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

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.

Correlation of weight and body composition with disease progression rate in patients with amyotrophic lateral sclerosis.

This study aims to observe the nutritional status of Chinese patients with amyotrophic lateral sclerosis (ALS), further investigating its effect on disease progression. One hundred consecutive newly diagnosed ALS patients and fifty controls were included. Weight and body composition were measured by bioelectrical impedance analysis at baseline and follow-ups. The revised ALS functional rating scale (ALSFRS-R) was used to calculate the rate of disease progression. Patients with ALS had a significantly lower BMI than controls, while no significant difference was found in body composition. Weight loss occurred in 66 (66%) and 52 (67.5%) patients at diagnosis and follow-up, respectively. Patients with significant weight loss (≥ 5%) at diagnosis had significantly lower BMI, fat mass (FM), and FM in limbs and trunk than those without. Fat-free mass (FFM), FM, and FM in limbs were significantly decreased along with weight loss at follow-up (p < 0.01). Patients with lower visceral fat index, lower proportion of FM, and higher proportion of muscle mass at baseline progressed rapidly during follow-ups (p < 0.05). Multivariate linear regression showed that FFM and weight at follow-up were independently correlated with disease progression rate at follow-up (p < 0.05). Weight loss is a common feature in ALS patients, along with muscle and fat wasting during the disease course. Body composition may serve as a prognostic factor and provide guidance for nutritional management in ALS patients.

Alterations in metabolic biomarkers and their potential role in amyotrophic lateral sclerosis.

BACKGROUND: Metabolic dysfunction has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the potential role of metabolic biomarkers in the progression of ALS and understand the possible metabolic mechanisms. METHODS: Fifty-two patients with ALS and 24 normal controls were included, and blood samples were collected for analysis of metabolic biomarkers. Basal anthropometric measures, including body composition and clinical features, were measured in ALS patients. The disease progression rate was calculated using the revised ALS functional rating scale (ALSFRS-R) during the 6-month follow-up. RESULTS: ALS patients had higher levels of adipokines (adiponectin, adipsin, resistin, and visfatin) and other metabolic biomarkers [C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide, and plasminogen activator inhibitor type 1] than controls. Leptin levels in serum were positively correlated with body mass index, body fat, and visceral fat index (VFI). Adiponectin was positively correlated with the VFI and showed a positive correlation with the ALSFRS-R and a negative correlation with baseline disease progression. Patients with lower body fat, VFI, and fat in limbs showed faster disease progression during follow-ups. Lower leptin and adiponectin levels were correlated with faster disease progression. After adjusting for confounders, lower adiponectin levels and higher visfatin levels were independently correlated with faster disease progression. INTERPRETATION: The current study found altered levels of metabolic biomarkers in ALS patients, which may play a role in ALS pathogenesis. Adiponectin and visfatin represent potential biomarkers for prediction of disease progression in ALS.

Clinical characteristics and prognosis of amyotrophic lateral sclerosis with autoimmune diseases.

INTRODUCTION: The occurrence of autoimmune diseases (AIDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported, but little is known about the associated clinical phenotype. This study aims to evaluate the clinical features and prognosis of ALS patients with AID. METHODS: This retrospective study was based on the ALS Registry dataset of Peking Union Medical College Hospital from 2013 to 2020. Clinical features and inflammatory biomarkers at registration were compared between ALS patients with coexisting AIDs and those without (controls). The medical records of immunotherapy were also collected. The Kaplan-Meier method and Cox proportional hazard model were used to study the survival of ALS patients. RESULTS: There are 26 (1.6%) ALS patients with AIDs in our database. The ALS patients with AIDs had older ages at onset and poorer respiratory function than controls (p<0.05). After propensity score matching by sex, onset age, and disease duration, the difference in respiratory function remained significant between groups. We found no differences in overall survival between ALS patients with and without AIDs before and after matching (p = 0.836; p = 0.395). Older age at onset, rapid disease progression, and lower erythrocyte sedimentation rate (ESR) were associated with shorter survival (p<0.05). Among ALS patients with AIDs, 8 (30.8%) had a history of immunotherapy and showed slightly prolonged survival compared with those without immunotherapy, but the results did not reach statistical significance (p = 0.355). CONCLUSIONS: Patients with coexisting ALS and AIDs had older onset age and poorer respiratory function but similar overall survival than those with pure ALS.

