Queen Square Research Articles

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p<0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p<0.05, from whole brain statistical parametric map analysis). This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies. This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

PERAN RTH ALUN-ALUN RATU ZALECHA TERHADAP KENYAMANAN LINGKUNGAN BERDASARKAN PERSEPSI MASYARAKAT DAN INDEKS KETIDAKNYAMANAN (Studi Kasus RTH Alun-Alun Ratu Zalecha, Martapura Kalimantan Selatan)

Based on statistical data (Banjar District in Figures, 2016), it was found that there was an increase in population density from 2013 to 115 people / km2, by 2014 117 people / km2 and 2015 by 119 souls / km2. To support human needs and activities, it takes a lot of space, especially built space. The purpose of this study is to analyze the public perception about the role of green space on environmental comfort in RTH Ratu Zalecha Square and analyze the role of RTH Queen Square Zalecha to the comfort of environment based on the index of discomfort. The research method used is survey method and quantitative descriptive analysis. The survey method aims to observe the condition of research sites such as physical condition and RTH characteristics. The survey also aims to determine the point of data collection, identify the green space structure, and take the microclimate primary data. The result of this research shows that the level of public perception on the comfort of RTH Alun-Alun Ratu Zalecha has positive effect for 84 respondent (87,5%) and 12 respondents (12,5%). This indicates that H0 is accepted which presumes that there is positive effect of RTH of Queen of Zalecha against the comfort of environment and H1 is rejected and Chi-Square calculation shows that X2H value is 96,47 bigger than X2 table 5% that is 5,991 so that H0 is accepted, meaning there is a significant difference between the three levels of public perception towards the comfort of the environment with the highest level of positive perception is in the category of a very influential role and affect the comfort of the environment. Based on observation data at the study location, the average daily discomfort index at location I (on the surface), location I (1.4 meters), location II (1.4 meters), location III (1.4) meters) between 80,2-81,7 which is in the interval of the value of DI&gt; 80, which means that 100% of respondents stated that all research locations in the category were uncomfortable for humans.

Learning from multiple annotators for medical image segmentation

Supervised machine learning methods have been widely developed for segmentation tasks in recent years. However, the quality of labels has high impact on the predictive performance of these algorithms. This issue is particularly acute in the medical image domain, where both the cost of annotation and the inter-observer variability are high. Different human experts contribute estimates of the ”actual” segmentation labels in a typical label acquisition process, influenced by their personal biases and competency levels. The performance of automatic segmentation algorithms is limited when these noisy labels are used as the expert consensus label. In this work, we use two coupled CNNs to jointly learn, from purely noisy observations alone, the reliability of individual annotators and the expert consensus label distributions. The separation of the two is achieved by maximally describing the annotator’s “unreliable behavior” (we call it “maximally unreliable”) while achieving high fidelity with the noisy training data. We first create a toy segmentation dataset using MNIST and investigate the properties of the proposed algorithm. We then use three public medical imaging segmentation datasets to demonstrate our method’s efficacy, including both simulated (where necessary) and real-world annotations: 1) ISBI2015 (multiple-sclerosis lesions); 2) BraTS (brain tumors); 3) LIDC-IDRI (lung abnormalities). Finally, we create a real-world multiple sclerosis lesion dataset (QSMSC at UCL: Queen Square Multiple Sclerosis Center at UCL, UK) with manual segmentations from 4 different annotators (3 radiologists with different level skills and 1 expert to generate the expert consensus label). In all datasets, our method consistently outperforms competing methods and relevant baselines, especially when the number of annotations is small and the amount of disagreement is large. The studies also reveal that the system is capable of capturing the complicated spatial characteristics of annotators’ mistakes.

Pathological Validation of the MDS Criteria for the Diagnosis of Multiple System Atrophy.

