patients with transventricularly implanted electrodes were retrospectively analyzed with regard to adverse events, lead placement, stimulation-related side effects, and changes in seizure frequency. Depression and quality-of-life scores were collected in a subgroup of 9 patients.

RESULTS All but 2 patients initially underwent bilateral implantation, and 84.4% of all DBS leads were successfully located within the ANT. The mean follow-up time was 46.57 ± 23.20 months. A seizure reduction > 50% was documented in 73.9% of patients, and 34.6% achieved an Engel class I outcome. In 3 patients, clinical response was achieved by switching the electrode contact or changing from the monopolar to bipolar stimulation mode. Unilateral implantation seemed ineffective, whereas bilateral stimulation with successful ANT implantation only on one side led to a clinical response. Double stimulation with additional vagus nerve stimulation was safe. Changes in cycling mode or stimulation amplitude influenced therapy tolerability and, only to a lesser extent, seizure frequency. Side effects were rare and typically vanished by lowering the stimulation amplitude or changing the active electrode contact. Furthermore, depression and aspects of quality of life significantly improved with ANT DBS treatment.

CONCLUSIONS The transventricular approach as well as double stimulation proved safe. The anteroventral ANT appeared to be the most efficacious stimulation site. This systematic investigation with reluctant medication changes allowed for the development of a better idea of the association between parameter changes and outcome in ANT DBS patients, but larger samples are still needed to assess the potential of bipolar stimulation and distinct cycling frequencies. Furthermore, more multifaceted and objective assessments of treatment outcome are needed to fully assess the effects of ANT DBS treatment.

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Microneurosurgical removal of thalamic lesions: surgical results and considerations from a large, single-surgeon consecutive series

J Neurosurg 135:458–468, 2021

The object of this study was to present the surgical results of a large, single-surgeon consecutive series of patients who had undergone transcisternal (TCi) or transcallosal-transventricular (TCTV) endoscope-assisted microsurgery for thalamic lesions.

METHODS This is a retrospective study of a consecutive series of patients harboring thalamic lesions and undergoing surgery at one institution between February 2007 and August 2019. All surgical and patient-related data were prospectively collected. Depending on the relationship between the lesion and the surgically accessible thalamic surfaces (lateral ventricle, velar, cisternal, and third ventricle), one of the following surgical TCi or TCTV approaches was chosen: anterior interhemispheric transcallosal (AIT), posterior interhemispheric transtentorial subsplenial (PITS), perimedian supracerebellar transtentorial (PeST), or perimedian contralateral supracerebellar suprapineal (PeCSS). Since January 2018, intraoperative MRI has also been part of the protocol. The main study outcome was extent of resection. Complete neurological examination took place preoperatively, at discharge, and 3 months postoperatively. Descriptive statistics were calculated for the whole cohort.

RESULTS In the study period, 92 patients underwent surgery for a thalamic lesion: 81 gliomas, 6 cavernous malformations, 2 germinomas, 1 metastasis, 1 arteriovenous malformation, and 1 ependymal cyst. In none of the cases was a transcortical approach adopted. Thirty-five patients underwent an AIT approach, 35 a PITS, 19 a PeST, and 3 a PeCSS. The mean follow-up was 38 months (median 20 months, range 1–137 months). No patient was lost to follow-up. The mean extent of resection was 95% (median 100%, range 21%–100%), and there was no surgical mortality. Most patients (59.8%) experienced improvement in their Karnofsky Performance Status. New permanent neurological deficits occurred in 8 patients (8.7%). Early postoperative (< 3 months after surgery) problems in CSF circulation requiring diversion occurred in 7 patients (7.6%; 6/7 cases in patients with high-grade glioma).

