Changes In Amyotrophic Lateral Sclerosis Research Articles

Disentangling the Relationship Between Social Cognition, Executive Functions, and Behaviour Changes in Amyotrophic Lateral Sclerosis (S18.009)

Disentangling the Relationship Between Social Cognition, Executive Functions, and Behaviour Changes in Amyotrophic Lateral Sclerosis (S18.009)

Serum cytokines profile changes in amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. MethodsIn Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). ResultsThe levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50–0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25–175.59] vs 116.44 [102.43–122.19]pg/ml, p < 0.0015). ConclusionIn this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.

Peripheral immune markers and amyotrophic lateral sclerosis: a Mendelian randomization study.

The peripheral immune system changes in amyotrophic lateral sclerosis (ALS), but the causal relationship between the two is still controversial. In this study, we aimed to estimate the causal relationship between peripheral immune markers and ALS using a two-sample Mendelian randomization method. Genome-wide association study (GWAS) data on peripheral blood immune traits from European populations were used for exposure, and ALS summary statistics were used as the outcome. The causal relationship was evaluated by inverse variance weighting, MR-Egger, and weighted median methods and verified by multiple sensitivity analysis. We found that the increase of one standard deviation of lymphocyte count is related to reducing ALS risk. CD3 on effector memory CD4+ T cell, HLA DR+ CD4+ T cell, effector memory CD8+ T cell, terminally differentiated CD8+ T cell and CD28- CD8+ T cell is also a protective factor for ALS. Among the circulating immune protein, the increase of one standard deviation of α-2-macroglobulin receptor-associated protein (α-2-MRAP) and C4b showed associated with low risk of ALS, while Interleukin-21 (IL-21) increases the risk of ALS. Our study further reveals the important role of peripheral immune activity in ALS.

Sonographic Phrenic Nerve Changes in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity of the affected patients, limits daily activities, and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. Forty-six participants were included in our study, with 23 patients in the ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as an additional diagnostic tool for ALS.

Primary care blood tests show lipid profile changes in pre-symptomatic amyotrophic lateral sclerosis.

Multiple sources of evidence suggest that changes in metabolism may precede the onset of motor symptoms in amyotrophic lateral sclerosis. This study aimed to seek evidence for alterations in the levels of blood indices collected routinely in the primary care setting prior to the onset of motor symptoms in amyotrophic lateral sclerosis. Premorbid data, measured as part of routine health screening, for total cholesterol, high-density and low-density lipoprotein cholesterol, triglyceride, glycated haemoglobin A1c and creatinine were collected retrospectively from (i) a cohort of amyotrophic lateral sclerosis patients attending a specialist clinic (n = 143) and (ii) from primary care-linked data within UK Biobank. Data were fitted using linear mixed effects models with linear b-splines to identify inflection points, controlling for age and sex. In specialist amyotrophic lateral sclerosis clinic cases, models indicated decreasing levels of total and low-density lipoprotein cholesterol prior to an inflection point in the years before symptom onset (total cholesterol 3.25 years, low-density lipoprotein cholesterol 1.25 years), after which they stabilized or rose. A similar pattern was observed in amyotrophic lateral sclerosis cases within UK Biobank, occurring several years prior to diagnosis (total cholesterol 7 years, low-density lipoprotein cholesterol 7.25 years), differing significantly from matched controls. High-density lipoprotein cholesterol followed a similar pattern but was less robust to sensitivity analyses. Levels of triglyceride remained stable throughout. Glycated haemoglobin temporal profiles were not consistent between the clinic and biobank cohorts. Creatinine level trajectories prior to amyotrophic lateral sclerosis did not differ significantly from controls but decreased significantly in the symptomatic period after an inflection point of 0.25 years after symptom onset (clinic cohort) or 0.5 years before diagnosis (UK Biobank). These data provide further evidence for a pre-symptomatic period of dynamic metabolic change in amyotrophic lateral sclerosis, consistently associated with alterations in blood cholesterols. Such changes may ultimately contribute to biomarkers applicable to population screening and for pathways guiding the targeting of preventative therapy.

