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A Pestronk

Publications and source records attributed to A Pestronk.

At least 55 records · Page 3Linked to original sources
PubMed1997

Polyneuropathies associated with high titre antisulphatide antibodies: characteristics of patients with and without serum monoclonal proteins.

OBJECTIVES: Previous studies of small numbers of patients have shown that antisulphatide autoantibodies are associated with polyneuropathies having a prominent sensory component. However, clinical and electrodiagnostic features are variable. The range of clinical and electrodiagnostic findings in 19 patients with polyneuropathies and high titre (> 4500) serum IgM antisulphatide antibodies is described, together with testing for serum monoclonal (M) proteins. METHODS: About 20000 serum samples that were referred to the clinical laboratory from 1990 to the end of 1994 were screened by enzyme linked immunosorbent assay (ELISA) for specific high titre antisulphatide antibodies. The clinical and electrodiagnostic data in 23 patients with positive results were reviewed. IgM binding to peripheral nerve structures was also evaluated in these patients. RESULTS: Nineteen patients had predominantly distal, symmetric pansensory loss. Patients with IgM antisulphatide antibodies and no serum M protein usually had clinical syndromes that included: (1) neuropathic pain or dysaesthesiae, (2) no functionally significant weakness, and (3) an axonal neuropathy on electrodiagnostic testing. On immunocytochemical studies serum IgM from the patients without M proteins usually (nine of 10; 90%) bound to peripheral nerve axons, but never to myelin. Patients with antisulphatide antibodies and a serum M protein, usually IgM, were more likely than patients without a serum M protein, to have syndromes with: (1) no pain or dysaesthesiae, (2) motor abnormalities, and (3) a demyelinating polyneuropathy by electrodiagnostic criteria. In immunocytochemical studies serum IgM most often bound to either peripheral nerve myelin or endoneurial structures. CONCLUSION: Patients with polyneuropathy and high titre serum IgM antisulphatide antibodies can be classified into subgroups according to the presence or absence of a serum M protein. Patients without an M protein are more likely to have pure sensory syndromes, pain, an axonal neuropathy, and serum IgM binding to axons. Patients with a serum M protein commonly had syndromes with prominent motor involvement, no pain, and a demyelinating neuropathy.

Adult↗
PubMed1997

Serum IgM monoclonal autoantibody binding to the 301 to 314 amino acid epitope of beta-tubulin: clinical association with slowly progressive demyelinating polyneuropathy.

We identified five patients with IgM monoclonal autoantibodies that bound to human brain tubulin. In a companion study, we found that IgM in these sera selectively recognized one of three epitopes on tubulin. IgM from three patients bound selectively to a small epitope on human beta-tubulin comprising amino acids 301 to 314. The other two sera recognized tubulin amino acids 215 to 235 and 315 to 336. In this study, we compared the clinical syndromes in these patients with the tubulin epitope recognized by their serum IgM. The three patients with IgM binding to tubulin amino acids 301 to 314 all had chronic inflammatory demyelinating polyneuropathy (CIDP) syndromes with slowly progressive weakness, hyporeflexia, and electrophysiologic studies consistent with demyelination. Two of these patients had significant asymmetry to their weakness. The two other patients had diagnoses of polyradiculopathy and amyotrophic lateral sclerosis with no evidence of peripheral nerve demyelination. We conclude that IgM monoclonal anti-tubulin antibodies have some association with demyelinating polyneuropathy syndromes, but may occur in patients with other clinical syndromes as well. A stronger association with demyelinating polyneuropathies may occur if the anti-tubulin antibodies recognize the 301 to 314 amino acid epitope on tubulin. This tubulin epitope, or a similar one on another molecule, could play an important antigenic role in the development of demyelinating polyneuropathies with features of CIDP.

Aged↗
PubMed1997

Multifocal motor neuropathy: serum IgM binding to a GM1 ganglioside-containing lipid mixture but not to GM1 alone.

