Nucleus In Patients Research Articles

The cytoplasmic-nuclear transport of DDX3X promotes immune-mediated liver injury in mice regulated by endoplasmic reticulum stress

Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3XΔHep) mice and control (DDX3Xfl/fl) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury.

Evoked resonant neural activity long-term dynamics can be reproduced by a computational model with vesicle depletion

Subthalamic deep brain stimulation (DBS) robustly generates high-frequency oscillations known as evoked resonant neural activity (ERNA). Recently the importance of ERNA has been demonstrated through its ability to predict the optimal DBS contact in the subthalamic nucleus in patients with Parkinson's disease. However, the underlying mechanisms of ERNA are not well understood, and previous modelling efforts have not managed to reproduce the wealth of published data describing the dynamics of ERNA. Here, we aim to present a minimal model capable of reproducing the characteristics of the slow ERNA dynamics published to date. We make biophysically-motivated modifications to the Kuramoto model and fit its parameters to the slow dynamics of ERNA obtained from data. Our results demonstrate that it is possible to reproduce the slow dynamics of ERNA (over hundreds of seconds) with a single neuronal population, and, crucially, with vesicle depletion as one of the key mechanisms behind the ERNA frequency decay in our model. We further validate the proposed model against experimental data from Parkinson's disease patients, where it captures the variations in ERNA frequency and amplitude in response to variable stimulation frequency, amplitude, and to stimulation pulse bursting. We provide a series of predictions from the model that could be the subject of future studies for further validation.

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting-state functional magnetic resonance imaging.

The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed-based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well-matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus-central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area-parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions.

Smaller hypothalamic subregion with paraventricular nucleus in patients with panic disorder.

In panic disorder (PD), functional disturbance of the hypothalamus-pituitary-adrenal (HPA) axis has been considered. However, in neuroimaging studies of PD, the hypothalamus and pituitary gland are poorly studied.We investigated the volume of PD patients' hypothalamus and pituitary gland, enrolling 38 PD patients and 38 healthy controls. Severity of PD was mild to moderate according to the Panic Disorder Severity Scale, and the illness duration was relatively short (median = 2.8 years). The hypothalamus' gray matter was automatically extracted and segmented, whereas the pituitary gland was manually traced. Regarding the hypothalamus, the paraventricular nucleus (PVH), which produces the corticotropin-releasing hormone, was of interest.The volumes of the pituitary and the bilateral anterior-superior hypothalamic subunits, where the PVH would be located, were compared by the multiple regression analyses controlling for age and intracranial content volume. To compensate for limitation in the abovementioned segmentation and analyses, the voxel-based morphometry with small volume correction (VBM-SVC) targeting the whole hypothalamus was also performed.The multiple regression analyses did not find significant effect of PD diagnosis on the volumes. However, in the VBM-SVC analysis, volume reduction of the PVH was suggested in PD even when patients who experienced PD for ≥ 3 years were excluded [peak coordinate (x, y, z = -2, 3, -8), FWE-corrected P = .022 (cluster-level) and 0.003 (peak-level), voxel size = 63]. Our results suggested structural alteration of the PVH in PD patients for the first time, indicating importance of the HPA-axis in PD pathology.

The volume and structural covariance network of thalamic nuclei in patients with Wilson's disease: an investigation of the association with neurological impairment.

This study aimed to examine the volumes of thalamic nuclei and the intrinsic thalamic network in patients with Wilson's disease (WDs), and to explore the correlation between these volumes and the severity of neurological symptoms. A total of 61 WDs and 33 healthy controls (HCs) were included in the study. The volumes of 25 bilateral thalamic nuclei were measured using structural imaging analysis with Freesurfer, and the intrinsic thalamic network was evaluated through structural covariance network (SCN) analysis. The results indicated that multiple thalamic nuclei were smaller in WDs compared to HCs, including mediodorsal medial magnocellular (MDm), anterior ventral (AV), central median (CeM), centromedian (CM), lateral geniculate (LGN), limitans-suprageniculate (L-Sg), reuniens-medial ventral (MV), paracentral (Pc), parafascicular (Pf), paratenial (Pt), pulvinar anterior (PuA), pulvinar inferior (PuI), pulvinar medial (PuM), ventral anterior (VA), ventral anterior magnocellular (VAmc), ventral lateral anterior (VLa), ventral lateral posterior (VLp), ventromedial (VM), ventral posterolateral (VPL), and right middle dorsal intralaminar (MDI). The study also found a negative correlation between the UWDRS scores and the volume of the right MDm. The intrinsic thalamic network analysis showed abnormal topological properties in WDs, including increased mean local efficiency, modularity, normalized clustering coefficient, small-world index, and characteristic path length, and a corresponding decrease in mean node betweenness centrality. WDs with cerebral involvement had a lower modularity compared to HCs. The findings suggest that the majority of thalamic nuclei in WDs exhibit significant volume reduction, and the atrophy of the right MDm is closely related to the severity of neurological symptoms. The intrinsic thalamic network in WDs demonstrated abnormal topological properties, indicating a close relationship with neurological impairment.