Blood-brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia.

OBJECTIVE: We aim to investigate blood-brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD) and further determine the effect of these factors on the survival of ALS. METHODS: This was a retrospective study of 113 ALS patients, 12 ALS-FTD patients, and 40 disease controls hospitalized between September 2013 and October 2020. CSF parameters including total protein (TP), albumin (Alb), immunoglobulin-G (IgG), and MBP were collected and compared between groups. The CSF-TP, CSF-Alb, CSF-IgG, and CSF/serum quotients of Alb and IgG (QAlb, QIgG) were used to reflect the BBB status. Patients were followed up until December 2020. Cox regression and Kaplan-Meier method were used for survival analysis. RESULTS: The CSF-TP, CSF-Alb, and CSF-IgG concentrations were significantly higher in patients than controls (p < 0.01). Increased CSF-TP and CSF-IgG was found in 45 (39.8%) and 27 (23.9%) ALS patients, while in 7 (58.3%) and 5 (41.7%) ALS-FTD patients. The level of CSF-Alb, CSF-IgG, and CSF-MBP were significantly higher in patients with ALS-FTD than ALS. MBP showed a moderate accuracy in the distinction between ALS-FTD and ALS (AUC = 0.715 ± 0.101). No difference in MBP was found between patients and controls. Kaplan-Meier analysis indicated that a higher CSF-TP, CSF-IgG, QIgG, or QAlb was significantly associated with shorter survival. Cox regression model showed that CSF-TP, CSF-IgG, and QIgG were independent predictors of survival. CONCLUSION: Our findings suggested that BBB dysfunction was more prominent in ALS-FTD than ALS and associated with a worse prognosis. Further studies are needed to determine the role of CSF-MBP as a biomarker in ALS.

Monitoring Value of Multimodal Magnetic Resonance Imaging in Disease Progression of Amyotrophic Lateral Sclerosis: A Prospective Observational Study.

BACKGROUND: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. METHODS: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. RESULTS: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. CONCLUSION: Multimodal MRI could be used to monitor short-term brain changes in ALS patients.

The correlation between white matter hyperintensity and balance disorder and fall risk: An observational, prospective cohort study.

OBJECTIVE: The presence of an association between white matter hyperintensity (WMH) and the risk of falls in older people is uncertain, with little supporting prospective evidence available at present. We aimed to determine whether WMH was associated with dysfunctions of balance and gait, and other sensorimotor factors leading to falls, and the independent factors related to falls in older Chinese people. The protective effect of exercise against falls was also addressed. METHODS: In a representative sample of hospital-based individuals aged 50 years and older in China, the patients' history of falls, magnetic resonance imaging data, scores on the 9-item Berg Balance Scale (BBS-9) test and timed up-and-go test (TUGT), and sensorimotor measures of computerized dynamic posturography (CDP) were analyzed. Incident falls were recorded prospectively over a 12-month period. Using regression modeling, the association between the risk of falls and baseline WMH was estimated. RESULTS: Only individuals with severe WMH were at an increased risk of falls, and CDP was more sensitive than BBS-9 in detecting WMH-related balance and gait dysfunction. However, WMH was not an independent predictor of falls. Taller height and overweight or obese body habitus were identified as novel protective factors for falls. Female, fall history, and increased TUGT score were identified as independent risk factors for falls in older Chinese people. CONCLUSION: Although WMH was associated with an increased risk of falls, it was not an independent predictor.