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Non-Commercial Use Only Neurology International 2018; volume 10:7473 Cognitive impairment in neuromuscular diseases: Introduction Correspondence: Francisco Victor Costa Marinho, Federal University of Piauí, Brazil. A systematic review Neuromuscular diseases present a wide Brain Mapping and Plasticity Laboratory- Av. variety of clinical manifestations, but their São Sebastião nº2819 – Nossa Sra. de Fátima effects on the cognitive function spectrum Marco Orsini,1,2 Ana Carolina – Parnaíba, PI, CEP: 64202-020, Brazil. are still poorly understood.1 In contrast to the Tel.: +55.86.994178117. Andorinho de F. Ferreira,3 studies on how altered executive functions in E-mail: [email protected] 3,4 Anna Carolina Damm de Assis, mental disorders such as anxiety, depression 3 2 Thais Magalhães, Silmar Teixeira, and bipolar disorder can affect motor perfor- Key words: Cognitive Impairment; Victor Hugo Bastos,2 Victor Marinho,2 mance,2-4 the mechanisms by which essen- Neuromuscular Diseases; Motor Neuron Thomaz Oliveira,2 Rossano Fiorelli,1 tially motor dysfunctions can affect cogni- Diseases; Dystrophinopathies; Mitochondrial Acary Bulle Oliveira,4 tive performance still remain poorly under- Disorders. 5 stood and studied.5-8 Although it is known Marcos R.G. de Freitas Contributions: the authors contributed equally. that neuromuscular diseases mainly affect 1Master’s Program in Health Applied the motor functioning of the patient, the cog- Sciences, Severino Sombra University, Conflict of interest: the authors declare no nitive effects of these conditions can be sig- Vasssouras, Rio de Janeiro; 2Brain potential conflict of interest. nificant.5 This can occur from molecular Mapping and Plasticity Laboratory, defects that significantly affect neuromotor Funding: none. Federal University of Piauí, Parnaíba; functioning but also participate in the func- 3Department of Neurology, Federal tioning of neural networks involved in cogni- Received for publication: 31 October 2017. Fluminense University, Rio de Janeiro; tive processes, leading to dysfunctions of Revision received: 4 December 2017. 4Department of Neurology, Federal executive, behavioral and psychosocial func- Accepted for publication: 12 December 2017. University of São Paulo; 5Department of tions.6-8 For example, mutations in the dys- This work is licensed under a Creative Neurology, Federal University of Rio de trophin protein gene, responsible for the Commons Attribution NonCommercial 4.0 Janeiro, Brazil Duchenne Muscular Dystrophy (DMD) phe- onlyLicense (CC BY-NC 4.0). notype, concurrently affect the stability and function of muscle fibers and central nervous ©Copyright M. Orsini et al., 2018 system (CNS) function. However, the com- Licensee PAGEPress, Italy Neurology International 2018; 10:7473 Abstract plex nature of neuromuscular diseasesuse and the different effects on cognition make it dif- doi:10.4081/ni.2018.7473 Neuromuscular diseases are multifactorial ficult to understand the neuropathological pathologies characterized by extensive muscle process.7,8 puter-based literature search was conducted fiber damage that leads to the activation of Three large, heterogeneous groups of in two main databases: ISI Web of Science satellite cells and to the exhaustion of their neuromuscular diseases have been implicat- and PubMed (2003-present) were initially pool, with consequent impairment of neurobi- ed in cognitive alterations. i) Motor Neuron performed in October 2017 using relevant ological aspects, such as cognition and motor Diseases, neurological disorders that affect search terms: (e.g. [Cognitive Impairment control. To review the knowledge and obtain a the neurons that control voluntary motor and Neuromuscular Diseases] [Motor broad view of the cognitive impairment on activity;9,10 ii) Muscular dystrophies, repre- Neuron Diseases and Cognitive Neuromuscular Diseases. Cognitive impair- sented mainly by dystrophinopathies, dis- Impairment] [Cognitive Impairment and ment in neuromuscular disease was explored; eases caused by hereditary defects in the Dystrophinopathies] [Cognitive a literature search up to October 2017 was dystrophin protein gene;11 iii) Impairment and Mitochondrial Disorders]. conducted, including experimental studies, Mitochondrial disorders, which are caused Abstracts were examined for references to case reports and reviews written in English. by mutations in cytoplasmic or nuclear the research question and if the study Keywords included Cognitive Impairment, mitochondrial DNA, which alter the struc- appeared relevant, then the full text was 10,12 Neuromuscular Diseases, MotorNon-commercial Neuron ture and mitochondria function. Often retrieved. As selection criteria: (a) Diseases, Dystrophinopathies and neuromuscular disease comes from an Experimental