Multimodal Investigation of Deep Gray Matter Nucleus in Patients with Multiple Sclerosis and Their Clinical Correlations: A Multivariate Pattern Analysis Study.

Deep gray matter (DGM) nucleus are involved in patients with multiple sclerosis (MS) and are strongly associated with clinical symptoms. We used machine learning approach to further explore microstructural alterations in DGM of MS patients. One hundred and fifteen MS patients and seventy-one healthy controls (HC) underwent brain MRI. The fractional anisotropy (FA), mean diffusivity (MD), quantitative susceptibility value (QSV) and volumes of the caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were measured. Multivariate pattern analysis, based on a machine-learning algorithm, was applied to investigate the most damaged regions. Partial correlation analysis was used to investigate the correlation between MRI quantitative metrics and clinical neurological scores. The area under the curve of FA-based classification model was 0.83, while they were 0.93 for MD and 0.81 for QSV. The Montreal cognitive assessment scores were correlated with the volume of the DGM and the expanded disability status scale scores were correlated with the MD of the GP and PT. The study results indicated that MS patients had involvement of DGM with the CN being the most affected. The atrophy of DGM in MS patients mainly affected cognitive function and the microstructural damage of DGM was mainly correlated with clinical disability.

Cerebellar deep brain stimulation for the treatment of movement disorders in cerebral palsy.

Cerebral palsy (CP) represents the most common childhood physical disability that encompasses disorders of movement and posture attributed to nonprogressive disturbances that occurred in the developmental fetal or infant brain. Dyskinetic CP (DCP), the second most common type of CP after spastic forms, refers to a subset of patients in whom dystonia and choreoathetosis are the predominant motor manifestations. Most children with CP have abnormal brain MRI studies indicative of cortical and deep gray matter damage consistent with hypoxic ischemic encephalopathy, which may preclude or suggest decreased efficacy of standard deep brain stimulation (DBS) targets. The cerebellum has been posited as an attractive target for treatment of DCP because it is frequently spared from hypoxic ischemic damage and has shown promise in alleviating patient symptoms both in early work in the 1970s and in more recent case series with DBS. The authors performed bilateral cerebellar DBS implantation, targeting the dentate nucleus (DN) and cerebellar outflow pathway, in 3 patients with DCP. Leads were connected to a pulse generator that senses local field potentials during chronic continuous DBS. The authors report their surgical methods, examples of chronic cerebellar local field potential recordings, and preliminary clinical outcomes. Motor outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale. Three patients 14-22 years old with DCP and MRI evidence of structural damage to the basal ganglia were offered cerebellar stimulation targeting the DN. All patients tolerated the procedure well and demonstrated improvement in subjective motor function as well as objective improvement in the Burke-Fahn-Marsden Dystonia Rating Scale movement subscale, although the range of responses was variable (19%-40%). Patients experienced subjective improvement in motor function including ease of hand movements and coordination, gait, head control, speech, decreased overflow, and diminished muscle tightness. DBS of the dentate nuclei in patients with DCP appears to be safe and shows preliminary evidence of clinical benefit. New chronic sensing technology may allow for determination of in vivo mechanisms of network disruption in DCP and allow for further understanding of the effects of neuromodulation on brain physiology. Larger studies with long-term follow up will be required to further elucidate the clinical benefits of this therapy. This report addresses a gap in the literature regarding the technical approach to image-based stereotactic targeting and chronic neural recording in the DN.

