88th ENMC International Workshop: on chronic inflammatory demyelinating polyneuropathy

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1 Neuromuscular Disorders 12 (2002) Workshop report 88th ENMC International Workshop: Childhood chronic inflammatory demyelinating polyneuropathy (including revised diagnostic criteria), Naarden, The Netherlands, December 8 10, 2000 Yoram Nevo a, Haluk Topaloǧlu b a Tel-Aviv, Israel b Ankara, Turkey 1. Introduction The European Neuromuscular Center (ENMC) consortium on chronic inflammatory demyelinating polyneuropathy (CIDP held its first meeting in Naarden, The Netherlands, 8 10 December, Fourteen active participants from Australia, Canada, France, Germany, Israel, Italy, The Netherlands, Sweden, Turkey, UK and the USA attended the Workshop. Chronic inflammatory demyelinating polyneuropathy is a treatable chronic disorder of the peripheral nervous system, with predominantly motor involvement and an insidious onset over a period of months, or recurrent episodes. In children and adults both proximal and distal muscles are affected. Muscle stretch reflexes are absent or depressed. Laboratory findings include elevated cerebrospinal fluid protein with no increase of mononuclear cells. Electrophysiological and pathological studies show evidence of demyelination. Although in some children the course is monophasic with complete recovery, in others it is protracted, being either a slow-progressive, or relapsingremitting course, and resulting in prolonged morbidity and disability. 2. Differences in CIDP between adults and children The workshop was opened by P.K. Thomas (London, UK), who pointed out the differences in CIDP between adults and children. CIDP in adults is encountered in a number of different clinical variants: the commonest is a symmetric distal, generalized, or more rarely, proximally accentuated, predominantly motor syndrome. Less common variants include widespread multifocal neuropathy, focal brachial plexus, and isolated limb nerve and initial cranial nerve presentations, ataxic sensory neuropathy, and generalized neuropathy associated with multifocal central nervous system (CNS) involvement. In older subjects, usually in midlife or beyond, CIDP may be associated with benign monoclonal immunoglobulin-g (IgG) or, rarely IgA paraproteinemia. In children, most cases present with symmetric, mainly motor polyneuropathy, gait disturbance being the salient manifestation. A subacute onset evolving over 2 3 months seems to occur more frequently in children than in adults. Apart from a single description of a case associated with CNS involvement (presented in this Workshop by Dr Kornberg), the variant forms described in adults have not been documented. This may be a reflection of the smaller total number of cases. CIDP with paraproteinemia has not been described in children. CIDP in children responds to the same treatment modalities in adults, but the outcome appears to be more favorable. The subacute form responds satisfactorily in both children and in adults. 3. Clinical Characteristics Basil T. Darras (Boston, USA) reported that only 11 children with CIDP were seen at the Children s Hospital, Boston, during the last 10 years, which is approximately one case per year. Evidence of demyelination was found in all cases. Axonal features were noted in two cases. In a single case, the course was monophasic but chronic progressive. In 10 cases, the course was polyphasic with two to nine relapses, most of which were related to changes in treatment. The clinical findings were very similar to that published in the literature on CIDP in children, except for the fact that in this series the male:female ratio was reversed due to a far higher number of females in this group of /02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S (01)

2 196 Y. Nevo, H. Topaloǧlu / Neuromuscular Disorders 12 (2002) patients. Four of the eleven patients (36%) had a rather acute onset with a Guillain Barré type illness and then went on to develop a remitting-relapsing course. All four patients were discharged with a diagnosis of Guillain Barré syndrome (GBS); on review of their medical records, it seems that at initial presentation they could not be distinguished clinically from patients with GBS. 4. Electrodiagnostic features Antonino Uncini (Chieti, Italy) reported on seven children with a chronic indolently progressive neuropathy, in whom it was clinically difficult to distinguish CIDP from an inherited demyelinating neuropathy [1]. For this purpose he used four electrophysiological indicators of segmental or non-uniform conduction abnormalities within the individual nerves, or between different nerves. These abnormalities are considered characteristic of an acquired demyelinating neuropathy: (1) conduction block, which is the hallmark of focal demyelination; (2) terminal latency index which compares conduction in the distal and intermediate nerve segments; (3) conduction velocity difference.10 m/s between nerves of upper or lower limbs; (4) combination of