IgM anti-GM1 antibodies are associated with motor neuropathy syndromes, including multifocal motor neuropathy (MMN). We compared the ability of serum IgM from patients with multifocal motor neuropathy to bind to GM1 ganglioside alone and to GM1 as a component of a lipid mixture that also contained galactocerebroside and cholesterol (GGC). Our results showed that high-titer selective serum IgM binding to GGC has strong specificity for MMN. Further, over 40% more serums from patients with MMN have high-titer serum IgM binding to GGC than to GM1 alone. The specific composition and structure of the lipid mixture altered the ability of serum IgM to bind to GM1 ganglioside. Substitutions of other lipids for galactocerebroside or cholesterol could completely inhibit the antibody binding. We conclude that serum IgM anti-GGC autoantibodies have specificity for MMN and their binding is strongly influenced by the lipid environment of GM1 ganglioside.

Cholesterol Esters↗
PubMed1997

A beneficial effect of oxandrolone in the treatment of Duchenne muscular dystrophy: a pilot study.

We treated 10 boys with Duchenne muscular dystrophy with oxandrolone, an anabolic steroid, for 3 months. The mean of the changes in the average muscle score was an improvement of 0.315 +/- 0.097. The expected mean change in muscle score after 3 months from natural history data is a loss of 0.1. The difference of 0.415 between the actual and expected values is significant at p < 0.01. This preliminary evidence suggests that oxandrolone treatment may provide a degree of functional benefit for children with Duchenne muscular dystrophy that is similar to that after prednisone administration.

Anabolic Agents↗
PubMed1997

Multifocal motor neuropathy. Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates.

IgM anti-GM1 antibodies occur with increased frequency in the serum of patients with multifocal motor neuropathy (MMN). We tested the ability of serum IgM from patients with MMN to bind to GM1 ganglioside covalently bound to secondary amino groups on ELISA plates (Co-GM1). The Co-GM1 technique detected high titer (> 1,800), selective, serum IgM binding to GM1 ganglioside in 85% of our MMN patients (23/27), a significantly greater frequency compared with figures of 37% and 52% found using our previous testing methods. Selective IgM anti-GM1 antibodies showed disease specificity. The only other patients with selective, high-titer IgM anti-GM1 antibodies had either chronic motor neuropathy without conduction block or acute immune neuropathy in China. No patient from the amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré, or systemic immune disorder control groups had selective IgM anti-GM1 antibodies at titers greater than 1,800 detected using Co-GM1 ganglioside as ELISA antigen. Titers of IgM anti-GM1 antibodies in MMN (averaging 31,000 +/- 15,000) were more than fourfold higher with Co-GM1 than with previous anti-GM1 assay methods, using conventional ELISA plates with GM-1 antigen alone (7,200 +/- 4,400) or in a lipid environment (3,600 +/- 1,300). We conclude that using ELISA testing with Co-GM1 antigen, serum anti-GM1 autoantibodies are a useful marker for MMN, because they are present in 85% of MMN patients and, at titers greater than 1,800, have strong specificity for immune-mediated motor neuropathies.

Amyotrophic Lateral Sclerosis↗
PubMed1997

A skeletal muscle-specific form of decorin is a target antigen for a serum IgM M-protein in a patient with a proximal myopathy.

We described a myopathy in a patient, B.J., with Waldenström's macroglobulinemia and a serum IgM M-protein that binds to a glycoprotein located in skeletal muscle endomysium. The objective of this study was to identify and characterize the endomysial antigen. The antigenic protein was purified using sequential differential solubility steps, size exclusion chromatography, and anion exchange chromatography. We subjected the deglycosylated protein and several proteolytic fragments to sequence analysis. We used immunohistochemistry, Western blot, and ELISA to study the binding of the IgM monoclonal and the anti-decorin core protein antibodies to the muscle antigen before and after deglycosylation. Sequence analysis revealed amino acid residues with 100% homology to human decorin. The anti-decorin core protein antibody bound to the purified antigen by ELISA and Western blot methods and bound to skeletal muscle endomysium in a histologic pattern similar to the human IgM M-protein from the patient B.J. Deglycosylation experiments revealed that the human IgM M-protein from B.J. serum recognized a carbohydrate epitope on decorin, probably containing chondroitin sulfate. A skeletal muscle-specific form of the proteoglycan decorin, with a chondroitin sulfate-like epitope, is a target antigen for the IgM M-protein in our patient with Waldenström's macroglobulinemia and a myopathy. These results are the first demonstration of the binding of a human IgM M-protein to an endomysial antigen. The anti-decorin IgM may be relevant to disease pathogenesis because the patient studied had a myopathy with IgM monoclonal antibodies deposited in the muscle endomysium.

