Assessment of demyelination, edema, and gliosis byin vivo determination of T1 and T2 in the brain of patients with acute attack of multiple sclerosis

Background: Imatinib (IM) is a chemotherapy medication metabolized by CYP3A4 to Ndesmethyl imatinib (NDI), which shows similar pharmacologic activity to the parent drug. Although methods for determination of IM and/or NDI have been developed extensively, only few observations have been addressed to simultaneously determine IM and NDI in biological tissues such as liver, kidney, heart, brain and bone marrow. Methods: A validated LC-MS/MS method was developed for the quantitative determination of imatinib (IM) and N-desmethyl imatinib (NDI) from rat plasma, bone marrow, brain, heart, liver and kidney. The plasma samples were prepared by protein precipitation, and then the separation of the analytes was achieved using an Agilent Zorbax Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with gradient elution running water (A) and methanol (B). Mass spectrometric detection was achieved by a triplequadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Results: This method was used to investigate the pharmacokinetics and the tissue distributions in rats following oral administration of 25 mg/kg of IM. The pharmacokinetic profiles suggested that IM and NDI are disappeared faster in rats than human, and the tissue distribution results showed that IM and NDI had good tissue penetration and distribution, except for the brain. This is the first report about the large penetrations of IM and NDI in rat bone marrow. Conclusion: The method demonstrated good sensitivity, accuracy, precision and recovery in assays of IM and NDI in rats. The described assay was successfully applied for the evaluation of pharmacokinetics and distribution in the brain, heart, liver, kidney and bone marrow of IM and NDI after a single oral administration of IM to rats.

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PO-0836 Determination Of Cognitive Functioning Disorders Incidence In Children With Multiple Sclerosis

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307384.1467 ◽

2014 ◽

Vol 99 (Suppl 2) ◽

pp. A526.4-A527

Author(s):

K Gücüyener ◽

S Soysal ◽

U Yilmaz ◽

E Demir ◽

E Gurkas ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Functioning

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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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Spatiotemporal distribution of white matter lesions in relapsing–remitting and secondary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512442756 ◽

2012 ◽

Vol 18 (11) ◽

pp. 1577-1584 ◽

Cited By ~ 14

Author(s):

Lukas Filli ◽

Louis Hofstetter ◽

Pascal Kuster ◽

Stefan Traud ◽

Nicole Mueller-Lenke ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Disease Progression ◽

Spatiotemporal Distribution ◽

Centrum Semiovale ◽

Cross Sectional ◽

Secondary Progressive ◽

Lateral Ventricles ◽

Relapsing Remitting ◽

T1 And T2

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS lesions show a typical distribution pattern and primarily affect the white matter (WM) in the periventricular zone and in the centrum semiovale. Objective: To track lesion development during disease progression, we compared the spatiotemporal distribution patterns of lesions in relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). Methods: We used T1 and T2 weighted MR images of 209 RRMS and 62 SPMS patients acquired on two different 1.5 Tesla MR scanners in two clinical centers followed up for 25 (± 1.7) months. Both cross-sectional and longitudinal differences in lesion distribution between RRMS and SPMS patients were analyzed with lesion probability maps (LPMs) and permutation-based inference. Results: MS lesions clustered around the lateral ventricles and in the centrum semiovale. Cross-sectionally, compared to RRMS patients, the SPMS patients showed a significantly higher regional probability of T1 hypointense lesions ( p≤0.03) in the callosal body, the corticospinal tract, and other tracts adjacent to the lateral ventricles, but not of T2 lesions (peak probabilities were RRMS: T1 9%, T2 18%; SPMS: T1 21%, T2 27%). No longitudinal changes of regional T1 and T2 lesion volumes between baseline and follow-up scan were found. Conclusion: The results suggest a particular vulnerability to neurodegeneration during disease progression in a number of WM tracts.

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