Clinical Tests for Predicting Fallers Among Ambulatory Patients with Amyotrophic Lateral Sclerosis: A Preliminary Cohort Study

Regression Analysis ◽

Gait Speed ◽

Linear Regression Analysis ◽

Lower Limbs ◽

Outcome Variable ◽

Functional Reach Test ◽

Als Patients ◽

Lateral Sclerosis ◽

Ankle Dorsiflexors

Background: Few studies have examined falls and their predictors in patients with amyotrophic lateral sclerosis (ALS). Objective: The aim of this study was to survey fall incidence and to identify variables predicting the presence or absence of falls occurring within 3 months after discharge of patients with ALS from hospital. Methods: The following variables were evaluated in 14 patients with ALS: timed up and go test (TUG), functional reach test, 10-m comfortable gait speed, single-leg stance time, manual muscle test (MMT) scores for the lower limb, total modified Ashworth scale score for the lower limbs, fear of falling, and pull test score. The primary outcome variable was the occurrence of a fall within 3 months after discharge. The fall rate was calculated based on fall record forms. The specific circumstances of each fall were also recorded. Univariate and multiple regression analyses were used to identify fall predictors. Results: Seven of the 14 ALS patients (50%) experienced a fall within 3 months. Five fallers reported experiencing a fall that had caused injury, and three reported experiencing a fall that had required a hospital visit. Univariate logistic regression analysis identified TUG time, gait speed and MMT of the ankle dorsiflexors as factors associated with falls (p = 0.02–0.04). Multiple linear regression analysis of fall numbers identified age and TUG time as predictor models (p = 0.03). Conclusion: TUG time and MMT of ankle dorsiflexors may help predict falls in ALS patients. Validation studies in larger cohorts are needed.

Predictors of Depression in Caucasian Patients with Amyotrophic Lateral Sclerosis in Romania

Brain Sciences ◽

10.3390/brainsci10080470 ◽

2020 ◽

Vol 10 (8) ◽

pp. 470

Author(s):

Motataianu Anca ◽

Andone Sebastian ◽

Radu Cristina ◽

Bajko Zoltan ◽

Barcutean Laura ◽

...

Keyword(s):

Functional Disability ◽

Rating Scale ◽

Linear Regression Analysis ◽

Occupational Status ◽

Multiple Linear Regression Analysis ◽

Disease Evolution ◽

Prevalence Of Depression ◽

Als Patients ◽

Depression remains an underdiagnosed comorbidity which significantly decreases the quality of life in amyotrophic lateral sclerosis (ALS) patients. We aimed to investigate the prevalence of depression in a cohort of ALS patients with more than one year of disease evolution. A total of 50 ALS patients were evaluated with the Beck Depression Inventory II (BDI-II) and cognition, using the Mini-Cog Standardized Instrument (MCSI). The clinical disability was evaluated using the ALS Functional Rating Scale (ALSFRS). The prevalence of depression was 42.8%. A lower BDI-II score was significantly correlated with a higher education level, the spouse as a caregiver, spiritual devotion, and employment status (p < 0.05). A multiple linear regression analysis between the BDI-II score as the dependent variable and various independent variables such as spirituality, caregiver status, educational level, and occupational status revealed that only the type of caregiver (spouse or parent/child) significantly affected the BDI-II total score (p = 0.006). The functional disability significantly correlated with loss of appetite and loss of libido (p < 0.001). A high education, spiritual devotion, high ALSFRS, and the presence of the spouse as the caregiver were associated with the absence of depression.

Characterization of Fasciculation Potentials (FPs) in Amyotrophic Lateral Sclerosis (ALS) and Peripheral Nerve Hyperexcitability Syndromes (PNH)

BioMed Research International ◽

10.1155/2021/6631664 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Hua Wang ◽

Bin Liu ◽

Jiyou Tang

Keyword(s):

