Diagnosis and investigation
The diagnosis is made on the basis of nerve conduction studies. Conduction slowing and prolonged distal motor latencies occur in both CIDP and hereditary demyelinating neuropathy, but CIDP is distinguished by the presence of motor conduction block, temporal dispersion, and asymmetric involvement, indicating a multifocal process. F-responses are delayed and often absent. Such abnormalities should be present in at least three nerves to meet diagnostic criteria. Some nerves may appear to be normal or to have axonal neurophysiology, so the diagnosis may be missed if too few nerves are tested and proximal conduction block is not specifically sought. A nerve biopsy is sometimes diagnostic, but not necessary and now not routinely done. Most patients with CIDP have axonal degeneration without demyelination on sural nerve biopsy. Serum protein electrophoresis should be done initially and annually thereafter, because the development of a paraprotein may indicate an alternative diagnosis and treatment (see later). Measurement of serum autoantibodies is not usually helpful. The CSF protein is raised in at least 80% of patients. A minority of patients has evidence of coexistent asymptomatic CNS demyelination on magnetic resonance imaging or evoked potential examination.

Immune modulating treatment
Corticosteroids were the first accepted treatment but entered clinical practice without today’s high standards of evidence. Corticosteroids induce at least short term improvement in 65–95% of patients (level 1a and 4 evidence). There are many regimens. We prefer oral prednisolone 1.5 mg/kg on alternate days in a single morning dose with careful review and dose adjustment at two weekly intervals for 12 weeks, when a judgement needs to be made about whether to continue or switch to IVIg. Improvement begins after 1–4 weeks (but occasionally months), and reaches a plateau at about six months. Occasional patients deteriorate on steroids by an unknown mechanism, especially those with pure motor forms of CIDP or with multifocal motor neuropathy with conduction block. Prednisolone is cheap but has serious long term adverse effects. Osteoporosis prophylaxis should be started at the same time.

Plasma exchange was efficacious in two sham controlled randomised trials (level 1b evidence). One trial used PE twice weekly for three weeks, and the other used four exchanges in the first week, three in the second, two in the third, and one in the fourth. To maintain improvement PE has to be repeated at intervals as short as four weeks. Its usefulness is limited by its inconvenience, venous access problems, requirement for hospital attendance and specially trained staff, and adverse events. Complications, usually from the use of a central venous catheter, were reported in one series in 17% of 381 procedures and one was fatal.

IVIg appeared efficacious in three of four randomised trials and the efficacy was supported by a meta-analysis border=0 width=8 height=7 src="polyneuropathy_37_files/image001.gif" title="" v:shapes="_x0000_s1027">, level 1a evidence).⁹ Unfortunately its benefit lasts only 2–12 weeks, so that treatment has to be repeated and is very expensive. Approximately two thirds of patients respond, of whom one third improve and need no further treatment and two thirds require repeated courses. The initial dose should be 0.4 g/kg daily for five days (smaller doses were less effective), but maintenance doses can usually be reduced to 0.4–2.0 g/kg in total and given over 1–2 days. Crossover trials have shown no significant short term difference between IVIg and PE (courses of similar cost) or between IVIg and oral prednisolone.

 
In summary, prednisolone, IVIg and PE are probably equally effective in the short term, and have not been compared in the long term, so the choice depends mainly on cost, adverse effects, and personal preference. We usually recommend starting treatment with oral prednisolone in patients for whom there are no contraindications (obesity, hypertension, diabetes, ulcer history). If it is not effective we use IVIg, followed by PE. In pure motor CIDP we start with IVIg. Immunosuppressive agents, initially azathioprine, are mostly used in patients who have failed to respond to the above treatments. Their effects have probably not been fairly tested, as these patients often have significant axonal degeneration..

Azathioprine is a broad spectrum immunosuppressive agent and may have a steroid sparing action. Several small case series suggested improvement with 3 mg/kg daily but the effect onset may be delayed by 3–12 months (level 3 evidence). The only randomised trial showed no major effect at 2 mg/kg for nine months, but was underpowered. Side effects include nausea, diarrhoea, rash, leucopenia, altered liver function (requiring long term blood monitoring), infection, and a theoretical risk of neoplasia. Azathioprine is metabolised by thiopurine methyl transferase and 10% of the population are heterozygotes and 0.3% homozygotes for its deficiency. Measurement of enzyme values identifies the heterozygotes, whose dose should be halved, and homozygotes, who should probably not be given the drug. It should not be used with allopurinol.

Cyclophosphamide is an alkylating agent, which predominantly depletes B lymphocytes. Intravenous cyclophosphamide in pulses of 1 g/m² monthly for up to six months induced notable improvement in 12 of 15 patients in one series. It is probably effective (level 3 evidence) but risks serious side effects on the bladder, marrow, and gonads. Oral cyclophosphamide 2 mg/kg is a simpler alternative with fewer short term side effects.

Cyclosporin A particularly inhibits T lymphocyte proliferation. In the largest series, all 14 patients improved either in disability or in relapse rate (level 3 evidence). Over half had adverse effects, including nephrotoxicity, hypertension, nausea, oedema, and hirsutism, so lower doses are now recommended, starting at 3–7 mg/kg daily and maintenance at 2–3 mg/kg.

Interferons are naturally occurring cytokines. Beta interferon 1a (Rebif) down regulates inflammatory responses and was beneficial in some small series at 44 µg subcutaneously three times weekly for about six months. The one randomised trial showed no benefit, but used only 22 µg three times weekly for three months in patients resistant to other treatments. Alpha interferon upregulates immune responses, and has been reported occasionally to cause CIDP and other autoimmune diseases. Nevertheless, it may be beneficial in CIDP, and 15 of 26 patients improved with alpha interferon 2a 2-3 MIU subcutaneously three times weekly for six weeks. Both interferons are very expensive but usually have only minor adverse effects.

There are a few reports of the efficacy in CIDP of methotrexate, tacrolimus (FK506), mycophenolate, etanercept, and autologous stem cell transplantation.

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