47‐Year‐Old Man with Left Leg Numbness

Clinical History and Imaging

A 47‐year‐old white, right‐handed man presented with abrupt onset of left leg numbness while he was at work. He walked around to try to restore circulation when it suddenly became paralyzed and noticed his left arm and leg began to contract rhythmically and involuntarily. There was no report of eye deviation, face involvement, or loss of consciousness. At the time of arrival to the hospital, the movements had stopped. He had no prior history of seizure or stroke. His past medical history was significant for migraine headaches, sinus allergies, chronic uveitis and a history of parathyroidectomy in the past. He had an episode of severe uveitis at age eight with bilateral eye redness and soreness and was treated with steroids and Cytoxan. His medications were oxymetazoline nasal spray for nasal congestion and daily prednisolone eyedrops. He has a 20‐year history of tobacco use and drinks alcohol socially. He denied any unusual exposure history and to his knowledge had never been exposed to tuberculosis. His family history was notable for a mother with breast cancer, and sister with Sjögren's syndrome who had uveitis as well.

On admission vital signs were unremarkable. He was awake, alert, and following commands. The physical and neurological exam was only remarkable for decreased sensation to light touch on his left lower extremity. Complete blood cell count and metabolic panel were all within normal limits. He was started on phenytoin 100 milligrams po tid and dexamethasone 8 milligrams iv q4h. MRI of the brain demonstrated an intra‐axial mass in the post‐central gyrus, measuring 2.7 × 1.5 × 2.2 cm: it was slightly hyperintense on T1, enhanced with gadolinium peripherally and hypointense on FLAIR with surrounding edema (Figure 1a). A CT scan of the chest, abdomen and pelvis demonstrated paraesophageal and mediastinal adenopathy with calcifications and was otherwise negative. Given his history and clinic findings, he was felt to most likely have metastatic disease to the brain and resection was recommended. A craniotomy was performed with resection of the right parietal brain mass.

Figure 1.

1a, b, c and d

Neuropathological Findings

Histologic examination of the resected specimen showed cerebral gray and white matter. At the gray‐white matter junction, multiple non caseating granulomata were identified (Figure 1b). The adjacent gray and white matter showed reactive gliosis but no evidence of a neoplastic process was noted. Scattered blood vessels with perivascular lymphocytes were also present including the leptomeninges. Each granuloma was composed of histiocytes with a peripheral rim of benign lymphocytes (Figure 1c) which were further characterized as T‐cell using immunohistochemistry for CD3 (figure 1d). Before arriving at the diagnosis, several other entities (fungal or mycobacterial infection) were ruled out with special stains including Periodic acid‐Schiff (PAS) and acid fast bacilli (AFB). Because of the presence of perivascular lymphocytic cuffing, vasculitis of the central nervous system (CNS) was considered; however, it was ruled out by the absence of fibrinoid necrosis (necrosis of the vascular wall due to the inflammatory infiltrate). Another important diagnosis that needed to be ruled out was a lymphoproliferative neoplasm involving the CNS. While angiocentric lymphocytic infiltrate is a common finding in lymphomas of the CNS, the lymphocytes looked cytologically normal and flow cytometry showed no clonal lymphocytic population. What is the diagnosis?

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.

Abstract

A 47‐year‐old white male with a history of uveitis, hypercalcemia and nephrolithiasis presented with acute onset partial seizure. On exam he had decreased sensation to light touch on his left lower extremity. A Brain MRI revealed a right frontal mass, which was initially thought to be a metastatic lesion or a primary brain tumor. However, biopsy of the lesion revealed it to be a non‐caseating granulomatous lesion consistent with neurosarcoidosis.