Queen Square Research Articles

Data-driven neuroanatomical subtypes of primary progressive aphasia.

The primary progressive aphasias are rare, language-led dementias, with three main variants: semantic, non-fluent/agrammatic, and logopenic. Whilst semantic variant has a clear neuroanatomical profile, the non-fluent/agrammatic and logopenic variants are difficult to discriminate from neuroimaging. Previous phenotype-driven studies have characterised neuroanatomical profiles of each variant on MRI. In this work we used a machine learning algorithm known as SuStaIn to discover data-driven neuroanatomical "subtype" progression profiles and performed an in-depth subtype-phenotype analysis to characterise the heterogeneity of primary progressive aphasia. Our study included 270 participants with primary progressive aphasia seen for research in the UCL Queen Square Institute of Neurology Dementia Research Centre, with follow-up scans available for 137 participants. This dataset included individuals diagnosed with all three main variants (semantic: n=94, non-fluent/agrammatic: n=109, logopenic: n=51) as well as individuals with un-specified primary progressive aphasia (n=16). A data set of 66 patients (semantic n=37, non-fluent/agrammatic: n=29) from the ALLFTD North American cohort study, was used to validate our results. MRI scans were segmented and SuStaIn was employed on 19 regions of interest to identify neuroanatomical profiles independent of the diagnosis. We assessed the assignment of subtypes and stages, as well as their longitudinal consistency. We discovered four neuroanatomical subtypes of primary progressive aphasia, labelled S1 (left temporal), S2 (insula), S3 (temporoparietal), S4 (frontoparietal), exhibiting robustness to statistical scrutiny. S1 correlated strongly with semantic variant, while S2, S3, and S4 showed mixed associations with the logopenic and non-fluent/agrammatic variants. Notably, S3 displayed a neuroanatomical signature akin to a logopenic only signature, yet a significant proportion of logopenic cases were allocated to S2. The non-fluent/agrammatic variant demonstrated diverse associations with S2, S3, and S4. No clear relationship emerged between any of the neuroanatomical subtypes and the unspecified cases. At first follow up 84% of patients' subtype assignment was stable, and 91.9% of patients' stage assignment was stable. We partially validated our findings in the ALLFTD dataset, finding comparable qualitative patterns. Our study, leveraging machine learning on a large primary progressive aphasia dataset, delineated four distinct neuroanatomical patterns. Our findings suggest that separable spatio-temporal neuroanatomical phenotypes do exist within the PPA spectrum, but that these are noisy, particularly for nfvPPA and lvPPA. Furthermore, these phenotypes do not always conform to standard formulations of clinico-anatomical correlation. Understanding the multifaceted profiles of the disease, encompassing neuroanatomical, molecular, clinical, and cognitive dimensions, holds potential implications for clinical decision support.

PRECIOUS study (PREterm Caesarean/vaginal birth and IVH/OUtcomeS): does mode of birth reduce the risk of death or brain injury in very preterm babies? A cohort and emulated target trial protocol

IntroductionVery preterm babies are at risk of poor neurodevelopmental outcomes and death. Intraventricular haemorrhage (IVH) after birth is the most prevalent cause of this. Birth by caesarean section may protect...

SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients

IntroductionSuccessful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased...

‘A divine right to photograph’: E. Graeme Robertson’s (1903–1975) historical motion pictures of National Hospital staff in 1933

ABSTRACT In the course of researching and writing the first-ever book length biography of Edward Graeme Robertson’s (1903–1975) eventful life and career in Australasian neurology, a rare 1933 cinema film recording of National Hospital staff at Queen Square has recently been rediscovered. Graeme completed his residency in neurology at Queen Square in the early 1930s and maintained close connections with his colleagues in London, thoughtfully recording them at different times using early movie cameras. Two versions of Graeme’s 1933 film have been preserved, and there are also other color clips of his colleagues from later in life in the UCL Neurology archives and Robertson family collection. These remarkable films contain images of several historically significant neurologists, including Gordon Morgan Holmes (1876–1965), Samuel Alexander Kinnier Wilson (1878–1937), Derek Denny-Brown (1901–1981), Macdonald Critchley (1900–1997), and several others. We provide a contextual summary of the many clips recorded alongside an in-depth inventory of all the personalities represented in the 1933 film. Selected photographs are used to indicate the contents of these remarkable films.

