Format
Sort by
Items per page

Send to

Choose Destination

Search results

Items: 1 to 20 of 26963

1.
Medicine (Baltimore). 2020 Jan;99(1):e18615. doi: 10.1097/MD.0000000000018615.

Effects of electroacupuncture on patients with chronic urinary retention caused by a lower motor neuron lesion: An exploratory pilot study.

Author information

1
Department of Acupuncture, Guang'an Men Hospital, China Academy of Chinese Medical Sciences, Beijing.
2
Guiyang University of Chinese Medicine, Guiyang, China.

Abstract

Chronic urinary retention (CUR) is defined as a non-painful bladder that remains palpable or percussible after the patient has passed urine. Acupuncture may decrease PVR and improve bladder function in patients with neurogenic CUR. The aim of this study was to preliminarily observe the effectiveness of electroacupuncture (EA) for patients with CUR caused by a lower motor neuron lesion and to provide some therapeutic data for further study.This study was a pilot study of 30 patients with CUR caused by a lower motor neuron lesion. Patients were treated with EA for 12 weeks with 36 sessions of EA.Responders were defined as participants with a decline in postvoid residual urine (PVR) volume after spontaneous urination of ≥50% from baseline. The proportion of responders, change in PVR volume from baseline after spontaneous urination, and the proportion of patients with severe difficulty with urination, who required assistance with bladder emptying and with stool retention, were measured at weeks 4, 8, and 12.Thirty patients were included in this study, and 23 completed 12 weeks of treatment. The proportion of responders at weeks 4, 8, and 12 was 6.67%, 28%, and 43.48%, respectively. Decrease in PVR volume, compared with baseline, was significant at all asessment timepoints. The proportion of patients with severe difficulty with urination, who required assistance with bladder emptying and with stool retention, decreased after treatment.EA is a potential treatment for improving bladder function in patients with CUR caused by a lower motor neuron lesion.

PMID:
31895816
DOI:
10.1097/MD.0000000000018615
[Indexed for MEDLINE]
Free full text
Icon for Wolters Kluwer
2.
Fortschr Neurol Psychiatr. 2019 Dec;87(12):703-710. doi: 10.1055/a-0996-0994. Epub 2019 Dec 17.

[Spinal Muscular Atrophy - expert recommendations for the use of nusinersen in adult patients].

[Article in German; Abstract available in German from the publisher]

Author information

1
Klinik für Neurologie, Universitätsmedizin Essen.
2
Sektion für Translationale Neurodegeneration "Albrecht Kossel", Klinik und Poliklinik für Neurologie Universitätsmedizin Rostock.
3
Klinik und Poliklinik für Neurologie, Universitätsmedizin Rostock.
4
M.A. Friedrich-Baur-Institut, Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität.
5
Neurologische Klinik, Universitätsklinikum Heidelberg.
6
Klinik und Poliklinik für Neurologie, Technische Universität Dresden.
7
Klinik für Neurologie, Rehabilitations- und Universitätskliniken Ulm.

Abstract

With Nusinersen, a first causative treatment for 5q-associated spinal muscular atrophy (SMA) has been available in Europe since 2017. Real-world data from neuromuscular clinical centers in Germany increasingly show a therapeutic benefit of nusinersen also in adult SMA patients of both sexes: in many cases, relevant improvements in or at least a stabilization of motor functions are achieved, potentially leading to enhanced autonomy in activities of daily life and to improved quality of living. Even in patients with severe spinal deformities, intrathecal application is usually feasible and safe using imaging modalities. Regular systematic evaluation of the motor status with validated instruments is crucial for adequate monitoring of the therapeutic effects. The documentation in SMA registries enables systematic development of a database for further development of this novel treatment paradigm. Relevant aspects of this novel therapeutic principle were discussed at an experts conference in Frankfurt / Main in February 2019.

