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Journal of Reconstructive Microsurgery Jun 2024Lymphedema is a chronic condition, characterized by fluid buildup and tissue swelling and is caused by impairment of the lymphatic system. The lymph interpositional flap... (Clinical Trial)
Clinical Trial
BACKGROUND
Lymphedema is a chronic condition, characterized by fluid buildup and tissue swelling and is caused by impairment of the lymphatic system. The lymph interpositional flap transfer (LIFT) technique, in which lymph flow is restored with a flap that includes subdermal lymphatic channels, is an option for surgical reconstruction. The superficial circumflex iliac artery perforator (SCIP) flap can be used for this purpose. This study aimed to describe and characterize the lymphatic patterns within the vascular territory of the superficial circumflex iliac artery perforator flap.
METHODS
This cross-sectional multicenter study involved 19 healthy volunteers aged ≥18 years of both sexes assessing the bilateral SCIP flap zone. Superficial lymphatic patterns were evaluated at 4-, 14-, and 24-minutes after indocyanine green lymphography (ICG) injection. Standardized procedures were implemented for all participants in both hospitals.
RESULTS
The linear pattern was predominant bilaterally. The median number of lymphatic vessels and their length increased over time. Most lymphatic vessels in the superficial circumflex iliac artery perforator flap were oriented towards the inguinal lymph node. However, the left SCIP zone lymphatic vessels were directed opposite to the inguinal lymph node.
CONCLUSION
The two sides SCIP zones were not significantly different. The primary direction of the bilateral lymphatic vessels was towards the inguinal lymph node, although only single side lymphatic vessels were in the opposite direction. These findings emphasize the importance of assessing lymphatic axiality and coherent lymphatic patterns prior to undertaking the SCIP as an interposition flap, to ensure effective restoration of lymphatic flow.
PubMed: 38848754
DOI: 10.1055/a-2340-9629 -
Movement Disorders : Official Journal... Jun 2024Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and hereditary spastic paraplegia type 7 (SPG7) represent the most common genotypes of spastic ataxia...
BACKGROUND
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and hereditary spastic paraplegia type 7 (SPG7) represent the most common genotypes of spastic ataxia (SPAX). To date, their magnetic resonance imaging (MRI) features have only been described qualitatively, and a pure neuroradiological differential diagnosis between these two conditions is difficult to achieve.
OBJECTIVES
To test the performance of MRI measures to discriminate between ARSACS and SPG7 (as an index of common SPAX disease).
METHODS
In this prospective multicenter study, 3D-T1-weighted images of 59 ARSACS (35.4 ± 10.3 years, M/F = 33/26) and 78 SPG7 (54.8 ± 10.3 years, M/F = 51/27) patients of the PROSPAX Consortium were analyzed, together with 30 controls (45.9 ± 16.9 years, M/F = 15/15). Different linear and surface measures were evaluated. A receiver operating characteristic analysis was performed, calculating area under the curve (AUC) and corresponding diagnostic accuracy parameters.
RESULTS
The pons area proved to be the only metric increased exclusively in ARSACS patients (P = 0.02). Other different measures were reduced in ARSACS and SPG7 compared with controls (all with P ≤ 0.005). A cut-off value equal to 1.67 of the pons-to-superior vermis area ratio proved to have the highest AUC (0.98, diagnostic accuracy 93%, sensitivity 97%) in discriminating between ARSACS and SPG7.
CONCLUSIONS
Evaluation of the pons-to-superior vermis area ratio can discriminate ARSACS from other SPAX patients, as exemplified here by SPG7. Hence, we hereby propose this ratio as the Magnetic Resonance Index for the Assessment and Recognition of patients harboring SACS mutations (MRI-ARSACS), a novel diagnostic tool able to identify ARSACS patients and useful for discriminating ARSACS from other SPAX patients undergoing MRI. © 2024 International Parkinson and Movement Disorder Society.
PubMed: 38847051
DOI: 10.1002/mds.29871 -
Respiratory Medicine and Research May 2024
PubMed: 38843599
DOI: 10.1016/j.resmer.2024.101116 -
Science (New York, N.Y.) Jun 2024In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay...
