Association between nutritional status and disease severity using the amyotrophic lateral sclerosis (ALS) functional rating scale in ALS patients

Purpose: Static and dynamic analyses for identifying functional connectivity (FC) have demonstrated brain dysfunctions in amyotrophic lateral sclerosis (ALS). However, few studies on the stability of dynamic FC have been conducted among ALS patients. This study explored the change of functional stability in ALS and how it correlates with disease severity.Methods: We gathered resting-state functional magnetic resonance data from 20 patients with ALS and 22 healthy controls (HCs). The disease severity was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). We used a sliding window correlation approach to identify dynamic FC and measured the concordance of dynamic FC over time to obtain the functional stability of each voxel. We assessed the between-group difference in functional stability by voxel-wise two-sample t-test. The correlation between the functional stability index and ALSFRS-R in ALS patients was evaluated using Spearman's correlation analysis.Results: Compared with the HC group, the ALS group had significantly increased functional stability in the left pre-central and post-central gyrus and right temporal pole while decreased functional stability in the right middle and inferior frontal gyrus. The results revealed a significant correlation between ALSFRS-R and the mean functional stability in the right temporal pole (r = −0.452 and P = 0.046) in the ALS patients.Conclusions: ALS patients have abnormal stability of brain functional architecture, which is associated with the severity of the disease.

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Informal Caregiving in Amyotrophic Lateral Sclerosis (ALS): A High Caregiver Burden and Drastic Consequences on Caregivers’ Lives

Brain Sciences ◽

10.3390/brainsci11060748 ◽

2021 ◽

Vol 11 (6) ◽

pp. 748

Author(s):

Pavel Schischlevskij ◽

Isabell Cordts ◽

René Günther ◽

Benjamin Stolte ◽

Daniel Zeller ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Functional Status ◽

Disease Severity ◽

Caregiver Burden ◽

Rating Scale ◽

Depression Scale ◽

Anxiety And Depression ◽

Daily Routine ◽

Work Lives ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.

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Errata: Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

Journal of Methods and Measurement in the Social Sciences ◽

10.2458/v1i2.12366 ◽

2011 ◽

Vol 1 (2) ◽

Author(s):

Melinda F. Davis ◽

Katalin H. Scherer ◽

Timothy M. Miller ◽

F. John Meaney

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Muscular Dystrophy ◽

Disease Severity ◽

Muscle Weakness ◽

Respiratory Function ◽

Rating Scale ◽

Becker Muscular Dystrophy ◽

Progressive Muscle Weakness ◽

Lateral Sclerosis ◽

Disease Specific

Reports an error in Davis et al. (2010). The functional motor scale used in Davis et al. (2010) was the EK (Egen Klassifikation) Scale, rather than the Amyotrophic Lateral Sclerosis Functional Rating Scale (Steffensen et al., 2002; Cedarbaum & Stambler, 1997). Both scales are 10-item, disease-specific measures that assess mobility and respiratory function in individuals with progressive muscle weakness. This error does not change the conclusions. DOI:10.2458/azu_jmmss_v1i2_davis

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Altered Metabolic Profiles of the Plasma of Patients with Amyotrophic Lateral Sclerosis

Biomedicines ◽

10.3390/biomedicines9121944 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1944

Author(s):

Kuo-Hsuan Chang ◽

Chia-Ni Lin ◽

Chiung-Mei Chen ◽

Rong-Kuo Lyu ◽

Chun-Che Chu ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Area Under The Curve ◽

