1/11. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes.OBJECTIVE: Since the discovery of mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) ten years ago, testing for SOD1 gene mutations has become a part of the investigation of patients with suspected motor neuron disease. We searched for novel SOD1 mutations and for clinical characteristics of patients with these mutations. methods: Analysis was made of patient files at the Neurogenetic dna Diagnostic Laboratory at massachusetts General Hospital. We also scrutinized available medical records and examined patients with the different SOD1 mutations. RESULTS: One hundred and forty eight (148) of 2045 amyotrophic lateral sclerosis (ALS) patients carried a disease-associated mutation in the SOD1 gene. The most prevalent was the A4V missense mutation, found in 41% of those patients. Sixteen novel exonic mutations (L8V, F20C, Q22L, H48R, T54R, S591, V87A, T88deltaTAD, A89T, V97M, S105deltaSL, V118L, D124G, G141X, G147R, 11515) were found, bringing the total number of SOD1 gene mutations in ALS to 105. CONCLUSIONS: Mutations in the SOD1 gene are found both in sporadic and familial ALS cases without any definite predilection for any part of the gene. A common structural denominator for the 16 novel mutations or previously reported mutations is not obvious. Similarly, the nature of the putative acquired toxic function of mutant SOD1 remains unresolved. We conclude that patients with SOD1 mutations may infrequently show symptoms and signs unrelated to the motor systems, sometimes obscuring the diagnosis of ALS.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/11. Mechanical trauma as a risk factor in classic amyotrophic lateral sclerosis: lack of epidemiologic evidence.We have examined the relationship between mechanical injuries and the subsequent development of classic amyotrophic lateral sclerosis (ALS) through a critical review of the literature. Only prospective evaluation of a large cohort of trauma victims can provide an unbiased answer to this controversy. However, such an evaluation would be prohibitively expensive, and the results would not be available in our lifetime. The results of retrospective case-control studies are conflicting in part because of biases in the selection of patients and controls, poor definition of the nature and extent of the trauma and its chronological relationship to the onset of ALS, and a non-uniform approach to the collection of antecedent information. More rigorously designed studies show no association of ALS to antecedent trauma. The existing data thus do not suggest that mechanical trauma is a risk factor for ALS. Future case-control studies should conform to a standardized methodology. The critical analysis presented here of the research on the purported connection between mechanical injury and ALS may serve as a model for the evaluation of the role of trauma in other chronic diseases. Application of these methodological principles may bring increased scientific rigor to assessing the frequently litigated question of what constitutes a true trauma sequela.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
3/11. neostigmine: an alternative treatment for constipation.constipation is a common complication of amyotrophic lateral sclerosis (ALS), especially as the disease progresses. While ALS patients may experience disturbed gastrointestinal motility due to the nature of the disease and decreased physical activity, the constipation is not usually caused by mechanical obstruction. Acute colonic pseudo-obstruction (ACPO) is a syndrome characterized by massive dilation of the colon without mechanical obstruction. Recent studies have shown neostigmine may be an effective treatment for ACPO. Through a case study, the author discusses the use of neostigmine and its nursing implications on a patient with ALS.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/11. Effects of lumbar sympathetic ganglion block for a patient with amyotrophic lateral sclerosis (ALS).A 59-year-old man with amyotrophic lateral sclerosis (ALS) received lumbar epidural and sympathetic ganglion blocks to increase regional blood flow and improve his clinical symptoms. After a lumbar epidural block (0.5% mepivacaine), the skin temperature of his affected lower extremities rose by 7.0 degrees C and became close to that of the intact side, and the distance he was able to walk with his cane increased from 2 to 8 m. The clinical effects produced by the lumbar sympathetic ganglion block (99.5% alcohol) were sustained for approximately 8 weeks after the first block and for approximately 6 weeks after the second block. There were no particular adverse effects or complications associated with these nerve block procedures. Epidural and sympathetic ganglion blocks for an ALS patient, albeit their effects are of a transient nature, may improve related clinical symptoms, and were thought to play a contributory role in improving our patient's quality of life.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/11. Speech deterioration in amyotrophic lateral sclerosis: a case study.Few detailed reports have been published on the nature of speech and voice changes during the course of amyotrophic lateral sclerosis (ALS). The subject of this case study is a woman who was diagnosed as having ALS with bulbar signs at the age of 53. speech intelligibility, pulmonary function, and selected speech and voice functions were tested during an approximately 2-year course of her disease. Over this period, her speech intelligibility, as measured by a multiple-choice word identification test, declined from 98% to 48%. Phonetic features that were most affected during the intelligibility decline included voicing contrast for syllable-initial and syllable-final consonants, place of articulation contrasts for lingual consonants, manner of articulation for lingual consonants, stop versus nasal manner of production, features related to the liquid consonants, and various features related to syllable shape. An acoustic measure, average slope of the second-formant frequency, declined in association with the intelligibility reduction and is thought to reflect the loss of lingual motoneurons. Her pulmonary function also declined over the observation interval, with particularly severe reduction in measures of air flow. Oral diadochokinesis and measures of vocal function (including jitter, shimmer, and signal-to-noise ratio) were highly variable across test sessions. These results are discussed in terms of the challenges they present to sensitive assessment of change and to management of the communication disability in ALS.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
