Progressive Atrophy Research Articles

What Is Brain Damage and Does Electroconvulsive Therapy Cause It?

Surveys show public misperceptions and confusion about brain damage and electroconvulsive therapy (ECT). Fictional movies have misrepresented ECT to suggest brain damage and to ridicule mental illness and psychiatric patients. "Brain damage" has become a colloquial expression without consistent meaning. In contrast, brain injury is the medical term for destruction of brain cells, such as from kinetic impact (concussion), hypoxia, or infection. Studies of both high-resolution magnetic resonance imaging (MRI) and enzyme assays find that causes of brain injury are accompanied by observable structural changes on MRI and elevated blood and cerebrospinal fluid levels of brain enzymes that leak from injured brain cells. Concussion is also followed by intracerebral bleeding, progressive brain atrophy, diffuse axonal injury, cranial nerve injury, and 2-4 fold increased risk for dementia. In contrast, there is no evidence that ECT produces any of these. Studies of ECT patients find no brain edema, structural change persisting 6 months, or elevated levels of leaked brain enzymes. Statistical comparisons between brain injury and ECT effects indicate no similarity ( P < 0.00000001). Moreover, the kinetic, thermal, and electrical effects of ECT are far below levels that could possibly cause harm. This robust evidence shows that there is no basis to claim that ECT causes brain injury.

The Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplants.

Tacrolimus (TAC) has a narrow therapeutic window and patient-specific pharmacokinetic variability. In our study, we analyzed the association between TAC exposure, metabolism, and kidney graft outcomes (function, rejection, and histological lesions). TAC trough (C0), coefficient of variation (TAC CV), concentration/dose ratio (C/D), and biomarkers related to kidney injury molecule-1 (KIM-1) and neutrophil gelatinase lipocalin (NGAL) were analyzed. We examined 174 patients who were subjected to a triple immunosuppressive regimen and underwent kidney transplantation between 2017 and 2022. Surveillance biopsies were performed at the time of kidney implantation and at three and twelve months after transplantation. We classified patients based on their Tac C/D ratios, classifying them as fast (C/D ratio < 1.05 ng/mL × 1/mg) or slow (C/D ratio ≥ 1.05 ng/mL × 1/mg) metabolizers. TAC exposure/metabolism did not significantly correlate with interstitial fibrosis/tubular atrophy (IF/TA) progression during the first year after kidney transplantation. TAC CV third tertile was associated with a higher chronicity score at one-year biopsy. TAC C/D ratio at three months and Tac C0 at six months were associated with rejection during the first year after transplantation. A fast TAC metabolism at six months was associated with reduced kidney graft function one year (OR: 2.141, 95% CI: 1.044-4.389, p = 0.038) and two years after transplantation (OR: 4.654, 95% CI: 1.197-18.097, p = 0.026), and TAC CV was associated with reduced eGFR at three years. uNGAL correlated with IF/TA and chronicity scores at three months and negatively correlated with TAC C0 and C/D at three months and one year. Conclusion: Calculating the C/D ratio at three and six months after transplantation may help to identify patients at risk of suffering acute rejection and deterioration of graft function.

