Multifocal motor neuropathy

We present a review of the literature on multifocal motor neuropathy (MMN), a rare neurological disorder which has features in common with both chronic inflammatory demyelinating neuropathy and lower motor neuron disease. Clinically, MMN is characterised by slowly progressive asymmetrical limb weakness, usually most prominent in the forearms. Weakness may be associated with muscle wasting, fasciculations and decreased tendon reflexes. Serum anti-GM1 ganglioside antibody titres may be increased. The diagnostic hallmark of MMN is the electrophysiological demonstration of persistent localised motor conduction blocks, with otherwise normal or near-normal motor and sensory conduction velocities. The pathogenesis of MMN has not been elucidated completely. There is, however, substantial evidence for an autoimmune mechanism. Based on the possible involvement of the immune system in the pathogenesis of MMN the therapeutic efficacy of several immunomodulatory drugs has been tested. Treatment of MMN patients with human immunoglobulin or cyclophosphamide is usually followed by a marked improvement of strength. The finding that MMN is a potentially treatable disorder underscores the importance of distinguishing MMN from lower motor neuron disease, for which no effective therapy is currently available.     

Hereditary motor and sensory neuropathies. Clinical and molecular genetic aspects

Hereditary motor sensory neuropathies are a heterogeneous group of inherited diseases of the peripheral nerves. In this review the clinical and genetic differences between the sub-groups of this disease will be discussed. Since the discovery of a 1.5 mb duplication on chromosome 17 p11.2-12 in most patients with a hereditary motor sensory neuropathy and a variety of different mutations on chromosomes 1 and X in other patients with a similar disease profile, Dycks' clinical classification needs to be re-evaluated. In this review Dycks' taxonomy of heridihary neuropathies will be compared to a new genetic classification and a relevant diagnostic procedure proposed when a hereditary neuropathy is suspected.     

Central motor conduction in motor neuron disease

Central motor conduction time (CMCT) to abductor digiti minimi (ADM) and tibialis anterior (TA) was measured in 21 patients of motor neuron disease (MND). In the upper limb, the motor pathways were inexcitable in 13 and central motor conduction time (CMCT-ADM) was prolonged in 7 sides. In the lower limbs the motor pathways were inexcitable in 10 and CMCT-TA was prolonged in 14 sides. The CMCT abnormalities did not follow a constant pattern but were randomly distributed and were asymmetric in the upper limbs in 7 and lower limbs in 3 patients. Asymmetric and randomly focal abnormalities in central motor conduction in our patients are consistent with asymmetric and focal neuronopathy in MND.     

Peripheral neuropathies caused by perhexiline maleate. Apropos of 7 cases]

In the OHH, during the years 1969 to 1974, 28 patients were operatively treated because of delayed callusformation or pseud-arthrosis, following a fracture of the shaft of the humerus. It was possible to inquire about and to re-examine 20 patients. The operative treatment had, when possible been achieved by osteosynthesis through plates (25 cases). Each of the so treated cases lead to healing of the bone, additional nerve lesion did not in one case occur because of the operation. Objectively seen, there existed in 7 patients a slight, final restriction of movements, for the abduction and outside rotation in the shoulder joint. 6 patients complained of being sensitive to weather changes. The different treatment method of the fracture of the humerus and pseudarthrosis was discussed.     

The foot in hereditary motor and sensory neuropathies in children

We investigated the regulation of COX-2 expression and activity by adenosine receptors in rat microglial cells. The selective adenosine A2a-receptor agonist CGS21680 and the non-selective adenosine A1- and A2-receptor agonist 5'-N-ethylcarboxiamidoadenosine (NECA) induced an increase in COX-2 mRNA levels and the synthesis of prostaglandin E2 (PGE2). The adenosine A1-receptor agonist cyclopentyladenosine (CPA) was less potent, and the adenosine A1-receptor-specific agonist N6-2-(-aminophenylo)ethyladenosine (APNEA) showed only marginal effects. Microglia expressed adenosine A1-, A2a-, and A3-, but not A2b-receptor mRNAs, whereas astroglial cells expressed adenosine A2b- but not A2a-receptor mRNA. The adenosine A2a-receptor selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837) inhibited both CGS21680-induced COX-2 expression and PGE2 release. CGS21680-increased PGE2 levels were inhibited by dexamethasone, by the nonsteroidal antiinflammatory drug meloxicam, and by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536). CGS21680 and NECA both increased intracellular cAMP levels in microglial cells. Dibutyryl cAMP as well as forskolin induced the release of PGE2. The results strongly suggest that adenosine A2a-receptor-induced intracellular signaling events cause an up-regulation of the COX-2 gene and the release of PGE2. Apparently, the cAMP second messenger system plays a crucial role in COX-2 gene regulation in rat microglial cells. The results are discussed with respect to neurodegenerative disorders of the CNS such as Alzheimer's disease, in which activated microglia are critically involved and COX inhibitors may be of therapeutic benefit.     

