The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Points) are defined at the end of the "Major Recommendations" field.
Guillain-Barré Syndrome (GBS)
Intravenous immunoglobulin (IVIG) 0.4 g/kg/day for 5 days or plasma exchange (PE) can be used as first-line treatment and are considered to be equally effective (level A). IVIG has lesser side effects than PE and this would favour IVIG over PE treatment (level B). IVIG treatment after PE, as standard combination, does not produce significant extra benefit and cannot be recommended (level B). Combining high-dose intravenous methylprednisolone with IVIG may have a minor short-term benefit (level C). Children, who generally have a better prognosis, should be treated with IVIG as first-line treatment (level C). Patients who improve after IVIG and then relapse should preferentially be retreated with a second course of IVIG (good practice point). In patients who seem to be unresponsive to the first course of IVIG a second course may be tried, but evidence supporting such a strategy is lacking (good practice point). No recommendations can be given whether mildly affected
Guillain-Barré Syndrome patients or patients with Miller Fisher syndrome should be treated with IVIG.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Patients with very mild symptoms which do not or only slightly interfere with activities of daily living may be monitored without treatment (good practice point). Treatment should be considered for patients with moderate or severe disability. IVIG (2 g/kg in 2 to 5 days) (level A) or corticosteroids (1 mg/kg or 60 mg daily) (level B) can be used as first-line treatment in sensorimotor CIDP. The presence of relative contraindications to either treatment should influence the choice (good practice point). For pure motor CIDP IVIG treatment should be first choice and if corticosteroids are used, patients should be monitored closely for deterioration (good practice point). If a patient responds to IVIG, attempts should be made at intervals to reduce the dose to discover whether the patient still needs IVIG and what dose is needed (good practice point). It is important to avoid deterioration sometimes seen just before the next IVIG course. The treatment intervals should be such that this deterioration does not happen. If a patient becomes stable on intermittent IVIG the dose should be reduced before the frequency of administration is lowered (good practice point). These recommendations are in line with the European Federation of Neurological Societies (EFNS) guideline on the management of CIDP previously published (Hughes et al., 2006).
Multifocal Motor Neuropathy (MMN)
As there is no other treatment of proven benefit, the recommendation is to use IVIG (2 g/kg in 2 to 5 days) as a first-line treatment (level A). If the initial IVIG treatment is effective, repeated infusions should be considered (level C). A considerable number of patients need prolonged treatment, but attempts should be made to decrease the dose to discover whether a patient still needs IVIG (good practice point). Furthermore, the frequency of maintenance therapy should be guided by the individual response, whereby typical treatment regimens are 1 g/kg every 2 to 4 weeks or 2 g/kg every 4 to 8 weeks (good practice point). A recent European guideline on the management of MMN summarizes the other treatment options (European Federation of Neurological Societies et al., 2006).
Paraproteinaemic Demyelinating Neuropathy
IVIG should be considered as initial treatment of demyelinating IgM monoclonal gammopathy of undetermined significance (MGUS)-related neuropathy (level B). As long as long-term effects and cost-benefit aspects are not known, routine use of IVIG cannot be recommended in patients without significant disability (good practice point). However, in patients with significant disability or rapid worsening, IVIG may be tried, although its efficacy is not proven (good practice point). In patients with CIDP-like neuropathy, the detection of paraproteinaemia does not justify a different therapeutic approach from CIDP without a paraprotein.
Paraneoplastic Syndromes
Intravenous immunoglobulin therapy may be tried in paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS) and opsoclonus-ataxia especially in paediatric neuroblastoma patients (good practice point). No clear recommendations of the effect of IVIG in paraneoplastic neuromyotonia, cerebellar degeneration, limbic encephalitis or sensory neuropathy can be made due to lack of data.
Inflammatory Myopathies
Dermatomyositis (DM)
IVIG is recommended as a second-line treatment in combination with prednisone for patients with DM who have not adequately responded to corticosteroids (level B). IVIG is recommended, in combination with immunosuppressive medication, as a measure to lower the dose of steroids in patients with DM (level C). IVIG is not recommended as monotherapy for DM (good practice point). In severe, life-threatening DM, IVIG can be considered as the first-line treatment together with other immunosuppressive therapy (good practice point).
Inclusion Body Myositis (IBM)
IVIG can not be recommended for the treatment of sporadic inclusion body myositis (IBM) (level A).
Polymyositis
IVIG may be considered amongst the treatment options for patients with polymyositis not responding to first-line immunosuppressive treatment (level C).
Myasthenia Gravis (MG)
Intravenous immunoglobulin is an effective treatment for acute exacerbations of MG and for short-term treatment of severe MG (level A). IVIG is similar to PE regarding effect. This treatment is safe also for children, during pregnancy, and for elderly patients with complicating disorders. There is not sufficient evidence to recommend IVIG for chronic maintenance therapy in MG alone or in combination with other immunoactive drugs.
Post-Polio Syndrome (PPS)
IVIG has a minor to moderate positive effect on muscle strength and some aspects of quality of life in PPS (class I evidence). As long as responding subgroups, long-term effects, dosing schedules and cost-benefit aspects are not known, routine use of IVIG for PPS cannot be recommended (good practice point). However, in the very few patients with especially rapid progression of muscle weakness and atrophy, especially if there are indications of ongoing low-grade inflammation in the spinal cord, IVIG may be tried if a rigorous follow-up of muscle strength and quality of life can be undertaken (good practice point).
IVIG in Multiple Sclerosis
The negative results of the Prevention of Relapses with IVIG (PRIVIG) Study challenge recommendations for IVIG as a second-line treatment for relapsing-remitting multiple sclerosis (RRMS). However, IVIG could still be considered as a second or third-line therapy in RRMS if conventional immunomodulatory therapies are not tolerated because of side effects or concomitant diseases (level B), and in particular in pregnancy where other therapies may not be used (good clinical practice point). IVIG cannot be recommended for treatment in secondary progressive MS (level A). IVIG does not seem to have any valuable effect as add-on therapy to methylprednisolone for acute exacerbations (level B) and cannot be recommended as treatment for chronic symptoms in MS (level A). In clinically isolated syndromes and in primary progressive MS there is not sufficient evidence to make any recommendations.
Other Demyelinating Diseases of Central Nervous System
IVIG may have a favourable effect in the treatment of acute-disseminated encephalomyelitis (ADEM), and, therefore, it should be tried (0.4 g/kg/day for 4 to 5 consecutive days) in patients with lack of response to high-dose steroids (good practice point). The cycles may be repeated. PE could also be considered in patients with a lack of response to high-dose steroids.
Stiff-Person Syndrome (SPS)
In patients with stiff-person syndrome incompletely responding to diazepam and/or baclofen and with significant disability requiring a cane or a walker due to truncal stiffness and frequent falls, the recommendation is to use IVIG (2 g/ kg in 2 to 5 days) (level A based on class I evidence).
Drug-Resistant Epilepsy
IVIG seems to have a favourable effect in Rasmussen's encephalitis (RE) and may be tried in selected patients that are refractory to other therapies (good practice point). IVIG has been administered at doses of 0.4 g/kg/day for 4 to 5 consecutive days, the cycles may be repeated after 2 to 6 weeks.
Definitions:
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Rating of Recommendations for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good Practice Points Where there was a lack of evidence but consensus was clear, the Task Force has stated their opinion as good practice points.
