Pattern of pareses in 5q-spinal muscular atrophy.

Background: This prospective study investigates the pattern of pareses in 5q-associated spinal muscular atrophy (SMA) to identify disease-specific characteristics and potential differences from amyotrophic lateral sclerosis (ALS) and spinobulbar muscular atrophy (SBMA). Detailed knowledge about pareses patterns in SMA facilitates differential diagnosis and supports therapeutic monitoring.

Methods: Between January 2021, and June 2021, 66 SMA patients (59.

Respiratory function in adult patients with spinal muscular atrophy treated with nusinersen - a monocenter observational study.

Background/objective: Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue.

Methods: We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2.

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland.

Benchmarking the CoW with the TopCoW Challenge: Topology-Aware Anatomical Segmentation of the Circle of Willis for CTA and MRA.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task.

Paradoxical increase of neurofilaments in SMA patients treated with onasemnogene abeparvovec-xioi.

Background/objective: Neurofilament light chain (NfL) has been proposed as a biomarker reflecting disease severity and therapy response in children with spinal muscular atrophy type 1 and 2 (SMA1 and 2). The objective of this study was to examine how serum NfL changes after gene replacement therapy (GRT) with onasemnogene abeparvovec-xioi.

Methods: We measured NfL in serum probes from 19 patients (10 SMA 1 and 6 SMA 2; 15 previously treated with nusinersen or risdiplam; 12 male) before and at variable time points after GRT.

Assessing the effects of a drought experiment on the reproductive phenology and ecophysiology of a wet tropical rainforest community.

Climate change is expected to increase the intensity and occurrence of drought in tropical regions, potentially affecting the phenology and physiology of tree species. Phenological activity may respond to a drying and warming environment by advancing reproductive timing and/or diminishing the production of flowers and fruits. These changes have the potential to disrupt important ecological processes, with potentially wide-ranging effects on tropical forest function.

Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.

5q-associated spinal muscular atrophy (SMA) is a rare genetic disease caused by mutations in the SMN1 gene, resulting in a loss of functional SMN protein and consecutive degeneration of motor neurons in the ventral horn. The disease is clinically characterized by proximal paralysis and secondary skeletal muscle atrophy. New disease-modifying drugs driving SMN gene expression have been developed in the past decade and have revolutionized SMA treatment.

Health-Related Quality of Life in Spinal Muscular Atrophy Patients and Their Caregivers-A Prospective, Cross-Sectional, Multi-Center Analysis.

Spinal muscular atrophy (SMA) is a disabling disease that affects not only the patient’s health-related quality of life (HRQoL), but also causes a high caregiver burden (CGB). The aim of this study was to evaluate HRQoL, CGB, and their predictors in SMA. In two prospective, cross-sectional, and multi-center studies, SMA patients (n = 39) and SMA patient/caregiver couples (n = 49) filled in the EuroQoL Five Dimension Five Level Scale (EQ-5D-5L) and the Short Form Health Survey 36 (SF-36).

3D-printed facet-attached optical elements for connecting VCSEL and photodiodes to fiber arrays and multi-core fibers.

Multicore optical fibers and ribbons based on fiber arrays allow for massively parallel transmission of signals via spatially separated channels, thereby offering attractive bandwidth scaling with linearly increasing technical effort. However, low-loss coupling of light between fiber arrays or multicore fibers and standard linear arrays of vertical-cavity surface-emitting lasers (VCSEL) or photodiodes (PD) still represents a challenge. In this paper, we demonstrate that 3D-printed facet-attached microlenses (FaML) offer an attractive path for connecting multimode fiber arrays as well as individual cores of multimode multicore fibers to standard arrays of VCSEL or PD.

Glial fibrillary acidic protein in cerebrospinal fluid of patients with spinal muscular atrophy.

Objective: Activated astroglia is involved in the pathophysiology of neurodegenerative diseases and has also been described in animal models of spinal muscular atrophy (SMA). Given the urgent need of biomarkers for treatment monitoring of new RNA-modifying and gene replacement therapies in SMA, we examined glial fibrillary acidic protein concentrations in cerebrospinal fluid (cGFAP) as a marker of astrogliosis in SMA.

Methods: 58 adult patients and 21 children with genetically confirmed 5q-associated SMA from four German motor neuron disease specialist care centers and 30 age- and sex-matched controls were prospectively included in this study.

Prevalence of Anti-Adeno-Associated Virus Serotype 9 Antibodies in Adult Patients with Spinal Muscular Atrophy.

5q-associated spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that leads to progressive muscle atrophy and weakness. The disease is caused by a homozygous deletion or mutation in the survival of motor neuron 1 () gene, resulting in insufficient levels of SMN protein. Onasemnogene abeparvovec-xioi (OA) is a nonreplicating vector based on adeno-associated virus serotype 9 (AAV9) that contains the full-length human gene.

Progress in spinal muscular atrophy research.

Purpose Of Review: The development of new therapies has brought spinal muscular atrophy (SMA) into the spotlight. However, this was preceded by a long journey - from the first clinical description to the discovery of the genetic cause to molecular mechanisms of RNA and DNA technology.

Recent Findings: Since 2016, the antisense oligonucleotide nusinersen has been (FDA) approved for the treatment of SMA, followed by the gene replacement therapy onasemnogene abeparvovec-xioi in 2019 and the small-molecule risdiplam in 2020.

Validity and reliability of the German multidimensional fatigue inventory in spinal muscular atrophy.

