Ss Spinal Neurosarcoidosis Mimicking an Idiopathic Inflammatory Demyelinating Syndrome Necraj Kumar, MD; Elliot M, Frohman, MD, PhD Background: Intramedullary neurosarcoidosis may be the first and only manifestation of the disease and may mimic an idiopathic inflammatory demyelin- ling syndrome both clinically and on neuroimaging results, Metheds and Results: Two patients who were seen initially witha relapsing-remitting neurologic course and 1 cervical intramedullary lesion on magnetic resonance imaging findings are reported. Both proved to have net- rosarcoidosis. A computed axial tomographic scan of the chest showed hilar adenopathy, which provided a clue to the diagnosis, Conelustons: Symptoms duc to an intramedullary cer vical lesion ean be the first manifestation of neurosarcotd- sis, The clinical course can mimic a demyelinating ill- ness. high index of suspicion and a search for sarcoidosis atextraneural sites are required foran early diagnosis, Se- roid treatment is associated with a favorable outcome. “Arch Neurol. 2004;61:586-589 From the Department of Neurology, Mayo Clini Rochester, Minn (Dr Kumar) and the Department of Neurology and Ophthalmology The University of Texas Southiestern Medical Center at Dallas (Dr Frohman). Downloaded From: https: LINICAL INVOLVEMENT OF the central and/or periph- eral nervous system ac ccurs in 5% of patients with sarcoidosis.' On autopsy about L4 bof patients with sarcoidosis have central nervous system involvement Ap- proximately 50% of patients with neuro- sarcoidosis initially have neurologic mani- {estations. In the remainder of patients, the neurologic manifestations appear within 2 ars of the diagnosis of sarcoidosis.’ The ‘most common sites of involvement in sar coidosis are the lungs and pulmonary lymph nodes. Neurosarcoidosis is most commonly associated with granuloma- tous infiltrates involving the meninges, hy- pothalamus, pituitary gland, and cranial nerves.” Spinal sarcoidosis is relatively un- common and can manifest as intramedul- lary lesions, intradural extramedullary oF extradural lesions, cauda equina syn- drome, and arachnoidiis." We report 2 pa- tients with a cervical cord lesion in con- junction with clinical manifestations suggestive of a myelopathy. In both pa- tients, a diagnosis of an idiopathic inflam- matory demyelinating syndrome was con- sidered likely. Further, the results of ‘magnetic resonance imaging (MRI) showed characteristics that were distinctively con- spicuous for an intra-axial process with a concomitant leptomeningeal component. (aepnuyreo) ARCH NEDROUNOUaT, APE Sor ees J CASE L 27-year-old African American woman ‘was symptomatic with numbness involy- ing the right arm, trunk, and leg in De cember 1997. This resolved spontane- ously in 2 weeks. In September 1998, she developed numbness involving the me- dial aspect of both hands, The MRI r. sults ofthe cervical spine showed a gado- liniui-cnhancing lesion within the spinal cord at Co-7 (Figure 1). the lesion ap- peared tobe localized to the posterior pect of the spinal cord. On sagittal s quences, i was dificult to differentiate Whether the lesion was exclusively intra tial or whether there vas @ component of leptomeningcal involvement. The MRI resulls of the brain were normal. Cere- brospinal fluid studies; levels of anti- nuclear antibodies, angiotensin-con- verting enzymes, and vitamin Bs syphilis and Lyme serologies; and chest radio- griphic and purified protein derivativeskin test results were all normal. The patient was treated with intravenous methylpred- nisolone (1 g daily for 3 days) and im- proved significantly. She was diagnosed as having an idiopathic inflammatory demsy- clinating syndrome. In February 1999, she developed an episode of right facial murmb- (©2004 American Medical Association, All rights reserved. jamanetwork.comy on 02/22/2021Downloaded From: https: Figure 4. SagitalT-wightad (A) and axial (8 that appar to Rae abroad tase verte surlace fhe cord ness with right facial hypesthesia, which resolved spon- taneously in a few days. Her general medical and neu- rologic examination results were unremarkable. Repeated cervical spine MRI results showed persistent enhance- ment ofthe cervical cord lesion, Repeated brain MRI re- sults Were again unremarkable ‘A computed axial tomographic scan ofthe chest re- vealed hilar adenopathy, and diffuse echogenic lesions were scen in the liver and spleen on the abdominal com- puted axial tomographic scan, A repeated angiotensin- converting enzyme level test showed values were el- evated at 121 U/L (reference range, 7-46 U/L) Transbronchial biopsy results identified noncaseating grinulomas consistent with sarcoidosis, She was pre- scribed oral prednisone at 60 mg/d. She developed no re currence of neurologic symptoms; the spinal cord le- sion and anglotensin-converting enzyme levels decreased, and the prednisone was tapered across 1 year. CASE 2 ‘A 3o-year-old man had been symptomatic since July 1999 With