PMID:
31847032
DOI:
10.1055/a-0996-0994
[Indexed for MEDLINE]
Icon for Georg Thieme Verlag Stuttgart, New York

Conflict of interest statement

Der Beitrag entstand im Rahmen eines von Biogen unterstützten Expertenworkshops, in dem die Autoren beratend tätig waren.T. Hagenacker ist als Berater für Advisory Boards, sowie als Referent für Fortbildungsveranstaltungen und wissenschaftliche Veranstaltungen der Firma Biogen tätig. Außerdem hat er finanzielle Forschungsuntertützung von Biogen erhalten. M.C. Walter hat an Advisory boards der Firmen, Avexis, Biogen, Novartis, Roche, Santhera, Sarepta, PTC Therapeutics, Ultragenyx, Wave Sciences teilgenommen, hat Vortragshonorare von Novartis, Biogen, Ultragenyx, Santhera, PTC Therapeutics erhalten und war als Ad-Hoc-Beraterin für AskBio, Audentes Therapeutics, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, PTC Therapeutics tätig.M. Weiler hat an wissenschaftlichen Veranstaltungen teilgenommen, die von der Firma Biogen gesponsort wurden. Er ist zudem als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen der Firma Biogen tätig.A. Hermann ist als Berater für Advisory Boards der Firma Biogen und DESITIN tätig.C. Kamm hat an wissenschaftlichen Veranstaltungen teilgenommen, die von der Firma Biogen gesponsert wurden. Er ist zudem als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen der Firma Biogen tätig.C.D. Wurster ist als Beraterin für Advisory Boards sowie als Referentin für Fortbildungsveranstaltungen der Firma Biogen tätig. Sie ist zudem als Beraterin der Firma Hoffmann-La Roche tätig.R. Günther hat an wissenschaftlichen Veranstaltungen teilgenommen, die von der Firma Biogen gesponsort wurden. Er ist zudem als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen der Firma Biogen tätig.C. Kleinschnitz ist als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen und wissenschaftliche Veranstaltungen der Firma Biogen, Novartis und Roche tätig.

3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 Dec 10;36(12):1175-1178. doi: 10.3760/cma.j.issn.1003-9406.2019.12.006.

[Supplementary value of denaturing high performance liquid chromatography for routine prenatal diagnosis of spinal muscular atrophy by multiple ligation-dependent probe amplification].

[Article in Chinese]

Author information

1
Department of Obstetrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, China. 390266277@qq.com.

Abstract

OBJECTIVE:

To explore the feasibility of high performance liquid chromatography (DHPLC) combined with multiple ligation-dependent probe amplification (MLPA) for the prenatal diagnosis of spinal muscular atrophy (SMA).

METHODS:

Three families who had given birth to children with SMA type I were subjected to prenatal diagnosis. Peripheral blood samples were collected from the three couples, and 10 mL amniotic fluid was taken for each fetus through amniocentesis at 16-24 gestational week. Following DNA extraction, maternal contamination was excluded by STR analysis. Copy numbers of the SMN genes were detected by denaturing high performance liquid chromatography (DHPLC). Relative copy number of SMN1, SMN2 and reference genes was detected with a MLPA P021 assay kit.

RESULTS:

The three couples were all found to harbor heterozygous deletion of exon 7 of the SMN1 gene by DHPLC. MLPA analysis also suggested that the three couples were all carriers of SMA mutations. The fetus of family 1 harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus had SMA. The fetus of family 2 also harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, while the copy number of SMN2 gene was normal, suggesting that the fetus was a SMA patient too. The fetus of family 3 harbored heterozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus was a carrier.

CONCLUSION:

DHPLC can effectively screen carriers of SMA mutations. Combined DHPLC and MLPA can provide accurate diagnosis for fetuses with a high risk for SMA.

[Indexed for MEDLINE]
4.
Adv Exp Med Biol. 2019;1189:233-265. doi: 10.1007/978-981-32-9717-3_9.

Co-signaling Molecules in Neurological Diseases.

Author information

1
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Abou Haidar Neuroscience Institute and Nehme and Therese Tohme Multiple Sclerosis Center, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon. sk88@aub.edu.lb.