Peripheral Nerve ◽

Detection Rate ◽

Firing Frequency ◽

Lower Limbs ◽

Detection Rates ◽

Significant Difference ◽

Peripheral Nerve Hyperexcitability ◽

Als Patients ◽

This study is aimed at investigating the features of fasciculation potentials (FPs) in amyotrophic lateral sclerosis (ALS) and peripheral nerve hyperexcitability syndromes (PNH). Needle electrophysiologic examination (EMG) was performed for 5-15 muscles in the ALS and PNH patients. The spontaneous activity of fasciculations and fibrillations/sharp-waves (fibs-sw) was recorded. The distribution, firing frequency, and waveform parameters of FPs in muscles were calculated and compared. In total, 361 muscles in ALS patients and 124 muscles in PNH patients were examined, with the FP detection rates of 45.1% and 53.2%. Moreover, the ALS patients with the upper limb onset had the highest FP detection rate. Fasciculations occurred more frequently in the upper limbs than in the lower limbs in ALS and PNH. The detection rate of fibs-sw in the bulbar muscle was relatively low, which could be elevated when combining fibs-sw and FPs. Benign FPs in PNH were of smaller amplitude, shorter duration, and fewer phases/turns, compared with malignant FPs in ALS. The FP area in PNH was significantly smaller than that in ALS. The incidence of polyphasic FPs in ALS was distinctly greater than that in PNH. The firing frequency of FPs in PNH was higher than that in ALS. There was no significant difference in the amplitude, duration, phases and turns, and area of FPs between groups with and without fibs-sw in the muscles of normal strength in ALS. Conclusively, it is necessary to detect the FPs in the thoracic and bulbar muscles of patients suspected having ALS. FP parameters in ALS are significantly different from PNH.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

Current Neurovascular Research ◽

10.2174/1567202617666200409125227 ◽

2020 ◽

Vol 17 (3) ◽

pp. 275-285 ◽

Cited By ~ 5

Author(s):

Si Chen ◽

Qiao Liao ◽

Ke Lu ◽

Jinxia Zhou ◽

Cao Huang ◽

...

Keyword(s):

Motor Neurons ◽

Rat Model ◽

Microglial Activation ◽

Transgenic Rat ◽

Intragastric Administration ◽

Behavioral Deficits ◽

Als Patients ◽

Lateral Sclerosis ◽

Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

Plasma Creatinine Level Does Not Predict Respiratory Function in Amyotrophic Lateral Sclerosis

Journal of Neuromuscular Diseases ◽

10.3233/jnd-200583 ◽

2021 ◽

pp. 1-5

Author(s):

João Morgadinho ◽

Ana Catarina Pronto-Laborinho ◽

Vasco A. Conceição ◽

Marta Gromicho ◽

Susana Pinto ◽

...

Keyword(s):

Creatinine Level ◽

Cox Regression ◽

Functional Decline ◽

Plasma Creatinine ◽

Plasma Creatinine Level ◽

Decline Rate ◽

Respiratory Outcome ◽

Als Patients ◽

In amyotrophic lateral sclerosis (ALS) lower plasma creatinine level has been associated with shorter survival and faster functional decline. It has not been clear if creatinine is associated with respiratory outcome. We analyzed retrospectively a population of unselected ALS patients. Multiple-regression and Cox-regression analyses were performed. We included 233 patients, mean age 62.8, mean disease duration of 18.6 months. At baseline, creatinine was significantly associated with ALSFRS-R, but not with its decline rate. No predictive value was disclosed for FVC, or their decline rate, or with survival. We did not confirm that creatinine is a marker of respiratory outcome.

Coping strategies among amyotrophic lateral sclerosis (ALS) patients: an integrative review

Journal of Neurology ◽

10.1007/s00415-021-10472-2 ◽

2021 ◽

Author(s):

Georgiana Soares Leandro ◽

Mário Emílio Teixeira Dourado Júnior ◽

Glauciane Costa Santana ◽

Luan Samy Xavier Dantas

Keyword(s):

Coping Strategies ◽

Integrative Review ◽

Als Patients ◽

Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis

Scientific Reports ◽

10.1038/s41598-020-80378-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

James C. Dodge ◽

Jinlong Yu ◽

S. Pablo Sardi ◽

Lamya S. Shihabuddin

Keyword(s):