CONCLUSIONS Endoscope-assisted microsurgery allows for the removal of thalamic lesions with acceptable morbidity. Surgeons must strive to access any given thalamic lesion through one of the four accessible thalamic surfaces, as they can be reached through either a TCTV or TCi approach with no or minimal damage to normal brain parenchyma. Patients harboring a high-grade glioma are likely to develop a postoperative disturbance of CSF circulation. For this reason, the AIT approach should be favored, as it facilitates a microsurgical third ventriculocisternostomy and allows intraoperative MRI to be done.

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Gamma Knife central lateral thalamotomy for the treatment of neuropathic pain

J Neurosurg 135:228–236, 2021

The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain.

METHODS Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol–5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months.

RESULTS Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8–10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8–10) to 5.5 (mean -41.33%, p = 0.01). MPQ scores significantly decreased (mean -22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean -16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively.

CONCLUSIONS Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.

 

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Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

Neurosurgery DOI:10.1093/neuros/nyaa141

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.

OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.

METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MTT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps. RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r 2 = 0.24, P = .01) and is ∼30% smaller (P = .015) in responders than in non-responders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot. C

CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

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Stereotactic radiosurgery for arteriovenous malformations of the basal ganglia and thalamus: an international multicenter study

J Neurosurg 132:122–131, 2020

Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.

METHODS The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation- induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.

RESULTS The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).

CONCLUSIONS SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

 

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Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy

Neurosurgery 84:160–168, 2019

Focused ultrasound thalamotomy (FUS-T) was recently approved for the treatment of refractory essential tremor (ET). Despite its noninvasive approach, FUS-T reinitiated concerns about the adverse effects and long-term efficacy after lesioning.

OBJECTIVE: To prospectively assess the outcomes of FUS-T in 10 ET patients using tractography-based targeting of the ventral intermediate nucleus (VIM).

METHODS: VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo, were assessed independently by the Tremor Research Group.We analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilisitic tractography. Quantitative diffusionweighted imaging changes were also studied in fiber tracts of interest.

RESULTS: The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3mo(tremor score: 18.3±6.9 vs 8.1±4.4, P=.001).Nomotorweakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex.

CONCLUSION: This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes.

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Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes

Neurosurgery 83:76–85, 2018

Thalamic glioblastomas (GBMs) represent a significant neurosurgical challenge. In view of the low incidence of these tumors, outcome data and management strategies are not well defined.

OBJECTIVE: To identify the natural history and factors associated with survival in patients with thalamic glioblastoma.

METHODS: A retrospective review of all patients with thalamic glioblastoma over a 10-yr period was performed. Presenting clinical, radiological, and outcome data were collected. Chi-squared and Fisher’s exact tests were used to compare clinical characteristics across tumor groups. Cox proportional hazard models were utilized to investigate variables of interest with regard to overall survival.

RESULTS: Fifty-seven patients met inclusion criteria, with a median age of 53 and median Karnofsky Performance Scale (KPS) score of 80. The most common presenting symptoms were weakness, confusion, and headache. Hydrocephalus was present in 47% of patients preoperatively. Stereotactic biopsy was performed in 47 cases, and 10 patients underwent craniotomy. The median overall survival was 12.2 mo. Higher KPS, younger age, and cerebrospinal fluid (CSF) diversionwere correlatedwith better overall survival univariately, respectively, while the presence of language deficits at initial presentation was associated with poorer survival. In multivariate analysis, the only significant predictor of survival was presenting KPS.

CONCLUSION: The overall survival of patients with thalamic glioblastoma is comparable to unresectable lobar supratentorial GBMs. Younger patients and those with good presenting functional status had improved survival. Midbrain involvement by the tumor is not a negative prognostic factor. Improved therapies are needed, and patients should be considered for early trial involvement and aggressive upfront therapy.

 

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Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound

J Neurosurg 128:875–884, 2018

Ultrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal.

METHODS Ten Yorkshire swine (Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage.

RESULTS LIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (~ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage.

CONCLUSIONS These results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.

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Clinical course of untreated thalamic cavernous malformations: hemorrhage risk and neurological outcomes

J Neurosurg 127:480–491, 2017

The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs.

