Hydroxychloroquine in combination with platinum doublet chemotherapy as first-line treatment for extensive-stage small cell lung cancer (Study 15): A randomised phase II multicentre trial.

Background: Most patients with small-cell lung cancer (SCLC) present with extensive-stage (ES) disease and have a poor prognosis despite achieving high initial response rates to platinum-based doublet chemotherapy. This study evaluated whether adding hydroxychloroquine (HCQ) to chemotherapy could improve outcomes.

Methods: This was a randomised multicentre phase II trial.

Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson's disease.

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 (spectral domain optical coherence tomography) in 100 people with PD and 29 controls, with longitudinal cognitive assessments at baseline, 18 months and 36 months.

Multimodal Analysis of the Visual Pathways in Friedreich's Ataxia Reveals Novel Biomarkers.

Background: Optic neuropathy is a near ubiquitous feature of Friedreich's ataxia (FRDA). Previous studies have examined varying aspects of the anterior and posterior visual pathways but none so far have comprehensively evaluated the heterogeneity of degeneration across different areas of the retina, changes to the macula layers and combined these with volumetric MRI studies of the visual cortex and frataxin level.

Methods: We investigated 62 genetically confirmed FRDA patients using an integrated approach as part of an observational cohort study.

Optical coherence tomography angiography (OCT angiography) in anterior ischemic optic neuropathy (AION): A systematic review and meta-analysis.

Purpose: To summarize the evidence available on optical coherence tomography angiography (OCTA) in patients with anterior ischemic optic neuropathy (AION).

Methods: Systematic searches were conducted on PubMed, Embase, Web of Science, Scopus, Cochrane, and Google Scholar Databases. The quality assessment of the included studies was performed using Newcastle -Ottawa Scale.

A patient-reported outcome measure for patients with pituitary adenoma undergoing transsphenoidal surgery.

Purpose: Pituitary adenomas affect patients' quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While clinical outcomes can assess treatment efficacy, they do not capture variations in QoL. We present the development and validation of a patient reported outcome measure (PROM) for patients with pituitary adenomas undergoing transsphenoidal surgery.

Neurology and the histiocytoses: a case of Rosai-Dorfman-Destombes disease.

The histiocytoses are a group of rare disorders characterised by the accumulation of neoplastic or non-neoplastic activated histiocytes in various tissues. Phenotypes vary widely from cutaneous lesions or lymphadenopathy that regress spontaneously to disseminated disease with poor prognosis. Neurological symptoms can be a presenting feature or appear during the course of disease.

An unusual presentation of thymoma: dysgeusia, ulcerative colitis, keratoconjunctivitis sicca, autoimmune retinopathy and myasthenia gravis.

A 41-year-old female presented with dysgeusia, dry eyes, nyctalopia with progressive visual field constriction (due to autoimmune retinopathy) and gastrointestinal symptoms (due to ulcerative colitis). She was subsequently admitted to intensive care with a myasthenic crisis, and CT of the thorax demonstrated a thymoma.Following thymectomy and adjuvant radiotherapy, she has remained in complete remission from her ulcerative colitis and myasthenia gravis, her retinopathy has stabilised and there has been no thymoma recurrence over a 10-year postoperative period.

Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C.

Introduction: Mitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy.

Summary: We report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing.

Evidence That Pupil Size and Reactivity Are Determined More by Your Parents Than by Your Environment.

A classic twin study to evaluate the relative contributions of genetic and environmental factors to resting pupil size and reactivity. Pupillometry was performed on 326 female twins (mean age 64 years) from the TwinsUK Adult Twin Registry, assessing resting pupil diameter in darkness and increasing levels of ambient light, alongside dynamic pupillary characteristics. Maximum-likelihood structural equation models estimated the proportion of trait variance attributable to genetic factors.

Retinal Architecture in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Insights into Disease Pathogenesis and Biomarkers.

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) causes unique retinal abnormalities, which have not been systematically investigated.

Objective: To deeply phenotype the retina in ARSACS in order to better understand its pathogenesis and identify potential biomarkers.

