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)

Since the relationships between traditional assessments in ALS patients have not been defined, three clinical and four electrophysiological assessments were performed in a cross-sectional study of 87 ALS patients. The clinical assessments produced Norris ALS scores, muscle strength scores and illness durations (DUR). The electrophysiological assessments produced scores for motor unit interference pattern, denervation potentials, compound muscle action potential, and fasciculations. The individual muscle scores were averaged to produce mean scores, and Spearman rank correlations were performed on the mean scores. The association between Norris ALS and mean muscle strength (MMS) scores is significant (p less than .001, rs = 0.84), and these scores are significantly correlated with mean interference pattern (0.77, 0.82), mean denervation potential (-0.63, -0.70), and mean compound muscle action potential scores (0.55, 0.60), respectively. Correlations between IP and DP scores (-0.71), IP and CMAP scores (0.62), and DP and CMAP (-0.56) scores are also significant. Scatterplots of the data and regression lines suggest linear relationships between each of these assessments. Illness duration and fasciculation scores are not strongly correlated (rs less than 0.55) with any of the other clinical or electrophysiological assessments.
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PMID:Clinical and electrophysiological assessments in ALS patients. 179 45

We have estimated the distribution of conduction velocities (DCV) of large myelinated fibers in the median nerves of 10 normal subjects and a patient with amyotrophic lateral sclerosis (ALS) who had a de-efferented hand, using three different computer-based methods: a 2CAP method, which tests both motor and sensory nerve fibers; and 2MAP and CMAP methods, which test only the alpha motor fibers. The magnitudes of the parameters DCVmax, DCVmean, DCVpeak, and DCVrange all were very similar in the two motor estimations, but all were significantly higher (P less than 0.001 in each case) in the mixed nerve estimates; the differences presumably represent the properties of the faster-conducting sensory fiber population. The 2CAP DCV from the de-efferented nerve resembled those from normal mixed nerve. Compared with DCV analysis, conventional measures of maximal motor and sensory CV were found to be relatively poor indices of the conduction properties of their respective large, myelinated, nerve fiber populations.
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PMID:Conduction velocity distributions of the human median nerve: comparison of methods. 716 95

Glutamate excitotoxicity is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We report the results of a double blind, placebo controlled, trial using 100 mg of oral daily lamotrigine (3,5-diamino-6-(2,3 dichlorophenyl)-1,2,4-triazine) which inhibits glutamate release. 67 patients were entered and at trial termination of 1.5 years 15 had withdrawn (9 active and 6 placebo) and 12 had died (6 active and 6 placebo). Mean age at entry was 57.5 years for the active and 58.6 years for the placebo groups. Patients were seen at 3 monthly intervals and scored according to neurological deficit based upon age of onset, bulbar and respiratory involvement, ambulation and functional disability. The mean change in clinical scores for the active versus placebo groups over the trial period was 7.1 +/- 3.3 and 9.0 +/- 3.3 respectively (0.05 < p < 0.10). Changes in cortical threshold and MEP/CMAP ratios to magnetic stimulation also did not differ significantly between the two groups. We conclude that lamotrigine in the doses administered does not alter the course of ALS.
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PMID:Anti-glutamate therapy in amyotrophic lateral sclerosis: a trial using lamotrigine. 790 90

Transcranial magnetic stimulation (TMS) mapping was performed regularly on 11 patients with amyotrophic lateral sclerosis (ALS). Map area decreased by 25% (P = 0.03) and normalized volume decreased by 47% (P = 0.01) in those patients who were mapped four times over a period of 11.6 months. The center of gravity (CoG) position moved randomly along the interaural line by distances larger than could be explained by experimental error (P = 0.002). Central conduction time, threshold, and motor evoked potential:compound muscle action potential (MEP:CMAP) amplitude ratio did not change significantly with time (P > 0.05). There were significant linear correlations between strength and CMAP amplitude and between map area and volume. No correlation was found between strength or CMAP amplitude and area or volume. The changes in map parameters were attributed primarily to loss of cortical cells. These results indicate that map parameters may be more sensitive to cortical neuronal loss than other TMS parameters.
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PMID:Cortical muscle representation in amyotrophic lateral sclerosis patients: changes with disease evolution. 1056 81

Charcot-Marie-Tooth disease type 1A (CMT1A), the most frequent form of CMT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17. Patients with CMT1A typically have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes. In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and motor unit number estimates correlated with clinical disability, while motor NCV did not. In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not. Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to large calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration.
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PMID:Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. 1086 62

This study compares two common techniques for motor unit number estimation, multiple point stimulation and statistical method, to determine which is more reproducible. Surface recorded motor unit action potentials (SMUPs) of the left hypothenar muscle group were measured on 20 controls and 10 ALS patients. For multiple point, 10 different threshold SMUPs were recorded. For statistical method, mean SMUP amplitude was measured at several stimulus levels, typically spanning >40% of CMAP amplitude range. Both techniques were performed twice, results averaged, electrodes changed, and all recording repeated. For controls, mean of two motor unit number estimation (MUNE) (+/- standard deviation) was 60 (+/-5) for statistical method, and 108 (+/-38) for multiple point. For ALS patients, these values were 21 (+/-16) for statistical method and 55 (+/-39) for multiple point. Test-retest correlation coefficients and coefficients of variation for mean of two MUNE were 0.98 and 7% for statistical method, and 0.90 and 12% for multiple point, respectively. Statistical method was more reproducible and faster than multiple point, supporting its utility in monitoring rates of MUNE change.
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PMID:Comparison of multiple point and statistical motor unit number estimation. 1100 87