METHODS This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed.

RESULTS A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (c2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336–5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275–4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic presentation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272–9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815–6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023–15.855, p < 0.001) had a greater chance of worsened neurological status.

CONCLUSIONS This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

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The nondecussating pathway of the dentatorubrothalamic tract in humans

The nondecussating pathway of the dentatorubrothalamic tract in humans

J Neurosurg 124:1406–1412, 2016

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.

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Endovascular Management of Deep Arteriovenous Malformations

Endovascular management AVM

Neurosurgery 78:34–41, 2016

The management of arteriovenous malformations (AVMs) in the basal ganglia, insula, and thalamus is demanding for all treatment modalities.

OBJECTIVE: To define safety and outcomes of embolization used as a stand-alone therapy for deep-seated AVMs.

METHODS: A cohort of 22 patients with AVMs located in the basal ganglia, thalamus, and insula who underwent embolization between January 2008 and December 2013.

RESULTS: Eighteen of 22 (82%) patients had anatomic exclusion. The mean size was 2.98 6 1.28 cm, and the mean number of sessions was 2.1 per patient. Most patients presented with hemorrhage (82%, n = 18), and 3 (14%) patients were in a deteriorated neurological status (modified Rankin Scale .2) at presentation. Sixty-eight percent of ruptured AVMs had size #3 cm. A single transarterial approach was performed in 9 (41%) cases, double catheterization was used in 4 (18%), and the transvenous approach was required in 8 (36%) cases. Procedure-related complications were registered in 3 (14%) cases. One death was associated with treatment, and complementary radiosurgery was required in 2 (9%) patients.

CONCLUSION: Embolization therapy appears to be safe and potentially curative for certain deep AVMs. Our results demonstrate a high percentage of anatomic obliteration with rates of complications that may approach radiosurgery profile. In particular, embolization as stand-alone therapy is most suitable to deep AVMs with small nidus size (#3 cm) and/or associated with single venous drainage in which microsurgery might not be indicated.

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Deep Brain Stimulation in Gilles de la Tourette Syndrome

Deep Brain Stimulation in Gilles de la Tourette Syndrome

Neurosurgery 78:91–100, 2016

Gilles de la Tourette syndrome (GTS) is a severe neuropsychiatric disorder with childhood onset, characterized by disabling motor and vocal tics lasting for more than 1 year and associated with a wide range of psychiatric comorbidities. Pharmacological treatment is indicated for moderate to severe GTS patients. However, when GTS is refractory to conventional medical and behavioral treatments, deep brain stimulation (DBS) can be considered as a last resort therapeutic avenue.

OBJECTIVE: To evaluate the efficacy of DBS and its comorbidities in the largest pool of GTS patients to date.

METHODS: Our cohort study was based on 48 patients’ refractory to conventional treatment who underwent DBS for GTS at Galeazzi Institute, Milan, Italy. An exhaustive preoperative and a follow-up battery of tests was performed including the Yale Global Tic Severity Rating Scale, the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Subjective Social Impairment on a 10-point Visual Analogue Scale tests.

RESULTS: Eleven patients in whom the device was removed for inflammatory complications or for poor compliance were excluded from final analysis. Twenty-seven of the remaining 37 patients had a Yale Global Tic Severity Rating Scale score at the last follow-up that was less than 35. Of the 37 patients, in 29 cases (78%) a reduction of more than 50% of the Yale Global Tic Severity Rating Scale score was observed.

CONCLUSION: The clinical efficacy of DBS in GTS is promising. Although DBS is associated with risks, as is any surgical intervention, DBS should be considered as a last resort therapeutic option in carefully selected GTS patients.

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The 6 thalamic regions: surgical approaches to thalamic cavernous malformations, operative results, and clinical outcomes

The 6 thalamic regions- surgical approaches to thalamic cavernous malformations, operative results, and clinical outcomes

J Neurosurg 123:676–685, 2015

The ideal surgical approach to thalamic cavernous malformations (CMs) varies according to their location within the thalamus. To standardize surgical approaches, the authors have divided the thalamus into 6 different regions and matched them with the corresponding surgical approach.

