An index based on 12 electrophysiological parameters (conduction velocities, F-latencies, and amplitudes) was constructed to obtain an overall estimation of peripheral nerve conduction. The index was expressed as the mean deviation (in SD) compared to controls standardized for age or height. The stability of the index was tested by repeated examinations during intervals of several months in healthy subjects. The use of a compound index enabled detection of slight impairments of nerve conduction. The relatively low interrecording variability of the index makes it suitable to follow the progression of a polyneuropathy.

Adolescent↗

PubMed1993

Autoreactive T and B cell responses to myelin antigens after diagnostic sural nerve biopsy.

To study whether nervous tissue trauma provokes myelin antigen autoreactive T and B cell responses in humans we examined consecutive blood samples from 7 patients with polyneuropathy undergoing diagnostic sural nerve biopsy and 8 control patients undergoing other types of minor surgery. The antigen-specific T cells were assessed by enumerating cells secreting interferon-gamma (IFN-gamma) in response to the myelin components P0, P2, myelin basic protein (MBP) and myelin associated glycoprotein (MAG), and to 4 selected MBP peptides. B cell mediated immunity was assessed by counting numbers of cells secreting antibodies directed against the myelin proteins. On day 7 after biopsy, there were 3-10-fold increased numbers of T and B cells reactive with P0, P2, MBP and MAG in blood of polyneuropathy patients compared to controls, while levels of cells recognizing purified protein derivate or responding to phytohemagglutinin (PHA) did not differ significantly. Comparison of prebiopsy levels on day 0 with post-biopsy levels on day 7 in the polyneuropathy patients revealed a significant increase in T cells recognizing P0, P2 and MAG, and in B cells secreting IgG antibodies against P0 and P2. On day 14 after nerve biopsy these differences were no longer seen. We suggest that in patients with polyneuropathy, sural nerve biopsy with the ensuing wallerian degeneration and myelin breakdown causes transiently increased levels of circulating myelin autoreactive T and B cells. It remains to be determined if this has a physiological role in nerve trauma responses and/or affects the clinicopathological course of the peripheral neuropathy.

Adolescent↗

PubMed1993

Susceptibility to demyelinating polyneuropathy in plasma cell dyscrasia may be influenced by amino acid position 9 of the HLA-DR beta chain.

Fifty-five patients with plasma cell dyscrasias were investigated by genomic typing for HLA-DR and -DQ genes by restriction fragment length polymorphism, neurophysiology and for presence of anti-myelin-associated glycoprotein (MAG) antibodies. In 26 patients, a polyneuropathy (PN) of demyelinating type was established. Among these individuals, an association was found with the presence of a tryptophan amino acid residue at position 9 of the DR beta chain (P < 0.01). This position is part of the first hypervariable region of the DR beta chain, and may be of importance in determining preferential peptide-binding capacity of the HLA-DR molecule. The presence of anti-MAG antibodies in 15 out of 17 patients with an IgM M-component and demyelinating PN (14 of these 15 individuals carrying a tryptophan at position 9) supports the pathogenic role of an autoimmune response against MAG. The finding of an HLA class II association may indicate a pathogenic role of T cell immunity in this condition.

Adult↗

PubMed1992

Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I).

Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1). Analysis of T-cells primed for myelin antigens, by studies of IFN-gamma secretion in response to antigen in vitro, showed that both HMSN I and other polyneuropathy patients had low (but significant) numbers of T-cells recognizing whole PNS-myelin. Increased numbers of IgG- and IgM-producing cells were found in blood and bone marrow in the HMSN I patients. Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay. Many cells in the cerebrospinal fluid produced antibodies against MAG. Thus, there was a strong general activation of B- and T-cells in HMSN I while the immunity directed toward peripheral nerve was only slightly elevated. It is an open question if this immune activation is related to the primary gene defect or a secondary event to the nerve damage. The pathogenetic importance of the immune response in maintaining the nerve damage in HMSN I is unclear.

Adult↗

PubMed1992

Calcium antagonists suppress experimental allergic neuritis (EAN).

We examined the influence of Ca++ antagonist drugs on immune response and the clinical course of experimental allergic neuritis (EAN). The Ca++ antagonists verapamil and flunarizine suppressed actively induced EAN in Lewis rats in a dose-dependent fashion when given continuously by osmotic pumps from the day of immunization. If given from onset of clinical signs, day 10 after immunization, verapamil alone had therapeutic effects. The beneficial effects of the drugs seem to be mediated primarily by an action on the autoimmune response, since in vitro lymphocyte proliferation in response to nervous tissue antigens was dose-dependently inhibited by both drugs, whereas the in vitro conductivity of demyelinated sciatic nerve was not significantly affected by the Ca++ antagonists. The suppressive effect on lymphocyte proliferation could partially be bypassed by protein kinase C activating phorbol ester alone or in combination with the Ca++ ionophore ionomycin, confirming a non-toxic effect of the Ca++ antagonists on lymphocytes.