Methods: We evaluated 29 patients with ARSACS, 66 with spinocerebellar ataxia (SCA), 38 with autosomal recessive cerebellar ataxia (ATX), 22 with hereditary spastic paraplegia (SPG), 21 cases of papilledema, and 20 healthy controls (total n = 196 subjects).

Brain MRI and Ophthalmic Biomarkers of Intracranial Pressure.

Objective: To evaluate the utility of brain MRI and ophthalmic biomarkers for the prediction of intracranial hypertension, we have studied the association between 6 biomarkers and 24-hour intracranial pressure (ICP) monitoring results in 45 patients.

Methods: This single-center observational study includes patients who underwent 24-hour ICP monitoring, brain MRI (within 3 months), and ophthalmic assessment (during ICP monitoring). Six biomarkers were investigated: pituitary gland shape, vertical tortuosity of the optic nerve, distension of the optic nerve sheath, optic disc protrusion (MRI), papilledema (slit lamp biomicroscopy), and spontaneous venous pulsations (SVP, infrared video recordings).

Sequence of clinical and neurodegeneration events in Parkinson's disease progression.

Dementia is one of the most debilitating aspects of Parkinson's disease. There are no validated biomarkers that can track Parkinson's disease progression, nor accurately identify patients who will develop dementia and when. Understanding the sequence of observable changes in Parkinson's disease in people at elevated risk for developing dementia could provide an integrated biomarker for identifying and managing individuals who will develop Parkinson's dementia.

Multimodal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy.

Objective: The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR-Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response.

Methods: We conducted a cohort study of 13 individuals (7 women, 21-69 years of age) with autonomic failure and gAChR-Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS-31) autonomic symptom questionnaires.

Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease.

Background: Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage.

Objective: To identify a biomarker for neurological involvement in WD.

Visual tests predict dementia risk in Parkinson disease.

Objective: To assess the role of visual measures and retinal volume to predict the risk of Parkinson disease (PD) dementia.

Methods: In this cohort study, we collected visual, cognitive, and motor data in people with PD. Participants underwent ophthalmic examination, retinal imaging using optical coherence tomography, and visual assessment including acuity and contrast sensitivity and high-level visuoperception measures of skew tolerance and biological motion.

Automated Pupillometry Using a Prototype Binocular Optical Coherence Tomography System.

Purpose: To determine the test-retest reliability and diagnostic accuracy of a binocular optical coherence tomography (OCT) prototype (Envision Diagnostics, El Segundo, California, USA) for pupillometry.

Design: Assessment of diagnostic reliability and accuracy.

Methods: Fifty participants with relative afferent pupillary defects (RAPDs) confirmed using the swinging flashlight method (mean age 49.

Association of Intracranial Pressure and Spontaneous Retinal Venous Pulsation.

Importance: A convenient and reliable method for noninvasive intracranial pressure assessments is desirable to reduce the need for invasive procedures (eg, intracranial pressure monitoring and lumbar punctures) and allow clinicians to identify and treat patients with intracranial hypertension in a timely manner.

Objective: To determine whether infrared video assessment of spontaneous retinal venous pulsation is associated with intracranial pressure and is a valid tool to indicate the presence or absence of raised intracranial pressure in patients without papilledema.

Design, Setting, And Participants: A single-center prospective study was conducted at a tertiary referral center between January 2017 and May 2018.

Spontaneous Venous Pulsations Detected With Infrared Videography.

Background: Assessment of spontaneous venous pulsation (SVP) is commonly undertaken to help determine whether intracranial pressure (ICP) is elevated. Previous studies using direct ophthalmoscopy or slit-lamp assessments have found that SVP is not observed in 67%-81% of subjects with normal ICP, and that interobserver agreement when grading SVP is poor.

Methods: Patients (n = 105) undergoing clinically indicated retinal OCT scans, who were all believed to have normal ICP, had 10-second infrared video recordings performed with the Heidelberg Spectralis OCT system (Heidelberg Engineering GmbH, Heidelberg, Germany).