Childhood chronic inflammatory demyelinating polyneuropathy: clinical course and long-term outcome

doi:10.1016/S0960-8966(00)00119-X

Neuromuscular Disorders

Volume 10, Issue 6, 1 August 2000, Pages 398-406

https://doi.org/10.1016/S0960-8966(00)00119-X Get rights and content

Abstract

We reviewed the clinical history, electrophysiologic and pathologic findings, and response to therapy of 16 children with chronic inflammatory demyelinating polyneuropathy. The majority presented with lower limb weakness. Sensory loss was uncommon. The illness was monophasic in seven children, relapsing in six, and three had a slowly progressive course. All patients were treated with immunosuppressive agents. In 11, the initial treatment was prednisolone. All had at least a short-term response but five went on to develop a relapsing course. Intravenous immunoglobulin was the initial treatment in four patients. Three responded rapidly, with treatment being stopped after a maximum of 5 months. In resistant chronic inflammatory demyelinating neuropathy, in addition to prednisolone and immunoglobulin, plasma exchange, azathioprine, cyclosporine, methotrexate, cyclophosphamide and pulse methylprednisolone were tried at different times in different patients. On serial neurophysiologic testing slowing of nerve conduction persisted for long periods after clinical recovery. Follow-up was for an average of 10 years. When last seen 14 patients were asymptomatic, two having mild residual deficits. Childhood chronic inflammatory demyelinating neuropathy responds to conventional treatment and generally has a favourable long-term outcome.

Introduction

Chronic inflammatory demyelinating neuropathy (CIDP) is rare in childhood. The literature on outcome in paediatric CIDP has described wide variation in course and ultimate prognosis. Of 12 children followed for at least 12 months by Simmons et al. [1] ten were asymptomatic and two had non-disabling symptoms when last seen, with eight off treatment for periods as long as 15 years. In contrast, Nevo et al. painted a more gloomy picture and proposed that there were two populations of children with CIDP. One group had rapid progression to peak disability, a monophasic course and early complete resolution of symptoms and signs. The second, larger, group showed clinical progression for 3 months or longer. Therapy was required for prolonged periods and there was considerable long-term morbidity [1].

Our impression was that the long-term outlook in this condition was, overall, favourable, and this prompted this study. We also examined the role of serial nerve conduction studies and the response to therapy with newer immunosuppressive agents.

Section snippets

Patients

We reviewed the medical records on all patients (eight) admitted to the Royal Alexandra Hospital for Children, Sydney, with a diagnosis of CIDP between 1973 and 1998. Eight patients referred from other specialist centres in New South Wales, or whose nerve biopsies had been reviewed by one of the investigators, (R.A.O), were also included. Seven of these patients were briefly described in a previous, primarily adult, study of CIDP [3].

All patients were under 14 years at the time of presentation

Clinical measures

Composite MRC scores for measurement of power was calculated for each patient [8]. The sum of the MRC scores for the shoulder abductors, wrist extensors, hip flexors and ankle dorsiflexors was added and divided by four. Functional status was also calculated according to the Rankin score [9] (0, asymptomatic; 1, symptoms non-disabling and not interfering with lifestyle; 2, symptoms leading to some restriction of lifestyle but no interference with the patient's ability to look after himself; 3,

Clinical findings

Eleven of the 16 children were female. The average age at presentation was 6 years 3 months (range 2 years 2 months to 13 years 9 months). Duration of symptoms at presentation varied from 5 days to 12 months (average 13 weeks). Antecedent events were described in nine patients, predominantly upper respiratory tract infections. Time to clinical nadir varied between 21 and 365 days.

At presentation all patients had difficulty walking. Weakness was clearly more severe in the lower limbs in eight

Acknowledgements

The authors wish to thank Professor J.M. McLeod and Drs J.H. Antony, J. Chaitow, H.M. Johnston, G. Wise and I. Wilkinson for permission to include their patients in this series.

References (21)

Y. Nevo
Childhood chronic inflammatory demyelinating polyneuropathy
Eur J Paediatr Neurol
(1998)
M. Vermeulen et al.
Plasma and gamma-globulin infusion in chronic inflammatory polyneuropathy
J Neurol Sci
(1985)
R.V. Colan et al.
Steroid-responsive polyneuropathy with subacute onset in childhood
J Pediatr
(1980)
K. Taku et al.
Gammaglobulin therapy in a case of chronic relapsing dysimmune polyneuropathy
Brain Dev
(1990)
Z. Simmons et al.
Chronic inflammatory demyelinating polyradiculoneuropathy in children: II. Long-term follow-up, with comparison to adults
Muscle Nerve
(1997)
Y. Nevo et al.
Childhood chronic inflammatory demyelinating neuropathies: clinical course and long-term follow up
Neurology
(1996)
P.A. McCombe et al.
Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases
Brain
(1987)
R.A. Lewis et al.
The electrodiagnostic distinctions between chronic familial and acquired demyelinative polyneuropathies
Neurology
(1982)
F. Cai et al.
Study of nerve conduction and late responses in normal Chinese infants, children and adults
J Child Neurol
(1997)
Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Report from an Ad Hoc...