Abstract

Inflammation plays an important role in the onset and progression of many neurological diseases. As the central nervous system (CNS) constitutes a highly specialized environment where immune activation can be detrimental, it is crucial to understand mechanisms by which the immune system is regulated during neurological diseases. The system of co-signaling pathways provides the immune system with the means to fine-tune immune responses by turning on and off immune cell activation. Studies of co-signaling molecules in neurological diseases and their animal models have highlighted the complexities of immune regulation within the CNS and the intricacies of the interplay between the different cells of the immune system and how they interact with the resident cells of the CNS. This complexity poses challenges when targeting co-signaling pathway to treat neurological diseases and may explain why no drugs targeting these pathways have been successfully developed this far. Here, we will review the current literature on some important co-signaling pathways in multiple sclerosis (MS), Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and ischemic stroke to understand these pathways in mediating and controlling neuroinflammation.

KEYWORDS:

Alzheimer’s disease; Amyotrophic lateral sclerosis; Costimulatory molecules; Ischemic stroke; Multiple sclerosis; Neurological diseases; Parkinson’s disease

PMID:
31758537
DOI:
10.1007/978-981-32-9717-3_9
[Indexed for MEDLINE]
Icon for Springer
5.
Zhonghua Yi Xue Za Zhi. 2019 Nov 19;99(43):3413-3416. doi: 10.3760/cma.j.issn.0376-2491.2019.43.012.

[Application value of motor unit number index in patients with amyotrophic lateral sclerosis].

[Article in Chinese; Abstract available in Chinese from the publisher]

Author information

1
Department of neurology, Peking University Third Hospital, Beijing 100191, China.

Abstract

Objective: To investigate the application value of motor unit number index (MUNIX) for diagnosis and assessment progress in patients with amyotrophic lateral sclerosis (ALS). Method: Sixty healthy controls and 60 ALS patients in the clinic were enrolled from May 2017 to December 2018. The bilateral deltoid, abductor digiti minimi, quadriceps femoris and tibialis anterior muscles of the subjects were detected by MUNIX method, and the negative peak amplitude of compound muscle action potential (CMAP) of ulnar nerve, femoral nerve, peroneal nerve, axillary nerve in bilateral was collected. MUNIX and motor unit size index (MUSIX) of muscles were compared between ALS group and control group. The difference between the MUNIX abnormal rate of muscles and abnormal rate of the corresponding CMAP negative peak amplitude in ALS patients was further compared. Meanwhile, the correlation between the disease course of ALS patients and MUNIX and MUSIX was analyzed. Results: Compared with the control group, the MUNIX values of the deltoid, abductor digiti minimi, quadriceps femoris and tibialis anterior decreased significantly (97±24 vs 183±38, 48±17 vs 191±39, 54±15 vs 159±22, 49±16 vs 147±25, all P<0.05). MUSIX values increased ((175±32) μV vs (47±15) μV, (189±34) μV vs (54±16) μV, (170±30) μV vs (49±13) μV, (190± 36) μV vs (48± 14) μV, all P<0.05)). In ALS patients, the abnormal rate of MUNIX was respectively 81%, 87%, 75% and 89%. The negative peak amplitude abnormal rate of corresponding neuralCMAP was 35%, 40%, 31% and 36%, respectively, with a significant difference (P<0.05). There was a negative correlation between MUNIX value and the course of disease in ALS patients (P<0.05), and a positive correlation between MUSIX value and the course of disease (P<0.05). Conclusion: The MUNIX technique exhibits the features of quantifying the proximal upper and lower limb muscles and assessing the loss of motor units in motor neuron degeneration.

KEYWORDS:

Amyotrophic lateral sclerosis; Compound muscle action potential; Motor unit number index; Motor unit size index; Skeletal muscle

[Indexed for MEDLINE]
Icon for Chinese Medical Association Publishing House Ltd.
6.
J Phys Chem Lett. 2019 Dec 19;10(24):7740-7744. doi: 10.1021/acs.jpclett.9b02868. Epub 2019 Dec 3.

An Allosteric Pathway in Copper, Zinc Superoxide Dismutase Unravels the Molecular Mechanism of the G93A Amyotrophic Lateral Sclerosis-Linked Mutation.