The recent International Parkinson and Movement Disorder Society diagnostic criteria for multiple system atrophy (MDS-MSA) have been developed to improve diagnostic accuracy although their diagnostic properties have not been evaluated. The aims were to validate the MDS-MSA diagnostic criteria against neuropathological diagnosis and compare their diagnostic performance to previous criteria and diagnosis in clinical practice. Consecutive patients with sporadic, progressive, adult-onset parkinsonism, or cerebellar ataxia from the Queen Square Brain Bank between 2009 and 2019 were selected and divided based on neuropathological diagnosis into MSA and non-MSA. Medical records were systematically reviewed, and clinical diagnosis was documented by retrospectively applying the MDS-MSA criteria, second consensus criteria, and diagnosis according to treating clinicians at early (within 3 years of symptom onset) and final stages. Diagnostic parameters (sensitivity, specificity, positive/negative predictive value, and accuracy) were calculated using neuropathological diagnosis as gold standard and compared between different criteria. Three hundred eighteen patients (103 MSA and 215 non-MSA) were included, comprising 248 patients with parkinsonism and 70 with cerebellar ataxia. Clinically probable MDS-MSA showed excellent sensitivity (95.1%), specificity (94.0%), and accuracy (94.3%), although their sensitivity at early stages was modest (62.1%). Clinically probable MDS-MSA outperformed diagnosis by clinicians and by second consensus criteria. Clinically established MDS-MSA showed perfect specificity (100%) even at early stages although to the detriment of low sensitivity. MDS-MSA diagnostic accuracy did not differ according to clinical presentation (ataxia vs. parkinsonism). MDS-MSA criteria demonstrated excellent diagnostic performance against neuropathological diagnosis and are useful diagnostic tools for clinical practice and research. © 2023 International Parkinson and Movement Disorder Society.

Clinical Diagnostic Accuracy of Parkinson's Disease: Where Do We Stand?

Clinical diagnostic accuracy of Parkinson's disease (PD) remains suboptimal. Changes in disease concept may have improved clinical diagnostic accuracy in the past decade. However, current clinical diagnostic criteria have not been validated against neuropathological confirmation. This study aims to provide up-to-date clinical diagnostic accuracy data and validate current clinical diagnostic criteria for PD against neuropathology. A retrospective review of medical records of consecutive patients with parkinsonism from the Queen Square Brain Bank was performed between 2009 and 2019. Clinical diagnosis was documented at early (within 5 years of motor symptom onset) and final stages and categorized by movement disorder experts or regular clinicians. Movement Disorder Society Parkinson's disease (MDS-PD) diagnostic criteria were retrospectively applied. Diagnostic accuracy parameters (sensitivity, specificity, positive/negative predictive value, and accuracy) were calculated using neuropathological diagnosis as the gold standard. A total of 267 patients (141 PD and 126 non-PD parkinsonism) were included. Clinical diagnostic accuracy was 97.2% for experts, 92.5% for the MDS clinically probable PD criteria, and 90.3% for clinicians. Similar figures were obtained when applied at an early stage (91.5%, 89.5%, and 84.2% diagnostic accuracy, respectively). MDS clinically established early PD criteria demonstrated very high specificity (98.4%) at early stages. Our results showed an important improvement in PD clinical diagnostic accuracy in clinical practice over the past decade, more marked at early stages of the disease. MDS-PD diagnostic criteria is a valid tool in clinical practice and research for the identification of PD patients showing excellent sensitivity and specificity, although movement disorder experts' diagnosis remains the gold standard PD diagnosis during life. © 2023 International Parkinson and Movement Disorder Society.

A subtle presentation of a treatable cause of predominant hemidystonia with minimal ataxia: Expert commentary

In this issue of Parkinsonism and Related Disorders (Movements Disorders Round), Wrigley et al. (Reta Lila Weston Institute, UCL, Queen Square Institute of Neurology, London, UK) present an interesting case report of an 18-year-old patient, with an ataxia-dystonia syndrome [1]. Dystonia was the predominant presentation, classified as right hemidystonia (with writer's cramp in the right hand and dystonia in the right foot), associated with mild signs of cerebellar ataxia and with minimal deficit of vibratory sensitivity in the right lower limb [1].

Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy.

