Executive Dysfunctions and Event-Related Brain Potentials in Patients with Amyotrophic Lateral Sclerosis

Electrocortical and behavioral effects of chronic immobility on word processing

Further studies on the erythrocyte uptake of lead in vitro in amyotrophic lateral sclerosis (ALS) patients and controls: Abnormal eythrocyte fragility in ALS

Background: In recent years, the role of iron metabolism in amyotrophic lateral sclerosis (ALS) attracts more and more attention, and some studies have focused on the link between abnormal serum iron indicators and ALS. However, there are still big conflicts and inconsistency among different studies. To study the possible relationship between ALS and disturbed iron metabolism, we conducted this meta-analysis to conclude characteristics of abnormal serum iron-status indicator changes in ALS patients.Methods: We searched and screened main databases, including the PubMed, Embase, and Cochrane Library, to find studies related to the association between iron metabolism and ALS. The Revman 5.3 software was used to conduct meta-analysis.Results: Eleven studies were finally included in our analysis, composed of 1,599 ALS patients and 1,255 controls in total. The results showed that the ferritin level was much higher in ALS patients compared with controls (MD = 70.48, 95% CI [51.41, 89.55], p < 0.00001), and the transferrin level was decreased in ALS patients compared with controls (SMD = −0.28, 95% CI [−0.38, −0.18], p < 0.00001), while there was no statistical difference in iron levels (SMD = 0.48, 95% CI [−0.07, 1.03], p = 0.09) between ALS patients and controls.Conclusions: Our research finds unusual changes in several indicators representing iron status, which suggest possible iron metabolism abnormalities in ALS patients. That may provide evidence for the link between iron metabolism and the pathogenesis of ALS.

Objective The coronavirus disease 2019 (COVID-19) pandemic has resulted in a shortage of medical resources, including ventilators, personal protective equipment, medical staff, and hospital beds. We investigated the impact of COVID-19 in amyotrophic lateral sclerosis (ALS) patients, their families, caregivers, and medical experts. Methods We conducted a nationwide ALS webinar about COVID-19 in May 2020 and sent a questionnaire to those enrolled. Results A total of 135 participants (31 ALS patients; 23 families and caregivers of ALS patients; 81 medical experts) responded to this cross-sectional self-report questionnaire. The results showed that tracheostomy and invasive ventilation (TIV) was used in 22.6% of ALS patients, whereas 77.4% of ALS patients were not under TIV. Among non-TIV patients (n=24), 79.2% did not want TIV in the future. However, 47.4% of non-TIV patients not wanting a tracheostomy in advanced stages replied that they would want an emergency tracheostomy if they developed COVID-19-related pneumonia. These results suggest that ALS patients may be receptive to emergency treatments for reasons other than ALS. In addition, approximately half of the ALS patients agreed with the policy of not ventilating the elderly or ALS patients in case of a ventilator shortage. Furthermore, compared with medical experts, few ALS patients reported that the chance for ALS patients to obtain work was higher due to the increasing availability of remote work. Conclusions This survey indicates that the COVID-19 pandemic might be associated with increased distress about access to care and work, inducing contradictory responses and potential hopelessness among ALS patients.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron (MN) degeneration, frequently overlapping with frontotemporal dementia (FTD). Protein aggregation is a hallmark of these disorders, yet the role of aggregates in ALS pathogenesis remains unclear. Previously, stomatin-like protein 2 (SLP2) and prohibitin (PHB) aggregates were identified in a model of CHCHD10-related ALS (Chchd10S59L/+ mice). This study raises the question of the presence and possible involvement of these aggregates in ALS beyond CHCHD10-associated motor neuron disease (MND). Using immunohistofluorescence, we analyzed SLP2/PHB expression in the spinal MNs and hippocampus of two ALS mouse models: FusΔNLS and Sod1G86R. Additionally, post-mortem spinal cord tissues from 27 ALS and ALS-FTD patients were analyzed. SLP2/PHB aggregates were identified in spinal MNs and the hippocampus of FusΔNLS mice but not in Sod1G86R mice. In ALS patients, SLP2/PHB aggregation was observed in four cases, including two with C9ORF72 mutations. Interestingly, aggregates were absent in SOD1-associated ALS patients. These findings suggest that SLP2/PHB aggregation is not specific to CHCHD10 variants but may contribute to the pathogenesis of ALS from different origins. The age-related accumulation of these aggregates highlights their potential role in disease progression and as therapeutic targets. Future studies should investigate their mechanistic contributions across different ALS subtypes.

