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Alzheimer's & Dementia : the Journal of... Jun 2024Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our...
INTRODUCTION
Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types.
METHODS
We conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control (N = 28), progressive supranuclear palsy (PSP) (N = 18), and AD (N = 21) cases.
RESULTS
Protein co-expression network analysis identified unique cerebrovascular modules significantly correlated with amyloid plaques, cerebrovascular amyloid angiopathy (CAA), and/or tau pathology. The protein products within AD genetic risk loci were concentrated within cerebrovascular modules. The overlap between differentially abundant proteins in AD cerebrospinal fluid (CSF) and plasma with cerebrovascular network highlighted a significant increase of matrisome proteins, SMOC1 and SMOC2, in CSF, plasma, and brain.
DISCUSSION
These findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases.
Topics: Humans; Biomarkers; Alzheimer Disease; Proteomics; Male; Aged; Female; Brain; Tauopathies; Supranuclear Palsy, Progressive; Cerebral Amyloid Angiopathy; Middle Aged; Aged, 80 and over; tau Proteins
PubMed: 38713744
DOI: 10.1002/alz.13821 -
Journal of Neural Transmission (Vienna,... Oct 2023Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the...
Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations.
Topics: Humans; Supranuclear Palsy, Progressive; Mental Disorders; Brain; Anxiety; Behavioral Symptoms
PubMed: 37535119
DOI: 10.1007/s00702-023-02676-9 -
BMC Anesthesiology Jul 2023Dexmedetomidine is a medication that has analgesic, sedative, and anti-anxiety properties. In the clinical, it is often used to prevent common complications associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Dexmedetomidine is a medication that has analgesic, sedative, and anti-anxiety properties. In the clinical, it is often used to prevent common complications associated with strabismus surgery, including postoperative delirium, postoperative nausea and vomiting, postoperative pain, and oculocardiac reflex. However, its effectiveness and side effects of the present studies are different. The sample sizes of the present studies on the prevention of complications of dexmedetomidine are small. Therefore, this study evaluates the efficacy of dexmedetomidine in preventing anesthesia-related complications in strabismus surgery through a systematic review and meta-analysis.
METHODS
Literature was retrieved from 10 commonly used databases and randomized controlled trials published up to May 2022 were sought. The included studies compared the intervention effects of dexmedetomidine versus placebo on anesthesia-related complications in surgery. The occurrence rates of postoperative delirium, postoperative nausea and vomiting, postoperative pain, and oculocardiac reflex in patients undergoing strabismus surgery were evaluated. Statistical analyses and forest plots were generated using Review Manager and STATA software. Binary outcomes were measured using relative risk (RR) with a 95% confidence interval for each outcome. The Cochrane risk of bias tool was used to assess the bias and risk in the studies that met the inclusion criteria.
RESULTS
A total of 13 articles were ultimately included in the analysis, comprising 1,018 patients who underwent strabismus surgery. The dexmedetomidine group, compared to the placebo group, demonstrated significant reductions in the incidence of postoperative delirium (RR = 0.73, P = 0.001), severe postoperative delirium (RR = 0.45, P = 0.005), postoperative nausea and vomiting (RR = 0.48, P < 0.0001), and the need for supplemental analgesia postoperatively (RR = 0.60, P = 0.004). Additionally, subgroup analysis revealed that intravenous administration of dexmedetomidine significantly reduced the incidence of oculocardiac reflex (RR = 0.50, P = 0.001). In contrast, intranasal administration of dexmedetomidine did not have a significant effect on the incidence of oculocardiac reflex (RR = 1.22, P = 0.15). There was a significant difference between the subgroups (P = 0.0005, I2 = 91.7%).
CONCLUSION
Among patients undergoing strabismus surgery, the use of dexmedetomidine can alleviate postoperative delirium and reduce the incidence of postoperative nausea and vomiting, as well as postoperative pain. Moreover, intravenous administration of dexmedetomidine can lower the occurrence rate of the oculocardiac reflex.
