Evaluation of Cognitive Impairment in Pediatric Multiple Sclerosis with Machine Learning: An Exploratory Study of miRNA Expressions

2021 ◽

Author(s):

Gabriella Casalino ◽

Giovanna Castellano ◽

Arianna Consiglio ◽

Nicoletta Nuzziello ◽

Gennaro Vessio

Keyword(s):

Machine Learning ◽

Multiple Sclerosis ◽

Expression Profiles ◽

Healthy Children ◽

Multifactorial Diseases ◽

Hyperactivity Disorder ◽

Pediatric Multiple Sclerosis ◽

Mirna Expression Profiles ◽

Selection Algorithms ◽

Expression Classification

Abstract MicroRNAs (miRNAs) are a set of short non-coding RNAs that play significant regulatory roles in cells. The study of miRNA data produced by Next-Generation Sequencing techniques can be of valid help for the analysis of multifactorial diseases, such as Multiple Sclerosis (MS). Although extensive studies have been conducted on young adults affected by MS, very little work has been done to investigate the pathogenic mechanisms in pediatric patients, and none from a machine learning perspective. In this work, we report the experimental results of a classification study aimed at evaluating the effectiveness of machine learning methods in automatically distinguishing pediatric MS from healthy children, based on their miRNA expression profiles. Additionally, since Attention Deficit Hyperactivity Disorder (ADHD) shares some cognitive impairments with pediatric MS, we also included patients affected by ADHD in our study. Encouraging results were obtained with an artificial neural network model based on a set of features automatically selected by feature selection algorithms. The results obtained show that models developed on automatically selected features overcome models based on a set of features selected by human experts. Developing an automatic predictive model can support clinicians in early MS diagnosis and provide new insights that can help find novel molecular pathways involved in MS disease.

Download Full-text

Posterior brain damage and cognitive impairment in pediatric multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000000309 ◽

2014 ◽

Vol 82 (15) ◽

pp. 1314-1321 ◽

Cited By ~ 28

Author(s):

M. A. Rocca ◽

M. Absinta ◽

M. P. Amato ◽

L. Moiola ◽

A. Ghezzi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Brain Damage ◽

Pediatric Multiple Sclerosis

Download Full-text

Cognitive impairment in pediatric multiple sclerosis

Neurological Sciences ◽

10.1007/s10072-010-0437-8 ◽

2010 ◽

Vol 31 (S2) ◽

pp. 215-218 ◽

Cited By ~ 18

Author(s):

A. Ghezzi ◽

B. Goretti ◽

E. Portaccio ◽

M. Roscio ◽

M. P. Amato

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Pediatric Multiple Sclerosis

Download Full-text

A Pilot Longitudinal Evaluation of MicroRNAs for Monitoring the Cognitive Impairment in Pediatric Multiple Sclerosis

Applied Sciences ◽

10.3390/app10228274 ◽

2020 ◽

Vol 10 (22) ◽

pp. 8274

Author(s):

