Resolution-dependent estimates of lesion volumes in MRI studies of the brain in multiple sclerosis

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

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Signal quality as Achilles’ heel of graph theory in functional magnetic resonance imaging in multiple sclerosis

Scientific Reports ◽

10.1038/s41598-021-86792-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Johan Baijot ◽

Stijn Denissen ◽

Lars Costers ◽

Jeroen Gielen ◽

Melissa Cambron ◽

...

Keyword(s):

Multiple Sclerosis ◽

Signal To Noise Ratio ◽

Pearson Correlation ◽

Signal Quality ◽

Network Parameters ◽

Fmri Signal ◽

Noise Ratio ◽

Global And Local ◽

The Brain ◽

Local Brain

AbstractGraph-theoretical analysis is a novel tool to understand the organisation of the brain.We assessed whether altered graph theoretical parameters, as observed in multiple sclerosis (MS), reflect pathology-induced restructuring of the brain's functioning or result from a reduced signal quality in functional MRI (fMRI). In a cohort of 49 people with MS and a matched group of 25 healthy subjects (HS), we performed a cognitive evaluation and acquired fMRI. From the fMRI measurement, Pearson correlation-based networks were calculated and graph theoretical parameters reflecting global and local brain organisation were obtained. Additionally, we assessed metrics of scanning quality (signal to noise ratio (SNR)) and fMRI signal quality (temporal SNR and contrast to noise ratio (CNR)). In accordance with the literature, we found that the network parameters were altered in MS compared to HS. However, no significant link was found with cognition. Scanning quality (SNR) did not differ between both cohorts. In contrast, measures of fMRI signal quality were significantly different and explained the observed differences in GTA parameters. Our results suggest that differences in network parameters between MS and HS in fMRI do not reflect a functional reorganisation of the brain, but rather occur due to reduced fMRI signal quality.

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827 Central Sleep Apnea in a patient with Multiple Sclerosis

SLEEP ◽

10.1093/sleep/zsab072.824 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A322-A323

Author(s):

Rahul Dasgupta ◽

Sonja Schütz ◽

Tiffany Braley

Keyword(s):

Multiple Sclerosis ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Sleep Disordered Breathing ◽

Central Sleep Apnea ◽

Progressive Multiple Sclerosis ◽

Obstructive Sleep ◽

Increased Risk ◽

Demyelinating Lesions ◽

The Brain

Abstract Introduction Sleep-disordered breathing is common in persons with multiple sclerosis (PwMS), and may contribute to debilitating fatigue and other chronic MS symptoms. The majority of research to date on SDB in MS has focused on the prevalence and consequences of obstructive sleep apnea; however, PwMS may also be at increased risk for central sleep apnea (CSA), and the utility of methods to assess CSA in PwMS warrant further exploration. We present a patient with secondary progressive multiple sclerosis who was found to have severe central sleep apnea on WatchPAT testing. Report of case(s) A 61 year-old female with a past medical history of secondary progressive multiple sclerosis presented with complaints of fragmented sleep. MRI of the brain, cervical spine, and thoracic spine showed numerous demyelinating lesions in the brain, brainstem, cervical, and thoracic spinal cord. Upon presentation, the patient noted snoring, witnessed apneas, and daytime sleepiness. WatchPAT demonstrated severe sleep apnea, with a pAHI of 63.3, and a minimum oxygen saturation of 90%. The majority of the scored events were non-obstructive in nature (73.1% of all scored events), and occurred intermittently in a periodic fashion. Conclusion The differential diagnosis of fatigue in PwMS should include sleep-disordered breathing, including both obstructive and central forms of sleep apnea. Demyelinating lesions in the brainstem (which may contribute to impairment of motor and sensory networks that control airway patency and respiratory drive), and progressive forms of MS, have been linked to both OSA and CSA. The present data illustrate this relationship in a person with progressive MS, and offer support for the WatchPAT as a cost-effective means to evaluate for both OSA and CSA in PwMS, while reducing patient burden. PwMS may be at increased risk for CSA. Careful clinical consideration should be given to ordering appropriate sleep testing to differentiate central from obstructive sleep apnea in PwMS, particularly for patients with demyelinating lesions in the brainstem. Support (if any) 1. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med. 2014 Feb 15;10(2):155–62. doi: 10.5664/jcsm.3442. PMID: 24532998; PMCID: PMC3899317.

