Typical Onset Research Articles

The brain-gut axis, inflammatory bowel disease and bioelectronic medicine.

The hallmark of inflammatory bowel diseases (IBD) is chronic intestinal inflammation with typical onset in adolescents and young adults. An abundance of neutrophils is seen in the inflammatory lesions, but adaptive immunity is also an important player in the chronicity of the disease. There is an unmet need for new treatment options since modern medicines such as biological therapy with anti-cytokine antibodies still leave a substantial number of patients with persisting disease activity. The role of the central nervous system and its interaction with the gut in the pathophysiology of IBD have been brought to attention both in animal models and in humans after the discovery of the inflammatory reflex. The suggested control of gut immunity by the brain-gut axis represents a novel therapeutic target suitable for bioelectronic intervention. In this review, we discuss the role of the inflammatory reflex in gut inflammation and the recent advances in the treatment of IBD by intervening with the brain-gut axis through bioelectronic devices.

The Effect of Upstream Orography on the Onset of Sundowner Winds in Coastal Santa Barbara, CA

AbstractThe impact of upstream terrain on the diurnal variability of downslope windstorms on the south‐facing slopes of the Santa Ynez Mountains (SYM) is investigated using numerical simulations. These windstorms, called Sundowners due to their typical onset around sunset, have intensified all major wildfires in the area. This study investigates the role of the orography upstream of the SYM in the diurnal behavior of Sundowners. Two types of Sundowners are examined: western sundowners (winds with dominant northwesterly direction) and eastern Sundowners (winds with dominant northeasterly direction). By using semi‐idealized simulations, in which we progressively reduce the upstream terrain, we show that the onset of the lee slope jet occurs in the late afternoon only when the flow approaches the SYM from the northeast, after interacting with a considerably higher mountain barrier. We demonstrate that during the eastern regime, the progressive reduction of the upstream terrain results in strong lee slope winds throughout the day. Conversely, the diurnal cycle of downslope winds during the western regime is less sensitive to the reduction of the upstream terrain. The Sundowner diurnal cycle during the eastern regime can be explained by boundary‐layer processes in the valley and the blocking effect of high mountains upstream of the SYM. These results contribute to a better understanding of the influence of upstream orography in the cycle and intensity of downslope windstorms in coastal mountains.

Living with narcolepsy during adolescence: A qualitative study

RATIONALE: Narcolepsy is a chronic sleep disorder, with typical onset in childhood or adolescence. Features of narcolepsy include excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hallucinations and disturbed nocturnal sleep. The constellation of symptoms may be challenging for patients to manage. Adolescents with narcolepsy report poor quality of life and mental health concerns. OBJECTIVE: The objective of this report was to understand the experience of living with narcolepsy as an adolescent and its impact on daily functioning, relationships and mental health. METHODS: In-depth, semistructured interviews with adolescents with narcolepsy were conducted from May to August 2019 at the Hospital for Sick Children in Toronto, Canada. Interview questions focused on perceptions of 1) disease symptoms, 2) mental health, 3) daily functioning, 4) relationships and 5) coping. Interviews were digitally audio-recorded for verbatim transcription, coded by two researchers and analyzed using NVivo qualitative data computer software. RESULTS: Eighteen adolescents with narcolepsy (age range = 10-17, mean age = 14.4 ± 2.0, 72.2% male) participated. The findings suggest some of the common symptoms of narcolepsy (eg, EDS) are often experienced as unpleasant, while vivid dreaming may be pleasant. Emotional challenges such as frustration with symptoms and worries about the future are common. Participants emphasize the importance of ongoing support from others (eg, clinical team, teachers) to help with coping with chronic illness. CONCLUSION: Living with narcolepsy poses unique challenges for adolescents and impacts their psychosocial health. We recommend increased psychosocial support from mental health professionals, educational resources for schools and teachers, and peer support groups for adolescent narcolepsy patients.

Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. European Commission, Voyager Therapeutics, and EuroAtaxia.

Overview of lithium's use: a nationwide survey

BackgroundLithium is considered the gold standard treatment for bipolar disorder (BD). Current clinical guidelines and scientific evidence support its use as a first-line treatment in BD. However, over the last two decades, there has been a downward tendency in lithium's use in several developed countries. Based on a nationwide survey, this study's objective is to analyze in a large sample of psychiatrists relevant issues of the use of lithium salts in BD.MethodsData were collected through an anonymous survey sent by email among 500 psychiatrists who belong to a National Society of Psychiatry (Spanish Society of Biological Psychiatry). The survey is a self-administered questionnaire consisting of 21 items on the most key aspects of lithium's use (indication, dosage, monitoring, and information for patients).Results212 psychiatrists completed the survey. 70% of psychiatrists prescribe lithium to more than 50% of patients diagnosed with BD. Adverse effects are the main reason not to use lithium salts. Over 75% of the participants consider lithium salts the treatment of choice for the maintenance phase of BD, both in women and men. Most of the participants (> 50%) start lithium after the first affective episode, use conservative plasma concentrations (0.6–0.8 mmol/L), and generally prescribe it twice a day. 57% of psychiatrists who treat patients under 18 do not use lithium in this population. About 70% of the survey respondents use official protocols to inform and monitor patients on lithium treatment.ConclusionsFrom the results of the present study, it can be concluded that the use of lithium in Spain is in line with the recommendations of the main international clinical guidelines and current scientific literature. The first reason not to prescribe lithium in our country is the perception of its adverse effects and not the aspects related to its practical use or its effectiveness. Considering that BD is a chronic disease with a typical onset in adolescence, the low rate of prescription of lithium salts in patients under 18 must be thoroughly studied.

Association of History of Psychopathology With Accelerated Aging at Midlife

Individuals with mental disorders are at an elevated risk of developing chronic age-related physical diseases. However, it is not clear whether psychopathology is also associated with processes of accelerated aging that precede the onset of age-related disease. To test the hypothesis that a history of psychopathology is associated with indicators of accelerated aging at midlife. This prospective cohort study was based on the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand. Members were followed up to age 45 years (until April 2019). Data were analyzed from January 6 to December 7, 2020. Mental disorders were assessed in 6 diagnostic assessments from ages 18 to 45 years and transformed through confirmatory factor analysis into continuous measures of general psychopathology (p-factor) and dimensions of internalizing, externalizing, and thought disorders (all standardized to a mean [SD] of 100 [15]). Signs of aging (biological pace of aging; declines in sensory, motor, and cognitive functioning; and facial age) were assessed up to age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. Of the original 1037 cohort participants, 997 were still alive at age 45 years, of whom 938 (94%) were assessed (474 men [50.5%]). Participants who had experienced more psychopathology exhibited a faster pace of biological aging (β, 0.27; 95% CI, 0.21-0.33; P < .01); experienced more difficulties with hearing (β, 0.18; 95% CI, 0.12-0.24; P < .01), vision (β, 0.08; 95% CI, 0.01-0.14; P < .05), balance (β, 0.20; 95% CI, 0.14-0.26; P < .01), and motor functioning (β, 0.19; 95% CI, 0.12-0.25; P < .01); experienced more cognitive difficulties (β, 0.24; 95% CI, 0.18-0.31; P < .01); and were rated as looking older (β, 0.20; 95% CI, 0.14-0.26; P < .01). Associations persisted after controlling for sex, childhood health indicators, maltreatment, and socioeconomic status and after taking into account being overweight, smoking, use of antipsychotic medication, and the presence of physical disease. Tests of diagnostic specificity revealed that associations were generalizable across externalizing, internalizing, and thought disorders. In this cohort study, a history of psychopathology was associated with accelerated aging at midlife, years before the typical onset of age-related diseases. This link is not specific to any particular disorder family but generalizes across disorders. Prevention of psychopathology and monitoring of individuals with mental disorders for signs of accelerated aging may have the potential to reduce health inequalities and extend healthy lives.