Topics: Humans; Postoperative Nausea and Vomiting; Dexmedetomidine; Emergence Delirium; Pain, Postoperative; Strabismus; Anesthesia
PubMed: 37491215
DOI: 10.1186/s12871-023-02215-9 -
The Journal of Neuroscience : the... Oct 2023Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across...
Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals and are linked with worse prognosis, and lack improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system. Here we test the hypothesis that structural variation of the LC explains response inhibition deficits in PSP and PD. Twenty-four people with idiopathic PD, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls undertook a stop-signal task and ultrahigh field 7T magnetization-transfer-weighted imaging of the LC. Parameters of "race models" of go- versus stop-decisions were estimated using hierarchical Bayesian methods to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between LC integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. PSP caused a distinct pattern of abnormalities in inhibitory control with a paradoxically reduced threshold for go responses, but longer nondecision times, and more lapses of attention. The variation in response inhibition correlated with the variability of LC integrity across participants in both clinical groups. Structural imaging of the LC, coupled with behavioral modeling in parkinsonian disorders, confirms that LC integrity is associated with response inhibition and LC degeneration contributes to neurobehavioral changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimization of noradrenergic treatment is likely to benefit from stratification according to LC integrity. Response inhibition deficits contribute to clinical symptoms and poor outcomes in people with Parkinson's disease and progressive supranuclear palsy. We used cognitive modeling of performance of a response inhibition task to identify disease-specific mechanisms of abnormal inhibitory control. Response inhibition in both patient groups was associated with the integrity of the noradrenergic locus coeruleus, which we measured using ultra-high field MRI. We propose that the imaging biomarker of locus coeruleus integrity provides a trans-diagnostic tool to explain individual differences in response inhibition ability beyond the classic nosological borders and diagnostic criteria. Our data suggest a potential new stratified treatment approach for Parkinson's disease and progressive supranuclear palsy.
Topics: Humans; Supranuclear Palsy, Progressive; Parkinson Disease; Locus Coeruleus; Bayes Theorem; Parkinsonian Disorders
PubMed: 37669861
DOI: 10.1523/JNEUROSCI.0289-22.2023 -
European Journal of Ophthalmology Sep 2023In this report we illustrate the ophthalmologic assessment of two patients affected by Proteus Syndrome (PS), an extremely rare genetic disorder. Case #1 describes a 26...
In this report we illustrate the ophthalmologic assessment of two patients affected by Proteus Syndrome (PS), an extremely rare genetic disorder. Case #1 describes a 26 year old male patient followed for multiple ophthalmic anomalies: a limbal dermoid cyst, a unilateral cataract, bilateral nystagmus, severe myopia and unilateral optic nerve head drusen. Case #2 describes a 20 year old female patient referred to our Ophthalmology Department for a routine ophthalmologic evaluation after being treated for 3 years with Miransertib (an experimental AKT-pathway inhibitor). Both patients underwent a complete ophthalmologic examination and a multimodal imaging evaluation. The multimodal imaging approach has revealed useful to evaluate both cases in detail and to keep track of disease evolution over time, moreover providing helpful features to further characterize this rare syndrome.
Topics: Male; Female; Humans; Young Adult; Adult; Proteus Syndrome; Eye Abnormalities; Nystagmus, Pathologic; Diagnostic Imaging; Myopia; Abnormalities, Multiple
PubMed: 36113118
DOI: 10.1177/11206721221125852 -
Journal of AAPOS : the Official... Feb 2024To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis.
PURPOSE
To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis.
METHODS
The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements.
RESULTS
A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups.
CONCLUSIONS
In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.
Topics: Child; Humans; Case-Control Studies; Retrospective Studies; Craniosynostoses; Acrocephalosyndactylia; Strabismus; Orbit
PubMed: 38219920
DOI: 10.1016/j.jaapos.2023.10.006 -
BMC Neurology Sep 2023Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia....
