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 angiotensin-converting enzyme (ACE) in cerebrospinal fluid (CSF) for the diagnosis of neurosarcoidosis. The diagnosis of sarcoidosis, a multisystem granulomatous disorder 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 neurologic symptoms occur in the absence of other organ system abnormalities, the diagnosis of neurosarcoidosis is especially problematic. Measurement of CSF levels of ACE has been advocated as a means of distinguishing between neurosarcoidosis and other nonsarcoid neurologic disease 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.1Rubinstein I Hoffstein V Angiotensin-converting enzyme m neurosarcoidosis (letter].Arch Neural. 1987; 44: 249-250Crossref PubMed Scopus (7) Google Scholar, 2Chan Seem CP Norfolk G Spokes EG CSF angiotensin-converting enzyme in neurosarcoidosis 1 letter).Lancet. 1985; 1: 456-457Abstract PubMed Scopus (39) Google Scholar, 3Ahmed S Angiotensin-converting enzyme and neurosarcoidosis llettej].Chest. 1991; 99: 1054Crossref Scopus (4) Google Scholar, 4Rubinstein I Central nervous system sarcoidosis |letterJ.J Neurosurg. 1986; 65: 265PubMed Google Scholar In the largest study reported in the literature, CSF ACE levels were determined in 32 patients with sarcoidosis, including 20 with a diagnosis 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,5Oksaner V Fynrquist F Somer H Qronhagen-Rlska C Angiotensin converting enzyme in cerebrospinal fluid: a new assay.Neurology. 1985; 35: 1220-1223Crossref PubMed Google Scholar and in 13% of patients with other neurologic diseases.6Oksanen V New cerebrospinal fluid, neurophysiological and neuroradiological examinations in the diagnosis and follow-up of neurosarcoidosis.Sarcoidosis. 1987; 4: 105-110PubMed Google Scholar Despite this apparent lack of sensitivity 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 conducted 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 diagnosis, considerable overlap in the CSF ACE levels between the two groups (Table 1) limited the usefulness of the test for individual patients. 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 normal CSF ACE level, and 5 of 93 patients (5%) without neurosarcoidosis had an elevated CSF ACE level. Five of the 17 patients in whom neurosarcoidosis was diagnosed were receiving prednisone at the time the ACE levels were measured. Although this factor limits the conclusions of our review, we believe it also limits the clinical utility of CSF ACE determinations because the question of neurologic involvement often arises in patients who are receiving prednisone therapy for sarcoidosis.Table 1Cerebrospinal Fluid Levels of Angiotensin-Converting Enzyme in 110 Mayo Clinic Patients With Suspected NeurosarcoidoslsCSF ACE level (U/L)*ACE = angiotensin-converting enzyme; CSF = cerebrospinal fluid.†Reference range, 0 to 61.Diagnosis of neurosarcoidosi sNo. of patientsMeanMedianRangeYes170.530.410.05–2.01No930.250.250.01–l.28* ACE = angiotensin-converting enzyme; CSF = cerebrospinal fluid.† Reference range, 0 to 61. Open table in a new tab We believe that there is insufficient evidence to support the routine use of CSF ACE levels for the diagnosis of neurosarcoidosis. In accordance with our position that tests that do not provide clinically useful information represent an unnecessary contribution to the overall cost of medical care, we have discontinued performing this test in our laboratory. We believe that additional efforts are needed to develop other diagnostic modalities for the diagnosis of neurosarcoidosis and that further use of CSF ACE levels should be done in the context of prospective studies. CorrectionMayo Clinic ProceedingsVol. 75Issue 3PreviewIn the Letter to the Editor by Dale and O'Brien entitled “Determination of Angiotensin-Converting Enzyme Levels in Cerebrospinal Fluid Is Not a Useful Test for the Diagnosis of Neurosarcoidosis,” published in the May 1999 issue of Mayo Clinic Proceedings (Mayo Clin Proc. 1999;74:535), an error occurred in the dagger footnote to Table 1. The footnote should read as follows: “Reference range, 0 to 0.61 [not 61].” Full-Text PDF