Schizophrenia: Complement Cleaning or Killing.

Schizophrenia is a psychiatric disorder with a typical onset occurring during adolescence or young adulthood. The heterogeneity of the disorder complicates our understanding of the pathophysiology. Reduced cortical synaptic densities are commonly observed in schizophrenia and suggest a role for excessive synaptic elimination. A major pathway hypothesised to eliminate synapses during postnatal development is the complement system. This review provides an overview of genetic and functional evidence found for the individual players of the classical complement pathway. In addition, the consequences of the absence of complement proteins, in the form of complement protein deficiencies in humans, are taken into consideration. The collective data provide strong evidence for excessive pruning by the classical complement pathway, contributing to cognitive impairment in schizophrenia. In future studies, it will be important to assess the magnitude of the contribution of complement overactivity to the occurrence and prevalence of phenotypic features in schizophrenia. In addition, more insight is required for the exact mechanisms by which the complement system causes excessive pruning, such as the suggested involvement of microglial engulfment and degradation of synapses. Ultimately, this knowledge is a prerequisite for the development of therapeutic interventions for selective groups of schizophrenia patients.

Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations

BackgroundATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. AimWe aimed to describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. MethodsA retrospective chart review of a cohort of seven patients was conducted. Response to open-label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. ResultsPatients (age 2.5–20 years) had symptom onset at an early age (6 days–1 year). Seizures were either focal or generalized. Common features were: drug resistance, recurrent status epilepticus, etc., severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks–4.8 years) with some improvements reported in all five. ConclusionsOur observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure–function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.

Quantitative MRI Differences Between Early versus Late Onset Alzheimer's Disease.

Investigators report greater parietal tau deposition and alternate frontoparietal network involvement in early onset Alzheimer's Disease (EOAD) with onset <65years as compared with typical late onset AD (LOAD). To determine whether clinical brain MRI volumes reflect these differences in EOAD compared with LOAD. This study investigated the clinical MRI scans of 45 persons with Clinically Probable AD with onset <65years, and compared them to 32 with Clinically Probable AD with onset ≥65years. Brain volumes on their T1 MRI scans were quantified with a volumetric program. Receiver operating curve analyses were performed. Persons with EOAD had significantly smaller parietal lobes (volumetric percentiles) than LOAD. Late onset Alzheimer's Disease had a smaller left putamen and hippocampus. Area Under the Curve was 96.5% with brain region delineation of EOAD compared to LOAD. This study indicates parietal atrophy less than 30% of normal on clinical MRI scans is suggestive of EOAD compared to LOAD.

The effect of Non-Motor symptoms on Health-Related quality of life in patients with young onset Parkinson’s Disease: A single center Vietnamese Cross-Sectional study