Nicoletta Nuzziello ◽

Arianna Consiglio ◽

Rosa Gemma Viterbo ◽

Flavio Licciulli ◽

Sabino Liuni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Target Genes ◽

Information Processing Speed ◽

Cross Sectional ◽

Pediatric Multiple Sclerosis ◽

Multiple Data ◽

Maturation Factor ◽

Early Markers ◽

Differentially Expressed Mirnas

MicroRNAs (miRNAs), a class of non-coding RNAs, seem to play a key role in complex diseases like multiple sclerosis (MS), as well as in many cognitive functions associated with the disease. In a previous cross-sectional evaluation on pediatric MS (PedMS) patients, the expression of some miRNAs and their target genes were found to be associated with the scores of some neuropsychiatric tests, thus suggesting that they may be involved in early processes of cognitive impairment. To verify these data, we asked the same patients to be re-evaluated after a 1-year interval; unfortunately, only nine of them agreed to this further clinical and molecular analysis. The main results showed that 13 differentially expressed miRNAs discriminated the two time-points. Among them, the expression of miR-182-5p, miR-320a-3p, miR-744-5p and miR-192-5p significantly correlated with the attention and information processing speed performances, whereas the expression of miR-182-5p, miR-451a, miR-4742-3p and miR-320a-3p correlated with the expressive language performances. The analysis of mRNA expression uncovered 58 predicted and/or validated miRNA-target pairs, including 23 target genes, some of them already associated with cognitive impairment, such as the transducing beta like 1 X-linked receptor-1 gene (TBL1XR1), correlated to disorders of neurodevelopment; the Snf2 related CREBBP activator protein gene (SRCAP) that was found implicated in a rare form of dementia; and the glia maturation factor beta gene (GMFB), which has been reported to be implicated in neurodegeneration and neuroinflammation. No molecular pathways involving the most targeted genes survived the adjustment for multiple data. Although preliminary, these findings showed the feasibility of the methods also applied to longitudinal investigations, as well as the reliability of the obtained results. These findings should be confirmed in larger PedMS cohorts in order to identify early markers of cognitive impairment, towards which more efficient therapeutic efforts can be addressed.

Download Full-text

Psychiatric diagnoses and cognitive impairment in pediatric multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513504249 ◽

2013 ◽

Vol 20 (5) ◽

pp. 588-593 ◽

Cited By ~ 31

Author(s):

Deborah Weisbrot ◽

Leigh Charvet ◽

Dana Serafin ◽

Maria Milazzo ◽

Thomas Preston ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Psychiatric Disorder ◽

Global Assessment ◽

Neuropsychological Test ◽

Psychiatric Evaluation ◽

Psychiatric Diagnoses ◽

Global Assessment Scale ◽

Psychiatric Interview ◽

Pediatric Multiple Sclerosis

Background: Pediatric multiple sclerosis (MS) represents approximately 5% of the MS population; information regarding clinical features is slowly accumulating. Cognitive and psychiatric impairments frequently occur, but remain poorly understood. Objectives: To describe psychiatric diagnoses among children with MS referred for psychiatric assessment and their relation to cognitive impairment. Methods: Forty-five pediatric MS patients (aged 8 to 17 years) were referred for outpatient psychiatric evaluation including a psychiatric interview (K-SADS), a clinician-based global assessment of functioning (Children’s Global Assessment Scale, CGAS), a neurologic examination including the Expanded Disability Status Scale (EDSS), and a neuropsychological test battery. Results: The most common categories of psychiatric diagnoses were anxiety disorders ( n=15), attention deficit hyperactivity disorder (ADHD, n=12), and mood disorders ( n=11). Cognitive impairment was classified in 20/25 (80%) of patients meeting criteria for a psychiatric disorder versus 11/20 (55%) of those without psychiatric disorder ( p=0.08). Those diagnosed with anxiety or mood disorder had the highest frequency of cognitive impairment, with a significantly higher rate when compared with those with psychiatric diagnoses in other categories ( p=0.05). Conclusions: A variety of psychiatric diagnoses can occur in children with pediatric MS. Many of these children also had cognitive impairment, particularly those in the mood and anxiety groups.

Download Full-text

Resting State Functional Connectivity Abnormalities Are Associated with Cognitive Impairment in Patients with Pediatric Multiple Sclerosis (P03.130)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.p03.130 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. P03.130-P03.130

Author(s):

M. Filippi ◽

M. Rocca ◽

M. Amato ◽

P. Valsasina ◽

M. Absinta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Functional Connectivity ◽

Resting State ◽

Resting State Functional Connectivity ◽

Pediatric Multiple Sclerosis

Download Full-text

Regional hippocampal involvement and cognitive impairment in pediatric multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515598569 ◽

2015 ◽

Vol 22 (5) ◽

pp. 628-640 ◽

Cited By ~ 13

Author(s):

Maria A Rocca ◽

Maria E Morelli ◽

Maria P Amato ◽

Lucia Moiola ◽

Angelo Ghezzi ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Cognitive Impairment ◽

Magnetic Resonance ◽

Dentate Gyrus ◽

Hippocampal Volume ◽

Cognitively Impaired ◽

Lesion Volume ◽

Resonance Imaging ◽

Pediatric Multiple Sclerosis

Objectives: We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics. Methods: From 53 pediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired. Results: Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired ( n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus. Conclusions: Hippocampal subregions have different vulnerability to damage in pediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests.

Download Full-text