Streamlining quantification of age‐related vocal atrophy

AbstractObjectivesAge‐related vocal atrophy (ARVA) has a significant impact on voice, communication, and quality of life. Vocal folds are bowed with incomplete glottic closure during phonation. Efficient quantification of vocal fold atrophy and collection of voice recordings in clinic remains challenging. The primary focus of this study is to describe a novel method for quantifying vocal atrophy and obtaining voice recordings in clinic among patients with ARVA.MethodsPatients with ARVA were included. Voice recordings were collected during the clinic visit, and acoustic analysis was subsequently performed. A novel mobile application was used to quantify the bowing index (BI).ResultsThe study included 10 patients with ARVA, with a mean age of 72.7 ± 6.8 years and body mass index (BMI) of 24.9 ± 2.4 kg/m2. Calculation of BI was feasible with a mean of 9.9 ± 1.8 units. On average, the audio recording took 2.6 ± 0.4 min, and subsequent analysis required 7.1 ± 1.8 min. Mean continuous speech f0 was 212.1 ± 10.1 and 134.2 ± 31.5 Hz for male and female patients, respectively. Smoothed cepstral peak prominence was 8.9 ± 1.5 dB (male) and 8.5 ± 0.3 dB (female), and maximum phonation time between male and female patients was 16.7 ± 9.8 and 13.8 ± 1.9 s, respectively.ConclusionWe present a feasible and streamlined method for quantification of vocal fold atrophy in the clinic among patients with ARVA. The accuracy and reliability of this new method are areas of ongoing investigation. Quantification of vocal atrophy may help with clinical decisions, including diagnosing vocal atrophy and tracking treatment progress. Moreover, this method may improve research data acquisition without burdening patients and clinicians with additional time‐consuming tasks.Level of evidence: 4.

Long-term clinical observation of patients with heterozygous KIF1A variants.

KIF1A-related disorders (KRDs) encompass recessive and dominant variants with wide clinical variability. Recent genetic investigations have expanded the clinical phenotypes of heterozygous KIF1A variants. However, there have been a few long-term observational studies of patients with heterozygous KIF1A variants. A retrospective chart review of consecutive patients diagnosed with spastic paraplegia at Miyagi Children's Hospital from 2016 to 2020 identified six patients with heterozygous KIF1A variants. To understand the long-term changes in clinical symptoms, we examined these patients in terms of their characteristics, clinical symptoms, results of electrophysiological and neuroimaging studies, and genetic testing. The median follow-up period was 30 years (4-44 years). This long-term observational study showed that early developmental delay and equinus gait, or unsteady gait, are the first signs of disease onset, appearing with the commencement of independent walking. In addition, later age-related progression was observed in spastic paraplegia, and the appearance of axonal neuropathy and reduced visual acuity were characteristic features of the late disease phenotype. Brain imaging showed age-related progression of cerebellar atrophy and the appearance of hyperintensity of optic radiation on T2WI and FLAIR imaging. Long-term follow-up revealed a pattern of steady progression and a variety of clinical symptoms, including spastic paraplegia, peripheral neuropathy, reduced visual acuity, and some degree of cerebellar ataxia. Clinical variability between patients was observed to some extent, and therefore, further studies are required to determine the phenotype-genotype correlation.

Frequency of RPGRIP1 and MAP9 genetic modifiers of canine progressive retinal atrophy, in 132 breeds of dog.

Variants in RPGRIP1 and MAP9, termed RPGRIP1ins44 and MAP9del respectively, are both associated with a form of canine progressive retinal atrophy referred to as RPGRIP1-CRD and have both been demonstrated to modify the development and progression of this disease. In the current study both variants were genotyped in at least 50 dogs of 132 diverse breeds and the data reveal that both segregate in multiple breeds. Individually, each variant is common within largely non-overlapping subsets of breed, and there is a negative correlation between their frequencies within breeds that segregate both variants. The frequency of both variants exceeds 0.05 in a single breed only, the Miniature Longhaired Dachshund. These data indicate that both variants are likely to be ancient and predate the development and genetic isolation of modern dog breeds. That both variants are present individually at high frequency in multiple breeds is consistent with the hypothesis that homozygosity of either variant alone is not associated with a clinically relevant phenotype, whereas the negative correlation between the two variants is consistent with the application of selective pressure, from dog breeders, against homozygosity at both loci, probably due to the more severe phenotype associated with homozygosity at both loci.

