scholarly journals Fronto-limbic disconnection in patients with multiple sclerosis and depression

2018 ◽  
Vol 25 (5) ◽  
pp. 715-726 ◽  
Author(s):  
Quinten van Geest ◽  
Rosa E Boeschoten ◽  
Matthijs J Keijzer ◽  
Martijn D Steenwijk ◽  
Petra JW Pouwels ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Neuropsychological Testing ◽  
Uncinate Fasciculus ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Brain Volumes ◽  
Functional Changes ◽  
Severity Of Depression ◽  
Magnetic Resonance Imaging Mri

Background: The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important. Objective: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients. Methods: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression. Results: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found. Conclusion: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center

2017 ◽  
Vol 24 (7) ◽  
pp. 942-950 ◽  
Author(s):  
Kyle Smoot ◽  
Kateri J Spinelli ◽  
Tamela Stuchiner ◽  
Lindsay Lucas ◽  
Chiayi Chen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Community Health Center ◽  
Dimethyl Fumarate ◽  
Clinical Relapse ◽  
Disease Modifying Therapy ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Previous Disease ◽  
Relapsing Multiple Sclerosis

Background: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. Objective: To track DMF patients’ tolerability, disease progression, and lymphopenia. Methods: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. Results: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-β (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). Conclusion: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

Extracranial venous stenosis is an unlikely cause of multiple sclerosis

2010 ◽  
Vol 16 (11) ◽  
pp. 1341-1348 ◽  
Author(s):  
Bassem Yamout ◽  
Aline Herlopian ◽  
Zeinab Issa ◽  
Robert H Habib ◽  
Ahmad Fawaz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Disease Onset ◽  
Clear Correlation ◽  
Clinical Relapse ◽  
Venous Stenosis ◽  
Relapsing Remitting ◽  
Similar Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Secondary Phenomenon

Background: Extracranial venous stenosis (EVS) has recently been implicated as the primary cause of multiple sclerosis (MS). Objective: The aim of this study was to determine the presence of EVS in MS patients. Methods: We performed selective extracranial venography on 42 patients with early MS (EMS): clinically isolated syndrome (CIS) or relapsing—remitting MS (RRMS) of less than 5 years duration, and late MS (LMS): RRMS of more than 10 years duration. Magnetic resonance imaging (MRI) and clinical relapse data were reviewed for all patients with EVS. Results: EVS was present in 7/29 patients with EMS and 12/13 patients with LMS, a highly significant statistical difference ( p< 0.001). Only 3/42 patients (all in the LMS group) had two vessel stenoses, while the rest had only one vessel involved. EVS was seen in 1/11 patients with CIS compared with 6/18 RRMS patients of less than 5 years duration. Disease duration was greater in patients with EVS overall ( p < 0.005). LMS remained an independent predictor of EVS following multivariate adjustment for gender, age at disease onset and Expanded Disability Status Scale (EDSS) (Adjusted Odds Ratio = 29 (3—298); p = 0.005]. Within the EMS group, patients with ( n = 7) and without ( n = 22) EVS had similar EDSS and disease duration, suggesting similar disease severity. No clear correlation could be found between site of EVS and anatomic localization of either clinical relapses or MRI gadolinium-enhancing lesions. Conclusions: We conclude that EVS is an unlikely cause of MS since it is not present in most patients early in the disease and rarely involves more than one extracranial vein. It is likely to be a late secondary phenomenon.

scholarly journals Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients

2016 ◽  
Vol 23 (7) ◽  
pp. 963-972 ◽  
Author(s):  
Ludwig Schlemm ◽  
Claudia Chien ◽  
Judith Bellmann-Strobl ◽  
Jan Dörr ◽  
Jens Wuerfel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Dentate Nucleus ◽  
Alternative Explanation ◽  
Disease Duration ◽  
Gadopentetate Dimeglumine ◽  
Progressive Neurodegeneration ◽  
Magnetic Resonance Imaging Mri ◽  
T1 Hyperintensity ◽  
Multiple Sclerosis Patients

Background: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). Objective: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. Methods: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). Results: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs −0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR ( p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration. Conclusion: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd-BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity.