slowly progressive numbness involving the hands and feet, Cervical spine MRI results were remarkable for an en hancing intramedullary lesion at C4-C5. A biopsy of the lesion was performed, and a review of the slides revealed evidence of mild acute inflaammation and benign Hbrous Uissue, He was given steroids in the postoperative period, (aepeay TED) TECH NEDROUVOL@T APES cl cord magnate reanance mages shoving dos lated enhancing nama estan (rons) and his paresthesias showed significant improvement. In October 1999, he developed a recurrence ofthe paresthe- sias, which progressed slowly intially and then more rap- ily for the months prior to his evaluation, He was symp- tomatic with numbness below the neck and decreased ability to appreciate hot and cold sensations, on the right side more than the elt, He had difficulty opening jars and some coordination difficulty with his legs, His neuro- logic examination results showed decreased perception of pinprick, temperature, and touch from C4 downward, on the right side more than the left. Strength, tone, and co- ordination were intact. His reflexes were symmetrically brisk, and the plantar responses were flexor. His gait was, normal, and Romberg test resuils were negative Cervical spine MRL results (Figure 2) revealed a 2-cm lesion inthe dorsal part ofthe cervical cord at C4-C5. The lesion appeared to be infiltrated over the posterior cord surface and showed pronounced contrast enhancement. Also noted were anterior and posterior leplomeningeal enhancements, Brain and thoracic cord MRI results were normal, Normal values were obtained from a hemo- gram, and for vitamin B,,, folate, liver enzymes, angio- tensin-converting enzymes, immunoelectrophoresis, thy- rolropin, and antinuclear antibodies. Evoked potential studies (brainstem, visual, and somatosensory) and re sults of spinal fluid analysis were normal. A computed axial tomographic scan of the chest showed bilateral hilar and mediastinal adenopathy. Thefigure 2. SopitalT-usightd cena cord magne reeonacs image soning a hyactaee2-m lion with ervieacorda te C4 lees. 8, Pesigadonium Twit magts resonates age shang protouced conta, ‘hamid ard dol portions fethaneeent wih ane and pater plomeningel nksnesmen ar). bronchoalveolar lavage showed numerous macrophages and sparse inflammatory cells, predominantly histio- cytes, Transbronchial biopsy results showed a compact, well-cireumscribed noncaseatin Langerhans and foreign body-type multinucleated giant cells with abundant eosinophilic cytoplasin, eb} Wis rare for intramedullary spinal sarcoidosis to be thei snuloma composed of Uial or only manifestation of the disease.** In our 2 re- ported cases, there were no systemic symptoms. Never- theless, both had hilar adenopathy, which led to the diagnosis of neurosarcoidosis, The age range for intra- medullary sarcoidosis s 15 1068 years (median, 35 years). In spinal sarcoidosis, the cervical region is most com- monly involved.* The clinical picture is usually that of « myelopathy with paraparesis, quadriparesis, hypesthe- sias, and bladder and bowel dysfunction all being well- described symptoms.” Intramedullary neurosarcoidosis is known to mimic a spinal cord tumor both clinically and radiologically. Spontaneous remissions and relapses and steroid-induced improvement can lead to a clinical pic- lure that resembles an inflammatory demyelinating dis- case, This is well illustrated by the 2 cases presented, Both patients had an enhancing cervical cord le- sion that appeated to infiltrate over the posterior cord surface, The second ease described had ev terior and posterior leptomeningeal enhancement. It has been suggested that with early inflammation there is lin- cat leptomeningeal enhancement along the surface of the spinal cord.” Spread of the leptomeningeal inflamma- Lory process to the Virchow-Robin spaces is believed to resull in parenchymal involvement, which appearsas di butragular margin (trou) win > With consolida- fuse cord enlargement on MRI results don, 1 of more discrete masses form, and with resoli- tion ofthe inflammatory phase, the cord returns to normal Ultimately, these processes eat culminate in spi- nal cord atrophy.” The MRI characteristics of spinal new- rosarcoid lesions depend on the stage ofthe illness, Most findings can be relatively nonspecific, but the presence of an infiltrating lesion with meningeal and intramedul- lary enhancement should increase the suspicion for sar- coidosis or other granulomatous diseases. Enhance- ment patterns are variable and can include linear leplomeningeal enhancement or focal, multifocal, oF dif fuse intraparenchymal enhancement; often, there is a broad base on the cord surface and the enhancement does not involve the full cord thickness.