Lens subluxation combined with parry-romberg syndrome: case report

BackgroundParry-Romberg syndrome (PRS) is a rare progressive degenerative disorder of unknown etiology. Here we report a rare case of PRS combined with lens subluxation in Eye and ENT hospital of Fudan University, Shanghai. To our knowledge, it is the first reported case of PRS combined with lens subluxation that has been managed surgically with phacoemulsification and CTR placement and IOL implantation in Shanghai.Case presentationA 60-year-old woman was referred for “right visual blur for 2 years” and had persistent right facial paralysis of unknown etiology since the age 12. She had right facial muscle atrophy and paralysis. Eye examination also showed the right eyelid pseudoptosis, enophthalmos, age-related cataract combined with lens subluxation existed in the right eye. The patient was diagnosed as age-related cataract and lens subluxation in the right eye and progressive hemifacial atrophy (Parry-Romberg syndrome). We conducted a combined phacoemulsification, IOL and CTR implantation and pupilloplasty surgery for the patient under general anesthesia and the postoperative UCVA was 20/30 and remained for 1 year’s follow up.ConclusionsHere we reported a rare case of PHA combined with lens subluxation in China. After appropriate eye surgery, the patient achieved satisfying vision result in the right eye.

Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia.

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

When Two Eyes Don't Suffice-Learning Difficult Hyperfluorescence Segmentations in Retinal Fundus Autofluorescence Images via Ensemble Learning.

Hyperfluorescence (HF) and reduced autofluorescence (RA) are important biomarkers in fundus autofluorescence images (FAF) for the assessment of health of the retinal pigment epithelium (RPE), an important indicator of disease progression in geographic atrophy (GA) or central serous chorioretinopathy (CSCR). Autofluorescence images have been annotated by human raters, but distinguishing biomarkers (whether signals are increased or decreased) from the normal background proves challenging, with borders being particularly open to interpretation. Consequently, significant variations emerge among different graders, and even within the same grader during repeated annotations. Tests on in-house FAF data show that even highly skilled medical experts, despite previously discussing and settling on precise annotation guidelines, reach a pair-wise agreement measured in a Dice score of no more than 63-80% for HF segmentations and only 14-52% for RA. The data further show that the agreement of our primary annotation expert with herself is a 72% Dice score for HF and 51% for RA. Given these numbers, the task of automated HF and RA segmentation cannot simply be refined to the improvement in a segmentation score. Instead, we propose the use of a segmentation ensemble. Learning from images with a single annotation, the ensemble reaches expert-like performance with an agreement of a 64-81% Dice score for HF and 21-41% for RA with all our experts. In addition, utilizing the mean predictions of the ensemble networks and their variance, we devise ternary segmentations where FAF image areas are labeled either as confident background, confident HF, or potential HF, ensuring that predictions are reliable where they are confident (97% Precision), while detecting all instances of HF (99% Recall) annotated by all experts.

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK

Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

A Post-Marketing Surveillance Study of Nusinersen for Spinal Muscular Atrophy in Routine Medical Practice in China: Interim Results.

Spinal muscular atrophy (SMA) is a rare, autosomal recessive, neuromuscular disease that leads to progressive muscular weakness and atrophy. Nusinersen, an antisense oligonucleotide, was approved for SMA in China in February 2019. We report interim results from a post-marketing surveillance phase 4 study, PANDA (NCT04419233), that collects data on the safety, efficacy, and pharmacokinetics of nusinersen in children with SMA in routine clinical practice in China. Participants enrolled in PANDA will be observed for 2years following nusinersen treatment initiation. The primary endpoint is the incidence of adverse events (AEs)/serious AEs (SAEs) during the treatment period. Efficacy assessments include World Health Organization (WHO) Motor Milestones assessment, the Hammersmith Infant Neurological Examination (HINE), and ventilation support. Plasma and cerebrospinal fluid (CSF) concentrations of nusinersen are measured at each dose visit. Fifty participants were enrolled as of the January 4, 2023, data cutoff: 10 with infantile-onset (≤ 6months) and 40 with later-onset (> 6months) SMA. All 50 participants have received at least one dose of nusinersen; 6 have completed the study. AEs were experienced by 45 (90%) participants and were mostly mild/moderate; no AEs led to nusinersen discontinuation or study withdrawal. Eleven participants experienced SAEs, most commonly pneumonia (n = 9); none were considered related to study treatment. Stability or gain of WHO motor milestone was observed and mean HINE-2 scores improved in both subgroups throughout the study. No serious respiratory events occurred,and no permanent ventilation support was initiated during the study. Pre-dose nusinersen CSF concentrations increased steadily through the loading-dose period, with no accumulation in plasma after multiple doses. Nusinersen was generally well tolerated with an acceptable overall safety profile, consistent with the known safety of nusinersen. Efficacy, safety, and nusinersen exposure are consistent with prior observations. These results support continuing PANDA and evaluation of nusinersen in Chinese participants with SMA. ClinicalTrials.gov identifier, NCT04419233.

