Evaluation Of Amyotrophic Lateral Sclerosis Research Articles

Forced Expiratory Volume in One Second Quotient (FEV1Q) as a Prognostic Factor in Amyotrophic Lateral Sclerosis Patients: Comparing Its Predictive Value to Other Lung Function Measurements.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the first and second motor neurons. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) have conventionally served as indicators of respiratory muscle strength. Recently, FEV1Q (FEV1 divided by the sex-specific first percentile values of absolute FEV1 in adults with lung disease) has been suggested as a predictor of mortality. While FVC has been utilized as a prognostic factor, FEV1Q has not yet been examined. This retrospective unicenter study evaluated FEV1Q as a predictor of mortality in ALS patients, comparing its predictive efficacy with other measurements, including FEV1, FVC, sniff nasal inspiratory pressure, and maximal inspiratory pressure. The study utilized univariate analysis for each variable employing the Cox proportional hazards model to determine the statistical significance and predictive power of each measurement. Forty-five patients were included, female predominant (60%) and an average age at diagnosis of 69.2 ± 11 years. Almost all (95%) met the criteria for non-invasive ventilation (NIV) and initiated (93%) during the study period, a mean of 137 days after diagnosis. The mortality rate observed was 57%, occurring at a median of 398 days post-diagnosis. On average, patients underwent 1.7 pulmonary function tests, revealing a decline in various parameters, including FEV1, FEV1Q, and FVC. However, only FEV1Q was a statistically significant predictor of mortality (p < 0.0083) in a Cox regression analysis. A negative coefficient for FEV1Q indicated that higher values were associated with a reduced mortality risk, with an average FEV1Q of 2.68 observed at the time of death. FEV1Q emerged as the only statistically significant predictor of mortality among the evaluated respiratory measurements in ALS patients. This study is the first to focus on applying FEV1Q in the clinical evaluation of ALS, marking an initial step in understanding its potential role in patient follow-up. However, further studies are needed before these findings can be incorporated into clinical practice.

Feasibility assessment of using the MiToS staging system for conducting economic evaluation in amyotrophic lateral sclerosis

ABSTRACT Objectives This study assessed the feasibility of using the Milano-Torino staging (MiToS) system for conducting economic evaluation to measure health outcomes in amyotrophic lateral sclerosis (ALS). Methods A Markov model was developed using the MiToS system and evaluated with a hypothetical treatment versus standard of care. Health utilities and transition probabilities were derived from the literature. Four-time horizons (1, 5, 10, and 20 years) were examined. Treatment effects of 20–35% relative risk reduction (RRR) of progressing to the next MiToS stage were assessed. Three patient distribution scenarios were tested: (1) all patients began in stage 0; (2) patient distribution based on real-world TONiC study; (3) distribution based on the PRO-ACT database. Health outcomes (quality-adjusted life-years [QALYs], life-years [LYs]) were reported with a 3% discount rate. Results A time horizon of 10 years fully captured treatment benefits: incremental QALYs were 0.28–0.60, 0.21–0.45, and 0.26–0.55 for scenarios 1–3, respectively; incremental LYs were 0.56–1.17, 0.46–0.97, and 0.53–1.11, respectively. Conclusion MiToS-based staging can be used for conducting economic analyses in ALS. Estimated incremental QALY and LY gains were meaningful within the context of ALS, for hypothetical treatments with RRR of 20–35%.

Utilizing neurodegenerative markers for the diagnostic evaluation of amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1–42 in ALS patients and a control group.MethodsOur study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann–Whitney U-test.ResultsSignificant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1–42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS.ConclusionOur study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.

Swallowing sound evaluation using an electronic stethoscope and artificial intelligence analysis for patients with amyotrophic lateral sclerosis.