abnormal median sensory action potential in presence of normal sural. Five of seven patients had at least two positive indicators. He concluded that searching for indicators of segmental, non-uniform demyelination by an extensive electrophysiological study may help to differentiate chronic, indolently progressive CIDP from CMT1. Andrew Kornberg (Melbourne, Australia) reported on two patients who presented with GBS where early (within the first week) markedly slowed motor conduction velocities (case #1 median m/s, case #2 ulnar 16.0 m/s). Both children responded to intravenous gammaglobulin, but subsequently represented with a subacute demyelinating neuropathy. Dr Kornberg reviewed the Royal Children s Hospital experience of GBS and CIDP patients (119 and 8, respectively) and identified other GBS-like presentations with very slow early nerve conduction velocities that subsequently presented as subacute demyelinating neuropathy or CIDP. Reviewing the literature on GBS conduction, velocities are usually preserved in the first week of the illness. He suggested that the observation of markedly slowed conduction velocities in the first week of a GBS illness may indicate a longer duration of illness and suggest a more protracted clinical course. 5. Pathology The pathological findings of CIDP were described by P.K. Thomas (London UK). The abnormalities observed in nerve biopsies may be capricious. The most important changes are inflammatory infiltrates, often around epineurial blood vessels, but not invading the vessel walls. These are usually a mixture of CD4 and CD8 T lymphocytes. The most characteristic finding is macrophage-mediated stripping of myelin from axons. Continued cycles of demyelination and remyelination can result in concentric Schwann cell proliferation around nerve fibers (onion bulbs). Subperineural and endoneural edema is often evident with prominent variation between different fascicles in the nerve. Axonal loss is variable. 6. MRI in CIDP Jiri Vajsar (Toronto, Canada) presented MRI findings of the cauda equina in CIDP. Together with Midroni they evaluated 16 CIDP patients aged years. MRI was read blindly by two radiologists and results were compared with 13 control patients with various peripheral nerve diseases other than CIDP. Intrathecal nerve root enhancement was seen in 11/16 CIDP patients and in none of the controls. Intraforaminal (at the spinal ganglia) enhancement was seen in all patients and controls, and extraforaminal nerve root enhancement was seen in 4/16 CIDP patients only. Three CIDP patients showed nerve root enlargement, while only one control patient with Charcot Marie Tooth disease revealed the same enlargement of the roots. MRI findings did not correlate with either disease activity and/or severity, or with any clinical or laboratory features in CIDP patients. 7. Diagnostic criteria The diagnostic criteria for adult CIDP were presented by P.K. Thomas (London, UK) [2]. Y. Nevo (Tel Aviv, Israel) reviewed the adult CIDP research criteria published by J.R. Mendell [3] and the diagnostic criteria for childhood CIDP [4]. Recently new diagnostic criteria for adult CIDP were suggested by Saperstein et al. [5]. Following the workshop, revised diagnostic criteria for childhood CIDP were proposed (Supplement). The major changes were defining the mandatory clinical criteria as: progression of weakness over at least 4 weeks, as well as acute cases with rapid progression (GBS-like presentation) with relapsing or protracted course (over 1 year). This definition is different from previous clinical criteria (progression over 2 months) and includes acute relapsing, as well as sub-acute cases. It was the panel s view that collecting more data on the outcome of all these cases will shed light on the clinical course and outcome of different categories of childhood CIDP. Antonino Uncini (Chieti, Italy), Jiri Vajsar (Toronto, Canada) and Basil T. Darras (Boston, USA) proposed revised electrodiagnostic criteria for childhood CIDP. These criteria are presented in the revised diagnostic criteria of childhood CIDP (supplement). The view of the workshop participants was that nerve

3 Y. Nevo, H. Topaloǧlu / Neuromuscular Disorders 12 (2002) biopsy should not be a required mandatory laboratory criterion for the definite diagnosis of childhood CIDP. 8. Therapy Alan Pestronk (St. Louis, USA) reviewed the immune pathogenesis and possible mechanisms of action of immunomodulating therapy in CIDP. CIDP and multi-focal CIDP are a T-cell group of mediated neuropathies. The antibodies are of the IgM, IgA, and IgG type. The antigens are mostly unknown, but are proteins. These neuropathies are responsive to steroids, to T-cell immunosuppressants such as cyclosporin A and methotrexate, and also to azathioprine. IVIg and plasma exchange are also effective. Childhood CIDP seems to be a T-cell mediated disease. There are no reports of anti-gm1, anti-mag or other antibodies in pediatric CIDP. Pieter van Doorn (Rotterdam, The Netherlands) presented his experience since 1980 of an