Author information

1
Groningen Biomolecular Sciences and Biotechnology Institute , University of Groningen , Nijenborgh 4 , 9747 AG Groningen , The Netherlands.
2
Departamento de Ciencias del Ambiente, Facultad de Química y Biología , Universidad de Santiago de Chile (USACH) , Av. Libertador Bernardo O'Higgins 3363 , 9170022 Estacion Central , Chile.

Abstract

Several different mutations of the protein copper, zinc superoxide dismutase (SOD1) produce the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The molecular mechanism by which the diverse mutations converge to a similar pathology is currently unknown. The electrostatic loop (EL) of SOD1 is known to be affected in all of the studied ALS-linked mutations of SOD1. In this work, we employ a multiscale simulation approach to show that this perturbation corresponds to an increased probability of the EL detaching from its native position, exposing the metal site of the protein to water. From extensive atomistic and coarse-grained molecular dynamics (MD) simulations, we identify an allosteric pathway that explains the action of the distant G93A mutation on the EL. Finally, we employ quantum mechanics/molecular mechanics MD simulations to show that the opening of the EL decreases the Zn(II) affinity of the protein. As the loss of Zn(II) is at the center of several proposed pathogenic mechanisms in SOD1-linked ALS, the structural effect identified here not only is in agreement with the experimental data but also places the opening of the electrostatic loop as the possible main pathogenic effect for a significant number of ALS-linked SOD1 mutations.

PMID:
31747286
PMCID:
PMC6926953
DOI:
10.1021/acs.jpclett.9b02868
[Indexed for MEDLINE]
Free PMC Article
Icon for American Chemical Society Icon for PubMed Central
7.
Brain Nerve. 2019 Nov;71(11):1289-1301. doi: 10.11477/mf.1416201439.

[Immunotherapy Against Misfolded Proteins in ALS].

[Article in Japanese]

Author information

1
Department of Neurology, Shiga University of Medical Science.

Abstract

Protein misfolding crucially underlies the pathogenesis of amyotrophic lateral sclerosis (ALS). Mutant superoxide dismutase 1 (SOD1) and TAR DNA-binding protein 43kDa (TDP-43) are major causal proteins for familial and sporadic ALS, respectively, provoking diverse pathogenic pathways in both intracellular and extracellular environments. Of note, cell-to-cell spreading behavior is implicated in the progression of neurodegeneration, suggesting application in immunotherapies including vaccination, and antibody application as a molecular targeting therapy, due to strict antigen-specificity. Although immunotherapy of intravenous application of full-length immunoglobulin is aimed at targeting the extracellular proteins because of low access to the cytosol, it is therefore necessary to generate expression vectors for variable single chain fragments (scFv) that target intracellular proteins. Despite the advantages of scFv, such as low molecular size and the ability to apply molecular modifications adding proteolytic signals, safety and efficacy should be cautiously estimated in preclinical studies, using appropriate animal models. In ALS, we firstly succeeded in the vaccination of mutant SOD1 transgenic mice, which was followed by accumulating evidence showing the efficacy of immunization against misfolded SOD1. In TDP-43 proteinopathy, we are developing immunotherapy using intrabodies with proteolytic properties against mislocalized or aggregated forms of TDP-43 inside cells.

PMID:
31722315
DOI:
10.11477/mf.1416201439
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
8.
Brain Nerve. 2019 Nov;71(11):1279-1288. doi: 10.11477/mf.1416201438.

[Ropinirole Hydrochloride for ALS].

