Early detection of cognitive dysfunction in patients with multiple sclerosis: Implications on outcome

2019 ◽  
Vol 21 (2) ◽  
pp. 208-216
Author(s):  
Maged Abdel Naseer ◽  
Shereen Fathi ◽  
Dalia M. Labib ◽  
Dalia H. Khalil ◽  
Alshaimaa M. Aboulfotooh ◽  
...  

AbstractObjective:Cognitive impairment in multiple sclerosis (MS) has a complex relationship with disease progression and neurodegeneration. The aim of this study was to shed light on the importance of early detection of cognitive impairment in MS patients.Methods:The study comprised two groups of definite MS patients, relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), each with 25 patients. Physical disability was assessed using the Expanded Disability Status Scale (EDSS), while the risk of secondary progression was assessed using the Bayesian Risk Estimate for Multiple Sclerosis (BREMS). Cognitive functions were assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and Controlled Oral Word Association Test (COWAT). Assessment of neurodegeneration was done using optical coherence tomography (OCT) via quantification of retinal nerve fiber layer (RNFL).Results:MS patients with higher RNFL thickness demonstrated a larger learning effect size than patients who had lower values in RNFL thickness regardless of MS type. RRMS patients showed significant improvement in delayed recall after giving cues than SPMS. The symbol digit modalities test was the only neuropsychological test that showed a significant negative correlation with EDSS (P = 0.009). There was a statistically significant negative correlation between BREMS scores and performance in all neuropsychological tests.Conclusion:Inclusion of neurocognitive evaluation in the periodic assessment of MS patients is mandatory to detect patients at increased risk of secondary progression. The thickness of RNFL is suggested as a method to estimate the expected benefit of cognitive rehabilitation, regardless of MS type.

Author(s):  
Fiona Costello ◽  
William Hodge ◽  
Y. Irene Pan ◽  
Luanne Metz ◽  
Randy H. Kardon

Background:Optical coherence tomography (OCT) - measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS).Methods:Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON.Findings:Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically - affected eyes of non - MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non - MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302).Interpretation:Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non - MS patients over time.


2018 ◽  
Vol 12 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Christos Bakirtzis ◽  
Panagiotis Ioannidis ◽  
Lambros Messinis ◽  
Grigorios Nasios ◽  
Elina Konstantinopoulou ◽  
...  

About half of patients with multiple sclerosis exhibit cognitive impairment which negatively affects their quality of life. The assessment of cognitive function in routine clinical practice is still undervalued, although various tools have been proposed for this reason. In this article, we describe the potential benefits of implementing cognitive assessment tools in routine follow -ups of MS patients. Early detection of changes in cognitive performance may provide evidence of disease activity, could unmask depression or medication side-effects and provide suitable candidates for cognitive rehabilitation. Since apathy and cognitive deficiencies are common presenting symptoms in Progressive Multifocal Leukoencephalopathy, we discuss the utility of frequent monitoring of mental status in multiple sclerosis patients at increased risk. In addition, we propose a relevant algorithm aiming to incorporate a systematic evaluation of cognitive function in every day clinical practice in multiple sclerosis.


2016 ◽  
Vol 27 (3) ◽  
pp. 331-335 ◽  
Author(s):  
Isil Kurultay-Ersan ◽  
Sinan Emre

Purpose To evaluate the alterations in mean central choroidal, central macular, and disk retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) during Valsalva maneuver among patients with high refractive errors. Methods A total of 60 high myopic (≥-6.0 D) and 50 high hyperopic (≥ + 3.0 D) eyes of 58 patients aged 19-65 years with visual acuity of 20/20 and without any ophthalmologic or systemic diseases were evaluated by OCT before and after the Valsalva maneuver. The choroidal thickness was measured with enhanced depth imaging OCT method. Central macular thickness, disk RNFL thickness, and axial length were also assessed. Results Mean choroidal thickness increased significantly from 275.0 ± 27.2 μm at rest to 279.8 ± 31.6 μm after Valsalva maneuver in high myopic patients, and from 308.2 ± 27.3 μm to 313.6 ± 28.5 μm in high hyperopic patients (p<0.01 for each). A significant negative correlation of the choroidal thickness was noted with axial length (r = -0.509, p<0.01) and age (r = -0.224, p = 0.01) in the overall study population. Mean central macular thickness was 242.9 ± 44.4 μm and 254.0 ± 22.8 μm, while mean disk RNFL thickness was 81.6 ± 12.4 μm and 98.4 ± 13.3 μm in high myopic and hyperopic patients, respectively. Valsalva maneuver was not associated with significant change in central macular or disk RNFL thickness. Conclusions Significant association of Valsalva maneuver with an increase in choroidal thickness was noted among patients with high degree of myopia and hyperopia. Our findings emphasize the likelihood of increase in choroidal volume due to venous distension to be responsible for the increase observed in choroidal thickness after Valsalva maneuver.