open study of IVIg treatment of 85 patients, including 12 children. About 80% of patients improve after an initial course of IVIg (2 g IVIg/kg bodyweight). Response to IVIg was observed in all patients who had an untreated relapse in the past. Clinical experience suggests that a full IVIg course administered over 2 days (1 g/kg/day) may induce faster improvement compared to the standard dosage administered over 5 days (0.4 g/kg/day). Remission of disease after one or two IVIg courses is achieved in about 15% of patients, but the majority of patients need additional intermittent treatment with a dosage of g/kg once every 1 6 weeks (van Doorn, personal experience). A few patients now even need IVIg as the only treatment for over 15 years. In this series, the prognosis in children was not better compared to whole adult population. Others have suggested that patients with a younger age of onset may do better in general. The clinical response to IVIg is mostly good, but most patients need long-term IVIg treatment to maintain a good neurological condition. After long-term follow-up, most patients were in a good clinical condition. The results of a Cochrane Systematic Review on IVIg treatment in CIDP was presented by Ivo van Schaik (Amsterdam, The Netherlands). Five studies fulfilled all inclusion criteria. Only one study addressed the comparison between IVIg and plasma exchange. Both treatments seemed equally effective, but a useful analysis was not possible. Four studies addressed the comparison between IVIg and placebo. These were pooled and expressed as relative risks. The chance of improvement in disability within 1 month after IVIg treatment is 3.12-fold higher than after placebo (95% CI: ). This result should be interpreted with caution. Firstly, different disability scales were compared without any correction; secondly, both arms of cross-over studies were included and analyzed as a placebo-controlled study. To get around these problems, individual patient data (IPD) are necessary. Although children have been included the exact number is not known. The results of a Cochrane review on steroid treatment in CIDP were reported by Richard Hughes, London, UK. Published case series have concluded that steroids are beneficial in at least two-thirds of cases. In the only randomized trial [6] there were 35 evaluable patients, but seven were withdrawn because of breaches of protocol. With these patients omitted there was significantly more improvement in neurological impairment and median nerve motor conduction velocity in the patients who received prednisone, and those who did not. The conclusion that prednisone is beneficial cannot be regarded as robust, because of weaknesses in the trial design, including lack of allocation concealment, lack of observer blinding and withdrawal of patients so that an intention-to-treat analysis could not be conducted. Rudolf Korinthenberg (Freiburg, Germany) reported his experience in treating 12 boys and 9 girls with CIDP, whose data were collected from 15 German hospitals [7]. Treatment included corticosteroids, IVIg, azathioprine and plasmapheresis alone, or in combinations. Corticosteroids were successful in 8 of 11 patients as first line treatment; one child later showed a secondary loss of efficacy. Twelve patients received IVIg as the first treatment; in 11 this was successful. Eight required multiple doses for up to 48 months. At the end of the observation period in these 21 patients, 12 were off treatment for 3.8 (0.3 11) years and three were clinically stable, still being on treatment for 5 18 months. They were all free of symptoms, or showed only slight dysfunction. Six were still on treatment for years. Five showed a slight moderate impairment of gait, and one was unable to walk unaided. Marten Kyllerman (Gothenburg, Sweden) presented his policy to treat childhood CIDP by induction therapy with prednisolone 1 2 mg/kg for 6 weeks, tapered off during 4 6 weeks, and at the same time replaced by maintenance treatment with azathioprine 2 3 mg/kg for 2 3 years. This regimen was employed for more than 20 years in order to reduce relapses and to avoid corticosteroid dependency. Twenty children with CIDP, median age at onset 7.5 years, were re-investigated after a median of 12 years. None had had serious side-effects of the treatment. There were 1.7 relapses per patient in the subgroup with long-term combination treatment, compared to 2.8 in a subgroup with corticosteroids only, or corticosteroids combined with short-term combination treatment. Four of 20 had remaining mild distal muscle strength loss, and one was wheelchair bound. More than 30% had indications of a predisposing subclinical familial polyneuropathy complicated by the dysimmune reaction. In the discussion following this presentation, the workshop decided that since the distinction between hereditary and acquired neuropathies in childhood may be difficult, history of familial polyneuropathy will remain an exclusion criteria in the revised diagnostic criteria for childhood CIDP.