studies, case reports and Mitochondrial Disorders. Several cognitive already known molecular disorder that is reviews written in English; (b) Without evaluation scales, neuroimaging scans, genet- also associated with changes in brain func- restriction of publication dates of the paper ic analysis and laboratory applications in neu- tion and cognition, such as mitochondrial (c) Magnetic Resonance Imaging (MRI) romuscular diseases, especially when it comes myopathies. In other cases, neuromuscular scans, assessments with cognitive and func- to the Motor Neuron Diseases, disorders also have cognitive deficits, but tional scales applied to neuromuscular dis- Dystrophinopathies and Mitochondrial without a well-defined molecular alteration eases, and cognitive tasks healthy individu- Disorders. In addition, organisms model using such as Amyotrophic Lateral Sclerosis als and/or individuals with neuromuscular 8,13 rats in the genetic analysis and laboratory (ALS). In this context, the present diseases (e.g. children, young adults, mid- review aims to highlight the neurofunction- applications to verify the cognitive and neuro- dle-aged and elderly). In addition, experi- al and cognitive alterations in the main con- muscular impacts. Several studies indicate mental studies using rats were considered. genital neuromuscular disorders. that congenital molecular alterations in neuro- Criteria for exclusion were: (a) disserta- muscular diseases promote cognitive dysfunc- tions, book reviews, conference proceed- tions. Understanding these mechanisms may ings, or editorials. Data were extracted in the future guide the proper management of Materials and Methods based on study design and setting. The dis- the patient, evaluation, establishment of prog- cussion was written after observing com- nosis, choice of treatment and development of The systematic review was conducted mon points among the articles selected. innovative interventions such as gene therapy. in line with the PRISMA statement. A com- This observation was conducted in order to [Neurology International 2018; 10:7473] [page 3] Review analyze the papers results and answer the Examination (MMSE), Addenbrooke’s muscular diseases is greatly variable, and hypothesis of the present research. Cognitive Examination-Revised (ACE-R), significant cognitive impairment is California Verbal Learning Test (CVLT), observed only in some patients. Symptoms Study selection and data extraction Stroop Color and Word Test (SCWT). such as depression and anxiety as well as Three reviewers (M.O, S.T and V.M) Outcome: The primary outcome mea- deficits of visuospatial abilities, executive independently read the titles and/or sure was the potential ability to accurately functions, and naming have been frequently abstracts of the identified papers and elimi- assess neuromuscular diseases and their reported. Several MRI studies have shown nated irrelevant studies. Studies considered implications for cognitive impairment that neuromuscular diseases patients have eligible for inclusion were read in full and through screening: Genetic analysis, MRI generally more deficiencies of neural con- their suitability for inclusion was deter- scans, mobile transcutaneous sensor for tis- nections in the frontal, parietal and temporal mined independently by three reviewers sue blood gas tensions and cognitive Scales. regions and; these dysfunctions increase (M.O, S.T and V.M) Disagreements were Papers were assessed for eligibility with the progression of the disease. managed by consensus. However, if this based on title and abstract; 80 were classi- was not successful, consensus was sought fied as meeting eligibility criteria. The next by a fourth reviewer (M.R.G.F.). Data were stage of the winnowing process involved extracted based on study design and setting. full-text screening of the potentially rele- Discussion Some authors were contacted to provide vant papers; Eventually, 63 studies were supplementary information when insuffi- included in the review. Motor neuron diseases and cognitive cient data were provided in the study. The impairment authors of three studies were contacted for Motor Neuron Disease (MND) is a further information having read their titles degenerative disease caused by motor neu- and abstracts. Two replied; since it bases the Results ron degeneration, whether inferior or supe- review of literature fulfilled the inclusion rior. Amyotrophic Lateral Sclerosis (ALS), Seventeen experimental studies and 30 criteria. the most well-known form of MND, is a case reports with cognitive scales and neu- devastating severe disease that simultane- romuscular assessment using scales, as well only Study selection ously affects the lower motor neuron as genetic studies and neuroimaging studies 9,10 Studies were
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