Neuropathologic Validation and Diagnostic Accuracy of Presynaptic Dopaminergic Imaging in the Diagnosis of Parkinsonism.

Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism. Retrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism. All of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%). DAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations. This study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.

Editor Profile: Andrey Abramov.

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Professor Andrey Abramov is a cell biologist and biophysicist at University College London's Queen Square Institute of Neurology. He has served as an Editorial Board Member of The FEBS Journal since 2015.

The transition from cranial surgery to neurosurgery in East London, 1760–1960

ABSTRACT The emergence of neurosurgery from the practice of cranial surgery between the eighteenth and the twentieth centuries in London, UK, is well documented, including the role of Sir Victor Horsley, the first neurosurgical appointee at the National Hospital Queen Square in 1886. The process of this transition elsewhere in London and the subsequent foundation of other neurosurgical units are less well described. In East London, the status of St. Bartholomew’s Hospital (Barts) as the oldest London hospital still active on its original site and its comprehensive archives allow an unusually long history of surgical practice in the specialty to be studied. Using these archives and other primary and secondary sources, this article describes the transition of cranial surgery in East London from the general surgeons, limited to the treatment of brain and skull injury, to the specialized discipline of neurosurgery. We discuss the culmination of this process in the foundation of three neurosurgical units at London Hospital, Whitechapel, by Sir Hugh B. Cairns from 1927; at Barts Hospital, Smithfield, by John E. A. O’Connell from 1937; and at Oldchurch Hospital, Romford, by Leslie C. Oliver from 1945. Two modern neurosurgical units, in Whitechapel and Romford, have taken forward the work begun by this group.

The effects that secondary parkinsonian syndromes have on health status

Introduction and aim of work: The parkinsonian syndrome is a component of Parkinson's disease. A thorough neurological examination can detect symptoms belonging to the parkinsonian syndrome. Diagnosis using the Queen Square Brain Bank criteria is based on the presence of bradykinesia along with one additional symptom in the patient. These include muscle rigidity or resting tremors at a frequency of 4-6 Hz, or postural disturbances that cannot be explained by visual, vestibular, cerebellar, or deep sensory disorders. The parkinsonian syndrome can occur in idiopathic Parkinson's disease, hereditary disorders, secondary parkinsonism, or be part of an atypical parkinsonian syndrome. The aim of the study was to discuss the diagnostic features and differences in the occurrence of the parkinsonian syndrome as a component of Parkinson's disease, both within the context of other neurological disorders. Materials and methods: The foundation of the research was medical articles gathered from the Google Scholar database. The studies were conducted by analyzing keywords such as "parkinsonism," "drug-induced parkinsonism," and "vascular parkinsonism." Results: Secondary parkinsonism, or secondary parkinsonism syndrome, can be indicated by clinical features such as: disease onset below the age of 40, abrupt onset, rapid disease progression, symptoms related to medication use, and symptoms associated with the underlying condition. In addition to clinical evaluation, imaging studies are also employed. Various conditions can lead to the development of secondary parkinsonism, including hydrocephalus, brain tumors, encephalitis, cerebral atherosclerosis, traumatic brain injuries, medications, and poisoning. The aforementioned conditions exert different mechanisms of influence on the central nervous system.

Bayesian brain computing and the free-energy principle: an interview with Karl Friston.