Methods The regions were defined as Region 1 (anteroinferior), Region 2 (medial), Region 3 (lateral), Region 4 (posterosuperior), Region 5 (lateral posteroinferior), and Region 6 (medial posteroinferior). The senior author’s surgical experience with 46 thalamic CMs was reviewed according to this classification. An orbitozygomatic approach was used for Region 1; anterior ipsilateral transcallosal for Region 2; anterior contralateral transcallosal for Region 3; posterior transcallosal for Region 4; parietooccipital transventricular for Region 5; and supracerebellar-infratentorial for Region 6.

Results Region 3 was the most common location (17 [37%]). There were 5 CMs in Region 1 (11%), 9 in Region 2 (20%), 17 in Region 3 (37%), 3 in Region 4 (6%), 4 in Region 5 (9%), and 8 in Region 6 (17%). Complete resection was achieved in all patients except for 2, who required a second-stage operation. The mean follow-up period was 1.7 years (range 6 months–9 years). At the last clinical follow-up, 40 patients (87%) had an excellent or good outcome (modified Rankin Scale [mRS] scores 0–2) and 6 (13%) had poor outcome (mRS scores 3–4). Relative to their preoperative condition, 42 patients (91%) were unchanged or improved, and 4 (9%) were worse.

Conclusions The authors have presented the largest series reported to date of surgically treated thalamic CMs, achieving excellent results using this methodology. In the authors’ experience, conceptually dividing the thalamus into 6 different regions aids in the selection of the ideal surgical approach for a specific region.

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The 6 thalamic regions: surgical approaches to thalamic cavernous malformations, operative results, and clinical outcomes

Cavernous_Malformation_of_Thalamus

J Neurosurg (123)3: 676-685

The ideal surgical approach to thalamic cavernous malformations (CMs) varies according to their location within the thalamus. To standardize surgical approaches, the authors have divided the thalamus into 6 different regions and matched them with the corresponding surgical approach.

METHODS
The regions were defined as Region 1 (anteroinferior), Region 2 (medial), Region 3 (lateral), Region 4 (posterosuperior), Region 5 (lateral posteroinferior), and Region 6 (medial posteroinferior). The senior author’s surgical experience with 46 thalamic CMs was reviewed according to this classification. An orbitozygomatic approach was used for Region 1; anterior ipsilateral transcallosal for Region 2; anterior contralateral transcallosal for Region 3; posterior transcallosal for Region 4; parietooccipital transventricularfor Region 5; and supracerebellar-infratentorial for Region 6.

RESULTS
Region 3 was the most common location (17 [37%]). There were 5 CMs in Region 1 (11%), 9 in Region 2 (20%), 17 in Region 3 (37%), 3 in Region 4 (6%), 4 in Region 5 (9%), and 8 in Region 6 (17%). Complete resection was achieved in all patients except for 2, who required a second-stage operation. The mean follow-up period was 1.7 years (range 6 months-9 years). At the last clinical follow-up, 40 patients (87%) had an excellent or good outcome (modified Rankin Scale [mRS] scores 0–2) and 6 (13%) had poor outcome (mRS scores 3–4). Relative to their preoperative condition, 42 patients (91%) were unchanged or improved, and 4 (9%) were worse.

CONCLUSIONS
The authors have presented the largest series reported to date of surgically treated thalamic CMs, achieving excellent results using this methodology. In the authors’ experience, conceptually dividing the thalamus into 6 different regions aids in the selection of the ideal surgical approach for a specific region.

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Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor

Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor- A Diffusion Tensor Imaging Study

Neurosurgery 75:657–670, 2014

Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control.

OBJECTIVE: To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation.

METHODS: A total of 11 patients (aged 64 6 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBMMNI 152).

RESULTS: Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center.

CONCLUSION: Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

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