Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed proton magnetic resonance spectroscopy (1H-MRS) in three patients with amyotrophic lateral sclerosis (ALS) to evaluate the distribution and extent of cortical neuronal damage as demonstrated by decreased N-acetyl-aspartate (NAA) levels. We examined primary motor (precentral gyrus) and parietal neocortical (superior parietal gyrus) regions. ALS was defined with lower and upper motor neuron signs. Compared with matched healthy controls, ALS patients had a significant decrease in NAA levels in the primary motor cortex (p < 0.001) compared with parietal regions and homologous regions in healthy controls. Two clinical applications can be extracted: first, the upper motor neuron signs present in the ALS, come from a neuronal loss within the primary motor cortex and may explain the frontal syndrome associated with ALS. Second clinical applications of 1H-MRS could include identification of extent of upper motor neuron involvement, aiding diagnosis of syndromes presenting with an ALS-like syndrome.
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PMID:Reduced brain N-acetyl-aspartate in frontal lobes suggests neuronal loss in patients with amyotrophic lateral sclerosis. 883 60

We performed proton magnetic resonance spectroscopy (1H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr/PCr). We examined the spectra acquired from a 20 x 20 x 20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, as well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients with both upper and lower motor neuron signs had a significantly decreased concentration of NAA (9.13 +/- 0.28 mM, mean +/- SEM) in the primary motor cortex when compared with healthy controls (10.03 +/- 0.22 mM). In conclusion, the slightly decreased concentration of NAA in the primary motor cortex from ALS patients may represent a loss of neurons in this region.
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PMID:Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy. 948 13

Proton magnetic resonance spectroscopy (1H-MRS) and proton magnetic resonance spectroscopic imaging (1H-MRSI) have been used to identify neuronal dysfunction and/or loss in vivo in patients with various neurological diseases, including amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Both long and short echo time (TE) proton spectroscopy reveal the brain metabolites choline (Cho), creatine/phosphocreatine (Cr), and N-acetyl (NA) groups. Because NA groups are localized to mature neurons and Cr is homogeneously distributed throughout the brain, the NA/Cr ratio is considered an index of neuronal integrity. Long TE proton spectroscopic studies have revealed significantly decreased NA/Cr values in the sensorimotor cortex and brainstem of patients with ALS, consistent with neuronal dysfunction and/or loss. The amount of NA/Cr decrease appears to be directly proportional to the degree of clinical upper motor neuron deficit. Short TE 1H-MRS and 1H-MRSI also reveal other metabolites such as glutamate (Glu) and glutamine (Gln), which have been implicated in the ALS/MND disease process. Preliminary results of short TE 1H-MRSI of the medulla in patients with ALS/MND have revealed significantly decreased NA/Cr values and abnormally elevated Glu+Gln/Cr ratios, compared to control individuals. The latter values were higher in patients with more rapid disease. Although it is unclear whether the elevation of Glu+Gln/Cr precedes or follows the neuronal (and axonal) degeneration in the medulla of these patients, its occurrence provides in vivo evidence of abnormal glutamate metabolism in the CNS parenchyma of patients with ALS/MND.
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PMID:MR spectroscopy in amyotrophic lateral sclerosis/motor neuron disease. 941 54

Proton magnetic resonance spectroscopy (1H-MRS) was used to measure the in vivo signal of N-acetylaspartate (NAA), a putative neuronal marker, in the brain of the mutant wobbler mouse, a model of motor neuron disease. The ratio of NAA to creatine-phosphocreatine, an internal standard, was significantly lower in five affected wobbler mice (0.79+/-0.05; mean+/-s.d.) than in five unaffected littermates (0.98+/-0.10, p = 0.006). Ubiquitin and phosphorylated heavy neurofilament immunoreactivities were increased in cortical neurons of affected animals. This is the first demonstration of cerebral neuronal pathology in the wobbler mouse, supporting its use as a model of amyotrophic lateral sclerosis. In vivo IH-MRS and correlative postmortem study of wobbler mouse brain will allow temporal monitoring of neuronal degeneration and responsiveness to neuroprotective pharmacotherapies.
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PMID:Neuronal pathology in the wobbler mouse brain revealed by in vivo proton magnetic resonance spectroscopy and immunocytochemistry. 980 13

Modern stereological methods provide precise and reliable estimates of the number of neurons in specific regions of the brain. The total number of neurons in the neocortex and motor cortex from eight patients suffering from amyotrophic lateral sclerosis (ALS) and nine controls was estimated. No attempt was made to estimate subpopulations of neurons such as the number of giant pyramidal cells of Betz. No difference was found in the average number of neurons in neocortex in ALS and controls, 21.7 and 22.3 x 10(9), respectively, and 1.33 and 1.29 x 10(9) in motor cortex, respectively. In the light of our stereological measurements, results obtained from in-vivo proton magnetic resonance spectroscopy (1H-MRS), suggesting neuronal loss in ALS, may instead be due to neuronal metabolic dysfunction and/or alteration in the size or the volume fraction of the neurons.
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PMID:Unchanged total number of neurons in motor cortex and neocortex in amyotrophic lateral sclerosis: a stereological study. 1075 88

