Inherited Neuromuscular Disorders: Which Role for Serum Biomarkers?

Lupica, Antonino; Stefano, Vincenzo Di; Gagliardo, Andrea; Iacono, Salvatore; Pignolo, Antonia; Ferlisi, Salvatore; Torrente, Angelo; Pagano, Sonia; Gangitano, Massimo; Brighina, Filippo

doi:10.3390/brainsci11030398

Cited by 6 publications

(6 citation statements)

References 174 publications

(228 reference statements)

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“…It is our plan to investigate these issues in future studies. While preparing interventional studies in CMT1A, it would be of interest to understand correlations between impairment, disability, QoL, and disease biomarkers ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A

et al. 2022

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IntroductionCharcot-Marie-Tooth type 1A (CMT1A) comprises ~50% of all CMT cases. CMT1A is a slowly progressive motor and sensory neuropathy that leads to significant disability. We aimed to investigate the quality of life (QoL) in Serbian patients with CMT1A and to assess sociodemographic and clinical features associated with their QoL.Material and MethodsForty-five genetically confirmed patients with CMT1A were included −60% women [age 50.4 ± 12.6 years, disease duration 22 (12.5–31.5) years]. SF-36, Medical Research Council (MRC) Sum Score, CMT Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS), Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used in the study.ResultsRegarding SF-36, Mental Health and Social Functioning were the scales with the best achievements, whereas Role Physical was the worst domain. Worse QoL in patients with CMT1A was associated with elder age (rho = −0.34, p < 0.05), longer disease duration (rho = −0.31, p < 0.05), more pronounced muscle weakness measured by MRC-SS (rho = 0.43, p < 0.01), presence of tremor (p < 0.05), worse CMTES (rho = −0.68, p < 0.01), more severe disability in upper (rho = −0.70, p < 0.01) and lower limbs (rho = −0.61, p < 0.01) measured by ONLS scores, use of walking aids (p < 0.01), and with depression (p < 0.01) and fatigue (p < 0.01). Worse scores on CMTES (beta = −0.43, p < 0.01), BDI (beta = −0.39, p < 0.01), and FSS (beta = −0.36, p < 0.01) were significant independent predictors of worse QoL in patients with CMT1A (adjusted R2 = 0.77, p < 0.001).ConclusionBesides impairment made directly by CMT1A itself, QoL in these patients was also strongly affected by the presence of depression and fatigue. Since CMT1A is still not a curable disease, it is of interest to identify factors associated with QoL that are amenable to treatment.

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Section: Discussionmentioning

confidence: 99%

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A

et al. 2022

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“…Nowadays, hereditary transtiretin amyloidosis is a tractable disorder, for which a prompt diagnosis is needed, and biomarkers are on demand ( 14 ). Many molecules have been studied for cardiac phenotypes, such as serum retinol-binding protein 4 or B-type natriuretic peptide and transtiretin ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, there are only a few studies on biomarkers for nerve damage in ATTRv. Of interest, serum neurofilament light chain has been recently studied in ATTRv ( 16 ); however, there are only preliminary results available ( 14 ), that show a correlation with the severity of polyneuropathy, thus proposing NfL as a biomarker for nerve damage.…”

Section: Discussionmentioning

confidence: 99%

Motor Conduction Studies and Handgrip in Hereditary TTR Amyloidosis: Simple Tools to Evaluate the Upper Limbs