There are more references available in the full text version of this article.

Cited by (89)

Neurologic Conditions Associated with Cavus Foot Deformity
2021, Clinics in Podiatric Medicine and Surgery
Immunomodulatory and immunosuppressor therapies in refractory chronic inflammatory demyelinizing polyneuropathy. Review of the literature
2021, Neurologia Argentina
La polineuropatía desmielinizante inflamatoria crónica (CIDP) se define como una neuropatía inmunomediada con recaídas y remisiones o un curso progresivo en el tiempo superior a 2 meses. En la mayoría de los casos el tratamiento con glucocorticoides, inmunoglobulina intravenosa (IgIV) o plasmaféresis (PE) permite la estabilización del cuadro clínico o logra la remisión completa.
Un grupo de pacientes, sin embargo, bien es refractario a dichos tratamientos o dependiente de los mismos, convirtiéndose en verdaderos desafíos, por lo cual hay necesidad de opciones terapéuticas eficaces y seguras como segunda o tercera línea de tratamiento.
El objetivo de la siguiente revisión es analizar la eficacia y la seguridad del rituximab y otros inmunomoduladores propuestos para el tratamiento de la CIDP refractaria.
Se realizó una revisión de la literatura científica sobre los distintos tratamientos en la CIDP. Para la búsqueda bibliográfica se utilizaron las bases de datos PubMed y Cochrane, utilizando como palabras claves: azatioprina, ciclofosfamida, micofenolato, CIDP y rituximab. Se incluyeron artículos en inglés, francés y español. Finalmente se seleccionaron 33 artículos.
El rituximab es una buena opción terapéutica en aquellos pacientes con CIDP refractaria que requieren tratamientos de segunda línea, siendo particularmente efectivo en las nodo-paranodopatías seropositivas. Aunque no existen trabajos comparativos entre los inmunosupresores de segunda línea randomizados doble ciego, el rituximab demostró una considerable efectividad, escasos efectos adversos y potencialmente menor tiempo de respuesta, en comparación con otros agentes inmunomoduladores utilizados.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is defined as an immune-mediated neuropathy with relapses and remissions or a progressive course over time greater than 2 months. In most cases, treatment with Glucocorticoids, intravenous immunoglobulin (IVIG) or plasmapheresis (PE) allows stabilization of the clinical picture or achieve complete remission. However, a group of patients is either refractory to these treatments or depends on them, becoming real challenges, for which there is a need for effective and safe therapeutic options as a second or third line of treatment.
The objective of the following review is to analyze the efficacy and safety of rituximab and other proposed immunomodulators for the treatment of refractory CIDP.
A review was carried out on the scientific literature that addressed the topic of treatment of CIDP. The PubMed and Cochrane databases were used for the bibliographic search. Keywords: Azathioprine, Cyclophosphamide, Mycophenolate, Inflammatory Demyelinating Polyneuropathy, Rituximab. Articles in English, French and Spanish were included. Finally, 33 articles were selected.
Rituximab is a good therapeutic option in those patients with refractory CIDP who require second-line treatments, being particularly effective in seropositive node-paranodopathies. Although there are no comparative studies between double blind randomized second line immunosuppressants, rituximab demonstrated considerable effectiveness, few adverse effects, and potentially shorter response time, compared to other immunumodulatory agents used.
Magnetic resonance neurography in diagnosing childhood chronic inflammatory demyelinating polyradiculoneuropathy
2021, Brain and Development
Peripheral nerve imaging is increasingly recognized as a powerful tool to evaluate nerve hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth diseases (CMT), whereas data in pediatric patients are limited.
We describe the case of a 15-year-old Japanese girl with asymmetric demyelinating polyneuropathy, who, at the age of 10 years, was initially diagnosed with a demyelinating form of CMT. Fluorescence in situ hybridization for peripheral myelin 22 was negative, and already-known pathogenic variants were not detected by whole-genome sequencing, and nerve conduction studies revealed multifocal conduction blocks. Over the next 5 years, the patient showed gradual improvement in muscle weakness and sensory disturbance without immunological treatment and was referred to our hospital.
At the age of 15 years, magnetic resonance (MR) neurography showed asymmetric multifocal fusiform enlargement of nerve roots, brachial and lumbosacral plexuses, and intermediated nerve trunks, as well as cranial nerves. Based on the MR neurography findings and multifocal nerve conduction blocks, she was diagnosed as having multifocal CIDP (multifocal demyelinating sensory and motor neuropathy [MADSAM]) according to the European Federation of Neurological Societies/Peripheral Nerve Society diagnostic criteria.