Mechanisms and consequences of weight gain after deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Body weight gain in combination with metabolic alterations has been observed after deep brain stimulation (DBS) of subthalamic nucleus (STN) in patients with Parkinson’s disease (PD), which potentially counteracts the positive effects of motor improvement. We aimed to identify stimulation-dependent effects on motor activities, body weight, body composition, energy metabolism, and metabolic blood parameters and to determine if these alterations are associated with the local impact of DBS on different STN parcellations. We assessed 14 PD patients who underwent STN DBS (PD-DBS) before as well as 6- and 12-months post-surgery. For control purposes, 18 PD patients under best medical treatment (PD-CON) and 25 healthy controls (H-CON) were also enrolled. Wrist actigraphy, body composition, hormones, and energy expenditure measurements were applied. Electrode placement in the STN was localized, and the local impact of STN DBS was estimated. We found that STN DBS improved motor function by ~ 40% (DBS ON, Med ON). Weight and fat mass increased by ~ 3 kg and ~ 3% in PD-DBS (all P ≤ 0.005). fT3 (P = 0.001) and insulin levels (P = 0.048) increased solely in PD-DBS, whereas growth hormone levels (P = 0.001), daily physical activity, and VO2 during walking were decreased in PD-DBS (all P ≤ 0.002). DBS of the limbic part of the STN was associated with changes in weight and body composition, sedentary activity, insulin levels (all P ≤ 0.040; all r ≥ 0.56), and inversely related to HOMA-IR (P = 0.033; r = − 0.62). Daily physical activity is decreased after STN DBS, which can contribute to weight gain and an unfavorable metabolic profile. We recommend actigraphy devices to provide feedback on daily activities to achieve pre-defined activity goals.

Long-term efficacy of deep brain stimulation of the subthalamic nucleus in patients with pharmacologically intractable epilepsy: a case series of six patients.

Epilepsy is one of the widespread neurological illnesses, and about 20-40% of epilepsy patients are pharmacoresistant. We aimed to assess the long-term efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) for drug-resistant epilepsy. We included pharmacologically intractable epilepsy patients who had STN-DBS at the Chinese People's Liberation Army General Hospital between June 2016 and December 2018. We retrospectively evaluated pre- and postoperative clinical outcomes, including seizure frequency, seizure type, anti-seizure medication, cognitive function, anatomical target coordinates, stimulation parameters, and adverse events following the surgical procedure. Six patients with a mean follow-up of 49.3 ± 10.2 months, were included. Seizure frequency decreased by an average of 64.0% after STN-DBS at last year follow-up (p = 0.046), and one patient (1/6) achieved seizure-free status. For seizure type, anti-seizure medication, and cognitive function, there were no significant differences between pre-and post-operation (p > 0.05). In terms of stimulation parameters, the pulse width, amplitude, and frequency were 58.3 ± 9.4 μsec, 2.5 ± 0.7 V, and 122.5 ± 15.7 Hz, respectively. None of the patients showed normal electroencephalography during the electroencephalography reexamination. There were no surgery-related complications, and chronic STN stimulation was generally well tolerated in five patients. However, one patient (1/6) had a difficulty of dyskinesia in the right arm. In conclusion, neuromodulation of the STN by DBS is a promising option for patients with pharmacologically intractable epilepsy, especially for whose epileptic zone originates mainly from the frontoparietal region and who are unsuitable for resective surgery. Further prospective multicenter studies with a larger sample size are necessary for further exploration.

Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson's disease.

This study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson's disease (PD), so as to explore its application value in assessing the severity of Parkinson's disease. A total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson's Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated. The caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05). 11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.

Volume alterations of the hippocampus and amygdala in patients with schizophrenia and persistent auditory hallucinations.

Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.

The applied value in brain gray matter nuclei of patients with early-stage Parkinson’s disease : a study based on multiple magnetic resonance imaging techniques