Multimodal MRI improves diagnostic accuracy and sensitivity to longitudinal change in amyotrophic lateral sclerosis

BackgroundRecent advances in MRI acquisitions and image analysis have increased the utility of neuroimaging in understanding disease-related changes. In this work, we aim to demonstrate increased sensitivity to disease progression as well as improved diagnostic accuracy in Amyotrophic lateral sclerosis (ALS) with multimodal MRI of the brain and cervical spinal cord.MethodsWe acquired diffusion MRI data from the brain and cervical cord, and T1 data from the brain, of 20 participants with ALS and 20 healthy control participants. Ten ALS and 14 control participants, and 11 ALS and 13 control participants were re-scanned at 6-month and 12-month follow-ups respectively. We estimated cross-sectional differences and longitudinal changes in diffusion metrics, cortical thickness, and fixel-based microstructure measures, i.e. fiber density and fiber cross-section.ResultsWe demonstrate improved disease diagnostic accuracy and sensitivity through multimodal analysis of brain and spinal cord metrics. The brain metrics also distinguished lower motor neuron-predominant ALS participants from control participants. Fiber density and cross-section provided the greatest sensitivity to longitudinal change. We demonstrate evidence of progression in a cohort of 11 participants with slowly progressive ALS, including in participants with very slow change in ALSFRS-R. More importantly, we demonstrate that longitudinal change is detectable at a six-month follow-up visit. We also report correlations between ALSFRS-R and the fiber density and cross-section metrics.ConclusionsOur findings suggest that multimodal MRI is useful in improving disease diagnosis, and fixel-based measures may serve as potential biomarkers of disease progression in ALS clinical trials.

N°192 – Does electrophysiologic analysis of H-reflex pathway reveal spinal excitability changes in amyotrophic lateral sclerosis? A multicenter study with H-reflex recorded from soleus and unconventional muscles

N°192 – Does electrophysiologic analysis of H-reflex pathway reveal spinal excitability changes in amyotrophic lateral sclerosis? A multicenter study with H-reflex recorded from soleus and unconventional muscles

Izmenjen profil masnih kiselina eritrocita pacijenata sa amiotrofičnom lateralnom sklerozom - korelacija sa trajanjem bolesti

Background: Recent literature data highlights metabolic changes in amyotrophic lateral sclerosis (ALS). To explore possible early metabolic changes, we aimed to analyse the fatty acids (FA) composition of erythrocytes in newly diagnosed als patients and to see whether fatty acid levels correlate with the ALSFRS-R score or disease duration. Methods: The severity of motor function involvement was assessed by the ALSFRS-R scale at the initial evaluation. The fatty acid profile of erythrocyte membranes was analysed by gas-liquid chromatography. The study comprised 26 clinically diagnosed als patients, with mean ALSFRS-R 38±8. The control group included 26 healthy volunteers. Results: Significantly higher levels of palmitic acid and total saturated FAs were detected in als patients. In als patients, total monounsaturated FA, palmitoleic, vaccenic, and oleic acid were also significantly increased. The levels of eicosapentaenoic acid, docosapentaenoic acid, total polyunsaturated FA (PUFA) and n-6 PUFA were significantly lower in als patients. Additionally, a-linolenic acid, the precursor of the n-3 PUFA family, was not detected in als patients. We found no significant correlation between the ALSFRS-R score and the abundance of individual FAs analysed. A moderate negative correlation was found between disease duration and DHA level, and a positive correlation was detected with MUFA. Conclusion: Experimental evidence presented may contribute to shaping a beneficial nutritional intervention.

Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterized by the degeneration of motor neurons and loss of various muscular functions. Dyslipidaemia is prevalent in amyotrophic lateral sclerosis with aberrant changes mainly in cholesterol ester and triglyceride. Despite this, little is known about global lipid changes in amyotrophic lateral sclerosis or in relation to disease progression. The present study incorporated a longitudinal lipidomic analysis of amyotrophic lateral sclerosis serum with a comparison with healthy controls using advanced liquid chromatography-mass spectrometry. The results established that diglyceride, the precursor of triglyceride, was enriched the most, while ceramide was depleted the most in amyotrophic lateral sclerosis compared with controls, with the diglyceride species (18:1/18:1) correlating significantly to neurofilament light levels. The prenol lipid CoQ8 was also decreased in amyotrophic lateral sclerosis and correlated to neurofilament light levels. Most interestingly, the phospholipid phosphatidylethanolamine and its three derivatives decreased with disease progression, in contrast to changes with normal ageing. Unsaturated lipids that are prone to lipid peroxidation were elevated with disease progression with increases in the formation of toxic lipid products. Furthermore, in vitro studies revealed that phosphatidylethanolamine synthesis modulated TARDBP expression in SH-SY5Y neuronal cells. Finally, diglyceride, cholesterol ester and ceramide were identified as potential lipid biomarkers for amyotrophic lateral sclerosis diagnosis and monitoring disease progression. In summary, this study represents a longitudinal lipidomics analysis of amyotrophic lateral sclerosis serum and has provided new insights into multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.