Action Potentials↗

PubMed1992

The effect of weight-bearing pressure on the plantar circulation in diabetes mellitus.

Patients with diabetic neuropathy are prone to ulceration on the sole of the foot, especially in areas with high weight-bearing pressure. The relationship between weight-bearing pressure and nutritive skin circulation in the plantar region was studied. Gait analysis was performed with the EMED Gait Analysis System and the skin circulation was measured by fluorescein flowmetry in ten neuropathic diabetic patients and in eight healthy controls. The critical plantar foot pressure above which nutritional blood flow in the skin was arrested was 3 N cm-2 or more in both diabetic and control subjects. Below 3 N cm-2 the blood flow was independent of weight-bearing pressure both in diabetic and control subjects (correlation coefficient r = -0.01 and -0.19, respectively). Thus, our results indicate that the nutritional blood flow in the plantar region is not decreased in patients with diabetic neuropathy.

Adult↗

PubMed1992

Improvement of nerve conduction in diabetic neuropathy. A follow-up study 4 yr after combined pancreatic and renal transplantation.

Eighteen patients with long-standing insulin-dependent (type 1) diabetes mellitus and polyneuropathy were studied after combined pancreatic and renal transplantation. Repeated tests were performed on peripheral nerve function (electroneurography) and on autonomic function (R-R test) 6 mo and 1, 2, and 4 yr after the transplantation. Eighteen diabetic patients with only a kidney graft served as controls. After initial improvement of nerve conduction in both groups, probably caused by the elimination of uremia, further improvement was seen only in the euglycemic pancreas-graft recipients. Improvement of autonomic (parasympathetic) function was slight after 48 mo and was similar in both groups.

Adult↗

PubMed1992

Effect of stilbene-type anion channel blockers on the immune response during experimental allergic neuritis (EAN).

We have studied the role of anion channel gating for the autoimmune response in experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM). The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell function was assessed by measurement of proliferation and by counting of interferon-gamma (IFN-gamma) secreting cells (IFN-gamma-sc) in response to BPM and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of spontaneous proliferative activity as well as of proliferation in response to the antigenic stimulus BPM. In contrast, the drug caused a decrease of proliferation of cells stimulated with PHA. The number of cells induced to IFN-gamma secretion was reduced by SITS. The suppressive effect was dependent on the degree of activity of cells without drugs. Cultures showing high numbers of BPM reactive T cells were more easily suppressed than cultures with low numbers of BPM reactive T cells. Our results suggest that anion channel gating is involved in the triggering of T cells to IFN-gamma secretion. The anion channel signal pathway in lymphocytes could be a target for pharmacological intervention in inflammatory disorders. In the presently used autoimmune model, EAN, the net effect of in vivo treatment with SITS resulted in worsening of clinical signs and increased inflammatory cell infiltration in sciatic nerve, whereas the in vitro conductivity of sciatic nerve was not significantly affected by the drug. Thus anion channel gating seems to regulate activities of immune cells, and drugs with anion channel blocking properties may have effects that enhance autoimmune disease.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1992

Diabetic neuropathy four years after pancreas transplantation.

Explore the source record for details and available documents.

Diabetes Mellitus, Type 1↗

PubMed1991

Antibodies to myelin-associated glycoprotein are found in cerebrospinal fluid in polyneuropathy associated with monoclonal serum IgM.

Antibodies to myelin-associated glycoprotein (MAG) have been demonstrated in the serum samples from about half the patients with polyneuropathy associated with serum IgM monoclonal component. We examined cerebrospinal fluid (CSF) and serum samples from 13 patients with this disease by enzyme-linked immunosorbent assay for anti-MAG IgM antibodies. We detected these antibodies in both CSF and serum samples in 10 of the patients; in three of them the antibodies were at higher levels in the CSF. The remaining three patients had anti-MAG IgM antibodies in the CSF only. Intrathecal production of anti-MAG IgM antibodies is thus common in polyneuropathy associated with IgM monoclonal component. In three patients, examined on two occasions from 1 to 7 years, high anti-MAG IgM antibody levels persisted in CSF and serum samples. Among 165 patients with other neurologic diseases, including 60 with multiple sclerosis and 60 control subjects with tension headache, anti-MAG IgM antibodies were detected in the CSF from three patients (two with multiple sclerosis, one with aseptic meningitis), and in the serum sample of one patient with multiple sclerosis. Whether the frequent occurrence of anti-MAG IgM antibodies in CSF and their intrathecal synthesis has pathogenetic relevance for the development of polyneuropathy associated with IgM monoclonal component is unsure.