4 198 Y. Nevo, H. Topaloǧlu / Neuromuscular Disorders 12 (2002) Antonino Uncini (Chieti, Italy) reviewed the issue of interferons (IFNs) in CIDP. In the early nineties four independent reports described a rapid and quite dramatic improvement in five CIDP patients (one was a child) treated with type-i IFNs. These patients were severely affected, and unresponsive, or with a short-lived response to other treatments. In 1998, Gorson et al. [8] published the results of an open study using IFNg on 16 CIDP patients with moderate disability. The results were less encouraging: Nine patients improved in MRC and sensory score, but not in Rankin functional score. The recent, first double-blind, randomized controlled study utilizing IFNg in 10 patients showed no difference with the placebo in eight clinical measures and neurophysiological findings [9]. In conclusion, after the initial enthusiasm there is insufficient data as to whether type-i IFNs may have a place in CIDP therapy, and presently its use should be limited to patients refractory to conventional treatment. 9. Variant cases in childhood CIDP Andrew Kornberg (Melbourne, Australia) reported on a child with CIDP and CNS demyelination indistinguishable from multiple sclerosis. This 8-year-old girl presented 3 years previously with a 3-month history of progressive difficulty in walking. Examination showed increased tone, hyper-reflexia, bilateral clonus and upgoing plantars in her lower limbs. An MRI of the spine showed an expanded intra-medullary lesion at T5-T6 with peripheral enhancement and mass effect. A biopsy of the lesion was considered consistent with a low-grade astrocytoma. However, the features were relatively subtle and she was treated with dexamethasone and made a rapid recovery. She was lost to follow-up and re-presented with a 3 4 month history of slowly progressive upper and lower limb weakness. Investigations showed evidence of peripheral nerve demyelination with prolonged distal latencies, markedly slowed conduction velocities, conduction block and abnormalities in F-wave latencies. In addition, MRI of her brain revealed demyelination indistinguishable from multiple sclerosis. MRI of her spinal cord showed enhancement of the cauda equina nerve roots with no nodular components and no evidence of the tumour previously seen. CSF examination showed an elevated protein level. This suggested that the initial spinal presentation was a demyelinating event. Dr Kornberg stated that this case illustrates that CNS demyelination and CIDP can occur in childhood. Haluk Topaloǧlu (Ankara, Turkey) reported a case of chronic inflammatory neuropathy with central nervous system involvement in a girl who had been followed-up for 16 years. She initially presented with axonal form of GBS at 4 years of age. She showed gradual improvement over the months and again became ambulant. Approximately 10 years later, she relapsed with increasing motor weakness over days, preceded by generalized convulsions. CT scan and MRI of the brain were normal. Her repeated nerve conduction studies always denoted axonal damage. In due course she developed bilateral internuclear ophthalmoplegia which lasted about 6 months. Laboratory work-up was not in favor of known entities such as mitochondrial cytopathies. She became refractory to all modalities of treatment to include IVIg infusions, methotrexate and cyclosporin. Since age 16 she is wheel-chair bound. 10. Outcome Yoram Nevo (Tel Aviv, Israel) reviewed the outcome, course and prognosis of childhood CIDP. Nevo et al. [10] followed-up 13 patients for 1 13 years; three recovered during the first year, and 10 had residual weakness after an average follow-up of 6 years. Two subgroups were delineated. Three of four children who progressed to peak disability over less than 3 months had a monophasic course and complete recovery. None of the other nine children whose symptoms developed over 3 months to several years completely recovered. Seven had mild disability, and in two it was severe. Hattori et al. [11] described 10 children with CIDP. Children with rapid progression (,3 months) were more responsive to steroids. Rankin score after 1 6 years follow-up was 1 in 5 cases, 2 in 2 cases, 3 in 2 cases, 4 in 1 case. Simmons et al. [12] described 12 children, 10 (83%) of whom relapsed. At the end of a long-term follow-up 10 patients had a Rankin score of 0 and 2 patients scored 1. They found no correlation between rapid onset of symptoms and overall outcome or response to therapy in childhood CIDP. Association between rapid onset and better outcome was also not found in Drs Darras and Korinthenberg s patients. Pieter van Doorn (Rotterdam, The Netherlands) summarized the topic of outcome measures in CIDP. To assess outcome one needs to use clinical relevant scales that are simple, reliable, valid, and responsive in time. Different levels of assessment can be distinguished: impairment; disability; handicap; and quality of life. As yet, normal values for scales on these levels have been mainly obtained