BackgroundYoung onset Parkinson’s disease (YOPD) is a distinct entity from typical late onset Parkinson’s disease (LOPD). The influene of non-motor features on the health - related quality of life (HRQoL) in LOPD has been previously reported, but little is known about the impact of non-motor features in YOPD. ObjectiveThe aim of this study was to explore the relationship between non-motor burden and HRQoL in patients with YOPD. MethodsThis was an observational, cross-sectional study in patients with a PD, whose age at disease onset ranged from 21 to 40 years (YOPD). Participants were assessed with the MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS) and the 39-item Parkinson’s Disease Questionnaire (PDQ-39; range 0–100). Spearman’s rank test was used to identify correlations between NMSS domains and several dimension of HRQoL. Stepwise multiple linear regression analysis was performed to identify the independent predictors of HRQoL as measured by PDQ-39 summary index. Results89 patients with YOPD mean (SD) age = 42.15 (5.84) participated. Patients reported 10.17 (4.74) non-motor symptoms, the most common (75%) and severe (median = 3) of which was was fatigue (IQR = 7). The most frequently reported and severely affected NMSS domain was sleep/fatigue (89.9%, median = 8; IQR = 13) followed by mood/cognition (83.1%, median = 6; IQR = 18) and attention/memory (82%, median = 5; IQR = 8). The mean (SD) summary index of PDQ-39 was 32.89 (16.8). The means (SD) of each PDQ-39 dimensions were: mobility 37.33 (21.96), ADL 42.93 (25.33), emotional well-being 39.77 (25.47), stigma 38.19 (28.44), social support 19.03 (22.89), cognition 29.59 (20.63), communication 26.96 (23.57), and bodily discomfort 29.96 (23.19). With the exception of gastrointestinal tract and sexual function, all other NMSS domain scores were correlated with the PDQ-39 summary index. The multivariate model revealed that three NMSS domains including sleep/fatigue, mood/cognition and attention/memory accompanied with UPDRS part III were independent predictors of HRQoL as measured by PDQ-39SI. ConclusionsNon-motor symptoms pertaining to sleep disturbances/fatigue, mood/cognition and attention/memory negatively impact HRQoL in patients with YOPD.

Results of an international Delphi consensus in epilepsy with myoclonic atonic seizures/ Doose syndrome

ObjectiveTo establish a standard framework for early phenotypic diagnosis, investigations, expected findings from investigations, evolution, effective therapies and prognosis in the syndrome of Epilepsy with myoclonic atonic seizures (EMAS) / Doose syndrome. MethodsA core study group (CSG) interested in EMAS was convened. CSG then identified and nominated 15 experts in the field of EMAS. This expert panel (EP) from English speaking nations was invited to participate in anonymous questionnaires. A literature review was provided to them (supplement 1). Three rounds of questionnaires were sent to identify areas of consensus, strength of consensus and areas of contention. ResultsStrong consensus was obtained regarding the clinical phenotype of EMAS: myoclonic atonic seizure was identified among others as a mandatory seizure type with typical onset of afebrile seizures between one and six years. A new term “stormy phase” (SP) was designated to delineate a characteristic phenotypic evolution in EMAS patients associated with seizure worsening. Strong consensus regarding the existence and time of onset of the SP, mandatory investigations to be performed early and later in the clinical course of EMAS, first and second tier treatment and prognostic factors for poor outcome were identified. Areas of lack of consensus included some seizure types that are necessary to diagnose EMAS, interictal EEG findings that prognosticate the course of EMAS, overall duration of SP, time to complete remission, and best approach to treat drug resistant EMAS. SignificanceExpert consensus on core diagnostic criteria of EMAS necessary for natural history studies, phenotype-genotype correlations, and clinical trials including comparative studies was demonstrated. Areas of disagreements (especially prognostic features; treatment options) need further research.

Late- and Typical-Onset Heroin Use Among Older Adults Seeking Treatment for Opioid Use Disorder

Analyze 10-year trends in opioid use disorder with heroin (OUD-H) among older persons and to compare those with typical-onset (age <30 years) to those with late (age 30+) onset. Naturalistic observation using the most recent (2008-2017) Treatment Episode Data Set-Admissions (TEDS-A). Admission records in TEDS-A come from all public and private U.S. programs for substance use disorder treatment receiving public funding. U.S. adults aged 55 years and older entering treatment for the first time between 2008 and 2017 to treat OUD-H. Admission trends, demographics, substance use history. The number of older adults who entered treatment for OUD-H nearly tripled between 2007 and 2017. Compared to those with typical-onset (before age 30), those with late-onset heroin use were more likely to be white, female, more highly educated, and rural. Older adults with late-onset were more likely to be referred to treatment by an employer and less likely to be referred by the criminal justice system. Those with late-onset were more likely to use heroin more frequently but less likely to inject heroin than those with typical-onset. Those with typical onset were more likely to receive medication for addiction treatment than those with late-onset. Late-onset heroin use is increasing among older U.S. adults. Research is needed to understand the unique needs of this population better. As this population grows, geriatric psychiatrists may be increasingly called upon to provide specialized care to people with late-onset OUD-H.

