Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone

1994 ◽  
Vol 241 (4) ◽  
pp. 196-203 ◽  
Author(s):  
Shin-ichi Terao ◽  
Gen Sobue ◽  
Yoshio Hashizume ◽  
Terunori Mitsuma ◽  
Akira Takahashi
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Multiple System Atrophy ◽  
Special Reference ◽  
Neuronal Loss ◽  
Ventral Horn ◽  
Intermediate Zone ◽  
Lateral Sclerosis ◽  
Disease Specific

scholarly journals Motor Unit Number Estimation in Neuromuscular Disease

2008 ◽  
Vol 35 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Omid Rashidipour ◽  
K. Ming Chan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Unit ◽  
Neuromuscular Disease ◽  
Muscular Atrophy ◽  
Neuromuscular Diseases ◽  
Neuronal Loss ◽  
Response To Treatment ◽  
Motor Unit Number Estimation ◽  
Electrophysiological Method ◽  
Lateral Sclerosis

Motor unit number estimation (MUNE) is an electrophysiological method designed to quantify motor unit loss in target muscles of interest. Most of the techniques are noninvasive and are therefore well suited for longitudinal monitoring. In this brief review, we describe the more commonly used techniques and their applications in amyotrophic lateral sclerosis, poliomyelitis, spinal muscular atrophy and hereditary sensorimotor neuropathies. Findings in some of these studies offer important pathophysiological insights. Since conventional electrophysiologic methods are not sensible measures of motor neuronal loss, MUNE could play a potentially important role in the diagnosis, monitoring of disease progression and response to treatment in neuromuscular diseases in which motor unit loss is a major feature.

scholarly journals Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease

2015 ◽  
Vol 89 (15) ◽  
pp. 7660-7672 ◽  
Author(s):  
Leonardo M. Cortez ◽  
Jody Campeau ◽  
Grant Norman ◽  
Marian Kalayil ◽  
Jacques Van der Merwe ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Bile Acids ◽  
Prion Disease ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Disease Models ◽  
Orally Bioavailable ◽  
Prion Conversion ◽  
Lateral Sclerosis

ABSTRACTPrion diseases are fatal neurodegenerative disorders associated with the conversion of cellular prion protein (PrPC) into its aberrant infectious form (PrPSc). There is no treatment available for these diseases. The bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) have been recently shown to be neuroprotective in other protein misfolding disease models, including Parkinson's, Huntington's and Alzheimer's diseases, and also in humans with amyotrophic lateral sclerosis. Here, we studied the therapeutic efficacy of these compounds in prion disease. We demonstrated that TUDCA and UDCA substantially reduced PrP conversion in cell-free aggregation assays, as well as in chronically and acutely infected cell cultures. This effect was mediated through reduction of PrPScseeding ability, rather than an effect on PrPC. We also demonstrated the ability of TUDCA and UDCA to reduce neuronal loss in prion-infected cerebellar slice cultures. UDCA treatment reduced astrocytosis and prolonged survival in RML prion-infected mice. Interestingly, these effects were limited to the males, implying a gender-specific difference in drug metabolism. Beyond effects on PrPSc, we found that levels of phosphorylated eIF2α were increased at early time points, with correlated reductions in postsynaptic density protein 95. As demonstrated for other neurodegenerative diseases, we now show that TUDCA and UDCA may have a therapeutic role in prion diseases, with effects on both prion conversion and neuroprotection. Our findings, together with the fact that these natural compounds are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans, make these compounds promising alternatives for the treatment of prion diseases.IMPORTANCEPrion diseases are fatal neurodegenerative diseases that are transmissible to humans and other mammals. There are no disease-modifying therapies available, despite decades of research. Treatment targets have included inhibition of protein accumulation, clearance of toxic aggregates, and prevention of downstream neurodegeneration. No one target may be sufficient; rather, compounds which have a multimodal mechanism, acting on different targets, would be ideal. TUDCA and UDCA are bile acids that may fulfill this dual role. Previous studies have demonstrated their neuroprotective effects in several neurodegenerative disease models, and we now demonstrate that this effect occurs in prion disease, with an added mechanistic target of upstream prion seeding. Importantly, these are natural compounds which are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans with primary biliary cirrhosis. They have recently been proven efficacious in human amyotrophic lateral sclerosis. Therefore, these compounds are promising options for the treatment of prion diseases.

OP046 DISEASE-SPECIFIC ENTERAL NUTRITION IN AMYOTROPHIC LATERAL SCLEROSIS (ALS)

2011 ◽  
Vol 6 (1) ◽  
pp. 19
Author(s):  
I. Kushta ◽  
S. Lucia ◽  
M. Sabatelli ◽  
F. Rossi Fanelli ◽  
M. Muscaritoli
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Enteral Nutrition ◽  
Lateral Sclerosis ◽  
Disease Specific

Reduced brainN-acetyl-aspartate in frontal lobes suggests neuronal loss in patients with amyotrophic lateral sclerosis

