Prognostic factor of poor outcome in anti-MAG neuropathy: clinical and electrophysiological analysis of a French Cohort.

BACKGROUND: Anti-MAG polyneuropathy (anti-MAG PN) is an immune-mediated peripheral sensorimotor neuropathy characterized by distal demyelination and ataxia. However, this disorder, unlike other immune-mediated neuropathies, is difficult to treat in most cases. METHOD: We retrospectively collected all anti-MAG PN patients followed in two hospitals for a period of 12 years to determine prognostic factors, especially those that indicated a good response to the various therapeutic strategies used. RESULTS: Forty-seven patients were included in the study; of these, 61% had a classical 'distal demyelinating pattern', 34.2% had a 'CIDP-like pattern', and the others had an 'axonal pattern'. The most commonly used treatments were intravenous immunoglobulin (IVIg) as the first-line treatment and rituximab as the second- or third-line treatment. No prognostic factor was identified for IVIg, but electrophysiological parameters at onset were better in patients with a good response to rituximab than in non-responder patients, even though mild or high disability was observed in nearly half the patients at last examination. CONCLUSION: Even though disability seems to progress in most cases despite the treatments used, our results suggest that an early electrophysiological reduction in sensory nerves could be considered a 'red flag' for the prompt initiation of rituximab to try to delay long-term disability.

Outcome measures in immune-mediated neuropathies: the need to standardize their use and to understand the clinimetric essentials.

Peripheral neurological disorders like neuropathies may cause impairments (such as weakness and sensory deficits), which may lead to problems in daily life and social functioning with a possible decrement in quality of life expectations. Choosing the proper outcome measure to evaluate the therapeutic efficacy of an intervention at one of these levels of outcome should therefore be considered as fundamental to the design of randomized trials in peripheral neurological disorders. However, these choices are dependent not only on the proposed research purposes but also, and perhaps more importantly, on the fulfillment of the scientific needs of these measures. With an increasing demand for accuracy, a thorough and comprehensive evaluation of an outcome measure is needed to determine its simplicity, communicability, validity, reliability, and responsiveness before being clinically applicable, techniques that are being captured by the science of clinimetrics. Most neurologists are still unfamiliar with these rigorous methodological essentials or overlook some of them in their trial preparations because these are considered time consuming and mind numbing. This review will highlight, against the background of the international classification framework and clinimetric needs for outcome measures, the selected scales applied in published randomized controlled trials in patients with Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and gammopathy-related neuropathies. The need for comparison responsiveness studies between equally valid and reliable measures and to standardize their use is emphasized in these conditions. Finally, specific recommendations are given to move from classic to modern clinimetric approach when constructing, evaluating, and selecting outcome measures using new methods like Rasch analysis, accentuating the need of shifting toward a more modern era.

[The extent of the clinical manifestations of chronic polyradiculoneuropathy]. / Les limites cliniques du concept de polyradiculonévrite chronique.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is an autoimmune disease that target myelin sheats of peripheral nerves. Its diagnosis is often difficult to make, and a number of cases are probably not identified because of the clinical heterogeneity. Numerous sets of diagnostic criteria have sought to define CIDP but clinical criteria are generally not detailed. OBJECTIVES: To review the main clinical characteristics suggestive of CIDP (that means not compatible with a length-dependent axonal process) and the critical clinical points of the neuropathy which make the differential diagnosis with the main other forms of chronic auto immune neuropathy sometimes difficult. RESULTS: The main clinical characteristic are: a symmetric proximal and distal motor weakness predominantly affecting the lower limbs, a diffuse areflexia, a sensory deficit characterized by a preferential involvement of large fibers, an evolution which may be either chronic progressive or recurrent. These aspects raise many questions concerning overlap with other inflammatory neuropathies such as Guillain Barre syndrome, Lewis-Sumner neuropathy, chronic ataxic neuropathy. The distinction of a subgroup of CIDP associated with other diseases such as diabetes or HIV are also controversial. CONCLUSION: The growing body of knowledge on the pathogenesis of CIDP and clinical or electrophysiological differentiation of subforms may help to develop more effective therapies for CIDP in the next few years.

Nodo-paranodopathy, internodopathy and cleftopathy: Target-based reclassification of Guillain-Barré-like immune-mediated polyradiculoneuropathies in dogs and cats.

Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of routine work-up in human patients we evaluated tissues taken from companion animals affected by GBS-like polyradiculoneuropathy to screen for distribution of immune cells, targeted fibre components and segregating non-inflammatory lesions. We identified that immune responses were directed either at Schmidt-Lanterman clefts, the paranode-node complex or both. Based on infiltrative and non-inflammatory changes, four subtypes and/or stages were distinguished, some of which indicate localisation of primary target antigens while others represent convergent late stage pictures, as a consequence to epitope spreading. The impact of histological subtyping onto clinical management and prognosis remains to be evaluated in future clinical trials. Natural development and clinical manifestation of large animal dysimmune neuropathy may reflect human Guillain-Barré syndrome more accurately than experimental models and therefore provide complementary clues for translational research.

Subclass of IgG antibody to GM1 epitope-bearing lipopolysaccharide of Campylobacter jejuni in patients with Guillain-Barré syndrome.

Sera of patients who develop Guillain-Barré syndrome (GBS) subsequent to Campylobacter jejuni enteritis frequently have IgG anti-GM1 antibody. Lipopolysaccharide (LPS) of C. jejuni isolated from a GBS patient has a GM1 ganglioside-like structure. IgG subclass distribution of the anti-GM1 antibody in GBS patients is mainly restricted to IgG1 and IgG3. Since IgG antibodies to bacterial polysaccharide generally are restricted to IgG2 subclass, some investigators have assumed that either the general rules for immune response to LPS are broken in the patients or an alternative antigen has yet to be identified. To clarify whether the LPS participates in the production of the anti-GM1 antibody, we investigated the subclass of IgG antibody to the LPS that bears GM1-like structure. The subclasses of IgG antibody to the LPS were restricted predominantly to IgG1 and IgG3. The GM1 epitope-bearing LPS may function in the production of the anti-GM1 antibody in patients with GBS subsequent to C. jejuni infection.

Criteria for the diagnosis of the Guillain-Barré syndrome. A critique of the NINCDS guidelines.

The publication of "official" criteria for the diagnosis of the Guillain-Barré syndrome designed for the purpose of aiding epidemiological studies, has resulted in excluding from consideration a number of fragmentary and atypical cases. Because it is a syndrome and not a disease entity, the limits are arbitrary. Several of the criteria are confusing and contradictory; they ignore a vast amount of literature which clearly documents the variability of the signs and symptoms.

[A case of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome with positive anti-galactocerebroside (Gal-C) IgM antibody].

A 49-year-old man presented with hoarseness, dysphagia, muscle atrophy and weakness of deltoid, trapezius, sternocleidomastoid, rhomboid, anterior serratus, infraspinatus and supraspinatus. Anti-Gal-C IgM antibody was positive in the serum. The other antiganglioside antibodies (GM1, GM2, GM3, GD1a, GD1b, GD3, GT1a, GT1b, GQ1b, GA1, GalNAc-GD1a, GM1b) were negative. Patient contracted pneumonia but whether it was due to mycoplasma was not evident. Plasmapheresis improved his clinical state including a decrease of the antibody. This case was diagnosed pharyngeal-cervical-brachial variant of Guillain-Barré syndrome, and anti-Gal-C antibody seemed to be correlated with the pathogenesis of this syndrome. Gal-C is a major glycolipid of myelin and the cell membrane of the myelin-forming cell (oligodendrocytes and Schwann cells) and is free of specific localization and distribution. The mechanism how the anti-Gal-C IgM antibody induced bulbar paralysis and the symptoms localizing neck and upper limbs remains to be known.

[A case of pharyngeal-cervical-branchial variant of Guillain-Barré syndrome with IgG anti-GT1a antibody].

A 36-year-old man with pharyngeal-cervical-brachial variant of Guillain-Barré syndrome (PCB) was described. Neurologic examination revealed total ophthalmoplegia, pharyngeal-cervical-brachial weakness and hyporeflexia in the upper limbs, sparing power and tendon reflexes in the lower limbs. Enzyme-linked immunosorbent assay showed that he had high titer of IgG antibody to GT1a (1:32,000), which did not cross-react with GQ1 b or GD1a. Thin-layer chromatography immunostaining confirmed that his serum IgG reacted with GT1a. These findings show that IgG anti-GT1a antibody without cross-reactivity with GQ1b plays a role in the development of PCB.

[Guillain-Barré syndrome associated with anti-GQ1b antibody--nosological relationship between Fisher's syndrome and Guillain-Barré syndrome].