for the adult population. For reasons of clinical relevance, it is preferable to use scales that investigate disability or handicap, rather than scales measuring the level of impairment. Outcome measures that may be used are the Martin vigorimeter (.6 years), a muscle performance score (MRC sum score) and the 10 meter walking time (both difficult in very young children). When available, it is attractive to use more functional scales that evaluate ambulation or sitting, a child modified Rankin score, or a play-performance scale, as has been validated in children. R. Korinthenberg (Freiburg, Germany) reviewed the clinical scores used in studies on CIDP and GBS. Measurement of the clinical course in studies on chronic neuropathies has been performed using the Neurological Disability

5 Y. Nevo, H. Topaloǧlu / Neuromuscular Disorders 12 (2002) Score [13], standardized MRC scales on 6 30 muscle groups, quantitative myometry, psychometric motor performance tests, timed functional tests and ordinal functional scores. Functional scores are most easy to administer in prospective as well as in retrospective studies and, if constructed appropriately, their inter-rater reliability is high even in multicenter studies. Thus, in many studies performed in CIDP and GBS, changes in functional scores have been the primary aim of the statistical analysis. A functional score to be used in a study on childhood CIDP should be ordinal, i.e., that each step of the score should clearly depict an increased severity of dysfunction. Because the impairment of motor, sensory and vegetative function does not always occur in parallel, different scores for each of these domains are advisable. A score depicting quality of life in children cannot simply be taken from the adult literature (for example, Karnofsky scale, Rankin scale), because in adults usually quite different diseases have been addressed and self-care and independence have to be defined in a different way in children of varying ages. Acknowledgements We thank Professor V. Dubowitz, Professor A.E.H Emery and Professor A. Urtizberea for their scientific assistance. This Workshop was made possible thanks to the financial support of the European Neuromuscular Centre (ENMC) and ENMC main sponsors: Association Francaise contre les Myopathies (France) Deutche Gesellschaft für Muskelkranke (Germany) Telethon Foundation (Italy) Muscular Dystrophy Campaign (UK) Muskelsvindfonden (Denmark) Prinses Beatrix Fonds (The Netherlands) Schweizerische Stiftung für die Erforschung der Muskelkrankheiten (Switzerland) Verein zur Erforschung von Muskelkrankheiten bei Kindern (Austria) Vereninging Spierziekten Nederland (The Netherlands) And ENMC associate member: Muscular Dystrophy Association of Finland 11. Summary The workshop on childhood CIDP was the first meeting of a proposed Childhood CIDP Consortium. Clinical characteristics and the various available therapeutic options were discussed. The diagnostic criteria of childhood CIDP were revised. Initial practical considerations and optional therapeutic regimes to be used in future childhood CIDP trials were discussed. Dr Korinthenberg was chosen to suggest clinical scores for a paediatric CIDP study. The workshop decided on establishment of a childhood CIDP database on the ENMC Web site. Drs Haluk Topaloǧlu, Andrew Kornberg and Yoram Nevo were elected to perform this task. 12. Workshop participants: Professor Basil Darras, Boston, USA Dr Pieter van Doorn, Rotterdam, The Netherlands Professor Victor Dubowitz (ENMC) Professor Richard Hughes, London, UK Professor Rudolf Korinthenberg, Freiburg, Germany Dr Andrew Kornberg, Melbourne, Australia Dr Marten Kyllerman, Gothenburg, Sweden Professor Pierre Landrieu, Paris, France Dr Yoram Nevo, Tel-Aviv, Israel Professor Alan Pestronk, St. Louis, USA Dr Ivo van Schaik, Amsterdam, The Netherlands Professor P.K. Thomas, London, UK Professor Haluk Topaloǧlu, Ankara, Turkey Professor Antonino Uncini, Chieti, Italy Dr Jiri Vajsar, Toronto Canada Appendix A. Revised diagnostic criteria for childhood CIDP Mandatory clinical criteria: 1. Progression of muscle weakness in proximal and distal muscles of upper and lower extremities over at least 4 weeks, or alternatively when rapid progression (GBSlike presentation) is followed by relapsing or protracted course (more than 1 year). 2. Areflexia or hyporeflexia. A.1. Major laboratory features A.1.1. Electrophysiological criteria Must demonstrate at least three of the following four major abnormalities in motor nerves (or 2 of the major plus 2 of the supportive criteria): A Major 1. Conduction block or abnormal temporal dispersion in one or more motor nerves at sites not prone to compression. (a) Conduction block: at least 50% drop in negative peak area or peak-to-peak amplitude of proximal compound muscle action potential (CMAP) if duration of negative peak of proximal CMAP is,130% of distal CMAP duration. (b) Temporal dispersion: abnormal if duration of negative peak of proximal CMAP is.130% of distal CMAP duration.