A retrospective study of adult patients with Parry-Romberg syndrome.

Parry–Romberg syndrome (PRS), also known as progressive hemifacial atrophy, is characterized by atrophy of the skin and subcutaneous tissue, including muscle, bone and cartilage. PRS is a clinical diagnosis, although supportive imaging and histology may be obtained. We present a case series of 10 adult patients with a diagnosis of PRS seen at Massachusetts General Hospital and Brigham and Women’s Hospital from 2000 to 2021. Nine of 10 patients were women, with a mean (SD) age at onset of 27.3 (12.1) years and a mean (SD) of 12.4 (7.8) years between disease onset and diagnosis. Of the 10 patients, 4 had biopsies with supportive histopathology findings and 7 had positive imaging findings. Patients typically received both medical and surgical treatments.

Autonomic dysfunction and motor progression in multiple system atrophy: A 1-year prospective cohort study

Autonomic dysfunction and motor progression in multiple system atrophy: A 1-year prospective cohort study

Muscle atrophy is coupled with ferroptosis in the skeletal muscle of Friedreich’s ataxia

Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by an expansion of GAA repeats in the frataxin gene (FXN), resulting in frataxin deficiency. As frataxin is crucial for mitochondrial function by recruiting key iron components such as iron-sulfur clusters and hemes, FRDA is characterized by mitochondrial dysfunction along with abnormal iron metabolism. Recently, ferroptosis, an iron-dependent cell death, has been suggested to play an important role in the development of FRDA, yet if and how ferroptosis impacts FRDA-related muscle weakness has not been studied. Therefore, the objective of this study was to identify the role of ferroptosis in the skeletal muscle of FRDA using whole-body frataxin deficient mice (Fxnnull::YG8s(GAA)&gt;800, #030395, The Jackson Laboratory). FRDA mice (male, 3-months old) had a significantly smaller ratio of muscle mass to body mass, compared to strain-, age-, and sex-matched C57BL/6J control mice, suggesting that this animal model develops muscle atrophy as early as 3 months old upon frataxin deficiency. Furthermore, the FRDA muscles showed elevated non-heme iron levels, which were accompanied by altered iron regulatory protein expressions, including ferritin and ferroportin. In addition, mitochondrial function was decreased in the skeletal muscles of FRDA mice, as evidenced by significantly decreased protein levels of oxidative phosphorylation complexes (OXPHOS I, II, and III; decrease by 31%, 26%, and 15% compared to control, respectively), as well as other mitochondrial capacity markers such as nuclear factor erythroid 2-related factor 1 (Nrf1) and heme oxygenase-1 ( p=0.06). Notably, ferroptosis markers such as Nrf2 and glutathione peroxidase 4 were significantly downregulated in the skeletal muscles of FRDA mice, while apoptotic markers (p53 and caspase 3) were not altered. Collectively, ferroptosis could promote FRDA-related muscle atrophy, which is associated with abnormal mitochondrial iron status and function. Our results also suggest that ferroptosis may represent a novel target for correcting or ameliorating the development and progression of muscle atrophy in FRDA patients. Future studies are warranted to determine the molecular mechanism of ferroptosis in FRDA-related mitochondrial dysfunction and to develop therapeutic strategies for muscle weakness in FRDA or other types of ataxias. This study was supported in part by the NIH NS121394 and UMass Lowell Internal Seed Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chorioretinal Atrophic Lesions Evolution in Patients with Quiescent Myopic Choroidal Neovascularization Followed for More Than 10 Years.

