The dichoptic contrast ordering test: A method for measuring the depth of binocular imbalance.

In binocular vision, the relative strength of the input from the two eyes can have significant functional impact. These inputs are typically balanced; however, in some conditions (e.g., amblyopia), one eye will dominate over the other. To quantify imbalances in binocular vision, we have developed the Dichoptic Contrast Ordering Test (DiCOT). Implemented on a tablet device, the program uses rankings of perceived contrast (of dichoptically presented stimuli) to find a scaling factor that balances the two eyes. We measured how physical interventions (applied to one eye) affect the DiCOT measurements, including neutral density (ND) filters, Bangerter filters, and optical blur introduced by a +3-diopter (D) lens. The DiCOT results were compared to those from the Dichoptic Letter Test (DLT). Both the DiCOT and the DLT showed excellent test-retest reliability; however, the magnitude of the imbalances introduced by the interventions was greater in the DLT. To find consistency between the methods, rescaling the DiCOT results from individual conditions gave good results. However, the adjustments required for the +3-D lens condition were quite different from those for the ND and Bangerter filters. Our results indicate that the DiCOT and DLT measures partially separate aspects of binocular imbalance. This supports the simultaneous use of both measures in future studies.

Sex-Related Differences in Outcome of Patients Treated With Microaxial Percutaneous Left Ventricular Assist Device for Cardiogenic Shock.

BACKGROUND: The use of microaxial percutaneous left ventricular assist devices (pLVADs) in cardiogenic shock (CS) has increased in recent years, despite limited evidence, and data on sex disparities are particularly scarce. This study aimed to compare short-term outcomes between males and females. METHODS: Data were retrospectively collected from the Dresden Impella Registry, which is a large, prospective, single-centre registry that consecutively enrolled patients who received microaxial pLVAD. Inclusion criteria were CS due to left ventricular failure with serum lactate >4 mM. Patients with pLVAD other than Impella CP were excluded. The primary endpoint was the composite of all-cause mortality at 30 days or requirement of renal replacement therapy (RRT). Secondary endpoints were the components of the primary endpoint alone. Propensity score matched (PSM) analysis was used to adjust for baseline characteristics. RESULTS: A total of 319 male (69 years; body mass index, 26.7 kg/m2) and 113 female patients (74 years; 27.9 kg/m2) were included in the study. The primary composite endpoint occurred less frequently in female patients in the unmatched analysis (♂ 75.9% [n=239] vs ♀ 64.4% [n=72]; p=0.040) but not in the PSM analysis (♂ 81.1% [n=73] vs ♀ 68.9% [n=42]; p=0.056). However, females less frequently required RRT in both analyses (♂ 48.2% [n=126] vs ♀ 25.9% [n=25]; p=0.001; PSM: ♂ 49.1% [n=36] vs ♀ 23.3% [n=12]; p=0.007). All-cause mortality did not differ between the cohorts. CONCLUSIONS: This study showed no differences in all-cause mortality at 30 days between male and female patients receiving microaxial pLVAD in CS. Larger studies are required to confirm whether female sex is associated with reduced requirement of RRT in CS treated with microaxial pLVAD.

Increase in PVC-BSI during the second COVID-19 pandemic year: analysis of catheter and patient characteristics.

BACKGROUND: Increasing nosocomial infections during the COVID-19 pandemic have been reported. However, data describing peripheral venous catheter associated bloodstream infections (PVC-BSI) are limited. AIMS: To describe the epidemiology and risk factors for PVC-BSI during the COVID-19 pandemic. METHODS: We conducted retrospective cohort study of prospectively collected PVC-BSI data in a 2100 bed hospital network in Switzerland. Adult patients with a PVC inserted between January 1, 2020 and December 31, 2021 were included. Risk factors for PVC-BSI were identified through descriptive analysis of patient and catheter characteristics, and univariable marginal Cox models. RESULTS: 206,804 PVCs and 37 PVC-BSI were analysed. Most PVC-BSI were attributed to catheters inserted in the Emergency department (76%) or surgical wards (22%). PVC-BSI increased in 2021 compared to 2020 (hazard ratio 2021 vs. 2020 = 2.73; 95% confidence interval 1.19-6.29), with a numerically higher rate of Staphylococcus aureus (1/10, 10%, vs. 5/27, 19%) and polymicrobial infection (0/10, 0% vs. 4/27, 15%). PVC insertions, patient characteristics, and catheter characteristics remained similar across the study period. PVC-BSI risk was associated with admission to the intensive care unit (ICU), and use of wide gauge catheter ( < = 16G). CONCLUSION: Increased PVC-BSI during the COVID-19 pandemic was not explained by catheter or patient factors alone, and may result from system-wide changes. PVC-BSI events are primarily attributed to acute care settings, including the emergency department, surgical wards, and the ICU.