PurposeThis study compares the observation efficiency of brain gray matter nuclei of patients with early-stage Parkinson’s disease among various Magnetic Resonance Imaging techniques, which include susceptibility weighted imaging (SWI), quantitative susceptibility imaging (QSM), diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Based on the findings, this study suggests an efficient combination of scanning techniques for brain gray matter nuclei observation, aiming to provide an opportunity to advance the understanding of clinical diagnosis of early-stage Parkinson’s disease.MethodsForty examinees, including twenty patients who were clinically diagnosed with early Parkinson’s disease with a course of 0.5-6 years (PD group) and twenty healthy controls (HC group), underwent head MRI examination. Philips 3.0T (tesla) MR machine was used to measure the imaging indexes of gray matter nuclei in patients with early Parkinson’s disease. SWI, QSM, DTI and DKI were used for diagnosis. SPSS (Statistical Product and Service Solutions) 21.0 was used for data analysis.ResultsWhen SWI was used, fifteen PD patients and six healthy volunteers were diagnosed correctly. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic coincidence rate about the diagnosis of nigrosome-1 on imaging were 75.0%, 30.0%, 51.7%, 54.5% and 52.5% respectively. By contrast, when QSM was used, 19 PD patients and 11 healthy volunteers were diagnosed correctly. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic coincidence rate about the diagnosis of Nigrosome-one on imaging were 95.0%, 55.0%, 67.9%, 91.7% and 75.0% respectively. The mean kurtosis (MK) value within both the substantia nigra and thalamus, together with the mean diffusivity (MD) within both the substantia nigra and the head of caudate nucleus in PD group was greater than that of HC group. The susceptibility values within the substantia nigra, red nucleus, head of caudate nucleus and putamen of PD group was greater than that of HC group. The MD value in substantia nigra reveals the optimal diagnostic efficiency to distinguish the HC group and the PD group, followed by the MK value in substantia nigra. Specifically, the maximum area under ROC curve (AUC) of the MD value was 0.823, the sensitivity 70.0%, the specificity 85.0%, and the diagnostic threshold 0.414. The area under ROC curve (AUC) of the MK value was 0.695, the sensitivity 95.0%, the specificity 50.0%, and the diagnostic threshold was 0.667. Both of them were statistically significant.ConclusionsIn the early diagnosis of Parkinson’s disease, QSM is more efficient than SWI in observing nigrosome-1 in substantia nigra. In the early diagnosis of Parkinson’s disease, MD and MK values of substantia nigra in DKI parameters have higher diagnostic efficiency. The combined scanning of DKI and QSM has the highest diagnostic efficiency and provides imaging basis for clinical diagnosis of early Parkinson’s disease.

Biophysical indicators of the mucous membrane of the oral cavity, the microcirculatory channel and the oral fluid in patients with lichen ruber planus

Annotation. The work aims to conduct a biophysical assessment of the charge state of the buccal epithelium cells (BEC), the microcirculatory channel of the oral mucosa and oral fluid in patients with the erosive-ulcerative form of lichen planus. The problem is relevant due to the increasing number of lichen planus patients, the uncertain etiology of the disease, and the ongoing struggle to find treatment solutions. 11 patients aged 50-60 years with lichen planus (erosive-ulcerative form) were examined. All patients underwent a study of the charge state of the buccal epithelium cells. Buccal cell samples were collected on an empty stomach after rinsing the oral cavity with water, applying a gentle swabbing technique. A spectrocolorimeter of type “Pulsar” was used to assess the condition of the microcapillary channel of the oral mucosa. In addition, in patients with lichen planus, the stability of the pH of the oral fluid (ΔpH) was evaluated as one of the indicators of the level of non-specific resistance in the body and the oral cavity in particular. Five 1ml samples of oral fluid were taken from each patient to calculate the value of ΔpH, where pH value was determined using an ionometer immediately after sampling. An average value of ΔрН and the confidence interval of deviations (ΔрН) from the average value were calculated, taking into account the Student coefficient for five measurements and a confidence probability of 0.95. The results obtained from biophysical studies show a significant decrease in all studied indicators. The percentage of mobile nuclei in patients with the erosive-ulcerative form of lichen planus of the oral mucosa is two times lower than in healthy people of the same age. At the same time, the plasmalemma and nuclei displacement amplitudes, as well as their ratio, were reduced compared to the norm, which indicates a decrease in their charge and deterioration of the physiological state of cells and the body as a whole. We found that individuals with lichen planus exhibit a decreased efficiency of functional reactions in the oral cavity tissues, which requires the development and implementation of effective treatment and prevention measures.