BACKGROUND
Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia. Some studies reported MFS as an adverse effect of the COVID-19 vaccination. We aimed to have a detailed evaluation on demographic, clinical, and para-clinical characteristics of subjects with MFS after receiving COVID-19 vaccines.
MATERIALS AND METHODS
A thorough search strategy was designed, and PubMed, Web of Science, and Embase were searched to find relevant articles. Each screening step was done by twice, and in case of disagreement, another author was consulted. Data on different characteristics of the patients and types of the vaccines were extracted. The risk of bias of the studies was assessed using Joanna Briggs Institute (JBI) tools.
RESULTS
In this study, 15 patients were identified from 15 case studies. The median age of the patients was 64, ranging from 24 to 84 years. Ten patients (66.6%) were men and Pfizer made up 46.7% of the injected vaccines. The median time from vaccination to symptoms onset was 14 days and varied from 7 to 35 days. Furthermore,14 patients had ocular signs, and 78.3% (11/14) of ocular manifestations were bilateral. Among neurological conditions, other than MFS triad, facial weakness or facial nerve palsy was the most frequently reported side effect that was in seven (46.7%) subjects. Intravenous immunoglobulin (IVIg) was the most frequently used treatment (13/15, 86.7%). Six patients received 0.4 g/kg and the four had 2 g/kg. Patients stayed at the hospital from five to 51 days. No fatal outcomes were reported. Finally, 40.0% (4/15) of patients completely recovered, and the rest experienced improvement.
CONCLUSION
MFS after COVID-19 immunization has favorable outcomes and good prognosis. However, long interval from disease presentation to treatment in some studies indicates that more attention should be paid to MFS as the adverse effect of the vaccination. Due to the challenging diagnosis, MFS must be considered in list of the differential diagnosis in patients with a history of recent COVID-19 vaccination and any of the ocular complaints, ataxia, or loss of reflexes, specially for male patients in their 60s and 70s.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Young Adult; Ataxia; COVID-19; COVID-19 Vaccines; Drug-Related Side Effects and Adverse Reactions; Facial Paralysis; Miller Fisher Syndrome; Prognosis; Vaccination
PubMed: 37735648
DOI: 10.1186/s12883-023-03375-4 -
The American Surgeon Sep 2023Neuroblastomas are the most common extracranial solid malignancy in children with variable manifestations and complications depending on the presence of paraneoplastic...
BACKGROUND
Neuroblastomas are the most common extracranial solid malignancy in children with variable manifestations and complications depending on the presence of paraneoplastic syndromes.
MATERIALS AND METHODS
We performed a single institution retrospective cohort study of all patients less than 18 years old diagnosed with neuroblastoma or ganglioneuroblastoma between January 2002 and July 2022. Patients were identified through the pathology and cancer registry and cross-referenced with pediatric records. Patient demographics, clinical presentation, treatment, and outcomes were collected. A univariate descriptive analysis of the collected data was conducted.
RESULTS
In our study period, 130 children were diagnosed with neuroblastoma, and 15 were diagnosed with ganglioneuroblastoma. There were 12 children with a paraneoplastic syndrome identified, 8 with NBL and 4 with ganglioneuroblastoma (GNBL). The average age at diagnosis was 22 months. All but 1 underwent resection prior to treatment of paraneoplastic syndrome, and 4 children required neoadjuvant therapy. Neurological complications were the most common with 10 children (83%). The average time from symptom onset to diagnosis was 0.7 months. Eight children had complete resolution of their symptoms after treatment and resection, 2 children recently started treatment within a year, 1 had partial resolution, and 1 died during treatment. The presence of tumor-infiltrating lymphocytes occurred in 4 children with neurologic paraneoplastic syndromes. Six children had neuropil rich tumors.
CONCLUSION
The histological profile of paraneoplastic syndromes of neuroblastoma and ganglioneuroblastoma and their treatment across a single institution can be highly variable. The presence of tumor-infiltrating lymphocytes and neuropil may have an impact on paraneoplastic pathology.