2019 ◽  
Vol 11 ◽  
pp. 117957351988404
Author(s):  
Stijn Denissen ◽  
Alexander De Cock ◽  
Tom Meurrens ◽  
Luc Vleugels ◽  
Ann Van Remoortel ◽  
...  

Background: Cognitive dysfunction is a frequent manifestation of multiple sclerosis (MS) but its effect on locomotor rehabilitation is unknown. Objective: To study the impact of cognitive impairment on locomotor rehabilitation outcome in people with MS. Methods: We performed a retrospective analysis involving ambulatory patients with MS who were admitted for intensive, inpatient, multidisciplinary rehabilitation at the National Multiple Sclerosis Center of Melsbroek between the years 2012 and 2017. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was used to determine the cognitive status of subjects as either impaired (COG–) or preserved (COG+). Locomotor outcome was compared between groups with the difference in 6-minute walk test (6MWT) measured at admission and discharge (Δ6MWT). In addition, individual test scores of the BRB-N for attention (Paced Auditory Serial Addition Test 2” and 3”), visuospatial learning/memory (7/24 Spatial Recall Test), verbal learning/memory (Selective Reminding Test) and verbal fluency (Controlled Oral Word Association Test) were correlated to the Δ6MWT. Results: A total of 318 complete and unique records were identified. Both groups showed a significant within-group Δ6MWT during hospitalization (COG+: 47.51 m; COG–: 40.97 m; P < .01). In contrast, Δ6MWT values were comparable between groups. The odds of achieving a minimal clinical important difference on the 6MWT did not differ significantly between both groups. Only attention/concentration was significantly correlated with Δ6MWT (r = 0.16, P = .013). Conclusion: Cognitive impairment based on BRB-N results appears not to impede locomotor rehabilitation in ambulatory patients with MS. Attentional deficits are correlated to the extent of locomotor rehabilitation, suggesting the presence of a subtle effect of cognition.


2008 ◽  
Vol 14 (7) ◽  
pp. 906-912 ◽  
Author(s):  
J Toledo ◽  
J Sepulcre ◽  
A Salinas-Alaman ◽  
A García-Layana ◽  
M Murie-Fernandez ◽  
...  

Background Studying axonal loss in the retina is a promising biomarker for multiple sclerosis (MS). Our aim was to compare optical coherence tomography (OCT) and Heidelberg retinal tomography (HRT) techniques to measure the thickness of the retinal nerve fiber layer (RNFL) in patients with MS, and to explore the relationship between changes in the RNFL thickness with physical and cognitive disability. We studied 52 patients with MS and 18 proportionally matched controls by performing neurological examination, neuropsychological evaluation using the Brief Repetitive Battery-Neuropsychology and RNFL thickness measurement using OCT and HRT. Results We found that both OCT and HRT could define a reduction in the thickness of the RNFL in patients with MS compared with controls, although both measurements were weakly correlated, suggesting that they might measure different aspects of the tissue changes in MS. The degree of RNFL atrophy was correlated with cognitive disability, mainly with the symbol digit modality test ( r = 0.754, P < 0.001). Moreover, temporal quadrant RNFL atrophy measured with OCT was associated with physical disability. Conclusion In summary, both OCT and HRT are able to detect thinning of the RNFL, but OCT seems to be the most sensitive technique to identify changes associated with MS evolution.


Author(s):  
Mona A Elabd ◽  
Dina Abu Zeid ◽  
Marwa A Elhady ◽  
Maged A El Wakeel ◽  
Ghada M El-kassas ◽  
...  

Objective: The objective of this research was to evaluate oxidative stress status in children with β-thalassemia major.Methods: Our study was conducted in children with β-thalassemia aged from 5 to 15 years. Investigate the urinary excretion of human 8-oxo-7,8- dihydro-2′-deoxyguanosine, which will be analyzed by enzyme-linked immunosorbent assay. To investigate serum levels of antioxidant enzymes include glutathione s-transferase (GST) and catalase (CAT).Results: We found a significant elevation of the urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine level with p=0.001 compared to control group, a significant reduction of both GST and CAT p=0.05 and 0.03, respectively, compared to control group. There was a significant negative correlation between urinary 8-oxo-7,8-dihydro-2′-deoxyguanisine and CAT level, r=−0.378, p=0.016, hemoglobin - r=−0.610, p=0.001, hematocrit (%) - r=−0.478, p=0.002, while a significant positive correlation between urinary 8-oxo-7,8-dihydro-2′-deoxyguanisine and alanine aminotransferase - r=0.547, p=0.001, and serum ferritin - r=0.391, p=0.013. There was a significant negative correlation between CAT and serum ferritin - r=−0.320, p=0.44.Conclusion: We conclude that the strongly increased urinary excretion 8-oxo-7,8=dihydro-2′-deoxyguanisine indicates elevated lipid peroxidation induced DNA damage in internal organs such as the liver. These highly pro mutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma.