Support Vector ◽

Therapeutic Effects ◽

Targeted Metabolomics ◽

Svm Algorithm ◽

Als Patients ◽

Normal Controls ◽

Lateral Sclerosis

Currently, there is no objective biomarker to indicate disease progression and monitor therapeutic effects for amyotrophic lateral sclerosis (ALS). This study aimed to identify plasma biomarkers for ALS using a targeted metabolomics approach. Plasma levels of 185 metabolites in 36 ALS patients and 36 age- and sex-matched normal controls (NCs) were quantified using an assay combining liquid chromatography with tandem mass spectrometry and direct flow injection. Identified candidates were correlated with the scores of the revised ALS Functional Rating Scale (ALSFRS-r). Support vector machine (SVM) learning applied to selected metabolites was used to differentiate ALS and NC subjects. Forty-four metabolites differed significantly between ALS and NC subjects. Significant correlations with ALSFRS-r score were seen in 23 metabolites. Six of them showing potential to distinguish ALS from NC—asymmetric dimethylarginine (area under the curve (AUC): 0.829), creatinine (AUC: 0.803), methionine (AUC: 0.767), PC-acyl-alkyl C34:2 (AUC: 0.808), C34:2 (AUC: 0.763), and PC-acyl-acyl C42:2 (AUC: 0.751)—were selected for machine learning. The SVM algorithm using selected metabolites achieved good performance, with an AUC of 0.945. In conclusion, our findings indicate that a panel of metabolites were correlated with disease severity of ALS, which could be potential biomarkers for monitoring ALS progression and therapeutic effects.

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Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis

Acta Neurologica Belgica ◽

10.1007/s13760-020-01531-y ◽

2020 ◽

Author(s):

Cezar Thomas Suratos ◽

Naoko Takamatsu ◽

Hiroki Yamazaki ◽

Yusuke Osaki ◽

Tatsuya Fukumoto ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Phrenic Nerve ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Pulmonary Function Tests ◽

Cross Sectional ◽

The Right ◽

Als Patients ◽

Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons causing progressive weakness. It eventually involves the diaphragm which leads to respiratory paralysis and subsequently death. Phrenic nerve (PN) conduction studies and diaphragm ultrasound has been studied and correlated with pulmonary function tests in ALS patients. However, PN ultrasonography has not been employed in ALS. This study aims to sonographically evaluate the morphologic appearance of the PN of ALS patients. Thirty-eight ALS patients and 28 normal controls referred to the neurophysiology laboratory of two institutions were retrospectively included in the study. Baseline demographic and clinical variables such as disease duration, ALS Functional Rating Scale-Revised score, and ALS region of onset were collected. Ultrasound was used to evaluate the PN cross-sectional area (CSA) of ALS and control subjects. The mean PN CSA of ALS patients were 1.08 ± 0.39 mm on the right and 1.02 ± 0.34 mm on the left. The PN CSA of ALS patients were significantly decreased compared to controls (p value < 0.00001). The PN CSA of ALS patients was not correlated to any of the demographic and clinical parameters tested. This study demonstrates that ALS patients have a smaller PN size compared to controls using ultrasonography.

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Creatine Kinase and Progression Rate in Amyotrophic Lateral Sclerosis

Cells ◽

10.3390/cells9051174 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1174 ◽

Cited By ~ 1

Author(s):

Marco Ceccanti ◽

Valeria Pozzilli ◽

Chiara Cambieri ◽

Laura Libonati ◽

Emanuela Onesti ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Axonal Damage ◽

Mouse Strains ◽

Disease Rate ◽

Progression Rate ◽

Predisposing Factor ◽

Slow Progressors ◽

Als Patients ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no recognized clinical prognostic factor. Creatinine kinase (CK) increase in these patients is already described with conflicting results on prognosis and survival. In 126 ALS patients who were fast or slow disease progressors, CK levels were assayed for 16 months every 4 months in an observational case-control cohort study with prospective data collection conducted in Italy. CK was also measured at baseline in 88 CIDP patients with secondary axonal damage and in two mouse strains (129SvHSD and C57-BL) carrying the same SOD1G93A transgene expression but showing a fast (129Sv-SOD1G93A) and slow (C57-SOD1G93A) ALS progression rate. Higher CK was found in ALS slow progressors compared to fast progressors in T1, T2, T3, and T4, with a correlation with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores. Higher CK was found in spinal compared to bulbar-onset patients. Transgenic and non-transgenic C57BL mice showed higher CK levels compared to 129SvHSD strain. At baseline mean CK was higher in ALS compared to CIDP. CK can predict the disease progression, with slow progressors associated with higher levels and fast progressors to lower levels, in both ALS patients and mice. CK is higher in ALS patients compared to patients with CIDP with secondary axonal damage; the higher levels of CK in slow progressors patients, but also in C57BL transgenic and non-transgenic mice designs CK as a predisposing factor for disease rate progression.