Non-invasive, simple, and repetitive swallowing evaluation is required to prevent aspiration pneumonia in neurological care. We investigated the usefulness of swallowing sound evaluation in patients with amyotrophic lateral sclerosis (ALS) using our new electronic stethoscope artificial intelligence (AI) analysis tool. We studied patients with ALS who provided written informed consent. We used an electronic stethoscope, placed a Bluetooth-enabled electronic stethoscope on the upper end of the sternum, performed a 3-mL water swallow three times, and remotely identified the intermittent sound components of the water flow caused at that time by AI, with the maximum value as the swallowing sound index. We examined the correlation between the swallowing sound index and patient background, including swallowing-related parameters. We evaluated 24 patients with ALS (age 64.0 ± 11.8 years, 13 women, median duration of illness 17.5 months). The median ALS Functional Rating Scale-Revised (ALSFRS-R) score was 41 (minimum 18, maximum 47). In all cases, the mean swallowing sound index was 0.209 ± 0.088. A multivariate analysis showed that a decrease in the swallowing sound index was significantly associated with a low ALSFRS-R score, an ALSFRS-R bulbar symptom score, % vital capacity, tongue pressure, a Mann Assessment of Swallowing Ability (MASA) score, and a MASA pharyngeal phase-related score. Swallowing sound evaluation using an electronic stethoscope AI analysis showed a correlation with existing indicators in swallowing evaluation in ALS and suggested its usefulness as a new method. This is expected to be a useful examination method in home and remote medical care.

"Huoling Shengji granule" for amyotrophic lateral sclerosis: protocol for a multicenter, randomized, double-blind, riluzole parallel controlled clinical trial.

There is still a large demand for effective treatments to delay disease deterioration in amyotrophic lateral sclerosis (ALS). Typical symptoms of ALS are considered "flaccidity syndrome" in traditional Chinese medicine (TCM). Huoling Shengji Granule (HLSJ) is a TCM formula used to treat flaccidity syndrome. Results of preclinical tests and a previous clinical study support HLSJ as a novel drug for ALS patients. This trial proposed to examine whether a 48-week course of HLSJ is effective and safe for ALS patients diagnosed with the Chinese medicine syndrome of spleen qi insufficiency and kidney yang deficiency. In this phase II, multicenter, randomized, double-blind, riluzole parallel-controlled, superiority-design study, eligible participants had the equal opportunity to be assigned to receive either HLSJ or riluzole randomly. Eleven specialized ALS centers in Mainland China will recruit 144 patients for this trial. The primary and secondary outcomes included the change in the ALSFRS-R score and the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) from baseline to Week 48. Here, we endeavored to evaluate TCM for ALS using a standard evidence-based approach for the first time. In addition, the ROADS, a self-report linear-weighted questionnaire, was selected as a secondary outcome measure. We expect to offer a new reference for the outcome evaluation of ALS trials.Clinical trial registration:http://www.Chictr.org.cn, identifier ChiCTR2100044085.

18F-FDG PET/CT as a molecular biomarker in the diagnosis of amyotrophic lateral sclerosis associated with prostate cancer and progressive supranuclear palsy: A case report

Introduction Amyotrophic lateral sclerosis (ALS) is a neurodegenerative, multisystem disorder. Its clinical presentation typically consists of progressive focal muscle atrophy and weakness. In addition to motor disorders, the association between ALS and cancer has been researched, such as frontotemporal dementia and progressive supranuclear palsy. The diagnosis is based primarily on the clinical history, physical examination, electrodiagnostic tests (with an EMG needle), and neuroimaging, such as MRI and 18 F-FDG PET/CT. Presentation of the case A 67-year-old male patient was diagnosed with prostate adenocarcinoma with a clinical picture of muscle weakness in the lower limbs that caused falls and was associated with fasciculations in the thighs and arms, alterations in the tone of voice, poor memory, and difficulty articulating words. In the neurological assessment, he described walking supported by a walker with decreased strength in both lower limbs and sensitivity without alterations. The diagnoses of upper and lower motor neuron disease and probable ALS were integrated. Furthermore, the probable coexistence of frontotemporal dementia/disorder (FDD) with ALS was considered. The main findings in the 18 F-FDG PET/CT study was hypometabolism in the cortex of the bilateral motor and premotor areas, the anterior cingulate, both caudate and putamen, a metabolic pattern compatible with ALS, and progressive supranuclear palsy. Conclusion Through the PET/CT studies, we demonstrated a case in which ALS, prostate cancer and progressive supranuclear palsy coexisted molecularly; it was clinically difficult to diagnose. Molecular imaging has potential in the diagnostic and prognostic evaluation of ALS. It is crucial to identify the disease early and reliably through metabolic patterns that allow us to confirm the disease or differentiate it from other pathologies.