Orthostatic hypotension (OH) increases dementia risk in patients with Parkinson disease (PD), although the underlying mechanisms and whether a similar association between OH and cognitive impairment exists in other synucleinopathies remain unknown. The aim is to evaluate the association between OH and dementia risk in patients with PD, and cognitive impairment risk in patients with multiple system atrophy (MSA), and to explore relevant clinical and neuropathologic factors to understand underlying pathogenic mechanisms. This is a retrospective cohort study. Medical records throughout the entire disease course of consecutive patients with neuropathology-confirmed PD and MSA from the Queen Square Brain Bank were systematically reviewed. Time of onset and severity of OH-related symptoms were documented, and their association with other clinical and neuropathologic variables was evaluated. Dementia risk for patients with PD and cognitive impairment risk for patients with MSA were estimated using multivariable hazard regression. One hundred thirty-two patients with PD and 137 with MSA were included. Patients with MSA developed OH more frequently, earlier in the disease course and with more severe symptoms. Cumulative dementia prevalence was higher in patients with PD. Multivariable adjusted regression models showed that early OH, but not its symptom severity, increased dementia risk in patients with PD by 14% per year (hazard ratio [HR] = 0.86; 95% CI, 0.80-0.93) and cognitive impairment risk in patients with MSA by 41% per year (HR = 0.59; 95% CI, 0.42-0.83). Early OH was not associated with increased α-synuclein, β-amyloid, tau, Alzheimer, or cerebrovascular pathologies. No significant associations were found between severity of OH symptoms and other clinical or neuropathologic variables. Early OH, but not its symptom severity, increases the risk of cognitive impairment in patients with PD and MSA. OH is not associated with more extensive Lewy, β-amyloid, tau, Alzheimer, or cerebrovascular pathologies. It is likely that OH contributes to cognitive impairment in patients with PD and MSA by hypoxia-induced nonspecific neurodegeneration. Further research should evaluate whether improving brain perfusion by treating OH may modify the risk of dementia in these conditions.

Clinical and genetic features of Lewy body pathology in autosomal dominant and sporadic Alzheimer disease

AbstractBackgroundLewy body pathology (LBP) occurs in a substantial portion of individuals with autosomal dominant (ADAD) and sporadic Alzheimer disease (sAD) (Ringman, 2016; Cairns, 2015; Leverenz, 2007; Lippa, 1998). Whereas other non‐AD pathologies are frequent in sAD, LBP seems to be the most common co‐pathology in the relatively young ADAD population (Cairns, 2015). Knowledge of clinical and genetic characteristics of LBP in both ADAD and sAD is incomplete.MethodData from the National Alzheimer’s Coordinating Center, the Dominantly Inherited Alzheimer Network, the Queen Square Brain Bank at University College London and the Neurobiobank Munich were leveraged to compare individuals with ADAD and neuropathologically diagnosed sAD with and without LBP. Chi‐squared and Student’s t‐test were used for comparison of categorical and continuous variables respectively.ResultThe study included 139 ADAD and 4661 sAD autopsy cases. LBP occurred in 59% of ADAD and 38% of sAD cases. LBP was associated with a longer survival in both ADAD (10.1 vs. 8.6 years, p=0.024) and sAD (10.5 vs. 10.2 years, p=0.016). Memory disturbance occurred more frequently as the first clinical AD symptom in both AD variants when LBP was present (ADAD: 90 vs. 65%, p=0.005; sAD: 78 vs. 71%, p&lt;0.001). In both ADAD and sAD, the presence of at least one APOE e4 allele was more common in individuals with LBP (ADAD: 40 vs. 21%, p=0.047; sAD: 57 vs. 46%, p&lt;0.001). In ADAD, frequency of LBP did not differ between individuals with PSEN1 and APP mutations.ConclusionIn this investigation of 139 ADAD and 4661 sAD autopsy cases, LBP occurred in about 60% with ADAD and 40% with sAD. In both ADAD and sAD, the presence of LBP was associated with longer survival, higher frequency of memory disturbance as the first AD symptom and positive APOE e4 status. Further study of these associations may increase our understanding of the role of LBP in AD.

