Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis

Neurology ◽  
1997 ◽  
Vol 49 (5) ◽  
pp. 1292-1298 ◽  
Author(s):  
Ulf Ziemann ◽  
Martin Winter ◽  
Carl D. Reimers ◽  
Karin Reimers ◽  
Frithjof Tergau ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Silent Period ◽  
Intracortical Inhibition ◽  
Control Group ◽  
Cortical Silent Period ◽  
Healthy Control ◽  
Als Patients ◽  
Period Duration ◽  
Lateral Sclerosis

We investigated 14 patients with amyotrophic lateral sclerosis (ALS) by paired conditioning-test transcranial magnetic stimulation to test the hypothesis that the motor cortex is hyperexcitable in ALS. Intracortical(corticocortical) inhibition was significantly less in the ALS group than in an age-matched healthy control group (85.3 ± 27.0% versus 45.2± 15.5%, respectively; p < 0.0001). In contrast, intracortical facilitation, motor threshold, and cortical silent period duration in the ALS patients were not different from the control group. We suggest that the selective abnormality of intracortical inhibition is best compatible with an impaired function of inhibitory interneuronal circuits in the motor cortex that in turn renders the corticomotoneuron hyperexcitable.

scholarly journals Significance of Serological Markers in Neurological Function and Progression Rate of Amyotrophic Lateral Sclerosis

2021 ◽  
Author(s):  
Xiaowen Chen ◽  
Junrong Li ◽  
Yingying Lv ◽  
Wei Zhang ◽  
xiujian Xu ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Creatine Kinase ◽  
Uric Acid ◽  
Total Cholesterol ◽  
Cystatin C ◽  
Control Group ◽  
Progression Rate ◽  
Cholesterol Levels ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Objective The present study was to investigate the significance of creatinine, uric acid, creatine kinase, total cholesterol, triglyceride, HCY (Homocysteine), and cystatin C in neurological function and progression rate of amyotrophic lateral sclerosis. Methods According to the diagnostic criteria of EI-Escorial (2000), 103 patients with ALS were enrolled. All patients were given corresponding serological tests at the initial diagnosis. The Revised ALS Functional Rating Scale (ALSFRS-R) and Disease Progression Rate (DPR) were evaluated. The detected indexes in blood tests included creatinine, uric acid, creatine kinase, total cholesterol, triglycerides, homocysteine, and cystatin C. All data were input into the computer, and the data analysis was performed by SPSS22.0 statistical software.Results 1. There were significant differences in creatinine, uric acid, creatine kinase,
total cholesterol, HCY and cystatin C between the two groups (P<0.05). The levels of uric acid and creatinine of ALS group were lower than those of the control group, and the levels of creatine kinase, total cholesterol, triglyceride, HCY and cystatin C were higher than that in the control group.
2. The results from correlation analysis demonstrated that there was a significant correlation between ALSFRS-R and creatinine (P<0.01), the correlation coefficient was 0.567 (positive correlation); There was also a significant correlation between DPR and creatinine (P<0.01), and the correlation coefficient was -0.808 (negative correlation). The correlations of DPR with triglyceride and total cholesterol were significantly negative correlated (P<0.05), with -0.201 and -0.210 of correlation coefficients, respectively. The remaining indexes did not show any correlation with ALSFRS-R and DPR.
Conclusions 1. Uric acid and creatinine of ALS patients were lower than that in healthy people. Creatine kinase, triglyceride, total cholesterol, HCY, and cystatin C in ALS patients were higher than those in health controls. There were significant metabolic abnormalities in ALS patients.
2. Creatinine level is an independent risk factor affecting ALSFRS-R. The creatinine and total cholesterol levels are also the independent risk factors affecting DPR. Creatinine and total cholesterol levels could be used as reliable indicators to evaluate the ALSFRS-R and DPR of ALS patients.

scholarly journals Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis

2021 ◽  
Author(s):  
Xintong Guo ◽  
Xiaoxuan Liu ◽  
Shan Ye ◽  
Xiangyi Liu ◽  
Xu Yang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Eye Movement ◽  
Smooth Pursuit ◽  
Oculomotor System ◽  
Control Group ◽  
Clinical Markers ◽  
Square Wave ◽  
Movement Parameters ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Background and Purpose It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and the corresponding pattern has not yet been established. Furthermore, bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. Methods Patients with clinically definite, probable or laboratory-supported probable ALS (n=60) and a control group composed of their caregivers (n=30) underwent clinical assessments and standardized evaluations of the oculomotor system using videonystagmography. The gaze test, reflexive saccade test and smooth pursuit test were administered to all subjects. Results Eye movement abnormalities such as square-wave jerks, abnormal cogwheeling during smooth pursuit, and saccade hypometria were observed in ALS patients. Square-wave jerks (p<0.001) and abnormal cogwheeling during smooth pursuit (p=0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (p=0.004) and abnormal cogwheeling during smooth pursuit (p=0.031) were found to be more common in ALS patients with bulbar involvement (n=44) than in those without bulbar involvement (n=16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n=12) and spinal-onset patients (n=48). Conclusion ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. These abnormalities were observed more common in the ALS patients with bulbar involvement. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS.