Aged↗

PubMed1991

Central conduction and autonomic nervous function in HMSN I.

CNS conduction and autonomic nervous function were investigated in 15 patients with HMSN I. Central motor conduction time (CMCT) was estimated with magnetic brain stimulation and electrical nerve root stimulation. Somatosensory evoked potential (SEP) and visual evoked potential (VEP) were used for assessment of central sensory and visual conduction. Autonomic effector organ functions were assessed with the R-R variation test for parasympathetic function, and the sympathetic skin response test (SSR) for skin sympathetic sudomotor activity. Five of the patients had prolonged CMCT. Central sensory conduction was normal in 3, and slightly prolonged in 1 of the patients, but could not be estimated in 11 due to lack of response from the cervical recording. VEP was abnormal in 2 patients. R-R variations during normal breathing were low in 8 of 15 patients, and low also during deep breathing in 1 of 15. The SSR test was pathological in 5 of 15 patients. Thus, impaired central conduction and/or autonomic dysfunction was not an uncommon finding in patients with HMSN I.

Adult↗

PubMed1991

Improvement in diabetic neuropathy 4 years after successful pancreatic and renal transplantation.

We have studied the fate of diabetic neuropathy and autonomic function in 13 patients with long standing Type 1 (insulin-dependent) diabetes mellitus following combined pancreas and kidney transplantation. Fifteen diabetic patients with a kidney graft only served as controls. After initial improvement of the neuropathy in both groups, probably caused by the elimination of uraemia, a continuous improvement during the 48 months study was seen in the euglycaemic pancreas graft recipients only. Autonomic (parasympathetic) function improved only slightly and to a similar extent in both groups.

Action Potentials↗

PubMed1989

Neurogenic involvement in distal myopathy (Welander). Histochemical and morphological observations on muscle and nerve biopsies.

Patients with distal myopathy (Welander) were subjected to muscle biopsy from the anterior tibial muscle (n = 4) and to nerve biopsy from the sural nerve at the ankle (n = 5) in order to elucidate a possible neurogenic component of the disease. The type I muscle fibres had a larger mean cross-sectional area as compared to normal controls and an increased variation in fibre size with both hypertrophic and atrophic fibres in one and the same biopsy. A normal muscle fibre type composition was found in the patients. Structural muscle fibre abnormalities such as atrophic fibres, mainly angulated, split fibres, rimmed vacuoles and centrally located nuclei were found in all biopsies. A disorganization and loss of myofibrils as well as autolytic vacuoles were the most prominent findings at the ultrastructural level. Two patients had a moderate loss of myelinated sural nerve fibres. The mean nerve fibre density was decreased as compared to normal controls while the mean nerve fibre area and circular diameter were increased due to selective loss of small diameter (A-delta) nerve fibres. The muscle and nerve fibre abnormalities are discussed with reference to neuropathic and myopathic changes. Some muscle fibre abnormalities are typical for a neurogenic disorder while some others are mostly seen in myopathies but may also appear in neurogenic conditions. A neurogenic etiology in Welander distal myopathy is further supported by the finding of loss of small diameter nerve fibres in the sural nerve.

Adult↗

PubMed1989

Effect of ion channel blockers on immune response and course of experimental allergic neuritis.

The influence of the K+ channel blocker quinidine and the Ca++ channel blocker verapamil on in vivo and in vitro immune responses was tested in experimental allergic neuritis (EAN) of Lewis rats. Daily intraperitoneal injections of 4 mg quinidine produced a significant reduction of neurological deficits in EAN rats, whereas verapamil had no effect. In contrast, both drugs inhibited the in vitro proliferative response of regional lymph node cells to specific antigens of bovine peripheral myelin and purified protein derivative of tuberculin in a similar dose-dependent manner. Quinidine-treated EAN rats revealed considerably less inflammatory infiltration in target tissue than untreated EAN rats, shown immunohistochemically. Single injections of ion channel blockers into EAN rats did not improve nerve cell functions as measured by electrophysiological recordings of sciatic nerve. It is concluded that the dominant effect of quinidine in vivo is attributed to a reduction of the demyelinating autoimmune process. Hence ion channel blocking drugs can exert immunomodulatory effects, which may have implications for their clinical application.

Animals↗