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Biomedical subjects

Morris A Fisher

Publications and source records attributed to Morris A Fisher.

11 recordsLinked to original sources

Factors influencing F-wave latency detection of lumbosacral root lesions using a detection theory based model.

OBJECTIVE: To evaluate the F-wave dilution hypothesis; which implies that absolute F-wave latencies obscure the much smaller delay associated with slow intra-lesion conduction, such is caused by nerve root compression in lumbosacral radiculopathy. A corollary objective is to determine how F-wave measurement and pathological factors influence diagnostic accuracy. METHODS: An analytical model is developed based on signal detection theory and a number of simplifying assumptions. Diagnostic accuracy, quantified by the area under the receiver operating characteristic (ROC) curve, is determined for various model realizations derived from the clinical and experimental neurophysiology literature. A preliminary experimental validation of model predictions is also performed. RESULTS: Absolute F-wave latency does not influence the accuracy of focal lesion detection. F-wave latency variance and lesion pathology are the determinant factors. F-wave latencies and distal latencies are estimated to have qualitatively similar detection characteristics, although distal latencies have quantitatively better diagnostic efficacy for comparable focal pathology. Preliminary experimental results support the modeled dependence of diagnostic accuracy on latency variance and lesion severity. CONCLUSIONS: Absolute F-wave latency does not dilute slow conduction within focal lesions, such as in lumbosacral radiculopathy. The dominant measurement factor is F-wave latency variance. SIGNIFICANCE: To maximize the diagnostic utility of F-wave latencies, focus must be placed on reducing latency variance, such as through correction for demographic covariates. This model calls into question the F-wave dilution hypothesis.

Adolescent↗

Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Electrodiagnosis↗

Comparison of automated and manual F-wave latency measurements.

OBJECTIVE: F-waves are well-established clinical neurophysiological studies. F-wave analysis is now cumbersome limiting the usefulness of F-waves. This study evaluates the accuracy and reliability of an automated analysis method for F-wave latencies. METHODS: F-waves following 20 supramaximal stimuli recorded from the extensor digitorum brevis muscle of 80 limbs (55 subjects) were analyzed. F-wave latencies were determined using a computer program developed by NEUROMetrix (Waltham, MA). These results were compared in a blinded fashion with manual measurements of the same datasets by a clinical neurophysiologist with established expertise in F-waves. The manual measurements were repeated once. RESULTS: The yield rate of automated median F-wave latencies was 100% with a correlation coefficient (CC) of 0.996 when compared with manual assignment results. For individual F-wave latency measurements, comparable values were 90% and 0.977, respectively. The repeated manual measurements revealed a yield rate and CC for median latencies of 100% and 0.998, respectively, with comparable values for individual latency measurements of 95% and 0.992. CONCLUSIONS: These results indicate the feasibility of a reliable computerized automated analysis of F-wave latencies. SIGNIFICANCE: A reliable automated analysis of F-waves should add meaningfully to the value of these responses in clinical neurophysiology.

Adult↗

Physicians and the pharmaceutical industry: a dysfunctional relationship.

The pharmaceutical industry is one of the largest and most profitable industries in the world, and in the United States, the industry has a particularly privileged economic position. Yet the cost of drugs in the United States is higher than anywhere else, due largely to the fact that the industry is focusing increasingly on marketing rather than on the development of meaningful new medications: available evidence does not support claims of great expense for the development of new drugs. Because of its vast resources, the pharmaceutical industry has assumed an increasing influence in medicine, which, given the differences in values and priorities between medicine and the drug companies, is a cause for concern. The pharmaceutical industry has acted to maximize its profits in ways that frequently conflict with medicine's need for truth and full disclosure. Indeed, the industry has arguably worked to compromise physicians' judgments, as well as academic standards. As a result, despite government regulation there have been unnecessary adverse effects from drugs. The experience with butorphanol (Stadol) exemplifies problems in the current system and the harm that can result. Changes are suggested to make the pharmaceutical industry more responsive to the needs of patients and physicians.

Adverse Drug Reaction Reporting Systems↗

Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block.

Elevated levels of serum antibodies to neurofilament proteins have been associated with a variety of neurological diseases, including autoimmune disorders such as neuropathy with monoclonal gammopathy of undetermined significance (MGUS). The pathological significance of anti-neurofilament antibodies in sera of affected patients, however, remains unclear. In this study, we report our findings of polyclonal antibodies in sera from 4 of 16 IgG MGUS neuropathy patients that react strongly on immunoblot with a high molecular weight neurofilament protein (NFH). The effect of anti-NFH polyclonal antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-NFH antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly attenuated proximal-evoked motor nerve compound muscle action potential (CMAP) amplitudes in a complement-dependent manner. In contrast, ankle-evoked CMAP amplitudes were unaffected by intraneural injection of sera containing anti-NFH antibody. Anti-NFH serum-injected nerves showed changes in both axon caliber (shrinkage) and myelin ultrastructure (vesiculation and ovoid formation), suggestive of intramyelinic edema. Preincubation of sera containing anti-NFH antibody with purified NFH protein abolished immunoreactivity to NFH protein and neutralized the serum-mediated toxicity. The data suggest that anti-NFH polyclonal antibodies occurring in sera of some patients with IgG MGUS neuropathy may elicit peripheral nerve conduction block independent of the patients' IgG paraprotein. Anti-neural polyclonal antibodies in sera of IgG MGUS neuropathy patients may have a greater pathological significance than previously anticipated.