Detection and clinical correlation of leukocortical lesions in pediatric-onset multiple sclerosis on multi-contrast MRI

2018 ◽  
Vol 25 (7) ◽  
pp. 980-986 ◽  
Author(s):  
Josefina Maranzano ◽  
Christine Till ◽  
Haz-Edine Assemlal ◽  
Vladimir Fonov ◽  
Robert Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Three Dimensional ◽  
High Rate ◽  
Proton Density ◽  
Lesion Volume ◽  
3T Mri ◽  
Fluid Attenuated Inversion Recovery ◽  
Magnetic Resonance Imaging Mri ◽  
Pediatric Onset

Objective: To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). Methods: Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density–weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. Results: We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume ( p = 0.04) but not with thalamic volume, age at the time of the scan, or disease duration. The number of frontal CLs was associated with slower performance on the 9-HPT ( p = 0.05). Conclusion: Multi-contrast 3T MRI led to a high rate of CL detection, demonstrating that cortical pathology occurs even in pediatric-onset disease. Frontal lobe CL count was associated with reduced manual dexterity, indicating that these CLs are clinically relevant.

Evidence for early, non-lesional cerebellar damage in patients with multiple sclerosis: DTI measures correlate with disability, atrophy, and disease duration

2015 ◽  
Vol 22 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Michael Deppe ◽  
Karsten Tabelow ◽  
Julia Krämer ◽  
Jan-Gerd Tenberge ◽  
Patrick Schiffler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Duration ◽  
Diffusion Tensor ◽  
Early Stage ◽  
Cerebellar White Matter ◽  
Cerebellar Damage ◽  
Cerebellar Tissue ◽  
Magnetic Resonance Imaging Mri ◽  
Tissue Alterations

Background: Common symptoms of multiple sclerosis (MS) such as gait ataxia, poor coordination of the hands, and intention tremor are usually the result of dysfunctionality in the cerebellum. Magnetic resonance imaging (MRI) has frequently failed to detect cerebellar damage in the form of inflammatory lesions in patients presenting with symptoms of cerebellar dysfunction. Objective: To detect microstructural cerebellar tissue alterations in early MS patients with a “normal appearing” cerebellum using diffusion tensor imaging (DTI). Methods: A total of 68 patients with relapsing–remitting MS (RRMS) and without cerebellar lesions and 26 age-matched healthy controls were admitted to high-resolution MRI and DTI to assess microstructure and volume of the cerebellar white matter (CBWM). Results: We found cerebellar fractional anisotropy (FA) and CBWM volume reductions in the group of 68 patients. Interestingly, a subgroup of these patients that was derived by including only patients with early and mild MS ( N=23, median age 30 years, median Expanded Disability Status Scale =1.5, median duration 28 months) showed already cerebellar FA but no CBWM volume reductions. FA reductions were correlated with disability, atrophy, and disease duration. Conclusion: “Normal appearing” cerebellar white matter can be damaged in a very early stage of RRMS. DTI seems to be a sensitive tool for detecting this hidden cerebellar damage.

scholarly journals Comparison of self-rating of cognition and depression in patients with major depressive disorder

2020 ◽  
Vol 12 (2) ◽  
pp. 31-33
Author(s):  
Kishen Berra ◽  
Charles Nguyen ◽  
Peter Bota
Keyword(s):  
Major Depression ◽  
Cognitive Dysfunction ◽  
Neuropsychological Testing ◽  
Health Clinic ◽  
Self Assessment ◽  
Major Depressive ◽  
Content Type ◽  
Clinical Support ◽  
Severity Of Depression ◽  
Equivalent Test

Purpose The purpose of this paper is to discover if there is a correlation between scores on the Beck’s Depression Inventory (BDI) and the Cognitive and Physical Functioning Questionnaire (CPFQ) scores of 43 patients with major depression. Design/methodology/approach In total, 43 adult patients with major depression were evaluated during their regularly scheduled outpatient appointment in a mental health clinic. Findings There was an R2 value of 0.6544 between the patients’ scores, a moderate-to-strong correlation which matches other observations that cognitive impairment increases in conjunction with severity of depression. This correlation lends further clinical support to the legitimacy of using the CPFQ as a simpler alternative to traditional neuropsychological testing, with further testing of the correlation between CPFQ and traditional neuropsychological testing results being a worthwhile potential field of study. Originality/value Cognitive dysfunction is a frequent comorbidity in patients with depression, but while there is a brief and effective self- assessment for depression, the BDI, in common use, there is no equivalent test for cognitive dysfunction, and physicians are forced to rely on less accessible methods of neuropsychological testing.

