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Neurobiology of Disease Apr 2024White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures....
White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.
Topics: Humans; Mice; Animals; Diffusion Tensor Imaging; White Matter; Brain; Magnetic Resonance Imaging; Optic Atrophy
PubMed: 38408685
DOI: 10.1016/j.nbd.2024.106455 -
Cortex; a Journal Devoted To the Study... Sep 2023It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the...
It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts.
Topics: Humans; Gerstmann Syndrome; White Matter; Parietal Lobe; Brain; Agnosia
PubMed: 37478549
DOI: 10.1016/j.cortex.2023.05.016 -
JPGN Reports Aug 2023There are very few reports of Wolfram syndrome-2 (WFS2) in the literature, and understanding of involvement of the gastrointestinal (GI) tract in the syndrome is...
BACKGROUND
There are very few reports of Wolfram syndrome-2 (WFS2) in the literature, and understanding of involvement of the gastrointestinal (GI) tract in the syndrome is limited. Objectives: This study aims to describe the clinical presentations of a large number of WFS2 patients with specific focus on their GI manifestations.
METHODS
This is a retrospective case series study. Patients who were homozygous for the gene mutation were identified through the genetic department of Al-Makassed hospital. Their medical records were reviewed, and biometric data have been obtained. The data were collected and arranged on a data sheet, and descriptive analysis was done using SPSS.
RESULTS
Thirteen patients from 9 families were identified; diabetes mellitus was present in 6 of them, optic atrophy in 5, diabetes insipidus (DI) in 5, and deafness in 2. All of the patients had GI manifestations with abnormal findings on upper endoscopy. Dysmorphic facial features and abnormal findings on brain MRI were present in 3 of our patients. The GI manifestations including GI bleeding and severe ulcerations were the first to appear in 9 of them, while anemia in the remaining 4.
CONCLUSION
This is the largest study to date describing patients with WFS2. This study's evidence shows the prominent presence of GI involvement, and the severe findings on endoscopy, including duodenal, gastric, and esophageal ulcerations and strictures. Unlike in the Jordanian report, some of the patients in our report also have DI.
PubMed: 37600626
DOI: 10.1097/PG9.0000000000000339 -
Magnetic Resonance in Medical Sciences... Jun 2024Diffusion-weighted MRI (dMRI) provides a unique non-invasive view of human brain tissue properties. The present review article focuses on tractometry analysis methods...
Diffusion-weighted MRI (dMRI) provides a unique non-invasive view of human brain tissue properties. The present review article focuses on tractometry analysis methods that use dMRI to assess the properties of brain tissue within the long-range connections comprising brain networks. We focus specifically on the major white matter tracts that convey visual information. These connections are particularly important because vision provides rich information from the environment that supports a large range of daily life activities. Many of the diseases of the visual system are associated with advanced aging, and tractometry of the visual system is particularly important in the modern aging society. We provide an overview of the tractometry analysis pipeline, which includes a primer on dMRI data acquisition, voxelwise model fitting, tractography, recognition of white matter tracts, and calculation of tract tissue property profiles. We then review dMRI-based methods for analyzing visual white matter tracts: the optic nerve, optic tract, optic radiation, forceps major, and vertical occipital fasciculus. For each tract, we review background anatomical knowledge together with recent findings in tractometry studies on these tracts and their properties in relation to visual function and disease. Overall, we find that measurements of the brain's visual white matter are sensitive to a range of disorders and correlate with perceptual abilities. We highlight new and promising analysis methods, as well as some of the current barriers to progress toward integration of these methods into clinical practice. These barriers, such as variability in measurements between protocols and instruments, are targets for future development.
PubMed: 38866532
DOI: 10.2463/mrms.rev.2024-0007 -
Bioengineering (Basel, Switzerland) Aug 2023Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic...
Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague-Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1β levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1-4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.
PubMed: 37627826
DOI: 10.3390/bioengineering10080941 -
Scientific Reports Dec 2023Increased intrapelvic pressure (IPP) due to irrigation during flexible ureteroscopy (f-URS) can pose a risk of postoperative severe urinary tract infection associated...