Treatment of immune deficient neuropathies with intravenous polyvalent immunoglobulins. An open study of 16 cases

Between June 1989 and February 1992, in an open controlled study 16 patients with various types of polyneuropathy were treated with high-dose intravenous immunoglobulins (IgIV). Every month during 3 months, each patient received three courses of IgIV in doses of 0.4 g/kg/day during 5 successive days. The trial was discontinued in case of no response or if the neuropathy was considered as being in remission. In the other cases, at most one course of IgIV was given once a month if there was significant improvement (assessed by previously published clinical functional scales, electrophysiological examinations and titers of specific antibodies), or spaced at intervals which varied according to each patient, and sometimes in low doses. Results: 1) A first group of 6 patients had chronic demyelinating polyneuropathy with severe motor disability. The first infusions of IgIV resulted, in 4/6 cases, in a dramatic improvement which lasted under regularly spaced courses in lower doses. 2) Four patients had chronic neuropathy associated with monoclonal IgM gammopathy of undetermined significance (3 had anti-MAG and anti-SPG antibodies, and 1 had anti-GD1a and GD1b antibodies) and had not been improved by the usual immunosuppressive treatments. In 1 case the IgIV treatment had to be discontinued because of skin allergy. In the remaining 3 patients the clinical disorders (mainly the sensory ones) were reduced, but no significant improvement of neurophysiological or immunological data was observed. 3) Three patients had a purely multifocal motor neuropathy with persistent conduction blocks at EMG and high titers of anti-GM1 antibodies in 2/3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central motor conduction evaluation in glycogenosis type III

We report a 20-year-old man affected by glycogenosis type III with distal muscle weakness, more severe in distal leg muscles. The electromyogram showed myopathic features. Nerve conduction studies and central motor conduction after magnetic stimulation of the brain were normal. Our results suggest that there is no involvement of central motor pathways in this disease.     

Polyneuropathy caused by tuberculostatics. Study of motor nerve conduction in 29 patients

This paper presents the reconstruction of an unusual case of suicide. After raiding a branch-bank a robber fled shooting with his Sauer-Western revolver caliber .44 magnum at the pursuing policemen and succeeded in wrestling a pistol Walther caliber 7,65 mm from them. Under the fire of sub-machine guns he destroyed himself by a shot to the neck. Our investigations concerned a textile damage at the front of the sweater of the deceased surrounded by primer residue, showing characteristics of a close-up shot. The damage was identified as effect of explosion gases exhausting far-off the muzzle. The distance between this injury and the bullet hole corresponded with the length of the barrel of the Sauer-Western revolver and could be used for identification; it confirmed the diagnosis of a close-up shot at the neck, too. Collateral experiments with shots from distant ranges developed spadiceous melt figures of textile fibers around the bullet hole, the appearance of which is considered proof for a close-up shot commonly.     

Long term follow up of multifocal motor neuropathy with conduction block under treatment

OBJECTIVE: To determine the accuracy and potential harmfulness of the drug information in a newsgroup on the Internet, sci.med.pharmacy. DESIGN: In this cross-sectional study, two independent reviewers analyzed the nonsubjective drug information in this newsgroup. Drug information was classified as correct, incorrect or could not verify. Information was determined to have no harm, minor harm, moderate harm, or severe harm. RESULTS: About one-half of the drug information was found to be correct in this newsgroup. Although 68% of the drug information was found to result in no harm, 19.4% was classified as harmful. CONCLUSIONS: If drug information on the Internet contains inaccuracies, its ready accessibility may pose a public health problem. With the number of Internet users growing, health professionals need to be aware of the potential for dissemination of misinformation, and need to become familiar with the Internet and the various health information resources available to the public.     

