Angeliki Zarkali

University College London | UCL · Institute of Neurology

Parkinson’s disease is a common and debilitating neurodegenerative disorder, with over half of patients progressing to postural instability, dementia, or death within 10 years of diagnosis. However, the onset and rate of progression to poor outcomes is highly variable, underpinned by heterogeneity in underlying pathological processes. Quantitative...

Background Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to...

Parkinson’s disease (PD) is the second commonest neurodegenerative disorder and over half of patients progress to postural instability, dementia or death within 10 years of diagnosis. However, onset and rate of progression to poor outcomes is highly variable, underpinned by heterogeneity in the underlying pathological process. Improved biomarkers o...

Cortical cell loss is a core feature of Huntington Disease (HD), beginning many years before clinical motor diagnosis, during the premanifest stage. However, it is unclear how genetic topography relates to cortical cell loss. Here, we explore the biological processes and cell types underlying this relationship and validate this using cell-specific...

Purpose of Review To review recent structural and functional MRI studies of visual hallucinations in Parkinson’s disease. Recent Findings Previously, neuroimaging had shown inconsistent findings in patients with Parkinson’s hallucinations, especially in studies examining grey matter volume. However, recent advances in structural and functional MRI...

Background. Dementia is a common and devastating symptom of Parkinson’s disease (PD). Visual function and retinal structure are both emerging as potentially predictive for dementia in Parkinson’s but lack longitudinal evidence. Methods. We prospectively examined higher order vision (skew tolerance and biological motion) and retinal thickness (spec...

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the s...

Visual hallucinations are common in Parkinson’s disease and are associated with poorer quality of life and higher risk of dementia. An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinson’s disease and other Lewy-body diseases is that these arise due to aberrant hierarchic...

Hallucinations are a core feature of psychosis and common in Parkinson’s. Their transient, unexpected nature suggests a change in dynamic brain states, but underlying causes are unknown. Here, we examine temporal dynamics and underlying structural connectivity in Parkinson’s-hallucinations using a combination of functional and structural MRI, netwo...

Upregulation of functional network connectivity in the presence of structural degeneration is seen in the premanifest stages of Huntington’s disease (preHD) 10-15 years from clinical diagnosis. However, whether widespread network connectivity changes are seen in gene-carriers much further from onset has yet to be explored. We characterised function...

This scientific commentary refers to ‘Functional and structural brain network correlates of visual hallucinations in Lewy body dementia’ by Mehraram et al. (https://doi.org/10.1093/brain/awac094).

Rising demand and increasing workload in the face of constrained resources are factors known to con- tribute to clinician burnout. Emotional exhaustion, depersonalisation and career dissatisfaction are some of the consequences. In the USA, neurologists are amongst the clinicians with the highest rates of burnout, but is this also a problem for Brit...

Visual hallucinations are common in Parkinson’s (PD) and associated with worse outcomes. ¹ Neuroim- aging shows widespread but non-specific grey matter atrophy in PD-hallucinations ¹ ; white matter (WM) loss may be an earlier, more sensitive marker. To detect WM changes in PD-hallucinations we performed diffusion-weighted imaging in 105 patients wi...

Background Neurology training in the UK is governed by a national curriculum defining the outcomes every trainee must achieve. However, the delivery of neurology training and trainee satisfaction differs significantly across the UK1. The Association of British Neurologists Trainees (ABNT) recently completed a qualitative study of the highest and lo...

Introduction Visual dysfunction predicts Parkinson’s dementia but whether this translates to structural change is not known. We aimed to identify longitudinal white matter changes in Parkinson’s with low visual function and those who developed mild cognitive impairment(MCI). Methods We used fixel-based analysis to examine longitudinal white matter...

Visual hallucinations are common in Parkinson’s (PD) and associated with poorer prognosis. Imaging studies have shown white matter and functional changes in PD-hallucinations 1 2 but the biological factors underlying selective vulnerability of brain regions are unknown. We performed diffusion-weighted imaging in 100 PD patients (81 without hallucin...

Background The Association of British Neurology Trainees (ABNT) conducts a biennial census of neurology trainees. This acquires data on training, education, research, out of program experiences and trainees’ future plans, which are invaluable in shaping the future workforce. This is particularly important given the introduction and implementation o...

Quantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of...

Visual hallucinations are common in Parkinson’s disease and are associated with poorer quality of life and higher risk of dementia. An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinson’s disease and other Lewy-body diseases is that these arise due to aberrant hierarchic...