Neuroinflammation in posterior cortical atrophy and typical Alzheimer’s disease

AbstractBackgroundPosterior cortical atrophy (PCA) is a neurodegenerative, predominantly young‐onset syndrome most commonly caused by Alzheimer’s disease (AD). PCA presents with visual and spatial dysfunction attributed to occipito‐parietal or “posterior” brain regions rather than memory difficulties characteristic of typical Alzheimer’s disease (tAD) attributed to medial temporal regions. Whilst the underlying pathology of PCA and tAD are usually the same: Aβ plaques and tau neurofibrillary tangles (NFTs), imaging and neuropathological work points to a more posterior distribution of NFTs in PCA. Differences in inflammatory response have been proposed to relate to AD heterogeneity evident in PCA. This study compared neuroinflammation between PCA and tAD in relation to Aβ and tau at autopsy.MethodImmunohistochemistry for microglial markers (CD68, Iba1, HLA‐DR/DP/DQ) and Aβ/tau was carried out on the frontal, parietal, temporal and occipital brain regions of 26 clinically and pathologically phenotyped PCA cases and 27 age and gender‐matched tAD cases from UCL Queen Square Brain Bank. All PCA patients had a neuropathological diagnosis of AD (Table 1). Marker load was quantified as percentage surface area of the 4 brain regions using Image J software.ResultThis study showed significantly lower temporal CD68 load in the tAD compared with the PCA group, (reduced CD68% area: ‐ 0.88%; (95%CI [‐0.42,‐1.34]), p&lt;0.001). Frontal CD68 load was significantly lower in PCA compared with tAD, (reduced CD68% area: ‐0.54; (95%CI[‐1.01,‐0.07]), p = 0.025), see Fig 1A. Parietal tau was significantly higher in the PCA group compared with the tAD group (increased tau % area: 5.15%; (95% CI [0.55, 9.76]), p = 0.029. The highest observed tau load within the PCA group was in the frontal region and for tAD in the temporal region, see Fig 1B.ConclusionRegional increases in tau and decreases in markers of activated microglia differ between PCA and tAD. Discrepancies between tau and activated microglial markers are particularly apparent in temporal and frontal regions in tAD and PCA respectively. This may be in line with the notion of a disconnect between microglial phagocytic activity at later stages of Alzheimer’s disease leading to further accumulation of tau and subsequent neuronal death.

What do people with aphasia want from the Queen Square Intensive Comprehensive Aphasia Programme and do they achieve it? A quantitative and qualitative analysis of their short, medium, long-term and economic goals

ABSTRACT Background The most effective model for achieving therapist-delivered, high-dose SLT for People with Aphasia (PWA) is through Intensive Comprehensive Aphasia Programmes (ICAPs). ICAPs are often assessed using standardised outcome measures; however, as SLT is personalised, it is of interest to examine individualised goal-based outcome measures as well. In the Queen Square ICAP, we use a goal-setting approach (Goal Attainment Setting [GAS]) where the PWA and their therapist negotiate which goals to work on and over what timescales. This process involves recording and scoring the agreed goals, which makes them amenable to formal quantitative and qualitative analysis. Aims The aim of this study was twofold. Firstly, to test the hypothesis that a pre- versus post- ICAP analysis of individual’s goal scores would show statistically significant and clinically meaningful improvements. Secondly, to better understand what PWA wanted to achieve from the ICAP service, we performed a qualitative analysis across all agreed goals. Methods & Procedures Forty-four PWA who varied in aphasia severity from mild to severe took part. PWA jointly set goals with their therapists using the SMART framework (Specific, Measurable, Achievable, Relevant, and Time-Bound). The goals were split into four categories: short (3 weeks), medium (3-6 months), long-term (12 months) and economic, (defined as any outcome that will improve, either directly or indirectly, the economic system that the PWA lives within). Quantitative scores were obtained for each PWA both pre- and post- ICAP and were analysed using paired t-tests, with subsequent ANOVAs to investigate possible confounding factors. The qualitative analysis was carried out by two researchers not involved in delivering the ICAP. Data was collapsed across all goal categories and analysed using thematic analysis. Outcomes & Results Quantitatively, statistically significant gains were made across all four goal categories (ps < 0.001). Unstandardized effect-sizes were clinically significant (ΔGAS ~16). Qualitatively, we identified five main themes: staying connected with the world, understanding aphasia better, raising awareness, the importance of having a work identity and managing personal relationships. Conclusions Quantitative goal-setting for PWA in the context of an ICAP provides robust evidence that PWA can achieve a variety of aspirational goals given high enough doses of specialist input from SLTs and a clinical psychologist. Although the ICAP only spanned 3 weeks, PWA continued to reach medium, long-term and even economic goals up to a year post-recruitment. This is the first time that economic goals have been captured in PWA using GAS. The qualitative analysis describes what the PWA wanted to achieve from participating in our ICAP, while the quantitative analyses demonstrate how much they succeeded in doing so.