Assessment of social cognition impairments in patients with amyotrophic lateral sclerosis: How can it be improved? A systematic review.

Since amyotrophic lateral sclerosis (ALS) can be accompanied by executive dysfunction, it is hypothesised that ALS patients will have impaired performance on tests of cognitive inhibition. We predicted that ALS patients would show patterns of abnormal activation in extramotor regions when performing tests requiring the inhibition of prepotent responses (the Stroop effect) and the inhibition of prior negatively primed responses (the negative priming effect) when compared to healthy controls. Functional magnetic resonance imaging was used to measure activation during a sparse sequence block design paradigm investigating the Stroop and negative priming effects in 14 ALS patients and 8 healthy age- and IQ-matched controls. Behavioural measures of performance were collected. Both groups’ reaction times (RTs) reflected the Stroop effect during scanning. The ALS and control groups did not differ significantly for any of the behavioural measures but did show significant differences in cerebral activation during both tasks. The ALS group showed increased activation predominantly in the left middle temporal gyrus (BA 20/21), left superior temporal gyrus (BA 22) and left anterior cingulate gyrus (BA 32). Neither group’s RT data showed clear evidence of a negative priming effect. However the ALS group showed decreased activation, relative to controls, particularly in the left cingulate gyrus (BA 23/24), left precentral gyrus (BA 4/6) and left medial frontal gyrus (BA 6). Greater cerebral activation in the ALS group accompanying the performance of the Stroop effect and areas of decreased activation during the negative priming comparison suggest altered inhibitory processing in ALS, consistent with other evidence of executive dysfunction in ALS. The current findings require further exploration in a larger study.

A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan

BackgroundUsing in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients.MethodsIn this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup.ResultsWe found that compared with HCs, ALS patients had a significantly higher CP volume (p < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction (p = 0.006 and p < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score (r = -0.226; p = 0.005) and the Qalb (r = 0.479; p < 0.001) in ALS patients.ConclusionOur study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.

Objective To characterize the brain microstructure changes of amyotrophic lateral sclerosis (ALS) patients with various levels of cognitive impairment as measured by diffusion tensor imaging (DTI). Methods A total of 55 ALS patients and 20 healthy controls (HC) were enrolled in the Department of Neurology of Peking Union Medical College Hospital From September 2013 to March 2017, and all participants underwent neuropsychological assessments and DTI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n=27), ALS with cognitive impairment (ALS-Ci, n=17) and ALS-frontotemporal dementia (ALS-FTD, n=11) subgroups. Comparisons of voxel-based and atlas-based fractional anisotropy (FA) and mean diffusivity (MD) data were conducted among the four subgroups. Results In the voxel-based analyses, the FA showed significant differences in cingulate gyrus, corpus callosum, brain stem and cerebellum, and MD showed significant differences in bilateral frontal lobe, temporal lobe, cingulate gyrus, corpus callosum, and cerebellum among the four subgroups. Besides, when compared to ALS-Ci, ALS-Cn and HC groups in the order, the areas of involvement were larger and differences were more significant in ALS-FTD group. In the atlas-based analyses, the FA and MD of the corticospinal tracts revealed no difference within the patients groups, but decreased FA and increased MD were found compared to HC group. The ALS-FTD patients manifested widespread white matter fiber integrity damage and microstructure impairment in the extramotor areas compared to other three groups. Conclusion The brain white matter structural patterns of ALS patients correlate with their cognitive function, and there is a gradient of alterations across the ALS-Cn, ALS-Ci and ALS-FTD continuum. Key words: Amyotrophic lateral sclerosis; Cognition disorders; Frontotemporal dementia; Diffusion tensor imaging

BackgroundFasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS.MethodsEighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups.ResultsThe overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0–3) in ALS and 0 (0–0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs.DiscussionThe fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients.ConclusionsThe fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Reproductive and developmental behaviour in sheep: A.F. Fraser (Editor), in the Series Developments in Animal and Veterinary Sciences, Vol. 18. Elsevier Science Publishers, Amsterdam, 1985, 439 pp., Dfl. 160.00, US$59.25, ISBN 0-444-42444-X

Objective: Dysfunction of social cognition is well-recognized as one of amyotrophic lateral sclerosis (ALS) cognitive impairments. Previous studies have mostly associated social cognition subcomponents, including Theory of Mind (ToM), with executive dysfunction using highly-demanding tasks. In the present study, we investigate dysfunction of affective ToM in a sample of ALS patients without dementia and evaluate any possible associations both with executive and non-executive dysfunction. Methods: We included 42 ALS patients and 30 healthy controls (HC) and administered the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS). Affective ToM was examined based on the ECAS judgment of preference task; total score and type of errors (“favourite”, “unclassified”) were recorded for all participants. Results: A significant proportion of ALS patients (31%) were impaired on ToM task, scoring significantly lower compared to HC. Impairments in ToM task were more frequent (45%) in patients with cognitive impairment compared to those with intact cognition (15%). ALS patients showed significantly more errors on ToM task compared to HC. A significant association was found between ToM score and ECAS language and visuospatial abilities but not fluency, executive or memory function. Conclusion: Dysfunction of affective ToM appears prevalent in ALS patients without dementia, and associates with language and visuospatial abilities. These associations align with motor and extra-motor symptoms due to the degeneration across corresponding networks. Impaired ToM should be considered in clinical settings, since it might contribute to patients’ social life, as well as the burden of their caregivers and relatives.

Objective. The aim of this study was to assess iron status in a cohort of amyotrophic lateral sclerosis (ALS) patients compared to controls in order to evaluate these parameters as a risk factor or a modifying factor of ALS. Methods. We collected serum iron, ferritin, transferrin, total iron-binding capacity, and transferrin saturation coefficient (TSC) from 104 ALS patients at the time of diagnosis and from 145 controls. We reported phenotypic characteristics and evolution parameters such as ALSFRS-R and forced vital capacity at diagnosis and after one year of follow-up. In a first step we compared iron status between ALS patients and controls, and then we evaluated the relation between iron status and disease evolution of ALS patients using univariate and multivariate analysis. Results. We observed increased concentrations of serum iron (P = 0.002) and ferritin (P < 0.0001) and increased TSC (P = 0.017) in ALS patients. We also showed an association between markers of iron status and high body weight loss in ALS patients. The multivariate analysis of survival highlighted a significant relation between ferritin level and disease duration (P = 0.038). Conclusion. This is the first study showing a higher concentration of serum iron in ALS patients, strengthening the involvement of a deregulation of iron metabolism in ALS.

Objective of this study was to evaluate attentional control mechanisms in amyotrophic lateral sclerosis (ALS) using an auditory event-related potentials (ERPs) paradigm. Fifteen mild to moderate ALS patients and 15 healthy controls were administered a brief neuropsychological test battery and an ERPs paradigm assessing selective attention. Four types of auditory stimuli were presented in random order: short standard (200 Hz, 200 ms), long standard (200 Hz, 500 ms), short deviant (1000 Hz, 200 ms) and long deviant (1000 Hz, 500 ms). Participants had to respond to the long deviant stimuli only. During the task the electroencephalogram (EEG) was recorded. The N200, P300 and re-orienting negativity (RON) ERP components were analysed. Compared to controls ALS patients showed reduced amplitudes and delayed latencies of N200, P300 and RON. These results could be attributable to both an alteration in change detection resulting in a reduction of the allocation and re-orientation of attentional resources or a general slowing or reduction of neural processing efficiency in the same system. The ERPs results support the hypothesis that ALS involves extramotor cognitive functions including auditory attentional processing at all processing stages, early (200 ms) and late (300–600 ms). These data prove the usefulness and sensitivity of the auditory ERPs in detection of cognitive functions in ALS patients.