Microbiology of catheter associated bloodstream infection: differences according to catheter type.

OBJECTIVES: Catheter-associated bloodstream infections (CABSI) cause preventable morbidity. We compared the microbiological aetiology of CABSI across different types of central and peripherally inserted catheters. METHODS: We analysed prospectively collected CABSI data in a 2100-bed hospital network in Switzerland between 2016 and 2022. We included: short-term non-tunnelled central venous catheters (CVC); long-term catheters (tunnelled, or peripherally inserted central catheters); arterial catheters; dialysis catheters; and peripheral venous catheters (PVC). We used multivariable logistic regression models to describe risk of Staphylococcus aureus and Gram-negative pathogens according to catheter type. RESULTS: 416 CABSI episodes were included, including 60 episodes of S. aureus and 92 episodes of Gram-negative CABSI. Microbiological profile differed between catheter types. Together, PVC and dialysis catheters accounted for 43/60 (72%) of all S. aureus CABSI. After adjusting for age, sex and haematology/oncology care, odds of S. aureus were higher for haemodialysis catheters (OR 17.3, 95% CI 5.75-52.2, p <0.01) and PVC (OR 2.96, 95% CI 1.22-7.20, p=0.02) compared to short-term non-tunnelled CVC. Odds of Gram-negative organism as cause of CABSI were higher in long-term catheters versus short-term non-tunnelled CVC (OR 2.70, 95% CI 1.37-5.24). CONCLUSIONS: CABSI in catheters other than short-term non-tunnelled CVC are more commonly caused by virulent organisms including S. aureus and Gram-negative bacteria. Catheter type should be considered when selecting empirical antimicrobial therapies.

Polydopamine Nanoparticle-Based Combined Chemotherapy and Photothermal Therapy for the Treatment of Liver Cancer.

Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM-SRF-PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex ovo on HepG2 spheroid-grafted quail embryos. This comprehensive investigation, supported by proteomic analysis, showed the effectiveness of the proposed nanoplatform and strongly suggests further pre-clinical testing in the treatment of liver cancer.

Good-enough Care? How Patients' Perceptions of Counselors' Professional Skills Relate to Everyday Life in Forensic Long-stay Units.

The overall goal of long-term forensic care is to strive toward acceptable levels of adaptation and quality of life (QoL) of the forensic patient in the institutional context. While the bulk of the literature has focused on the deleterious consequences of personality pathology in this regard, research investigating the contribution of the quality of the therapeutic relationship has remained rather scant. Assuming that the perceived competence of the direct counselor, as perceived by patients, forms an important aspect in this regard, the central aim of this study was to investigate the relationship between patients' perceptions of their therapist's professional skills, their self-reported maladaptive behavior on the ward, and their experienced QoL. To this end, we recruited patients (N = 60) in long-stay forensic units and investigated their perceptions of 10 specific skills displayed by their therapist, along a "too little-too much" rating scale. The results revealed that patients who had the overall impression that their counselor was equipped with an adequate set of professional skills showed less maladaptive behavior and perceived a higher QoL on the ward. Conversely, at a more specific competence level, only a positive relationship between a counselor's predictability and self-reported QoL was found. Taken together, these results highlight that an overall professional skill evaluation matters in the context of forensic patients' adaptation and QoL in their long-stay units, with the counselor's predictability serving as a crucial aspect in obtaining the most favorable outcomes.

Association of institutional masking policies with healthcare-associated SARS-CoV-2 infections in Swiss acute care hospitals during the BA.4/5 wave (CH-SUR study): a retrospective observational study.