Editorial introductions.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Martin J. McKeownMartin J. McKeownDr McKeown is the John Nichol Chair in Parkinson's Research, Director at the Pacific Parkinson's Research Centre (PPRC), Professor in the Department of Medicine, and adjunct professor in the Department of Electrical and Computer Engineering at the University of British Columbia, Canada. The PPRC is deemed an International Centre of Excellence by the (US-based) Parkinson's Foundation. He did his Engineering Physics, Medicine and Neurology training at McMaster, University of Toronto, and University of Western Ontario, Canada respectively. He did a three-year research fellowship at the Computational Neurobiology Laboratory at the Salk Institute for Biological Studies in San Diego before being hired as an Assistant Professor of Medicine and Biomedical Engineering at Duke University, USA. He was recruited to UBC in 2003. He is currently the Medical Advisor to the Parkinson's Society of BC, and Chair, Research and Clinical Advisory committee, Parkinson Canada. His research interests include privacy-compliant video monitoring technologies for Parkinson's disease and non-invasive neuromodulation. Marie VidailhetMarie VidailhetMarie Vidailhet is Professor of Neurology, Head of the Movement Disorders section and of the Dystonia and rare movement disorders National Reference Centre at Salpêtrière Hospital, Sorbonne Université, France; Head of the Research Team (Movement, investigations, and of the Therapeutics MOV’IT research group) at Paris Brain Institute, ICM (co-head Stephane Lehéricy), Paris, France, focused on the pathophysiology of motor and behaviour dysfunctions in movement disorders including dystonia, tremor and Tourette syndrome. She part of the ERN (European Reference Network) and of several international working groups in movement disorders and Parkinson's disease. She held the positions of Head of Neurology Department, Saint-Antoine University Hospital, Pierre et Marie Curie University, from 1997 to 2007, and previously of Assistant Professor, then Associate Professor in Salpêtriere, Paris, France. As a Visiting Research Fellow, Institute of Neurology, Queen Square, London, UK, she worked at the Human Movement Balance Unit research section London, UK with Pr CD Marsden, JC Rothwell and Ph Thompson. She is involved in the Movement Disorders Society including the MDS-ES (European section) and in the European Academy of Neurology (EAN) as board, and in international mentorship and fellowships programs (EAN, MDS). She was Vice-chair du COST action BM1101 European network for dystonia. She co-authored over 400 publications (total H index 85) with her group, with a focus on pathophysiology of dystonia, tremors and Tourette syndrome, deep brain stimulation and non-invasive stimulation both for research and experimental therapeutics. The other focus is multimodal/neuroimaging characterization of Parkinson's disease and isolated REM sleep disorders, current research programs, JP-RD Eurodyscover E-Rare (Europe), Dystonia Coalition (USA) on dystonia and several collaborative programs on Parkinson's disease. She was awarded the MDS Presidential lecture (Stanley Fahn Lecture) and the Prix Memin-Pelletier (Biology) French Academy of Science.

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method.