Increased intrapelvic pressure (IPP) due to irrigation during flexible ureteroscopy (f-URS) can pose a risk of postoperative severe urinary tract infection associated with pyelovenous backflow. An automatic regulation system for maintaining safe IPP levels could enable surgeons to perform f-URS safely without postoperative complications. This study aimed to assess the measurement accuracy of an ultra-miniature fiber-optic pressure sensor incorporated into a small-caliper ureteroscope for assessing IPP and to develop an automatic irrigation system linked to this sensor. A porcine kidney was used for the ex vivo experiment. The nephrostomy catheter, connected to the conventional pressure transducer, was placed on the renal pelvis to evaluate the actual IPP (a-IPP). For measuring IPP using the fiber-optic pressure sensor (fo-IPP) built into the f-URS, a diaphragm pressure sensor of Φ250 μm was used. To establish an irrigation system, the optimal proportional-integral-derivative (PID) controller was explored to accurately adjust the irrigation pump flow rate. A high correlation between a-IPP and fo-IPP was confirmed across irrigation pressure values of 60-180 mbar (all, r ≥ 0.7, p < 0.001). When performing bolus irrigation, although fo-IPP showed relatively a higher peak value than a-IPP, the response time of fo-IPP was equivalent to that of a-IPP. After PID parameter optimization, our automatic irrigation system based on fo-IPP smoothly and accurately regulated the intended IPP set in the 5-20 mmHg range without overshooting. We successfully developed and demonstrated an automatic irrigation system regulating IPP based on the PID controller for f-URS, utilizing a fiber-optic pressure sensor. Further research, including in vivo studies, will be needed to assess clinical feasibility.
Topics: Animals; Swine; Ureteroscopes; Ureteroscopy; Pressure; Kidney; Kidney Pelvis; Postoperative Complications
PubMed: 38129475
DOI: 10.1038/s41598-023-47373-5 -
Frontiers in Endocrinology 2023Osteosclerotic metaphyseal dysplasia (OSMD, OMIM 615198) is an extremely rare autosomal recessive osteopetrosis disorder resulting in a distinctive pattern of...
BACKGROUND
Osteosclerotic metaphyseal dysplasia (OSMD, OMIM 615198) is an extremely rare autosomal recessive osteopetrosis disorder resulting in a distinctive pattern of osteosclerosis of the metaphyseal margins of long tubular bones. To date, only thirteen cases have been reported (eight molecularly confirmed). Five homozygous sequence variants in the leucine-rich repeat kinase 1 () gene have been identified to cause OSMD. We present two male siblings with OSMD with a novel variant.
CASES
The index case, now aged 6 years, was referred aged 9 months when diffuse sclerosis of the ribs and vertebral bodies, suggestive of osteopetrosis, was incidentally identified on a chest radiograph for suspected lower respiratory tract infection. Parents were consanguineous and of Pakistani origin. Further evaluation revealed developmental delay, nystagmus with bilateral optic nerve hypoplasia and severe visual impairment. Skeletal survey confirmed typical changes of OSMD, with widespread diffuse sclerosis and Erlenmeyer flask deformity of long bones. His older sibling, now aged 12 years, was 7 years at the time of referral and had similar clinical course and skeletal findings. Additionally, he had a chronic progressive osteonecrosis of the left mandible that required debridement, debulking and long-term antibiotics. Skeletal survey revealed findings similar to his sibling. Neither sibling had significant skeletal fractures or seizures. Unlike most previous reports suggesting sparing of the skull and lack of visual impairment, our patients had evidence of osteosclerosis of the cranium. Genetic screening for the common autosomal recessive and dominant pathogenic variants of osteopetrosis was negative. Whole Exome Sequencing (WES) followed by Sanger sequencing, identified a novel homozygous c.2506C>T p. (Gln836Ter) nonsense variant predicted to result in premature truncation of LRRK1 transcript.
CONCLUSION
Our cases confirm the autosomal recessive inheritance and expand the spectrum of genotype and phenotype of OSMD reported in the literature. Increasing reports of variants in this phenotype raise the question of whether should be included in targeted osteopetrosis panels. Bone histology in previous cases has shown this to be an osteoclast rich form of osteopetrosis raising the possibility that haematopoietic stem cell transplantation may be an appropriate treatment modality.
Topics: Humans; Male; Mutation; Optic Nerve; Osteopetrosis; Osteosclerosis; Protein Serine-Threonine Kinases; Ribs; Sclerosis; Vision Disorders; Child
PubMed: 37920250
DOI: 10.3389/fendo.2023.1258340 -
Bioengineering (Basel, Switzerland) Mar 2024Voicing: requires frequent starts and stops at various sound pressure levels (SPL) and frequencies. Prior investigations using rigid laryngoscopy with oral endoscopy...
UNLABELLED
Voicing: requires frequent starts and stops at various sound pressure levels (SPL) and frequencies. Prior investigations using rigid laryngoscopy with oral endoscopy have shown variations in the duration of the vibration delay between normal and abnormal subjects. However, these studies were not physiological because the larynx was viewed using rigid endoscopes. We adapted a method to perform to perform simultaneous high-speed naso-endoscopic video while simultaneously acquiring the sound pressure, fundamental frequency, airflow rate, and subglottic pressure. This study aimed to investigate voice onset patterns in normophonic males and females during the onset of variable SPL and correlate them with acoustic and aerodynamic data.