Single Trajectory Dual Targeting of Subthalamic Nucleus and Ventral Intermedius Thalamic Nucleus in Patients with Severe Tremor-Predominant Parkinson’s Disease (P4-11.001)

<h3>Objective:</h3> To describe clinical outcomes of severe tremor-predominant Parkinson’s Disease (PD) patients who underwent single trajectory dual targeting of the subthalamic nucleus (STN) and ventral intermedius nucleus of the thalamus (VIM). <h3>Background:</h3> Some patients with tremor-predominant PD have a sub-optimal response to STN-DBS, whereas those that undergo VIM-DBS may have inadequate improvement of rigidity or bradykinesia. Reports on the efficacy and safety of dual target STN-VIM DBS using single trajectory are scarce. <h3>Design/Methods:</h3> We retrospectively reviewed the charts of all PD patients who underwent dual target STN-VIM DBS from 2012–2022 in one center. All patients were implanted bilaterally with the Boston Scientific 8-contact 15.5mm electrodes under general anesthesia using the parietal approach. Primary outcome measure was reduction in motor Unified Parkinson’s Disease Rating Scale (m-UPDRS). Secondary outcome measures include change in levodopa equivalent daily dose (LEDD) post-DBS, and time to reaching the minimum LEDD post-DBS. <h3>Results:</h3> 12 patients (7 men) were identified. Mean age at time of surgery was 71.58±5.21 years. Mean duration of PD was 28.50±14.84 years. Mean m-UPDRS was 30.83±34.15 preDBS and 14.91±18.26 post-DBS (p&lt;0.00000006). Mean % reduction in m-UPDRS was 50.94±0.08 %. Mean pre-DBS LEDD was 792.85±458.64, whereas post-DBS LEDD was 14.28±37.79 (p= 0.004). 7/12 were on PD medications pre-DBS: 6/7 completely weaned off medications post-DBS, and 1/7 had 89% reduction in LEDD post-DBS. The mean time to reach minimum LEDD was 33±22.87 days. Transient side effects included dysarthria (4/12), imbalance (4/12), and headaches (2/12) which improved spontaneously. 2/12 had persistent headaches which were effectively controlled with opiates. 8/12 had neuropsychological testing (NPT) pre- and post-DBS: 4/8 had no change post-DBS, 2/8 had mild worsening and 2/8 had improvement. <h3>Conclusions:</h3> Dual target STN-VIM DBS is very effective in treating tremor/parkinsonism in tremor-predominant PD, allowing the majority of patients to wean off PD medications. Side effects are mostly transient. <b>Disclosure:</b> Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Adamas. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Revance. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyowa Kirin. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amneal. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Adamas. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. Dr. Evidente has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Evidente has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Ipsen. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurocrine. The institution of Dr. Evidente has received research support from Sunovion. The institution of Dr. Evidente has received research support from Pharma 2B. The institution of Dr. Evidente has received research support from Neuraly. The institution of Dr. Evidente has received research support from Revance. The institution of Dr. Evidente has received research support from CND. The institution of Dr. Evidente has received research support from Lundbeck. The institution of Dr. Evidente has received research support from Abbvie. The institution of Dr. Evidente has received research support from Acadia. The institution of Dr. Evidente has received research support from Aptinyx. Dr. Ponce has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. Dr. Ponce has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Dr. Ponce has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Miss Evidente has nothing to disclose. Dr. Garrett has nothing to disclose. Miss Evidente has nothing to disclose.

Periaqueductal gray matter echogenicity as a marker of migraine chronification: a case control study

BackgroundMigraine is one of the most prevalent and disabling medical diseases in the world. The periaqueductal gray matter and the red nucleus play an important role in its pathogenesis. Our aim was to evaluate the echogenicity of the periaqueductal gray matter and the red nucleus in patients with migraine, by means of transcranial ultrasound.MethodsIn this cross-sectional study, a group of patients with migraine (according to the International Classification of Headache Disorders) and a group of control subjects with comparable age-and-sex distribution were prospectively included. We evaluated the area and echogenicity of the periaqueductal gray matter and the red nucleus by means of transcranial ultrasound, both bedside and posteriorly analyzed with the medical image viewer Horos.ResultsWe included 115 subjects: 65 patients with migraine (39 of them with chronic migraine and 26 with episodic migraine), and 50 controls. Median disease duration in patients with chronic migraine was 29 (IQR: 19; 40) years, with a median of 18 (IQR: 14; 27) days of migraine per month. The area of the periaqueductal gray matter was larger in patients with chronic migraine compared to episodic migraine and controls (0.15[95%CI 0.12;0.22]cm2; 0.11[95%CI 0.10;0.14]cm2 and 0.12[95%CI 0.09;0.15]cm2, respectively; p = 0.043). Chronic migraine patients showed an intensity of the periaqueductal gray matter echogenicity lower than controls (90.57[95%CI 70.87;117.26] vs 109.56[95%CI 83.30;122.64]; p = 0.035). The coefficient of variation of periaqueductal gray matter echogenicity was the highest in chronic migraine patients (p = 0.009). No differences were observed regarding the area or intensity of red nucleus echogenicity among groups.ConclusionPatients with chronic migraine showed a larger area of echogenicity of periaqueductal gray matter, a lower intensity of its echogenicity and a higher heterogenicity within this brainstem structure compared to patients with episodic migraine and controls. The echogenicity of the periaqueductal gray matter should be further investigated as a biomarker of migraine chronification.