[Article in Japanese]

Author information

1
Department of Neurology and Stroke, Saitama medical university International medical center.

Abstract

Our laboratory previously established spinal motor neurons (MN) from induced-pluripotent stem cells (iPSCs) prepared from both sporadic and familial ALS patients, and successfully recapitulated disease-specific pathophysiological processes. We next searched for effective drugs capable of slowing the progression of ALS using a drug library of 1232 existing compounds and discovered that ropinirole hydrochloride prevented MN death. In December 2018, we started an investigator-initiated clinical trial testing ropinirole hydrochloride extended-release tablets in ALS patients. This is an on-going phase I/IIa randomized, double-blind, placebo-controlled, single-center, open-label continuation clinical trial (UMIN000034954). The primary aim is to assess the safety and tolerability of ropinirole hydrochloride in patients with ALS. We will also perform an efficacy evaluation using patient-derived iPSCs/MN. Major inclusion criteria were as follows: 1) 'clinically possible and laboratory-supported ALS', 'clinically probable ALS' or 'clinically definite ALS', according to the criteria for the diagnosis of ALS (El Escorial revised) and within 60 months after disease onset; 2) change in ALSFRS-R score of -2 to -5 points during the 12-week run-in period. Finally, 15 patients will be assigned to the active drug and 5 patients to the placebo. Our trial will be a touchstone trial for iPSC-based drug development strategies.

PMID:
31722314
DOI:
10.11477/mf.1416201438
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
9.
Brain Nerve. 2019 Nov;71(11):1270-1278. doi: 10.11477/mf.1416201437.

[Perampanel for Sporadic Amyotrophic Lateral Sclerosis].

[Article in Japanese]

Author information

1
Department of Neurology, Department of Neuropathogenesis, Tokyo Medical University.

Abstract

Disease-specific and site-selective deficiency of an RNA editing enzyme, adenosine deaminase acting on RNA 2 (ADAR2), has been demonstrated in sporadic amyotrophic lateral sclerosis (sALS) motor neurons. ADAR2 regulates Ca<sup>2+</sup> influx through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors via adenosine-to-inosine conversion at the glutamine/arginine site of GluA2 mRNA, which makes ADAR2 a key factor in acquired Ca<sup>2+</sup> resistance in motor neurons. Deficient ADAR2 of sALS motor neurons is supposed to lead to excessive Ca<sup>2+</sup> influx through AMPA receptors, resulting in TDP-43 pathology and nuclear pore complex pathology, and eventually motor neuronal death. We considered that AMPA receptor antagonists could strongly prevent excessive Ca<sup>2+</sup> influx through AMPA receptors and block motor neuronal degeneration in sALS. Perampanel, a selective non-competitive AMPA receptor antagonist, has been reported to prevent deterioration in a mouse model for sALS, in which ADAR2 is conditionally knocked out in motor neurons. Because of the therapeutic potency of perampanel for sporadic ALS, we have performed a multicenter randomized, double-blinded, placebo-controlled, parallel-group phase 2 clinical trial. The primary outcome measure is the change in ALS functional rating scale-revised after 48 weeks of treatment. The results of this study will be available in early 2020.

PMID:
31722313
DOI:
10.11477/mf.1416201437
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
10.
Brain Nerve. 2019 Nov;71(11):1261-1269. doi: 10.11477/mf.1416201436.

[JETALS: The Japanese Early-stage Trial of high dose methylcobalamin for ALS].

[Article in Japanese]

Author information

1
Department of Neurology, Tokushima University Hospital.

Abstract

High-dose methylcobalamin was found to be a therapeutic candidate for amyotrophic lateral sclerosis (ALS) through clinical experience. Our previous study (E0302-J081-761) has suggested that high-dose methylcobalamin (E0302) prolonged the overall survival and suppressed progression in ALS patients with a disease duration less than 12 months in, exploratory analyses. Therefore, we plan to conduct an investigator-initiated trial "The Japan Early-stage Trial of high dose methylcobalamin for ALS (JETALS)" to evaluate the efficacy and safety of E0302 for ALS patients within 12 months from onset. JETALS is a prospective, multicenter, placebo-controlled, double-blind, randomized Phase III study, conducted at 25 tertiary neurology centers, and is funded by the Japan Agency for Medical Research and Development. A total of 128 patients were randomized at a 1:1 ratio to receive intramuscular injection with E0302 50 mg or placebo, twice a week for 16 weeks. The primary endpoint is changes in the ALS Functional Rating Scale (ALSFRS-R) total score at 16 weeks. The patient enrollment period is from November 2017 to September 2019, and the follow-up is scheduled to end in March 2020. If the results are positive, we intend to apply for E0302 approval for methylcobalamin as a new drug for treating ALS.