2010 ◽  
Vol 17 (4) ◽  
pp. 457-467 ◽  
Author(s):  
J Sastre-Garriga ◽  
J Alonso ◽  
M Renom ◽  
MJ Arévalo ◽  
I González ◽  
...  

Background: Cognitive impairment is frequent in multiple sclerosis (MS) and lacks effective treatment. Cognitive rehabilitation is widely applied in neurorehabilitation settings. Functional magnetic resonance imaging (fMRI) may help in investigating changes in brain activity and provide a tool to assess the efficacy of rehabilitation. Aim: To investigate the effect on brain activity as measured by fMRI of a cognitive rehabilitation programme in patients with MS and cognitive impairment. Method: Fifteen patients with MS and cognitive impairment and five healthy subjects were recruited. Neuropsychological assessments were performed in patients with MS at study entry and after rehabilitation to assess cognitive changes. fMRI scans were performed at week −5 (baseline), week 0 (immediately before rehabilitation) and week 5 (immediately after rehabilitation). The fMRI paradigm was the Paced Auditory Serial Addition Test (PASAT). The cognitive rehabilitation programme was composed of 15 computer-aided drill and practice sessions and five non-computer-aided cognitive stimulation group sessions (over 5 weeks). Strict guidelines ensured comparability of all rehabilitation interventions. Results: Patients had increased brain fMRI activity after rehabilitation in several cerebellar areas when compared with healthy subjects. After rehabilitation, patients had significantly improved their performance on the backward version of the Digit Span Test ( p = 0.007) and on a composite score of neuropsychological outcomes ( p = 0.009). Conclusion: The results of the present study indicate that this cognitive rehabilitation programme increases brain activity in the cerebellum of cognitively impaired patients with MS. The role of fMRI in the assessment of neurorehabilitation schemes warrants further investigation.


2008 ◽  
Vol 14 (5) ◽  
pp. 609-614 ◽  
Author(s):  
V Pueyo ◽  
J Martin ◽  
J Fernandez ◽  
C Almarcegui ◽  
J Ara ◽  
...  

Objective To quantify axonal loss in the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS), with and without a history of optic neuritis, by means of ocular imaging technologies. Methods This cross-sectional study enrolled 50 patients with MS and 25 age- and sex-matched healthy controls. All patients underwent neurologic assessment and a complete ophthalmic examination that included visual acuity, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials (VEPs). Visual parameters and RNFL measurements were evaluated in MS eyes with a prior optic neuritis episode (MS-ON), with no prior episode (MS-NON) and control subjects. Results There were significant differences ( p < 0.05, analysis of variance) between MS-ON ( n = 25 eyes) and healthy eyes ( n = 25 eyes) for all RNFL parameters measured by OCT and GDx. Significant differences between MS-NON ( n = 75 eyes) and healthy eyes were also found for most of these parameters. RNFL thickness in the temporal quadrant was the parameter with the greatest differences between groups (71.79 μm in healthy eyes, 60.29 μm in MS-NON and 53.92 μm in MS-ON, p < 0.0005). Although there was a highly significant but moderate correlation between RNFL thickness and duration of the disease, no correlation was observed between RNFL thickness and neurologic impairment (Expanded Disability Status Scale). Conclusions Axonal loss was detected not only in MS eyes with a previous acute optic neuritis, but also in MS eyes with no known optic neuritis episode. Structural abnormalities correlate with functional assessments of the optic nerve.


2007 ◽  
Vol 14 (2) ◽  
pp. 177-182 ◽  
Author(s):  
JA Woolmore ◽  
MJ Stone ◽  
SL Holley ◽  
PM Jenkinson ◽  
A. Ike ◽  
...  

Cognitive impairment occurs in 45—65% of multiple sclerosis (MS) patients. The cannabinoid system may potentially be neuroprotective in MS. We examined the relationship between polymorphisms of the CNR1 gene and neuropsychological outcome in MS using a test and confirmatory sample of patients. One hundred and ninety-four MS patients were assessed over five key areas of neuropsychological function, which are most commonly impaired in MS. The first 97 patients formed the test sample. A further confirmatory sample of 97 patients was used to test association found in the test sample. The schedule included: Wisconsin card sorting test 64 version, Rey auditory verbal learning task immediate and delayed scores, controlled oral word association task, judgement of line orientation and symbol digit modalities task. Three single nucleotide polymorphisms (SNPs) were typed within the CNR1 gene. For the overall neuropsychological assessment score we used a multiple linear regression model with selected covariates to show that subjects with the AA genotype of the SNP RS1049353 were more impaired (mean -2.47, SD 5.75, P = 0.008, Bonferroni corrected P = 0.024) than the other subjects (mean 0.24, SD 4.24). This was not confirmed when the association was retested in the confirmatory sample. No associations were identified between these CNR1 variants and cognitive impairment in MS. Multiple Sclerosis 2008; 14: 177—182. http://msj.sagepub.com


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