scholarly journals Orbitofrontal-hypothalamic projections are disrupted in hypermetabolic murine ALS model and human patients

2020 ◽  
Author(s):  
David Bayer ◽  
Stefano Antonucci ◽  
Hans-Peter Müller ◽  
Luc Dupuis ◽  
Tobias Boeckers ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Mouse Model ◽  
Lateral Hypothalamus ◽  
Large Scale ◽  
Energy Homeostasis ◽  
Metabolic Phenotype ◽  
Metabolic Disturbances ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractIncreased catabolism is a new clinical manifestation of Amyotrophic Lateral Sclerosis. A dysfunction of lateral hypothalamus may drive hypermetabolism in ALS; however, Its causes and anatomical substrates are unknown. We hypothesize that disruption cortico-hypothalamic circuits may impair energy homeostasis in ALS. We used rAAV2 for large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik to quantify projections from the forebrain to the latera hypothalamus of the SOD1(G93A) ALS mouse model as well as of the FusΔNLS ALS mouse model. Expanded projections from agranular Insula, ventrolateral orbitofrontal and secondary motor cortex to lateral hypothalamus were found in two independent cohorts of the hypermetabolic SOD1(G93A) ALS model. The non-hypermetabolic FusΔNLS ALS mouse model display a loss of projections from motor cortex but no change in projections from insula and orbitofronal cortex. 3T DTI-MRI data on 83 ALS patients and 65 controls confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients. Converging murine and human data demonstrate the selective disruption of hypothalamic inputs in ALS as a factor contributing to the origin of hypermetabolism.Significance statementWe provide a circuit perspective of the recently identified and medically relevant hyper-metabolic phenotype of Amyotrophic Lateral Sclerosis. We demonstrate the selective involvement of orbitofrontal, insular and motor cortex projections to hypothalamus in murine ALS models and in human patients. The enhanced pipeline for large-scale registration, segmentation projections mapping, the identification of new circuits target of neurodegeneration, and the relevance of these circuits in metabolic disturbances make this work relevant not only for the investigation of ALS but also for other neurodegenerative disease as well as for all conditions characterized by systemic energy imbalances.

Cortical silent period in patients with amyotrophic lateral sclerosis

1999 ◽  
Vol 169 (1-2) ◽  
pp. 93-97 ◽  
Author(s):  
Gabriele Siciliano ◽  
Maria Laura Manca ◽  
Laura Sagliocco ◽  
Elena Pastorini ◽  
Alberto Pellegrinetti ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Silent Period ◽  
Cortical Silent Period ◽  
Lateral Sclerosis

scholarly journals An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosis post-mortem motor cortex and cerebrospinal fluid

2021 ◽  
Author(s):  
Tiziana Petrozziello ◽  
Ana C. Amaral ◽  
Simon Dujardin ◽  
Sali M.K. Farhan ◽  
James Chan ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Molecular Mechanisms ◽  
Rating Scale ◽  
Phosphorylated Tau ◽  
Post Mortem ◽  
Significant Difference ◽  
Depth Analysis ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractAlthough the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimer’s disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS.

Rapid Voice Tremor, or “Flutter,” in Amyotrophic Lateral Sclerosis

1992 ◽  
Vol 101 (6) ◽  
pp. 511-518 ◽  
Author(s):  
Arnold E. Aronson ◽  
William S. Winholtz ◽  
Lorraine Olson Ramig ◽  
Sandra R. Silber
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Matched Control ◽  
Normal Subjects ◽  
Control Group ◽  
Fast Fourier Transform Analysis ◽  
Frequency Components ◽  
Low Levels ◽  
Frequency Modulations ◽  
Als Patients ◽  
Lateral Sclerosis