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Functional and Endoscopic Indicators for Percutaneous Endoscopic Gastrostomy (PEG) in Amyotrophic Lateral Sclerosis Patients

Journal of Clinical Medicine ◽

10.3390/jcm7100352 ◽

2018 ◽

Vol 7 (10) ◽

pp. 352 ◽

Cited By ~ 3

Author(s):

Bebiana Conde ◽

Natália Martins ◽

Inês Rodrigues ◽

Ana Pimenta ◽

João Winck

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Ventilatory Support ◽

Functional Evaluation ◽

Oral Nutrition ◽

Additional Information ◽

Endoscopic Gastrostomy ◽

Discriminant Ability ◽

Als Patients ◽

Lateral Sclerosis

(1) Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition, whose bulbar involvement compromises language, swallowing, and airway protection. When oral nutrition is no longer adequate, percutaneous endoscopic gastroscopy (PEG) may be indicated. However, as exact timing is still debatable, we tried to find it. (2) Methods: A prospective cohort study was performed using fiber-optic endoscopic evaluation of swallowing (FEES), functional evaluation scales (ALS Functional Rating Scale-Revised (ALSFRS-R) and bulbar sub-score (ALSFRS-R-B)), lung function tests (like Forced Vital Capacity (FVC), Cough Peak Flow (CPF)) and anthropometric data. (3) Results: Twenty-three patients were enrolled (mean 65.4 ± 9.1 years, 60.9% males), 12 with spinal-onset. During the study period, 58 FEES were performed (1–4/patients). Even before formal the PEG indication, suggestions were given to correct the alterations found. PEG was placed in 12 patients, on average 21.8 months after diagnosis (FVC = 69.9% ± 26.7%, ALSFRS-R-B = 7.7 ± 3.7, ALSFRS-R = 28.9 ± 12.3), and being 91.7% under ventilatory support. ALSFRS-R-B, CPF, FVC, and ALSFRS-R showed significant discriminant ability for PEG placement. Sensitivity and specificity were, respectively, ALSFRS-R-B ≤ 8 (100/90.9), CPF ≤ 205 (83.3), FVC ≤ 74 (83.3/74.2), and ALSFRS-R < 29 (83.3/65.1). (4) Conclusions: FEES provide additional information beyond formal PEG indication. ALSFRS-R-B score ≤ 8 was found as a best functional and noninvasive indicator for PEG performance in ALS patients.

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Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Frontiers in Neuroscience ◽

10.3389/fnins.2021.675444 ◽

2021 ◽

Vol 15 ◽

Author(s):

Haining Li ◽

Qiuli Zhang ◽

Qianqian Duan ◽

Jiaoting Jin ◽

Fangfang Hu ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Correlation Analysis ◽

Disease Severity ◽

Structural Changes ◽

Diffusion Tensor ◽

Healthy Controls ◽

Significant Difference ◽

Als Patients ◽

And Diffusion ◽

Lateral Sclerosis

IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

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The Evaluation of Pain with Nociceptive and Neuropathic Characteristics from Three Different Perspectives in Amyotrophic Lateral Sclerosis Patients: A Case Controlled Observational Study in Southwestern China

Neural Plasticity ◽

10.1155/2021/5537892 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Ran An ◽

Yan Li ◽

Xianghua He ◽

Cheng Li ◽

Xin Li ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Neuropathic Pain ◽

Disease Duration ◽

Rating Scale ◽

Nociceptive Pain ◽

Southwestern China ◽

Substantial Impact ◽

Als Patients ◽

Normal Controls ◽

Lateral Sclerosis

Background. Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods. Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results. 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) ( p = 0.193 ). DN4 score ⩾ 4 was found in three ALS patients and one control ( p = 0.480 ). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) ( p < 0.001 ) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain ( p = 0.041 , 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients’ mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions. Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients’ mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score ⩾ 4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

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An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosis post-mortem motor cortex and cerebrospinal fluid

10.1101/2020.12.30.20248944 ◽

2021 ◽

Author(s):

Tiziana Petrozziello ◽

Ana C. Amaral ◽

Simon Dujardin ◽

Sali M.K. Farhan ◽

James Chan ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Cortex ◽

Molecular Mechanisms ◽

Rating Scale ◽

Phosphorylated Tau ◽

Post Mortem ◽

Significant Difference ◽

Depth Analysis ◽

Als Patients ◽

Lateral Sclerosis

AbstractAlthough the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimer’s disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS.

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