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

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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TDP-43–specific Autoantibody Decline in Patients With Amyotrophic Lateral Sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000937 ◽

2020 ◽

Vol 8 (2) ◽

pp. e937

Author(s):

Anne Kallehauge Nielsen ◽

Jonas Folke ◽

Sylwia Owczarek ◽

Kirsten Svenstrup ◽

Kristian Winge ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Disease Duration ◽

Rating Scale ◽

High Avidity ◽

Naturally Occurring ◽

Specific Autoantibody ◽

Normal Controls ◽

Lateral Sclerosis ◽

Isotype Igg1

ObjectiveWe hypothesize alterations in the quality and quantity of anti–43-kDa TAR DNA-binding protein (TDP-43) naturally occurring autoantibodies (NAbs) in patients with amyotrophic lateral sclerosis (ALS); therefore, we assessed relative binding properties of anti–TDP-43 NAbs composite in plasma from patients with ALS in comparison with healthy individuals.MethodsELISA competition assay was used to explore the apparent avidity/affinity of anti–TDP-43 NAbs in plasma from 51 normal controls and 30 patients with ALS. Furthermore, the relative levels of anti–TDP-43 NAbs within the immunoglobulin (Ig) classes of IgG (isotype IgG1-4) and IgMs were measured using classical indirect ELISA. The occurring results were hereafter correlated with the measures of disease duration and disease progression.ResultsHigh-avidity/affinity anti–TDP-43 NAbs levels were significantly reduced in plasma samples from patients with ALS. In addition, a significant decrease in relative levels of anti–TDP-43 IgG3 and IgM NAbs and a significant increase in anti–TDP-43 IgG4 NAbs were observed in ALS plasma vs controls. Furthermore, a decrease in global IgM and an increase in IgG4 levels were observed in ALS. These aberrations of humoral immunity correlated with disease duration, but did not correlate with ALS Functional Rating Scale–Revised scores.ConclusionsOur results may suggest TDP-43–specific immune aberrations in patients with ALS. The skewed immune profiles observed in patients with ALS could indicate a deficiency in the clearance capacity and/or blocking of TDP-43 transmission and propagation. The decrease in levels of high affinity/avidity anti-TDP-43 NAbs and IgMs correlates with disease progression and may be disease predictors.

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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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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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Amygdala Abnormalities Are Related to Anxiety in Patients With Sporadic Amyotrophic Lateral Sclerosis

10.21203/rs.3.rs-773227/v1 ◽

2021 ◽

Author(s):

Shuangwu Liu ◽

yuying zhao ◽

qingguo ren ◽

gaolang gong ◽

dong zhang ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Resting State ◽

Rating Scale ◽

Clinical Staging ◽

Bonferroni Correction ◽

Basal Nucleus ◽

Amygdala Volume ◽

Als Patients ◽

Disease Stages ◽

Lateral Sclerosis

Abstract To explore selective atrophy patterns and resting-state functional connection (FC) alterations in the amygdala at different stages of amyotrophic lateral sclerosis (ALS), and to determine any correlations between amygdala abnormalities and neuropsychiatric symptoms. We used the King’s clinical staging system for ALS to divide 83 consecutive patients with ALS into comparable subgroups at different disease stages. We investigated the pattern of selective amygdala subnucleus atrophy and analysed amygdala-based whole-brain FC analysis in the patients and 94 healthy controls (HCs). Cognitive and emotional functions were also evaluated using a neuropsychological test battery. There were no significant differences between King’s stage 1 ALS patients and HCs for any amygdala subnucleus volumes. Compared with HCs, King’s stage 2 patients had significantly lower left accessory basal nucleus and cortico-amygdaloid transition volumes after Bonferroni correction. Furthermore, after Bonferroni correction, King’s stage 3 patients demonstrated significant reductions in most subnucleus volumes as well as global amygdala volume compared with HCs. Notably, amygdala-based resting-state FC was unaltered in ALS patients until King’s stage 3. Specific subnucleus volumes were significantly associated with Mini-Mental State Examination scores and Hamilton Anxiety Rating Scale scores in ALS patients. In conclusions, our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed across King’s clinical disease stages, and our findings suggest that amygdala abnormalities are an important feature of patients with ALS. Moreover, amygdala volume may play an important role in anxiety and cognitive dysfunction in ALS patients.

