Final Diagnosis -- Neurosarcoidosis

DIAGNOSIS

Neurosarcoidosis.

DISCUSSION

Neurosarcoidosis is known as a great masquerader. It can involve any part of the nervous system during the course of its multisystem inflammatory nature, mimicking virtually all forms of neurological symptoms (3). It is estimated that about 5-15% of the patients develop neurologic symptoms due to neurosarcoidosis. The most common manifesting locations in the nervous system include cranial nerves, the pituitary and the hypothalamus, brain stem and spinal cord (3) (2,5,9,10). Multiple or less common solitary intracranial mass lesions are seen about 5-10% of neurosarcoidosis cases (3, 9) The pathogenesis of sarcoidosis is non-caseating granulomas, which is similar to other granulomatous disorders such as tuberculosis, parasites, lymphoma, coccidiomycosis, and as a matter of fact, sarcoidosis is a diagnosis of exclusion. Microbiologic studies can rule out infectious etiologies. The most common systemic manifestations of sarcoidosis result from involvement of intra-thoracic lymph nodes, lungs, ocular and skin lesions (4, 5)

Neurosarcoidosis should be kept in mind in differential diagnosis of a wide variety of neurological conditions especially when there is a suggestive finding from the clinical scenario. In our case, we initially thought the nature of the solitary intracranial space occupying lesion in a 47-year-old Caucasian man was a brain neoplasm, most likely a metastasis, glioma or lymphoma. However, upon reviewing his past medical history, the possibility of neurosarcoidosis was very likely.

Pulmonary and intra-thoracic lymph node involvement can be seen in more than 90% of patients with sarcoidosis (5, 6). The most common symptoms are cough and some respiratory difficulties due to interstitial lung disease, which were noted in our patient too but was attributed and treated as allergy symptoms. It is reported that about 23-26% of patients with sarcoidosis develop uveitis during its course and 2-10% of patients with uveitis have sarcoidosis (1). Other forms of ocular involvement such as keratoconjunctivitis sicca very similar to Sjögren's syndrome or even secondary cataract have also been reported in the literature (7). Hypercalcemia and nephrolithiasis can complicate sarcoidosis. The incidence of hypercalcemia ranges from 2 to 63% depending on a number of variables such as exposure to sun light, genetics, dietary calcium and skin color (4). Hypercalciuria occurs more frequently than hypercalcemia. Although our patient had a history of parathyroidectomy in the past and his hypercalcemia and renal stone disease were attributed to his hyperparathyroidism, we didn't find any imaging documentation in his medical record, suggesting that sarcoidosis might have contributed to the hypercalcemic state. Sarcoidosis is more frequently seen in African Americans, Irish and Scandinavian decedents. Its incidence is about three times higher in blacks than white Americans (4, 5) However, it can affect all races at any ages (5).

The diagnosis of sarcoidosis is usually made by biopsy in the context of clinical settings. The pathologic hallmark of sarcoidosis is non caseating granulomata, which are mainly composed of lymphocytes, multi-nucleated giant cells, epithelioid histiocytes, and fibroblasts (8). Other diagnostic tests such as measuring ACE levels can be helpful but are less accurate (5).

The patient's sister's diagnosis is significant because sarcoidosis has been noted to cluster in families, and it is generally thought that there are inherited genetic predispositions to the disease. In addition, sarcoidosis can present with dry eyes and dry mouth (ocular and parotid involvement) and can be difficult to distinguish from Sjögren's. The patient appeared to have plump cheeks, which may have been due to a slightly stocky build. However his parotid glands felt slightly firm, raising the question of Heerfordt syndrome. This is also known as uveoparotid fever and consists of uveitis, parotid enlargement, and cranial nerve palsies (4).

From our case presentation, it is possible that neurosarcoidosis can present as a solitary intracranial mass lesion and should be considered in the differential diagnosis especially in constellation of other findings such as intra-thoracic lymphadenopathy, uveitis or hypercalcemia.

REFERENCES

1. Babu BM, Rathinam SR. (2010) Intermediate uveitis. Indian J Ophthalmol.58(1):21-27.
2. Hoitsma E, Drent M, Sharma OP. (2010) A pragmatic approach to diagnosing and treating neurosarcoidosis in the 21st century. Curr Opin Pulm Med.16(5):472-479.
3. Hoitsma E, Faber CG, Drent M, Sharma OP (2004) Neurosarcoidosis: a clinical dilemma. Lancet Neurol.3(7):397-407.
4. Holmes J, Lazarus A (2009) Sarcoidosis: extrathoracic manifestations. Dis Mon.55(11):675-692.
5. Lannuzzi MC, Rybicki BA, Teirstein AS (2007) Sarcoidosis. N Engl J Med.357(21):2153-2165.
6. Lazarus A (2009) Sarcoidosis: epidemiology, etiology, pathogenesis, and genetics. Dis Mon.55(11):649-660.
7. Rothova A (2000) Ocular involvement in sarcoidosis. Br J Ophthalmol.84(1):110-116.
8. Terushkin V, Stern BJ, Judson MA, Hagiwara M, Pramanik B, Sanchez M, Prystowsky S (2010)Neurosarcoidosis: presentations and management. Neurologist.16(1):2-15.
9. Uruha A, Koide R, Taniguchi M (2009) Unusual Presentation of Sarcoidosis: Solitary Intracranial Mass Lesion Mimicking a Glioma. J Neuroimaging.
10. Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, Scadding JW, Thompson EJ, Chamoun V, Miller DH, McDonald WI, Mitchell D (1999) Central nervous system sarcoidosis--diagnosis and management. QJM.92(2):103-117.

Contributed by Ali Mahta, MD, Ryan Y Kim, BA, Ali G. Saad, MD, Santosh Kesari, MD, PhD