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Biomedical subjects

D R Cornblath

Publications and source records attributed to D R Cornblath.

At least 109 records · Page 6Linked to original sources
PubMed1990

Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis.

Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p less than 0.01) by 100 to 200% in patients with ALS. Similarly, the concentrations of the excitatory neuropeptide N-acetyl-aspartyl glutamate and its metabolite, N-acetyl-aspartate, were elevated twofold to threefold in the cerebrospinal fluid from the patients. There was no relationship between amino acid concentrations and duration of disease, clinical impairment, or patient age. In the ventral horns of the cervical region of the spinal cord, the level of N-acetyl-aspartyl glutamate and N-acetyl-aspartate was decreased by 60% (p less than 0.05) and 40% (p less than 0.05), respectively, in 8 patients with ALS. Choline acetyltransferase activity was also diminished by 35% in the ventral horn consistent with motor neuron loss. We conclude that excitatory amino acid metabolism is altered in patients with ALS. Based on neurodegenerative disease models, these changes may play a role in motor neuron loss in ALS.

Adult↗
PubMed1990

Paramyotonia congenita or hyperkalemic periodic paralysis? Clinical and electrophysiological features of each entity in one family.

The nosological distinction between paramyotonia congenita (PC) and hyperkalemic periodic paralysis (HPP) continues to generate debate. Recently, electrophysiological signs thought to be specific for each entity have been described and have been used to bolster the argument that the two disorders are distinct. We report a particularly instructive family wherein individual members had clinical features of either PC or HPP and electrophysiological features of both. We suggest that PC and HPP represent part of the spectrum of a single genetic disorder. Evoked response testing, with exercise and cold provocation, may be useful in determining the physiologic pattern that predominates in any one individual.

Adult↗
PubMed1990

Soluble interleukin-2 receptor and soluble CD8 in serum and cerebrospinal fluid during human immunodeficiency virus-associated neurologic disease.

We have measured levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in serum and cerebrospinal fluid (CSF) of 127 human immunodeficiency virus (HIV)-seropositive and 51 HIV-seronegative individuals. Serum levels of sIL-2R and sCD8 were higher in HIV+ than in HIV- individuals. HIV+ individuals were grouped by neurological status: asymptomatic, abnormal on neuropsychological screening, HIV-related meningitis, inflammatory demyelinating polyneuropathy, opportunistic central nervous system (CNS) infections and HIV-related dementia, myelopathy or sensory neuropathy. Serum levels of sIL-2R and sCD8 were higher in all HIV+ categories compared to HIV- individuals. Patients with HIV-related meningitis had higher levels of sIL-2R and sCD8 than asymptomatic HIV+ individuals, and inflammatory polyneuropathy patients had higher levels of sCD8. CSF levels of sCD8 were higher in all categories of HIV+ than in HIV- individuals. Patients with HIV-related meningitis, inflammatory neuropathy and opportunistic infections had higher levels than asymptomatic individuals. Examination of the time course showed that serum and CSF levels of sIL-2R and sCD8 increased to very high levels during acute HIV infections. Serum levels then declined over several months to relatively stable elevated levels. By 1-2 years after HIV infection sIL-2R was relatively low in CSF, while sCD8 remained elevated with a gradual decrease over the subsequent years of follow-up.

Antigens, CD↗
PubMed1990

Quantitative analysis of endoneurial T-cells in human sural nerve biopsies.

We used immunocytochemical methods on sural nerve biopsies from 42 patients with peripheral neuropathy to identify mononuclear cells, determine whether lymphocytic infiltration occurs in a variety of neuropathies, and identify the subtypes of lymphocytes. Immunostained cells were present in 76% of nerve biopsies. CD3+ cells (T lymphocytes) were greatest in density (cells/mm2). In patients whose CD4:CD8 T cell ratio was measured also in blood and cerebrospinal fluid, the CD4:CD8 T cell ratio was similar in all three compartments. These findings suggest that T lymphocytes are frequently present in nerves obtained from patients with various types of neuropathies and raise questions about factors that attract T lymphocytes into nerve that may be important in pathogenesis.

