scholarly journals MRI Volumetric Analysis of the Thalamus and Hypothalamus in Amyotrophic Lateral Sclerosis

2022 ◽  
Vol 13 ◽  
Author(s):  
Shan Ye ◽  
Yishan Luo ◽  
Pingping Jin ◽  
Yajun Wang ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Brain Volume ◽  
Volumetric Analysis ◽  
Motor Dysfunction ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Healthy Controls ◽  
Whole Brain ◽  
Left And Right ◽  
Lateral Sclerosis

Background: Increasing evidence has shown that amyotrophic lateral sclerosis (ALS) can result in abnormal energy metabolism and sleep disorders, even before motor dysfunction. Although the hypothalamus and thalamus are important structures in these processes, few ALS studies have reported abnormal MRI structural findings in the hypothalamus and thalamus.Purpose: We aimed to investigate volumetric changes in the thalamus and hypothalamus by using the automatic brain structure volumetry tool AccuBrain®.Methods: 3D T1-weighted magnetization-prepared gradient echo imaging (MPRAGE) scans were acquired from 16 patients with ALS with normal cognitive scores and 16 age-, sex- and education-matched healthy controls. Brain tissue and structure volumes were automatically calculated using AccuBrain®.Results: There were no significant differences in bilateral thalamic (F = 1.31, p = 0.287) or hypothalamic volumes (F = 1.65, p = 0.213) between the ALS and control groups by multivariate analysis of covariance (MANCOVA). Left and right hypothalamic volumes were correlated with whole-brain volume in patients with ALS (t = 3.19, p = 0.036; t = 3.03, p = 0.044), while the correlation between age and bilateral thalamic volumes tended to be significant after Bonferroni correction (t = 2.76, p = 0.068; t = 2.83, p = 0.06). In the control group, left and right thalamic volumes were correlated with whole-brain volume (t = 4.26, p = 0.004; t = 4.52, p = 0.004).Conclusion: Thalamic and hypothalamic volumes did not show differences between patients with normal frontotemporal function ALS and healthy controls, but further studies are still needed.

scholarly journals Brain Volumetric Changes and Cognitive Functions in Epileptic Patients

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A Ashour ◽  
A M A Nassef ◽  
E M Awad ◽  
A M Hazzou ◽  
M A Nada ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Brain Volume ◽  
Control Group ◽  
Healthy Controls ◽  
Whole Brain ◽  
Significant Difference ◽  
Epileptic Patients ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy ◽  
And Control

Abstract Background Epilepsy is a serious common neurological disorder that can affect any age. Cognitive functions are highly prevalent in patients with epilepsy and is more likely to occur in patients with idiopathic generalized epilepsy (IGE). Associations were found between cognitive functions and brain volume loss in patients with epilepsy. Objective This work was carried out to assess the volumetric changes in brain of epileptic patients to use it as a biomarker for cognitive dysfunction in adult and adolescent patients with epilepsy. Patients and Methods A case control study was conducted to include 61 patients, 20 of which diagnosed with idiopathic generalized epilepsy (IGE), 21 with temporal lobe epilepsy (TLE) and 20 with frontal lobe epilepsy (FLE) who were selected from the epilepsy outpatient clinic in Ain Shams university hospitals along with 23 age and sex matched healthy controls. Both cases and control groups were subjected to Magnetic resonance imaging MRI brain volumetry and detailed cognitive testing. An informed consent was taken from each adult patient, guardian of adolescent patient and healthy control. Results Statistically significant difference in comprehension subcategory of the Wechsler adult intelligence scale (WAIS) between patients with IGE and healthy controls denoting poorer social judgment in the IGE group. The IGE group also showed poorer performance in digit symbol subcategory of the same test denoting worse psychomotor speed and sustained attention. Also, significant difference in similarities subcategory was found between TLE group and control group denoting poorer abstract thinking among the TLE group. The IGE and TLE groups also showed lower attention and concentration than control group in the mental control subcategory of the Wechsler memory scale (WMS) yet failed to show superiority over each other. No statistically significant difference was found on comparing the whole brain volume between cases and control groups. A statistically significant direct relationship was found between the arithmetic subcategory of WAIS and the whole brain volume of the patients among the patients of the FLE group. Conclusion Patients with IGE had worse psychomotor speed, sustained attention and concentration than healthy controls in addition to poorer social judgment. Also, patients with TLE showed lower attention and concentration together with poorer abstract thinking despite normal IQ. The study also concluded that increased whole brain volume in patients with frontal lobe epilepsy is associated with better mathematical problem solving.

