Intracerebral bleeding in a patient with neurosarcoidosis while on corticosteroid therapy.

Abstract: Neurosarcoidosis can have variable clinical manifestations. Intracerebral bleeding is very rare in the setting of neurosarcoidosis and has been reported only twice. In this report, we describe a patient with neurosarcoidosis who had intracerebral bleeding while on corticosteroid therapy, despite apparent clinical improvement.

Key Words: corticosteroids, intracerebral bleeding, neurosarcoidosis

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Sarcoidosis is a granulomatous disease of unknown cause that can involve multiple organs including the lungs, lymph nodes, liver, skin, eyes, and musculoskeletal system. (1) Central nervous system (CNS) involvement has been described in only 5% of cases and in the setting of disease in other organ systems. (2) Intracerebral bleeding as a manifestation or complication of sarcoidosis is extremely rare and has been reported only twice. (3,4) We describe a patient with neurosarcoidosis who had intracerebral bleeding while on corticosteroid therapy.

Case Report

A 25-year-old, previously healthy male was admitted to the American University of Beirut Medical Center with severe headache for 2 weeks and diplopia. There was no associated vomiting or alteration in the level of consciousness. On physical examination, the patient was afebrile, but he had pendular nystagmus, diplopia in all directions, and no gag reflex. The white blood cell count was 8,300/[mm.sup.3], with 57% neutrophils. Magnetic resonance imaging of the brain revealed a large infiltrating mass involving the brain stem, vermis, and thalamus, containing a hemorrhagic focus and a cystic complex component, and that demonstrated partial contrast enhancement predominantly in the brain stem component. The appearance was compatible with a primary CNS tumor (Figure, A). Serology for human immunodeficiency virus, syphilis, toxoplasmosis, hydatid, toxocariasis, and cysticercosis was unrevealing. Chest radiography revealed fine diffuse reticulonodular infiltrates in both lung fields. The tuberculin skin test result was negative. Serum angiotensin-converting enzyme (ACE) level was slightly elevated, at 50 U/L (normal range, 12 to 68 U/L). A computed tomography (CT) scan of the chest and abdomen revealed pretracheal lymph node enlargement with diffuse reticulonodular infiltrates, as well as multiple hypodense lesions in the spleen. Bronchoscopy showed no endobronchial lesions. A blind transbronchial biopsy specimen revealed noncaseating granulomas. Fungal and acid-fast stains on the lung tissue were negative. The patient was started on prednisone at 1 mg/kg per day (80 mg) for the presumptive diagnosis of sarcoidosis and was discharged. He had some improvement in his symptoms over the following week, and the dose of prednisone was dropped to 60 mg/d. One month later, he was readmitted with acute severe headache, vomiting, worsening diplopia, unsteadiness, and left upper extremity weakness. Physical examination revealed left-sided mouth deviation, inability to adduct the eyes bilaterally on conjugate gaze, and normal motor power. Magnetic resonance imaging of the brain revealed multiple foci of hemorrhage in the pontine area within the previously described brain stem lesion. There were also signs of hydrocephalus. The mass in the mesencephalus and the pons had decreased in size (Figure, B). Prothrombin, partial thromboplastin, and bleeding times were all within normal range. ACE level had decreased to 12 U/L. The bronchoalveolar fluid cultures for fungi and mycobacteria had remained negative. Repeat CT scan of the chest and abdomen showed a decrease in the reticulonodular pulmonary infiltrates and almost complete clearing of the splenic nodules. The mediastinal lymph nodes were unchanged. The patient received methylprednisolone at 1 g daily for 3 days and methotrexate at 2.5 g 3 times per week, which resulted in steady gradual clinical improvement. Twelve months later, he remains on low-dose steroids and methotrexate with no residual neurologic deficits.

Discussion

The spectrum of neurosarcoidosis is broad and includes involvement of the meninges, brain parenchyma, peripheral nerves, and spinal cord. (5) Because of the wide range of neuroradiologic findings and nonspecific clinical signs and symptoms, intracranial sarcoidosis can be mistaken for primary or metastatic brain tumors. (6,7) Several reports in the literature have described cases of neurosarcoidosis presenting as a mass in the cerebellopontine angle, (8) sphenoid wing, (9) brain stem, (10) fronto-temporal area, (11) cerebellum, (11) cavernous sinus, (12) and pituitary gland. (13) CT scan is generally not helpful in distinguishing brain lesions caused by sarcoidosis from other intracerebral masses. (14) Ultimately, the diagnosis of neurosarcoidosis relies on the combination of a compatible clinical and radiographic picture, the presence of noncaseating granulomas on histologic examination with negative mycobacterial and fungal cultures, and the lack of exposure to agents associated with granulomatous lung disease. (15) CNS tissue for pathologic confirmation is often difficult to obtain. However, since in most cases the disease is not confined to the CNS, tissue sampling from other organs may help in the diagnostic process. (2)

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Intracerebral bleeding in patients with sarcoidosis has been reported in two cases. The first report by Lavrnic et al (3) described a young woman with pulmonary sarcoidosis who had intracerebral hemorrhage 2 months after starting corticosteroid therapy. There was no evidence of neurosarcoidosis in that patient. The second case by Cipri et al (4) is that of a young man who presented with intracerebral bleeding and who later was found to have multiple intracerebral lesions. The diagnosis of sarcoidosis was confirmed by biopsy revealing noncaseating granulomas. In our patient, the disappearance of the splenic lesions, the decrease in the size of the mesencephalic and pontine mass, the marked improvement in the pulmonary infiltrates, and the decrease in the ACE level were all objective indications of response to corticosteroid therapy. It was therefore unusual for intracerebral bleeding to occur in the setting of such improvement.

Conclusion

Although rare, intracerebral bleeding is a concern in patients with neurosarcoidosis despite apparent response to therapy.

There are more things in heaven and earth, Horatio, than are dreamt of
in your philosophy.
--William Shakespeare, Hamlet

Acknowledgment

The authors thank Thurayya Arayssi, MD, for reviewing the manuscript and for her valuable input.

Accepted August 10, 2004.

References

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12. Strickland-Marmol LB, Fessler RG, Rojiani AM. Necrotizing sarcoid granulomatosis mimicking an intracranial neoplasm: clinicopathologic features and review of the literature. Mod Pathol 2000;13:909-913.

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RELATED ARTICLE: Key Points

* Neurosarcoidosis can masquerade as a brain tumor.

* Intracerebral bleeding can occur as a complication of neurosarcoidosis.

* Intracerebral bleeding with sarcoidosis can occur despite apparent response to corticosteroid therapy.

Ghenwa K. Dakdouki, MD, Zeina A. Kanafani, MD, Gisele Ishak, MD, Mukbil Hourani, MD, and Souha S. Kanj, MD

From the Division of Infectious Diseases and the Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut, Lebanon.

Reprint requests to Dr. Souha S. Kanj, American University of Beirut Medical Center Hamra, PO Box 113-6044, Beirut 110 32090, Lebanon. E-mail: [e-mail]