Biopsy↗
PubMed1990

Steroid-responsive myeloneuropathy in a man dually infected with HIV-1 and HTLV-I.

Two human retroviruses, HIV-1 and HTLV-I, have been associated with myelopathies in addition to other neurologic disorders. We report an American dually infected with HIV-1 and HTLV-I who developed steroid-responsive myeloneuropathy. This 28-year-old bisexual man developed interstitial pneumonitis and a transient midthoracic sensory level followed by the evolution of a slowly progressive spastic paraparesis and sensorimotor neuropathy. Serologic studies demonstrated coinfection with both HIV-1 and HTLV-I. Peripheral blood absolute CD4 count was persistently within the normal range. Cranial MRI was normal and spinal MRI showed T3-T10 atrophy. Serial CSF analyses demonstrated marked intrathecal synthesis of anti-HTLV-I IgG, lymphocytic pleocytosis, elevated protein and immunoglobulin G, and oligoclonal bands. HIV-1 was isolated from CSF but not from peripheral nerve. Lymphoproliferative studies confirmed spontaneous proliferation in both blood and CSF. Soluble interleukin 2 receptor and soluble CD8 were greatly elevated in blood and CSF when compared with patients with HIV-related vacuolar myelopathy and seronegative patients with other causes of myelopathy. Nerve biopsy showed epi- and endoneurial CD8+ lymphocytic infiltration without vasculitis; muscle biopsy showed features of acute and chronic denervation. A 6-week course of prednisone produced sustained improvement in leg strength and walking times. We speculate that the myeloneuropathy was caused by HTLV-I in the setting of coinfection with HIV-1.

AIDS Dementia Complex↗
PubMed1989

Low prevalence of neurological and neuropsychological abnormalities in otherwise healthy HIV-1-infected individuals: results from the multicenter AIDS Cohort Study.

Accurate description of the prevalence of neurological impairment in healthy individuals who are infected with human immunodeficiency virus type 1 (HIV-1) has relevance for public health policy, for employment issues, and for planning future health needs. Within the Multicenter AIDS Cohort Study, we determined the cross-sectional prevalence of neurological abnormalities in 270 HIV-1 seropositive homosexual and bisexual men in Centers for Disease Control Groups II and III, using a control group of 193 HIV-1 seronegative homosexual men. Utilizing a neurological and neuropsychological screening battery, we found no differences in the prevalence of neuropsychiatric symptoms or in neuropsychological performance. One hundred nineteen subjects with abnormalities on screening tests completed additional neuropsychological testing and had neurological examinations. The majority had normal results and the frequency of neurological abnormalities and impaired neuropsychological performance was not significantly increased among HIV-1 seropositive subjects. Most of the abnormalities could be attributed to causes other than HIV-1. One subject had mild HIV-1-related dementia, yielding a prevalence of 3.7:1,000 (95% confidence interval: 0.19-23.7:1,000). Magnetic resonance imaging demonstrated sulcal prominence and focal areas of high signal intensity in white matter in 63% of HIV-1 seropositive subjects and 48% of uninfected control subjects. Abnormalities in cerebrospinal fluid were noted in 23 (85%) of 27 HIV-1-infected individuals. Our studies indicate that the prevalence of dementia and other HIV-1-related neurological disorders is very low among healthy HIV-1 seropositive homosexual men. The confounding effects of factors such as substance abuse or preexisting medical conditions must be considered in the neurological evaluation of such patients.

AIDS Dementia Complex↗
PubMed1989

Neuropathological changes in early HIV-1 dementia.