BACKGROUND: In the initial phase of the SARS-CoV-2 pandemic, masking has been widely accepted in healthcare institutions to mitigate the risk of healthcare-associated infection. Evidence, however, is still scant and the role of masks in preventing healthcare-associated SARS-CoV-2 acquisition remains unclear.We investigated the association of variation in institutional mask policies with healthcare-associated SARS-CoV-2 infections in acute care hospitals in Switzerland during the BA.4/5 2022 wave. METHODS: SARS-CoV-2 infections in hospitalized patients between June 1 and September 5, 2022, were obtained from the "Hospital-based surveillance of COVID-19 in Switzerland"-database and classified as healthcare- or community-associated based on time of disease onset. Institutions provided information regarding institutional masking policies for healthcare workers and other prevention policies. The percentage of healthcare-associated SARS-CoV-2 infections was calculated per institution and per type of mask policy. The association of healthcare-associated SARS-CoV-2 infections with mask policies was tested using a negative binominal mixed-effect model. RESULTS: We included 2'980 SARS-CoV-2 infections from 13 institutions, 444 (15%) were classified as healthcare-associated. Between June 20 and June 30, 2022, six (46%) institutions switched to a more stringent mask policy. The percentage of healthcare-associated infections subsequently declined in institutions with policy switch but not in the others. In particular, the switch from situative masking (standard precautions) to general masking of HCW in contact with patients was followed by a strong reduction of healthcare-associated infections (rate ratio 0.39, 95% CI 0.30-0.49). In contrast, when compared across hospitals, the percentage of health-care associated infections was not related to mask policies. CONCLUSIONS: Our findings suggest switching to a more stringent mask policy may be beneficial during increases of healthcare-associated SARS-CoV-2 infections at an institutional level.

Phenotyping grapevine resistance to downy mildew: deep learning as a promising tool to assess sporulation and necrosis.

BACKGROUND: Downy mildew is a plant disease that affects all cultivated European grapevine varieties. The disease is caused by the oomycete Plasmopara viticola. The current strategy to control this threat relies on repeated applications of fungicides. The most eco-friendly and sustainable alternative solution would be to use bred-resistant varieties. During breeding programs, some wild Vitis species have been used as resistance sources to introduce resistance loci in Vitis vinifera varieties. To ensure the durability of resistance, resistant varieties are built on combinations of these loci, some of which are unfortunately already overcome by virulent pathogen strains. The development of a high-throughput machine learning phenotyping method is now essential for identifying new resistance loci. RESULTS: Images of grapevine leaf discs infected with P. viticola were annotated with OIV 452-1 values, a standard scale, traditionally used by experts to assess resistance visually. This descriptor takes two variables into account the complete phenotype of the symptom: sporulation and necrosis. This annotated dataset was used to train neural networks. Various encoders were used to incorporate prior knowledge of the scale's ordinality. The best results were obtained with the Swin transformer encoder which achieved an accuracy of 81.7%. Finally, from a biological point of view, the model described the studied trait and identified differences between genotypes in agreement with human observers, with an accuracy of 97% but at a high-throughput 650% faster than that of humans. CONCLUSION: This work provides a fast, full pipeline for image processing, including machine learning, to describe the symptoms of grapevine leaf discs infected with P. viticola using the OIV 452-1, a two-symptom standard scale that considers sporulation and necrosis. If symptoms are frequently assessed by visual observation, which is time-consuming, low-throughput, tedious, and expert dependent, the method developed sweeps away all these constraints. This method could be extended to other pathosystems studied on leaf discs where disease symptoms are scored with ordinal scales.

Is childhood lying shaped by callous-unemotional traits or does lie-telling make children more callous-unemotional? A longitudinal between- and within-person perspective.

The current study aims to advance knowledge on the causal interrelationship between childhood CU traits and lying both at a between- and a within-person perspective across a significant developmental period of mid-childhood to mid-adolescence. Cross-lagged panel models and Random-intercept cross-lagged panel models were used to investigate the prospective associations between lying and the distinct subcomponents of CU traits, including Callousness, Uncaring, and Unemotional in a sample of 719 children (T1; Mage = 10.73 years, SDage = 1.38, range = 7-15 years, 54.4% girls) across four assessment points. Results supported large vulnerability effects at the between-person level across time, indicating that CU traits predominantly influence the subsequent development of lying, with Callousness and Uncaring showing most profound effects on subsequent developmental processes of lying. At the within-person level, fluctuations in CU traits and lying were overall meaningfully related, but no causal relationship could be empirically determined. These findings provide a differentiated etiological viewpoint on the intertwinement of CU traits and lying at a young age, and underscore the importance of an early identification of children with callous and uncaring tendencies in order to prevent more persistent lying in adolescence.