Biosensing system for drug evaluation of amyotrophic lateral sclerosis based on muscle bundle and nano-biohybrid hydrogel composed of multiple motor neuron spheroids and carbon nanotubes

Amyotrophic lateral sclerosis (ALS) results in muscle atrophy due to degeneration of the neuromuscular junctions (NMJs), the synapse responsible for the transmission of signals between motor neurons (MNs) and skeletal muscles. Even though NMJ models have been developed, in vitro drug evaluation models for ALS disease are still lacking due to the absence of a sensing system and immature NMJs in a model system. Moreover, a three-dimensional (3D) biosensing system that can observe drug-induced muscle recovery and movement still does not exist. In this study, we developed the first 3D NMJ biosensing system for drug evaluation of ALS based on muscle bundle and the 3D nano-biohybrid hydrogel composed of multiple motor neuron spheroids (multi-MNSs) and carboxylated carbon nanotubes (CNT-COOH). For the fabrication of biosensor-integrated NMJs, the use of multi-MNSs increased the number of neurites, which in combination with the muscle bundle, resulted in increased NMJ formation. In addition, the use of CNT-COOH in the 3D nano-biohybrid hydrogel induced neurogenesis of multi-MNSs, increased hydrogel conductivity, and formed more mature and functional NMJs. ALS-MNSs obtained from induced pluripotent stem cells (iPSCs) of sporadic ALS patients were added to the 3D nano-biohybrid hydrogel to examine the effects of bosutinib, one of the drug candidates for ALS treatment, leading to the recovery of contraction of the connected muscle bundle. The proposed 3D NMJ biosensing system using 3D nano-biohybrid hydrogel can be an extraordinary platform for drug screening of diverse neuromuscular diseases and toxicity assessment.

Biosensing System for Drug Evaluation of Amyotrophic Lateral Sclerosis Based on Muscle Bundle and Nano-Biohybrid Hydrogel Composed of Multiple Motor Neuron Spheroids and Carbon Nanotubes

Biosensing System for Drug Evaluation of Amyotrophic Lateral Sclerosis Based on Muscle Bundle and Nano-Biohybrid Hydrogel Composed of Multiple Motor Neuron Spheroids and Carbon Nanotubes

PND53 Predictive Models Leveraging Machine Learning and Real-World Data for Early Diagnosis: An Application in Amyotrophic Lateral Sclerosis

To assess the utility of machine learning for predicting early diagnosis of amyotrophic lateral sclerosis (ALS) based on real-world data (RWD). We identified 4779 patients with ALS and without primary lateral sclerosis from the Optum® de-identified Electronic Health Record (EHR) dataset (2007-2020), and 47,781 patients as the control cohort who did not have ALS and were demographically matched by age and gender in a 1:10 target to control ratio. Mutual information was used to explore and identify features in RWD, including lab, microbiology, and natural language processing biomarkers available in EHR, by comparing the target population (ALS patients) with the demographically matched control cohort. We trained various machine learning models (eg, logistic regression, random forest, gradient boosting, support vector machines, neural networks, soft voting) spanning different periods of time relative to a defined index date and compared their performance in predicting early diagnosis of ALS. Predictive models trained with gradient boosting on data closer to the defined index date, including lab tests from EHR, performed the best and had a very low false positive rate (AUC=0.9463). This model suggested that the top 5 predictors of an undiagnosed ALS patient were muscle weakness (generalized), normal thyroid stimulating hormone levels, dysphagia (unspecified), cramp of limb/abnormal involuntary movements, and other musculoskeletal symptoms referable to limbs. Many of the features were diagnoses that could be considered for an earlier evaluation of ALS in clinical practice. Indeed, the model had a sensitivity of 1%, specificity >99.0%, and was able to identify with a precision of 63% patients not yet identified with ALS, suggesting that early screening for ALS would be beneficial. This study highlights opportunities of leveraging machine learning utilizing EHR RWD to identify features that predict early diagnosis of ALS.

Psychometric Properties of Preference-Based Measures for Economic Evaluation in Amyotrophic Lateral Sclerosis: A Systematic Review.