Early pathological abnormalities in human immunodeficiency virus (HIV-1)-related dementia have not been well documented. We report a homosexual man with fatigue and intermittent diarrhea in whom early HIV-1-related dementia was demonstrated during neurological screening in the Multicenter AIDS Cohort Study. Within 4 months he died of massive epistaxis, and the brain revealed astrocytosis of white matter and mild pallor of myelin staining in the absence of inflammation, multinucleated giant cells, and brain atrophy.

AIDS Dementia Complex↗
PubMed1989

Spontaneous diabetes mellitus in a rhesus monkey: neurophysiological studies.

Peripheral neuropathy is a common complication of human diabetes, but its occurrence in spontaneously diabetic monkeys is unknown. Four months after developing diabetes, a 22-year-old female rhesus monkey had nerve conduction studies which were compared with control data obtained from 9 nondiabetic rhesus monkeys. In the diabetic monkey, median and ulnar sensory action potential amplitudes and the median motor distal latency differed from controls by more than two standard deviations. Conduction velocities in the diabetic monkey were less than the mean values in controls, although none were beyond two standard deviations of control means. These electrophysiologic abnormalities are similar to those described in human diabetes and suggest that the spontaneously diabetic monkey peripheral nervous system may be a suitable model of experimental diabetic neuropathy.

Animals↗
PubMed1989

Electrodiagnosis of human colchicine myoneuropathy.

Colchicine may produce a neuromuscular disorder even when given in customary doses. We report the electrodiagnostic features in eight pathologically proven cases of colchicine-induced myoneuropathy. Myopathic motor unit potentials and early recruitment were found in proximal limb and truncal muscles, frequently with fibrillations, positive sharp waves, or complex repetitive discharges. These electromyographic findings correlated with the course of the weakness, which rapidly resolved within weeks of drug discontinuation, indicating that the major functional disturbance in the patients was myopathy. The accompanying signs of axonal neuropathy persisted longer, with little functional consequence. Although often misrecognized as polymyositis, colchicine myoneuropathy was identifiable by the rapid clinical and electrophysiologic improvement following drug withdrawal as well as by its distinctive morphology.

Aged↗
PubMed1989

Anti-GM1 ganglioside antibodies with differing fine specificities in patients with multifocal motor neuropathy.

Antibodies to gangliosides were detected in sera from three of 19 patients with chronic inflammatory polyneuropathy (CIP) by a thin-layer chromatogram overlay technique. All three of the patients fell into a clinical subset of the group that had multifocal motor neuropathy, and in all three patients the antibodies reacted with GM1 ganglioside. However, the fine specificities of the antibodies differed as demonstrated by cross-reactivity with different gangliosides in each of the three patients. The antibodies in patient 1 reacted with GM1, GD1b, and asialo-GM1 suggesting that the terminal Gal(beta 1-3)GalNAc moiety that is common to these three glycolipids is an important part of the epitope(s). This was confirmed by showing reactivity of the antibodies with Gal(beta 1-3)GalNAc conjugated to bovine serum albumin. Patient 2 had antibodies that did not react with GD1b, but cross-reacted with GM2 ganglioside suggesting that the epitope(s) involved the inner portion of the oligosaccharide moiety that is shared between GM1 and GM2. Patient 3 had antibodies that reacted with GM1 and asialo-GM1, but they did not cross-react with either GD1b or GM2. These results provide further evidence for a relationship between motor nerve syndromes and anti-GM1 antibodies and also suggest that GM1 could be a principal target antigen since other reactive gangliosides differed among the patients. However, the possible pathogenic effects of anti-GM1 antibodies on motor nerves remain to be established.

Antibodies↗
PubMed1989

Identification of mononuclear cells in CSF of patients with HIV infection.