In an attempt to clarify the origin and frequency characteristics of a rapid voice tremor, or “flutter,” in patients with amyotrophic lateral sclerosis (ALS), eight patients (four men and four women; ages 42 to 70 years) who had ALS and rapid voice tremor and an age-and sex-matched control group of eight subjects were asked to sustain the vowel /a/ and their voices were recorded for later analysis. Each segment of phonation was demodulated into amplitude and frequency components. From each subject's 8-second amplitude and frequency signals, a fast Fourier transform analysis was done on a 1-second segment previously identified perceptually as having the most apparent tremor or flutter. The results showed that patients with ALS had multiple combinations of levels and frequencies for amplitude and frequency modulations in comparison with control subjects, who had consistently low levels of modulations. In an attempt to quantify the tremor or flutter in ALS, amplitude and frequency modulations were not clearly or predominantly represented at one point along the spectrum. Nevertheless, these frequency and amplitude modulations are more prominent in patients with ALS than in normal subjects. The origins of these aberrant frequency and amplitude modulations in ALS patients remain obscure, although speculation is that they are of peripheral rather than central nervous system origin.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Weidong Pan ◽  
Xiaojing Su ◽  
Jie Bao ◽  
Jun Wang ◽  
Jin Zhu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Amyotrophic Lateral Sclerosis ◽  
Rating Scale ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference ◽  
Als Patients ◽  
And Control ◽  
Lateral Sclerosis ◽  
Basic Treatment

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

scholarly journals Cortical interneuron-mediated inhibition delays the onset of amyotrophic lateral sclerosis

Brain ◽  
2020 ◽  
Vol 143 (3) ◽  
pp. 800-810 ◽  
Author(s):  
C Sahara Khademullah ◽  
Afif J Aqrabawi ◽  
Kara M Place ◽  
Zahra Dargaei ◽  
Xinyi Liang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Intracortical Inhibition ◽  
Motor Deficits ◽  
Cortical Interneuron ◽  
Neuronal Populations ◽  
Cortical Hyperexcitability ◽  
Symptom Progression ◽  
Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis is a fatal disease resulting from motor neuron degeneration in the cortex and spinal cord. Cortical hyperexcitability is a hallmark feature of amyotrophic lateral sclerosis and is accompanied by decreased intracortical inhibition. Using electrophysiological patch-clamp recordings, we revealed parvalbumin interneurons to be hypoactive in the late pre-symptomatic SOD1*G93A mouse model of amyotrophic lateral sclerosis. We discovered that using adeno-associated virus-mediated delivery of chemogenetic technology targeted to increase the activity of the interneurons within layer 5 of the primary motor cortex, we were able to rescue intracortical inhibition and reduce pyramidal neuron hyperexcitability. Increasing the activity of interneurons in the layer 5 of the primary motor cortex was effective in delaying the onset of amyotrophic lateral sclerosis-associated motor deficits, slowing symptom progression, preserving neuronal populations, and increasing the lifespan of SOD1*G93A mice. Taken together, this study provides novel insights into the pathogenesis and treatment of amyotrophic lateral sclerosis.

scholarly journals The Role of Osteopontin in Amyotrophic Lateral Sclerosis: A Systematic Review

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Seyed Vahid Mousavi ◽  
Elmira Agah ◽  
Abbas Tafakhori
Keyword(s):  
Animal Model ◽  
Amyotrophic Lateral Sclerosis ◽  
Cortical Neurons ◽  
Human Studies ◽  
Cochrane Library ◽  
Control Group ◽  
Model Studies ◽  
Als Patients ◽  
Lateral Sclerosis

Context: Osteopontin (OPN) is a matrix phosphoprotein expressed by a variety of tissues and cells, including the immune system and the nervous system. Previous studies have shown that OPN may have a role in neurodegenerative diseases, including multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Objectives: The present study aimed to systematically review studies investigating the role of OPN in amyotrophic lateral sclerosis (ALS) patients or the disease animal model. Evidence Acquisition: We searched the Cochrane Library, PubMed, Web of Science, and Scopus to find relevant articles published up to January 20, 2019. Both human and animal model studies of ALS were considered. Results: A total of nine articles (four human studies and five animal model studies) were included. Two of the human studies reported that the CSF levels of OPN were higher among ALS patients compared to controls. The other two human studies found that OPN levels in cortical neurons did not differ significantly between ALS cases and the non-neurological control group. One of the studies found that the expression level of OPN in astrocytes was similar between ALS patients and the control group, but the level of microglial OPN significantly increased in ALS cases. Four of the animal model studies reported that the expression of OPN mRNA in spinal cord microglia significantly increased during the disease progression. The remaining animal model study found that OPN was selectively expressed by fast fatigue-resistant and slow motor neurons (MNs), which are resistant to ALS, and that the OPN expression was low among fast-fatigable MNs. Conclusions: Prompt microglial activation is a hallmark pathology of ALS, and OPN is among the most widely expressed proteins by these activated glial cells. Therefore, OPN might have a role in ALS pathogenesis. The existing evidence is not sufficient to justify whether OPN has a neurotoxic or neuroprotective role in ALS. We encourage researchers to investigate the role of OPN in ALS pathogenesis more extensively.

Sign in / Sign up

Export Citation Format

Share Document