Changes in Retinal OCT and Their Correlations with Neurological Disability in Early ALS Patients, a Follow-Up Study

Background: To compare early visual changes in amyotrophic lateral sclerosis (ALS) patients with healthy controls in a baseline exploration, to follow-up the patients after 6 months, and to correlate these visual changes with neurological disability. Methods: All patients underwent a comprehensive neurological and ophthalmological examination. A linear mixed analysis and Bonferroni p-value correction were performed, testing four comparisons as follows: Control baseline vs. control follow-up, control baseline vs. ALS baseline, control follow-up vs. ALS follow-up, and ALS baseline vs. ALS follow-up. Results: The mean time from the diagnosis was 10.80 ± 5.5 months. The analysis of the optical coherence tomography (OCT) showed: (1) In ALS baseline vs. control baseline, a macular significantly increased thickness of the inner macular ring temporal and inferior areas; (2) in ALS follow-up vs. ALS baseline, a significant macular thinning in the inner and outer macular ring inferior areas; (3) in ALS follow-up vs. ALS baseline, a significant peripapillary retinal nerve fiber layer (pRNFL) thinning in the superior and inferior quadrants; and (4) ALS patients showed a moderate correlation between some OCT pRNFL parameters and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Conclusion: The OCT showed retinal changes in patients with motoneuron disease and could serve as a complementary tool for studying ALS.

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Prognosis of amyotrophic lateral sclerosis with cognitive and behavioural changes based on a sixty-month longitudinal follow-up

PLoS ONE ◽

10.1371/journal.pone.0253279 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0253279

Author(s):

Shan Ye ◽

Pingping Jin ◽

Lu Chen ◽

Nan Zhang ◽

Dongsheng Fan

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Survival Time ◽

Progression Rate ◽

Behavioural Changes ◽

Significant Difference ◽

Long Term Follow Up ◽

Behaviour Changes ◽

Als Patients ◽

Lateral Sclerosis

Objective Approximately 50% of amyotrophic lateral sclerosis (ALS) patients have cognitive and behavioural dysfunction in varying degrees and forms. Previous studies have shown that cognitive and behavioural changes may indicate a poor prognosis, and cognitive function gradually deteriorates over the course of disease, but the results of different studies have been inconsistent. In addition, there are relatively limited long-term follow-up studies tracking death as an endpoint. The purpose of this study was to investigate the clinical prognostic characteristics of ALS patients with cognitive behavioural changes through long-term follow-up in a cohort. Methods A total of 87 ALS patients from 2014 to 2015 in the Third Hospital of Peking University were selected and divided into a pure ALS group, an ALS with behavioural variant of frontotemporal dementia (ALS-bvFTD) group, and an ALS with cognitive and behaviour changes group. All patients were followed up for 60 months. The main end point was death and tracheotomy. Results There was no significant difference in survival curve between pure ALS and ALS with cognitive and behavioural change group, but the survival time of ALS-bvFTD group was significantly lower than the other two groups (P < 0.001). For those who was followed up to the endpoint, the survival time of the ALS-bvFTD group was significantly shorter than that of the pure ALS group (t = 5.33, p < 0.001) or the ALS with cognitive and behaviour changes group (t = 4.25, p < 0.001). The progression rate of ALS Functional Rating Scale–Revised (FRS-R) scores from recruitment to endpoint was significantly faster in the ALS-bvFTD group than in the pure ALS group (z = 2.68, p = 0.01) or the ALS with cognitive and behavioural changes group (z = 2.75, p = 0.01). There was no significant difference in survival time (t = 0.52, P = 0.60) or FRS-R score progression rate (z = 0.31, p = 0.76) between the pure ALS group and the ALS with cognitive and behavioural changes group. The total Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) score was positively correlated with survival time (r = 0.38, p = 0.01). Conclusion ALS-bvFTD patients have shorter survival time. The total ECAS score may be correlated with survival time.

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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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Ocular Involvement in Friedreich Ataxia Patients and Its Relationship with Neurological Disability, a Follow-Up Study

Diagnostics ◽

10.3390/diagnostics10020075 ◽

2020 ◽

Vol 10 (2) ◽

pp. 75

Author(s):

Pilar Rojas ◽

Ana I. Ramírez ◽

Rosa de Hoz ◽

Manuel Cadena ◽

Antonio Ferreras ◽

...