Symmetry of normal motor and sensory nerve conduction measurements

Nerve conduction measurements in normal subjects are assumed to be symmetric, but the normal limits of symmetry have not been determined. Full data on the limits of symmetry for commonly studied nerves are important in the clinical interpretation of nerve conduction data. We selected normal electrodiagnostic studies from archived electromyographic laboratory reports that included bilateral measurements of motor and sensory nerves. Symmetry of nerve conduction measures was confirmed, and only the median and ulnar sensory nerves had significant deviations from symmetry, supporting subclinical nerve damage in the most common dominant hand. The limits of symmetry were determined by calculating the 95th percentile for the differences between sides. For motor and sensory nerves, the range of 95th percentile limits was narrower for measures in upper extremity nerves compared to lower extremity nerves. Several reasons are offered for the wider limits of symmetry in lower extremity nerves.     

Multifocal choroiditis with subretinal fibrosis

We report 2 cases of multifocal choroiditis associated with subretinal fibrosis on whom the fluorescein fundus angiography (FAG) and the indocyanine green infrared angiography (IA) were performed. Case 1 was a moderately myopic 14-year-old girl who had no ocular symptoms. She had numerous small, round, discrete, partially conflued lesions with subretinal fibrosis scattered in the periphery and one discrete relatively large lesion along the superotemporal arcade in her left fundus. Subretinal fibrosis had progressed in the superior lesion. Some lesions had coalesced into a sword-like pattern over a period of 2 years. Case 2 was a high myopic 18-year-old man who had distorted vision in his right eye. He had some small whitish round lesions with one small choroidal neovascular tissue and subretinal fibrosis in the posterior pole and a sword-like lesion in the inferior periphery. Another choroidal neovascular tissue developed near the macula during the 6-month follow-up period. In FAG, the centers of the lesions hypofluoresced corresponding to the pigmentation and the edges hyperfluoresced. Some of the lesions showed window-defects and others tissue-staining. In IA, all the whole lesions hypofluoresced from an early stage of the angiography and some major choroidal vessels were visible through them. The hypofluorescent areas persisted into the late phase. The hypofluorescent areas of the IA were larger than those seen in FAG and in funduscopy. These findings indicate that the choriocapillaris was initially damaged and consequently the structures of the lesions partly disappeared at the level of the retinal pigment epithelium-choriocapillaris complex.     

Peripheral neuropathies associated with monoclonal proteins

Peripheral neuropathies associated with monoclonal proteins have received considerable attention as a clinically important group of chronic late-onset neuropathies. When a monoclonal protein is found in patients with peripheral neuropathy of unknown cause, as occurs in 10% of such cases, usually no associated disease is discovered; hence MGUS. Less often, disorders such as multiple myeloma, AL amyloidosis, Waldenstr?m's macroglobulinemia, osteosclerotic myeloma, and lymphoma are found. Demyelinating neuropathies associated with MGUS of all classes, but particularly IgM, Waldenstr?m's macroglobulinemia, and osteosclerotic myeloma typically follow an indolently progressive course, and frequently respond to treatments aimed at interfering with putative underlying immune mechanisms. By contrast, axonal neuropathies associated with MGUS, multiple myeloma, and AL amyloidosis have generally shown no response to therapy. Recently, IgM monoclonal and polyclonal antibodies directed against human peripheral nerve antigens including MAG and various glycolipids such as GM1 ganglioside have been found in patients with specific neuropathy syndromes. Anti-MAG antibodies occur in predominantly sensory demyelinating neuropathies, whereas elevated titers of anti-GM1 ganglioside antibodies are associated with lower motor neuron syndromes with multifocal motor conduction block. Although the evidence for autoimmune mechanisms in some monoclonal protein-associated neuropathies is mounting, a causal connection between monoclonal proteins and these neurologic syndromes has yet to be established.     

Intrastriatal adenosine A1 receptor antisense oligodeoxynucleotide blocks ethanol-induced motor incoordination

Intrastriatal administration of a 21-mer phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A1 receptor blocked ethanol-induced motor incoordination in the rat and reduced striatal adenosine A1 receptor content, as judged by specific binding of the A1-specific ligand 8-cyclopentyl-1,3-dipropylxanthine (Bmax = 0.350 +/- 0.07, Kd = 1.87 +/- 0.50 nM). No effect upon striatal adenosine A2 receptor content was observed (Bmax = 0.415 +/- 0.04, Kd = 13.13 +/- 1.25 nM) with the A2-specific ligand 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine. A mismatched control oligodeoxynucleotide of identical G-C base composition and general sequence structure was without effect on adenosine A1 receptor (Bmax = 0.666 +/- 0.11, Kd = 1.32 +/- 0.27 nM) or adenosine A2 receptor content (Bmax = 0.501 +/- 0.08; Kd = 14.65 +/- 1.82 nM) or ethanol-induced motor incoordination. These results confirm an important role of the striatal adenosine A1 receptor in mediating certain motor-related physiological effects of ethanol.     