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Acoustic Analysis ◽  
Speaking Rate ◽  
Disease Stage ◽  
Healthy Controls ◽  
Tongue Movement ◽  
Major Barrier ◽  
Syllable Repetition ◽  
Oral Diadochokinesis ◽  
Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

scholarly journals Improved Long-Term Survival with Edaravone Therapy in Patients with Amyotrophic Lateral Sclerosis: A Retrospective Single-Center Study in Japan

2021 ◽  
Vol 14 (8) ◽  
pp. 705
Author(s):  
Hideki Houzen ◽  
Takahiro Kano ◽  
Kazuhiro Horiuchi ◽  
Masahiro Wakita ◽  
Azusa Nagai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rank Test ◽  
Positive Pressure ◽  
Control Group ◽  
Single Center ◽  
Term Survival ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Lateral Sclerosis

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2–64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan–Meier analysis, which revealed that the median survival durations were 49 (9–88) and 25 (8–41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.

scholarly journals Lingual–Alveolar Contact Pressure During Speech in Amyotrophic Lateral Sclerosis: Preliminary Findings

2017 ◽  
Vol 60 (4) ◽  
pp. 810-825 ◽  
Author(s):  
Jeff Searl ◽  
Stephanie Knollhoff ◽  
Richard J. Barohn
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Healthy Volunteers ◽  
Contact Pressure ◽  
Statistical Difference ◽  
Healthy Controls ◽  
Perceptual Judgments ◽  
Before And After ◽  
Preliminary Study ◽  
Contact Pressures ◽  
Lateral Sclerosis

Purpose This preliminary study on lingual–alveolar contact pressures (LACP) in people with amyotrophic lateral sclerosis (ALS) had several aims: (a) to evaluate whether the protocol induced fatigue, (b) to compare LACP during speech (LACP-Sp) and during maximum isometric pressing (LACP-Max) in people with ALS (PALS) versus healthy controls, (c) to compare the percentage of LACP-Max utilized during speech (%Max) for PALS versus controls, and (d) to evaluate relationships between LACP-Sp and LACP-Max with word intelligibility. Method Thirteen PALS and 12 healthy volunteers produced /t, d, s, z, l, n/ sounds while LACP-Sp was recorded. LACP-Max was obtained before and after the speech protocol. Word intelligibility was obtained from auditory–perceptual judgments. Results LACP-Max values measured before and after completion of the speech protocol did not differ. LACP-Sp and LACP-Max were statistically lower in the ALS bulbar group compared with controls and PALS with only spinal symptoms. There was no statistical difference between groups for %Max. LACP-Sp and LACP-Max were correlated with word intelligibility. Conclusions It was feasible to obtain LACP-Sp measures without inducing fatigue. Reductions in LACP-Sp and LACP-Max for bulbar speakers might reflect tongue weakness. Although confirmation of results is needed, the data indicate that individuals with high word intelligibility maintained LACP-Sp at or above 2 kPa and LACP-Max at or above 50 kPa.

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 Magnetic resonance findings in amyotrophic lateral sclerosis using a spin echo magnetization transfer sequence: preliminary report

1999 ◽  
Vol 57 (4) ◽  
pp. 912-915 ◽  
Author(s):  
ANTÔNIO JOSÉ DA ROCHA ◽  
ANTONIO CARLOS MARTINS MAIA JUNIOR ◽  
ROBERTO GOMES NOGUEIRA ◽  
HENRIQUE MANOEL LEDERMAN
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Magnetic Resonance ◽  
Preliminary Report ◽  
Corticospinal Tract ◽  
Spin Echo ◽  
Magnetization Transfer ◽  
Control Group ◽  
Spin Echo Sequence ◽  
Lateral Sclerosis

We present the magnetic resonance (MR) findings of five patients with amyotrophic lateral sclerosis (ALS) using a spin-echo sequence with an additional magnetization transfer (MT) pulse on T1-weighted images (T1 SE/MT). These findings were absent in the control group and consisted of hyperintensity of the corticospinal tract. Moreover we discuss the principles and the use of this fast but simple MR technique in the diagnosis of ALS

scholarly journals Design and analysis of a clinical trial using previous trials as historical control

2019 ◽  
Vol 16 (5) ◽  
pp. 531-538 ◽  
Author(s):  
David Alan Schoenfeld ◽  
Dianne M Finkelstein ◽  
Eric Macklin ◽  
Neta Zach ◽  
David L Ennist ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Sample Size ◽  
Standard Error ◽  
Controlled Trial ◽  
Sample Size Calculation ◽  
Control Group ◽  
Controlled Trials ◽  
Number Of Patients ◽  
Lateral Sclerosis

Background/AimsFor single arm trials, a treatment is evaluated by comparing an outcome estimate to historically reported outcome estimates. Such a historically controlled trial is often analyzed as if the estimates from previous trials were known without variation and there is no trial-to-trial variation in their estimands. We develop a test of treatment efficacy and sample size calculation for historically controlled trials that considers these sources of variation.MethodsWe fit a Bayesian hierarchical model, providing a sample from the posterior predictive distribution of the outcome estimand of a new trial, which, along with the standard error of the estimate, can be used to calculate the probability that the estimate exceeds a threshold. We then calculate criteria for statistical significance as a function of the standard error of the new trial and calculate sample size as a function of difference to be detected. We apply these methods to clinical trials for amyotrophic lateral sclerosis using data from the placebo groups of 16 trials.ResultsWe find that when attempting to detect the small to moderate effect sizes usually assumed in amyotrophic lateral sclerosis clinical trials, historically controlled trials would require a greater total number of patients than concurrently controlled trials, and only when an effect size is extraordinarily large is a historically controlled trial a reasonable alternative. We also show that utilizing patient level data for the prognostic covariates can reduce the sample size required for a historically controlled trial.ConclusionThis article quantifies when historically controlled trials would not provide any sample size advantage, despite dispensing with a control group.