BackgroundThe characteristic symptom of coronavirus disease 2019 (COVID-19) is respiratory distress, but neurological symptoms are the most frequent extra-pulmonary symptoms. This study aims to explore the current status and hot topics of neurology-related research on COVID-19 using bibliometric analysis.MethodsPublications regarding neurology and COVID-19 were retrieved from the Web of Science Core Collection (WoSCC) on March 28 2022. The Advanced search was conducted using “TS = (‘COVID 19’ or ‘Novel Coronavirus 2019’ or ‘Coronavirus disease 2019’ or ‘2019-nCOV’ or ‘SARS-CoV-2’ or ‘coronavirus-2’) and TS = (‘neurology’or ‘neurological’ or ‘nervous system’ or ‘neurodegenerative disease’ or ‘brain’ or ‘cerebra’ or ‘nerve’)”. Microsoft Excel 2010 and VOSviewer were used to characterize the largest contributors, including the authors, journals, institutions, and countries. The hot topics and knowledge network were analyzed by CiteSpace and VOSviewer.ResultsA total of 5,329 publications between 2020 and 2022 were retrieved. The United States, Italy, and the United Kingdom were three key contributors to this field. Harvard Medical School, the Tehran University of Medical Sciences, and the UCL Queen Square Institute of Neurology were the major institutions with the largest publications. Josef Finsterer from the University of São Paulo (Austria) was the most prolific author. Tom Solomon from the University of Liverpool (UK) was the most cited author. Neurological Sciences and Frontiers in Neurology were the first two most productive journals, while Journal of Neurology held the first in terms of total citations and citations per publication. Cerebrovascular diseases, neurodegenerative diseases, encephalitis and encephalopathy, neuroimmune complications, neurological presentation in children, long COVID and mental health, and telemedicine were the central topics regarding the neurology-related research on COVID-19.ConclusionNeurology-related research on COVID-19 has attracted considerable attention worldwide. Research topics shifted from “morality, autopsy, and telemedicine” in 2020 to various COVID-19-related neurological symptoms in 2021, such as “stroke,” “Alzheimer's disease,” “Parkinson's disease,” “Guillain–Barre syndrome,” “multiple sclerosis,” “seizures in children,” and “long COVID.” “Applications of telemedicine in neurology during COVID-19 pandemic,” “COVID-19-related neurological complications and mechanism,” and “long COVID” require further study.

Diagnosing Premotor Multiple System Atrophy: Natural History and Autonomic Testing in an Autopsy-Confirmed Cohort.

Nonmotor features precede motor symptoms in many patients with multiple system atrophy (MSA). However, little is known about differences between the natural history, progression, and prognostic factors for survival in patients with MSA with nonmotor vs motor presentations. We aimed to compare initial symptoms, disease progression, and clinical features at final evaluation and investigate differences in survival and natural history between patients with MSA with motor and nonmotor presentations. Medical records of autopsy-confirmed MSA cases at Queen Square Brain Bank who underwent both clinical examination and cardiovascular autonomic testing were identified. Clinical features, age at onset, sex, time from onset to diagnosis, disease duration, autonomic function tests, and plasma noradrenaline levels were evaluated. Forty-seven patients with autopsy-confirmed MSA (age 60 ± 8 years; 28 men) were identified. Time from symptom onset to first autonomic evaluation was 4 ± 2 years, and the disease duration was 7.7 ± 2.2 years. Fifteen (32%) patients presented with nonmotor features including genitourinary dysfunction, orthostatic hypotension, or REM sleep behavior disorder before developing motor involvement (median delay 1-6 years). A third (5/15) were initially diagnosed with pure autonomic failure (PAF) before evolving into MSA. All these patients had normal supine plasma noradrenaline levels (332.0 ± 120.3 pg/mL) with no rise on head-up tilt (0.1 ± 0.3 pg/mL). Patients with MSA with early cardiovascular autonomic dysfunction (within 3 years of symptom onset) had shorter survival compared with those with later onset of cardiovascular autonomic impairment (6.8 years [5.6-7.9] vs 8.5 years [7.9-9.2]; p = 0.026). Patients with early urinary catheterization had shorter survival than those requiring catheterization later (6.2 years [4.6-7.8] vs 8.5 years [7.6-9.4]; p = 0.02). The survival of patients with MSA presenting with motor and nonmotor symptoms did not differ (p > 0.05). Almost one-third of patients with MSA presented with nonmotor features, which could predate motor symptoms by up to 6 years. Cardiovascular autonomic failure and early urinary catheterization were predictors of poorer outcomes. A normal supine plasma noradrenaline level in patients presenting with PAF phenotype is a possible autonomic biomarker indicating later conversion to MSA.

