Case records of the Massachusetts General Hospital. Case 22-2006--a 77-year-old man with a rapidly progressive gait disorder.
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Biomedical subjects
Publications and source records attributed to Didier P Cros.
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The development of the personal computer has simplified the process of quantitating sensory thresholds using various testing algorithms. We reviewed the technical aspects and reproducibility of different methods to determine threshold for light touch-pressure, vibration, thermal, and pain stimuli. Clinical uses and limitations of quantitative sensory testing (QST) were also reviewed. QST is a reliable psychophysical test of large- and small-fiber sensory modalities. The results of QST are highly dependent on methodology and the full cooperation of the subject. QST has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. The use of QST in research and patient care should be limited to instruments and their corresponding methodologies that have been shown to be reproducible. Literature data do not allow conclusions regarding the relative merits of individual QST instruments.
Quantitative sensory testing is a reliable way of assessing large and small sensory nerve fiber function. Sensory deficits may be quantified and the data used in parametric statistical analysis in research studies and drug trials. It is an important addition to the neurophysiologic armamentarium, because conventional sensory nerve conduction tests only the large fibers. QST is a psychophysical test and lacks the objectivity of NCS. The results are subject to changes owing to distraction, boredom, mental fatigue, drowsiness, or confusion. When patients are consciously or unconsciously biased toward an abnormal QST result, no psychophysical testing can reliably distinguish these patients from those with organic disease. QST tests the integrity of the entire sensory neuraxis and is of no localizing value. Dysfunction of the peripheral nerves or central nervous system may give rise to abnormalities in QST. As is true for other neurophysiologic tests, QST results should always be interpreted in light of the patient's clinical presentation. Quantitative sensory testing has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. Because longitudinal QST studies of patients in drug trials are usually performed over a period of several months to a few years, reproducibility studies on the placebo-control group should be included. For individual patients, more studies are needed to determine the maximum allowable difference between two QSTs that can be attributed to experimental error. The reproducibility of thermal thresholds may not be as good as that of vibration threshold. Different commercially available QST instruments have different specifications (thermode size, stimulus characteristics), testing protocols, algorithms, and normal values. Only QST instruments and their corresponding methodologies that have been shown to be reproducible should be used for research and patient care. The data in the literature do not allow conclusions regarding the superiority of any QST instruments. The future of QST is promising; however, many factors can affect QST results. As is true for other neurophysiologic tests, QST is susceptible to many extraneous factors and to misuse when not properly interpreted by the clinician.
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Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior horn cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the same chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.