In diagnostics of ALS the electrophysiologic investigation should be able to evaluate two fundamental processes: the primary process of the loss of some motoneuros--denervation, and secondary process of reinnervation. The most important diagnostic methods include the quantitative electromyography (EMG) evaluating several parameters of the motor unit potential (MUP) and of the maximal effort pattern. The earliest features are the signs of spontaneous activity (denervation) and the elevation of MUP amplitude and area (reinnervation). Finding of spontaneous activity in the tongue muscles as well as in the paraspinal muscles is of great diagnostic value. SFEMG may early detect increased density of muscle fibres (FD) and jitter elongation as signs of recent reinnervation. Electroneurography is critical in differentiation against the multifocal motor neuropathy with conduction block and other polyneuropathies. The aim of the electrophysiological investigations is also the evaluation of the intensity of lesion in the muscle investigated and, indirectly, the evaluation of the progress of the disease in serial studies. It might play a great role in prognosing and in monitoring of therapeutical trials. The abnormalities in the maximal effort pattern presenting as decrease of recording density and amplitude as well as of bioelectric activity indicate in the quantitative EMG a high degree of lesion. Those signs are accompanied by altered MUP parameters: decrease of MUP amplitude and area as compared with the former stages of reinnervation. Those signs express decompensation and denervation predominating over reinnervation. In SFEMG they present as FD decrease and in Macro-EMG as decrease of amplitude as compared to the reinnervation period. Serial investigations of amplitude of the potential resulting from supermaximal stimulation (CMAP), quantitative evaluation of the maximal voluntary isometric contraction (MVIC) and the assessment of the number of motor units (MUNE) are further valuable methods in monitoring of ALS progress.
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PMID:[Electrophysiological investigation s in diagnosis and evaluation of ALS progress]. 1173 77

The anterior horn cell diseases, with the exception of polio, are progressive degenerative diseases of the motor neurons. These disorders include SMA types I to III in children and familial and sporadic ALS and its variants (PMA, PLS, and PBP), Kennedy's disease, and SMA type IV in adults. The electrodiagnostic study is a crucial step in the diagnostic process for all of these disorders. In general, motor NCS may be normal or reveal low CMAP amplitudes with relatively normal conduction velocities. Sensory NCS, except in the case of Kennedy's disease, are normal. The NEE is notable for the often abundant presence of abnormal spontaneous activity, including fibrillation potentials and positive sharp waves, fasciculation potentials, and complex repetitive discharges. Motor unit morphology is abnormal, with polyphasic motor units and large amplitude and duration MUAPs when the disease is slowly progressive. Recruitment in affected muscles is reduced with abnormally rapidly firing motor units. To diagnose a widespread disorder of the motor neurons, abnormalities must be present in multiple muscles with different nerve root and peripheral nerve innervation in multiple limbs. The Lambert Criteria and the El Escorial Criteria are the two most widely accepted sets of electrodiagnostic criteria for ALS. The electrodiagnostic diagnosis must be supported by appropriate history and physical examination findings and the exclusion, via neuroimaging and laboratory testing, of other diseases that may mimic a generalized disorder of the motor neurons.
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PMID:Amyotrophic lateral sclerosis and other motor neuron diseases. 1279 19

The Neurophysiological Index (NI) consists of a mathematical derivation of three standardised neurophysiological measurements. Since these measurements are part of routine practice in any clinical neurophysiology laboratory, calculation of the NI is within the capability of any laboratory. The NI is derived from the CMAP, the DML and the F-wave frequency (CMAP amplitude/DML) x F frequency %), representing aspects of the effects of denervation and reinnervation, of degeneration of the terminal part of the motor axons, and of the excitability of anterior horn cells. We have shown that this simple index is reproducible in consecutive studies of normal subjects and of patients with ALS (intra-rater reliability), and is sensitive to change. In ALS, the NI differentiates rapidly and slowly progressive disease at least as sensitively as other measures in common use, including the ALS-FRS. We propose that the NI could be used as a sensitive measure of change during the course of ALS and its treatment. In combination with relevant measures of clinical benefit, such as ALS-FRS and a QoL measure, this could simplify trial design and allow more rapid determination of the efficacy of putative new therapies in clinical trials.
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PMID:The Neurophysiological Index in ALS. 1551 88

Fasciculations are a characteristic feature of amyotrophic lateral sclerosis (ALS), and can arise proximally or distally in the motor neuron, indicating a widespread disturbance in membrane excitability. Previous studies of axonal excitability properties (i.e. threshold electrotonus, strength-duration time constant) have suggested respectively that change in potassium or sodium channels may be involved. To reinvestigate these changes and explore their correlation with disease stage, multiple axonal excitability properties (threshold electrotonus, strength-duration time constant, recovery cycle and current-threshold relationship) were measured for the median nerve at the wrist in 58 ALS patients, and compared with 25 age-matched controls. In ALS, there were greater changes in depolarizing threshold electrotonus (i.e. less accommodation) (P < 0.001) and greater supernormality in the recovery cycles (P < 0.001). These abnormalities were more prominent in patients with moderately reduced CMAP (1-5 mV). Modelling the excitability changes in this group supported the hypothesis that axonal potassium conductances are reduced, resulting in increased supernormality despite membrane depolarization. The tendency for strength-duration time constant to be prolonged in ALS was only significant for patients with normal CMAP amplitude (>5 mV). Patients with severely reduced CMAP (<1 mV) alone showed reduced threshold changes to hyperpolarizing current. These results suggest a changing pattern of abnormal membrane properties with disease progression. First, persistent Na+ conductance increases, possibly associated with collateral sprouting, and then K(+) conductances decline. Both changes cause axonal hyperexcitability, and may contribute to the generation of fasciculations. These serial changes in axonal properties could provide insights into the pathophysiology of ALS, and implications for future therapeutic options.
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PMID:Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage. 1646 88


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