Chloramine Disinfection of Levofloxacin and Sulfaphenazole: Unraveling Novel Disinfection Byproducts and Elucidating Formation Mechanisms for an Enhanced Understanding of Water Treatment.

The unrestricted utilization of antibiotics poses a critical challenge to global public health and safety. Levofloxacin (LEV) and sulfaphenazole (SPN), widely employed broad-spectrum antimicrobials, are frequently detected at the terminal stage of water treatment, raising concerns regarding their potential conversion into detrimental disinfection byproducts (DBPs). However, current knowledge is deficient in identifying the potential DBPs and elucidating the precise transformation pathways and influencing factors during the chloramine disinfection process of these two antibiotics. This study conducts a comprehensive analysis of reaction pathways, encompassing piperazine ring opening/oxidation, Cl-substitution, OH-substitution, desulfurization, and S-N bond cleavage, during chloramine disinfection. Twelve new DBPs were identified in this study, exhibiting stability and persistence even after 24 h of disinfection. Additionally, an examination of DBP generation under varying disinfectant concentrations and pH values revealed peak levels at a molar ratio of 25 for LEV and SPN to chloramine, with LEV contributing 11.5% and SPN 23.8% to the relative abundance of DBPs. Remarkably, this research underscores a substantial increase in DBP formation within the molar ratio range of 1:1 to 1:10 compared to 1:10 to 1:25. Furthermore, a pronounced elevation in DBP generation was observed in the pH range of 7 to 8. These findings present critical insights into the impact of the disinfection process on these antibiotics, emphasizing the innovation and significance of this research in assessing associated health risks.

Does Spinocerebellar ataxia 27B mimic cerebellar multiple system atrophy?

BACKGROUND: Whether spinocerebellar ataxia 27B (SCA27B) may present as a cerebellar multiple system atrophy (MSA-C) mimic remains undetermined. OBJECTIVES: To assess the prevalence of FGF14 (GAA)≥250 expansions in patients with MSA-C, to compare SCA27B and MSA-C clinical presentation and natural history. METHODS: FGF14 expansion screening combined with longitudinal deep-phenotyping in a prospective cohort of 195 patients with sporadic late-onset cerebellar ataxia. RESULTS: After a mean disease duration of 6.4 years, 111 patients were not meeting criteria for MSA-C while 24 and 60 patients had a final diagnosis of possible and probable MSA-C, respectively. 16 patients carried an FGF14 (GAA)≥250 expansion in the group not meeting MSA-C criteria (14.4%), 3 patients in the possible MSA-C group (12.5%), but none among probable MSA-C cases. SCA27B patients were evolving more slowly than probable MSA-C patients. CONCLUSIONS: FGF14 (GAA)≥250 expansion may account for MSA look-alike cases and should be screened among slow progressors.

Increased Peripheral Venous Catheter Bloodstream Infections during COVID-19 Pandemic, Switzerland.

Studies suggest that central venous catheter bloodstream infections (BSIs) increased during the COVID-19 pandemic. We investigated catheter-related BSIs in Switzerland and found peripheral venous catheter (PVC) BSI incidence increased during 2021-2022 compared with 2020. These findings should raise awareness of PVC-associated BSIs and prompt inclusion of PVC BSIs in surveillance systems.

Comparison of clinical outcomes over time of inpatients with healthcare-associated or community-acquired coronavirus disease 2019 (COVID-19): A multicenter, prospective cohort study.

