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

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.

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

10.1101/2020.12.30.20248944 ◽

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.

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Correlations Between Median Nerve Sonography and Conduction Study Results and Functional Scales in Amyotrophic Lateral Sclerosis

ACTA MEDICA IRANICA ◽

10.18502/acta.v57i11.3264 ◽

2020 ◽

Author(s):

Parvaneh Deilami ◽

Shadi Ghourchian ◽

Bahram Haghi Ashtiani ◽

Sara Esmaeili ◽

Maryam Bahadori ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Median Nerve ◽

Rating Scale ◽

Normal Population ◽

Compound Muscle Action Potential ◽

Cross Sectional ◽

Study Results ◽

Significant Difference ◽

Als Patients ◽

Lateral Sclerosis

We aimed to compare the sonographic measurement of median nerve cross-section area (CSA) in patients with Amyotrophic Lateral Sclerosis (ALS) and healthy individuals. The effect of duration of the disease on correlations between paraclinical findings and ALS functional rating scale (ALSFRS) were secondarily aimed to be evaluated. The cross-sectional study was approved by the Ethical Committee of Iran University of Medical Sciences and conducted between January 2017 and December 2018. We evaluated the median nerve surface area by means of sonography in 35 ALS patients and 35 healthy controls. Compound muscle action potential (CMAP) amplitudes during nerve conduction study and ALSFRS were recorded by the same trained specialist. Data were analyzed using SPSS software version 18. We did not find a significant difference between CSA in ALS patients and the normal population (P>0.05). Comparing to normal individuals, the mean CMAP decreased significantly in ALS patients (6.6±3.07 mV versus 10.25±2.2 mV, P<0.001). ALSFRS correlated with both CSA of the median nerve at the wrist (P:<0.001, r:0.78) and the CMAP (P:<0.001, r:0.74) that were confirmed by regression models designed to consider the effect of disease duration on these correlations. CSA was not different between ALS patients and the normal population, but CMAP decreased in ALS patients. ALSFRS correlated with both CSA and CMAP of the median nerve.

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G-CSF (filgrastim) treatment for amyotrophic lateral sclerosis: protocol for a phase II randomised, double-blind, placebo-controlled, parallel group, multicentre clinical study (STEMALS-II trial)

BMJ Open ◽

10.1136/bmjopen-2019-034049 ◽

2020 ◽

Vol 10 (3) ◽

pp. e034049

Author(s):

Paolina Salamone ◽

Giuseppe Fuda ◽

Federico Casale ◽

Giuseppe Marrali ◽

Christian Lunetta ◽

...

Keyword(s):

Clinical Trial ◽

Amyotrophic Lateral Sclerosis ◽

Phase Ii ◽

Rating Scale ◽

Bone Marrow Cells ◽

Double Blind ◽

Double Blind Placebo ◽

Parallel Group ◽

Als Patients ◽

Lateral Sclerosis

IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurological disorder characterised by a selective degeneration of motor neurons (MNs). Stem cell transplantation is considered as a promising strategy in neurological disorders therapy and the possibility of inducing bone marrow cells (BMCs) to circulate in the peripheral blood is suggested to investigate stem cells migration in degenerated ALS nerve tissues where potentially repair MN damage. Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates haematopoietic progenitor cells, mobilises BMCs into injured brain and it is itself a neurotrophic factor for MN. G-CSF safety in humans has been demonstrated and many observations suggest that it may affect neural cells. Therefore, we decided to use G-CSF to mobilise BMCs into the peripheral circulation in patients with ALS, planning a clinical trial to evaluate the effect of G-CSF administration in ALS patients compared with placebo.Methods and analysisSTEMALS-II is a phase II multicentre, randomised double-blind, placebo-controlled, parallel group clinical trial on G-CSF (filgrastim) and mannitol in ALS patients. Specifically, we investigate safety, tolerability and efficacy of four repeated courses of intravenous G-CSF and mannitol administered in 76 ALS patients in comparison with placebo (indistinguishable glucose solution 5%). We determine increase of G-CSF levels in serum and cerebrospinal fluid as CD34+cells and leucocyte count after treatment; reduction in ALS Functional Rating Scale-Revised Score, forced vital capacity, Scale for Testing Muscle Strength Score and quality of life; the adverse events/reactions during the treatment; changes in neuroinflammation biomarkers before and after treatment.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Azienda Ospedaliera Universitaria ‘Città della Salute e della Scienza’, Torino, Italy. Results will be presented during scientific symposia or published in scientific journals.Trial registration numberEudract 2014-002228-28.

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Efficacy and Safety of Bumetanide in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Clinical Trial

10.21203/rs.3.rs-265649/v1 ◽

2021 ◽

Author(s):

Soraya Mehrabi ◽

Mohsen Sedighi ◽

Bahram Haghi Ashtiani ◽

Motahareh Afrakhteh ◽

Elahe Shahriari ◽

...