1996 ◽  
Vol 18 (3) ◽  
pp. 241-243 ◽  
Author(s):  
Maurice Giroud ◽  
Paul Walker ◽  
David Bernard ◽  
Martine Lemesle ◽  
Didier Martin ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuronal Loss ◽  
Frontal Lobes ◽  
Lateral Sclerosis

scholarly journals Neuropathology of Speech Network Distinguishes Bulbar From Nonbulbar Amyotrophic Lateral Sclerosis

2019 ◽  
Vol 79 (3) ◽  
pp. 284-295
Author(s):  
Sanjana Shellikeri ◽  
Julia Keith ◽  
Sandra E Black ◽  
Lorne Zinman ◽  
Yana Yunusova
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Dna Binding ◽  
Cognitive Deficits ◽  
Regional Distribution ◽  
Neuronal Loss ◽  
Dna Binding Protein ◽  
Motor Functions ◽  
Bulbar Symptoms ◽  
Bulbar Onset ◽  
Lateral Sclerosis

Abstract Bulbar amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative subtype affecting speech and swallowing motor functions as well as associated with the burden of cognitive deficits. The neuroanatomical underpinnings of bulbar ALS are not well understood. The aim of this study was to compare neuropathology of the speech network (SpN) between 3 cases of bulbar-onset ALS (bALS), 3 cases of spinal-onset ALS (sALS) with antemortem bulbar ALS (sALSwB) against 3 sALS without antemortem bulbar ALS (sALSnoB) and 3 controls. Regional distribution and severity of neuronal loss, TDP-43 (transactive response DNA-binding protein of 43 kDa), and tau proteinopathy were examined. All 3 bALS cases showed marked neuronal loss and severe proteinopathy across most SpN regions; sALSwB cases showed no neuronal loss but mild and variable TDP-43 pathology in focal regions; sALSnoB cases demonstrated an absence of pathology. Two bALS cases had coexisting tauopathy in SpN regions, which was not noted in any sALS cases. The findings suggested that bALS may have a distinct neuropathological signature characterized by marked neuronal loss and polypathology in the SpN. Milder TDP-43 pathology in the SpN for sALSwB cases suggested a link between severity of bulbar ALS and SpN damage. Findings support a clinicopathologic link between bulbar symptoms and pathology in the SpN.

scholarly journals Multiple System Atrophy and Amyotrophic Lateral Sclerosis in a Family With Hexanucleotide Repeat Expansions inC9orf72

2014 ◽  
Vol 71 (6) ◽  
pp. 771 ◽  
Author(s):  
Jill S. Goldman ◽  
Catarina Quinzii ◽  
Jane Dunning-Broadbent ◽  
Cheryl Waters ◽  
Hiroshi Mitsumoto ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Multiple System Atrophy ◽  
Hexanucleotide Repeat ◽  
Repeat Expansions ◽  
Lateral Sclerosis

Cerebellar neuronal loss in amyotrophic lateral sclerosis cases with ATXN2 intermediate repeat expansions

2016 ◽  
Vol 79 (2) ◽  
pp. 295-305 ◽  
Author(s):  
Rachel H Tan ◽  
Jillian J Kril ◽  
Ciara McGinley ◽  
Mohammad Hassani ◽  
Masami Masuda-Suzukake ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuronal Loss ◽  
Repeat Expansions ◽  
Lateral Sclerosis

scholarly journals Systemic Dental Pulp Stem Cell Secretome Therapy in a Mouse Model of Amyotrophic Lateral Sclerosis

2019 ◽  
Vol 9 (7) ◽  
pp. 165 ◽  
Author(s):  
Junmei Wang ◽  
Kirstin Zuzzio ◽  
Chandler L. Walker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Dental Pulp ◽  
Ventral Horn ◽  
Trophic Factors ◽  
Future Research ◽  
Therapeutic Benefits ◽  
Dental Pulp Stem Cell ◽  
Lateral Sclerosis ◽  
Post Onset

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron (MN) disease with no cure. Accumulating evidence indicates ALS involves a complex interaction between central glia and the peripheral immune response and neuromuscular interface. Stem cell secretomes contain various beneficial trophic factors and cytokines, and we recently demonstrated that administration of the secretome of adipose-derived stem cells (ASCs) during early neuromuscular junction (NMJ) denervation in the mutant superoxide dismutase (mSOD1G93A) ALS mouse ameliorated NMJ disruption. In the present study, we hypothesized that administration of dental pulp stem cell secretome in the form of conditioned medium (DPSC-CM) at different stages of disease would promote NMJ innervation, prevent MN loss and extend lifespan. Our findings show that DPSC-CM significantly improved NMJ innervation at postnatal day (PD) 47 compared to vehicle treated mSOD1G93A mice (p < 0.05). During late pre-symptomatic stages (PD70-P91), DPSC-CM significantly increased MN survival (p < 0.01) and NMJ preservation (p < 0.05), while reactive gliosis in the ventral horn remained unaffected. For DPSC-CM treated mSOD1G93A mice beginning at symptom onset, post-onset days of survival as well as overall lifespan was significantly increased compared to vehicle treated mice (p < 0.05). This is the first study to show therapeutic benefits of systemic DPSC secretome in experimental ALS, and establishes a foundation for future research into the treatment effects and mechanistic analyses of DPSC and other stem cell secretome therapies in ALS.

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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