Objective The aim of this review was to synthesize the psychometric properties of generic preference-based measures (PBMs) of health-related quality of life (HRQL) in Amyotrophic Lateral Sclerosis (ALS). Methods A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were searched from inception to April 2019: OVID Medline, Embase, PsycINFO, and CINAHL. Studies were included if (1) the sample represented individuals with ALS, (2) a generic PBM was utilized and reported on, and (3) information on the psychometric property of a generic PBM was provided. Results Ninety-one articles were screened, and 39 full-text articles were reviewed. Seven full-text articles were included in this review. The mean age of participants ranged from 58.1 to 63.8 years, and mean time since diagnosis ranged from 20.5 to 44.6 months. Two generic PBMs were found, the EQ-5D-3L (n = 6) and the Quality of Well-Being Self-Administered (QWB-SA) scale (n = 1). Convergent validity of the EQ-5D-3L was large against a global scale of self-perceived health (r = 0.60) and small to large against ALS specific HRQL measures (r = 0.19 to 0.75). For the QWB-SA scale, correlations were small against a generic measure (r = 0.21) and large against ALS specific measures (r = 0.55). The EQ-5D-3L discriminated across different disease severity; however, floor effects were reported. Conclusion This review highlights the need for more rigorously designed studies to assess the psychometric properties of generic PBMs in ALS and the development of an ALS specific PBM that adequately reflects the health concerns of individuals with ALS.

ULTRASOUND IN THE DIAGNOSIS AND MONITORING OF AMYOTROPHIC LATERAL SCLEROSIS: A REVIEW.

Neuromuscular ultrasound is complementary to electrodiagnostic (EDx) testing and is useful in enhancing the diagnosis of mononeuropathies, peripheral nerve trauma, and demyelinating polyneuropathies. There is increasing interest in using ultrasound both to aid in the diagnosis of amyotrophic lateral sclerosis (ALS) and to monitor its progression. In this article we review the relevant literature on ultrasound in ALS. Ultrasound is more sensitive than EDx in identifying fasciculations in patients with ALS. It can detect decreased muscle thickness, increased muscle echointensity and echovariance, and reduced peripheral nerve size in these patients. Ultrasound is also a helpful tool in assessment of diaphragm function. Although additional studies are required to define the exact role of ultrasound in the evaluation and monitoring of ALS, it can improve the diagnostic yield in patients when ALS is suspected, but insufficiently supported, by clinical and EDx examinations. Muscle Nerve 60: 114-123, 2019.

Considerations for Clinical Neuropsychological Evaluation in Amyotrophic Lateral Sclerosis.

The clinical neuropsychologist has the opportunity to be uniquely involved in the evaluation and treatment of individuals with amyotrophic lateral sclerosis (ALS). We review the current literature that defines cognitive and behavioral symptoms in ALS, including current knowledge of the neuropathological and genetic underpinning for these symptoms. There are unique considerations for clinical neuropsychological evaluation and clinical research in ALS and we highlight these in this review. Specifically, we shed light on special factors that contribute to our understanding of cognitive and behavioral impairment in ALS, including co-morbid symptoms, differential diagnosis, and considerations for longitudinal tracking of phenotypes. We discuss the rationale for proposing a specific approach to such as cognitive screening, test selection, response modality consideration, and test-retest intervals. With this didactic overview, the clinical neuropsychologist has the potential to learn more about the heterogeneous presentation of motor and neuropsychological symptoms in ALS. Furthermore, the reader has the opportunity to understand what it takes to develop a valid assessment approach particularly when the phenotype of ALS remains undefined in some regards. This clinical practice review sets the stage for the clinical neuropsychologist to further contribute to our clinical and scientific understanding of ALS and cognition.

