I. N. van Schaik

European federation of neurological societies/peripheral nerve society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background:  Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System.

EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases

Despite high‐dose intravenous immunoglobulin (IVIG) is widely used in treatment of a number of immune‐mediated neurological diseases, the consensus on its optimal use is insufficient. To define the evidence‐based optimal use of IVIG in neurology, the recent papers of high relevance were reviewed and consensus recommendations are given according to EFNS guidance regulations. The efficacy of IVIG has been proven in Guillain‐Barré syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis (MG) and short‐term treatment of severe MG (level A recommendation), and some paraneoplastic neuropathies (level B). IVIG is recommended as a second‐line treatment in combination with prednisone in dermatomyositis (level B) and treatment option in polymyositis (level C). IVIG should be considered as a second or third‐line therapy in relapsing–remitting multiple sclerosis, if conventional immunomodulatory therapies are not tolerated (level B), and in relapses during pregnancy or post‐partum period (good clinical practice point). IVIG seems to have a favourable effect also in paraneoplastic neurological diseases (level A), stiff‐person syndrome (level A), some acute‐demyelinating diseases and childhood refractory epilepsy (good practice point).

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2–5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2–4 weeks or 2 g/kg every 4–8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

Diagnostic value of GM1 antibodies in motor neuron disorders and neuropathies: a meta-analysis.

We performed a meta-analysis on the diagnostic value of IgM anti-GM1 antibodies. The reported frequencies of IgM anti-GM1 antibodies ranged from 0 to 100% for patients with multifocal motor neuropathy (MMN), from 0 to 33% in the Guillain-Barre syndrome, from 0 to 65% in amyotrophic lateral sclerosis (ALS), from 0 to 77% in chronic inflammatory demyelinating neuropathy, and from 0 to 81% in lower motor neuron disease (LMND). However, using funnel graphs and a chi-square test we determined that the method of ELISA was the most important factor explaining these differences. After allowing for two factors--the use of detergent and the duration and temperature of serum incubation--studies became homogeneous in all but the LMND group of method A (no detergent, duration of serum incubation 5 hours) and the ALS group of method B (no detergent, duration of serum incubation at least 12 hours [overnight]). Since the anti-GM1 antibody assay serves to confirm clinical suspicion of MMN rather than to exclude the disease, specificity is more important than sensitivity. ELISA methods that do not use detergent and that incubate serum overnight resulted in a specificity of 90% and sensitivity of 38% in the comparison of MMN and LMND. With these values we calculated incremental ruling-in and ruling-out gain curves. Prior probabilities between 20 and 60% for having MMN changed to post-test probabilities between 50 and 85%, which is of clinical importance. In conclusion, ELISA is a useful diagnostic test to demonstrate IgM anti-GM1 antibodies provided the methods do not use detergent and do incubate serum overnight. NEUROLOGY 1995;45: 1570-1577

Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation

Objective: In patients who remain in a coma after cardiopulmonary resuscitation (CPR), the bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SSEP) 24 hours after admission invariably correlates with a poor neurologic outcome. Nowadays, CPR patients are treated with mild hypothermia, with simultaneously administered sedative drugs, hampering clinical neurologic assessment. We investigated whether SSEP performed during hypothermia can reliably predict a poor neurologic outcome. Methods: Between July 2006 and April 2008, this multicenter prospective cohort study included adult comatose patients admitted after CPR and treated with induced mild hypothermia (32–34°C). SSEP was performed during hypothermia, and in patients who remained comatose after rewarming, a second SSEP was performed. Neurologic outcome was assessed 30 days after admission with the Glasgow Outcome Scale. Results: Seventy-seven consecutive patients were included in 2 hospitals. In 13 patients (17%), the cortical N20 response during hypothermia was bilaterally absent. In 9 of these 13 patients in whom SSEP could be repeated during normothermia, the N20 response was also absent, yielding a positive predictive value of 1.00 (95% confidence interval [CI] 0.70–1.00). All 13 patients with absent SSEP during hypothermia had a poor neurologic outcome, yielding a positive predictive value of 1.00 (95% CI 0.77–1.00). Conclusions: The results of this pilot study show that bilaterally absent cortical N20 responses of median nerve somatosensory evoked potentials performed during mild hypothermia after resuscitation can predict a poor neurologic outcome. We started a larger multicenter prospective cohort study to confirm these results.