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How COVID-19 pandemic changed our management strategies for amyotrophic lateral sclerosis (ALS) patients: Egyptian study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00331-2 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Hebatallah R. Rashed

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

North Africa ◽

Rating Scale ◽

Management Strategies ◽

Office Visits ◽

Bulbar Onset ◽

A Prospective Study ◽

Als Patients ◽

Lateral Sclerosis

Abstract Background There are several studies that have discussed the efficacy of telemedicine with amyotrophic lateral sclerosis (ALS) patients; however, this approach is still preliminary in Egypt and in North Africa. The objective of the current study is to discuss current experience with telemedicine in monitoring patients in the specialized ALS clinic in Egypt. Efficacy of Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in monitoring disease progression remotely will be discussed. Results This is a prospective study. Forty-three ALS patients were included in this study in the period between July 1, 2020, and February 6, 2021. Fifty-three telemedicine encounters and 13 post-telemedicine office visits were available. None of the participating patients had COVID-19 infection. Eight patients showed decline in ALSFRS score. ALSFRS-R score reported during telemedicine encounters was confirmed during office visits. Three bulbar onset ALS patients had gastrostomy, and 2 bulbar onset ALS patients had Botox injection for drooling. All eight patients with declining ALSFRS-R were maintained on non-invasive ventilation (NIV) based on their symptoms. Conclusion This is the first study discussing telemedicine in the field of ALS in Egypt and North Africa. ALSFRS-R showed feasibility and reliability in detecting disease progression remotely.

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Open Randomized Clinical Trial on JWSJZ Decoction for the Treatment of ALS Patients

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/347525 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Weidong Pan ◽

Xiaojing Su ◽

Jie Bao ◽

Jun Wang ◽

Jin Zhu ◽

...

Keyword(s):

Clinical Trial ◽

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Control Group ◽

Efficacy And Safety ◽

Significant Difference ◽

Als Patients ◽

And Control ◽

Lateral Sclerosis ◽

Basic Treatment

Objective. To investigate the efficacy and safety of the traditional Chinese medicine Jiawei Sijunzi (JWSJZ) decoction for the treatment of patients with amyotrophic lateral sclerosis (ALS).Methods. Forty-eight patients with ALS were divided into a JWSJZ group (n=24) and a control group (n=24) using a randomized number method. Together with the basic treatment for ALS, JWSJZ decoction was added to the treatment regimen of patients in the JWSJZ group or Riluzole was administered to the control group for 6 months. Neurologists evaluated the treated and control patients using the ALS functional rating scale (ALSFRS) before, 3 and 6 months after starting the additional treatments.Results. The ALSFRS scores in both groups were lower 3 and 6 months after treatment than before. There was a significant difference at 6 months after treatment between the subgroups of patients with ALS whose limbs were the initial site of attack. No serious adverse effects were observed in the JWSJZ group.Conclusion. JWSJZ decoction may be a safe treatment for ALS, and may have delayed the development of ALS, especially in the subgroup of patients in whom the limbs were attacked first when compared with Riluzole treatment.

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

Brain Sciences ◽

10.3390/brainsci9120337 ◽

2019 ◽

Vol 9 (12) ◽

pp. 337 ◽

Cited By ~ 5

Author(s):

Pilar Rojas ◽

Rosa de Hoz ◽

Ana I. Ramírez ◽

Antonio Ferreras ◽

Elena Salobrar-Garcia ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

P Value ◽

Ophthalmological Examination ◽

Fiber Layer ◽

Neurological Disability ◽

Als Patients ◽

Lateral Sclerosis ◽

Visual Changes

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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