Keyword(s):

Clinical Trial ◽

Amyotrophic Lateral Sclerosis ◽

Placebo Group ◽

Motor Unit ◽

Rating Scale ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

Cortical Hyperexcitability ◽

Als Patients ◽

Lateral Sclerosis

Abstract Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the terminal degenerative disease of the motor units. This clinical trial was aimed to investigate the modulatory effect of bumetanide on physiological symptoms of ALS patients.Methods: This was a double-blind, placebo-controlled trial in which ALS patients were randomized 1:1 to receive bumetanide (2 mg daily) or matching placebo group for up to 4 months. Motor Unit Number Index (MUNIX), motor unit size index (MUSIX), and ALS Functional Rating Scale, revised (ALSFRS-R) was assessed before and after treatment as following bumetanide treatment.Results: 18 patients were allocated to bumetanide and 18 to the placebo group. In final analysis, 16 patients in bumetanide and 15 patients in the placebo group completed the trial. Patients in the placebo group showed a significant decrease in MUNIX value for all examined muscles after treatment, while MUNIX value for trapezius in bumetanide group increased significantly (p˂0.05). MUZIX value for tibialis anterior and trapezius (p˂0.05) improved significantly after bumetanide administration, whereas trapezius (p˂0.05) and abductor pollicis brevis (p˂0.01) in the placebo group showed a significantly decreased value. ALSFRS-R score decreased significantly in the placebo group after treatment (p˂0.001), but ALSFRS-R in bumetanide group improved significantly (p˂0.05). Three adverse effects (polyuria, vertigo, orthostatic hypotension) in bumetanide group were judged to be related to bumetanide.Conclusion: Bumetanide treatment might be effective in modulation of ALS symptoms possibly due to the hyperpolarization of GABA actions and mitigation of cortical hyperexcitability.

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Embitterment in war veterans with posttraumatic stress disorder (PTSD)

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.354 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S359-S360 ◽

Cited By ~ 1

Author(s):

D. Sabic ◽

A. Sabic

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Health Center ◽

Rating Scale ◽

Stress Disorder ◽

World Health ◽

Control Group ◽

War Veterans ◽

Significant Difference ◽

And Control

The aim of this study was to analyse frequency of embitterment in war veterans with Posttraumatic stress disorder (PTSD) as well as the potential impact of embitterment on the development of chronic PTSD.Patients and methodsIt was analyzed 174 subjects (from Health Center Zivinice/mental health center) through a survey conducted in the period from March 2015 to June 2016, of which 87 war veterans with PTSD and control subjects 87 war veterans without PTSD. The primary outcome measure was the post-traumatic embitterment disorder self-rating scale (PTED Scale) who contains 19 items designed to assess features of embitterment reactions to negative life events. Secondary efficacy measures included the clinician-administered PTSD scale–V (CAPS), the PTSD checklist (PCL), the combat exposure scale (CES), the Hamilton depression rating scale (HAM-D), the Hamilton anxiety rating scale (HAM-A) and the World health organization quality of life scale (WHOQOL-Bref). All subjects were male. The average age of patients in the group war veterans with PTSD was 52.78 ± 5.99. In the control group, average age was 51.42 ± 5.98. Statistical data were analyzed in SPSS statistical program.ResultsComparing the results, t-tests revealed significant difference between group veterans with PTSD and control group (t = −21,21, P < 0.0001). War veterans group with PTSD (X = 51.41, SD = 8,91), control group (X = 14.39, SD = 13.61).ConclusionEmbitterment is frequent in war veterans with PTSD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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

10.21203/rs.3.rs-667353/v1 ◽

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.

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Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis

10.21203/rs.3.rs-1114560/v1 ◽

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.

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The effect of autologous leukocyte platelet rich fibrin on the rate of orthodontic tooth movement: A prospective randomized clinical trial

European Journal of Dentistry ◽

10.4103/ejd.ejd_424_17 ◽

2018 ◽

Vol 12 (03) ◽

pp. 350-357 ◽

Cited By ~ 4

Author(s):

Azita Tehranchi ◽

Hossein Behnia ◽

Fereydoun Pourdanesh ◽

Parsa Behnia ◽

Nelson Pinto ◽

...

Keyword(s):

Clinical Trial ◽

Tooth Movement ◽

Random Effect ◽

Random Effect Model ◽

Orthodontic Tooth Movement ◽

Control Group ◽

Extraction Socket ◽

Effect Model ◽

Significant Difference ◽

And Control

ABSTRACT Objective: The aim of this study was to evaluate the effect of LPRF, placed in extraction sockets, on orthodontic tooth movement (OTM). Materials and Methods: Thirty extraction sockets from eight patients (five males, three females, with a mean age of 17.37 years; range 12–25 years) requiring extraction of first premolars based on their orthodontic treatment plan participated in this split-mouth clinical trial. In one randomly selected quadrant of each jaw, the extraction socket was preserved as the experimental group by immediate placement of LPRF in the extraction socket. The other quadrant served as the control group for secondary healing. Immediately, the teeth adjacent to the defects were pulled together by a NiTi closed-coil spring with constant force. A piece of 0.016 × 0.022-inch stainless steel wire was used as the main arch wire. The amount of OTM was measured on the study casts at eight time points with 2-week intervals for 3 months. Analysis of random effect model was performed for the purpose of comparison between the experimental and control groups. Results: According to the random effect model, a statistically significant difference was found between the experimental and control group in rate of OTM (P = 0.006). Conclusion: According to the results, application of LPRF, as an interdisciplinary approach combining orthodontics and surgery, may accelerate OTM, particularly in extraction cases.