The free-energy principle entails the Bayesian brain hypothesis that can be implemented by many schemes considered in this field. The combination of multimodal brain imaging and free-energy minimization has shown promise in unraveling complex brain dynamics and understanding the interactions among distinct brain regions. The Bayesian mechanics of brain computing gives a unique route to understanding authentic (neuromimetic) intelligence and, more importantly, points towards the development of brain-inspired intelligence. NSR spoke to a leading theoretical neuroscientist and authority on brain imaging-Karl Friston, the inventor of statistical parametric mapping, voxel-based morphometry and dynamic causal modeling. Friston is also known for his contributions to theoretical biology in the form of the free-energy principle and applications such as active inference. Friston is currently the Scientific Director of the Wellcome Trust Centre for Neuroimaging, Professor of Neuroscience at Queen Square Institute of Neurology, University College London and Honorary Consultant at The National Hospital for Neurology and Neurosurgery, UK.

More than one way to improve a CAT: Outcomes and reflections on two iterations of the Queen Square Intensive Comprehensive Aphasia Programme

ABSTRACT Background The field of human expert performance teaches us that high quality, high-dose guided practice is required to make large gains in cognitively driven acts. The same also seems to be true for people with acquired brain injury, yet therapy services for people with aphasia (PWA) have traditionally not been designed with this in mind. Intensive Comprehensive Aphasia Programmes (ICAPs) are one way to address the chronic under-dosing of therapy that most PWA experience. Aims There are several ways to deliver an ICAP; here we describe two iterations of our Queen Square ICAP. There was a 20-month COVID-induced pause between the Year 1 (Y1) and Year 2 (Y2) ICAP groups. We analyse ICAP-induced changes in both groups of PWA on a series of key outcome measures that span the International Classification of Functioning, Disability and Health, covering language impairment and function as well as mood and social participation. Methods & Procedures Forty-six PWA took part in Y1 and 44 in Y2. The PWA were all in the chronic stage post stroke and varied in aphasia severity from mild to severe, with the Y2 group being more impaired than Y1. Quantitative data was collected before and after the ICAP. The Y2 therapy team provided independent reflections on their experiences of delivering an ICAP. Outcomes & Results ICAP-related changes in outcome measures (impairment, function and goal attainment) were generally comparable for the Y1 and Y2 groups, with both groups’ speech production abilities improving the most. Both groups made clinically and statistically significant gains on the main quality of life measure. Participation in the ICAP made a big difference to PWAs’ self-confidence ratings. Their mood ratings also improved significantly, although they were not, on average, in the depressed range at baseline (directly pre-ICAP). All improvements achieved in both groups were maintained at the 3-month follow-up, highlighting the lasting effects that ICAPs can provide. Conclusions Evidence continues to accrue that ICAPs are an efficient way of increasing the dose of expert coaching required for people with chronic aphasia to make clinically meaningful improvements in their communicative abilities and quality of life. The main challenge remaining is convincing health-care providers to invest in them.