Cognitive and behavioral changes in amyotrophic lateral sclerosis

BACKGROUND. Amyotrophic lateral sclerosis (ALS) is not limited only to motor impairment, and can also manifest with cognitive and behavioral disorders. Currently these presentations of ALS are unrecognized. Hence the research of ALS variants with cognitive and behavioral impairments is necessary.&#x0D; AIM. To study the frequency and clinical characteristics of ALS variants with cognitive and behavioral impairments.&#x0D; MATERIAL AND METHODS. The patients were recruited in 20202021. All patients with definite and possible ALS according to El Escorial criteria were included. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) was used to assess cognitive and behavioral changes. 44 patients, 26 males and 18 females, aged 39 to 77 years (median of age 61 years, interquartile range 53.574.5). Statistical analysis was performed using IBM SPSS Statistics 21. Continuous data were analyzed using the MannWhitney test, categorical data was analyzed by exact Fisher criteria. A p-value less than 0.05 was statistically significant.&#x0D; RESULTS. In 43.2% of patients cognitive and/or behavioral changes were observed. The majority of patients (approximately 20%) suffered from a variant of ALS with cognitive impairment, which was mostly presented with executive and social cognitive dysfunction. ALS with behavioral impairment was observed at 9% of patients, which mostly presented with apathy and disinhibition. A combination of cognitive and behavioral impairment was registered in 7% of patients. In another 7% of patients severity of cognitive and behavioral impairment reached a degree of dementia and corresponded to frontotemporal degeneration.&#x0D; CONCLUSION. This cognitive and behavioral impairment is observed in a substantial number of patients with ALS and mostly presented with moderate executive and social cognitive dysfunction, as well as apathy and less often disinhibition.

The Metabolomic Profile in Amyotrophic Lateral Sclerosis Changes According to the Progression of the Disease: An Exploratory Study.

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative pathology of the upper or lower motor neuron. Evaluation of ALS progression is based on clinical outcomes considering the impairment of body sites. ALS has been extensively investigated in the pathogenetic mechanisms and the clinical profile; however, no molecular biomarkers are used as diagnostic criteria to establish the ALS pathological staging. Using the source-reconstructed magnetoencephalography (MEG) approach, we demonstrated that global brain hyperconnectivity is associated with early and advanced clinical ALS stages. Using nuclear magnetic resonance (1H-NMR) and high resolution mass spectrometry (HRMS) spectroscopy, here we studied the metabolomic profile of ALS patients’ sera characterized by different stages of disease progression—namely early and advanced. Multivariate statistical analysis of the data integrated with the network analysis indicates that metabolites related to energy deficit, abnormal concentrations of neurotoxic metabolites and metabolites related to neurotransmitter production are pathognomonic of ALS in the advanced stage. Furthermore, analysis of the lipidomic profile indicates that advanced ALS patients report significant alteration of phosphocholine (PCs), lysophosphatidylcholine (LPCs), and sphingomyelin (SMs) metabolism, consistent with the exigency of lipid remodeling to repair advanced neuronal degeneration and inflammation.