A linguistic analysis of future narratives in adolescents with Complex Regional Pain Syndrome and their pain-free peers.

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition that often develops after injury, with a typical onset in adolescence. The impact of chronic pain is far-reaching, with many adolescents reporting atypical developmental trajectories compared with peers. Social Comparison Theory offers a framework for understanding how such comparisons influence well-being, whereby a heightened sense of disparity places adolescents at risk of poor cognitive, affective and social outcomes. Using a novel linguistic analysis programme, this study aims to investigate cognitive, affective and social language used by adolescents with CRPS in comparison to their peers during a task reflecting on their futures. A story completion task was completed by adolescents with CPRS (n=49) and adolescents without pain (n=48). This task involved asking adolescents to describe their imagined future. Narratives were analysed using a novel linguistic analysis programme, focusing on the cognitive, affective and social dimensions. Findings revealed significant group differences in how adolescents with CRPS described their imagined futures. Adolescents with CRPS used significantly fewer positive affect and more negative affect, anger and sadness words, and greater insight and discrepancy words. No significant groups differences were found for social words. Substantial differences in cognitive and affective words were found between adolescents with and without CRPS. Findings provide novel insights into current understandings of cognitive, affective and social processes in adolescents living with chronic pain, particularly with regard to adolescent developmental trajectories, and may in turn highlight potential targets in psychosocial interventions for adolescents living with chronic pain. Social comparisons are commonly undertaken by adolescents with CRPS in relation to peers, increasing risk for poor cognitive, affective and social outcomes. Findings promote the potential importance of targeting psychosocial factors in treatments for paediatric chronic pain.

17033 Morphologically discordant Stevens-Johnson syndrome in a geriatric patient

A 90-year-old man was hospitalized for pubic symphysis osteomyelitis when he developed a tender, pruritic, erythematous eruption on the chest on hospital day 3. The eruption progressed to the back and extremities by day 4 when dermatology was consulted. Recent medications included cephalexin and piperacillin/tazobactam started 39 days and 3 days before onset, respectively. Notably, the patient had used each in the past uneventfully. Initial physical exam revealed coalescent erythematous macules on the neck, trunk, upper extremities, and proximal thighs with confluent erythema on the back. Nikolsky sign was positive. Desquamation of the lower lip was noted without oral cavity involvement. There were no bullae nor erosions. The patient was afebrile and had right axillary lymphadenopathy. Labs demonstrated transaminitis and eosinophilia. Shave biopsy of the right shoulder showed full thickness epidermal necrosis, consistent with Stevens-Johnson syndrome (SJS). Piperacillin/tazobactam was discontinued and the patient was treated with intravenous immunoglobulin with eventual full recovery from partial sloughing of skin on his back. Excluding mild denudation of the lip and a positive Nikolsky sign, initial presentation showed no classic features of SJS. Furthermore, the typical onset of SJS is 5-28 days after initiation of a new medication; our patient’s two antibiotics were started outside of this timeline. Our initial concern for SJS was further decreased by the uneventful past use of each antibiotic. While the incidence and mortality rates of SJS in elderly patients are higher, the tendency of this population to display atypical features is unclear and warrants further investigation.

