Polyneuropathy

Journal of Neurology Neurosurgery and Psychiatry 2003;74:ii9
© 2003

MANAGEMENT OF INFLAMMATORY NEUROPATHIES

Robert D M Hadden¹ and Richard A C Hughes²

 Immunisations stimulate the immune system and rarely triggerautoimmune disease. GBS is a rare complication of modern influenza vaccine affecting one in a million recipients. In a retrospective survey, the risk of relapse following immunisation after GBS or CIDP was low but not absent. For GBS the risk of relapse severe enough to require treatment was at most 1.2%. Accordingly the GBS Support Group Medical Advisory Board recommends avoiding immunisations during the first year after the disease onset, and balancing the risks and benefits of immunisation for eachpatient on an individual basis. The same applies to CIDP inwhich the use of tetanus toxoid causes particular concern. It seems sensible to avoid immunisations that are not specifically necessary, though the risk–benefit ratio may be more favorable in patients on immunosuppressive therapy.

 Multifocal motor neuropathy with conduction block (MMN) is a rare slowly progressive motor neuropathy which is related toor a variant of CIDP. There are sometimes minor sensory symptoms but not signs. It usually affects predominantly the upper limbs in an asymmetrical fashion. It can be confused clinically with motor neurone disease because of the cramps and fasciculations. About 50% have IgM antibodies to ganglioside GM1. Diagnosis depends on the demonstration of short focal areas of partial motor conduction block caused by demyelination at sites not vulnerable to entrapment. Sensory conduction is normal acrossthe same segments. Even if no definite conduction block is found in an otherwise typical case, a trial of treatment may be indicated.

IVIg gave rapid dramatic benefit in three small randomized trials, and is the only proven effective treatment (level 1b evidence). About 20% of otherwise typical patients do not respond. Unfortunately, IVIg usually needs to be repeated frequently, every 4–12 weeks, and despite its use the weakness continues to increase. Response may be better in patients with more conduction blocks and antiganglioside GM1 antibodies, and worse in those with older age, widespread weakness, and high creatine kinase. Thereis insufficient evidence to support any particular second line treatment, but cyclophosphamide is often used. Steroids oftencause the disease to worsen, by an unknown mechanism, and should be avoided. Plasma exchange usually has no effect.

PARAPROTEINAEMIC DEMYELINATING NEUROPATHY

 About 10% of patients with an acquired demyelinating neuropathyhave a paraprotein. When a paraprotein is detected, the patient should be investigated with a skeletal survey looking for an isolated plasmacytoma that may be surgically excised, and a bone marrow biopsy looking for myeloma, etc. Treatment of the cause of the paraprotein may improve the neuropathy. Most paraproteins are monoclonal gammopathies of uncertain significance (MGUS), and not usually treated, but the paraprotein concentration should be monitored regularly looking for a rapid rise that may herald malignant transformation. Paraproteinaemic demyelinating neuropathy is a heterogeneous group of conditions. The following may be distinguished.

1. The best defined and most common syndrome is a slowly progressive, predominantly sensory neuropathy associated with IgM paraprotein, in which the paraprotein is a monoclonal antibody to myelin associated glycoprotein (MAG). Electron microscopy shows characteristic widely spaced myelin. There is often a postural tremor. The disease usually progresses slowly over years and is rarely disabling. Nerve conduction studies usually show uniform symmetrical conduction slowing and with notably prolonged distal motor latencies. Treatment is difficult. Mild slowly progressive disease is best left untreated. In more severe cases, IVIg has a transient beneficial effect (level 1b evidence). Fludarabine and rituximab have seemed effective in small series of severely affected patients.
2. Chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins,and disialoganglioside antibodies (CANOMAD) is a rare paraproteinaemic neuropathy similar to chronic MFS, which may respond to IVIg.
3. The POEMS syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes is occasionally identified. It may be associated with myeloma, usually osteosclerotic, and Castleman’s disease. Steroids, azathioprine, melphalan,and cyclophosphamide have all been used empirically and there is no evidence on which to select any of these treatments.
4. Neuropathy with an IgA or IgG paraprotein may resemble CIDP and respond to the same treatments. Rarely there is an underlying solitary myeloma and treatment of this can be curative. Since a paraprotein is not always evident at presentation it is worth repeating serum protein electrophoresis in treatment resistantCIDP. Other possible treatments include chlorambucil, fludarabine, and rituximab.

General management of chronic neuropathy
General management includes foot care, appropriate shoes orboots, ankle and wrist splints, weight reduction, physiotherapy, occupational therapy, and counselling. Fatigue is common but there is no evidence whether antidepressants or exercise programmes help. Autonomic involvement is not uncommon in CIDP or after GBS, and erectile impotence may respond to sildenafil. There are excellent patient support groups for GBS and CIDP based in the USA (cidpusa.org)