Data‐driven neuroanatomical subtype trajectories of primary progressive aphasia

AbstractBackgroundPrimary progressive aphasia (PPA) is an atypical neurodegenerative dementia with three main clinical variants: semantic (svPPA), non‐fluent/agrammatic (nfvPPA) and logopenic (lvPPA). While svPPA is typically associated with left anterior temporal lobe atrophy, neuroimaging findings in nfvPPA, lvPPA and PPA not otherwise specified (PPA‐nos) are more variable. We therefore applied unsupervised machine learning to one of the largest databases of PPA magnetic resonance imaging (MRI) scans ever acquired.MethodBaseline MRI scans were collected from 273 people with PPA participating in the longitudinal research programme in the Queen Square Dementia Research Centre (svPPA n = 97; nfvPPA n = 109; lvPPA n = 51; PPA‐nos n = 16). Longitudinal scans were collected from 138 participants. We used Subtype and Stage Inference (SuStaIn), a model that combines disease progression modelling with unsupervised machine learning to identify subgroups of patients following a similar trajectory. We standardised the data with respect to cognitively normal controls (n = 360). Based on clinicians’ input we chose 19 brain regions of interest to model from those generated by GIF (Cardoso et al. 2012). The model was fit using baseline data, selecting the appropriate number of subtypes using cross‐validation (Young et al. 2018).ResultCross‐validation supported four subtypes of spatiotemporal atrophy (Figure 1). Clinical variant representation per subtype assignment (1/2/3/4) was: svPPA (n = 74/15/4/4), nfvPPA (n = 3/35/21/44), lvPPA (n = 1/18/30/2) and PPA‐nos (n = 7/4/3/2) (Figure 2). Subtype 1 showed early decline in the left anterior temporal lobe and sparing of the left frontal lobe. Subtype 2 showed early decline of the left insula and sparing of the temporal pole. Subtype 3 showed initial atrophy of the left temporoparietal junction; Subtype 4 showed early atrophy in the left precentral gyrus. Statistical analysis of posterior distributions found low similarity between subtypes (Hellinger distance > 0.66) (Figure 3), validating the presence of four distinct subtypes.ConclusionWhile the data‐driven atrophy subtypes did not align perfectly with clinical variants, we found a correspondence between Subtype 1 and svPPA, the most coherent PPA variant. Subtypes 2,3 and 4 were associated with nfvPPA and lvPPA, corroborating work suggesting these diagnostic terms encompass multiple clinical phenotypes. Future work will investigate the association between clinical diagnosis, longitudinal subtype, and clinical measures.

Data‐driven neuroanatomical subtype trajectories of primary progressive aphasia

AbstractBackgroundPrimary progressive aphasia (PPA) is an atypical neurodegenerative dementia with three main clinical variants: semantic (svPPA), non‐fluent/agrammatic (nfvPPA) and logopenic (lvPPA). While svPPA is typically associated with left anterior temporal lobe atrophy, neuroimaging findings in nfvPPA, lvPPA and PPA not otherwise specified (PPA‐nos) are more variable. We therefore applied unsupervised machine learning to one of the largest databases of PPA magnetic resonance imaging (MRI) scans ever acquired.MethodBaseline MRI scans were collected from 273 people with PPA participating in the longitudinal research programme in the Queen Square Dementia Research Centre (svPPA n = 97; nfvPPA n = 109; lvPPA n = 51; PPA‐nos n = 16). Longitudinal scans were collected from 138 participants. We used Subtype and Stage Inference (SuStaIn), a model that combines disease progression modelling with unsupervised machine learning to identify subgroups of patients following a similar trajectory. We standardised the data with respect to cognitively normal controls (n = 360). Based on clinicians’ input we chose 19 brain regions of interest to model from those generated by GIF (Cardoso et al. 2012). The model was fit using baseline data, selecting the appropriate number of subtypes using cross‐validation (Young et al. 2018).ResultCross‐validation supported four subtypes of spatiotemporal atrophy (Figure 1). Clinical variant representation per subtype assignment (1/2/3/4) was: svPPA (n = 74/15/4/4), nfvPPA (n = 3/35/21/44), lvPPA (n = 1/18/30/2) and PPA‐nos (n = 7/4/3/2) (Figure 2). Subtype 1 showed early decline in the left anterior temporal lobe and sparing of the left frontal lobe. Subtype 2 showed early decline of the left insula and sparing of the temporal pole. Subtype 3 showed initial atrophy of the left temporoparietal junction; Subtype 4 showed early atrophy in the left precentral gyrus. Statistical analysis of posterior distributions found low similarity between subtypes (Hellinger distance > 0.66) (Figure 3), validating the presence of four distinct subtypes.ConclusionWhile the data‐driven atrophy subtypes did not align perfectly with clinical variants, we found a correspondence between Subtype 1 and svPPA, the most coherent PPA variant. Subtypes 2,3 and 4 were associated with nfvPPA and lvPPA, corroborating work suggesting these diagnostic terms encompass multiple clinical phenotypes. Future work will investigate the association between clinical diagnosis, longitudinal subtype, and clinical measures.