Background Fixel‐based analysis (FBA) of diffusion MRI allows analysis of brain white matter (WM) tracts with greater specificity than voxel‐based approaches, including measures of microstructural fibre density (FD), macrostructural fibre cross section (FC), and representations of crossing fibres. We use FBA to explore early WM changes associated w...

Objective Visual hallucinations are common in Parkinson’s disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinat...

Background: Visual hallucinations in Parkinsons disease (PD) are transient, suggesting a change in dynamic brain states. However, the causes underlying these dynamic brain changes are not known. Methods: Focusing on fundamental network properties of integration and segregation, we used rsfMRI to examine alterations in temporal dynamics in PD patien...

Objective Depression is a common non-motor feature of Parkinson's disease (PD) which confers significant morbidity and is often challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not yet bee...

The mechanisms which are responsible for the selective vulnerability of specific neuronal populations in Parkinson’s disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions in 96 patients with Parkinson’s disease and 35 controls using quant...

Parkinson’s dementia is characterised by changes in perception and thought, and preceded by visual dysfunction, making this a useful surrogate for dementia risk. Structural and functional connectivity changes are seen in humans with Parkinson’s disease, but the organisational principles are not known. We used resting-state fMRI and diffusion-weight...

Background Visual dysfunction predicts dementia in Parkinson's disease (PD), but whether this translates to structural change is not known. The objectives of this study were to identify longitudinal white matter changes in patients with Parkinson's disease and low visual function and also in those who developed mild cognitive impairment. Methods W...

Visual hallucinations are common in Parkinson's disease and are associated with poorer prognosis. Imaging studies show white matter loss and functional connectivity changes with Parkinson's visual hallucinations, but the biological factors underlying selective vulnerability of affected parts of the brain network are unknown. Recent models for Parki...

Visual dysfunction predicts dementia in Parkinsons disease (PD), but whether this translates to structural change is not known. We aimed to identify longitudinal white matter changes in patients with Parkinsons disease and low visual function and also in those who developed mild cognitive impairment (MCI). We used fixel-based analysis to examine lo...

Family carers of people with Lewy body dementia (LBD) have a particularly high burden of care, as LBD has a faster rate of decline, greater physical dependence and additional neuropsychiatric disturbances compared with other dementias. Despite this, there are no evidence-based support services designed specifically for LBD carers. STrAtegies for Re...

Objective To investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia. Methods We performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or...

Parkinson’s dementia is a common and devastating part of Parkinson’s disease. Whilst timing and severity vary, dementia in Parkinson’s is often preceded by visual dysfunction. White matter changes, representing axonal loss, occur early in the disease process. Clarifying which white matter connections are affected in Parkinson’s with visual dysfunct...

Hallucinations are a common and distressing feature of many psychiatric and neurodegenerative conditions. In Lewy Body Disease, visual hallucinations are a defining feature, associated with worse outcomes; yet their mechanisms remain unclear and treatment options are limited. Here, we show that hallucinations in Lewy Body Disease are associated wit...

Visual hallucinations are a common and often distressing feature of Parkinson’s disease; they are ephemeral and capricious, making them difficult to study but tend to be more prominent in dim illumination. Flickering stimuli can induce simple hallucinations even in healthy individuals. We tested a stroboscope and an equivalent full-screen flickerin...

Introduction: Isolated monocular ischaemic events are thought to be low risk for stroke recurrence. In the presence of carotid stenosis however, the risks should not be treated similarly and surgical intervention should be considered at an early stage. The aim of this study was to determine the vascular risk profile and stroke recurrence in patien...

Introduction: Atrial fibrillation (AF) is a major cause of ischemic stroke and Transient Ischemic Attack (TIA) and investigation for paroxysmal AF is recommended following an embolic brain event. In contrast, retinal ischemic monocular blindness is traditionally considered most linked to carotid artery disease (CAS) and investigating for AF is les...

There is no consensus on how to structure and deliver neurology training. The General Medical Council’s annual National Training Survey indicates that the quality of UK neurology training is very variable, but does not explain this variation. We used the survey data to identify the four highest and lowest performing sites for neurology training acr...

Objectives/Aims Functional neurological disorders (FND) account for 20% of patients in neurology clinics and can lead to functional impairment, multiple re-attendances and significant cost. However, diagnosing FND remains challenging; identifying associated factors could aid earlier diagnosis. We aimed to determine the value of self-reported multi-...

Spatial configuration is extensively used in spatial analysis methods to predict navigational behavior; several studies have shown a correlation of global and local space syntax metrics with the distribution of pedestrians in different settings. However, recent studies have also shown correlation of human behavior with the visibility of relevant ob...

