scholarly journals Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

2016 ◽  
Vol 22 (11) ◽  
pp. 1421-1428 ◽  
Author(s):  
Seyed-Parsa Hojjat ◽  
Charles Grady Cantrell ◽  
Rita Vitorino ◽  
Anthony Feinstein ◽  
Zahra Shirzadi ◽  
...  

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.


2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.


2017 ◽  
Vol 24 (10) ◽  
pp. 1328-1336 ◽  
Author(s):  
Simone Migliore ◽  
Giuseppe Curcio ◽  
Alessandro Couyoumdjian ◽  
Anna Ghazaryan ◽  
Doriana Landi ◽  
...  

Background: Cognitive dysfunction affects 40%–65% of multiple sclerosis (MS) patients, most often affecting information processing speed and working memory, mediated by the pre-frontal cortex (PFC). Objective: Our study aimed to investigate PFC functioning through a task-switching protocol in relapsing-remitting multiple sclerosis (RRMS) patients without cognitive impairment. Methods: A total of 24 RRMS patients and 25 controls were enrolled. Two different tasks were performed in rapid and random succession, so that the task was either changed from one trial to the next one (switch trials) or repeated (repetition trials). Switch trials are usually slower than repetitions, causing a so-called switch cost (SC). Results: Patients had worse performance than controls only in the switch trials, as indicated by increased SC and reaction times. Moreover, patients showed a reduced ability to reconfigure the task-set for the execution of a new task and to disengage from the previous one. Conclusion: Our results showed a primary deficit in executive control processes involved in the task-switching performance in RRMS patients without cognitive impairment. This deficit may depend on the functional impairment of the PFC, which is essential to adjust behaviour rapidly and flexibly in response to environmental changes, representing one of the most sophisticated human abilities.


2021 ◽  
pp. 135245852110092
Author(s):  
Emanuele D’Amico ◽  
Aurora Zanghì ◽  
Aldo Eugenio Calogero ◽  
Francesco Patti

Scarce data are available about the impact of natalizumab (NTZ) and ocrelizumab (OCR) on male fertility in relapsing-remitting multiple sclerosis (RRMS). In this case–control prospective study, the gonadal steroids and the sperm parameters have been analysed at the time of the RRMS diagnosis and after 12 months from the beginning of the investigated therapies. Sixteen men with RRMS and sixteen matched healthy controls were included. At enrolment and after 12 months on therapy, the gonadal steroids and the sperm parameters of men with RRMS did not differ from the healthy controls. In conclusion, therapy with NTZ and OCR had no impact on fertility status in our cohort of men with RRMS. Further randomized and prospective studies are needed.


2019 ◽  
Vol 8 (12) ◽  
pp. 2216 ◽  
Author(s):  
Lorenzo Tonetti ◽  
Federico Camilli ◽  
Sara Giovagnoli ◽  
Vincenzo Natale ◽  
Alessandra Lugaresi

While relapsing–remitting is the most prevalent course of multiple sclerosis, the prognostic/predictive markers of the worsening of symptomatology are still debated. With reference to other diseases, the study of the circadian activity rhythm, according to the theoretical framework of the two-process model of sleep regulation and applying functional linear modeling, proved to be useful to identify a possible marker. The usefulness of the study of circadian activity rhythm in multiple sclerosis is strengthened by recent findings indicating a potential involvement of circadian factors in the multifactorial etiopathology of the disorder. The aim of the present study was to verify whether circadian activity rhythm of early relapsing–remitting multiple sclerosis patients presents specific alterations, through functional linear modeling. Thirty-five relapsing–remitting multiple sclerosis patients (24 females; mean age ± SD = 31.51 ± 7.74) and 35 healthy controls (24 females; mean age ± SD = 31.29 ± 8.02) were enrolled. They wore an actigraph around the non-dominant wrist for one week. Relapsing–remitting multiple sclerosis patients showed a peak in motor activity around 5:00 a.m., higher than that of healthy controls. The timing of the peak in motor activity in the patients could be explained according to the hyperactive hypothalamus-pituitary-adrenal axis and higher cortisol awakening response reported in these patients.


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