The auditory phenotype of behavioural variant frontotemporal dementia

AbstractBackgroundPatients with behavioural variant frontotemporal dementia commonly exhibit abnormal hedonic and other behavioural responses to sounds, however hearing dysfunction in this disorder is poorly characterised. Here we addressed this issue using the Queen Square Tests of Auditory Cognition (QSTAC) – a neuropsychological battery for the systematic assessment of central auditory functions (including pitch pattern perception, environmental sound recognition, sound localisation and emotion processing) in cognitively impaired people.MethodThe QSTAC was administered to 15 patients with behavioural variant frontotempoal dementia, 24 patients with comparator dementia syndromes (primary progressive aphasia and typical Alzheimer’s disease) and 15 healthy age‐matched individuals. Participants also had pure tone audiometry to assess peripheral hearing function and a comprehensive general neuropsychological assessment.ResultAfter accounting for nonverbal executive and peripheral hearing performance, patients with behavioural variant frontotemporal dementia showed deficits of environmental sound and auditory emotion recognition and sound localisation, compared both with healthy controls and patients with Alzheimer’s disease. Patients with behavioural variant frontotemporal dementia were further differentiated from primary progressive aphasia patients on their performance across QSTAC (sound recognition and localisation) subtests.ConclusionBehavioural variant frontotemporal dementia has a distinct phenotype of auditory cognitive dysfunction which likely contributes to the hearing alterations that many patients with this diagnosis experience in daily life. Our findings call attention to an under‐recognised issue in frontotemporal dementia that warrants further clinical interpretation and the development of management strategies tailored to real‐world acoustic environments.

Group psychotherapy format guided self‐help for patients with FNSD awaiting inpatient multidisciplinary treatment: A pilot study

AbstractBackgroundWe describe our experience of developing Guided Self Help for patients with Functional Neurological Symptom Disorder as group therapy, delivered remotely, via Zoom.AimsThe aims of the current study are (a) to describe how the original Queen Square Guided Self‐Help (QGSH) was adapted for group therapy, and (b) to present a service evaluation of the first 8 months of running QGSH therapy groups remotely.MethodsWe carried out a review after 8 months, from 11 May 2021 until 31 January 2022.ResultsA total of 16 patients were treated in three groups. Assessing our outcomes in terms of Yalom's framework for group psychotherapy, we found that the group provided 10/11 of Yalom's therapeutic factors. Patient satisfaction was high.DiscussionWe outline for plans for further devaluation and development, including the development of a stand‐alone group.ConclusionThe group therapy format is a promising addition to our service.

Research trends and hotspots of glial fibrillary acidic protein within the area of Alzheimer's disease: a bibliometric analysis.

Our aim was to analyze the trends and hotspots on glial fibrillary acidic protein (GFAP) within the area of Alzheimer's disease (AD) by using a bibliometric method, which is currently missing. All articles and reviews on GFAP within the area of AD from inception to December 31, 2022, were searched from the Web of Science Core Collection. Full records were derived, imported into Microsoft Excel, and analyzed by BIBLIOMETRC, VOSviewer, and CiteSpace. In total, 2,269 publications, including 2,166 articles, were ultimately included. The number of publications from 81 countries/regions and 527 academic journals increased annually. The top three prolific countries and institutions were the USA, China, and England, the University of Gothenburg (Sweden), Universidade Federal Rio Grande do Sul (Brasilia), and UCL Queen Square Institute of Neurology (England). Henrik Zetterberg from the University of Gothenburg, Kaj Blennow from the University of Gothenburg, and Alexei Verkhratsky from the University of Manchester were the top three prolific and cited authors; Journal of Alzheimer's Disease, Brain Research, and Neuroscience contributed the most publications. The top key areas of research included "molecular, biology, and genetics" and "molecular, biology, and immunology," and the top published and linked meaningful keywords included oxidative stress, inflammation/neuroinflammation, microglia, hippocampus, amyloid, cognitive impairment, tau, and dysfunction. Based on the bibliometric analysis, the number of publications on GFAP within the area of AD has been rapidly increasing, especially in the past several years. Oxidative stress and inflammation are research hotspots, and GFAP in body fluids, especially blood, could be used for large-scale screening for AD.

