Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study

Li, Jin-Yue; Dai, Yi; Sun, Xuxu; Ren, Haitao; Shen, Dongchao; Yang, Xunzhe; Liu, Mingsheng

doi:10.1002/brb3.2997

Cited by 4 publications

(1 citation statement)

References 40 publications

(38 reference statements)

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“…More recent studies (Kläppe et al: cutoff 56.4 pg/mL, Verde et al: cutoff 49–62 pg/mL [ 34 , 41 ]) as well as studies focusing on selected, well-characterized mimics (Gille et al: 55 pg/mL versus hereditary spastic paraplegia [ 40 ]) found similar cutoffs. For CSF pNfH, our optimal cutoff of ≥ 715.50 pg/mL was well in the range of previously reported cutoffs (Kläppe et al: 726 pg/mL; Poesen et al: 768 pg/mL; Steinacker et al: 560 pg/mL; Chen et al: 437 ng/L; Li et al: 395 pg/mL, Li et al: 1104 pg/mL [ 32 – 34 , 42 – 44 ]). Of note, the one MMN patient with serum NfL above the optimal cutoff presented with comorbid diabetes mellitus type 2.…”

Section: Discussionsupporting

confidence: 80%

Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy

Wohnrade,

Seeliger,

Gingele

et al. 2024

J Neurol

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Objective To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN). Methods This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients (n = 24) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden’s index), and correlations with demographic characteristics were calculated. Results Neurofilament concentrations were significantly higher in MND compared to MMN (p < 0.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman’s rho 0.68, p < 0.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were ≥ 44.15 pg/mL (serum NfL) and ≥ 715.5 pg/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease. Conclusion Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis.

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Section: Discussionsupporting

confidence: 80%

Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy

Wohnrade,

Seeliger,

Gingele

et al. 2024

J Neurol

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Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study

Dai

Sun

et al. 2023

Brain and Behavior

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Background: Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) were two major motor neuron diseases with similar symptoms and poor outcomes.This study aimed to identify potential biomarkers in disease monitoring and differential diagnosis of adult SMA patients with sporadic ALS patients. Methods:This was a pilot study with ten adult SMA patients and ten ALS patients consecutively enrolled during hospitalization. Serum and cerebrospinal fluid (CSF) samples were collected for assessment of neurofilament light (NFL) and phosphorylated neurofilament heavy chain (pNFH). Serum creatine kinase (CK) and creatinine (Cr) were also compared between groups. The receiver operating characteristic (ROC) curves were used to identify differentiated values among ALS and SMA patients.Results: Serum Cr, CSF NFL, and CSF pNFH levels of ALS patients were significantly higher than those of the adult SMA patients (p < .01). Serum CK and Cr were strongly correlated with baseline ALSFRS-R scores in SMA patients (p < .001). The ROC curves revealed an area under the curve (AUC) of 0.94 in serum Cr with a cut-off value of 44.5 µmol/L (Sensitivity 90%, Specificity 90%). AUC from the ROC curve of CSF NFL and CSF pNFH were 1.0 and 0.84, with cut-off values of 1275 pg/mL and 0.395 ng/mL, respectively (Sensitivity and Specificity of 100% and 100% in CSF NFL; Sensitivity and Specificity of 90% and 80% in CSF pNFH). Conclusion:CSF NFL and pNFH might be useful biomarkers for differential diagnosis of adult SMA and ALS.

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The dynamic of changes of pNFH levels in the CSF compared with the motor scales’ scores during three years of nusinersen treatment in children with spinal muscular atrophy types 2 and 3

Badina,

Sporea,

Bejan

et al. 2024

Balneo and PRM Research Journal

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Neurofilaments are crucial in neuronal cytoskeleton formation, influencing axonal growth and impulse modulation. This study focuses on understanding the dynamics of the phos-phorylated neurofilament heavy subunit (pNFH) in pediatric spinal muscular atrophy (SMA) pa-tients undergoing Nusinersen treatment. The presence of five neurofilament types, particularly pNFH, is explored as a potential biomarker. SMA, an autosomal recessive disease impacting motor neurons, is characterized by disease severity linked to the number of SMN2 gene copies. Approved drugs, including Nusinersen, have demonstrated efficacy in enhancing motor activity. Methods: A retrospective analysis was conducted on 18 pediatric SMA patients treated with Nusinersen from October 2018 to July 2023. Cerebrospinal fluid (CSF) samples were utilized to assess pNFH levels. Motor scales were employed to evaluate performance, focusing on patients with varying SMN2 gene copies. Results: Following the initiation of Nusinersen treatment, a substantial decrease in pNFH levels was observed in CSF samples. Motor scales indicated improved performance, partic-ularly in patients with more SMN2 copies. However, the correlation between pNFH levels and motor improvement was not strongly evident, suggesting a limited role as a prognostic indicator within this timeframe. Conclusion: Nusinersen effectively reduced pNFH levels in pediatric SMA patients, showcasing promising outcomes in motor function. However, the predictive value of pNFH remains inconclusive, emphasizing the need for further research. Study limitations, including the rarity of SMA, the absence of a control group, and the disease's dynamic nature over time, should be considered when interpreting these findings.

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Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study

Cited by 4 publications

References 40 publications

Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy

Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy

Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study

The dynamic of changes of pNFH levels in the CSF compared with the motor scales’ scores during three years of nusinersen treatment in children with spinal muscular atrophy types 2 and 3

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