PMID:
31722312
DOI:
10.11477/mf.1416201436
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
11.
Brain Nerve. 2019 Nov;71(11):1253-1260. doi: 10.11477/mf.1416201435.

[Application of Hepatocyte Growth Factor for Amyotrophic Lateral Sclerosis].

[Article in Japanese]

Author information

1
Department of Neurology, Tohoku University School of Medicine.

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder characterized by the death of upper and lower motor neurons. About 10% of all ALS cases are familial, and we have identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan (Nishiyama A, 2017). From studies of the TDP43, FUS, and C9orf72 genes, perturbations of RNA processing can be highly adverse in motor neurons. Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. We administered human recombinant HGF (hrHGF) by continuous intrathecal delivery to transgenic rats at onset of paralysis for 4 weeks. Intrathecal administration of hrHGF attenuated motor neuron degeneration and prolonged the duration of the disease by 63% (Ishigaki A, 2007). To translate this strategy to human treatment, we induced a contusive cervical spinal cord injury in the common marmoset, a primate, and then administered hrHGF intrathecally. We conducted a first-in-human phase I trial of intrathecal hrHGF in 15 Japanese patients with ALS (Warita H, 2019). Based on the results, we are conducting a phase II trial of intrathecal hrHGF for patients with ALS.

PMID:
31722311
DOI:
10.11477/mf.1416201435
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
12.
Brain Nerve. 2019 Nov;71(11):1245-1251. doi: 10.11477/mf.1416201434.

[Edaravone: A New Treatment for ALS].

[Article in Japanese]

Author information

1
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

Abstract

In 1993, a mutation in the superoxyde dismutase gene, SOD1, was found causative for familial ALS, suggesting that free radical-related injury may be involved in ALS pathogenesis. Therefore, clinical trials were conducted with ALS patients using a free radical scavenger, edaravone, which was already approved for acute phase treatment of cerebral infarction in Japan. Because edaravone showed a therapeutic effect in suppressing the progression of ALS symptoms, it was approved as a new therapeutic agent in Japan, in June, 2015. In this article, we discuss the recent progress of basic and clinical research for the development of new ALS treatments.

PMID:
31722310
DOI:
10.11477/mf.1416201434
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
13.
Brain Nerve. 2019 Nov;71(11):1236-1244. doi: 10.11477/mf.1416201433.

[The Current State of Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex in the Kii Peninsula, Japan, 2019].

[Article in Japanese]

Author information

1
Mie University, Graduate School of Regional Innovation Studies, Kii ALS/PDC Research Center.

Abstract

Recent papers of amyotrophic lateral sclerosis/parkinsonism-dementia complex in the Kii peninsula, Japan (Kii ALS/PDC), published since 2015, were reviewed The studies included transition element of scalp hair analysis, dopaminergic PET study, review of life style changes in the high incident area, neurotoxic BMAA analysis, a clinical report of a migration case, comprehensive neuropathological study, cerebellar tau pathology, nitrative stress in the central nervous system study, optinurin pathology in the spinal cord, and tau PET study. Tau PET was advocated to be a new useful tool for diagnosis, even in the early stage of ALS/PDC with tauopathy. The etiology of Kii ALS/PDC remainds unknown. There are patients and healthy residents within the same environment in the high incidence foci, therefore it is difficult to explain this result by exposure to environmental factors alone. From the genetic viewpoint, rare-disease and rare-variant model may be applied to Kii ALS/PDC. Because there was an immigrant who was diagnosed neuropathologically, and a drastic decrease of the prevalence in the past several decades in the high incident area, it is feasible that Kii ALS/PDC is a multifactorial disease caused by both risk genes and environmental factors. Identifying risk genes and environmental factors for Kii ALS/PDC may contribute to the prevention of neurodegenerative diseases.

PMID:
31722309
DOI:
10.11477/mf.1416201433
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
14.
Brain Nerve. 2019 Nov;71(11):1227-1235. doi: 10.11477/mf.1416201432.