In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express μ-opioid receptors (μORs). Disrupting μOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.
Topics: Animals; Male; Mice; Analgesics, Opioid; Connectome; Mice, Inbred C57BL; Neurons; Opioid-Related Disorders; Oxycodone; Parabrachial Nucleus; Prefrontal Cortex; Pyramidal Cells; Receptors, Opioid, mu; Reward; Substance Withdrawal Syndrome; Transcriptome; Avoidance Learning
PubMed: 38843332
DOI: 10.1126/science.adn0886 -
Proceedings of the National Academy of... Jun 2024Punishment such as electric shock or physical discipline employs a mixture of physical pain and emotional distress to induce behavior modification. However, a neural...
Punishment such as electric shock or physical discipline employs a mixture of physical pain and emotional distress to induce behavior modification. However, a neural circuit that produces behavior modification by selectively focusing the emotional component, while bypassing the pain typically induced by peripheral nociceptor activation, is not well studied. Here, we show that genetically silencing the activity of neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus blocks the suppression of addictive-like behavior induced by footshock. Furthermore, activating CGRP neurons suppresses not only addictive behavior induced by self-stimulating dopamine neurons but also behavior resulting from self-administering cocaine, without eliciting nocifensive reactions. Moreover, among multiple downstream targets of CGRP neurons, terminal activation of CGRP in the central amygdala is effective, mimicking the results of cell body stimulation. Our results indicate that unlike conventional electric footshock, stimulation of CGRP neurons does not activate peripheral nociceptors but effectively curb addictive behavior.
Topics: Animals; Parabrachial Nucleus; Calcitonin Gene-Related Peptide; Mice; Neurons; Behavior, Addictive; Male; Dopaminergic Neurons; Cocaine; Behavior, Animal
PubMed: 38843183
DOI: 10.1073/pnas.2401929121 -
Frontiers in Surgery 2024Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG),...
Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial. This study presents the case of a 19-year-old female with clinical and imaging hallmarks of DIPG, who underwent a biopsy of a tumor in the region of the right middle cerebellar peduncle. Her lesional cells were negative for H3K27M alterations and had low-grade histologic features. Next-generation sequencing revealed a frameshift mutation in the gene as the likely driver mutation. These features suggest a diagnosis of a low-grade glioma associated with loss of function, with far-reaching consequences regarding both treatment strategy and prognosis. This case provides support for the utility of diagnostic tissue biopsy in cases of suspected DIPG.
PubMed: 38840975
DOI: 10.3389/fsurg.2024.1356660 -
ENeuro Jun 2024Social behavior is important for our well-being, and its dysfunctions impact several pathological conditions. Although the involvement of glutamate is undeniable, the...
Social behavior is important for our well-being, and its dysfunctions impact several pathological conditions. Although the involvement of glutamate is undeniable, the relevance of vesicular glutamate transporter type 3 (VGluT3), a specific vesicular transporter, in the control of social behavior is not sufficiently explored. Since midbrain median raphe region (MRR) is implicated in social behavior and the nucleus contains high amount of VGluT3+ neurons, we compared the behavior of male VGluT3 knock-out (KO) and VGluT3-Cre mice, the latter after chemogenetic MRR-VGluT3 manipulation. Appropriate control groups were included. Behavioral test battery was used for social behavior (sociability, social discrimination, social interaction, resident intruder test) and possible confounding factors (open field, elevated plus maze, Y-maze tests). Neuronal activation was studied by c-Fos immunohistochemistry. Human relevance was confirmed by VGluT3 gene expression in relevant human brainstem areas. VGluT3 KO mice exhibited increased anxiety, social interest, but also aggressive behavior in anxiogenic environment and impaired social memory. For KO animals, social interaction induced lower cell activation in the anterior cingulate, infralimbic cortex, and medial septum. In turn, excitation of MRR-VGluT3+ neurons was anxiolytic. Inhibition increased social interest 24 h later but decreased mobility and social behavior in aggressive context. Chemogenetic activation increased the number of c-Fos+ neurons only in the MRR. We confirmed the increased anxiety-like behavior and impaired memory of VGluT3 KO strain and revealed increased, but inadequate, social behavior. MRR-VGluT3 neurons regulated mobility and social and anxiety-like behavior in a context-dependent manner. The presence of VGluT3 mRNA on corresponding human brain areas suggests clinical relevance.