™™ A decrease in MRI enhancement can be seen as patients improve.” In neurosarcoidosts, extradural spinal disease is rare and can involve the vertebral bodies." Sarcoid spon- dylodiseitis and paraspinal mass have been reported, Enlarged cervical nerve roots, not evident om MRI re- sults but evident on a myelogram, have been de- scribed." Intradural extramedullary space occupying the leston'” and intraspinal epidural mass secondary to sat- coidosis can occur, Intradural extramedullary findings include pial enhancement, root nodules, and clumping, Enhancing cauda equina lesions mim- fcking subarachnoid tumor seeding can occur." Intra- appear as an enhancing intramedullary lesion, cord enlargement, cord atrophy oF diffuse and focal T2-weighted signal hyperintensi- ties.” The only abnormality may be abnormal enhance: ment with normal cord appearance on T1- and T weighted images.” Multiple small nodules on enhanced T1-weighted cervical cord MRI results ean occur." Cases medullary disease can intially‘of spinal sarcoidosis with unique MRI findings due to he- mosiderin deposition®? and caleification” in the lesion have been described. Also described is a case of spinal sarcoidosis mimicking syringomyelia on MRI results.” 1m both our patients, the diagnosis was provided by transbronchial biopsy results. Infact, in our second pa- tient, the spinal cord biopsy’ results did not provide the di- agnosis, The granulomas inthe spinal cord and brain are ‘often poorly formed, are smaller than the systemic le- sions, and have fewer giant cells For this reason, the spinal cord lesions can mimic an intramedullary tumor on frozen section.** Further attempts at wide surgical exei- sion can lead to increased morbidity. Case reports of pax tients undergoing spinal cord biopsy in intramedullary spi- nal sarcoidosis suggest a high morbidity and mortality." Intramedullary spinal sarcoidosis should be care fully considered as a possibility in a patient with known sarcoidosis who develops a radiculopathy or myelopa- thy. On rare occasions, intramedullary spinal sarcoid~ ‘osis may be the initial manifestation of sarcoidosis, Mani- festation mimicking a cord neoplasm is more common, bbut a relapsing-remitting neurologic course can occur. ‘An infiltrating intramedullary cord lesion with lepto- meningeal enhancement should bring to mind the pos- sibility of sarcoidosis. A systematic search for evidence of extrancural sites of involvement should be manda- tory in such cases. Even inthe absence of systemic symp- toms, targeting such sites for potential biopsy can result in the identification ofthe disease process with substan- tially less morbidity than sampling neural tissue. A high index of suspicion for the diagnosis is required because carly intervention is associated with a favorable out- ‘come. Progressive deterioration, nontesponsiveness 10 ste- roids, and an enlarging cord mass should prompt recon- LaF, Gasman Ro atc inthe haan pi: pect of anes ard aoa response'o strod hap. 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J Comput Asst, Tomogr 188216880652 naga, Hara Yamoto M, Yoshida. Acae of sad oases: hye ve roo sling dems mysegahy pines. Fi sho Shia. 109232384360, Barua Glsuer FE, SR, Sih GH. acids ofthe carve pial e- rales ep. Nevosurpey 1783216218 Weissmen Lage Kel BaeaK Abel. nasi piu saci is case report Neursurgey 19869-17918, uz Post MD, Gas Wt Infanmstay nits pr vil pte. Nerimagng Cin A195 40-25. ace MK Tats, Tusa S Kong, Tuoinen lad newoss- ois: MR ings ad pablo colton. Acta Fala 2002 Ser. ine Ese AD. Sarcoidosis of te cna neous syst, Neroimagng ‘lin, 10-114- 158 oft an Wang prs regener ae sideration of the diagnosis. In such cases, performing a Mra Src es pergasaycramet biopsy of neural tissue may be inevitable 21 Yona Yu Stel Hope Sha Ac sets pn essing Accepted for publication August 13,2003. sacar Thathorcontbutions: Sid concept and design (Drs 2 Wate Sa Tank Wl AR np otras Kumarand Frohman); acquisition of data (Drs Kumar and Men Ra DOR TES TET : 2 Wan Mae oa AB Gn. tanta Frohman); analysis ard interpretation of data (Dts Kumar" MGM E ewe Sone bo erate and Frohman): drafingfthe manuscript (Drs Kumar and 2 Wane ace hes Asal ewe pdr oping Frobinan); crt revision ofthe manuscript or important htt pasa asian icing speech intellectual content (Dr Frohman); administrative, techni- os eee Shih Eusabe Alsen Spins eord sacoidoss WY ‘al, and material support (Dr Kumar); study supervision (De (esha erie Cn Frohman) 25 Sar Path Ks DA Mopaticmsaroos gps ae Corresponding author Eliot M. Frohman, MD, PhD, > ates i ay 1 DBT Deparment of Newolagy and Ophthalmology, The Unie 2 Tanna owe at aman asa, Ys Si ‘caper pre myepny. ipa 7 re of ne Souter ade Ceterat Dall 5229 ag. Ler oar ote 8 mans ros elliot jrohman@utsouthwestern. cd). Sime se Soin snare tsuen: N27 22 Sonn pet Rhu Semen pr sei fpr na 7 29 86 EE itn 0, ce ena aed sari Sis mpl acoA Ararat ab 708 1 Sams Kn A ne, Sat as Sanco: 5 faa Ser Lamy odo fic pots inane Ao hr hes 7 in negate eas 2. Rr Cal Seco cneptingereen neh, 92a ater an et anti st gee aap. Ann Pa S672 ropa rey Pc errr (©2004 American Medical Ass ‘Downloaded From: https:/jamanetwork.com/ on 02/22/2021 lation, All rights reserved.