Action Potentials↗

H reflexes and F waves. Fundamentals, normal and abnormal patterns.

H reflexes and F waves have become integral parts of the electrodiagnostic examination in general, and nerve conduction studies in particular. They supplement the sensory and motor conduction studies by assessing the entire nerve segments including proximal portions of the motor and sensory axons. H reflexes and F waves have their own advantages and limitations, similarities and differences. These "late" responses are useful in patients with radiculopathies, plexopathies, and peripheral polyneuropathies, including the Guillain-Barre syndrome. They are also helpful in spinal cord disorders.

Brachial Plexus Neuropathies↗

Electrophysiology of radiculopathies.

The anatomy, pathophysiology, and clinical evaluation of radiculopathies are discussed. Defining whether root injury is present and which roots are involved can be difficult but critical for patient management. In conjunction with clinical and radiological information, studies that establish physiological abnormalities of roots should be helpful and important. Clinical neurophysiological studies for radiculopathies are performed frequently but have yet to achieve a universally accepted role in the evaluation of these patients. Electrophysiological techniques for the evaluation of radiculopathies are reviewed. Needle electromyography is the best established of these procedures but has the disadvantage of requiring injury to motor fibers of both a certain degree and distribution. Nerve conduction studies may rarely be abnormal in radiculopathies but are needed to be certain other conditions that may produce similar symptoms and signs are not present. H reflexes and F waves probably have roles in the evaluation of radiculopathies but published reports about F waves in radiculopathies have been marred by inadequate methodology. There is evidence based on large series of patients that somatosensory evoked potentials can be helpful for evaluating patients with multilevel injury such as spinal stenosis, patients where electrophysiological studies may have their greatest clinical utility. Further work using either electrical stimulation with needles or magnetic stimulation of roots seems warranted. The demonstration of meaningful electrophysiological changes with activities that reproduce radicular symptoms may be a promising experimental approach. Available information does not necessarily answer critical questions about the role of electrophysiology in patients with radiculopathies. This cannot be done using analyses based on current ideas about evidence based medicine given the absence of a 'gold standard' for defining radiculopathies as well the absence of blinded studies. The available information provides strong arguments for further investigations evaluating different clinical neurophysiological techniques in the same patient, and for evaluating the value of these techniques by concentrating on their clinical import.

Electrodiagnosis↗

Antibodies to L-periaxin in sera of patients with peripheral neuropathy produce experimental sensory nerve conduction deficits.

L-Periaxin is a PDZ-domain protein localized to the plasma membrane of myelinating Schwann cells and plays a key role in the stabilization of mature myelin in peripheral nerves. Mutations in L-periaxin have recently been described in some patients with demyelinating peripheral neuropathy, suggesting that disruption of L-periaxin function may result in nerve injury. In this study, we report the presence of autoantibodies to L-periaxin in sera from two of 12 patients with diabetes mellitus (type 2)-associated neuropathy and three of 17 patients with IgG monoclonal gammopathy of undetermined significance (MGUS) neuropathy, an autoimmune peripheral nerve disorder. By comparison, anti-L-periaxin antibodies were not present in sera from nine patients with IgM MGUS neuropathy or in sera from 10 healthy control subjects. The effect of anti-L-periaxin serum antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-L-periaxin antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly (p < 0.005, n = 3) attenuated sensory-evoked compound muscle action potential (CMAP) amplitudes in the absence of temporal dispersion. In contrast, motor-evoked CMAP amplitudes and latencies were not affected by intraneural injection of sera containing anti-L-periaxin antibody. Light and electron microscopy of anti-L-periaxin serum-injected nerves showed morphologic evidence of demyelination and axon enlargement. Depleting sera of anti-L-periaxin antibodies neutralized the serum-mediated effects on nerve function and nerve morphology. Together, these data support anti-L-periaxin antibody as the pathologic agent in these serum samples. We suggest that anti-L-periaxin antibodies, when present in sera of patients with IgG MGUS- or diabetes-associated peripheral neuropathy, may elicit sensory nerve conduction deficits.

Aged↗

Characterizing neuropathies associated with monoclonal gammopathy of undetermined significance (MGUS): a framework consistent with classifying injuries according to fiber size.

Neuropathies associated with monoclonal gammopathy of undetermined significance (MGUS) occur frequently in the elderly. Data from 42 consecutive elderly patients with a MGUS-associated neuropathy - 12 patients with IgM MGUS, 25 patients with IgG MGUS, 5 patients with IgA MGUS - were evaluated prospectively using quantifiable clinical criteria and quantitative sensory testing. Results consistent with preferential injury to large fibers were found in patients with IgM isotypes (P <.005) but not in patients with IgG isotypes (P <.0005 to.0004). These findings support an immunologic origin for at least some MGUS-associated neuropathies and provide information important for the clinical evaluation of neuropathies in the elderly.

Aged↗