Keyword(s):

Friedreich Ataxia ◽

P Value ◽

Ocular Involvement ◽

Ganglion Cell Complex ◽

Optic Coherence Tomography ◽

Fiber Layer ◽

Neurological Disability ◽

Follow Up Study ◽

Best Parameter

Background: This study compared functional and structural visual changes in Friedreich ataxia (FRDA) patients with healthy controls (HC) and correlated these changes with neurological disability. Methods: Eight FRDA Spanish patients and eight HC were selected from 2014 to 2018. Best corrected visual acuity (BCVA), visual field (VF), optic coherence tomography (OCT), and neurological disability measured by “scale for the assessment and rating of ataxia” (SARA) were taken in a basal exploration and repeated after 6 months. A linear mixed analysis and Bonferroni p-value correction were performed. Results: FRDA baseline and follow-up patients showed statistically significant decreases in BCVA, VF, and OCT parameters compared with the HC. Some of the VF measurements and most of the OCT parameters had an inverse mild-to-strong correlation with SARA. Moreover, the analysis of the ROC curve demonstrated that the peripapillary retinal nerve fiber layer (pRNFL) average thickness was the best parameter to discriminate between FRDA patients and HC. Conclusions: The follow-up study showed a progression in OCT parameters. Findings showed a sequential effect in pRNFL, ganglion cell complex (GCC), and macula. The VF and the OCT could be useful biomarkers in FRDA, both for their correlation with neurological disease as well as for their ability to evaluate disease progression.

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Impact of Percutaneous Endoscopic Gastrostomy (PEG) on the Evolution of Disease in Patients with Amyotrophic Lateral Sclerosis (ALS)

Nutrients ◽

10.3390/nu13082765 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2765

Author(s):

Juan J. López-Gómez ◽

María D. Ballesteros-Pomar ◽

Beatriz Torres-Torres ◽

Begoña Pintor-De la Maza ◽

María A. Penacho-Lázaro ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Percutaneous Endoscopic Gastrostomy ◽

Anthropometric Parameters ◽

Endoscopic Gastrostomy ◽

Frequent Event ◽

The Mean ◽

Als Patients ◽

Prevalent Symptom ◽

Lateral Sclerosis

Dysphagia is a highly prevalent symptom in Amyotrophic Lateral Sclerosis (ALS), and the implantation of a percutaneous endoscopic gastrostomy (PEG) is a very frequent event. The aim of this study was to evaluate the influence of PEG implantation on survival and complications in ALS. An interhospital registry of patients with ALS of six hospitals in the Castilla-León region (Spain) was created between January 2015 and December 2017. The data were compared for those in whom a PEG was implanted and those who it was not. A total of 93 patients were analyzed. The mean age of the patients was 64.63 (17.67) years. A total of 38 patients (38.8%) had a PEG implantation. An improvement in the anthropometric parameters was observed among patients who had a PEG from the beginning of nutritional follow-up compared to those who did not, both in BMI (kg/m2) (PEG: 0 months, 22.06; 6 months, 23.04; p < 0.01; NoPEG: 0 months, 24.59–23.87; p > 0.05). Among the deceased patients, 38 (40.4%) those who had an implanted PEG (20 patients (52.6%) had a longer survival time (PEG: 23 (15–35.5) months; NoPEG 11 (4.75–18.5) months; p = 0.01). A PEG showed a survival benefit among ALS patients. Early implantation of a PEG produced a reduction in admissions associated with complications derived from it.

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γ' Fibrinogen as a Predictor of Survival in Amyotrophic Lateral Sclerosis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.715842 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ana Catarina Pronto-Laborinho ◽

Catarina S. Lopes ◽

Vasco A. Conceição ◽

Marta Gromicho ◽

Nuno C. Santos ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Positive Impact ◽

Enzyme Linked Immunosorbent Assay ◽

Fibrinogen Concentration ◽

Respiratory Impairment ◽

Increased Risk ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder related to neuroinflammation that is associated with increased risk of thrombosis. We aimed to evaluate γ' fibrinogen plasma level (an in vivo variant of fibrinogen) as a biomarker in ALS, and to test its role as a predictor of disease progression and survival. Sixty-seven consecutive patients with ALS were followed and the results were compared with those from 82 healthy blood donors. Patients were clinically evaluated at the time of blood sampling and on follow-up (every 3 months for the beginning of the follow-up until death) by applying the revised ALS Functional Rating Scale. Human plasma γ' fibrinogen concentration was quantified using a specific two-site sandwich kit enzyme-linked immunosorbent assay. We found, for the first time, a positive association between γ' fibrinogen concentration and survival in ALS patients: patients with higher γ' fibrinogen plasma levels survived longer, and this finding was not influenced by confounders such as age, gender, respiratory impairment, or functionality (ALSFRS-R score). Since increased levels have a positive impact on outcome, this novel biomarker should be further investigated 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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