Background and purpose: Ischaemic visual loss is often considered a lower risk factor than other transient ischaemic attacks (TIA). We aimed to determine the recurrence risk, prevalence and management of vascular risk factors in these patients. Methods: The study took place in the University College Hospital London daily TIA clinic, main referra...

Glial fibrillary acidic protein antibody-positive meningoencephalomyelitis is a newly described, possibly under-recognised, severe inflammatory condition of the nervous system. The clinical presentation is variable but most commonly is a combination of meningitis, encephalitis and myelitis; other manifestations may include seizures, psychiatric sym...

Arachnoiditis is a rare complication of subarachnoid haemorrhage (SAH) with less than 30 cases reported. It commonly presents following a posterior fossa aneurysm, with haemomyelia being the proposed trigger of inflammatory response.We present a case and review the literature. A 55 year old right-handed carpenter, presented with three week history...

Transverse myelitis (TM) is often the first presentation of inflammatory central nervous system or systemic diseases; cause is not always identified with 30% of cases labelled idiopathic. Fourteen cases have been reported in patients with hepatitis C infection (HCV); often atypical, extensive and recurrent. We present a case and review the literatu...

Introduction Ocular events are considered lower risk than other transient ischaemic attacks (TIA). We aimed to determine recurrence risk, prevalence and management of vascular risk factors. Setting University College Hospital London daily TIA-clinic, main referral centre for North-Central London. Consecutive records for all patients with transient...

Introduction Atrial fibrillation (AF) in patients with ischaemic ocular events is often under-investigated. We aimed to determine the prevalence of AF in these patients. Setting University College Hospital London daily TIA clinic, main referral centre for North-Central London. Consecutive records for all patients with transient or permanent ischae...

Background In NHNN, 388 patients received 203,571 g of IVIG (£35/g) during 2014/15 amounting to 3127 patient days (£250/person/day). The majority of the 91.7% on long-term treatment are neuromuscular patients. Aims In 2011 the Department of Health updated guidelines for monitoring and dosing of IVIg. This is an audit of a new, consultant-led IVIg...

Objectives Regular intravenous immunoglobulin (IVIg) is commonly used for autoimmune neurological conditions. In our hospital, 388 patients received 203,571 grams of IVIg in 2014/15 amounting to 3127 patient-days. Given potential side effects, cost and impact to patients, we reconfigured our service to improve clinical assessment prior to IVIg admi...

Objectives Moyamoya disease is a rare progressive intracranial vasculopathy, leading to recurrent cerebrovascular events. Revascularisation surgery is advocated as the treatment of choice despite little evidence supporting benefit over conservative management. We reviewed the outcome of patients attending an adult moyamoya clinic in our tertiary ce...

Rapidly progressive encephalopathy in an HIV-positive patient presents a major diagnostic and management challenge. CD8+ encephalitis is a severe but treatable form of HIV-related acute encephalopathy, characterised by diffuse perivascular and intraparenchymal CD8+ lymphocytic infiltration. It can occur in patients who are apparently stable on anti...

Angeliki Zarkali and colleagues look at what factors are deterring doctors in training from pursuing a career in general practice

Professor Sir Bruce Keogh, the national medical director, and Dr Bob Winter, the national clinical director for emergency preparedness, have released an important announcement on Ebola to frontline staff.1 2 In line with the key messages from the guidance on Ebola from Public Health England and the guidelines from the College of Emergency Medicine,...

Handover is the system by which responsibility for patient care is transferred between healthcare professionals. A significant aspect of handover is the existence of an escalation plan for each patient in case of deterioration over the weekend. According to the Royal College of Physicians, all patients should have a clear escalation plan documented...

Background Methotrexate (MTX) has been used for many years as treatment for Rheumatoid Arthritis (RA), and remains the first line disease modifying therapy with a well established efficacy and safety profile. Side effects include gastrointestinal (GI) symptoms, deranged liver function, pneumonitis and bone marrow suppression. Subcutaneous (SC) MTX...

Background: The monoclonal antibodies represent novel therapeutic options for many clinical entities. This study aimed to study the frequency of the off-label use to total use of different monoclonal antibodies in clinical practice. Methods: This study systematically searched the PubMed and Scopus databases for relevant studies. Results: Fifte...

The number of citations received is considered an index of study quality and impact. We aimed to examine the factors associated with the number of citations of published articles, focusing on the article length. Original human studies published in the first trimester of 2006 in 5 major General Medicine journals were analyzed with regard to the numb...