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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Frontotemporal dementia (clinical Pick's disease) is a relatively common, but underdiagnosed degenerative disease in the presenium. Estimated prevalence ranges from 6-12% of dementias. The behavioural, aphasic and extrapyramidal presentations are labeled FTD-behavioural variant, Primary Progressive Aphasia (PPA) and Corticobasal Degeneration/Progressive Supranuclear Palsy (CBD/PSP). The diagnostic features and course of each are described and their overlap in the evolution of the illness is emphasized. The neuropathology ranges from the most common tau negative ubiquitin positive amyotrophic lateral sclerosis (ALS) type inclusions to the tau positive classical Pick bodies and more or less distinct changes of PSP and CBD. The genetics of the relatively frequent tau mutations and the yet unsolved problem of tau negative families are discussed. The tau negative cases tend to be associated with the behavioural presentation and semantic dementia and the tau positive ones with PPA and the CBD/PSP syndrome. However the overlap is too great to split the disease. A glossary to navigate the proliferating terminology is included.
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PMID:Progress in clinical neurosciences: Frontotemporal dementia-pick's disease. 1673 22

Summary Amyotrophic lateral sclerosis (ALS) is a devastating motoneuronal degenerative disease, which is inevitably fatal in adults. ALS is characterized by an extensive loss of motoneurons in the cerebrospinal axis, except for those motoneurons that control eye movements and bladder contraction. The reason for this selectivity is not known. Systematic differences have been found in the organization of excitatory synaptic transmission in ALS-resistant vs. ALS-susceptible motor nuclei. However, although motoneurons express high levels of glycine receptors (GlyR) and GABA(A) receptors (GABA(A)R), no such studies have been carried out yet for inhibitory synaptic transmission. In this study, we compared the subunit composition, patterns of expression, density and synaptic localization of inhibitory synaptic receptors in ALS-resistant (oculomotor, trochlear and abducens) and ALS-vulnerable motoneurons (trigeminal, facial and hypoglossi). Triple immunofluorescent stainings of the major GABA(A)R subunits (alpha1, alpha2, alpha3, and alpha5), the GlyR alpha1 subunit and gephyrin, were visualized by confocal microscopy and analysed quantitatively. A strong correlation was observed between the vulnerability of motoneurons and the subunit composition of GABA(A)R, the GlyR/GABA(A)R density ratios and the incidence of synaptic vs. extrasynaptic GABA(A)R. These differences contrast strikingly with the uniform gephyrin cluster density and synaptic GlyR levels recorded in all motor nuclei examined. These results suggest that the specific patterns of inhibitory receptor organization observed might reflect functional differences that are relevant to the physiopathology of ALS.
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PMID:Differential expression of GABAA and glycine receptors in ALS-resistant vs. ALS-vulnerable motoneurons: possible implications for selective vulnerability of motoneurons. 1682 6

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to motor neuron cell death, but recent studies suggest that non-neuronal cells may contribute to the pathological mechanisms involved. Myostatin is a negative regulator of muscle growth whose function can be inhibited using neutralizing antibodies. In this study, we used transgenic mouse and rat models of ALS to test whether treatment with anti-myostatin antibody slows muscle atrophy, motor neuron loss, or disease onset and progression. Significant increases in muscle mass and strength were observed in myostatin-antibody-treated SOD1(G93A) mice and rats prior to disease onset and during early-stage disease. By late stage disease, only diaphragm muscle remained significantly different in treated animals in comparison to untreated controls. Myostatin inhibition did not delay disease onset nor extend survival in either the SOD1(G93A) mouse or rat. Together, these results indicate that inhibition of myostatin does not protect against the onset and progression of motor neuron degenerative disease. However, the preservation of skeletal muscle during early-stage disease and improved diaphragm morphology and function maintained through late stage disease suggest that anti-myostatin therapy may promote some improved muscle function in ALS.
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PMID:Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis. 1683 7

The impact of amyotrophic lateral sclerosis and consequent disability on everyday life can be assessed with generic or specific and/or functional quality of life scales. Generic scales SF36, SIP (Sickness Impact Profiles) and SIP/ALS 19, SEIQoL have been validated for the assessment of quality of life in SLA. A specific scale has also been worked out and validated in this disease, the ALSAQ-40 scale. The ALSFRS (ALS Functional Rating Scale) is a tool validated to evaluate the patient's functional capacities. However, the patient's quality of life felt does not depend only on the disease course but also the patient's previous psychological profile, the environmental, social conditions and spiritual aspirations. The absence of a cognitive deficit makes the patient particularly lucid about the progressive degradation of health status. Evaluation must be carried out with individually for each patient, taking into account the social and familial environments, to appreciate real living conditions, and the impact of this degenerative disease.
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PMID:[Handicap and quality of life evaluation in amyotrophic lateral sclerosis]. 1712 12