et al. 2022

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PurposeHereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. The clinical phenotype is heterogeneous, and characterized by a multisystemic disease affecting the sensorimotor and autonomic functions along with other organs.Materials and MethodsAll the patients were assessed by complete neurological assessment, neurophysiological evaluation, of the median nerve, and handgrip analysis. The data are presented as means and standard deviations. Parametric and non-parametric assessments have been performed to identify differences between groups. Pearson's correlation has been carried out when appropriate.ResultsTwenty patients with ATTRv (66.1 ± 8.4 years; eight females) and 30 controls (61.1 ± 11.6 years; 16 females) were enrolled. Handgrip strength was reduced in patients with ATTR in both right and left hands compared to the controls. Significant differences were found between patients and controls in the right (handgrip right, HGSR TTR 21.1 ± 13 kg vs. HGSR Control 29.4 ± 11.3 kg, p = 0.017) and left (handgrip left, HGSL TTR 22.2 ± 10.7 kg. vs. HGSL Control 31 ± 11.3 kg, p = 0.007). NIS and CMAP amplitude of the median nerve were related to HGS measures for both hands in patients with ATTRv.ConclusionsThe progression of bilateral carpal tunnel syndrome is related to neurophysiological data in the median nerve in ATTRv. Also, handgrip measures might represent an important tool for the assessment of disease progression in ATTRv. We propose using a combination of CMAP amplitude and HGS for the assessment of hand motor strength in ATTRv.

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“…It is worthy to note that, in some cases of AOA2, the AFP levels may be normal initially [ 14 ]; therefore, AFP levels assessments should be repeated during the course of an ataxia of unknown etiology. It should be noted that we did not check the patient’s IgA or IgG levels; however, they may be of diagnostic value in AT [ 15 ]. Other clues that favor the diagnosis of AOA2 in comparison to the other differentials include no ocular telangiectasis or immunodeficiency (to exclude AT and ATLD), teenage onset (AOA1, AOA4, and AT typically have an onset < 10 years), normal albumin (more commonly decreased in AOA1), and cholesterol levels (more commonly increased in AOA1) [ 13 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel SETX Mutation in a Taiwanese Patient with Autosomal Recessive Cerebellar Ataxia Detected by Targeted Next-Generation Sequencing, and a Literature Review

2022

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Ataxia with oculomotor apraxia type 2 (AOA2), also known as autosomal recessive spinocerebellar ataxia with axonal neuropathy-2 (SCAN2) (OMIM #606002), is a neurodegenerative disorder characterized by early-onset progressive cerebellar ataxia, polyneuropathy, and elevated levels of alpha-fetoprotein. It is caused by mutations in the SETX (OMIM #608465) gene. The prevalence of this disease is widely varied, from non-existent up to 1/150,000, depending on the region. Until now, no cases of AOA2/SCAN2 have been reported in Taiwan. Methods: Next-generation sequencing was used to detect disease-causing mutations of SETX in a Taiwanese patient presenting with autosomal recessive cerebellar ataxia, polyneuropathy, and elevated alpha-fetoprotein. The candidate mutations were further confirmed by polymerase chain reaction (PCR) and Sanger sequencing. Results: A compound heterozygous mutation of SETX c.6859C > T (p.R2287X) and c.7034-7036del was identified. The c.6859C > T (p.R2287X) has been previously found in a Saudi Arabia family, whereas c.7034-7036del is a novel mutation. Both mutations were predicted by bioinformatics programs to be likely pathogenic (having a damaging effect). We also reviewed the literature to address the reported clinical features of AOA2 from different populations. Conclusions: To our knowledge, we are the first to report a Taiwanese patient with AOA2/SCAN2, a result obtained by utilizing next-generation sequencing. The literature review shows that ataxia, polyneuropathy, and elevated AFP are common features and ocular motor apraxia (OMA) is a variable sign of AOA2 from different populations. OMA is rare and saccadic ocular pursuit and nystagmus are common in East Asian AOA2.

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Inherited Neuromuscular Disorders: Which Role for Serum Biomarkers?

Cited by 6 publications

References 174 publications

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A

Motor Conduction Studies and Handgrip in Hereditary TTR Amyloidosis: Simple Tools to Evaluate the Upper Limbs

A Novel SETX Mutation in a Taiwanese Patient with Autosomal Recessive Cerebellar Ataxia Detected by Targeted Next-Generation Sequencing, and a Literature Review

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