Neuroanatomical considerations for optimizing thalamic deep brain stimulation in Tourette syndrome.

OBJECTIVE: Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly used to treat severe Tourette syndrome, yielding promising outcomes. However, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. The authors aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses, including therapeutic and side effects. METHODS: The authors collected data from 8 patients with Tourette syndrome who were treated with DBS. The authors selected the active contact following threshold tests of acute side effects and gradually increased the stimulation intensity within the therapeutic window such that acute and chronic side effects could be avoided at each programming session. The patients were carefully interviewed, and stimulation-induced side effects were recorded. Clinical outcomes were evaluated using the Yale Global Tic Severity Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Hamilton Depression Rating Scale. The DBS lead location was evaluated in the normalized brain space by using a 3D atlas. The volume of tissue activated was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects. RESULTS: The mean follow-up period was 10.9 ± 3.9 months. All clinical scales showed significant improvement. Whereas the volume of tissue activated associated with therapeutic effects covers the centromedian and ventrolateral nuclei and showed an association with motor networks, those associated with paresthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed an association with limbic networks. CONCLUSIONS: This study addresses the importance of accurate implantation of DBS electrodes for obtaining standardized clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.

Network Substrates of Centromedian Nucleus Deep Brain Stimulation in Generalized Pharmacoresistant Epilepsy.

Deep brain stimulation (DBS), specifically thalamic DBS, has achieved promising results to reduce seizure severity and frequency in pharmacoresistant epilepsies, thereby establishing it for clinical use. The mechanisms of action are, however, still unknown. We evidenced the brain networks directly modulated by centromedian (CM) nucleus-DBS and responsible for clinical outcomes in a cohort of patients uniquely diagnosed with generalized pharmacoresistant epilepsy. Preoperative imaging and long-term (2-11 years) clinical data from ten generalized pharmacoresistant epilepsy patients (mean age at surgery = 30.8 ± 5.9 years, 4 female) were evaluated. Volume of tissue activated (VTA) was included as seeds to reconstruct the targeted network to thalamic DBS from diffusion and functional imaging data. CM-DBS clinical outcome improvement (> 50%) appeared in 80% of patients and was tightly related to VTAs interconnected with a reticular system network encompassing sensorimotor and supplementary motor cortices, together with cerebellum/brainstem. Despite methodological differences, both structural and functional connectomes revealed the same targeted network. Our results demonstrate that CM-DBS outcome in generalized pharmacoresistant epilepsy is highly dependent on the individual connectivity profile, involving the cerebello-thalamo-cortical circuits. The proposed framework could be implemented in future studies to refine stereotactic implantation or the parameters for individualized neuromodulation.

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome.

The efficacy of deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is accepted, but whether the efficacy of DBS treatment in the Japanese population is equivalent to those reported internationally and whether adverse effects are comparable are not yet known. This study evaluated the clinical practice and outcome of DBS for TS in a Japanese institution. This study included 25 consecutive patients with refractory TS treated with thalamic centromedian-parafascicular nucleus DBS. The severity of tics was evaluated with the Yale Global Tic Severity Scale (YGTSS) before surgery, at 1 year after surgery, and at the last follow-up of 3 years or more after surgery. The occurrence of adverse events, active contact locations, and stimulation conditions were also evaluated. YGTSS tic severity score decreased by average 45.2% at 1 year, and by 56.6% at the last follow-up. The reduction was significant for all aspects of the scores including motor tics, phonic tics, and impairment. The mean coordinates of active contacts were 7.62 mm lateral to the midline, 3.28 mm posterior to the midcommissural point, and 3.41 mm above anterior commissure-posterior commissure plane. Efficacy and stimulation conditions were equivalent to international reports. The stimulation-induced side effects included dysarthria (32.0%) and paresthesia (12.0%). Device infection occurred in three patients (12.0%) as a surgical complication. The DBS device was removed because of infection in two patients. DBS is an effective treatment for refractory TS, although careful indication is necessary because of the surgical risks and unknown long-term outcome.

Minimally invasive trans-sulcal parafascicular surgical resection of cerebral tumors: translating anatomy to early clinical experience.

The minimally invasive port-based trans-sulcal parafascicular surgical corridor (TPSC) has incrementally evolved to provide a safe, feasible, and effective alternative to access subcortical and intraventricular pathologies. A detailed anatomical foundation is important in mitigating cortical and white matter tract injury with this corridor. Thus, the aims of this study are (1) to provide a detailed anatomical construct and overview of TPSCs and (2) to translate an anatomical framework to early clinical experience. Based on regional anatomical constraints, suitable parafascicular entry points were identified and described. Fiber tracts at both minimal and increased risks for each corridor were analyzed. TPSC-managed cases for metastatic or primary brain tumors were retrospectively reviewed. Adult patients 18 years or older with Karnofsky Performance Status (KPS) ≥ 70 were included. Subcortical brain metastases between 2 and 6 cm or primary brain tumors between 2 and 5 cm were included. Patient-specific corridors and trajectories were determined using MRI-tractography. Anatomy: The following TPSCs were described and translated to clinical practice: superior frontal, inferior frontal, inferior temporal, intraparietal, and postcentral sulci. Clinical: Eleven patients (5 males, 6 females) were included (mean age = 52 years). Seven tumors were metastatic, and 4 were primary. Gross total, near total, and subtotal resection was achieved in 7, 3, and 1 patient(s), respectively. Three patients developed intraoperative complications; all recovered from their intraoperative deficits and returned to baseline in 30 days. A detailed TPSC anatomical framework is critical in conducting safe and effective port-based surgical access. This review may represent one of the few early translational TPSC studies bridging anatomical data to clinical subcortical and intraventricular surgical practice.