A comparison of eating disorder symptomatology, psychological distress and psychosocial function between early, typical and later onset anorexia nervosa

ObjectiveEpidemiological studies suggest that the incidence of anorexia nervosa (AN) is increasing in younger populations, with some evidence that clinical differences occur according to age of onset (AOO), which may impact prognostic outcomes. The current study sought to compare eating disorder (ED) symptomatology, psychological distress and psychosocial function between early onset (EO), typical onset (TO) and later onset (LO) AN in a large sample of treatment-seeking patients with a diagnosis of AN.MethodsParticipants included 249 individuals with a diagnosis of AN who were assessed at an outpatient ED service. The sample was divided into three groups based on AOO; those with an AOO ≤14 years (N = 58) were termed ‘EO-AN’, those with an AOO between 15 and 18 years (N = 113) were termed ‘TO-AN’ and those with an AOO of > 18 years (N = 78) were termed ‘LO-AN’. Comparisons were made between AOO groups on assessments of ED symptomatology, psychological distress and psychosocial function.ResultsEO-AN patients reported a significantly longer illness duration than both TO-AN and LO-AN groups. After controlling for effect of illness duration, the EO-AN group demonstrated significantly higher ED symptomatology and dysmorphic concern compared to the LO-AN group. The EO-AN group demonstrated significantly decreased cognitive flexibility compared to both the TO-AN and LO-AN groups.DiscussionThese findings suggest that clinical differences do occur according to AOO in AN whereby EO-AN may represent a more severe form of illness that is not attributable to increased illness duration. Treatment strategies which specifically address patients with EO-AN may improve long term health outcomes and recovery.

Partial Achilles Tendon Rupture-A Neglected Entity: A Narrative Literature Review on Diagnostics and Treatment Options.

Partial ruptures in the Achilles tendon are rather uncommon and are often misinterpreted as aggravated Achilles tendinopathy, and not always considered as a differential diagnosis. The aim of this literature review was to characterize typical symptoms, to provide an overview of available diagnosis and treatment options, and to give reference points for future research. There were few studies and sparse knowledge of scientific value, making it difficult to give evidence-based recommendations. Based on the few studies and the authors’ clinical experience, a diagnosis should be based on a patient’s history with a typical sharp onset of pain and inability to fully load the tendon. Previous intratendinous cortisone injections might be present. Clinical findings are a localized tender region in the tendon and often weakness during heel raises. Ultrasound and Doppler examinations show a region with an irregular and bulging superficial tendon line, often together with localized high blood flow. Magnetic resonance Imaging (MRI) shows a hyperintense signal in the tendon on T1 and T2-weighted sequences. First-line therapy should be a conservative approach using a 2 cm heel lift for the first 6 weeks and avoiding tendon stretching (for 12 weeks). This is followed by a reduced heel lift of 1 cm and progressive tendon loading at weeks 7–12. After 12 weeks, the heel lift can be removed if pain-free, and the patient can gradually start eccentric exercises lowering the heel below floor level and gradually returning to previous sport level. If conservative management has a poor effect, surgical exploration and the excision of the partial rupture and suturing is required. Augmentation procedures or anchor applications might be useful for partial ruptures in the Achilles insertion, but this depends on the size and exact location. After surgery, the 12 to 14-week rehabilitation program used in conservative management can be recommended before the patient’s return to full tendon loading activities.

Unsteady thrust on an oscillating wind turbine: Comparison of blade-element momentum theory with actuator-line CFD

Floating platforms are being deployed and developed further for offshore wind power generation in deep water. Platforms undergo surge and pitch in waves, causing their supported wind turbine to oscillate back and forth. An important input to modelling the platform – and hence hub – motion are the forces, moments and energy dissipation provided by the turbine rotor. Blade-element momentum theory (BEMT) provides a numerically-efficient method of calculating these quantities in steady flow, but its application to an oscillating turbine is largely untested. To test how appropriate a quasi-steady BEMT methodology is for this application, BEMT (with a high-axial-induction-factor correction) is compared with CFD using an actuator-line representation of the NREL 5 MW design, typical of the type of turbine that might be deployed. For simplicity we assume constant rotor speed and pitch angle. The paper demonstrates that, for typical wave periods and onset wind, a quasi-steady BEMT model provides a good description of loads on an oscillating turbine rotor and provides near-identical results to CFD for forces and power dissipation. However, a common time-dependent BEMT variant does not improve predictions in this application, but proves detrimental to power prediction. The paper also derives a simple formula, based on steady-flow load characteristics, to estimate dissipative damping by the rotor.