Peripheral motor and sensory nerve conduction studies in haemodialysis patients. A study of 54 patients

Peripheral motor and sensory nerve conduction velocities were studied prospectively in 54 chronic haemodialysis patients. The most sensitive parameters for the detection of polyneuropathy were the deep peroneal nerve motor conduction velocity, the sural nerve sensory conduction velocity and the H-reflex latency and H-index of the S1 roots. All patients examined were found to present at least one abnormal nerve conduction parameter. In the present study the side of the arteriovenous shunt had no statistically significant effect on the sensory and motor nerve conduction velocities in the upper extremities. There was a significant correlation between H-reflex latency and H-reflex index, and between H-reflex latency and sural nerve sensory conduction velocity.     

Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression

Infection of Shiga toxin (Stx)-producing Escherichia coli induces hemolytic uremic syndrome (HUS) in 10 to 15% of cases in infants and young children. Although the endothelial cell damage induced by Stx is widely believed to be a primary event of renal dysfunction in HUS, the precise mechanism remains to be elucidated. We were able to examine the kidney obtained at autopsy of a child who died after HUS associated with Stx-producing Escherichia coli O157:H7 infection, and immunohistochemistry indicated the deposition of Stxl and Stx2 in a portion of the distal tubular epithelia. To our knowledge, this is the first report to show the presence of Stx in human tissue of a patient with HUS, and the results obtained in this study provide evidence that Stx indeed migrates into the kidney and binds to renal tubules during Stx-producing Escherichia coli infection.     

Inactivation of brainstem motor nuclei blocks expression but not acquisition of the rabbit's classically conditioned eyeblink response.

Rabbits were eyeblink conditioned while their accessory abducens nucleus (ACC), facial nucleus ( FN), and surrounding reticular formation (RF) were temporarily inactivated with microinjections of muscimol to determine whether these structures are critically involved in acquisition of the conditioned eyeblink response (CR). Rabbits performed no CRs or unconditioned responses (URs) during inactivation training. Training was continued without inactivation and rabbits performed the CR at asymptotic levels from the start of training without inactivation. They had fully learned the CR while their ACC, FN, and RF were inactivated, despite performing no CRs or URs at all during inactivation. These results rule out any critical role for neurons within the ACC, FN, or surrounding RF in acquisition of the classically conditioned eyeblink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multifocal glioma of the brain. Case report

A case is presented in which two separate concurrent astrocytomas of the brain in the same patient were successfully operated on. The patient has been followed for 3 years and remains well. The authors believe that the diagnosis of multifocal tumors can be established on clinical grounds when the tumors are remote from each other, and when there has been no recurrence of neoplasm between the lesions after a long follow-up period. It is felt that a more optimistic approach to the treatment of multifocal tumors may yield good results.     

Membranous glomerulonephritis associated with inflammatory demyelinating peripheral neuropathies

A 55-year-old man with chronic inflammatory demyelinating polyradiculoneuropathy developed the nephrotic syndrome. Renal biopsy showed stage I membranous glomerulonephritis. Review of the literature revealed the association of these two rare syndromes, considered to be due to immunologic dysfunction, in two other cases, as well as several cases of the acute form of demyelinating peripheral polyradiculoneuropathy. The nephrotic syndrome appears to be persistent in the chronic form of the peripheral neuropathy but reversible in its acute form following immunosuppressive therapy. The possibility of a common immunopathogenesis in the association of membranous glomerulonephritis and inflammatory demyelinating peripheral neuropathies deserves further scrutiny.     

A new method to determine pudendal nerve motor latency and central motor conduction time to the external anal sphincter

By placing the earth electrode between the site of the stimulus and the site of derivation, peripheral motor latency to the external anal sphincter can be determined and thus central motor conduction time (CMCT) can be calculated. In 18 volunteers we found a total motor conduction time of 19.4 msec (S.D. 1.71) after stimulation of the motor cortex and recording above the external anal sphincter. Latency was 5.6 msec (S.D. 0.66) when stimulated above L1 and pudendal latency (MEPuL) after stimulation above S3 was 2.5 msec (S.D. 0.32). CMCT to L1 (TMCT minus MCT to L1) was 13.8 msec (S.D. 1.13) and to S3 (TMCT minus MEPuL) it was 16.9 msec (S.D. 1.67). This method allows us to locate spinal dysfunction more precisely and also improves diagnosis of a possible neuropathy of the pudendal nerve.