Clinical Research Directory

Disease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches

Diagnosis of ALS/FTD disease spectrum is challenging because it largely relies on clinical symptoms. Identifying novel biomarkers is essential for a paradigm shift towards a more precise biological-based diagnosis. To achieve this aim, having access to proper specimens and analytical methods is crucial. Our team of experts in neurology, biology, chemistry, physics, and AI will explore ALS/FTD from novel perspectives using transcriptomics, proteomics, genomics and other innovative approaches to analyzing easily accessible tissues. The seed amplification assay (SAA) will be also exploited to detect pathological TDP-43. This project aims to create disease fingerprints useful for patient stratification and monitoring of disease progression, and to evaluate the therapeutic efficacy in clinical trials, thus overcoming the limits of clinical interpretation. Discovering new biomarkers and cellular pathways will improve the diagnosis and treatment of these devastating diseases.

Evaluating Raised Intracranial Pressure Using MR Elastography

Investigators will compare magnetic resonance (MR) elastography measurements to other forms of noninvasive methods of detecting raised intracranial pressure, including optical coherence tomography (OCT) imaging measurements of the retinal nerve fiber layer (RNFL) and indirect signs of raised intracranial pressure on magnetic resonance imaging (MRI).

Prospective Ocular Imaging for Intracranial Pressure Evaluation

This is a prospectively recruiting, database development study collecting images and videos of the spontaneous venous pulsation at the back of people's eyes - this is a pulse one can see on examination of the back of the eye, originating from the blood vessels around the nerve that connects the eye to the brain (the optic nerve), and is present in most people who have normal pressure around the brain. However, in people with raised pressure in the brain, this pulse disappears as the pressure rises. Many things can cause the pressure around the brain to increase, including tumours, swellings and trauma. The investigators want to test if high-quality images and videos of this pulse, taken using both hand-held and larger, fixed-platform machines, can be used to train a software tool to automatically detect this pulse. The investigators want to collect these images and videos in 2 groups of patients: those with no known or suspected brain pressure problems, and those who are suspected to have raised pressure and/or are due to undergo measurement of the pressure around the brain, called lumbar punctures or intracranial pressure bolt monitoring. These tests to check the pressure around the brain are invasive - they involve inserting needles in the back or directly into the brain to measure the pressure, and carry risks. The value of these two groups of people will be to help train the software to reasonably say whether a pulse is present or absent and, hopefully, estimate what the pressure around the brain may be without the need for an invasive test.

Astronaut Vision Issues in a Ground Analog Population: Polycystic Ovary Syndrome

The investigators have documented a genetic predisposition for some astronauts to develop ophthalmologic issues (e.g., choroidal folds, cotton wool spots, optic disc edema). Women with polycystic ovary syndrome (PCOS) have several characteristics similar to those described in astronauts, including: higher homocysteine concentrations, increased incidence of intracranial hypertension, increased retinal nerve fiber layer thickness, increased incidence of white matter hyperintensities on MRI, increased androgen concentrations (or androgen responses to space flight), and indices of altered carbohydrate metabolism. Women with PCOS have not been evaluated in detail regarding the occurrence of other anomalies observed in astronauts including choroidal folds, optic disc edema and cotton wool spots as well as changes in cycloplegic refraction, and optic nerve sheath diameter. While researchers have evaluated one-carbon metabolism pathway polymorphisms re: PCOS, and initial studies show an association with certain one-carbon polymorphisms, none have looked at the complete set of SNPs proposed here. This study will evaluate women with PCOS and/or idiopathic intracranial hypertension (IIH) to assess one-carbon biochemistry and genetics and their possible correlation with ophthalmologic findings. The investigators aim to clarify the relationship of one carbon metabolism and ophthalmic findings in astronauts and patients with PCOS and/or IIH.

Ocular Perfusion in Patients With Idiopathic Intracranial Hypertension

The proposed study aims to evaluate optic nerve head blood flow and microcirculation in patients with idiopathic intracranial hypertension. For this purpose, optic nerve head blood flow will be examined in patients with IIH before and after therapy and additionally compared with healthy age- and sex-matched control subjects. In addition, other parameters will be measured, in particular retinal blood flow, retinal oxygen saturation and retinal neurovascular coupling.

ICP & Outflow Study

This study aims to investigate the relationship between intracranial pressure (ICP) and aqueous outflow (the flow of the eye's internal fluid out of the eye), in patients with increased intracranial pressure (idiopathic intracranial hypertension (IIH)). Through observing changes in aqueous outflow facility in patients scheduled for lumbar Puncture (LP) as part of their routine care the objectives we aim to answer include: * Investigating the effect of lumbar puncture induced reduction in ICP on patients with known or suspected IIH, compared to control patients, who will be receiving LP for reasons not pertaining to high pressure. * Comparing pre lumbar puncture aqueous outflow facility between patients with idiopathic intracranial hypertension and control patients. Outside of the standard care provided for these patients as part of their scheduled lumbar puncture, they will have measurements of their eye taken before and after their lumbar puncture.

Biomarkers in the Etiology of Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is a condition characterized by an increase in intracranial pressure (ICP), papilledema with a risk of permanent visual loss, and severe headaches that profoundly affect quality of life. To date the exact pathophysiology of IIH remains unknown. IIH is considered a complex neurometabolic and neuroendocrine disorder, favored by female gender, and obesity. In the majority of patients (80% of the cases) IIH is associated with obstruction of cerebral venous drainage with stenosis of the transverse sinus. This stenosis may be the main underlying cause in the so-called "venogenic" form of IIH. Equally, in the absence of a stenosis, obstruction may occur when otherwise normal venous sinuses are compressed by the increased ICP, the so-called "non-venogenic" form of IIH. An innovative treatment of IIH with associated venous stenosis includes stenting of the transverse sinus stenosis. This strategy may allow resolution of papilledema and ICP reduction rates up to 80%. Although the pathogenesis of IIH is still poorly understood, inflammatory mechanisms, autoimmune reactions, and hormonal abnormalities of notably androgens, have been proposed to contribute to its pathophysiology. The function of the blood-brain barrier (BBB) has been studied by determining the prevalence of extravasation of endogenous proteins such as fibrinogen. A growing body of the literature shows a correlation between increased ICP and metabolic/hormonal changes. The improvement of IIH treated with acetazolamide and/or stenting appears to correlate with the reduction of ICP. Yet the association of this reduction with metabolic changes at the peripheral and central blood level as well as the CSF remains unclear. The search for specific inflammatory, immunological and hormonal biomarkers in patients with IIH and their variation in relation to the ICP should provide a better understanding of its etiology.

Exploratory Study on the Efficacy and Safety of Semaglutide for Idiopathic Intracranial Hypertension Treatment

This study aims to investigate the safety and efficacy of semaglutide in patients with Idiopathic intracranial hypertension.

Venous Sinus Stenting With the River Stent in IIH

The objective of the study is to show that stenting the transverse-sigmoid sinus with the River stent is safe and has probable benefit to relieve clinical symptoms in subjects with idiopathic intracranial hypertension (IIH). The study will enroll 39 IIH subjects with moderate to severe visual field loss or severe headaches that have failed medical therapy. The primary safety endpoint is the rate of major adverse event at 12 months The primary probable benefit endpoint is a composite at 12 months of absence of significant sinus stenosis and clinically relevant improvement.