FINAL DIAGNOSIS: NEUROSARCOIDOSIS
Postmortem studies have demonstrated that central nervous system involvement of sarcoidosis is more common than the actual clinical manifestations of this disease would suggest (3). In fact, clinically silent neurosarcoidosis may also be demonstrated radiographically in up to 10% of patients with known systemic sarcoidosis (6) Despite this, only approximately 5% of all patients who suffer from sarcoidosis will report neurological symptoms (7). Patients who present with neurosarcoidosis in the absence of systemic manifestations are exceedingly rare (2)
Recognizing neurosarcoidosis in the absence of systemic disease is a diagnostic challenge as there are no clinical or radiographic features unique to this disease. Meningitis, encephalopathy, seizures and hydrocephalus are only a few of the nonspecific presentations neurosarcoid patients may exhibit. Signs and symptoms of central nervous system involvement classically mimic other disease processes such as autoimmune, vascular or demyelinating processes (1).
The imaging findings of neurosarcoid are also nonspecific and may involve any part of the neuroaxis. Lesions may be either enhancing or nonenhancing in the parenchyma, meninges and bone. Nevertheless, there are findings that may favor neurosarcoid. Leptomeningeal enhancement, diffuse or nodular, is the most common radiographic finding in neurosarcoid, present in 40% of cases (6). Intraparenchymal lesions are seen as nonenhancing periventricular white matter lesions that have high signal intensity on T2 and FLAIR, as seen in this patient (figure 5 and 6). These findings may be difficult to distinguish from demyelinating or vascular processes. Mass lesions within the parenchyma may also enhance, mimicking a primary or metastatic tumor (2). The literature suggests that in the context of known systemic disease, MRI may be up to 97% sensitive for central nervous system involvement (2,3). In the absence of known sarcoidosis, the specificity and sensitivity of the above mentioned findings are substantially less. MRI remains the study of choice for monitoring progression of disease.
As there are no individual clinical or pathologic features specific for this disorder, the diagnosis of sarcoidosis requires clinicopathologic correlation and the exclusion of other causes of granulomatous inflammation. Non-necrotizing granulomas, often perivascular in location with relatively sparse lymphocytic infiltration (i.e., naked granulomas), are the histologic hallmark of sarcoidosis. Since tuberculosis, fungi, spirochetes and other disorders may cause identical pathology, a purely histologic diagnosis of sarcoidosis can not be made (7). Hence, most pathologic specimens should not be signed out more definitively than "non-necrotizing granulomatous inflammation consistent with sarcoidosis". In contrast with meningitis or cerebritis caused by microorganisms, the clinical course of neurosarcoidosis is typically more indolent and the CSF glucose is usually normal. A history of systemic sarcoidosis is also very helpful in the diagnosis of neurosarcoidosis. When the diagnosis of neurosarcoidosis is suspected in the absence of systemic findings, tissue biopsy from enhancing lesions should be strongly considered to direct further treatment.
We have presented a patient with subclinical systemic sarcoidosis, who presented with progressive encephalopathy and seizures thought to be secondary to hepatic failure. Autopsy revealed clear evidence of systemic sarcoidosis also involving the central nervous system. The patient's hepatic failure may have overshadowed the clinical consideration of other potential underlying etiologies. A history of mediastinal lymphadenopathy was discovered only after extensive review of the patient's medical records. In the absence of clinical pulmonary disease, this finding was not further evaluated. While hepatic encephalopathy may have accounted for the patient's confusion and seizure disorder, it is less likely that it could account for MRI findings in the cerebellum and leptomeninges, both of which were suggestive of neurosarcoidosis. As encephalopathy and seizures have a reported incidence of 5-10% in patients with neurosarcoidosis, this disease process could have accounted for this patient's presentation (7). In fact, the post mortem studies demonstrated leptomeningeal involvement of the cerebral cortex, cerebellum and midbrain by sarcoidosis, which may be compatible both with the imaging studies and clinical findings in this patient.
Contributed by Luis M. Tumialán, M.D., Meenakshi Gupta, M.D., Stephen Hunter, M.D., Luis Tumialán, M.D.