42. Muscle ultrasound as a further tool in diaphragmatic muscle evaluation in Amyotrophic Lateral Sclerosis

Respiratory failure is an unavoidable stage in patients with Amyotrophic Lateral Sclerosis (ALS). Generally, diaphragmatic function is investigated by electromyography of the diaphragm muscle (DM) and electroneurography of the phrenic nerve. In our study we evaluated the usefulness of ultrasonography for morphological (thickness and echogenicity) and functional (changes during the respiratory dynamics) assessment of DM, correlating these findings with respiratory function and disease severity scores, in order to underline if this approach can replace the current diagnostic methods. We assessed 11 ALS patients (9 m e 2 f, mean age: 63.9 + 9.5 yy) and 11 healthy subjects, age- and gender-matched, using a Telemed Echo-wave II ultrasound. Mean DM thickness at rest (2.18 vs 3.45 mm), as well as thickness variations during breathing (0.4 vs 1.16 mm) were reduced in all patients, or abolished in 3 severe cases. Occasionally fasciculations were noticed, rarely fibrillation. Those findings did not correlate with forced vital capacity, maximum inspiratory and expiratory pressure. Ultrasound of DM resulted as an easy and rapid tool, devoid of discomfort and risks for ALS patients and able to provide further informations to assess and predict respiratory failure severity, allowing to plan therapeutic strategies.

Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: development of an imaging biomarker.

Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS.

Amyotrophic lateral sclerosis: Analysis of ALS cases in a predominantly admixed population of Ecuador

Recent studies suggest amyotrophic lateral sclerosis (ALS) prevalence, incidence, and age of onset are heterogeneous across populations. These include studies from South America (SA) where lower prevalence, earlier onset, and reduced survival time of ALS are reported. However, the scarcity of epidemiological and clinical data confounds effective comparison. To investigate ALS incidence in the predominantly admixed population of Ecuador, we analyzed patient data. We analyzed case data from two major hospitals. To confirm diagnosis, we evaluated clinical and EMG examinations in a cohort of patients. For 2000–2012, we found 116 patients with ALS diagnosis in the two hospitals. Crude incidence was 0.2–0.6 per 100,000. Median age of onset was 54.3 (+ 15.06 SD). Clinical re-evaluation found misdiagnosis in three cases in the cohort. In conclusion, ALS incidence in the Ecuadorian hospital population is in accord with rates reported in recent studies for other admixed populations, and lower than that in the United States and Europe. Our study found that appropriate EMG administration and interpretation for the purposes of supporting a diagnosis of ALS with current consensus guidelines prevent adequate use of this test as an essential tool in the evaluation and diagnosis of ALS. Training for required standardization in Ecuador is recommended.

Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia

Administration of mesenchymal stromal cells (MSC) improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 cells and glial cells (astrocytes, microglia) (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice) in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM) attenuated staurosporine (STS) - induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells, we found that glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) gene expression in astrocytes were significantly enhanced by MSC CM, with differential responses of non-transgenic and mutant astrocytes. Expression of Vascular Endothelial Growth Factor (VEGF) in NSC-34 cells was significantly upregulated upon MSC CM-treatment. MSC CM significantly reduced the expression of the cytokines TNFα and IL-6 and iNOS both in transgenic and non-transgenic astrocytes. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1) was also upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment. Correspondingly, MSC CM increased the respective receptor, CX3CR1, in mutant SOD1G93A transgenic microglia. Our data demonstrate that MSC modulate motor neuronal and glial response to apoptosis and inflammation. MSC therefore represent an interesting candidate for further preclinical and clinical evaluation in ALS.

Incidence of Amyotrophic Lateral Sclerosis Among American Indians and Alaska Natives

More thorough evaluation of amyotrophic lateral sclerosis (ALS) and motor neuron disease in unique populations could provide clues to etiologies for these idiopathic conditions, and educational programs for American Indian and Alaska Native (AI/AN) people and health care professionals on reservations could improve awareness, understanding, diagnosis, and treatment. In the ongoing search for susceptibility genes, studying particular racial groups, such as AI/ANs,might facilitate the identification of new mutations. To provide better understanding of ALS and secondarily of motor neuron disease among AI/AN people by estimating the incidence and prevalence among AI/ANs served by the Indian Health Service health care system. Analysis of electronic records for AI/ANs with ALS and with motor neuron disease separately for the calendar years 2002-2009 using inpatient and outpatient visit data from the Indian Health Service, which provides health care to eligible AI/ANs nationwide. Cases were defined by at least 2 inpatient or outpatient visits with the diagnosis. Crude and age-adjusted incidence and prevalence rates were calculated. Seventy-one AI/ANs were diagnosed with ALS, yielding an average annual crude incidence rate of 0.63 cases per 100 000 and an age-adjusted incidence of 0.92. The median age at onset was 56.0 years and was higher among women than men (62.0 vs 55.0 years; P=.06). Age-specific incidence increased to 70 to 74 years. The crude and age-adjusted point prevalence rates were 2.00 and 4.12, respectively. The crude and age-adjusted incidence rates for motor neuron disease were 1.08 and 1.50, respectively. The annual rates were unchanged across the study period. The incidence of ALS among AI/ANs appears to be lower than that reported for white populations, a finding congruent with reports of other minority populations. Community-based studies are important to confirm these findings and to examine reasons for the low rate of ALS among AI/ANs.

