Baumann, T.

Brutsche, M.

Fluri, F.

Sollberger, M.

Sonnet, S.

Steck, A.

Tamm, M.

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J Neurol (2004) 251 : 760–761DOI 10.1007/s00415-004-0432-1M. SollbergerF. FluriT. BaumannS. SonnetM. TammA. J. SteckM. BrutscheSuccessful treatment of steroid-refractoryneurosarcoidosis withinfliximabReceived: 20 November 2003Received in revised form: 21 January 2004Accepted: 6 February 2004Sirs: Sarcoidosis is a systemic,granulomatous disorder of un-known origin, rarely affecting thenervous system [1]. There are pa-tients with chronic disease whosecourse is progressive while on ther-apy with corticosteroids and im-munosuppressive medicaments [2].Several lines of evidence indicatethat tumor-necrosis factor-α (TNF-α) plays a key role in the inflam-matory process of some human au-toimmune diseases [3]. Infliximab,a chimeric monoclonal human-murine IgG antibody directedspecifically against TNF-α, hasproved effective not only in refrac-tory rheumatoid arthritis andCrohn’s disease, but also in sys-temic sarcoidosis [4, 5]. We report acase of neurosarcoidosis refractoryto previous treatments in which in-fliximab was associated with amarkedly improved clinical out-come.In April 2001 a 45-year-old mandeveloped slowly progressivenumbness and paresthesia of thefeet, ascending to the knee, erectiledysfunction and adynamia. Un-steadiness in walking and pares-thesia of the hands followedrapidly. Examination in October2001 showed signs of a rightvestibulo-cochlear dysfunction to-gether with distally pronouncedsensory disturbances of the lowerextremities and gait ataxia.Laboratory investigations dis-closed a hypogonadotropic hypo-gonadism. The cerebrospinal fluidanalysis revealed an elevated pro-tein level of 4344 mg/L (normal180–480 mg/L), a lymphocytosis of47x106/L (< 4.7x106/L) and an ele-vated serum angiotensin-convert-ing enzyme of 8 U/L (< 3 U/L).Nerve conduction studies indicateda demyelinating, sensorimotorpolyneuropathy of the upper andlower extremities. MRI of the brainrevealed a prominent infundibu-lum with homogeneous gadolin-ium-enhancement. MRI of the lum-bar spinal cord showed nopathology. Computed tomographyof the chest disclosed bilateral hilarand mediastinal lymphadenopathywith normal lung parenchyma.Biopsy findings of a hilar lymphnode were consistent with sar-coidosis.The patient was treated withoral prednisone 50 mg daily, lead-ing to an about 50 % regression ofthe sensory symptoms within 3months. Because of a Cushing’ssyndrome, associated with osteope-nia, azathioprine (200 mg/day) wasinitiated in February 2002 in con-junction with prednisone taper to10 mg/day.Three months later the patientdeveloped a subacute conus-syn-drome with an arachnoiditis at theconus-cauda level (Fig.). Adminis-tration of intravenous methylpred-nisolone (500 mg/day for 3 days),followed by augmentation of pred-nisone to 20 mg/day was withouteffect. Over the next 6 months thesensory disturbances, the vertigoand the unsteadiness in walkingprogressed.Because of the continuous dete-rioration of the neurological condi-tion while on immunosuppressivetherapy, infliximab (500 mg,5 mg/kg of body weight) was ad-ministered intravenously in Febru-ary 2003 in conjunction with aza-thioprine taper to 50 mg/day.Infliximab was given again at 2, 8,14, 20 and 26 weeks without ad-verse effects. A few days after thefirst dose the numbness of the feetand the fatigue diminished, fol-lowed within weeks by regressionof the gait ataxia and withinmonths by regression of the auto-nomic dysfunctions.Examination in September2003, after 6 infliximab applica-tions, showed diminution of theright vestibulo-cochlear dysfunc-tion, the spinal cord symptomsand the gait ataxia. The distallypronounced sensory disturbancesof the lower extremities were simi-lar to those at the onset of the dis-ease. MRI of the lumbar spinalcord and the brain disclosed com-plete resolution of the lesions(Fig.) and cerebrospinal fluidanalysis showed a normalization ofthe cell number (3x106/L) and adecrease of the protein level to904 mg/L. Nerve conduction stud-ies showed no significant improve-ment compared to baseline.Our patient presented with abiopsy-proven progressive neu-rosarcoidosis, involving the hy-pophysis, the right vestibulo-cochlear nerve, the spinal cord andthe peripheral nervous system, re-fractory to corticosteroids and aza-thioprine. He experienced a re-markable clinical improvementwith infliximab. There were no ad-verse effects associated with inflix-imab. Our findings are consistentwith two recent case reports inwhich infliximab proved effectivefor patients with refractory neu-rosarcoidosis [6, 7].LETTER TO THE EDITORSJON 1432761References1. Lower EE, Broderick JP, Brott TG,Baughman RP (1997) Diagnosis andmanagement of neurological sarcoido-sis. Arch Intern Med 157:1864–18682. Zajicek JP, Scolding NJ, Foster O,Rovaris M, Evanson J, Moseley IF, et al.(1999) Central nervous system sar-coidosis–diagnosis and management.QJ Med 92:103–1173. Andreakos ET, Foxwell BM, BrennanFM, Maini RN, Feldmann M (2002) Cy-tokines and anti-cytokine biologicals inautoimmunity: present and future. Cy-tokine Growth Factor Rev 13:299–3134. Baughman RP, Lower EE (2001) Inflix-imab for refractory sarcoidosis. Sar-coidosis Vasc Diffuse Lung Dis 18:70–745. Yee AM, Pochapin MB (2001) Treatmentof complicated sarcoidosis with inflix-imab anti-tumor necrosis factor-alphatherapy. Ann Intern Med 135:27–316. Pettersen JA, Zochodne DW, Bell RB,Martin L, Hill MD (2002) Refractoryneurosarcoidosis responding to inflix-imab. Neurology 59:1660–16617. Katz JM, Bruno MK, Winterkorn JM,Nealon N (2003) The pathogenesis andtreatment of optic disc swelling in neu-rosarcoidosis: a unique therapeutic re-sponse to infliximab. Arch Neurol60:426–430M. Sollberger () · F. Fluri · T. Baumann ·A. J. SteckDepartment of NeurologyUniversity HospitalPetersgraben 44031 Basel, SwitzerlandTel.: +41-61/265-5431Fax: +41-61/265-4491E-Mail: marcsollberger@hotmail.comS. SonnetDepartment of NeuroradiologyUniversity HospitalPetersgraben 44031 Basel, SwitzerlandM. Tamm · M. BrutscheDepartment of PneumologyUniversity HospitalPetersgraben 44031 Basel, SwitzerlandFig. Initial and post-treatment MRI-studies: Sagittal T2 weighted (A) and contrast-enhanced T1 weighted (B)MRI of lumbar spine before treatment show nodular hypointense, contrast-enhanced leptomeningeal lesionssurrounding conus and cauda equina with enlargement at the conus-cauda level. Post-treatment sagittal T2weighted (C) and contrast-enhanced T1 weighted (D) MRI of lumbar spine show complete remission of the le-sions with normal appearance of the conus and cauda equina.

Successful treatment of steroid-refractory neurosarcoidosis with infliximab

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Successful treatment of steroid-refractory neurosarcoidosis with infliximab

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