Neurosarcoïdose et mycophénolate mofétil

doi:10.1016/S0035-3787(07)90423-3

Revue Neurologique

Volume 163, Issue 4, April 2007, Pages 471-475

https://doi.org/10.1016/S0035-3787(07)90423-3 Get rights and content

Résumé

Introduction

La neurosarcoïdose est une pathologie rare (5 cas pour 1 million d’habitants) et d’étiologie inconnue. L’atteinte neurologique est révélatrice de la sarcoïdose dans 50 p. 100 des cas, et elle reste limitée au système nerveux dans 10 p. 100 des cas. Son polymorphisme clinique et iconographique rend son diagnostic difficile. La corticothérapie en première intention, puis les immunosuppresseurs classiques sont préconisés, mais leurs contre-indications, leurs effets secondaires, et leurs toxicités ne sont pas négligeables. Lorsque la neurosarcoïdose devient résistante aux traitements usuels, l’attitude thérapeutique n’est pas codifiée. Le mycophénolate mofétil (MMF) est utilisé dans de nombreuses pathologies neurologiques dysimmunitaires, avec des résultats très satisfaisants et une bonne tolérance, mais aucun cas de neurosarcoïdose traitée par MMF n’est actuellement rapporté.

Cas clinique

Nous rapportons l’observation de 2 patientes présentant une neurosarcoïdose traitée par MMF et corticoïdes.

Conclusion

Une efficacité clinico-radiologique rapide et durable a pu être notée, permettant une diminution progressive de la corticothérapie, avec une excellente tolérance clinique et biologique.

Summary

Introduction

Neurosarcoidosis is a rare (5 cases for one million) immune-mediated disease generally observed in young adults. Neurological symptoms are present in the half of patients, and symptoms remain limited to neurological system in 10p.cent. Histological criteria are mandatory to prove the diagnosis. The sensitivity and complications of biopsy are variable. The best sensitivity appears to be achieved with muscle biopsies which in addition have a lower risk of complications. Neurosarcoidosis is usually treated with corticosteroid therapy and immunosuppressive drugs (cyclophosphamide, cyclosporine, aziathoprine, methotrexate), but frequently resists standard schedules. In addition the many contraindications, side effects and cumulated toxicities of immunosuppressive drugs compromises their use. Knowledge of the effectiveness of other treatments would therefore be useful. Mycophenolate mofetil (MMF) has been used for treatment of many immune-mediated neurological diseases, like polymyositis, multifocal motor neuropathy, myasthenia or chronic inflammatory demyelinating polyradiculoneuropathy. MMF is efficient and well tolerated, but there is no case-report about neurosarcoidosis.

Case report

We report two observations of young patients (14 and 27 years) with a diagnosis of resistant neurosarcoidosis treated with MMF (2 g/j) and corticosteroids. A significant and rapid effectiveness was clinically and radiologically observed, with good clinical and hematologic tolerance.

Conclusion

The MMF seems to be an interesting rescue treatment for neurosarcoidosis. Further evaluation is needed.