scholarly journals T73. COGNITIVE CLUSTERING IN SCHIZOPHRENIA SPECTRUM DISORDER AND THE ASSOCIATION WITH BRAIN VOLUME

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S259-S259
Author(s):  
Priscilla Oomen ◽  
Marieke Begemann ◽  
Hannah de Muinck Keizer ◽  
Iris Sommer
Keyword(s):  
Hierarchical Clustering ◽  
Brain Volume ◽  
Spectrum Disorder ◽  
Healthy Controls ◽  
Cognitive Profiles ◽  
Schizophrenia Spectrum Disorder ◽  
Whole Brain ◽  
Schizophrenia Spectrum ◽  
Significant Difference ◽  
Cluster 2

Abstract Background Cognitive impairment is a core feature of schizophrenia spectrum disorder (SSD), and appears in both mild and severe forms. As cognition is crucial for functioning in daily life, it is important to understand these impairments. Large heterogeneity exists within these cognitive impairments, and different cognitive profiles may be associated with dissimilar structural brain volumes. Such cognitive brain profiles may be relevant biomarkers for more homogeneous subclasses to be used for both prognosis and choice of optimal care. Methods The population consisted of 85 individuals with schizophrenia spectrum disorder (mean age 27 years, 64 males) and 40 healthy controls (mean age 24 years, 31 males). To identify cognitive clusters, hierarchical clustering analyses were conducted using performance on the Brief Assessment of Cognition in Schizophrenia (BACS) battery. The emerging cognitive clusters were compared in performance on the BACS, diagnosis and whole brain volume. Results Hierarchical clustering analyses revealed three cognitive profiles: cluster 1 “relatively intact” cluster 2 “mild-moderate impairment” and cluster 3 “severe impairment”. Cluster 1 comprised of 68% healthy controls vs 32% SSD patients, whereas clusters 3 comprised of 89% SSD patients vs 11% healthy controls. Cluster 2 was a rather mixed cluster with 25% healthy controls and 75% SSD patients. Whole brain volume shows a continuum towards smaller brain volume in the more impaired clusters with a significant difference shown in whole brain volume between cluster 1 and 3. Discussion These findings support the concept that cognitive heterogeneity among individuals with schizophrenia spectrum disorder can be reduced by using cognitive clustering methods. Furthermore, cognitive clusters are associated with brain volume sizes, indicating different underlying brain structure. Future research should focus on the predictive power of such clusters.

scholarly journals CSF chitinase proteins in amyotrophic lateral sclerosis

2019 ◽  
Vol 90 (11) ◽  
pp. 1215-1220 ◽  
Author(s):  
Alexander G Thompson ◽  
Elizabeth Gray ◽  
Alexander Bampton ◽  
Dominika Raciborska ◽  
Kevin Talbot ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Area Under The Curve ◽  
Neuronal Loss ◽  
Progression Rate ◽  
Healthy Controls ◽  
Reactive Protein ◽  
Classifier Performance ◽  
Disease Progression Rate ◽  
Csf Levels ◽  
Lateral Sclerosis

ObjectiveTo evaluate the classifier performance, clinical and biochemical correlations of cerebrospinal fluid (CSF) levels of the chitinase proteins Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1) and Chitinase-3-like protein 2 (CHI3L2) in amyotrophic lateral sclerosis (ALS).MethodsCSF levels of CHIT1, CHI3L1, CHI3L2, phosphorylated neurofilament heavy chain (pNFH) and C-reactive protein were measured by ELISA in a longitudinal cohort of patients with ALS (n=82), primary lateral sclerosis (PLS, n=10), ALS-mimic conditions (n=12), healthy controls (n=25) and asymptomatic carriers of ALS-causing genetic mutations (AGC; n=5).ResultsCSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p<0.001) and ALS-mimics (CHIT1, p<0.001; CHI3L1, p=0.017; CHI3L2, p<0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p<0.001). Chitinase levels were similar in AGCs and healthy controls. Chitinase proteins distinguished ALS from healthy controls (area under the curve (AUC): CHIT1 0.92; CHI3L1 0.80; CHI3L2 0.90), mimics (AUC: CHIT1 0.84; CHI3L1 0.73; CHI3L2 0.88) and, to a lesser extent, PLS (AUC: CHIT 0.73; CHI3L1 0.51; CHI3L2 0.82) but did not outperform pNFH. CHIT1 and CHI3L2 correlated with disease progression rate (Pearson’s r=0.49, p<0.001; r=0.42, p<0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (r=−0.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable.ConclusionsCSF chitinase proteins may have limited value as independent diagnostic and stratification biomarkers in ALS, but offer a window into non-autonomous mechanisms of motor neuronal loss in ALS, specifically in assessing response to therapies targeting neuroinflammatory pathways.

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