Using immunocytochemical methods, CSF lymphocyte subpopulations were examined in different neurologic disorders associated with human immunodeficiency virus (HIV) infection. CSF pleocytosis was observed in asymptomatic neurologically normal subjects, in patients with aseptic meningitis, and those with inflammatory demyelinating neuropathies, but infrequently in subjects with AIDS dementia complex. The distribution of CSF lymphocyte subpopulations in HIV-infected patients differed from control subjects showing decreases in percentages of T helper (CD4) cells and increases in T suppressor (CD8) cells. Peripheral blood and CSF CD4:CD8 ratios were inverted in all of the neurologic disorders studied. In all disorders, the changes in CSF composition of mononuclear cells paralleled alterations in peripheral blood and in patients with AIDS dementia complex, there was a relationship between the severity of dementia and blood and CSF CD4 lymphocyte proportions.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Differential effects of prednisone and cyclophosphamide on autoantibodies in human neuromuscular disorders.

We compared the effects of treatment of patients with prednisone or cyclophosphamide on a series of different types of autoantibodies. Levels of antiacetylcholine receptor (anti-AChR) antibodies and of antibodies to GM1 and GD1a gangliosides were measured in patients with a variety of neuromuscular disorders before and after treatment. Most patients had several autoantibodies present. We showed that prednisone treatment resulted in a reduction in titers of anti-AChR but not antiganglioside antibodies. Cyclophosphamide treatment produced a reduction of antiganglioside antibody titers. An intravenous and oral regimen was more effective than a single intravenous course of cyclophosphamide. We conclude that an immunosuppressive medication such as prednisone may reduce levels of some autoantibodies while producing no change in others, even in an individual patient. In addition, cyclophosphamide can suppress autoantibodies that prednisone does not. These differences in immunopharmacologic responses suggest that there are several distinct mechanisms of autoantibody production in humans. The utility of immunosuppressive medications in specific disease processes may be related in part to the mechanism of production of pathogenic antibodies.

Autoantibodies↗
PubMed1989

Compression syndromes due to hypertrophic nerve roots in hereditary motor sensory neuropathy type I.

Three patients with hereditary motor sensory neuropathy type I developed neurologic deficits attributable to hypertrophic nerve roots. Compression of the cervical spinal cord by enlarged nerve roots occurred in our index patient. Multilevel decompressive laminectomies relieved the myelopathy. An unrelated patient who had syncope precipitated by neck rotation had hypertrophied nerve roots that eroded into the transverse foramina in juxtaposition to the vertebral arteries. In a 3rd patient, compression of hypertrophied nerve roots within the thecal sac and neural foramina was associated with spinal claudication and radiculopathy, respectively.

Adult↗
PubMed1989

Peripheral neuropathy in diabetic monkeys.

Peripheral neuropathy is a significant complication of human diabetes and a source of morbidity. Appropriate experimental models may aid in understanding its pathogenesis and in developing therapeutic strategies. We sought to determine whether spontaneously diabetic obese adult monkeys developed peripheral neuropathy and whether it occurred early or late in relation to the onset of hyperglycemia. We studied nerve conduction in both motor (peroneal, median, and ulnar) and sensory (median and ulnar) nerves in 13 adult male rhesus monkeys, 4 overtly diabetic and 9 nondiabetic (mean age 21 +/- 2 and 16 +/- 2 yr, respectively, NS; mean fasting plasma glucose 14.5 +/- 3.4 and 4.4 +/- 0.6 mM, P = .001). The diabetic animals had significantly reduced motor conduction velocities and prolonged F-wave latencies. Motor-evoked amplitudes did not differ. In the diabetic monkeys, nerve conduction times were increased in motor fibers, which could be identified as early as 2 yr after the onset of hyperglycemia. These abnormalities are similar to those seen in humans and suggest further study of these animals as a primate model of human diabetic neuropathy.

Animals↗
PubMed1988

Plasmapheresis and Guillain-Barré syndrome: analysis of prognostic factors and the effect of plasmapheresis.