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Targeting the Brain Lesions Using Peptides: A Review Focused on the Possibility of Targeted Drug Delivery to Multiple Sclerosis Lesions

Pharmacological Research ◽

10.1016/j.phrs.2021.105441 ◽

2021 ◽

pp. 105441

Author(s):

Atefeh Rayatpour ◽

Mohammad Javan

Keyword(s):

Multiple Sclerosis ◽

Drug Delivery ◽

Targeted Drug Delivery ◽

Brain Lesions ◽

Targeted Drug ◽

The Brain

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The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients

Scientific Reports ◽

10.1038/srep14265 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 5

Author(s):

Damiano M. Rovituso ◽

Cathrina E. Duffy ◽

Michael Schroeter ◽

Claudia C. Kaiser ◽

Christoph Kleinschnitz ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cell ◽

Glatiramer Acetate ◽

Cell Response ◽

Brain Antigen ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

The Brain

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The brain 3β-HSD up-regulation in response to deteriorating effects of background emotional stress: an animal model of multiple sclerosis

Metabolic Brain Disease ◽

10.1007/s11011-021-00708-5 ◽

2021 ◽

Author(s):

Sogol Meknatkhah ◽

Monireh-Sadat Mousavi ◽

Pouya Sharif Dashti ◽

Leila Azizzadeh Pormehr ◽

Gholam Hossein Riazi

Keyword(s):

Multiple Sclerosis ◽

Animal Model ◽

Emotional Stress ◽

The Brain

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Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

Biological Research For Nursing ◽

10.1177/10998004211050082 ◽

2021 ◽

pp. 109980042110500

Author(s):

Pamela Newland ◽

Yelyzaveta Basan ◽

Ling Chen ◽

Gregory Wu

Keyword(s):

Multiple Sclerosis ◽

Inflammatory Markers ◽

Pearson Correlation ◽

Correlation Coefficients ◽

The United States ◽

Biological Mechanisms ◽

The Central Nervous System ◽

Brain And Spinal Cord ◽

The Brain

Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system (CNS), afflicts over one per thousand people in the United States. The pathology of MS typically involves lesions in several regions, including the brain and spinal cord. The manifestation of MS is variable and carries great potential to negatively impact quality of life (QOL). Evidence that inflammatory markers are related to depression in MS is accumulating. However, there are barriers in precisely identifying the biological mechanisms underlying depression and inflammation. Analysis of cytokines provides one promising approach for understanding the mechanisms that may contribute to MS symptoms. Methods: In this pilot study, we measured salivary levels of interleukin (IL)-6, IL-1beta (β), and IL-10 in 24 veterans with MS. Descriptive statistics were reported and Pearson correlation coefficients were obtained between cytokines and depression. Results: The anti-inflammatory cytokine IL-10 was significantly negatively associated with depression in veterans with MS (r = −0.47, p = .024). Conclusion: Cytokines may be useful for elucidating biological mechanisms associated with the depression and a measure for nurses caring for veterans with MS.

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Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

Journal of Pediatric Neurology ◽

10.1055/s-0041-1736599 ◽

2021 ◽

Author(s):

Sandesh Kini ◽

Yellanthoor Ramesh Bhat ◽

Lakshmikanth Halegubbi Karegowda

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Case Report ◽

Demyelinating Disease ◽

Oligoclonal Bands ◽

Initial Manifestation ◽

Demyelinating Disorder ◽

The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

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