The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, good practice point) are defined at the end of the "Major Recommendations" field.
Myasthenia Gravis
After the diagnosis of myasthenia gravis (MG) is established, an acetylcholine esterase inhibitor should be introduced. Thymoma patients should have thymectomy (TE). Acetylcholine receptor (AChR)-antibody positive early-onset patients with generalized MG and insufficient response to pyridostigmine therapy should be considered for TE, ideally within 1 year of disease onset. Immunosuppressive medication should be considered in all patients with progressive MG symptoms. The Task Force members recommend starting with prednisolone covered by bisphosphonate and antacid. If long-term treatment with steroids is expected, a steroid-sparing agent, usually azathioprine should be introduced. Non-responders or patients intolerant to this regime should be considered for treatment with one of the other recommended immunosuppressive drugs. Recommendation levels are generally B, C or good practice points.
Lambert–Eaton Myasthenic Syndrome
Evidence from small, randomized, controlled trials showed that both 3,4-diaminopyridine and intravenous immunoglobulin (IvIg) improved muscle strength scores and compound muscle action potential amplitudes in Lambert–Eaton myasthenic syndrome (LEMS) patients (class I evidence).
First-line treatment is 3,4-diaminopyridine. An additional therapeutic effect may be obtained if combined with pyridostigmine. If symptomatic treatment is insufficient immunosuppressive therapy should be started, usually with a combination of prednisone and azathioprine. By analogy to MG, other drugs like ciclosporin or mycophenolate can be used, although evidence of benefit is limited to case series reports (class IV evidence) (level C recommendation).
For patients with a paraneoplastic LEMS it is essential to treat the tumour. Chemotherapy is the first choice in small-cell lung cancer (SCLC) and this will have an additional immunosuppressive effect. The presence of LEMS in a patient with SCLC improves tumour survival. For a more detailed description of LEMS consult the National Guideline Clearinghouse (NGC) summary of the European Federation of Neurological Societies (EFNS) guideline, Management of Paraneoplastic Neurological Syndromes: Report of an EFNS Task Force.
Neuromyotonia (Peripheral Nerve Hyperexcitability)/Isaacs Syndrome
Neuromyotonia usually improves with symptomatic treatment, although evidence is case reports and case series (class IV evidence). Carbamazepine, phenytoin, lamotrigine and sodium valproate can be used, if necessary in combination.
Neuromyotonia often improves and can remit after treatment of an underlying cancer. In patients whose symptoms are debilitating or refractory to symptomatic therapy, immunomodulatory therapies should be tried. Plasma exchange often produces useful clinical improvement lasting about 6 weeks accompanied by a reduction in electromyography (EMG) activity and a fall in voltage-gated potassium channels (VGKC) antibody titres. Single case studies suggest that IvIg can also help. There are no good trials of long-term oral immunosuppression. However, prednisolone, with or without azathioprine or methotrexate, has been useful in selected patients (class IV evidence) (good practice point).
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
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations
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 point When only class IV evidence was available but consensus could be reached, the Task Force has offered advice as good practice point.