The time course of recovery in the Guillain-Barré syndrome is known to vary widely, but factors associated with differences have not been previously defined. In this study we used multivariate analysis to identify such factors and to determine whether the presence or absence of specific factors would influence treatment decisions, particularly the use of plasmapheresis. Data from 245 patients randomized into conventional and plasmapheresis arms were used to assess the time to walk independently (Grade 2), the time to improve one grade, and the percentage improved at 4 weeks. Individually, many factors were associated with outcome. In the multivariate analysis, four factors correlate with poorer outcomes: mean amplitude of compound muscle action potential on stimulating distally of 20% of normal or less, older age, time from onset of disease of 7 days or less, and need for ventilatory support. The most powerful predictor of outcome was the abnormal mean amplitude of compound muscle action potential on stimulating distally. Plasmapheresis, the only variable the physician can influence, has a beneficial effect over and above any or all of these factors. The plasmapheresis patients on continuous flow machines had better outcomes than those on intermittent flow machines. From these data, tables of expected outcome probabilities have been developed.

Adult↗
PubMed1988

Motor conduction studies in Guillain-Barré syndrome: description and prognostic value.

The North American study of plasmapheresis in Guillain-Barré syndrome (GBS) included early, standardized electrodiagnostic testing in 210 of the 245 patients. To determine the types of abnormalities and the relation to outcome, we analyzed the prospectively collected motor conduction data obtained during the first 30 days of illness. For each parameter of motor conduction data, means were computed based on institutional normal data. Mean distal motor and F wave latencies commonly were abnormal in these early studies. In univariate analysis, mean compound muscle action potential (CMAP) amplitude from distal and proximal stimulation and mean motor conduction velocity were found to be related to the four predetermined outcome measures. In multivariate analysis of the motor conduction parameters, mean distal CMAP amplitude was the single best predictor of prognosis; other measures did not add to its predictive value. In further multivariate analysis of all factors relating to outcome, mean distal CMAP amplitude was determined to be the most powerful predictor of outcome, followed by plasmapheresis. These two factors were always statistically significant over and above all other variables. Our results indicate that prognostic information can be obtained from motor conduction studies even when performed early in the course of GBS; a mean distal CMAP amplitude of 0 to 20% of the lower limit of normal is associated with a markedly increased probability of a poor outcome. Nevertheless, even in patients with a low mean distal CMAP amplitude, the predicted outcome is improved with plasmapheresis therapy.

Action Potentials↗
PubMed1988

Serum antibodies to gangliosides in Guillain-Barré syndrome.

To determine whether antibodies to acidic glycolipids of nervous tissue are present in patients with Guillain-Barré syndrome (GBS), sera from patients with GBS and appropriate control subjects were tested by a thin-layer chromatogram overlay technique. Chromatograms on which the whole ganglioside fractions from peripheral nerve and brain had been separated were overlaid with appropriate dilutions of the patients' sera (1:100 or greater), and antibody binding was revealed with a radiolabeled or peroxidase-labeled second antibody. Antibodies to ganglioside antigens were detected in 5 of 26 patients with GBS. IgG antibodies in 1 patient reacted strongly with LM1 (sialosyl paragloboside), the major ganglioside of human peripheral nervous system myelin, and its hexaose analog (sialosyl lactosaminyl paragloboside), a minor ganglioside of human peripheral nervous system myelin. The antibody titer in this patient fell 8-fold over 6 weeks coincident with clinical improvement. IgG from 2 other patients with GBS reacted with GD1b ganglioside, and the antibody titers in these patients also decreased substantially with clinical improvement. IgM antibodies in the sera from 2 other patients reacted with GD1a and GT1b gangliosides, which have a shared terminal carbohydrate sequence. Antibodies to gangliosides were not detected in the sera from 19 patients with other neurological diseases or from 10 normal subjects, and the frequency with which antiganglioside antibodies occurred in the patients with GBS was significantly greater than that in the combined control subjects (p less than 0.01). The results demonstrate relatively high levels of antibodies to gangliosides in some GBS patients.

Adult↗