Morphometric Analysis of Subthalamic Nuclei in Patients of Deep Brain Stimulation in Parkinson’s Disease

Morphometric Analysis of Subthalamic Nuclei in Patients of Deep Brain Stimulation in Parkinson’s Disease

Volumetric assessment of individual thalamic nuclei in patients with drug-naïve, first-episode major depressive disorder.

Despite the previous inconsistent findings of structural and functional abnormalities of the thalamus in patients with major depressive disorder (MDD), the disruption of the thalamic nuclei in the pathophysiology of this disorder has not yet been adequately studied. Therefore, we investigated the volumetric changes of thalamic subregions and their nuclei in drug-naïve, first-episode MDD patients. We also investigated the association between HAM-D scores, a clinical scale frequently used to evaluate the severity of depression and thalamic nuclei volumes in MDD patients. This study included 76 drug-naïve MDD patients and an equal number of healthy subjects. Magnetic resonance imaging (MRI) data were obtained using a 3T MR system and thalamic nuclei volumes were evaluated using FreeSurfer ver.7.11. The volumetric differences were compared by one-way analysis of covariance (ANCOVA) and to ensure that effects were not accounted for by other factors, age, sex, and ETICV variables were included as covariates. We observed significant volume reductions of the left whole thalamus (p < 0.003) and several thalamic nuclei mostly on the left side in the MDD group compared with healthy controls (HCs). Furthermore, we have revealed weak negative correlations between several thalamic nuclei volumes and HAM-D total and subscale scores. This is the first research study to investigate alterations of the various thalamic nuclei volumes in MDD patients compared with HCs. Moreover, we first analyzed the association between individual thalamic nuclei volumes and HAM-D subscale scores. Though our study may be restricted at certain levels, especially by the demographic difference between the two groups, they possibly contribute at a preliminary level to understanding the thalamic structural changes at its subregions in patients with drug-naïve, first-episode MDD.

Volumetric differences of thalamic nuclei in children with trisomy 21.

Histological studies have shown alterations of thalamic nuclei in patients with Down syndrome (DS). The correlation of these changes on MRI (magnetic resonance imaging) is unclear. Therefore, this study investigates volumetric differences of thalamic nuclei in children with DS compared to controls. Patients were retrospectively identified between 01/2000 and 10/2021. Patient inclusion criteria were: (1) 0-18years of age, (2) diagnosis of DS, and (3) availability of a brain MRI without parenchymal injury and a non-motion-degraded volumetric T1-weighted sequence. Whole thalamus and thalamic nuclei (n = 25) volumes were analyzed bilaterally relative to the total brain volume (TBV). Two-sided t-tests were used to evaluate differences between groups. Differences were considered significant if the adjusted p-value was <0.05 after correction for multiple hypothesis testing using the Holm-Bonferroni method. 21 children with DS (11 females, 52.4%, mean age: 8.6 ± 4.3years) and 63 age- and sex-matched controls (32 females, 50.8%, 8.6 ± 4.3years) were studied using automated volumetric segmentation. Significantly smaller ratios were found for nine thalamic nuclei and the whole thalamus on the right and five thalamic nuclei on the left. TBV was significantly smaller in patients with DS (p < 0.001). No significant differences were found between the groups for age and sex. In this exploratory volumetric analysis of the thalamus and thalamic nuclei, we observed statistically significant volumetric changes in children with DS. Our findings confirm prior neuroimaging and histological studies and extend the range of involved thalamic nuclei in pediatric DS.