To evaluate the progression of chorioretinal atrophic areas associated with myopic choroidal neovascularization (CNV) in high myopic patients followed by a minimum period of 10 years. Patients with myopic CNV lesions that achieved clinical and structural remissions over 10 years of follow-up were included. Medical records were reviewed for CNV characterization and treatment, best-corrected visual acuity at baseline (BCVA0), immediately after the last treatment (BCVA1) and at the latest visit (BCVA2). Fundus autofluorescence (FAF) was used to quantify the amount of atrophic area increase per year associated with the treated myopic CNV lesion. The first FAF performed after treatment suspension (FAF1) was compared with the most recent exam (FAF2). Thirty-six eyes from 36 patients were included. Mean total follow-up was 12.38 ± 2.68 years. Mean number of intravitreal injections (IVI) was 12.50 ± 12.40 and 25% of the eyes had previous treatment with photodynamic therapy (PDT). Mean improvement between BCVA0 and BCVA1 was 5.58 ± 15.98 letters (p < 0.001). However, a drop of 8.03 ± 12.25 letters was noticed between BCVA1 and BCVA2. FAF1 was 6.34 ± 4.92mm2 and increased to 9.88 ± 7.56mm2 (3.54 ± 3.79mm2 variation p < 0.001). The mean growth rate of the atrophic area was 0.89 ± 0.84mm2 per year. BCVA2 negatively correlated with FAF2 (k = -0.498, p = 0.002) being worse in patients with higher atrophic area growth rate (k = -0.341, p = 0.042). Eyes treated with PDT needed less IVI (5.89 ± 5.21 vs 14.70 ± 13.36, p = 0.008) but had larger FAF1 (9.80 ± 5.33 vs 5.19 ± 4.27, p = 0.013) and FAF2 (16.05 ± 7.10 vs 7.83 ± 6.63, p = 0.003). Hypothyroidism was associated with higher atrophy growth rate (1.55 ± 1.15 vs 0.73 ± 0.67, p = 0.016). This research demonstrates the importance of chorioretinal atrophy progression after myopic CNV lesions regression and its impact on visual prognosis, reporting a mean yearly growth of 0.89 mm2 in atrophic areas. Previous treatment with PDT and hypothyroidism were identified as risk factors associated with larger atrophic areas and worse visual outcomes.

Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer's Disease.

Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer's disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aβ]-negative cognitively unimpaired, 6 Aβ-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18F-florbetaben PET for Aβ, 18F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aβ and tau standardized uptake value ratio and cognition. Cross-sectionally, lower BF volume was not independently associated with higher cortical Aβ, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aβ accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aβ and tau burden. Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.

Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD.

Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD. Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss. The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA.

A rare case of hereditary ataxia: Gordon Holmes syndrome: a review of the literature

Gordon Holmes syndrome is an extremely rare, autosomal recessive condition with characteristic features of cerebellar progressive ataxia, cerebellar atrophy, and hypogonadotropic hypogonadism, which was first described in 1908 by the British neurologist of the same name. Two genes have to date been frequently associated with this syndrome, RNF216 and PNPLA61. A 23-year-old man presented with secondary sexual character deficiency and progressive difficulty in gait persisting for several years. He was eventually immobilized after seven years of ongoing symptoms and was definitively diagnosed with Gordon Holmes syndrome after genetic testing revealed RNF216 gene mutation.