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Sarcoidosis is an immune-mediated, multisystem, inflammatory disorder of unknown etiology, which primarily affects pulmonary and lymphatic systems as well as skin. The pathologic hallmark of sarcoidosis is noncaseating epithelioid granulomas, which develop in the affected organs. Uncommonly, both central and peripheral nervous systems are affected by sarcoidosis, and patients with neurosarcoidosis present with a wide spectrum of neurologic manifestations due to the widespread nature of the underlying illness. While nervous system involvement in sarcoidosis is uncommon, in a certain number of patients, neurologic symptoms can be the initial and exclusive manifestation of sarcoidosis. Neurosarcoidosis is a great imitator of other pathologies and high clinical vigilance is required to diagnose it correctly. A discussion of the clinical features, underlying pathophysiology, and present management options for neurosarcoidosis is presented.
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In 2 series of patients with neurosarcoidosis, less than half achieved significant improvement on corticosteroid therapy, and most relapsed when corticosteroids were reduced to less than the 20 to 25 mg/d range.70,77 For these reasons, corticosteroid-sparing medications are often considered, including hydroxychloroquine,78 chloroquine,78 methotrexate,77 mycophenolate mofetil,79,80 azathioprine,81 cyclophosphamide,77,82 infliximab,83,84 and adalimumab.85 Although based on limited data, infliximab seems to be particularly effective.84,86,87
Neurosarcoidosis as an MS Mimic: The trials and tribulations of making a diagnosis
2015, Multiple Sclerosis and Related Disorders
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For prolonged courses of prednisone above 20 mg per day, prophylaxis against opportunistic infection including Pneumocystis jirovecii should be considered. Steroid sparing medications used for that purpose include azathioprine, methotrexate, hydroxychloroquine, cyclosporine A (Vargas and Stern, 2010; Stern, 2004; Hoitsma et al., 2010; Lacomis, 2011) and mycophenolate mofetil (Moravan and Segal, 2009; Chaussenot et al., 2007). Mycophenolate mofetil has primarily been used to treat mucocutaneous and gastrointestinal manifestations of sarcoidosis, but has now also shown good tolerability and efficacy in the treatment of neurosarcoidosis (Chaussenot et al., 2007).
The clinical presentation of neurosarcoidosis is varied as multiple levels of the neuraxis may be affected. When central nervous system involvement occurs, making an accurate diagnosis of the condition can be challenging, especially given the current definition for definite neurosarcoidosis requires histologic confirmation of the affected tissue (brain biopsy). This article will review our current knowledge and manifestations of neurosarcoidosis, discuss the current diagnostic approach as well as the challenges associated with a condition requiring histologic confirmation, discuss the current treatment approach, and highlight the challenges of this diagnosis with a few real-life clinical cases. We also highlight the selected differential diagnosis of neurosarcoidosis as well as multiple sclerosis which could mimic each other.
Spinal cord neurosarcoidosis
2014, American Journal of the Medical Sciences
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SN may be relatively refractory to corticosteroids compared with involvement of other organs with sarcoidosis.7,29 Frequently, effective treatment requires corticosteroids plus additional immunosuppressant therapy including methotrexate, azathioprine, cyclosporine, leflunomide, mycophenolate mofetil, adalimumab and cyclophosphamide.27,29–35 More recently, infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been used to treat neurosarcoidosis resistant to corticosteroids4,27,30,36–39 and cyclophosphamide.40
Spinal cord neurosarcoidosis (SN) is problematic to diagnose because it mimics other inflammatory0020neurologic diseases. The authors report the clinical features of 29 SN cases.
They retrospectively reviewed the medical records of 29 histologically proven sarcoidosis patients with spinal cord involvement seen at 3 university medical centers. They collected clinical data including laboratory and radiological findings. Clinical outcomes were assessed retrospectively using the modified Rankin scale.
The cohort included high number of African Americans (16/29, 55%). The lung and intrathoracic lymph nodes were the most common confirmatory biopsy sites (18/29, 62%), whereas the spinal cord was a relatively uncommon one (4/29, 14%). The most common presenting symptoms were lower extremity weakness and paresthesias. Thoracic segment was most frequently involved (21/27, 78%). Lesions were mostly intramedullary (22/27, 81%), although nearly half involved the leptomeninges (13/27, 48%). The average size of a lesion spanned 3.9 spine segments (range, 1–9); 17 of 22 (77%) intramedullary patients had $3 spine segments involved. Angiotensin-converting enzyme levels in cerebrospinal fluid were elevated in only 2 of 11 (18%) patients. All patients received glucocorticosteroids. Additional immune-modulating agents were used in 24 of 29 (83%) patients. Scores on the modified Rankin scale at the final follow-up visit were improved.
Most SN cases were diagnosed indirectly based on extraneural tissue biopsy. Extended spinal cord lesion ($3 spine segments) may be useful to distinguish SN from multiple sclerosis. Cerebrospinal fluid analysis was of limited value. Most patients experienced clinical improvement with immunosuppressive treatment, but many required combination therapy.
Neurologic manifestations of sarcoidosis
2014, Handbook of Clinical Neurology
Citation Excerpt :
Mycophenolate mofetil is an inhibitor of monophosphate dehydrogenase, which is an important enzyme in purine synthesis, attenuates B and T cell proliferation. It has primarily been used to treat mucocutaneous and gastrointestinal manifestations of sarcoidosis, but has now also shown good tolerability and efficacy in the treatment of neurosarcoidosis (Chaussenot et al., 2007). It is increasingly used as the alternative drug of choice by the authors because of its ease of use, low toxicity profile, and apparent efficacy.
Neurologic manifestations occur in more than 5% of sarcoidosis patients and may be the presenting feature. Neurosarcoidosis can manifest in a myriad of ways including: cranial neuropathy, aseptic meningitis, mass lesions, encephalopathy, vasculopathy, seizures, hypothalamic-pituitary disorders, hydrocephalus, myelopathy, peripheral neuropathy, and myopathy. Because its etiology is unknown, its neurological manifestations are so diverse, and its diagnosis cannot be readily confirmed by laboratory tests, neurosarcoidosis poses many clinical problems. The diagnosis of neurosarcoidosis is usually based on the identification of characteristic neurologic findings in an individual with proven systemic sarcoidosis as established by clinical, imaging, or histologic findings. Although corticosteroids are regarded as the foundation of treatment, they are not always successful and have serious side-effects. Moreover, some patients with neurosarcoidosis are refractory to conventional therapy, and approximately 5–10% die. Optimal management of patients with neurosarcoidosis benefits from an understanding of the broad clinical spectrum of neurosarcoidosis, appreciation of the ways to best confirm a diagnosis, and awareness of the full range of treatment options, including the use of alternative therapies such as immunotherapy.

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Brève communicationNeurosarcoïdose et mycophénolate mofétilNeurosarcoidosis treated with mycophenolate mofetil: two cases

Résumé

Introduction

Cas clinique

Conclusion

Summary

Introduction

Case report

Conclusion

Chest

Chest

Chest

Lancet

The first case of sarcoidosis treated with mycophenolate mofetil

Br J Dermatol

Therapeutic considerations in patients with refractory neurosarcoidosis

Arch Neurol

Endobronchial biopsy positive sarcoidosis: relation to bronchoalveolar lavage and course of disease

Respir Med

Neurosarcoidosis: signs, course and treatment in 35 confirmed cases

Medicine

Neurological manifestations in sarcoidosis: review of the literature, with a report of 23 cases

Ann Intern Med

Neurosarcoïdose. neurology

Manifestations cliniques et approche thérapeutique de la neurosarcoïdose

Rev Neurol (Paris)

Statement on sarcoïdosis

Am J respire Crit Care Med

Radiation therapy for neurosarcoidosis: report of three cases from a single institution

Radiat Oncol Invest

The pathogenesis and treatment of optic disc swelling in neurosarcoidosis: a unique therapeutic response to infliximab

Arch neurol

Mycophenolate mofetil may serve as a steroid-sparing agent for sarcoidosis

Br J Dermatol

Brève communication
Neurosarcoïdose et mycophénolate mofétilNeurosarcoidosis treated with mycophenolate mofetil: two cases