121 The Queen Square tests of auditory cognition: defining hearing deficits and dis- ability in dementia

BackgroundHearing impairment has emerged as a potent association of cognitive decline in dementia and a promising treatment target. To realise this promise, we need to resolve fundamental questions concerning the roles of peripheral versus central auditory deficits in different dementias.MethodsUsing a novel psychoacoustic battery – the Queen Square Tests of Auditory Cognition (QSTAC)– we combined pre-existing and novel measures of peripheral and central hearing functions, to charac- terise discrete ‘auditory phenotypes’ across dementia syndromes. Customised auditory symptom ques- tionnaires (completed by patients’ caregivers) were used to capture daily-life hearing-related disability and care burden. Patient groups: Alzheimer’s disease, frontotemporal dementia, primary progressive aphasia (PPA) and control. Neuroanatomical associations of specific hearing deficits were assessed using voxel-based morphometry.ResultsSyndromic signatures of peripheral and central auditory dysfunction were identified. Alzheimer’s disease was associated with prominent impairments of auditory scene analysis and dichotic listening. PPA syndromes and behavioural variant FTD (BvFTD) were principally associated with deficits of sound pattern analysis, sound identity, emotion recognition and degraded speech perception, which stratified according to sub-syndrome (logopoenic, semantic, nonfluent).ConclusionsTaken together, our findings suggest that major dementias have characteristic and differenti- ated auditory phenotypes, reflecting a complex interplay of peripheral hearing and auditory cognitive dysfunction.jeremy.johnson@doctors.org.uk

Prof. Dr. Willian Harkness 1955-2021

We are deeply saddened by the passing of Dr. William Harkness. A gifted surgeon, a caring clinician, a visionary leader and devoted family man, William left an indelible impression on pediatric neurosurgery and the many people whose lives he touched. Dr. William was educated at Eton School and qualified in medicine in 1979, at the University of Birmingham. His neurosurgical training commenced at the Radcliffe Infirmary, Oxford and later continued in Birmingham. Upon completion of his specialist training in 1991, he was appointed as a consultant neurosurgeon at the National Hospital for Neurology and Neurosurgery, Queen Square and Great Ormond Street Hospital for Sick Children (GOSH), but it was the latter institution that became his professional home as he focused his career on pediatric neurosurgery, establishing a legendary partnership with Dr. Richard Hayward. Dr. William spent a year in North America undergoing training at UCLA, Seattle, Miami and Montreal. He enthusiastically embraced the multidisciplinary team approach, enabling him to establish a world-leading children’s epilepsy surgery service together with Helen Cross at GOSH. While this is where he had his greatest scientific impact, he was a consummate pediatric neurosurgeon who thought deeply and wrote on a wide range of conditions. William was known to be an exceptionally skillful surgeon, with many neurosurgical trainees citing him as the one of the leading technical neurosurgeons they had worked with. He served as clinical lead for pediatric neurosciences at GOSH and led the development of a national plan for epilepsy surgery services in Great Britain. Throughout his career William was an ardent advocate for pediatric neurosurgery, representing the specialty in many forums including the Society of British Neurological Surgeons. Dr. Willian was a participant in the first ever European Society for Pediatric Neurosurgery (ESPN) educational course, where he struck up a legendary friendship with the late Jim Goodrich, he went on to become one of the most sought-after lecturers worldwide, including many Latin American Courses of Pediatric Neurosurgery (LACPN). In ISPN, there are few who have contributed more to the society. Dr. William served as scientific chair, communications chair, treasurer and ultimately president, (2016-2017). Combining his organizational and technical skills, he worked with Jim Johnson to develop InterSurgeon, a web-based platform promoting international collaboration through linking neurosurgeons and related organisations across the world. Supported by among others, the ISPN, UAB and the G4Alliance, InterSurgeon has grown beyond neurosurgery and will be a lasting tribute to William’s vision and drive. Dr. William was also an integral member of the Global Neurosurgery Committee of the World Federation of Neurosurgical Societies (WFNS). He worked tirelessly to propel the field, and always made sure he was available to provide advice and assistance. During his time with the committee, he expanded the knowledge base on global neurosurgery, worked to align the multitude of projects in the field, and improved collaboration amongst neurosurgeons around the world. He married Philippa Lubomirski in 1982. She survives him as do their four children, Fran, Ed, Gabi and Letitia, their grandchildren, Arlo, Joanie, Betsy, Peggy and Ari, and his sister, Nicola. Above all else, we remember William’s devotion to his family most vividly. His beloved wife Philippa, who accompanied him on most of his travels. And his four children, Fran, Ed, Gabi and Letitia, their grandchildren, Arlo, Joanie, Betsy, Peggy and Ari, and his sister, Nicola. We extend our sincere condolences to his family and close friends