Long-term remission of CIDP after pulsed dexamethasone or short-term prednisolone treatment

Objective: Achieving long-term remission after a limited more intense treatment period would prevent prolonged use of corticosteroids or IV immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this prospective cohort study we present long-term follow-up data on patients included in a multicenter randomized controlled trial comparing 6 monthly pulses of dexamethasone with 8 months of daily prednisolone. Methods: Treatment effect was assessed with the Inflammatory Neuropathy Cause and Treatment disability scale and the Rivermead Mobility Index and was categorized using the CIDP Disease Activity Status (CDAS) scale. Results: By March 2011, 39 out of 40 patients were included with a median follow-up of 4.5 years. Cure (>5 years off treatment) or remission according to the CDAS criteria after 1 or 2 courses of pulsed dexamethasone or daily prednisolone was achieved in 10 out of 39 patients (26%). Half of the patients who were in remission after initial treatment experienced a relapse (median treatment-free interval: 17.5 months for dexamethasone, 11 months for prednisolone). Alternative diagnosis was made in 7 out of 12 (58%) who did not respond to any therapy and in none of the treatment-responsive patients. Conclusions: Cure or long-term remission can be achieved in about one-quarter of patients with CIDP after 1 or 2 courses of pulsed dexamethasone or 8-month daily prednisolone. In treatment-nonresponsive patients, the diagnosis CIDP should be reconsidered. Classification of Evidence: This study provides Class IV evidence that pulsed dexamethasone or 8-month daily prednisolone can lead to long-term remission in CIDP.

Investigation of serum response to PMP22, connexin 32 and P0 in inflammatory neuropathies

We investigated serological immune responses against three major peripheral nerve myelin constituents in patients with immune-mediated neuropathies. Connexin 32 (Cx32), myelin protein zero (MPZ, P(0)) and peripheral myelin protein 22 (PMP22) were produced in Chinese hamster ovary (CHO)-K1 cells. From a panel of 25 Guillain-Barré syndrome (GBS) and 24 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, only two patients showed reactivity towards Cx32 and P(0).

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinaemic demyelinating neuropathies: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society*

Background. Paraprotein‐associated neuropathies have heterogeneous clinical, neurophysiological, neuropathological and haematological features. Objectives. To prepare evidence‐based and consensus guidelines on the clinical management of patients with both a demyelinating neuropathy and a paraprotein (paraproteinaemic demyelinating neuropathy, PDN). Methods. Search of MEDLINE and the Cochrane library, review of evidence and consensus agreement of an expert panel. Recommendations. In the absence of adequate data, evidence based recommendations were not possible but the panel agreed the following good practice points: (1) Patients with PDN should be investigated for a malignant plasma cell dyscrasia. (2) The paraprotein is more likely to be causing the neuropathy if the paraprotein is immunoglobulin (Ig)M, antibodies are present in serum or on biopsy, or the clinical phenotype is chronic distal sensory neuropathy. (3) Patients with IgM PDN usually have predominantly distal and sensory impairment, with prolonged distal motor latencies, and often anti‐myelin associated glycoprotein antibodies. (4) IgM PDN sometimes responds to immune therapies. Their potential benefit should be balanced against their possible side‐effects and the usually slow disease progression. (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy, clinically, electrophysiologically, and in response to treatment. (6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato‐oncology advice.

Anti-GM1 antibodies in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg)

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and with a chronic polyneuropathy (non-CIDP) were studied for the presence of anti-GM1 antibodies. In pretreatment sera of CIDP patients, we found IgG anti-GM1 antibodies in 23%, IgM in 7%, and IgA in 14%. Predominantly motor involvement was associated with IgG and IgM anti-GM1 antibodies in CIDP patients (P = 0.002). Improvement after intravenous immunoglobulin (IVIg) therapy was not associated with anti-GM1 antibody titer before or after treatment. Anti-GM1 antibody titers before onset of treatment was not related to poor clinical outcome, although large clinical improvements after IVIg therapy were observed less often (P = 0.057) in patients with high titer anti-GM1 antibodies before treatment.