**3. IVIg in therapy of myasthenia gravis (MG)**

Myasthenia gravis (MG) is caused by autoantibodies against antigen in the post-synaptic neuromuscular membrane; in most patients against the acetylcholine receptor (AChR), in 5% against muscle-specific tyrosin kinase (MuSK), and in 5% against undefined antigen. A direct induction of muscle weakness by the autoantibodies has been shown.

The efficacy of IVIg in the treatment of MG has been confirmed by five controlled, prospective studies that are summarized in a Cochrane review. In acute exacerbations of MG, IVIG and PE have roughly the same efficacy, but when using IVIg the effect is slightly slower and there are less side effects (Gajdos et al, 2006).

The optimal dose of IVIG in MG has also been debated. So far no marked superiority of IVIg 2 g kg over 2 days compared to 1 g kg in a single day has been detected. The dose used has mostly been 2 g kg resulting in the improvement after 3–6 days. Although IVIg is an effective treatment for acute exacerbations of MG, it is not recommended as maintenance therapy. Importantly, IVIg is often used in preparing MG patients for thymectomy or other types of surgery in case they have severe weakness, bulbar symptoms, poor pulmonary function, or a thymoma, even though there are no controlled studies justifying this practice. IVIg therapy has also been considered as rescue therapy in worsening MG, exacerbations of the disease during pregnancy and before giving birth, and neonatal MG. IVIg is considered safe in children and in elderly patients (EFNS task force, 2008). Recommendations


Intravenous Immunoglobulins in Neurological Diseases: Established and Novel Clinical Applications 345

presenting feature of polymyositis. The onset is usually insidious and the distribution of weakness is typically symmetric and proximal. Myalgias occur in less than 30% of the

Only one non-RCT (evidence class III) and two case series (evidence class IV) on IVIg therapy for polymyositis have been published. Only the first one used IVIg exclusively in patients with polymyositis. This study reported clinical improvement in 71% of patients with significant improvement in muscle power, muscle disability scores, and creatinine kinase levels (P < 0.01). Steroid doses could be reduced after IVIg (P < 0.05) (Hughes et al,


Multiple sclerosis (MS) is a central nervous system chronic inflammatory disease that is characterized by an extensive and complex immune response. It is the most common demyelinating disease of the central nervous system in young adults. MS can cause a variety of symptoms**,** including changes in sensation, visual problems, muscle weakness, depression**,** difficulties with coordination and speech, severe fatigue, cognitive impairment, problems with balance, overheating, and pain**.** MS will cause impaired mobility and disability in more severe cases. Multiple sclerosis may take several different forms, with new symptoms occurring either in discrete attacks or slowly accruing over time. Between attacks, symptoms may resolve completely, but permanent neurologic problems often persist, especially as the disease advances. MS currently does not have a cure, though several treatments are available that may slow the appearance of new symptoms

Although earlier trials on the efficacy of IVIg in Relapsing Remitting MS (RRMS) have demonstrated a reduction in relapses, a recent study investigating the prevention of relapses with IVIg (PRIVIG trial) failed to confirm these earlier observations (Fazekas et al, 2008). In this study 127 patients with RRMS participated in a double blind, placebo-controlled trial, in which 44 and 42 patients received treatment with 0.2 or 0.4 g kg of IVIg and 42 patients received placebo every 4 weeks for 48 weeks. After 1 year, the proportion of relapse-free patients did not differ between the groups, and there was no difference in MRI activity assessed 6-weekly. The authors of the study suggested that the obtained results may be related to short disease duration and overall disease activity of the study population that

The efficacy of IVIg in the treatment of MS exacerbations has been addressed in small addon type studies that could not demonstrate any additional benefits due to addition of IVIg to conventional treatment of acute exacerbations with high-dose IV methylprednisolone. However, a recent study reported that IVIg might have a beneficial effect in patients with insufficient recovery from optic neuritis, if treatment with high-dose IV methylprednisolone fails (Achiron, 2008). No clinically significant effects were seen in progressive forms of MS, and consequently IVIg is not recommended in these conditions (Elovaara et al, 2010). Currently the main indication for the use of IVIg in MS is to reduce relapses during pregnancy or breastfeeding when other therapies may not be used safely (Haas & Homes,

was more like that observed in a population with a clinically isolated syndrome.

not responding to first line immunosuppressive treatment (level C).

**5. IVIg in therapy of demyelinating diseases of central nervous system** 

patiens (Dalakas & Hohlfeld, 2003).

2008).

2007).

Recommendations:

Recommendation:

**5.1 Multiple sclerosis (MS)** 

(Baumstarck-Barrau et al, 2011)