B-135 Research Trends and Hotspots of Glial Fibrillary Acidic Protein in Body Fluid for Alzheimer’s Disease: A Bibliometric Analysis

Abstract Background As the most common form of dementia, Alzheimer’s disease (AD) is prevalent worldwide. An increasing number of studies have focused on glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, for the development, diagnosis and prognosis of AD. Therefore, this study aimed to analyze trends and hotspots of GFAP in body fluid for AD by using a bibliometric method, which is missing in current publications. Methods We systematically searched the Web of Science Core Collection for published papers on GFAP in body fluid and AD. All articles and reviews from inception to December 31, 2022, were included in this study. Full records and cited references of all publications were derived, imported into Microsoft Excel, and analyzed by BIBLIOMETRC Online analysis platform and VOSviewer software. Results A total of 2269 publications including 2166 articles were ultimately included based on the inclusion criteria. The data showed that the number of published papers on GFAP in body fluid and AD is annually increasing, which was published in 81 countries/regions and 527 academic journals. Separately, the top 3 prolific countries/regions and institutions were USA, China and England, Univ Gothenburg (Sweden), Univ Fed Rio Grande do Sul (Brasilia) and UCL Queen Square Institute of Neurology (England). Journal of Alzheimer’s Disease, Brain Research, and Neuroscience contributed the most publications; Zetterberg, Henrik from Univ Gothenburg, Blennow, Kaj from Univ Gothenburg and Verkhratsky, Alexei from the University of Manchester were the top 3 prolific and cited authors. The most published and linked meaningful keywords included oxidative stress, inflammation, microglia, hippocampus and amyloid, which also annually increased in recent publications. Conclusion Based on a bibliometric analysis, the number of publications on GFAP in body fluid and AD are rapidly increasing, especially in the past several years. Oxidative stress and inflammation are research hotspots, and the diagnostic performance of GFAP in body fluid need to be further summarized and verified.

The Queen Square Encephalitis Multidisciplinary Team Meeting - experience over three years, pre and post the COVID-19 pandemic

BackgroundPatients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years. MethodsA retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses. ResultsOver the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management. ConclusionsMultidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base.

A Spotlight on Friedreich Ataxia: Optimising the Patient Journey from Diagnosis to Disease Management

This symposium was held on the first day of the European Academy of Neurology (EAN) Congress, with four main objectives: to raise awareness of Friedreich ataxia (FA) as a rare, progressive neurodegenerative disorder; to summarise the patient journey from identifying first symptoms in childhood and adolescence to reaching an accurate diagnosis; to discuss the burden of living with FA and highlight the benefit of improved communication and collaboration between members of the multidisciplinary team on reducing this burden on patients and their caregivers; and to summarise current management options within the field of FA and provide an overview of emerging therapies and active clinical trials. The symposium was chaired by Sylvia Boesch, a neurologist and senior staff member at the Medical University of Innsbruck, Austria, and Head of the Centre for Rare Movement Disorders, Innsbruck, Austria, who presented an overview of rare diseases in general and of FA. Mathieu Anheim, a neurologist at the Movement Disorders Unit, University Hospital of Strasbourg, France, followed with a description of the aetiology and symptomatology of FA. Lastly, Paola Giunti, a professorial research associate in the Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, UK, explained the best approach to FA management, including a summary of clinical trials for emerging therapies in FA.

Digital Biomarkers in Parkinson's Disease: Missing the Forest for the Trees?