6/11. Bulbar amyotrophic lateral sclerosis: patterns of progression and clinical management.patients with bulbar amyotrophic lateral sclerosis (ALS) are often referred to the otolaryngologist/head and neck surgeon and speech pathologist for evaluation and management of dysphagia and dysarthria. These patients comprise an unusual group because of the progressive and multi-system nature of their illness. The neuromuscular disabilities associated with bulbar ALS cause a myriad of related symptoms associated with swallowing, speech, and respiration. Although the rate of progression cannot be predicted, a general pattern of progression is noted. Bulbar disease accounts for the majority of the worst symptoms of ALS. The loss of the ability to swallow changes eating from a pleasurable task to a burden of survival. Loss of communication effectively imprisons the patient in a state of isolation. The progressive weakness of respiration, predominantly a spinal rather than bulbar manifestation, is the cause of death for nearly all ALS patients and is also discussed. The general patterns of progression of bulbar ALS are outlined in this paper. The development of symptoms are correlated with specific treatment recommendations to aid the clinician in devising an orderly plan of management for this progressive disease.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
7/11. Progressive speech deterioration and dysphagia in amyotrophic lateral sclerosis: case report.amyotrophic lateral sclerosis (ALS) is a degenerative neurologic disease having both upper and lower motor neuron signs and symptoms. When the speech musculature is involved, a mixed dysarthria and dysphagia usually result. In a 49-year-old man with ALS, dysarthria and dysphagia progressed from mild to severe forms over 17 months. Eleven months after the patient first experienced symptoms, neurologic examination showed fasciculations of the extremities and tongue, limb weakness, and hyperreflexia of the limbs and velopharyngeal mechanism. tongue strength was one-fourth that of normal. Lingual alternate motions rates for consonant-vowel syllables were also reduced. To enhance lingual strength and swallowing, a tongue-strengthening program was developed for use with articulation training; to augment velopharyngeal function, a palatal lift was fitted; and to increase extremity strength, physical therapy was initiated. Six months after the initial neurologic examination, medical and speech reevaluation showed progressive weakness of the body parts affected initially; continued decline in tongue strength and lingual alternate motion rate; hypoactive reflex activity, indicative of progressive involvement of the lower motor neuron system; and continued deterioration of articulation and phonation owing to the progressive nature of the disease.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
8/11. Intracytoplasmic inclusions (Bunina bodies) in amyotrophic lateral sclerosis.In an autopsy case of sporadic amyotrophic lateral sclerosis, there were intracytoplasmic eosinophilic inclusions of the Bunina type in motor neurons. Electron microscopically, these bodies were observed as amorphous substances, irregularly deposited around the endoplasmic reticulum to form masses. Similar small masses were also visible in mitochondria. These substances did not stain for acid phosphatase. By analytical electron microscopy they contained silicon. Bunina bodies, therefore, seem to be due to deposition of some metabolite, but their nature is still obscure.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
9/11. Analysis of abnormal articulatory dynamics in two dysarthric patients.By means of pellet tracking techniques using an X-ray microbeam system, observations of the articulatory movements of various types of dysarthric subjects were conducted. In selected cases, electromyography (EMG) was also performed. The data were specifically examined for range, velocity, and consistency (reproducibility) of the movements of the articulators, as well as the pattern of coordination of the different articulators involved. It was found in the case of ataxic dysarthria of cerebellar origin, for example, that the dynamic patterns were best represented as a difficulty in the initiation of purposeful movements and an inconsistency of articulatory movements, particularly in the repetitive production of a monosyllable. On EMG, breakdown of the rhythmical patterns in the articulatory muscles was quite obvious in the repetition of a monosyllable. In the case of amyotrophic lateral sclerosis (ALS), decrease in the range and velocity of movements was noted. This resulted from reduced neuromuscular units (NMU) activities manifested in clinical EMG. Analysis of the dynamic aspects of the dysarthrias is a promising approach for elucidating the nature of central problems of speech production and for a differential diagnosis of various types of dysarthrias.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
10/11. Bunina body formation in amyotrophic lateral sclerosis: a morphometric-statistical and trace element study featuring aluminum.Clinico-environmental and pathological variables were obtained from 10 patients with amyotrophic lateral sclerosis using particle-induced X-ray emission spectrometry (PIXE) and morphometric-statistical analysis. Statistical analysis identified a model that maximally predicts the Bb% (frequency of Bunina bodies) from a selected set, four variables: (1) nucleolar index, (2) magnesium (Mg) content, (3) aluminum (Al) content, and (4) duration of illness. Among them, only the Al content proved important. To determine their chemical nature, electron energy loss spectrometry (eels) was applied at the ultrastructural level; it revealed that within the motor neuron, Al strongly binds to the Bunina body as well as rough endoplasmic reticulum (rER), and lesser strongly to mitochondria and lipofuscin granule. Thus, it is chemically similar to the rER, providing preferential binding sites to aluminum. The Bunina bodies may be an end-product of the nucleic acid dysmetabolism at rER caused by Al along with Mg depletion.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
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