Amino Acid Sequence↗
PubMed1996

Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a study of 56 patients.

Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-red fibers are common in patients with sporadic inclusion body myositis, and multiple [correction of mutiple] mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.

Adult↗
PubMed1996

Neonatal perifascicular myopathy.

Perifascicular atrophy of muscle fibers is generally considered to be a specific feature of autoimmune myopathies, dermatomyositis in particular. We describe a neonate presenting with hypotonia and weakness. A biopsy revealed atrophic and regenerating muscle fibers in a perifascicular distribution, and abnormal alkaline phosphatase activity in neighboring perimysial connective tissue. The weakness was nonprogressive and improved on follow-up even though no long-term treatment was administered. We conclude that the presence of perifascicular myopathic changes and muscle fiber atrophy in infants presenting with hypotonia and weakness is neither diagnostic of progressive dermatomyositis, nor a necessary indication for immunosuppressive therapy.

Biopsy↗
PubMed1996

Neuropathy of metachromatic leukodystrophy: improvement with immunomodulation.

A 4-year-old child with metachromatic leukodystrophy was initially diagnosed with chronic immune demyelinating polyneuropathy and treated with immunosuppressive therapy. Physical examination revealed diffuse, distal > proximal weakness and areflexia. Electro-diagnostic studies revealed nerve conduction velocities that were slowed to variable degrees in different nerves. In the 18 months after institution of immunomodulating therapy, she had functionally significant improvement and a quantitative increase in her strength. Treatment was discontinued at age 6 years when the patient developed urinary incontinence, followed by loss of motor and cognitive skills. We conclude that immunomodulation early in the course of metachromatic leukodystrophy presenting as a neuropathy may result in temporary functional improvement. Whether the immunomodulation altered the disease progression or had direct effects on the function of the dysmyelinated axons is not known.

Azathioprine↗
PubMed1996

Congenital muscular dystrophy syndromes distinguished by alkaline and acid phosphatase, merosin, and dystrophin staining.

Congenital muscular dystrophy syndromes are characterized by congenital weakness, contractures, and dystrophic features on muscle biopsy. However, these syndromes are often difficult to diagnose precisely because their clinical and pathologic characteristics are not specific and resemble changes in other myopathies. We examined muscle biopsies from 20 children with a congenital muscular dystrophy syndrome. Disease controls with dystrophies or other myopathies (n=19) and normal individuals (n=15) were studied for comparison. In each biopsy we determined (1) numbers of muscle fibers with alkaline phosphatase (AlkP) staining, (2) numbers of acid phosphatase-(AcP) positive cells, (3) dystrophin levels by immunocytochemistry, and (4) the distribution of merosin and laminin-A staining. A ratio of AcP:AlkP staining was calculated for each biopsy. In nine patients with congenital muscular dystrophy (younger than 4 years of age) with normal dystrophin, the AcP:AlkP ratio was low (0.09 +/- 0.03). In contrast, in Duchenne muscular dystrophy, the AcP:AlkP ratio was 15 times higher (1.6 +/- 0.04, p=0.001). The three children with congetial muscular dystrophy syndromes and reduced dystrophin and one child with facioscapulohumeral dystrophy had AcP:AlkP ratios in the range of Duchenne muscular dystrophy patients (2.4 +/- 1.4). Low Ac:AlkP ratios were related to relative absence of AcP-positive cells. Merosin staining was absent in 5 of the 17 congenital muscular dystrophy biopsies tested. None of the 5 children with merosin-negative but all 12 with merosin-positive stains walked (p=0.0002). We conclude that a pattern of few AcP-positive cells in the setting of numerous AlkP staining muscle fibers has specificity for congenital muscular dystrophy syndromes and provides histopathologic support for the diagnosis. Reduced merosin in muscle predicts more severe weakness and long-term disability.