Objective: Fatigue is a common and burdensome symptom of spinal muscular atrophy. Given its complex interactions, different dimensions of fatigue need to be investigated. The Multidimensional Fatigue Inventory is a widely used instrument that captures five distinct dimensions.

Indigenous impacts on north Australian savanna fire regimes over the Holocene.

Fire is an essential component of tropical savannas, driving key ecological feedbacks and functions. Indigenous manipulation of fire has been practiced for tens of millennia in Australian savannas, and there is a renewed interest in understanding the effects of anthropogenic burning on savanna systems. However, separating the impacts of natural and human fire regimes on millennial timescales remains difficult.

The surgical management of intraoperative intracranial internal carotid artery injury in open skull base surgery-a systematic review.

Intraoperative internal carotid artery (ICA) injury during open skull base surgery is a catastrophic complication. Multiple techniques and management strategies have been reported for endoscopic skull base surgery; however, the literature on managing this complication in open skull base surgery is limited. To perform a systematic review and give an overview of the different techniques described to manage this complication intraoperatively, a systematic review was conducted in PubMed, Ovid Medline, Ovid Embase and Scopus for literature published until July 2021.

Increased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy.

Background: Studies regarding the impact of (neuro)inflammation and inflammatory response following repetitive, intrathecally administered antisense oligonucleotides (ASO) in 5q-associated spinal muscular atrophy (SMA) are sparse. Increased risk of hydrocephalus in untreated SMA patients and a marginal but significant increase of the serum/CSF albumin ratio (Qalb) with rare cases of communicating hydrocephalus during nusinersen treatment were reported, which confirms the unmet need of an inflammatory biomarker in SMA. The aim of this study was to investigate the (neuro)inflammatory marker chitotriosidase 1 (CHIT1) in SMA patients before and following the treatment with the ASO nusinersen.

Treatment expectations and perception of therapy in adult patients with spinal muscular atrophy receiving nusinersen.

Background And Purpose: This was an investigation of treatment expectations and of the perception of therapy in adult patients with 5q-associated spinal muscular atrophy (5q-SMA) receiving nusinersen.

Methods: A prospective, non-interventional observational study of nusinersen treatment in adult 5q-SMA patients was conducted at nine SMA centers in Germany. The functional status, treatment expectations and perceived outcomes were assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-extended (ALS-FRS-ex), the Measure Yourself Medical Outcome Profile (MYMOP2), the Treatment Satisfaction Questionnaire for Medication (TSQM-9) and the Net Promoter Score (NPS).

A global carbon and nitrogen isotope perspective on modern and ancient human diet.

Stable carbon and nitrogen isotope analyses are widely used to infer diet and mobility in ancient and modern human populations, potentially providing a means to situate humans in global food webs. We collated 13,666 globally distributed analyses of ancient and modern human collagen and keratin samples. We converted all data to a common "Modern Diet Equivalent" reference frame to enable direct comparison among modern human diets, human diets prior to the advent of industrial agriculture, and the natural environment.

Quality of Life in SMA Patients Under Treatment With Nusinersen.

Spinal Muscular Atrophy (SMA) is a severe neurodegenerative disease, characterized by progressive muscle weakness and atrophy. The approval of the antisense oligonucleotide (ASO) nusinersen now provides an effective pharmacological approach with the potential to slow down or stop disease progression with a potentially major impact on patients' well-being. This study evaluates quality of life (QoL) in pediatric and adult patients over the course of therapy with nusinersen.

Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment.

Objective: To determine whether serum creatine kinase activity (CK) and serum creatinine concentration (Crn) are prognostic and predictive biomarkers for disease severity, disease progression, and nusinersen treatment effects in adult patients with 5q-associated spinal muscular atrophy (SMA).

Methods: Within this retrospective, multicenter observational study in 206 adult patients with SMA, we determined clinical subtypes (SMA types, ambulatory ability) and repeatedly measured CK and Crn and examined disease severity scores (Hammersmith Functional Motor Scale Expanded, Revised Upper Limb Module, and revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Patients were followed under nusinersen treatment for 18 months.

Treatment satisfaction in 5q-spinal muscular atrophy under nusinersen therapy.

Background: Nusinersen was the first approved disease-modifying therapy for all 5q-spinal muscular atrophy (SMA) patients regardless of age or disease severity. Its efficacy in adults has recently been demonstrated in a large cohort by motor outcome measures, which were only partially suitable to detect changes in very mildly or severely affected patients. Patient-reported outcome measures (PROs) have been suggested as a valuable addition.

Executive function is inversely correlated with physical function: the cognitive profile of adult Spinal Muscular Atrophy (SMA).

Background: Spinal muscular atrophy (SMA) issues from mutations in the survival of motor neuron (SMN) 1 gene. Loss or reduction of the SMN protein results in progressive muscle weakness. Whether this protein deficiency also affects cortical function remains unclear.

Cognitive Performance of Patients with Adult 5q-Spinal Muscular Atrophy and with Amyotrophic Lateral Sclerosis.

Motor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), share several clinical similarities while differing substantially in etiology, disease onset and progression. Cognitive dysfunction, a clinically relevant non-motor feature in a substantial proportion of ALS patients, has been less frequently investigated in SMA. In this prospective multicenter cross-sectional study, cognitive function was assessed by the Edinburgh Cognitive (and Behavioural) ALS Screen (ECAS) and a German vocabulary test (Wortschatztest, WST) in 34 adult patients with SMA types 2-4 and in 34 patients with ALS.