Topics: Humans; Child; Infant; Adolescent; Ganglioneuroblastoma; Retrospective Studies; Neuroblastoma; Paraneoplastic Syndromes; Nervous System Diseases
PubMed: 37150742
DOI: 10.1177/00031348231175112 -
Journal of Child Neurology Mar 2024Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain...
INTRODUCTION
Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain volumes in pediatric opsoclonus-myoclonus ataxia syndrome patients compared with age- and sex-matched healthy children.
PATIENTS AND METHODS
This longitudinal case-control study included brain magnetic resonance imaging (MRI) scans from consecutive pediatric opsoclonus-myoclonus ataxia syndrome patients (2009-2020) and age- and sex-matched healthy control children. FreeSurfer analysis provided automatic volumetry of the brain. Paired tests were performed on the curvature of growth trajectories, with Bonferroni correction.
RESULTS
A total of 14 opsoclonus-myoclonus ataxia syndrome patients (12 female) and 474 healthy control children (406 female) were included. Curvature of the growth trajectories of the cerebral white and gray matter, cerebellar white and gray matter, and brainstem differed significantly between opsoclonus-myoclonus ataxia syndrome patients and healthy control children (cerebral white matter, = .01; cerebral gray matter, = .01; cerebellar white matter, < .001; cerebellar gray matter, = .049; brainstem, < .01).
DISCUSSION/CONCLUSION
We found abnormal brain maturation in the supratentorial brain, brainstem, and cerebellum in children with opsoclonus-myoclonus ataxia syndrome.
Topics: Humans; Female; Male; Longitudinal Studies; Opsoclonus-Myoclonus Syndrome; Magnetic Resonance Imaging; Brain; Child; Case-Control Studies; Child, Preschool; Adolescent; Organ Size
PubMed: 38544431
DOI: 10.1177/08830738241240181 -
Ceska a Slovenska Oftalmologie :... 2023To evaluate the state of binocular vision, the amount and direction of the ocular deviation before and after strabismus surgery in adult patients and to monitor the...
PURPOSE
To evaluate the state of binocular vision, the amount and direction of the ocular deviation before and after strabismus surgery in adult patients and to monitor the occurrence of postoperative complications.
METHODS
The retrospective study of 58 adult patients with selected types of strabismus who were surgically treated in the Eye Department of the Tomas Bata Regional Hospital in Zlín. We evaluated the amount and the degree of the primary ocular deviation and the binocular alignment before and after surgery, as well as the state of binocular vision after surgery and the occurrence of postoperative complications.
RESULTS
The average deviation in convergent strabismus before surgery was +23.46 degrees, after surgery +6.6 degrees, in divergent strabismus it was -21.5 degrees, after surgery -1.48 degrees, for vertical strabismus before surgery +12.5 degrees and +3.75 degrees after surgery and in paralytic strabismus +20 degrees before surgery and +3 degrees postoperatively. Preoperatively there was effectively no binocular vision in up to 63.9% of patients, superposition occurred in 31%, fusion in 5.1%. No patient had stereopsis before surgery. After surgery, superposition was present in 39.7%, fusion in 31% and stereopsis in 6.9% of patients. Only 22.4% of patients experienced no binocular vision after surgery. Of the selected 21 patients out of 58 with an observation period of at least 3 years, we observed an improvement or development of binocular vision functions after surgery in 12 patients and no improvement of binocular vision functions in 9 patients. In the first group, 58.3% had a stable deviation throughout the follow-up period. While in the second group the deviation was stable in only 33.3%. We can assume that the improvement in binocular vision function after strabismus surgery, leads to a greater longer-term stability of postoperative deviations.
CONCLUSION
Strabismus surgery in adult patients is an effective and safe method, which is not only a cosmetic procedure used to adjust the position of the eyes, but also enables us to induce or improve the state of binocular vision functions.
Topics: Adult; Humans; Retrospective Studies; Strabismus; Oculomotor Muscles; Vision, Binocular; Postoperative Complications; Ophthalmologic Surgical Procedures
PubMed: 38086701
DOI: 10.31348/2023/32