Acid Phosphatase↗
PubMed1996

Childhood chronic inflammatory demyelinating neuropathies: clinical course and long-term follow-up.

Chronic inflammatory demyelinating neuropathy (CIDP) is a rare disease in childhood. We reviewed the clinical characteristics, response to therapy, and long-term prognosis in 13 children (1.5 to 16 years of age) diagnosed with CIDP at Washington University Medical Center, St. Louis, and the Royal Children's Hospital, Melbourne, Australia, between 1979 and 1994. The most common presenting symptom (in 11/13 [85%]) was lower extremity weakness associated with difficulty in walking. Preceding events within 1 months of onset, mostly intercurrent infections or vaccinations, occurred in seven children (54%). The disease was monophasic in three children (23%). One relapse occurred in four (30%) and multiple relapses in six (46%). All patients had at least short-term response to steroids. Three children (23%) recovered completely during the first year. Ten children (77%) had residual weakness after an average follow-up of 6 years. There seems to be two populations of children with CIDP. One subgroup, with a favorable prognosis, progressed to peak disability over less than 3 months; these children often have a monophasic course with complete resolution of symptoms and signs and withdrawal from all medications by 1 year after onset. A second subgroup progressed for 3 months or longer; these children all required substantial does of prednisone for prolonged periods and had considerable long-term morbidity with persistent weakness.

Adolescent↗
PubMed1996

Selective staining of the cerebellar molecular layer by serum IgG in Miller-Fisher and related syndromes.

During 1 year, we used immunocytochemical staining of human cerebellum to screen 1,488 serums for IgG autoantibodies to Hu and Yo antigens. Three serums had none of the classically described patterns of IgG binding but instead, selectively stained the cerebellar molecular layer. Evaluation of clinical data showed that the patients had either typical Miller Fisher syndrome (MFS) or Guillain-Barré syndrome with ophthalmoplegia. Further analysis by ELISA, assay showed that all three serums had high titers of IgG anti-GQ1b autoantibodies. IgG autoantibody staining of human cerebellum, which is used for the diagnosis of paraneoplastic disorders, may have additional specificity for other, presumably autoimmune, syndromes such as MFS. The specificity of the serum IgG autoantibody binding to the cerebella molecular layer may be related to the ataxia that often occurs in these patients.

Adult↗
PubMed1995

Myopathy and paraproteinemia with serum IgM binding to a high-molecular-weight muscle fiber surface protein.

We evaluated a 69-year-old man with Waldenström's macroglobulinemia (IgM-kappa M-protein) and progressive weakness over 2 to 3 years. The neurological examination showed symmetrical, predominantly proximal weakness. Electrophysiological testing revealed small brief motor unit potentials with fibrillations and positive sharp waves consistent with an irritative myopathy. The muscle biopsy specimen showed myopathic changes including variation in fiber size and increased connective tissue but no inflammation. IgM-kappa but not IgM-lambda was deposited along the surface of muscle fiber membranes. Serum IgM-kappa but not IgM-lambda from the patient stained the surface of normal human muscle fibers but not other regions of muscle fibers or other tissues. The serum IgM-kappa at dilutions up to 1:512,000 bound to a high-molecular-weight muscle protein by Western and dot blot studies. By enzyme-linked immunosorbent assay and Western blot analysis, serum IgM-kappa bound specifically to the muscle protein and not to other muscle or neural antigens, including GM1 ganglioside, myelin-associated glycoprotein, and sulfatide. We conclude that the myopathy in our patient is probably related to the presence of serum IgM-kappa antibodies directed against a muscle surface antigen. Characterization of the target antigen, a high-molecular-weight protein located specifically in muscle, should further elucidate the pathogenesis of this presumably humorally mediated immune myopathy.

Aged↗
PubMed1995

Chronic motor neuropathies: diagnosis, therapy, and pathogenesis.

