Neurol. Croat. Vol. 61, 3-4, 2012

Coexistence of neurosarcoidosis and

L. Radolović Prenc1, S.Telarović2,3, I.Vidović1, J. Sepčić4, L. Labinac Peteh1

ABSTRACT - is a multisystem infl ammatory disease of unknown etiology that predominantly aff ects the and intrathoracic lymph nodes, but in 6% of cases it also occurs in central or peripheral nervous system. Multiple sclerosis (MS) is an immune-mediated infl ammatory disease that attacks myeli- nated axons in the . Coexistence of sarcoidosis and other autoimmune diseases like MS is rarely reported in the literature. We present a case report of a patient with coexisting sarcoidosis and 67 MS, with a positive family history of MS. Symptoms of sarcoidosis appeared three years before the onset of Number 3-4, 2012 symptoms typical for MS. Similarity of demyelinating lesions in the nervous system, increased IgG in cere- brospinal fl uid and good response to corticosteroid treatment point to similar etiology. Th e onset of diseases like sarcoidosis and MS in the same patient over a period of only a few years opens the question whether the two separate entities come in sequence or the onset of sarcoidosis occurs during development of typical clinical presentation of MS.

Key words: sarcoidosis, encephalomyelitis, multiple sclerosis

INTRODUCTION lymph nodes (Figs. 1 and 2), or pathologic skin nodes or bone cysts, especially in hands, and posi- Sarcoidosis is an infl ammatory disorder of un- tive (2). Cerebrospinal fl uid (CSF) anal- known origin, characterized by ysis shows increased IgG, pleocytosis with protein- in various organs (1). Th e disease can 1 occur suddenly or gradually, followed by complete Department of , Pula General Hospital, Pula, or partial remission. Typically, the diagnosis of sar- Croatia 2School of Medicine, University of Zagreb, Zagreb, coidosis is confi rmed by a pathologic radiological Croatia fi nding of the , hypercalciuria and hyperglob- 3Zagreb University Hospital Center, Department of Neu- ulinemia, anergy to skin tests, higher value of angi- rology, Zagreb, Croatia otensin-converting enzyme (ACE), epithelial gran- 4Professor Emeritus, Postgraduate Studies, School of ulomas in histopathologic analysis of mediastinal Medicine, University of Rijeka, Rijeka, Croatia R. Radolović Prenc et al. Coexistence of neurosarcoidosis and multiple sclerosis Neurol. Croat. Vol. 61, 3-4, 2012

Fig. 1. Sarcoidosis. Microscopic view of Fig. 2. Sarcoidosis. Microscopic appearance of granulomatous reaction in the lymph node (HE, X40). noncaseous granulomas in the lymph node, arrow (HE, X200). orrhachia, hypoglycorrhachia and impaired blood brain barrier (BBB) (3). in the concentration of beta-microglobulin, ACE in serum and CSF, hypercalciuria, positive Kveim Although sarcoidosis primarily aff ects the lungs, in test and fi nding of Kveim specifi c IgG in CSF (6). 6% of cases neurologic symptoms are the fi rst indi- Pathognomonic radiological fi ndings of the lung cators of the disease. Although the symptoms of and bone, and histopathologic confi rmation of epi- sarcoidosis are diff erent from those of multiple thelioid are very important for defi ni- sclerosis (MS), patients with sarcoidosis and MS tive diagnosis (7). are of similar ages and both have damage to , myelopathy, demyelinating lesions of the MR analysis of CNS shows periventricular white central nervous system (CNS) and IgG in CSF, matter damages in a quarter of patients with neu- which can result in inaccurate diagnosis (4). rosarcoidosis. Th ese changes are diffi cult to distin- guish from damages in MS. Infl ammatory lep- Some forms of sarcoidosis are diffi cult to distin- tomeningeal scarring (adhesions), thickening guish from MS, especially if sarcoidosis aff ects op- 68 around the chiasm and nerve roots, subependymal tic nerve and . Myelopathy in sarcoido- granulomas, and microinfarcts as a sis usually manifests as chronic progressive para- result of secondary angiopathy suggest sarcoidosis, paresis as a consequence of compression, ischemia but not MS (8). Persistent contrast imbibitions of and/or parenchymal damage. Along with positive parenchymal lesions are related to granulomatosis Lhermitte’s sign, the only distinction of this mye- damages in sarcoidosis, which is rare in MS (9).