The making, and makings, of Michael Hanna

Oh, it's confusing! The man makes the place; the place makes the man; it is not the place that makes the man, but the man that makes the place; the man makes the place and the place makes the man. Take your pick, for you can have your proverb the way you like it (just search Google). But for Michael Hanna, Professor of Clinical Neurology, Consultant Neurologist, Director of the University College London (UCL) Queen Square Institute of Neurology in London, UK (one of the world's leading research institutes, with some 1200 staff and students), and chair of the charity Muscular Dystrophy UK, it's the last option that surely fits best.

Spectrum of movement disorders: Experience of a one and half year of existence of the first specialized center in Senegal

BackgroundMovement disorders have different prevalence in different regions and they are little studied in Africa. ObjectivesEvaluate the prevalence and determine the spectrum of movement disorders in the first specialized center in Senegal. MethodsIt was a prospective study over on 18 months in adult outpatient clinic. Demographic, clinical, paraclinical data, including genetic test in collaboration with the Queen Square Institute of Neurology at UCL were collected. ResultsOne hundred and thirty four patients were followed up, representing a prevalence of 4.7%. Men represented 56% for a sex ratio of 1.3. The mean age of population was 47.7 ± 18 years with limits ranging from 16 to 81 years. Eighty-one patients (60.4%) had hyperkinetic and 53 patients (39.6%) had hypokinetic movements. Twenty-nine patients (21.6%) had tremors and 18 (13.4%) had dystonic movements. Ataxia and choreic movements were respectively in 11 (8.2%) and 10 patients (7.5%). Twenty-four patients (17.9%) were from a first-degree consanguineous. A genetic test on saliva samples was done in 16 patients (11.9%) and confirmed Huntington's disease in 8 patients of 6 families. Parkinson disease was the most frequent etiology (32.8%) followed by essential tremor (12.7%) and psychogenic tremor in 7.5%. Stroke accounted for 6% of the causes of MD (tremor, ballism, dystonia, ataxia and parkinsonism) and no etiology was found in 9%. ConclusionThe spectrum of movement disorders is very heterogeneous with a non-negligible frequency and diverse etiologies in neurological practice in Senegal.

Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer

IntroductionMultiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and...

Dr. Betty Clements

Women currently make up 45.9% of neurology residents and fellows1 although little is known about the individual women who broke gender barriers to train as neurologists. Grace Elizabeth "Betty" Clements (1918-1965) was the first woman trainee at the Mayo Clinic to practice neurology and later became a founder of the Barrow Neurological Institute. Prior to paving the way for future women trainees in neurology, she served as a Women Airforce Service Pilot (WASP) including flying atomic bomb planning missions during World War II. Following the war, her path to medicine included volunteering in the American Red Cross in the Philippines where she treated patients with Hansen's disease (leprosy). Clements returned to her home state to complete medical school at the University of Nebraska before seeking neurologic training at the Mayo Clinic in 1954. Following additional training at Queen Square, she became a founder of the Barrow Neurological Institute in Phoenix, Arizona. Many early women in neurology have remarkable backgrounds that have equipped them for their career in medicine which Clements exemplifies.

Establishing risk factors and outcomes for congenital hypothyroidism with gland in situ using population-based data linkage methods: study protocol

IntroductionThere has been an increase in the birth prevalence of congenital hypothyroidism (CH) since the introduction of newborn screening, both globally and in the UK. This increase can be accounted...