Motor Neuron ◽

Cholesterol Homeostasis ◽

Cholesterol Oxidation ◽

Therapeutic Approaches ◽

Cellular Survival ◽

Sporadic Als ◽

Human Motor ◽

Als Patients ◽

AbstractAberrant cholesterol homeostasis is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease that is due to motor neuron (MN) death. Cellular toxicity from excess cholesterol is averted when it is enzymatically oxidized to oxysterols and bile acids (BAs) to promote its removal. In contrast, the auto oxidation of excess cholesterol is often detrimental to cellular survival. Although oxidized metabolites of cholesterol are altered in the blood and CSF of ALS patients, it is unknown if increased cholesterol oxidation occurs in the SC during ALS, and if exposure to oxidized cholesterol metabolites affects human MN viability. Here, we show that in the SOD1G93A mouse model of ALS that several oxysterols, BAs and auto oxidized sterols are increased in the lumbar SC, plasma, and feces during disease. Similar changes in cholesterol oxidation were found in the cervical SC of sporadic ALS patients. Notably, auto-oxidized sterols, but not oxysterols and BAs, were toxic to iPSC derived human MNs. Thus, increased cholesterol oxidation is a manifestation of ALS and non-regulated sterol oxidation likely contributes to MN death. Developing therapeutic approaches to restore cholesterol homeostasis in the SC may lead to a treatment for ALS.

Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

Brain Sciences ◽

10.3390/brainsci11070906 ◽

2021 ◽

Vol 11 (7) ◽

pp. 906

Author(s):

Nimeshan Geevasinga ◽

Mehdi Van den Bos ◽

Parvathi Menon ◽

Steve Vucic

Keyword(s):

Motor Neurons ◽

Cortical Excitability ◽

Muscular Atrophy ◽

Close Relationship ◽

Bulbar Onset ◽

Als Patients ◽

Transcranial Magnetic Simulation ◽

Cortical Dysfunction ◽

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease.

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Diagnostics ◽

10.3390/diagnostics11071210 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1210

Author(s):

Júlia Costa ◽

Marta Gromicho ◽

Ana Pronto-Laborinho ◽

Conceição Almeida ◽

Ricardo A. Gomes ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Motor Neurons ◽

Neurological Diseases ◽

Disease Diagnosis ◽

Enzyme Linked Immunosorbent Assay ◽

Progression Rate ◽

Therapeutic Trials ◽

Als Patients ◽

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

Neurological Sciences ◽

10.1007/s10072-021-05188-0 ◽

2021 ◽

Author(s):

Fabiola De Marchi ◽

◽

Claudia Carrarini ◽

Antonio De Martino ◽

Luca Diamanti ◽

...

Keyword(s):

Time Course ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Multisystem Disorder ◽

Behavioral Impairment ◽

Behavioral Impairments ◽

Als Patients ◽

Disease Stages ◽

Abstract Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

Critical Review of Complementary and Alternative Medicine Use in Amyotrophic Lateral Sclerosis: Prevalence and Users’ Profile, Decision-Making, Information Seeking, and Disclosure in the Face of a Lack of Efficacy

Neurodegenerative Diseases ◽

10.1159/000492946 ◽

2018 ◽

Vol 18 (4) ◽

pp. 225-232 ◽

Cited By ~ 2

Author(s):

Jon Adams ◽

Michael Lee ◽

Wenbo Peng

Keyword(s):

Decision Making ◽

Alternative Medicine ◽

Complementary And Alternative Medicine ◽

Information Seeking ◽

Disease Process ◽

Cam Use ◽

Als Patients ◽

Lateral Sclerosis ◽

Complementary And Alternative

Background: Despite a lack of evidence of clinical efficacy for complementary and alternative medicine (CAM) use in amyotrophic lateral sclerosis (ALS), these medicines remain popular around the world. Objective: To examine the prevalence and cost of CAM use in ALS and CAM users’ profile, decision-making, information seeking, and disclosure among ALS patients. Methods: A comprehensive literature search was conducted of MEDLINE, CINAHL/SCOPUS, and AMED databases from their inception to April 2018. This review followed PRISMA guidelines and employed a quality scoring system to assess the included papers. Results: Seven papers met the inclusion criteria and were thematically analysed. ALS patients utilized a range of CAM therapies and/or products, with acupuncture and vitamins being the most frequently reported. CAM modalities were often employed concurrently with conventional medications throughout the disease process. Although some ALS patients reported positive experience regarding CAM use, many were reluctant to disclose their CAM use to their clinicians. Research focusing on CAM use in ALS remains ad hoc and restricted to only a few countries. The rigour and quality of this research field to date has been varied, predominantly drawing upon regional/localized data and failing to report CAM users’ characteristics. Conclusion: A proportion of ALS patients report utilizing CAM concurrently with conventional treatments. Such use, set amidst a dearth of evidence for the efficacy of CAM in ALS, poses potential direct and indirect risks to patient care, and medical providers should be mindful of and enquire about CAM use when treating ALS patients.