Low degree of cortical pathology is associated with benign course of multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 904-911 ◽  
Author(s):  
Massimiliano Calabrese ◽  
Alice Favaretto ◽  
Valentina Poretto ◽  
Chiara Romualdi ◽  
Francesca Rinaldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Brain Magnetic Resonance Imaging ◽  
Cortical Thinning ◽  
Low Degree ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Cortical Pathology ◽  
Magnetic Resonance Imaging Mri ◽  
Normal Cognition

Background: Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association. Materials and Methods: We followed 95 early relapsing–remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly. Results: At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients ( p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients ( p ranging between 0.001–0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal ( p = 0.036) and superior parietal gyrus ( p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume ( p = 0.006) and the cortical thickness of the temporal middle ( p < 0.001), insular long ( p < 0.001), superior frontal ( p < 0.001) and middle frontal gyri ( p < 0.001) as the most sensitive independent predictors of a favorable disease course. Conclusions: Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.

scholarly journals Triaging Patients with Multiple Sclerosis in the Emergency Department

2017 ◽  
Vol 19 (6) ◽  
pp. 290-296 ◽  
Author(s):  
Hesham Abboud ◽  
Karin Mente ◽  
Meagan Seay ◽  
Jeffrey Kim ◽  
Ashhar Ali ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Decision Making ◽  
Emergency Department ◽  
Medical Records ◽  
Disease Duration ◽  
Therapeutic Interventions ◽  
Resonance Imaging ◽  
Ed Visits ◽  
Magnetic Resonance Imaging Mri

Background: Patients with multiple sclerosis (MS) present to the emergency department (ED) for various reasons. Although true relapse is rarely the underlying culprit, ED visits commonly result in new magnetic resonance imaging (MRI) and neurology admissions. We studied ED visits in patients with MS and evaluated decision making regarding diagnostic/therapeutic interventions and visit outcomes. We identified potential areas for improvement and used the data to propose a triaging algorithm for patients with MS in the ED. Methods: We reviewed the medical records from 176 ED visits for patients with MS in 2014. Results: Ninety-seven visits in 75 patients were MS related (66.6% female; mean ± SD age, 52.6 ± 13.8 years; mean ± SD disease duration, 18.5 ± 10.5 years). Thirty-three visits were for new neurologic symptoms (category 1), 29 for worsening preexisting symptoms (category 2), and 35 for MS-related complications (category 3). Eighty-nine visits (91.8%) resulted in hospital admission (42.7% to neurology). Only 39% of ordered MRIs showed radiographic activity. New relapses were determined in 27.8% of the visits and were more prevalent in category 1 compared with category 2 (P = .003); however, the two categories had similar rates of ordered MRIs and neurology admissions. Conclusions: New relapse is a rare cause of ED visits in MS. Unnecessary MRIs and neurology admissions can be avoided by developing a triaging system for patients with MS based on symptom stratification.

Resting-state functional connectivity of anterior and posterior cerebellar lobes is altered in multiple sclerosis

2020 ◽  
pp. 135245852092277
Author(s):  
Gabriele Pasqua ◽  
Silvia Tommasin ◽  
Komal Bharti ◽  
Serena Ruggieri ◽  
Nikolaos Petsas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional Connectivity ◽  
Resting State ◽  
Structural Damage ◽  
Cognitive Disability ◽  
Resting State Functional Connectivity ◽  
Cognitive Domains ◽  
Composite Scale ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri

Background: Damage to the cerebellar sensorimotor and cognitive domains may underlie physical and cognitive disability. Objective: To investigate resting-state functional connectivity (FC) of sensorimotor and cognitive cerebellum, and clinical correlates in multiple sclerosis (MS). Methods: A total of 119 patients with MS and 42 healthy subjects underwent multimodal 3T-magnetic resonance imaging (MRI). Patients were evaluated using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Scale. After parcellation of sensorimotor (lobules I–V + VIII) and cognitive cerebellum (lobules VI, VII, IX, X), we calculated cerebellar resting-state FC using a seed-based approach. Results: In patients with MS, the sensorimotor cerebellum showed increased FC mainly with cerebellar, thalamic, and cortical (frontal, parietal, temporal) areas and decreased FC with insular areas; the cognitive cerebellum showed increased FC mainly with thalamic and cortical (temporal-occipital) areas, and decreased FC with frontal-insular areas. Both sensorimotor and cognitive cerebellar FC negatively correlated with disability, and positively with cognitive scores. Cerebellar structural damage only partially influenced results. Conclusion: The two neocerebellar circuits showed altered FC with subcortical and cortical areas. The association between increased sensorimotor and cognitive cerebellar FC and low levels of physical and cognitive disability suggests that altered FC might modulate the effects of cerebellar structural damage on clinical condition.

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