Monitoring respiratory muscle strength assists in early diagnosis of respiratory dysfunction as opposed to the isolated use of pulmonary function evaluation in amyotrophic lateral sclerosis

It was study the relationship between respiratory muscle strength and forced vital capacity (FVC) in patients with amyotrophic lateral sclerosis (ALS) versus healthy subjects. Pulmonary function and respiratory muscle strength [maximal inspiratory (PImax), maximal expiratory (PEmax) and sniff nasal inspiratory pressure (SNIP)] were assessed in patients with ALS and healthy subjects, matched using cutoffs established in the literature for impaired pulmonary function and respiratory muscle weakness. Twenty-eight ALS patients and 28 healthy subjects were studied. We found sensitivity and specificity for PImax, PEmax and SNIP of 75/58%, 81/67% and 75/67%. The Receiver Operating Characteristic curve (ROC curve) indicated that the variables PImax, PEmax and SNIP can identify differences in respiratory muscle strength between ALS and healthy individuals at 0.89, 0.9 and 0.82, respectively. A positive correlation was recorded between FVC (%) versus SNIP, PImax and PEmax. In ALS, monitoring respiratory muscle strength assists in early diagnosis of respiratory dysfunction as opposed to the isolated use of FVC.

Therapeutic Potential of N-Acetyl-Glucagon-Like Peptide-1 in Primary Motor Neuron Cultures Derived From Non-Transgenic and SOD1-G93A ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons (MN) in the motor cortex, brain stem, and spinal cord. In the present study, we established an ALS in vitro model of purified embryonic MNs, derived from non-transgenic and mutant SOD1-G93A transgenic mice, the most commonly used ALS animal model. MNs were cultured together with either non-transgenic or mutant SOD1-G93A astrocyte feeder layers. Cell viability following exposure to kainate as excitotoxic stimulus was assessed by immunocytochemistry and calcium imaging. We then examined the neuroprotective effects of N-acetyl-GLP-1(7-34) amide (N-ac-GLP-1), a long-acting, N-terminally acetylated, C-terminally truncated analog of glucagon-like peptide-1 (GLP-1). GLP-1 has initially been studied as a treatment for type II diabetes based on its function as insulin secretagogue. We detected neuroprotective effects of N-ac-GLP-1 in our in vitro system, which could be attributed to an attenuation of intracellular calcium transients, not only due to these antiexcitotoxic capacities but also with respect to the increasing knowledge about metabolic deficits in ALS which could be positively influenced by N-ac-GLP-1, this compound represents an interesting novel candidate for further in vivo evaluation in ALS.

Respiratory exercise in amyotrophic lateral sclerosis

We have evaluated the potential role of respiratory exercise by implementing specific inspiratory muscle training in a selected population of early-affected amyotrophic lateral sclerosis (ALS) patients. We studied 26 patients with ALS with normal respiratory function using two groups of patients in a parallel, control-group, randomized, delayed-start design. Patients in the first group (G1) started the active inspiratory exercise programme at entry and were followed for eight months, while the second group (G2) of patients followed a placebo exercise programme for the first four months and then active exercise for the second four-month period. The primary outcome measure was the ALSFRS. Respiratory tests, neurophysiological measurements, fatigue and quality of life scales were secondary outcomes. Analysis of covariance was used to compare changes between and within groups. Results showed that there was no significant difference between the two patient groups. Within-group analysis suggested that inspiratory exercise promotes a transient improvement in the respiratory subscore and in the maximal voluntary ventilation, peak expiratory flow, and sniff inspiratory pressure. In conclusion, there was no clear positive or negative outcome of the respiratory exercise protocol we have proposed, but we cannot rule out a minor positive effect. Exercise regimes merit more detailed clinical evaluation in ALS.