OBJECTIVE: To compare clinical outcomes over time of inpatients with healthcare-associated coronavirus disease 2019 (HA-COVID-19) versus community-acquired COVID-19 (CA-COVID-19). DESIGN: We conducted a multicenter, prospective observational cohort study of inpatients with COVID-19. SETTING: The study was conducted across 16 acute-care hospitals in Switzerland. PARTICIPANTS AND METHODS: We compared HA-COVID-19 cases, defined as patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test > 5 days after hospital admission, with hospitalized CA-COVID-19 cases, defined as those who tested positive within 5 days of admission. The composite primary outcome was patient transfer to an intensive care unit (ICU) or an intermediate care unit (IMCU) and/or all-cause in-hospital mortality. We used cause-specific Cox regression and Fine-Gray regression to model the time to the composite clinical outcome, adjusting for confounders and accounting for the competing event of discharge from hospital. We compared our results to those from a conventional approach using an adjusted logistic regression model where time-varying effects and competitive risk were ignored. RESULTS: Between February 19, 2020, and December 31, 2020, we included 1,337 HA-COVID-19 cases and 9,068 CA-COVID-19 cases. HA-COVID-19 patients were significantly older: median, 80 (interquartile range [IQR], 71-87) versus median 70 (IQR, 57-80) (P < .001). A greater proportion of HA-COVID-19 patients had a Charlson comorbidity index ≥ 5 (79% vs 55%; P < .001) than did CA-COVID-19 patients. In time-varying analyses, between day 0 and 8, HA-COVID-19 cases had a decreased risk of death or ICU or IMCU transfer compared to CA-COVID-19 cases (cause-specific hazard ratio [csHR], 0.43; 95% confidence interval [CI], 0.33-0.56). In contrast, from day 8 to 30, HA-COVID-19 cases had an increased risk of death or ICU or IMCU transfer (csHR, 1.49; 95% CI, 1.20-1.85), with no significant effect on the rate of discharge (csHR, 0.83; 95% CI, 0.61-1.14). In the conventional logistic regression model, HA-COVID-19 was protective against transfer to an ICU or IMCU and/or all-cause in-hospital mortality (adjusted odds ratio [aOR], 0.79, 95% CI, 0.67-0.93). CONCLUSIONS: The risk of adverse clinical outcomes for HA-COVID-19 cases increased substantially over time in hospital and exceeded that for CA-COVID-19. Using approaches that do not account for time-varying effects or competing events may not fully capture the true risk of HA-COVID-19 compared to CA-COVID-19.

Catheter size and risk of short-term peripheral venous catheter-associated bloodstream infections: an observational study.

OBJECTIVES: Short-term peripheral venous catheter-associated bloodstream infections (PVC-associated BSI) are disregarded in the literature because of their relatively low incidence. No data are available on the association between PVC diameter size and the risk of PVC-associated BSI. METHODS: Using a prospective database, we performed an observational study at the University of Geneva Hospitals from 1 January 2020 to 31 December 2021, including all patients with a PVC. We used univariable and multivariable marginal Cox regression models for clustered data to investigate the association between catheter size and PVC-associated BSI. The main variable of interest 'catheter size' was forced into our multivariable models. Confounders, which are thought to influence the risk of PVC-associated BSI, were used as adjustment factors. RESULTS: A total of 206 804 PVCs were included. In all, 10 806 of 201 413 (5.4%), 80 274 of 201 413 (39.9%), 93 047 of 201 413 (46.2%) and 17 286 of 201 413 (8.6%) PVCs measured ≤16G, 18G, 20G and ≥22G, respectively. The univariable analysis showed that diameters of ≤16G were significantly associated with a higher risk of PVC-associated BSI (hazard ratio [HR] 4.52, 95% CI, 1.14-18.00). Multivariable models confirmed these results (HR 4.65, 95% CI, 1.19-18.20). Sensitivity analyses including PVC inserted only in 2021 (HR 4.80, 95% CI, 1.21-19.10), for dwell time >2 days (HR 3.67, 95% CI, 0.92-14.65) and only in adults (HR 3.97, 95% CI, 0.97-15.39) showed similar results. DISCUSSION: Larger PVC size may increase the risk of PVC-associated BSI. Diameter size should be considered when selecting PVCs to reduce the burden of PVC-associated BSI.

Clinical and Electrophysiological Characterization of Essential Tremor in 18 Children and Adolescents.