Arousal and salience network connectivity alterations in surgical temporal lobe epilepsy.

It is poorly understood why patients with mesial temporal lobe epilepsy (TLE) have cognitive deficits and brain network changes that extend beyond the temporal lobe, including altered extratemporal intrinsic connectivity networks (ICNs). However, subcortical arousal structures project broadly to the neocortex, are affected by TLE, and thus may contribute to these widespread network effects. The authors' objective was to examine functional connectivity (FC) patterns between subcortical arousal structures and neocortical ICNs, possible neurocognitive relationships, and FC changes after epilepsy surgery. The authors obtained resting-state functional magnetic resonance imaging (fMRI) in 50 adults with TLE and 50 controls. They compared nondirected FC (correlation) and directed FC (Granger causality laterality index) within the salience network, default mode network, and central executive network, as well as between subcortical arousal structures; these 3 ICNs were also compared between patients and controls. They also used an fMRI-based vigilance index to relate alertness to arousal center FC. Finally, fMRI was repeated in 29 patients > 12 months after temporal lobe resection. Nondirected FC within the salience (p = 0.042) and default mode (p = 0.0008) networks, but not the central executive network (p = 0.79), was decreased in patients in comparison with controls (t-tests, corrected). Nondirected FC between the salience network and subcortical arousal structures (nucleus basalis of Meynert, thalamic centromedian nucleus, and brainstem pedunculopontine nucleus) was reduced in patients in comparison with controls (p = 0.0028-0.015, t-tests, corrected), and some of these connectivity abnormalities were associated with lower processing speed index, verbal comprehension, and full-scale IQ. Interestingly, directed connectivity measures suggested a loss of top-down influence from the salience network to the arousal nuclei in patients. After resection, certain FC patterns between the arousal nuclei and salience network moved toward control values in the patients, suggesting that some postoperative recovery may be possible. Although an fMRI-based vigilance measure suggested that patients exhibited reduced alertness over time, FC abnormalities between the salience network and arousal structures were not influenced by the alertness levels during the scans. FC abnormalities between subcortical arousal structures and ICNs, such as the salience network, may be related to certain neurocognitive deficits in TLE patients. Although TLE patients demonstrated vigilance abnormalities, baseline FC perturbations between the arousal and salience networks are unlikely to be driven solely by alertness level, and some may improve after surgery. Examination of the arousal network and ICN disturbances may improve our understanding of the downstream clinical effects of TLE.

Visualization of atrophy of medial temporal lobes and the septal nuclei in patients with transient ischaemic attack and controls

IntroductionTransient ischaemic attack (TIA) is associated with increased risk of cognitive decline and dementia as early as one-year post-event. Regional brain atrophy measurements may predict future cognitive decline. Aims: 1) To determine whether Medial Temporal Atrophy (MTA) scores and interseptal distance (ISD) measurements are greater in patients with TIA compared to controls; and 2) To determine whether MTA and ISD predicts cognitive change one year after TIA. MethodsBaseline demographic, vascular risk factors, structural imaging and cognitive tests scores were compared between 103 Patients with TIA and 103 age-and-sex-matched controls from the Predementia Neuroimaging of Transient Ischaemic Attack (PREVENT) Study. MTA was assessed using the Schelten's Scale, and ISD was calculated as the distance between the septal nucleus of each hemisphere. Multiple linear regression models were used to evaluate how MTA and ISD related to cognitive change after adjusting for covariates. ResultsPatients with TIA had larger ISD measurements (1.4 mm [SD=1.2] vs. 0.9 mm [SD=1.0]); p < 0.001) and higher right/left MTA scores (both p < 0.05) compared to controls. At baseline, controls performed significantly better on the RAVLT (total recall), BVMT (total and delayed recall) and the Trail Making Task (A and B) compared to patients with TIA. However, at one-year follow-up there was no evidence of decline in the patients with TIA compared with controls. Higher MTA and ISD scores were not associated with cognitive decline. ConclusionsPatients with TIA had higher MTA scores and ISD measurements than controls, but neither were predictors of cognitive decline at one year. Future studies with longer follow-up periods will be required to determine whether higher MTA scores and ISD predict risk of cognitive decline in patients with TIA.