Introduction: Assessing treatments for Alzheimer's disease (AD) relies on reliable tools for measuring AD progression. In this analysis, we evaluate the sensitivity of clinical progression measures in AD within randomized controlled trials (RCTs) with confirmed positive amyloid (Aβ+) status prior to trial enrollment.
Methods: Excluding trials targeting non-cognitive symptoms, we conducted meta-analyses on progression measures from 25 selected RCTs using R version 4.
Imaging Neurosci (Camb)
August 2023
Timelines of events, such as symptom appearance or a change in biomarker value, provide powerful signatures that characterise progressive diseases. Understanding and predicting the timing of events is important for clinical trials targeting individuals early in the disease course when putative treatments are likely to have the strongest effect. However, previous models of disease progression cannot estimate the time between events and provide only an ordering in which they change.
View Article and Find Full Text PDFNPJ Parkinsons Dis
May 2023
To better understand the pathological and phenotypic heterogeneity of progressive supranuclear palsy and the links between the two, we applied a novel unsupervised machine learning algorithm (Subtype and Stage Inference) to the largest MRI data set to date of people with clinically diagnosed progressive supranuclear palsy (including progressive supranuclear palsy-Richardson and variant progressive supranuclear palsy syndromes). Our cohort is comprised of 426 progressive supranuclear palsy cases, of which 367 had at least one follow-up scan, and 290 controls. Of the progressive supranuclear palsy cases, 357 were clinically diagnosed with progressive supranuclear palsy-Richardson, 52 with a progressive supranuclear palsy-cortical variant (progressive supranuclear palsy-frontal, progressive supranuclear palsy-speech/language, or progressive supranuclear palsy-corticobasal), and 17 with a progressive supranuclear palsy-subcortical variant (progressive supranuclear palsy-parkinsonism or progressive supranuclear palsy-progressive gait freezing).
View Article and Find Full Text PDFSerotonin syndrome (SS) (also referred to as serotonin toxicity) is a potentially life-threatening drug-induced toxidrome associated with increased serotonergic activity in both the peripheral (PNS) and central nervous systems (CNS). It is characterised by a dose-relevant spectrum of clinical findings related to the level of free serotonin (5-hydroxytryptamine [5-HT]), or 5-HT receptor activation (predominantly the 5-HT and 5-HT subtypes), which include neuromuscular abnormalities, autonomic hyperactivity, and mental state changes. Severe SS is only usually precipitated by the simultaneous initiation of 2 or more serotonergic drugs, but the syndrome can also occur after the initiation of a single serotonergic drug in a susceptible individual, the addition of a second or third agent to long-standing doses of a maintenance serotonergic drug, or after an overdose.
View Article and Find Full Text PDFObjectives: To assess the effects of botulinum toxin for prevention of migraine in adults.
Design: Systematic review and meta-analysis.
Data Sources: CENTRAL, MEDLINE, Embase and trial registries.
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology, characterized by elevated intracranial pressure frequently manifesting with chronic headaches and visual loss. Similar to polycystic ovary syndrome (PCOS), IIH predominantly affects obese women of reproductive age. In this study, we comprehensively examined the systemic and cerebrospinal fluid (CSF) androgen metabolome in women with IIH in comparison with sex-, BMI-, and age-matched control groups with either simple obesity or PCOS (i.
View Article and Find Full Text PDFImmune-mediated inflammation of the brain has been recognized for more than 50 years, although the initial descriptions were mainly thought to be secondary to an underlying neoplasm. Some of these paraneoplastic encephalitides express serum antibodies, but these were not thought to be pathogenic but instead have a T-cell-mediated pathophysiology. Over the last two decades, several pathogenic antibodies against neuronal surface antigens have been described in autoimmune encephalitis, which are amenable to immunotherapy.
View Article and Find Full Text PDFBackground: The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats.
Methods: We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose).
Objectives: Patients with idiopathic intracranial hypertension (IIH) usually require multiple lumbar punctures (LPs) during the course of their disease, and often report significant morbidity associated with the procedure. The aim of this study was to assess the patient's experience of diagnostic LP in IIH.
Design, Methods And Participants: A cross-sectional study of patients with IIH was conducted using an anonymous online survey, with the questions designed in collaboration with IIH UK (the UK IIH charity).
Background: Optical Coherence Tomography (OCT) imaging is being increasingly used in clinical practice for the monitoring of papilloedema. The aim is to characterise the extent and location of the Retinal Nerve Fibre Layer (RNFL) Thickness automated segmentation error (SegE) by manual refinement, in a cohort of Idiopathic Intracranial Hypertension (IIH) patients with papilloedema and compare this to controls.
Methods: Baseline Spectral Domain OCT (SDOCT) scans from patients with IIH, and controls with no retinal or optic nerve pathology, were examined.
Purpose: To use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)-defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions.
View Article and Find Full Text PDFBackground: Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process.
Methods: We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register.
Salvage laryngectomy (SL) is associated with high levels of morbidity. Rates of pharyngocutaneous fistulae (PCF) are as high as 35 % in some series. Patients at highest risk of such complications may be candidates for altered surgical management in terms of additional tissue transfer, or delayed tracheoesophageal puncture.
View Article and Find Full Text PDFIntroduction: Chronic subdural haematoma (CSDH) is one of the most common neurosurgical disorders and is especially prevalent in old age. The subdural evacuating port system (SEPS) has emerged in the last few years as a minimally invasive alternative to the standard procedure of burr-hole evacuation. NHS practice is evidence-driven and evidence from high-quality clinical studies is required prior to implementation of any changes.
View Article and Find Full Text PDFIntroduction: Glioblastomas are the commonest primary brain tumour and are considered one of the most heterogeneous tumour types. The introduction of a glioblastoma with oligodendroglial component (GBM + O) in the latest WHO Classification of Tumours of the Central Nervous System (1) was to help with this. There has been conflicting evidence as to whether this tumour conferred a better prognosis than classical glioblastoma (GBM).
View Article and Find Full Text PDFOur objective was to generate a prognostic classification method for amyotrophic lateral sclerosis (ALS) from a prognostic model built using clinical variables from a population register. We carried out a retrospective multivariate analysis of 713 patients with ALS over a 20-year period from the South-East England Amyotrophic Lateral Sclerosis (SEALS) population register. Patients were randomly allocated to 'discovery' or 'test' cohorts.
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