Pure motor neuropathy syndromes resemble amyotrophic lateral sclerosis variants with no upper motor neuron signs. Their identification is important, as, in contrast to amyotrophic lateral sclerosis, they are often immune mediated and treatable. Typically the immune-mediated motor neuropathy syndromes are distal and asymmetrical and progress slowly. The clinical features may help alert the clinician to the diagnosis, but other ancillary evidence such as abnormalities on electrophysiological testing and the presence of serum autoantibodies to neural antigens are helpful in making the diagnosis more secure. Electrophysiological abnormalities include not only motor conduction block but also other evidence of a demyelinative process such as prolonged distal latencies or F-wave abnormalities. High-titer anti-GM1 antibodies occur frequently but more specific patterns of reactivity may be especially helpful. Treatment of these motor neuropathy syndromes includes cyclophosphamide, which we use in combination with plasma exchange, and in some patients, human immune globulin. Clinical responses to therapy may occur within the first 2 to 4 months in patients with motor neuropathy syndromes with demyelinative features, but only become obvious 6 months or later after starting treatment in patients with predominantly axonal disorders.

Adult↗
PubMed1995

Anti-MAG antibody-associated polyneuropathies: improvement following immunotherapy with monthly plasma exchange and IV cyclophosphamide.

Treatment outcomes of sensory-motor polyneuropathies associated with anti-myelin-associated glycoprotein (MAG) antibodies have varied even with relatively intensive immunosuppression. We used plasma exchange and cyclophosphamide to treat four patients with anti-MAG antibody-associated polyneuropathies whose symptoms had progressed in the preceding year. Treatment courses consisted of five to seven monthly regimens of plasma exchange on 2 consecutive days followed by intravenous cyclophosphamide (1 g/m2). Effects of treatment were quantitatively measured with hand-held dynamometry. All four patients showed improvement in both strength and sensation in the 5 to 24 months after treatment. We conclude that selected patients with sensory-motor polyneuropathies associated with high-titer serum IgM autoantibodies against MAG may have quantitative and useful functional improvement after immunotherapy. The improvement continues after completion of treatment and may persist for 1 to 2 years or longer.

Antibodies↗
PubMed1995

Anti-rhodopsin antibodies in sera from patients with normal-pressure glaucoma.

PURPOSE: To explore further the potential role autoimmunity may play in the pathogenesis of normal-pressure glaucoma (NPG) in some patients, the authors examined the sera of patients with NPG for the presence of antibodies directed toward retinal antigens. METHODS: Using patient sera, immunoblotting was performed on subcellular fractions of retina, purified bovine rhodopsin, and immunoaffinity-purified recombinant human rhodopsin. A chemiluminescence-enzyme-linked immunosorbent assay (ELISA) to detect anti-rhodopsin antibodies was developed and used. RESULTS: A patient with NPG was found to have a high titer of immunoglobulin M-lambda antibody against a 40-kd retina-specific glycoprotein antigen subsequently identified as rhodopsin. ELISA analysis conducted on sera from 28 patients with NPG and 26 patients with primary open-angle glaucoma (POAG) revealed highly significant differences in anti-rhodopsin antibody activity between these groups (P < 0.0002, Mann-Whitney test). For example, the majority of patients with NPG (19/28; 68%) had anti-rhodopsin antibody activity higher than the highest value obtained from among 26 age-matched patients with POAG. CONCLUSIONS: An elevated anti-rhodopsin antibody count is related to NPG. This may indicate that there is an autoimmune component in the optic neuropathy in these patients. The specific role of these autoantibodies, if any, in the pathogenesis of the disease remains to be determined.

Aged↗
PubMed1995

Chronic motor neuropathies and lower motor neurone syndromes.

Immune-mediated motor neuropathies are most often disorders manifest clinically by slowly progressive, asymmetrical, distal weakness, starting in the hands more often than the legs. In some cases, electrophysiological findings show multifocal conduction block along the length of motor axons. Other patients have findings consistent with only axonal loss. Laboratory testing is unremarkable except for high-titre serum autoantibodies to GM1 and other neural antigens. Diagnosis of immune-mediated motor neuropathies provides an opportunity for effective immunomodulating therapy that can significantly improve quality of life in affected patients. The identification of antigenic targets of serum autoantibodies in patients with motor neuropathies lends hope that immunotherapies to specifically treat the autoimmune disorder can be developed.

Autoantibodies↗