Topics: Animals; Male; Social Behavior; Mice, Knockout; Humans; Anxiety; Raphe Nuclei; Mice; Neurons; Mice, Inbred C57BL; Behavior, Animal; Mice, Transgenic; Amino Acid Transport Systems, Acidic; Proto-Oncogene Proteins c-fos; Aggression
PubMed: 38839305
DOI: 10.1523/ENEURO.0332-23.2024 -
Neurologia Medico-chirurgica Jun 2024Internal neurolysis (IN) is a surgical procedure in which the trigeminal fibers are separated between the pons and porus trigeminus to relieve trigeminal neuralgia (TN)....
Internal neurolysis (IN) is a surgical procedure in which the trigeminal fibers are separated between the pons and porus trigeminus to relieve trigeminal neuralgia (TN). Recent investigations revealed that the number of nerve bundles made by IN varies, and immediate postoperative hypesthesia exceeded 90% and pain control rate at 1 year was 77%-93.5%. We present the preliminary experience of 18 patients who underwent IN for TN between June 2020 and June 2022. The Barrow Neurological Institute pain scale (BNI-PS) was recorded preoperatively and in June 2023, and the Barrow Neurological Institute hypesthesia scale (BNI-HS) was recorded preoperatively, immediate postoperatively and in June 2023. Intraoperatively, the number of bundles made by IN was reviewed. Preoperative BNI-PS ranged between VI and V. Two patients experienced BNI-HS II due to percutaneous procedure prior to IN. Intraoperatively, 3 bundles were made by IN in 7 patients, 4 bundles in 5, and 5 bundles in 6. Immediate postoperative BNI-HS I was recorded in 6 patients and II in 12 (66.7%). The last follow-up revealed that BNI-PS I and II were recorded in 13 patients (72.2%) and BNI-HS I and II in 6 patients, respectively. Our results demonstrated that the rates of immediate postoperative hypesthesia (66.7%) and pain control (72.2%) at 1 year or later were below those of previous reports. Therefore, we are currently combing to make at least 6 bundles. Detailed surgical technique and cardiac reflex alerts during the procedure are described.
PubMed: 38839296
DOI: 10.2176/jns-nmc.2023-0285 -
Clinical Genetics Jun 2024Microcephalic osteodysplastic primordial dwarfism type I (MOPDI) is a very rare and severe autosomal recessive disorder characterized by marked intrauterine growth...
Microcephalic osteodysplastic primordial dwarfism type I (MOPDI) is a very rare and severe autosomal recessive disorder characterized by marked intrauterine growth retardation, skeletal dysplasia, microcephaly and brain malformations. MOPDI is caused by biallelic mutations in RNU4ATAC, a non-coding gene involved in U12-type splicing of 1% of the introns in the genome, which are recognized by their specific splicing consensus sequences. Here, we describe a unique observation of immunodeficiency in twin sisters with mild MOPDI, who harbor a novel n.108_126del mutation, encompassing part of the U4atac snRNA 3' stem-loop and Sm protein binding site, and the previously reported n.111G>A mutation. Interestingly, both twin sisters show mild B-cell anomalies, including low naive B-cell counts and increased memory B-cell and plasmablasts counts, suggesting partial and transitory blockage of B-cell maturation and/or excessive activation of naive B-cells. Hence, the localization of a mutation in stem II of U4atac snRNA, as observed in another RNU4ATAC-opathy with immunodeficiency, that is, Roifman syndrome (RFMN), is not required for the occurrence of an immune deficiency. Finally, we emphasize the importance of considering immunodeficiency in MOPDI management to reduce the risk of serious infectious episodes.
PubMed: 38837402
DOI: 10.1111/cge.14571 -
Neuroradiology Jun 2024The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding...
PURPOSE
The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values.
METHODS
This retrospective study, spanning 2016-2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC.
RESULTS
The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values.
CONCLUSION
Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma's pure edema.
PubMed: 38834877
DOI: 10.1007/s00234-024-03385-0