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Proteostasis and ALS: protocol for a phase II, randomised, double-blind, placebo-controlled, multicentre clinical trial for colchicine in ALS (Co-ALS)

BMJ Open ◽

10.1136/bmjopen-2018-028486 ◽

2019 ◽

Vol 9 (5) ◽

pp. e028486 ◽

Cited By ~ 11

Author(s):

Jessica Mandrioli ◽

Valeria Crippa ◽

Cristina Cereda ◽

Valentina Bonetto ◽

Elisabetta Zucchi ◽

...

Keyword(s):

Clinical Trial ◽

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Phase Ii ◽

Mononuclear Cells ◽

Rating Scale ◽

Double Blind ◽

Peripheral Blood Mononuclear ◽

Double Blind Placebo ◽

Lateral Sclerosis

IntroductionDisruptions of proteasome and autophagy systems are central events in amyotrophic lateral sclerosis (ALS) and support the urgent need to find therapeutic compounds targeting these processes. The heat shock protein B8 (HSPB8) recognises and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs), as well as aggregating species of dipeptides produced in C9ORF72-related diseases. In ALS-SOD1 mice and in human ALS autopsy specimens, HSPB8 is highly expressed in spinal cord MNs that survive at the end stage of disease. Moreover, the HSPB8–BAG3–HSP70 complex maintains granulostasis, which avoids conversion of dynamic stress granules (SGs) into aggregation-prone assemblies. We will perform a randomised clinical trial (RCT) with colchicine, which enhances the expression of HSPB8 and of several autophagy players, blocking TDP-43 accumulation and exerting crucial activities for MNs function.Methods and analysisColchicine in amyotrophic lateral sclerosis (Co-ALS) is a double-blind, placebo-controlled, multicentre, phase II RCT. ALS patients will be enrolled in three groups (placebo, colchicine 0.01 mg/day and colchicine 0.005 mg/day) of 18 subjects treated with riluzole; treatment will last 30 weeks, and follow-up will last 24 weeks. The primary aim is to assess whether colchicine decreases disease progression as measured by ALS Functional Rating Scale - Revised (ALSFRS-R) at baseline and at treatment end. Secondary aims include assessment of (1) safety and tolerability of Colchicine in patiets with ALS; (2) changes in cellular activity (autophagy, protein aggregation, and SG and exosome secretion) and in biomarkers of disease progression (neurofilaments); (3) survival and respiratory function and (4) quality of life. Preclinical studies with a full assessment of autophagy and neuroinflammation biomarkers in fibroblasts, peripheral blood mononuclear cells and lymphoblasts will be conducted in parallel with clinic assessment to optimise time and resources.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Area Vasta Emilia Nord and by Agenzia Italiana del Farmaco (EUDRACT N.2017-004459-21) based on the Declaration of Helsinki. This research protocol was written without patient involvement. Patients’ association will be involved in disseminating the study design and results. Results will be presented during scientific symposia or published in scientific journals.Trial registration numberEUDRACT 2017-004459-21;NCT03693781; Pre-results.

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Influence of Therapeutic Play on the anxiety of hospitalized school-age children: Clinical trial

Revista Brasileira de Enfermagem ◽

10.1590/0034-7167-2016-0353 ◽

2017 ◽

Vol 70 (6) ◽

pp. 1244-1249 ◽

Cited By ~ 5

Author(s):

Sabrina Gisele Tobias da Silva ◽

Maiara Aurichio Santos ◽

Claudia Maria de Freitas Floriano ◽

Elaine Buchhorn Cintra Damião ◽

Fernanda Vieira de Campos ◽

...

Keyword(s):

Clinical Trial ◽

Statistical Significance ◽

School Age Children ◽

Control Group ◽

School Age ◽

Chi Square ◽

Number Of Children ◽

Significant Difference ◽

Therapeutic Play ◽

And Control

ABSTRACT Objective: To evaluate the effects of Dramatic Therapeutic Play (DTP) technique on the degree of anxiety in hospitalized school-age children. Method: Randomized clinical trial performed in two hospitals ofSão Paulo, between May and October 2015. The intervention consisted of the application of DTP and the outcome was evaluated through the Child Drawing: Hospital (CD: H) instrument. The Wilcoxon-Mann Whitney, Corrected t, Fisher’s exact and Chi-square tests were used in the analysis. Statistical significance was set at 5%. Results: In all, 28 children participated in the study. The majority of children (75%) had a low anxiety score, with a mean CD: H score of 73.9 and 69.4 in the intervention and control groups respectively, and with no significant difference. Conclusion: Children submitted to DTP had the same degree of anxiety as those in the control group. However, it is suggested that new studies be performed with a larger number of children in different hospitalization scenarios.

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