Treatment of peripheral nerve disorders

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Abstract
The beauty of looking after people with peripheral nerve disorders is the ability of the Schwann cells to remyelinate and peripheral nerve axons to re-grow. Peripheral nerve specialists should be the envy of stroke doctors and those who care for patients with degenerative disorders and Parkinson's disease. Nevertheless we have been relatively slow compared with our colleagues to capitalize on this advantage and provide the randomized controlled trials on which to base practice. The Cochrane Collaboration has developed methods for reducing bias in preparing reviews of the available evidence, which may not all be published, and its library provides a convenient source of references. Despite their rarity, the potential for interrupting ongoing nerve damage with immunomodulatory drugs has made the presumed autoimmune inflammatory neuropathies the target of many therapeutic trials. For instance in 1985, a large North American trial in Guillain–Barré syndrome established plasma exchange as an efficacious treatment, significantly hastening recovery when started in the first four weeks of the illness and especially the first week [1]. This result has been amply confirmed by other, notably French trials, and the evidence summarized in the relevant Cochrane review [2]. In 1992, van der Meché and colleagues [3] conducted a trial showing no difference in efficacy between intravenous immunoglobulin and plasma exchange, a conclusion which is matched by the updated systematic Cochrane review (Hughes et al. 2005, personal communication) which now includes two trials of intravenous immunoglobulin in children, one showing that 1.0 g/kg daily is effective in mild disease and one that 2.0 g/kg given over 2 days does not have any different effect from the same total dose spread over 5 days [4]. Against all expectations corticosteroids are not beneficial in Guillain–Barré syndrome. The most recent Dutch trial showed a trend towards more rapid recovery in those who received intravenous methylprednisolone 500 mg on five consecutive days in addition to intravenous immunoglobulin [5]. In a meta-analysis of all the corticosteroid trials, the updated Cochrane review does not show significant benefit from corticosteroids (Hughes et al. 2005, personal communication). There remains a dearth of studies designed to assess the best dose of intravenous immunoglobulin. Despite modern treatment 10–20% of patients die or are left disabled and more have persistent fatigue so that new therapeutic strategies are needed. Chronic inflammatory demyelinating polyradiculoneuropathy has also been convincingly shown in randomized trials to respond to plasma exchange and intravenous immunoglobulin at least in the short-term [6,7]. Despite only limited evidence from randomized controlled trials, case series and clinical experience suggest that corticosteroids are also effective [8]. Multifocal motor neuropathy responds to intravenous immunoglobulin but not usually to corticosteroids or plasma exchange [9]. For both chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy there is a dearth of information about the efficacy of immunosuppressive and immunomodulatory drugs and an urgent need for trials to try agents such as methotrexate, mycophenolate mofetil, ciclosporin and rituximab, which are frequently used on theoretical grounds alone. It is shocking that 50 years have gone by without the profession solving the simple question of whether corticosteroids are beneficial in Bell's palsy [10]. Although inflammatory, no serious proposals that it might be autoimmune have been made and much evidence points to herpes simplex virus infection being the causative mechanism. Consequently antiviral agents have been tried but only three small trials have been published and it remains unclear whether antiviral agents are effective [11]. In a condition with a high rate of spontaneous recovery non-randomized studies are unlikely ever to resolve whether treatments are beneficial.