The Effect of Blue-light Filtering Intraocular Lenses on the Development and Progression of Macular Atrophy in Eyes With Neovascular Age-related Macular Degeneration

PurposeTo assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD). DesignRetrospective clinical cohort study. MethodsnAMD patients with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All OCT scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. Using the Heidelberg software, the area of MA was manually evaluated and calculated (mm2) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event. ResultsIncluded were 373 eyes of 373 patients (mean age 78.6±6.7 years at surgery, 67.4% females). 206 eyes were implanted with BLF IOLs and 167 with non-BLF IOLs with comparable follow-up times (3164±1420 days vs. 3180±1403 days, respectively, P=0.908), and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine pre-existing and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P=0.598 and P=0.399, respectively). Both univariate Kaplan-Meier (P=0.366) and multivariate Cox regression analysis adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (HR 1.236, 95% CI 0.784-1.949, P=0.363). Final MA area at the last visit was 5.14±4.71mm2 for BLF IOLs and 8.56±9.17mm2 for non-BLF IOLs (P=0.028), with the mean annual MA area increase of 0.78±0.84mm2 and 1.26±1.32mm2, respectively (P=0.042). ConclusionsBLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of nAMD patients.

Clinical case of management of a patient with Duchenne muscular dystrophy caused by deletion of exons 50–52 of the DMD gene against the background of pathogenetic therapy with viltolarsen

Duchenne muscular dystrophy (DMD) is the most common lumbar-limb muscular dystrophy with an X-linked recessive type of inheritance. It is characterized by a debut at an early age, rapidly progressive atrophy of the striated musculature of the limbs, trunk, heart muscle, which leads to loss of motor skills, severe cardiovascular and respiratory complications.&#x0D; Currently, a number of new drugs have appeared for the pathogenic therapy of MDD, the effectiveness of which is the most during its early initiation in the ambulatory stage of the disease. One of the new methods of MDD treatment is antisense oligonucleotide therapy. The application of this type of therapy is possible for certain mutations in the DMD gene and is recommended immediately after diagnosis. At the moment, the duration of this method of treatment in the Russian Federation is only a few years.&#x0D; In our article we discuss a clinical case of the study of a patient suffering from Duchenne muscular dystrophy caused by the deletion of 50–52 exons in the DMD gene, who is on therapy with steroids and Viltolarsen.&#x0D; A special feature of the case is the late application of Viltolarsen from the age of 9 years. The results of the observation demonstrate a significant effect in stabilization of motor skills, of the functioning of the cardiovascular and respiratory systems, which gives a chance to slow down the course of the disease, improve the quality of life and increase its duration, even taking into account the late initiation of pathogenic therapy.

Lineage tracing reveals a novel PDGFRβ+ satellite cell subset that contributes to myo-regeneration of chronically injured rotator cuff muscle

Massive rotator cuff (RC) tendon tears are associated with progressive fibro-adipogenesis and muscle atrophy that altogether cause shoulder muscle wasting. Platelet derived growth factor β (PDGFRβ) lineage cells, that co-express PDGFRα have previously been shown to directly contribute to scar formation and fat accumulation in a mouse model of irreversible tendon and nerve transection (TTDN). Conversely, PDGFRβ+ lineage cells have also been shown to be myogenic in cultures and in other models of skeletal muscle injury. We therefore hypothesized that PDGFRβ demarcates two distinct RC residing subpopulations, fibro-adipogenic and myogenic, and aimed to elucidate the identity of the PDGFRβ myogenic precursors and evaluate their contribution, if any, to RC myo-regeneration. Lineage tracing revealed increasing contribution of PDGFRβ+ myo-progenitors to the formation of GFP+ myofibers, which were the most abundant myofiber type in regenerated muscle at 2 weeks post-TTDN. Muscle regeneration preceded muscle atrophy and both advanced from the lateral site of tendon transection to the farthest medial region. GFP+/PDGFRβ+Sca-1−lin−CXCR4+Integrin-β1+ marked a novel subset of satellite cells with confirmed myogenic properties. Further studies are warranted to identify the existence of PDGFRβ+ satellite cells in human and other mouse muscles and to define their myo-regenerative potential following acute and chronic muscle injury.