We aimed to increase confidence in the combined use of MRI and proton MR spectroscopy (1H-MRS) in diagnosis of amyotrophic lateral sclerosis (ALS). We investigated 12 patients with ALS, seven definite and five probable, taking into account clinical measures of motor neuron function. On T2-weighted images we found high signal in the corticospinal tract in six and low signal in the primary motor cortex in seven of the 12 patients. Atrophy of the precentral gyrus was apparent in all the patients apart from one with probable ALS. Absolute quantification of cerebral metabolites using 1H-MRS demonstrated a significantly lower mean concentration of N-acetylaspartate (NAA) in the precentral gyrus of patients with probable and definite ALS (8.5 +/- 0.62) than in control subjects (10.4 +/- 0.71; P < 0.001). NAA concentration in primary motor cortex correlated with Norris scale scores (r = 0.30; P < 0.0001) but not with the ALS Functional Rating Scale score or disease duration. Significantly lower levels of NAA were detected in patients with low signal in the motor cortex than in those without (P < 0.01). Mean choline (Cho) and creatine (Cr) values did not differ between patients with ALS and controls.
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PMID:Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis. 1130 49

Establishing the presence of upper motor neuron (UMN) pathology is essential for an accurate and definite diagnosis of ALS. However, clinical identification of UMN dysfunction can be difficult in early disease or if lower motor neuron signs are prominent. A routine technique such as magnetic resonance imaging is usually normal and non-specific. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive neuroimaging technique that has successfully demonstrated evidence of neuronal abnormalities in motor regions of the brain in ALS. This review discusses the advantages and limitations of employing 1H-MRS as an investigative tool in the diagnosis of ALS.
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PMID:Proton magnetic resonance spectroscopy (1H-MRS) in ALS. 1146 45

Transcranial magnetic stimulation (TMS) was compared to proton magnetic resonance spectroscopy (1H-MRS) for the detection of upper motor neuron loss or dysfunction in 49 ALS patients classified according to the El Escorial criteria. Abnormal NAA/Cho ratios were detected in 53% of ALS patients. Abnormal TMS results (i.e. cortical inexcitability or prolonged CMCT's) were obtained in 63% of ALS patients. If one or both methods were considered for diagnosis of upper motor neuron degeneration/dysfunction, the percentage of abnormal findings was 77%, whilst in 39% of all patients both methods produced abnormal results. Compared to TMS, 1H-MRS detected more patients with upper motor neuron involvement in the suspected El Escorial subgroup (42% versus 25%), whereas TMS detected more patients with upper motor neuron involvement in the possible (81% versus 50%), probable (71% versus 57%) and definite El Escorial subgroup (71% versus 64%). We conclude that the combined use of 1H-MRS and TMS increases diagnostic accuracy for the detection of upper motor neuron involvement in ALS patients.
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PMID:Proton magnetic resonance spectroscopy and transcranial magnetic stimulation for the detection of upper motor neuron degeneration in ALS patients. 1157 2

Neurodegeneration refers to a large clinically and pathologically heterogeneous disease entity associated with slowly progressive neuronal loss in different anatomical and functional systems of the brain. Neurodegenerative diseases often affect cognition, e.g. Alzheimer's disease (AD), dementia with Lewy bodies and vascular dementia, or different aspects of the motor system, e.g., amyotrophic lateral sclerosis, Parkinson's disease and ataxic disorders. Owing to increasing knowledge about the mechanisms leading to neurodegeneration, the development of treatments able to modify the neurodegenerative process becomes possible for the first time. Currently, clinical outcome measures are used to assess the efficacy of such treatments. However, most clinical outcome measures have a low test-retest reliability and thus considerable measurement variance. Therefore, large patient populations and long observation times are needed to detect treatment effects. Furthermore, clinical outcome measures cannot distinguish between symptomatic and disease-modifying treatment effects. Therefore, alternative biomarkers including neuroimaging may take on a more important role in this process. Because MR scanners are widely available and allow for non-invasive detection and quantification of changes in brain structure and metabolism, there is increasing interest in the use of MRI/MRS to monitor objectively treatment effects in clinical trials of neurodegenerative diseases. Particularly volumetric MRI has been used to measure atrophy rates in treatment trials of AD because the relationship between atrophic changes and neuron loss is well established and correlates well with clinical measures. More research is needed to determine the value of other MR modalities, i.e. diffusion, perfusion and functional MRI and MR spectroscopy, for clinical trials with neuroprotective drugs.
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PMID:Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS. 1698 15

Impaired mitochondrial energy production probably plays a role in motor neuron death in amyotrophic lateral sclerosis (ALS) and has been found not only in motor neurons but also in skeletal muscle of patients with ALS. 31P magnetic resonance spectroscopy (31P-MRS) has the potential to reflect the energy metabolism of skeletal muscle in vivo. We sought to determine whether an altered mitochondrial energy metabolism of the muscle cell in patients with SALS can be detected by 31P-MRS, and to this end we recorded 31P-MR spectra of the gastrocnemius muscle of patients with ALS under a standardized isometric muscle exercise protocol. In a prospective setting we compared ten patients with sporadic ALS and 38 age-matched controls. The patients were characterized by a disease duration of approximate 18 months and classified as having probable to definite ALS by means of the revised El Escorial criteria. The time constant of oxidative PCr recovery after aerobic (tau1) and ischaemic muscle contraction (tau2) was used to determine the capacity of mitochondrial ATP formation. We found that mitochondrial impairment in skeletal muscle of patients with ALS could not be confirmed by 31P-MRS and therefore cannot be used as a surrogate factor of the disease.
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PMID:A prospective study to evaluate the impact of 31P-MRS to determinate mitochondrial dysfunction in skeletal muscle of ALS patients. 1736 28


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