MATERIALS AND METHODS
Three healthy males and three healthy females were studied by simultaneous high-speed video laryngoscopy and recording with the production of the gesture [pa:pa:] at soft, medium, and loud voices. The fiber optic endoscope was threaded through a pneumotachograph mask for the simultaneous recording and analysis of acoustic and aerodynamic data.
RESULTS
The average increase in the sound pressure level (SPL) for the group was 15 dB, from 70 to 85 dB. The fundamental frequency increased by an average of 10 Hz. The flow was increased in two subjects, reduced in two subjects, and remained the same in two subjects as the SPL increased. There was a steady increase in the subglottic pressure from soft to loud phonation. Compared to soft to medium phonation, a significant increase in glottal resistance was observed with medium-to-loud phonation. Videokymogram analysis showed the onset of vibration for all voiced tokens without the need for full glottis closure. In loud phonation, there is a more rapid onset of a larger amplitude and prolonged closure of the glottal cycle; however, more cycles are required to achieve the intended SPL. There was a prolonged closed phase during loud phonation. Fast Fourier transform (FFT) analysis of the kymography waveform signal showed a more significant second- and third-harmonic energy above the fundamental frequency with loud phonation. There was an increase in the adjustments in the pharynx with the base of the tongue tilting, shortening of the vocal folds, and pharyngeal constriction.
CONCLUSION
Voice onset occurs in all modalities, without the need for full glottal closure. There was a more significant increase in glottal resistance with loud phonation than that with soft or middle phonation. Vibration analysis of the voice onset showed that more time was required during loud phonation before the oscillation stabilized to a steady state. With increasing SPL, there were significant variations in vocal tract adjustments. The most apparent change was the increase in tongue tension with posterior displacement of the epiglottis. There was an increase in pre-phonation time during loud phonation. Patterns of muscle tension dysphonia with laryngeal squeezing, shortening of the vocal folds, and epiglottis tilting with increasing loudness are features of loud phonation. These observations show that flexible high-speed video laryngoscopy can reveal observations that cannot be observed with rigid video laryngoscopy. An objective analysis of the digital kymography signal can be conducted in selected cases.
PubMed: 38671756
DOI: 10.3390/bioengineering11040334 -
Oncology Letters Oct 2023Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal...
Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal cholangiocarcinoma, which was successfully managed using stereotactic radiotherapy (SRT). A 67-year-old Japanese man underwent pancreaticoduodenectomy for distal cholangiocarcinoma. The pathological stage was T2N0M0 stage IIA, according to the Union for International Cancer Control 8th edition. After surgery, the patient received adjuvant chemotherapy with oral TS-1 for 1 month. A total of 2 months after surgery, the patient was readmitted to hospital due to decreased visual acuity. Fundoscopy revealed a macular hole in the right eye that accounted for the decreased visual acuity. Additionally, Goldmann three-mirror contact lens examination revealed a 4-mm choroidal mass with a yellowish color situated at a considerable distance from the optic nerve. Magnetic resonance imaging revealed an enhanced choroidal mass. Based on the findings of ophthalmologic examinations and the patient's history of cholangiocarcinoma, they were diagnosed with choroidal metastasis from distal cholangiocarcinoma. SRT was administered at a total dose of 40 Gy divided into 8 Gy fractions. A total of 1 year after SRT, the patient achieved complete remission without decreased visual acuity. The patient remains alive and in good health without recurrence, 4 years after the diagnosis of choroidal metastasis. To the best of our knowledge, this is the second reported case of intraocular metastasis from cholangiocarcinoma. In conclusion, SRT may provide an opportunity to control metastatic choroidal carcinoma without decreasing visual acuity.
PubMed: 37674862
DOI: 10.3892/ol.2023.14004 -
Cureus Dec 2023This is a case of an orbital abscess evidenced radiologically in a 41-year-old female with no comorbidities. She was healthy and had no history of trauma or infection of...
This is a case of an orbital abscess evidenced radiologically in a 41-year-old female with no comorbidities. She was healthy and had no history of trauma or infection of the adjacent structures. She denied having symptoms of upper or lower respiratory and urinary tract infections. The decision for surgical drainage was made following a slow response to antimicrobial agents after 24 hours, a progressive painful erythematous eyelid swelling, and further deterioration of vision. Her clinical condition and visual acuity improved following cutaneous incision and drainage. Culture and sensitivity results for urine and orbital abscess were positive for Staphylococcus (S.) aureus. The patient regained full visual recovery without any sequelae. In conclusion, an orbital abscess is a blinding and life-threatening condition that rarely occurs in immunocompetent individuals and uncommonly arises from distant sources. A high index of suspicion, early institution of appropriate diagnostic imaging, and aggressive medical and surgical treatment are necessary for a favorable visual outcome in orbital abscess cases.
PubMed: 38229775
DOI: 10.7759/cureus.50693