[Amyotrophic Lateral Sclerosis and Frontotemporal Dementia].

[Article in Japanese]

Author information

1
Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University.

Abstract

Amyotrophic lateral sclerosis (ALS) is often comorbid with frontotemporal dementia (FTD). Patients may exhibit language deficits as seen in progressive non-fluent aphasia (PNFA) or semantic dementia (SD). In behavioral variant FTD (bvFTD), cognitive impairments such as executive function, verbal fluency and language abnormalities are frequently seen, while apathy and disinhibition are major behavioral changes. Further, there are many ALS patients who do not fulfill the criteria for FTD but have mild cognitive and/or behavioral impairments. Appropriate evaluation of these conditions is necessary for non-pharmacological and pharmacological interventions.

PMID:
31722308
DOI:
10.11477/mf.1416201432
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
15.
Brain Nerve. 2019 Nov;71(11):1215-1225. doi: 10.11477/mf.1416201431.

[The Role of Patient Registry in the Care and Therapeutic Development for Patients with Amyotrophic Lateral Sclerosis: JaCALS].

[Article in Japanese]

Author information

1
Department of Neurology, Nagoya University Hospital.

Abstract

Amyotrophic lateral sclerosis (ALS) patient registries can assist in the provision of appropriate care to patients and promote therapeutic developments related to ALS. In Japan, a multicenter registration and follow-up system called the Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS) was built in 2006. Genomic DNA samples and B-cell lines of patients with ALS were stored and linked to clinical information. Information obtained from JaCALS shows the natural histories of Japanese patients with ALS, including their genetic backgrounds and clinical and genetic factors associated with disease progression and prognosis. Research efforts that focus on pathophysiology, identification of biomarkers related to progression and prognosis, and drug discoveries for patients with ALS are advanced using data obtained from JaCALS. In the future, we expect that JaCALS will be a source of real-world evidence, combining data from a large number of cases.

PMID:
31722307
DOI:
10.11477/mf.1416201431
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
16.
Brain Nerve. 2019 Nov;71(11):1209-1214. doi: 10.11477/mf.1416201430.

[The Propagation Hypothesis of Prion-like Protein Agregates in Neurodegenerative Diseases].

[Article in Japanese]

Author information

1
Dementia Research Project, Tokyo Metropolitan Institute of Medical Science.

Abstract

The most common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are known to be protein-misfolding diseases, and characterized by the presence of disease-specific protein aggregates in neuronal and glial cells. Recently, the propagation hypothesis of prion-like protein inclusions in neurodegenerative diseases has been proposed. Many studies have shown that aggregation-prone proteins such as tau, alpha-synuclein and TDP-43 can form aggregates in a seed-dependent and self-templating prion-like manner, and these aggregates can be transferred intercellularly to neighboring cells and seeded for further aggregation. Propagation of aggregated proteins in these diseases may therefore occur through mechanisms similar to those that underlie prion pathogenesis. If this hypothesis is verified in vivo, it will suggest new therapeutic strategies to block the propagation of aggregated proteins throughout the brain.

PMID:
31722306
DOI:
10.11477/mf.1416201430
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
17.
Brain Nerve. 2019 Nov;71(11):1190-1208. doi: 10.11477/mf.1416201429.

[Impact of C9orf72 on Japanese Patients with Amytrophic Lateral Sclerosis (ALS)/Frontotemporal Dementia (FTD)].

[Article in Japanese]

Author information

1
Department of Neurology, Ohkawara Neurosurgical Hospital.

Abstract

In 2011, C9orf72 hexanucleotide (GGGGCC) repeat expansion (HRE) in intron 1 was reported as the most common cause of sporadic and familial amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) in the Caucasian population. In the Japanese population, the C9orf72 repeat expansion was found to account for 0.2% cases of sporadic ALS and 2.6% of familial ALS. Notably, among individuals in the Kii peninsula which has recorded high incidence of ALS or ALS/PDC (parkinsonism-dementia complex), the frequency of C9orf72 repeat expansion was 20% (3/15) indicating high prevalence. It is important to obtain detailed family history of ALS and FTD to understand the cause of the diseases including the C9orf72 mutation.