Targeting the centromedian thalamic nucleus for deep brain stimulation.

OBJECTIVES: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM's neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI). METHODS: 19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest. RESULTS: The CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex. CONCLUSIONS: In the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP2RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.

Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study.

BACKGROUND: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Adverse Childhood Experiences and Amygdalar Reduction: High-Resolution Segmentation Reveals Associations With Subnuclei and Psychiatric Outcomes.

The aim of the present study was 2-fold: (1) to utilize improved amygdala segmentation and exploratory factor analysis to characterize the latent volumetric structure among amygdala nuclei and (2) to assess the effect of adverse childhood experiences (ACEs) on amygdalar morphometry and current psychiatric symptoms. To investigate these aims, structural (T1) MRI and self-report data were obtained from 119 emerging adults. Regression analysis showed that higher ACE scores were related to reduced volume of the right, but not the left, amygdalar segments. Further, exploratory factor analysis yielded a two-factor structure, basolateral and central-medial nuclei of the right amygdala. Stractual equation modeling analyses revealed that higher ACE scores were significantly related to a reduced volume of the right basolateral and central-medial segments. Furthermore, reduction in the right basolateral amygdala was associated with increased anxiety, depressive symptoms, and alcohol use. This association supports an indirect effect between early adversity and psychiatric problems via reduced right basolateral amygdalar volume. The high-resolution segmentation results reveal a latent structure among amygdalar nuclei, which is consistent with prior work conducted in nonhuman mammals. These findings extend previous reports linking early adversity, right amygdala volume, and psychopathology.

Subcortical electrophysiological activity is detectable with high-density EEG source imaging.

Subcortical neuronal activity is highly relevant for mediating communication in large-scale brain networks. While electroencephalographic (EEG) recordings provide appropriate temporal resolution and coverage to study whole brain dynamics, the feasibility to detect subcortical signals is a matter of debate. Here, we investigate if scalp EEG can detect and correctly localize signals recorded with intracranial electrodes placed in the centromedial thalamus, and in the nucleus accumbens. Externalization of deep brain stimulation (DBS) electrodes, placed in these regions, provides the unique opportunity to record subcortical activity simultaneously with high-density (256 channel) scalp EEG. In three patients during rest with eyes closed, we found significant correlation between alpha envelopes derived from intracranial and EEG source reconstructed signals. Highest correlation was found for source signals in close proximity to the actual recording sites, given by the DBS electrode locations. Therefore, we present direct evidence that scalp EEG indeed can sense subcortical signals.

Intracranial Erdheim-Chester Disease Mimicking Parafalcine Meningioma: Report of Two Cases and Review of the Literature.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis that typically occurs in middle-aged patients. It is usually characterized by multifocal osteosclerotic lesions of the long-bones, however many cases have extraskeletal involvement. Central nervous system (CNS) involvement is common, but isolated CNS involvement at presentation has rarely been reported. CASE DESCRIPTION: Here we report two cases of dural-based ECD mimicking meningioma on imaging with no other identified sites of disease. CONCLUSION: ECD is a rare disease, with isolated CNS involvement reported only a few times in the literature. The significance of this presentation requires additional study and long-term follow up.

Centromedian-thalamic and hippocampal electrical stimulation for the control of intractable epileptic seizures.

The following two different modulatory procedures to control intractable epileptic seizures are presented: (1) chronic electrical stimulation of the centromedian-thalamic nucleus (ESCM) for control of generalized tonic-clonic seizures and atypical absences, and (2) subacute hippocampal stimulation (SAHCS) and chronic hippocampal stimulation for control of nonlesional temporal lobe seizures. The ESCM antiepileptic effect seems to be the result of activation of a nonspecific reticulothalamocortical system responsible for generalized electrocortical responses (recruiting, desynchronization, negative direct current shifts, and three spike-wave complexes per second). The success of the ESCM procedure depends on the following predictor factors: case selection (primary and secondary tonic-clonic seizures and atypical absences of the Lennox Gastaut syndrome), ventriculographic and electrophysiologic definition of the optimal stereotactic targets (based on the anterior commissure, posterior commissure, and the vertical line perpendicular to the posterior commissure and electrocortical recruiting responses), periodic electrophysiologic monitoring of the reliability of ESCM in the absence of the patient's subjective sensations and with totally internalized subcutaneous stimulation systems (by recording scalp electrocortical recruiting, desynchronizing, and direct current responses), quantitative evaluation of clinical and EEG improvement, and analysis of the ON and OFF effects, taking into account a long-lasting (possibly plastic) effect of ESCM. SAHCS blocks clinical and EEG signs of temporal lobe epileptogenesis with no additional damage of the stimulated hippocampal tissue. Preliminary results suggest that this antiepileptic effect is, at least in part, the result of a physiologic inhibition of the stimulated hippocampal tissue, because after SAHCS the authors found the following: (1) increased threshold and decreased duration, propagation, and blockage of the clinical signs accompanied with the hippocampal afterdischarge; (2) flattening of the hippocampal-evoked response recovery cycles; (3) single photon emission computed tomographic hypoperfusion; and (4) increased concentration of benzodiazepine receptor binding at the stimulated hippocampal region. Chronic hippocampal stimulation persistently blocked temporal lobe epileptogenesis in one patient under open protocols during 24 months with no apparent additional alterations in recent memory.