Movement Disorders Clinical PracticeAccepted Articles VIEWPOINT Digital biomarkers in Parkinson's disease: missing the forest for the trees? Ashwani Jha MRCP PhD, Corresponding Author Ashwani Jha MRCP PhD [email protected] orcid.org/0000-0003-2835-6837 UCL Queen Square Institute of Neurology, London, UK Correspondence to: Ashwani Jha, Russell Square House, 10-12 Russell Square, 1st floor Stroke Research Centre, London, UK WC1B 5EH. E-mail: [email protected]Search for more papers by this authorAlberto J. Espay MD MSc, Alberto J. Espay MD MSc orcid.org/0000-0002-3389-136X James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USASearch for more papers by this authorAndrew J. Lees FRCP F.Med.Sci PhD, Andrew J. Lees FRCP F.Med.Sci PhD Reta Lila Weston Institute of Neurological Studies, Department of Clinical Movement Disorder and Neuroscience, Institute of Neurology, University College London, London, United KingdomSearch for more papers by this author Ashwani Jha MRCP PhD, Corresponding Author Ashwani Jha MRCP PhD [email protected] orcid.org/0000-0003-2835-6837 UCL Queen Square Institute of Neurology, London, UK Correspondence to: Ashwani Jha, Russell Square House, 10-12 Russell Square, 1st floor Stroke Research Centre, London, UK WC1B 5EH. E-mail: [email protected]Search for more papers by this authorAlberto J. Espay MD MSc, Alberto J. Espay MD MSc orcid.org/0000-0002-3389-136X James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USASearch for more papers by this authorAndrew J. Lees FRCP F.Med.Sci PhD, Andrew J. Lees FRCP F.Med.Sci PhD Reta Lila Weston Institute of Neurological Studies, Department of Clinical Movement Disorder and Neuroscience, Institute of Neurology, University College London, London, United KingdomSearch for more papers by this author First published: 12 April 2023 https://doi.org/10.1002/mdc3.13746 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/mdc3.13746. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Derek Denny-Brown: His Life in New Zealand and England 1901–1941 (P4-3.008)

<h3>Objective:</h3> To describe Denny-Brown’s early life and education in New Zealand, Oxford and London, and how they influenced his career in neurology <h3>Background:</h3> Denny-Brown is remembered for his career at Harvard University and Boston City Hospital (1941–1967), but less is known about his life before 1941. <h3>Design/Methods:</h3> Review of archives and historical manuscripts. <h3>Results:</h3> Denny-Brown was born in Christchurch, New Zealand in 1901, where his father worked for a life insurance company. His secondary schooling was in an isolated town on the west coast of New Zealand. He studied medicine at University of Otago where his interest in the nervous system was stimulated by the Professor of Anatomy, Percy Gowland. After graduating in 1924 he spent a year studying the tuatara brain. With Gowland’s encouragement, Denny-Brown secured a Beit Fellowship, which allowed him to study neurophysiology with Sherrington at Oxford. This resulted in publication of 15 papers, a D.Phil. and co-authorship of “Reflex Activity of the Spinal Cord”. Following his successful early career in basic neurophysiology, Denny-Brown trained in neurology at the National Hospital, Queen Square. He was appointed as neurologist at Queen Square and St. Bartholomew’s Hospital. In 1936 he worked with Fulton at Yale. His most significant publications in the 1930s were on fibrillation, fasciculation and myotonia and his self-experimentation on micturition and defecation. He was frustrated by lack of time available for research and in 1939 he applied successfully for appointment as Professor of Neurology at Harvard. His commitment to the British Army meant he was unable to take up that position until 1941. From 1939–1941 he conducted experimental research on head injury at St Hugh’s Military Hospital, Oxford. <h3>Conclusions:</h3> Denny-Brown’s career in neurology was shaped by his studies in neuroanatomy in New Zealand and neurophysiology in Oxford, and by Gowland, Sherrington and several British neurologists. <b>Disclosure:</b> Dr. Anderson has nothing to disclose. Dr. Gilman has nothing to disclose.