PMID:
31722305
DOI:
10.11477/mf.1416201429
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
18.
Brain Nerve. 2019 Nov;71(11):1183-1189. doi: 10.11477/mf.1416201428.

[Molecular Pathogenesis of Amyotrophic Lateral Sclerosis].

[Article in Japanese]

Author information

1
Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University.

Abstract

The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) has been studied through analysis of the function of the protein produced by the causative genes of familial ALS. The products of these genes are classified as RNA binding proteins, or proteins related to proteolytic systems. However, most case of familial ALS, and sporadic ALS show TAR DNA binding protein-43 (TDP-43) immune-positive cytoplasmic inclusions. Therefore, the molecular mechanism of formation of TDP-43 inclusions and dysfunction caused by TDP-43 inclusions has been studied. As for the mechanism of inclusion formation, non-membrane organelle formation by liquid-liquid phase separation (LLPS) is important. The ubiquitin-proteasome and autophagy systems are important for the degradation of these inclusions. Several genes associated with these systems have been identified as causative genes for ALS. The formation of cytoplasmic inclusions results in the loss of TDP-43 from the nucleus, resulting in abnormalities in RNA metabolism, through the alteration of spliceosomes and Gemini of coiled bodies. Furthermore, in ALS, the regulation of TDP-43 mRNA/protein expression levels has failed. Failure of the autoregulation system facilitates TDP-43 inclusion formation. Development of treatments for ALS based on these elucidated molecular mechanisms is desirable.

PMID:
31722304
DOI:
10.11477/mf.1416201428
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
19.
Brain Nerve. 2019 Nov;71(11):1169-1181. doi: 10.11477/mf.1416201427.

[Familial Amyotrophic Lateral Sclerosis].

[Article in Japanese]

Author information

1
Department of Neurology, Tohoku University Hospital.

Abstract

Amyotrophic lateral sclerosis (ALS) is the most rapidly progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem, and spinal cord. Riluzole and edaravone are the only approved drugs available in Japan to date. Approximately 10% of ALS cases are familial in rature, defined as the existence of disease-causing mutation. SOD1 is the most frequent causative gene for ALS among Japanese individuals, while C9orf72 mutation is more prevalent in Western countries. Genotype-phenotype correlation described in the literature of familial ALS enables to establish models of the disease. This review article describes the clinical characteristics of familial ALS based on each disease-causing mutation. The pathomechanism of ALS including proteostasis, RNA metabolism, and axonal pathology are discussed in detail. We also reviewed the status of development of therapeutic strategies for familial ALS based on analysis of animal models and induced pluripotent stem cells.

PMID:
31722303
DOI:
10.11477/mf.1416201427
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.
20.
Brain Nerve. 2019 Nov;71(11):1152-1168. doi: 10.11477/mf.1416201426.

[Neuropathology of Amyotrophic Lateral Sclerosis].

[Article in Japanese]

Author information

1
Institute for Medical Science of Aging Aichi Medical University.

Abstract

The basic neuropathology of amyotrophic lateral sclerosis (ALS) is defined as the involvement of the upper motor neurons system (UMN) and the lower motor neuron system (LMN), with variable degree and combination. The characteristic pathological feature of sporadic ALS is cytoplasmic mislocalization of nuclear TDP-43 and aggregation of abnormally phosphorylated TDP-43 inclusions in cytoplasm in LMN, UMN and glial cells. TDP-43 inclusions correlate with cell loss and distribute beyond the UMN and LMN system. It has been proposed that phosphorylated TDP-43 (pTDP-43) disseminates in a sequential pattern along the motor pathways, as suggested by the hypothesis of corticofugal ('prion-like') propagation of misfolded proteins in ALS.

PMID:
31722302
DOI:
10.11477/mf.1416201426
[Indexed for MEDLINE]
Icon for IGAKU-SHOIN Ltd.

Supplemental Content

Loading ...
Support Center