Longitudinal grey matter and metabolic contributions to cognitive changes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is characterized by rapidly evolving cognitive and brain impairments. While previous work revealed structural and functional alterations associated with cognitive decline in patients suffering from amyotrophic lateral sclerosis, the relationships between anatomo-functional changes and both disease’s progression and the evolution of cognitive performance remain largely unexplored. Here, we took advantage of repeated multi-modal acquisitions in patients with amyotrophic lateral sclerosis over 1 year to assess the longitudinal sequence of grey matter atrophy, glucose metabolism and cognitive changes. Results revealed metabolic and structural changes over frontal, thalamic and temporal regions. Both cortical hypermetabolism and hypometabolism (right temporal gyrus and right angular gyrus, respectively) were associated with cognitive performance and thalamic hypometabolism during the follow-up testing session. Furthermore, the inferior frontal gyrus atrophy mediated the relation between early hypometabolism in this region and the subsequent decline of the theory of mind abilities. Marked volume loss was associated with larger hypometabolism and impaired cognitive performance. To our knowledge, this is the first study to longitudinally examine both grey matter volume and metabolic alteration patterns in patients with amyotrophic lateral sclerosis, over a mean follow-up time of 1 year. We identify how changes of the inferior frontal gyrus critically underly later cognitive performance, shedding new light on its high prognostic significance for amyotrophic lateral sclerosis-related changes. These results have important implications for our understanding of structural and functional changes associated with amyotrophic lateral sclerosis and how they underly cognitive impairments.

Brain Metabolic Changes in Amyotrophic Lateral Sclerosis with SOD1 Mutations (P1-1.Virtual)

Brain Metabolic Changes in Amyotrophic Lateral Sclerosis with SOD1 Mutations (P1-1.Virtual)

Fiber‐specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis

To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis. We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables. The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p<0.05, familywise error-corrected), and the comparison of FCs revealed no region that was significantly different from another. Voxel-based morphometry showed cortical volume reduction in the regions, including the primary motor area. Clinical scores showed correlations with FD values in the CSTs (UMN score: rho=-0.530, p<0.001; central motor conduction time [CMCT] in the upper limb: rho=-0.474, p=0.008; disease duration: rho=-0.383, p=0.007; ALS Functional Rating Scale-Revised: rho=0.340, p=0.018). In addition, patients whose CMCT was not calculated due to unevoked waves also showed FD reduction in the CSTs. Our findings suggest that FD values in the CST estimated via FBA can be potentially used in evaluating UMN impairments.

Translation, cultural adaptation, and validation of a screening test for cognitive and behavioural changes in amyotrophic lateral sclerosis

Purpose To describe challenges of translating and culturally adapting the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen into Norwegian (ECAS-N), evaluate its content validity; provide age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance. Materials and methods Translation to Norwegian and back-translation to English complied with standard methods. Patients and ALS experts evaluated the relevance, comprehensiveness and comprehensibility of the translated ECAS (ECAS-N). Content validity indexes at the item level (I-CVI), scale level (S-CVI) and inter-rater agreement were calculated. Performance of controls determined norms for written and spoken verbal fluency (n = 559) and cut-off scores for abnormal performance (n = 85). Results High levels of content validity was achieved for all items of the ECAS-N, I-CVI, S-CVI and inter-rater agreement was 87.5%. Age- and education-balanced norms for written and spoken verbal fluency were produced. Cut-off scores of abnormal performance were slightly lower than the original ECAS. Conclusions The ECAS-N holds promise for detecting cognitive and behavioural impairment in Norwegian patients with ALS. Cut-off scores are situational and could slightly vary between different cultures. The ECAS-N can be used in international research, but researchers should be aware of the differences between the tests applied in the studies. Implications for rehabilitation The ECAS-N, a Norwegian version of the English-language ECAS was produced for clinical use in Norway. Rigorous translation methods were used, and expert-judged modifications were made for Norwegian-specific culture and language nuances. Determination of ECAS-N cut-off scores for abnormal cognition was guided by a biostatistician, are slightly lower than the original ECAS, and are based on results from an objectively calculated number of healthy Norwegians. A nuanced picture of cognitive impairment in ALS drawn from a well-developed scale as the ECAS-N can contribute to a management process better tailored to patients’- and carers’ individual needs.

Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants.

Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP‐43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP‐43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP‐43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer’s disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non‐FTLD related findings can influence the cognitive status, particularly in older age groups.