A 15-year-old man developed diplopia, ataxic gait and bulbar palsy. Two days after the onset of neurological symptoms, neurological examination revealed external ophthalmoplegia, cerebellar ataxia, and areflexia. Muscle weakness in the areas innervated by cranial nerves and in the four limbs, and glove and stocking type sensory impairment were also observed. On the 13th hospital day, CSF protein was elevated with normal cellularity. Serum IgM anti-GQ1b antibody was increased, which decreased concurrently with the clinical improvement. Recent studies have revealed the frequent presence of serum anti-GQ1b antibody in Fisher's syndrome. Therefore, this patient showed Fisher's syndrome at the beginning, then evolved to Guillain-Barré syndrome associated with anti-GQ1b antibody, which would support close association between Fisher's syndrome and Guillain-Barré syndrome.

[Guillain-Barré syndrome and acute disseminated encephalomyelitis (ADEM)].

I would like to report the results of our immunological study on Guillain-Barré syndrome (GBS) and to consider the relationship between GBS and acute disseminated encephalomyelitis (ADEM). First of all, I referred to the historical view of the diagnostic criteria of GBS. Immunological study on GBS started after the report of experimental allergic neuritis (EAN) by Waksman and Adams (1995). We made EAN rabbits by immunization with peripheral myelin and observed the process of motor paralysis. In EAN, humoral and cellular immune responses to P2 protein and its synthetic peptides were obtained in accordance with the motor weakness. In patients with GBS we also investigated the humoral and cellular immune responses to P2 protein. Anti-P2 protein antibody and sensitized lymphocytes against P2 protein and its synthetic peptides were detected in GBS as well as in EAN. We also detected antineural antibodies such as anti-P0, anti-galactocerebroside and anti-GM1 ganglioside antibodies in GBS. And also anti-GQ1b antibody was detected in patients with Fisher syndrome and GBS with ophthalmoplegia. More than 50 years ago, Baker (1943) described 5 forms of GBS including 1) abortive or mononeuritic 2) polyneuritic 3) spinal, 4) bulbar and 5) cerebral forms. Guillain (1953) didn't deny the bulbar and cerebral forms, although he apparently denied the spinal form of GBS with Babinski's sign. According to "Merritt's Textbook of Neurology", lesions of ADEM (postinfectious and postvaccinal encephalomyelitis) involved not only the brain and the spinal cord but also the peripheral nerve. Guillain (1953) objected against "Landry-Guillain-Barré syndrome" proposed by Haymaker and Kernohan (1949). Guillain (1953) described that Landry's ascending paralysis was different from GBS and Landry's paralysis must belong to category of ADEM, as van Bogaert also commented. In our recent study for T cell subsets in GBS and ADEM, significant increase in activated CD4 and helper inducer cells were observed in both GBS and ADEM, which suggested the presence of a common pathogenic mechanism in these diseases. After considering the classification of immunological nervous diseases, we would propose a clinical entity "acute immuno-logical nervous diseases" including GBS, Fisher syndrome and ADEM.

[Acquired dysimmune neuropathies. Clinical symptoms and classification]. / Neuropatías disinmunes adquiridas. Sintomatología clínica y clasificación.

INTRODUCTION: The neuropathies caused by dysimmunity have seen great changes in recent years. The different forms of clinical presentation, electrophysiological expression, associated anomalies seen on analytical tests, particularly the presence of antibodies to the various antigens of myelin are becoming better understood. This confirms their dysimmune nature and also offers unforeseen possibilities for the comprehension of etiopathogenic mechanisms and possible classifications of specific etiopathogenic factors. DEVELOPMENT: Based mainly on our own experience, in this paper we review current concepts of the three main dysimmune polyneuropathies, the Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuritis or CIDP and the motor multifocal neuropathies (MMN) with block-conduction or Lewis-Summer syndrome. Regarding the first condition, we particularly emphasize the convenience of establishing the broad classification needed by the variation in its clinical presentation, with regional and functional variants: among the latter we consider particularly the pure motor forms which in most cases are axonal forms with an etiopathogenic basis which is fairly well established and almost constantly associated with the presence of specific antibodies in the serum of patients with this condition. With reference to CIDP, we discuss the existence of atypical forms and the frequency of the relapsing form concerning the evolution. The MMN are the most recently discovered dysimmune neuropathies, according to both the literature and personal experience. We try to establish the difference between pure motor forms and those which also have sensory involvement (or MADSAM) and are called the Lewis-Sumner syndrome.

[Clinical course of the recurrent form of the Guillain-Barrè-Strohl syndrome]. / Przebieg kliniczny nawrotowej postaci zespolu Guillaina-Barrè-Strohla.

A case of recurrent Guillain-Barré-Strohl syndrome was observed in a girl aged 7 years. The child was cured.