**6.1 Lambert – eaton myasthenic syndrome (LEMS)**

Lambert-Eaton myasthenic syndrome (LEMS) is an immune-mediated disorder of the presynaptic neuromuscular transmission, which more frequently occurs as the remote effect of a neoplasm. The clinical features described are proximal weakness, especially in the lower limbs, with diminished tendon reflexes and post-tetanic potentiation. Autonomic symptoms are often reported, including pupil abnormalities, dry eyes and mouth, and erectile dysfunction (Maddison & Newsom-Davis, 2005).

LEMS is considered to respond best to immunosupressive treatment. However, there is only one report showing the beneficial but short-term effect of IVIg on the muscle strength in LEMS (class II evidence) and there is also a recent Cochrane review that has concluded that limited data from one placebo-controlled study show improvement in muscle strength after IVIg (Maddison & Newsom-Davis, 2005).

The IVIg response regarding improvement of muscle strength does probably not differ in paraneoplastic and non-paraneoplastic LEMS.

Recommendations:

346 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights




Neuromyelitis optica (NMO) termed also Devic's disease, is a demyelinating disease of the spinal cord and optic nerves that may manifest by recurrent attacks and tends to have a

There is only one case type study suggesting that monthly IVIg was associated with

Balo's concentric sclerosis is a severe demyelinating disease with poor prognosis. There is a case report suggesting that IVIg (0.4 g/kg/daily for 5 days) and interferon-beta-1a given post-partum may result partial neurological improvement (class IV evidence) (Airas et al,

Acute-disseminated encephalomyelitis (ADEM) is a monophasic immune-mediated demyelinating disease of the central nervous system that is associated with significant morbidity and mortality. Controlled studies on therapy in ADEM are not available. Standard treatment is high-dose steroids. The use of IVIg (0.4 g/kg/day for 5 days or 1 g/kg/2 days) has been reported in case reports and small series suggesting that IVIg may have favourable effects when used as an initial therapy in both adults and children (class IV evidence). IVIg may have beneficial effects also as second line therapy (class IV evidence) [149–152] especially in patients who could not receive or failed to respond to steroids (class IV evidence) or in patients with peripheral nervous system involvement and steroid failure (class IV evidence). Alternatively combination therapy by steroids and IVIG (class IV evidence) or steroids, IVIg and PE were suggested to have favourable effects especially if


Due to the rarity of immunologically mediated paraneoplastic diseases, there are very few

given early in the course of disease (class IV evidence) (EFNS task force 2008).

considered in patients with a lack of response to high-dose steroids.

prospective, randomized, double-blind and placebo-controlled studies.

**6. IVIg in therapy of paraneoplastic syndromes** 

(good clinical practice point).

**5.2 Neuromyelitis optica (NMO)** 

**5.3 Balo's concentric sclerosis** 

poor prognosis.

Recommendations:

2005).

methylprednisolone for acute exacerbations (level B)

cessation of relapses (class IV evidence) (Bakker & Metz, 2004).

**5.4 Acute disseminated encephalomyelitis (ADEM)** 

evidence to make any recommendations.


#### **6.2 Neuromyotonia**

Acquired neuromyotonia is a condition associated with muscle hyperactivity that includes muscle stiffness, cramps, myokymia, pseudomyotonia and weakness, most common in the limbs and trunk. The typical finding on electromyography is spontaneous motor unit discharges occurring in distinctive doublets, triplets, or longer runs with high intraburst frequency (Hart et al, 2002).

Only one case report describes the beneficial effect of IVIg in patient with neuromyotonia, whilst another case report demonstrated worsening after IVIG therapy (EFNS task force, 2008).

#### **6.3 Paraneoplastic opsoclonus ataxia syndrome (OMS)**

Opsoclonus refers to involuntary, conjugate, multivectorial, saccadic eye movements. It can occur as an isolated neurologic anomaly but, when it occurs with involuntary multifocal jerking movements of the skeletal musculature, the phenomenon is known as opsoclonus– myoclonus syndrome (OMS). The syndrome often includes features of ataxia, or incoordination with voluntary movements. In the setting of malignancy, opsoclonus is linked most clearly to neuroblastoma, occurring in 3% of childhood cases. Anti-neuronal antibodies, usually to nuclear antigens, are considered markers of immune system activation in this disorder, detected in 81% of pediatric patients (Pittock et al, 2003).

Symptoms in paraneoplastic opsoclonus - ataxia syndrome in paediatric neuroblastoma patients are stated to improve, although data concerning the long-term benefits of the treatment is lacking (class IV evidence). In adult patients the response is less immunosuppressive, although IVIg is suggested to accelerate recovery (class IV evidence) (EFNS task force, 2008).

Recommedation:


#### **6.4 Paraneoplastic cerebellar degeneration**

Cerebellar dysfunction is one of the most common paraneoplastic presentations of cancer. The tumours more commonly involved are small-cell lung cancer, gynaecological and breast

Intravenous Immunoglobulins in Neurological Diseases: Established and Novel Clinical Applications 349

stiffness and frequent falls. The recommendation is to use IVIg (2 g kg in 2–5 days) (EFNS


Post-polio syndrome (PPS) is characterized by new muscle weakness, muscle atrophy, fatigue and pain developing several years after acute polio. The prevalence of PPS in

Post-polio syndrome is caused by an increased degeneration of enlarged motor units, and some motor neurones cannot maintain all their nerve terminals. Muscle overuse may contribute. Immunological and inflammatory signs have been reported in the cerebrospinal

There are two RCTs of treatment with IVIg in PPS (class I evidence) including 155 patients. In the study with highest power, a significant increase of mean muscle strength of 8.3% was reported after two IVIg treatment cycles during 3 months. Physical activity and subjective

Post-polio syndrome is a chronic condition. Although a modest IVIG effect has been described short term, nothing is known about long-term effects. Responders and non-

Any relationship between the clinical response to IVIG treatment and PPS severity, cerebrospinal fluid inflammatory changes and cerebrospinal fluid changes after IVIg is unknown. Optimal dose and IVIG cycle frequency has not been examined. Cost-benefit




Drug-resistant infantile epilepsy (DRIE) syndromes include a number of diseases such as Landau-Kleffner syndrome (LKS), West syndrome, Lennox-Gastaut syndrome, severe myoclonic epilepsy or RE that typically manifest in childhood or adolescence and are

vitality also differed significantly in favour of the IVIG group (Farbu et al., 2007).

task force, 2008). Recommendations:

evidence).

**8. IVIg in therapy of post-polio syndrome (PPS)** 

fluid and central nervous tissue (EFNS task force, 2008).

patients with previous polio is 20–60%.

responders have not been defined.

evaluation has not been performed.

quality of life in PPS (class I evidence).

**9. IVIg in therapy of drug resistant epilepsy (DRIE)** 

characterized by epilepsy and progressive neurological dysfunction.

Recommendations:

practice point).

2008).

tumours, and Hodgkin's lymphoma. Neurological deficits are sometimes preceded by prodromal symptoms, such as a viral-like illness, dizziness, nausea, or vomiting that might be attributed to a peripheral vestibular process. These symptoms are followed by gait unsteadiness that rapidly develops into ataxia, diplopia, dysarthria, and dysphagia. Some patients have blurry vision, oscillopsia, and transient opsoclonus.Initial MRI is normal in most patients, although over time, MRI shows cerebellar atrophy and PET demonstrates hypometabolism (Dalmau & Rosenfeld, 2008).