6 200 Y. Nevo, H. Topaloǧlu / Neuromuscular Disorders 12 (2002) Recommendations: (a) Conduction block and temporal dispersion can be assessed only in nerves where amplitude of distal CMAP is.1 mv. (b) Supramaximal stimulation should always be used. 2. Reduction in conduction velocity (CV) in two or more nerves:,75% of the mean minus 2 standard deviations (SD) CV value for age. 3. Prolonged distal latency (DL) in two or more nerves:.130% of the mean 12 SD DL value for age. 4. Absent F waves or prolonged F wave minimal latency (ML) in two or more nerves:.130% of the mean 1 2SD F wave ML for age. 5. Recommendation: F wave study should include a minimum of 10 trials. A Supportive 1. When conduction block is absent, the following abnormal electrophysiological parameters are indicative of non-uniform slowing and thus of an acquired neuropathy: 2. Abnormal median sensory nerve action potential (SNAP) while the sural nerve SNAP is normal. 3. Abnormal minimal latency index (TLI) [1]. 4. Difference of.10 m/s in motor CVs between nerves of upper or lower limbs (either different nerves from the same limb for example left median versus left ulnar or the same nerve from different sides for example left versus right ulnar nerves). A.1.2. Cerebrospinal fluid (CSF studies) CSF protein.35 mg/dl. Cell count,10 cells/mm 3. A.1.3. Nerve biopsy features Nerve biopsy with predominant features of demyelination. A Exclusion criteria 1. Clinical features or history of a hereditary neuropathy, other diseases or exposure to drugs or toxins that are known to cause peripheral neuropathy. 2. Laboratory findings (including nerve biopsy or DNA studies) that show evidence for a different etiology other than CIDP. 3. Electrodiagnostic features of abnormal neuromuscular transmission, myopathy or anterior horn cell disease A Diagnostic criteria (must have no exclusion criteria): 1. Confirmed CIDP (i) Mandatory clinical features. (ii) Electrodiagnostic and CSF features. 2. Possible CIDP (i) Mandatory clinical features. (ii) One of the 3 laboratory findings. References [1] Uncini A, Parano E, Lange DJ, De Vivo DC, Lovelace RE. Chronic inflammatory demyelinating polyneuropathy in childhood: clinical and electrophysiological features. Child s Nerv Syst 1991;7: [2] Cornblath DR, Asbury AK, Albers JW, et al. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy. Neurology 1991;41: [3] Mendell JR. Chronic inflammatory demyelinating polyradiculoneuropathy. Annu Rev Med 1993;44: [4] Nevo Y. Childhood chronic inflammatory demyelinating polyneuropathy. Eur J Paediatr Neurol 1998;2: [5] Saperstein DS, Katz JS, Amato AA, Barohn RJ. Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve 2001;24: [6] Dyck PJ, O Brien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol 1982;11: [7] Korinthenberg R. Chronic inflammatory demyelinating polyradiculoneuropathy in children and their response to treatment. Neuropediatrics 1999;30: [8] Gorson KC, Ropper AH, Clark BD, et al. Treatment of chronic inflammatory demyelinating polyneuropathy with interferon-alpha 2a. Neurology 1998;50: [9] Hadden RD, Sharrack B, Bensa S, Soudain SE, Hughes RA. Randomized trial of interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 1999;53: [10] Nevo Y, Pestronk A, Kornberg AJ, et al. Childhood chronic inflammatory demyelinating neuropathies: clinical course and long term follow up. Neurology 1996;47: [11] Hattori N, Ichimura M, Aoki S, et al. Clinicopathological features of chronic inflammatory demyelinating polyradiculoneuropathy in childhood. J Neurol Sci 1998;154: [12] Simmons Z, Wald JJ, Albers JW. Chronic inflammatory demyelinating polyradiculoneuropathy in children: II. Long-term follow-up, with comparison to adults. Muscle Nerve 1997;20: [13] Dyck JP. Quantitating severity of neuropathy. In: Dyck JP, Thomas PK, editors. 3rd. Peripheral neuropathy1993. pp