Amyotrophic lateral sclerosis is a neurodegenerative disease, without any curative treatment. Clinical expression is variable and related to loss of motor neurons in the cortex, brain stem and spinal cord. There is little scientific evidence demonstrating the usefulness of physical therapy in this disease. Only stretching exercises, proprioceptive neuromuscular facilitation techniques and functional mobility training seem to have a real benefit in terms of spasticity, quality-of-life and pain. The main objective of physical therapy appears to be the preservation of optimal quality-of-life throughout the course of this incurable degenerative disease.
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PMID:[Physical therapy in amyotrophic lateral sclerosis]. 1712 19

The naturally occurring, non-essential amino acid beta-N-methylamino-L-alanine (BMAA) has been recently found in high concentrations in brain tissues of patients with tauopathies such as the Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex (ALS/PDC) in the South Pacific island of Guam and in a small number of Caucasian, North American patients with sporadic Alzheimer's disease. BMAA is produced by cyanobacteria that are present in all conceivable aquatic and/or terrestrial ecosystems and may be accumulated in living tissues in free and protein-bound forms through the process of biomagnification. Although its role in human degenerative disease is highly debated, there is mounting evidence in support of the neurotoxic properties of BMAA that may be mediated via mechanisms involving among others the regulation of glutamate. Glutamate-related excitotoxicity is among the most prominent factors in the etiopathogenesis of human neurodegenerative diseases. Due to the wide geographical distribution of cyanobacteria and the possible implications of BMAA neurotoxic properties in public health more research towards this direction is warranted.
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PMID:Is there a role for naturally occurring cyanobacterial toxins in neurodegeneration? The beta-N-methylamino-L-alanine (BMAA) paradigm. 1729 49

Progressive muscle atrophy (PMA) is a degenerative disease of the lower motor neuron. The course of the illness and the fatal prognosis correspond to those of amyotrophic lateral sclerosis (ALS). Neuropathologic and genetic findings support categorizing PMA within the spectrum of ALS, even though no clinical sign of a disorder of the upper motor neuron is demonstrable. The diagnosis of PMA is based on advanced extremity pareses and atrophies with a high progression rate. Respiratory insufficiency is determinative of the prognosis. Absent or late affection of bulbar functions is characteristic of the disease. Intraneuronal bunina bodies and ubiquitine-positive inclusions, which are established morphologic characteristics of ALS, are found post mortem. The treatment options of riluzol medication, respiratory therapy, and nutrition are analogous to those for typical ALS.
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PMID:[Progressive muscle atrophy. A rarely diagnosed variant of amyotrophic lateral sclerosis]. 1751 42

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron degenerative disease whose etiology and pathogenesis remain poorly understood. Most cases of ALS ( approximately 90%) are sporadic (SALS), occurring in the absence of genetic associations. Approximately 20% of familial ALS (FALS) cases are due to known mutations in the copper, zinc superoxide dismutase (SOD1) gene. Molecular evidence for a common pathogenesis of SALS and FALS has remained elusive. Here we use covalent chemical modification to reveal an attribute of spinal cord SOD1 common to both SOD1-linked FALS and SALS, but not present in normal or disease-affected tissues from other neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases and spinal muscular atrophy, a non-ALS motor neuron disease. Biotinylation reveals a 32-kDa, covalently cross-linked SOD1-containing protein species produced not only in FALS caused by SOD1 mutation, but also in SALS. These studies use chemical modification as a novel tool for the detection of a disease-associated biomarker. Our results identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between SALS and FALS.
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PMID:Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. 1763 19

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease involving the upper and lower motor neuron systems. Activated microglia are reported to enhance motor neuron death by secreting neurotoxic cytokines in SOD1-transgenic mice. Recent studies have provided evidence that chronic stimulation leads microglia to acquire an anti-inflammatory phenotype, characterized by activated morphology and induction of neuroprotective and immunoregulatory molecules. However, little information is available on the protective functions of microglia in the ALS spinal cord. To investigate the roles of microglia in ALS, we examined the appearance of ionized calcium-binding adaptor molecule 1-positive (Iba1-positive) microglia as correlated to the disease duration and immunohistochemical expression of neurogrowth factors in the ALS spinal cord. In this study, the number of Ibal-positive rod-like microglia significantly increased in the ALS spinal cord compared to controls. The number of ramified microglia was positively correlated with the number of normal-looking neurons and clinical duration of ALS patients; however, the number of rod-like microglia was not correlated with that of abnormal neurons, nor with the clinical duration of the disease. Some rod-like microglia were positive for anti-insulin-like growth factor-II (IGF II) and anti-leukemia inhibitory factor (LIF) immunostaining. Motor neurons in the ALS spinal cords also showed immunore-activity for IGF-II, LIF and the receptors of IGF-II and LIE Taken together, these findings suggest that at least some microglia might have a protective effect on motor neurons in the ALS spinal cord. Neuroprotective and/or neurotoxic effects of microglia on motor neurons should be further studied.
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PMID:Expression of insulin-like growth factor-II and leukemia inhibitory factor antibody immunostaining on the ionized calcium-binding adaptor molecule 1-positive microglias in the spinal cord of amyotrophic lateral sclerosis patients. 1764 40

Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.
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PMID:Report of an autopsy case of colon cancer with amyotrophic lateral sclerosis. 1782 8


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