A-256 A Unique Bilingual Phenotype in the Context of Late Onset MELAS

Abstract Objective Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a progressive disease with typical onset before age 40 characterized by eventual neurocognitive deterioration. This case study highlights bilingual-bicultural neuropsychological principles within the Socially Responsible Neuropsychology (SRN) model to illustrate the phenotypic presentation of bilingual late-onset MELAS. Method The case is a 56-year-old, right-handed, bilingual Latino male (L1 Spanish, L2 English) with 16 years of education in his country of origin and 22 years as an industrial engineer in the U.S. At age 52, he was diagnosed with MELAS after an abrupt episode of olfactory hallucinations and dysgraphia in both languages. MRI revealed acute infarcts in the right parietal lobe and left cerebellum. He was referred for neuropsychological assessment 4 years later to evaluate reported neurocognitive decline and deterioration of L2, and to assist in targeted treatment planning. Results The clinical interview revealed significant decline in both receptive and expressive L2 English language capabilities, particularly relative to baseline as an industrial engineer, with relative sparing of L1 Spanish. Consistent with prior acute right hemisphere strokes, the neurocognitive profile also revealed lateralized impairment in visuospatial skills and memory. Notably verbal learning and memory in the mesial temporal system was preserved. Conclusions This case study illustrates how late L2 acquisition can lead to bilateral language representation, altering the phenotype of late-onset MELAS. Application of the SRN model highlights the importance of including background information regarding language acquisition and current language use to illustrate a unique bilingual MELAS phenotype and its impact on language loss and recovery.

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey.

PurposeThe presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity.MethodsWe developed a 15-item online questionnaire on “Sudden Olfactory Loss (SOL) and COVID-19” that was administered during March 2020 to Italian general practitioners registered to a social media group.ResultsOne hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients.ConclusionSOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases.Level of evidence4.

Onset features and time to diagnosis in Friedreich\u2019s Ataxia

BackgroundIn rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich’s Ataxia (FRDA), a genetic disorder usually caused by homozygous GAA-repeat expansions.MethodsSix hundred eleven genetically confirmed FRDA patients were recruited within a multicentric natural history study conducted by the EFACTS (European FRDA Consortium for Translational Studies, ClinicalTrials.gov-Identifier NCT02069509). Age at first symptoms as well as age at first suspicion of FRDA by a physician were collected retrospectively at the baseline visit.ResultsIn 554 of cases (90.7%), disease presented with gait or coordination disturbances. In the others (n = 57, 9.3%), non-neurological features such as scoliosis or cardiomyopathy predated ataxia. Before the discovery of the causal mutation in 1996, median time to diagnosis was 4(IQR = 2–9) years and it improved significantly after the introduction of genetic testing (2(IQR = 1–5) years, p < 0.001). Still, after 1996, time to diagnosis was longer in patients with a) non-neurological presentation (mean 6.7, 95%CI [5.5,7.9] vs 4.5, [4.2,5] years in those with neurological presentation, p = 0.001) as well as in b) patients with late-onset (3(IQR = 1–7) vs 2(IQR = 1–5) years compared to typical onset < 25 years of age, p = 0.03).Age at onset significantly correlated with the length of the shorter GAA repeat (GAA1) in case of neurological onset (r = − 0,6; p < 0,0001), but not in patients with non-neurological presentation (r = − 0,1; p = 0,4). Across 54 siblings’ pairs, differences in age at onset did not correlate with differences in GAA-repeat length (r = − 0,14, p = 0,3).ConclusionsIn the genetic era, presentation with non-neurological features or in the adulthood still leads to a significant diagnostic delay in FRDA. Well-known correlations between GAA1 repeat length and disease milestones are not valid in case of atypical presentations or positive family history.