Clinical diagnosis of childhood CIDP is challenging because its neurological manifestations and nerve conduction study findings occasionally resemble those of inherited demyelinating neuropathies. MR neurography is helpful for the assessment of patterns of nerve hypertrophy; MADSAM-CIDP is characterized by multiple fusiform nerve enlargement, whereas CMT shows symmetric and diffuse nerve hypertrophy.
The MR neurography patterns would help in diagnosing pediatric demyelinating neuropathies.
Chronic inflammatory demyelinating polyneuropathy: Plasmapheresis or cyclosporine can be good treatment options in refractory cases
2019, Neuromuscular Disorders
Childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare condition, and the optimal treatment strategy is not well established, especially in refractory cases. We analyzed the clinical features and treatment outcomes of 14 cases of childhood CIDP with more than 12 months of follow-up. Of the 14 cases, 10 cases were considered refractory to the conventional first-line treatment. In the monophasic group (n = 6), plasmapheresis resulted in a better treatment response than did IVIG. Monophasic refractory cases (n = 4) were especially responsive to plasmapheresis. In the polyphasic group (n = 8), IVIG and plasmapheresis had comparable effects. Among them six polyphasic patients were refractory to the first-line treatment options and received additional immunosuppressants. Four treatment-refractory polyphasic patients received cyclosporine and achieved successful disease control. With regard to the long-term outcomes, six patients showed minimal symptoms and no relapse within 6 months. Our results suggest that early administration of plasmapheresis in a monophasic course and cyclosporine in a polyphasic course may be effective treatment options for refractory childhood CIDP.
Inflammatory Neuropathies
2017, Swaiman's Pediatric Neurology: Principles and Practice: Sixth Edition
Childhood CIDP: Study of 31 patients and comparison between slow and rapid-onset groups
2015, Brain and Development
Citation Excerpt :
Follow-up of nerve conduction studies was not analyzed in our series. Robust studies are also lacking on this topic in childhood, even if previous reports elicited a possible difference between clinical state and nerve conduction studies [5,8]. However, a recent work including 117 adult patients disclosed a correlation between electrophysiological measures and clinical response to treatment [17].
To describe 31 children presenting a CIDP; to compare patients with rapid-onset disease vs. patients with slow-onset disease, a rapid-onset disease being defined by a time to peak impairment of less than 8 weeks.
A retrospective chart review identified 31 patients completing criteria for childhood CIDP, with 24 “confirmed CIDP” and 7 “possible CIDP”. Data collected were time to peak impairment, clinical presentation, cerebrospinal fluid analysis, nerve conduction study, nerve biopsy, treatments. Evaluation at the end of follow-up was reported according to modified Rankin scale.
Thirteen patients (42%) exhibited symptoms in less than 2 months with more often cranial nerve abnormalities (38% vs. 6%, p = 0.059), and sensitive symptoms (62% vs. 11%, p = 0.0057). They evolved predominantly in a relapsing way (69% vs. 22%, p = 0.0047). Length of the disease was also longer in the rapid-onset group (5.5 years vs. 3.83 years) but without statistical difference. The slow-onset group exhibited more frequently ataxia at onset (28% vs. 8%, p > 0.05), and evolved predominantly in a progressive manner (61% vs. 15%, p > 0.05). Outcome was similar and good in the two groups. At least 3 out of the 4 major electrophysiological criteria were positive for 27/31 children (87%). Axonal involvement could be present very early. Immunoglobulins were given in 29 cases and corticosteroids in 22. A partial or complete recovery 1 month after first treatment was reported in 30 cases. Among second-line treatments, only azathioprine seemed effective in two out of three intractable children.
The differences noted between the two groups should be tested in wider populations. Electrophysiological criteria are restrictive and axonal involvement should be studied. Prospective trials are required to find out the best first and second line treatments.

View all citing articles on Scopus

View full text

Childhood chronic inflammatory demyelinating polyneuropathy: clinical course and long-term outcome

Abstract

Introduction

Section snippets

Patients

Clinical measures

Clinical findings

Acknowledgements

Eur J Paediatr Neurol

J Neurol Sci

J Pediatr

Brain Dev

Chronic inflammatory demyelinating polyradiculoneuropathy in children: II. Long-term follow-up, with comparison to adults

Muscle Nerve

Childhood chronic inflammatory demyelinating neuropathies: clinical course and long-term follow up

Neurology

Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases

Brain

The electrodiagnostic distinctions between chronic familial and acquired demyelinative polyneuropathies

Neurology

Study of nerve conduction and late responses in normal Chinese infants, children and adults

J Child Neurol