Determination of Angiotensin-Converting Enzyme Levels in Cerebrospinal Fluid Is Not a Useful Test for the Diagnosis of Neurosarcoidosis

Abstract

To the Editor. Recently , we questioned the clinical utility of determining the level of angiotens in-converting enzyme (ACE) in cerebrospinal fluid (CSF) for the diagno sis of neurosarcoidosis. The diagnosis of sarcoidosis, a multisystem granulomatous disor­ der of unknown etiology, is typically based on clinical signs and symptoms supported by radiographic findings and the presence of noncaseating epithelioid granulomas in more than one organ. Elevated serum levels of ACE, hypercalciuria, and hypercalcemia provide supportive, but not diagnostic, evidence of sarcoidosis . Approximately 5% of patients with sarcoidosis have neurologic involvement. When neurolog ic symptom s occur in the absence of other organ system abnormalities, the diagnosis of neuro­ sarco idosis is especially problematic. Measurement of CSF levels of ACE has been advocated as a means of distinguishing between neurosarcoidosis and other nonsarcoid neurologic dis­ ease ·processes. Although several scientific publications have supported the use of CSF ACE levels for the diagnosis of neurosarcoidosis , many of them are letters to the editor with little or no supporting data.! In the largest study reported in the literature, CSF ACE levels were determined in 32 patients with sarcoidosis, including 20 with a diagnosi s of neurosarcoidosis. This study reported elevated CSF ACE levels in 55% of patients with neurosarcoidosis, in 5% of patients with sarcoidosis not involving the central nervous system,' and in 13% ofpatients with other neurologi c diseases, Despite this apparent lack ofsensitiv­ ity and specificity, the authors concluded that the CSF level of ACE seems useful in the diagnosis of neurosarcoidosis. In an attempt to establish whether determination of CSF ACE levels should be a part of our laboratory test repertoire, we con­ ducted a retrospective chart review of 110 Mayo Clinic patients in whom the CSF level of ACE was measured to rule out neurosarcoidosis. Although CSF ACE levels were higher in patients with neurosarcoidosis than in patients without this diag­ nosis, considerable overlap in the CSF ACE levels between the two groups (Table I) limited the usefulnes s of the test for indi­ vidual patient s. The sensitivity and specificity of the test were 24% and 95%, respectively. In 5 of 9 patients (56%) with an elevated CSF ACE level, neurosarcoidosis was not diagnosed; 13 of 17 patients (76%) diagnosed with neurosarcoidosis had a nor­ mal CSF ACE level, and 5 of 93 patients (5 %) without neurosarcoidosis had an elevated CSF ACE level. Five of the 17 patient s in whom neurosarcoidosis was diagnosed were receiving