Validation and standardization of the Psycholinguistic Assessments of Language Processing in Aphasia (PALPA)

ABSTRACT Aims This study aimed to standardize and assess the psychometric properties of a selected protocol of subtests from the Psycholinguistic Assessments of Language Processing in Aphasia (PALPA), a battery of tests that measures a wide range of language abilities underpinned by a cognitive neuropsychological model of language processing. Methods One hundred healthy participants were recruited (mean age 64 ± 10.4 years) as part of a large population-based study assessing cognitive change in Amyotrophic Lateral Sclerosis (ALS) and were assessed using the PALPA protocol. Reliability was measured by means of internal consistency and test-retest reliability. Validity was assessed through an inter-correlational analysis between PALPA subtests and a correlational analysis between PALPA subtests and external variables. A supplementary validation study (n = 35) of the Auditory Sentence – Picture Matching subtest of the PALPA against the TROG-2, another test of grammatical and syntactic processing, was carried out. Results The PALPA protocol had good internal consistency (Cronbach’s alpha coefficient = 0.78). Intra-class correlations indicated moderate to excellent test-retest reliability (ICCs ranging from 0.62 to 0.93), with significant agreements (p <.05) between time points in most cases. Validity of PALPA subtests was demonstrated by significant positive correlations among PALPA subtests (especially between those measuring the same language construct, ranging from 0.41 to 0.74). Moreover, the PALPA subtests correlated equivalently with external variables such as age, years of education and IQ, which further supported construct validity. Conclusion This study has proven adequate reliability and validity of a standardized protocol of the PALPA. Based on results from the assessment of psychometric properties of the PALPA protocol studied, adjusted IQ-based PALPA scores were generated.

Wnt antagonist FRZB is a muscle biomarker of denervation atrophy in amyotrophic lateral sclerosis

Skeletal muscle and the neuromuscular junction are the earliest sites to manifest pathological changes in amyotrophic lateral sclerosis (ALS). Based on prior studies, we have identified a molecular signature in muscle that develops early in ALS and parallels disease progression. This signature represents an intersection of signaling pathways including Smads, TGF-β, and vitamin D. Here, we show that the Wnt antagonist, Frizzled Related Protein (FRZB), was increased in ALS muscle samples and to a variable extent other denervating disease but only minimally in acquired myopathies. In the SOD1G93A mouse, FRZB was upregulated in the early stages of disease (between 40 and 60 days) until end-stage. By immunohistochemistry, FRZB was predominantly localized to endomysial connective tissue and to a lesser extent muscle membrane. There was a significant increase in immunoreactivity surrounding atrophied myofibers. Because FRZB is a Wnt antagonist, we assessed β-catenin, the canonical transducer of Wnt signaling, and found increased levels mainly at the muscle membrane. In summary, we show that FRZB is part of a molecular signature of muscle denervation that may reflect disease progression in ALS. Our findings open up avenues for future investigation as to what roles FRZB and Wnt signaling might be playing in muscle denervation/reinnervation.

Tract-specific analysis improves sensitivity of spinal cord diffusion MRI to cross-sectional and longitudinal changes in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord. Corticospinal tract degeneration is a defining feature of ALS. However, there have been very few longitudinal, controlled studies assessing diffusion MRI (dMRI) metrics in different fiber tracts along the spinal cord in general or the corticospinal tract in particular. Here we demonstrate that a tract-specific analysis, with segmentation of ascending and descending tracts in the spinal cord white matter, substantially increases the sensitivity of dMRI to disease-related changes in ALS. Our work also identifies the tracts and spinal levels affected in ALS, supporting electrophysiologic and pathologic evidence of involvement of sensory pathways in ALS. We note changes in diffusion metrics and cord cross-sectional area, with enhanced sensitivity to disease effects through a multimodal analysis, and with strong correlations between these metrics and spinal components of ALSFRS-R.

Retinal changes in amyotrophic lateral sclerosis: looking at the disease through a new window.

Amyotrophic lateral sclerosis (ALS) is the most frequent degenerative disease affecting motor neurons (MN). ALS has been traditionally considered as a pure motor system disease; however, there are currently sufficient evidences supporting the involvement of other non-motor systems. Recently, the development and the implementation of the optical coherence tomography (OCT) have provided new data regarding the ocular involvement in the disease. In this sense, alterations in retinal nerve fiber layer thickness (RNFL), other retinal layers thicknesses such as outer nuclear layer (ONL) and inner nuclear layer (INL) and changes in the retinal blood vessels have been described in ALS patients. Interestingly, the study of ocular alterations in ALS appears not only as new biomarker tool, but also as a new opportunity to deep into the pathogenesis of the disease. In this article we will review and standardize published studies regarding OCT and ALS, emphasizing both their strengths and weaknesses.