Background: Essential tremor (ET) is considered the most frequent abnormal movement in the general population, with childhood onset in 5 to 30% of the patients. Methods: A multicenter, descriptive cross-sectional study enrolled patients ⩽18 years with a definite diagnosis of ET according to the International Parkinson and Movement Disorders Society criteria. Demographic data, clinical and electrophysiological characteristics of the tremor, neurological examination and impact on quality of life were collected. Results: 9 males and 9 females were included (mean age of 13.9 years). Tremor was characterized by : upper limb onset at a mean age of 6.5 years; at enrollment, upper limbs localization, and involvement of an additional body region in 28% of the patients; kinetic tremor in all of the patients combined with postural tremor in 17 and rest tremor in 3; tremor mean frequency of 7.6 Hz, mean burst duration of 82.7 ms; identification of mild myoclonic jerks on the polymyographic recordings in 7 patients; altered quality of life with worse emotional outcomes in girls and when a disease duration >5 years was suggested. Discussion: Childhood-onset ET is associated with delayed diagnosis and remarkable functional impact. Electromyographic identification of additional mild myoclonus is a new finding whose significance is discussed. Highlights: ET onset involved upper limbs and at inclusion, 28% of the patients exhibited involvement of an additional body region.ET impacted quality of life for all patients.Girls and patients affected for >5 years reported worse emotional outcomes.Mild myoclonic jerks were identified on 7/17 polymyographic recordings.

Sensorization of microfluidic brain-on-a-chip devices: Towards a new generation of integrated drug screening systems.

Brain-on-a-chip (BoC) devices show typical characteristics of brain complexity, including the presence of different cell types, separation in different compartments, tissue-like three-dimensionality, and inclusion of the extracellular matrix components. Moreover, the incorporation of a vascular system mimicking the blood-brain barrier (BBB) makes BoC particularly attractive, since they can be exploited to test the brain delivery of different drugs and nanoformulations. In this review, we introduce the main innovations in BoC and BBB-on-a-chip models, especially focusing sensorization: electrical, electrochemical, and optical biosensors permit the real-time monitoring of different biological phenomena and markers, such as the release of growth factors, the expression of specific receptors/biomarkers, the activation of immune cells, cell viability, cell-cell interactions, and BBB crossing of drugs and nanoparticles. The recent improvements in signal amplification, miniaturization, and multiplication of the sensors are discussed in an effort to highlight their benefits versus limitations and delineate future challenges in this field.

Case Report: Late Reactivation of Herpes B Virus After a Monkey Bite: A Case of Severe Meningoencephalitis.

Macacine alphaherpesvirus 1, also known as herpes B virus (BV), is an alphaherpesvirus endemic to several macaque species, capable of causing zoonotic infections in humans, with high mortality rates. Evidence of reactivation in humans has rarely been reported. Here we depict a case of BV reactivation after 54 years, leading to severe meningoencephalitis. This case supports the use of antiviral prophylaxis in patients surviving a confirmed BV central nervous system infection. We sequenced DNA from BV obtained from the patient's cerebrospinal fluid. Phylogenetic analysis showed significant divergence in the clustering of this particular BV strain compared with other known BVs. Therefore, additional efforts are needed to obtain a broader sequence landscape from BVs circulating in monkeys.

Infantile-onset parkinsonism, dyskinesia, and developmental delay: do not forget polyglutamine defects!

We present the phenotype of an infant with the largest ATN1 CAG expansion reported to date (98 repeats). He presented at 4 months with developmental delay, poor eye contact, acquired microcephaly, failure to thrive. He progressively developed dystonia-parkinsonism with paroxysmal oromandibular and limbs dyskinesia and fatal outcome at 17 months. Cerebral MRI disclosed globus pallidus T2-WI hyperintensities and brain atrophy. Molecular analysis was performed post-mortem following the diagnosis of dentatorubral-pallidoluysian atrophy (DRPLA) in his symptomatic father. Polyglutamine expansion defects should be considered when neurodegenerative genetic disease is suspected even in infancy and parkinsonism can be a presentation of infantile-onset DRPLA.

Natural History and Phenotypic Spectrum of GAA-FGF14 Sporadic Late-Onset Cerebellar Ataxia (SCA27B).

BACKGROUND: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established. OBJECTIVES: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients. METHODS: FGF14 expansions screening combined with longitudinal deep-phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis. RESULTS: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia. CONCLUSIONS: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.