Number 1-2, 2012 Number lopathy from the chronic progressive form of MS is clinical presentation. Damage to the can be related to optical neuritis in MS (1). CASE REPORT In 50% of cases of neurosarcoidosis, ACE is elevat- ed in CSF, but it is not a specifi c feature of the dis- A man born in the mountainous area had a posi- ease (5). Intrathectal synthesis of IgG is not com- tive family history of MS. At the age of 32, medi- mon, but the increased permeability of BBB in sar- astinoscopy was performed due to enlarged coidosis can be useful on diff erential diagnosis mediastinal lymph nodes, with diagnosis of pul- against MS. Some researches showed a specifi c, lo- monary sarcoidosis treated with corticosteroids for cally formed IgG in the CSF of patients with sar- 18 months. Th ree years later, at the age of 35, par- coidosis, with positive reaction to Kveim substanc- esthesias of the right lower extremity followed by es (Kveim specifi c IgG) (6). gradually increasing weakness were observed. Th ese symptoms were transient. At the age of 38, Th e possible relapsing-remitting course of the dis- he felt pain in the left eye, with fogging and occa- ease, demyelinating damage detected on magnetic sional double vision, and he was admitted to the resonance (MR) analysis of CNS and positive IgG hospital. in CSF make the diff erential diagnostic resolution of MS and sarcoidosis. Th e diagnosis is fi nally con- In somatic status, asthenia and less painless subcu- fi rmed by laboratory tests that indicate an increase taneous nodules in lower legs were found. In neu- Neurol. Croat. Vol. 61, 3-4, 2012 R. Radolović Prenc et al. Coexistence of neurosarcoidosis and multiple sclerosis

rologic status, a mild right pyramidal defi cit, ab- pronounced on the right side. Laboratory fi ndings sence of abdominal skin refl exes bilaterally, right showed a slightly elevated component of comple- sided dysmetria and horizontal nystagmus on the ment C3. Paraprotein concentrations in serum left eye and hemihypesthesia on the right side of were normal, as well as the values of ACE and Ca the forehead were recorded. Routine examination in serum and urine. Brain MRI verifi ed dissemi- showed mild lymphocytosis and lower values of se- nated lesions suggesting MS lesions rum Ca and Mg, but without hypercalciuria, and by their size, shape and arrangement, without spi- slightly elevated levels of serum ACE. Hepatitis nal cord lesions (Fig. 3). Th erapy with oral pred- markers and serology for toxoplasmosis, syphilis nisone resulted in improvement. Th e patient was and borreliosis were normal. Cryoglobulins and discharged as a case of MS. antinuclear and antimitochondrial antibodies were negative. Values of the complement components Six years later, at the age of 49, he was rehospital- were normal. Analysis of HLA typing showed A1, ized due to numbness of the right leg and ataxia. A2, B5, DR 5, DRW6. Th e papillae of both optic Somatic status was normal. Walking was atactic nerves were pale. Radiographic evaluation of the and paraparetic, the patient used a crutch, with bi- lungs and respiratory functions showed normal lateral horizontal nystagmus, right pyramidal and fi ndings. In CSF, protein values were normal with cerebellar defi cit and urinary urgency. He received 10 sediment cells, , monocytes and 500 mg methylprednisolone as pulsed therapy over plasma cells. fi ve days in a total dose of 2.5 g and then tetracos- actide hexaacetate depot 1 mg intramuscularly, one Th e patient was discharged as a case of neurosar- vial per week for one month. Defi nitive diagnosis coidosis. During hospital stay, he received ACTH was MS. (Alexander’s scheme), followed by improvement. Five years later, at the age of 43, he was rehospital- ized due to walking trouble. Somatic status was CONCLUSION normal. Neurologic examination showed para- paresis, more pronounced in the right leg, and Today, plenty of additional searching facilitates ataxia with heeling on the right side and horizontal and simplifi es the diff erential diagnosis of neuro- nystagmus on the left eye. Analysis of visual evoked sarcoidosis and MS, but coincidence of these two potentials (VEP) showed dysfunction of both optic diseases is always possible. However, concurrence of both diseases is rarely reported in the literatu- tracts and somatosensory evoked potentials (SSEP) 69 dysfunction of aff erent pathways bilaterally, more re (10). Number 1-2, 2012 Our patient was diagnosed with clinically defi ni- tive MS, with positive family history of MS. Th ree years before the onset of MS symptoms, he devel- oped symptoms of sarcoidosis. Th e occurrence of both diseases in the same patient within several years opens a question whether it was a sequence of two independent nosologic entity, or the occur- rence of sarcoidosis (initial) during development of the typical clinical features of MS. Th e infl uence of T cell groups (myelin reactive T cells) and cy- tokines could be a unique causal mechanism for the occurrence of immune defi ciency in both dis- eases. Th e similarity of demyelinating damages in the neural axis, IgG in CSF, and effi cient response to corticosteroid therapy in MS and sarcoidosis point to at least a partially common etiopathoge- netic circuit. Th e possibility that a disturbed im- mune system in the presence of one disease (neu- rosarcoidosis) led to clinical appearance of the Fig. 3. SE (TR 2500, TE 25/110, SE TR 500, TE 20) other disease (MS) for which there was a genetic Unequal multiple bilateral disseminated lesions in the predisposition is also a topic for debate (11,12). white substances. Th e shape, size and arrangement of According to the current knowledge, the patho- white matter damages indicate MS. logic changes in sarcoidosis are caused by cell-me- R. Radolović Prenc et al. Coexistence of neurosarcoidosis and multiple sclerosis Neurol. Croat. Vol. 61, 3-4, 2012

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