A spectrum of neurological diseases with elevated cerebrospinal fluid adenosine deaminase levels

Hideo Handa; Akiyuki Uzawa; Atsuhiko Sugiyama; Hajime Yokota; Manato Yasuda; Akio Kimura; Takayoshi Shimohata; Satoshi Kuwabara

doi:10.1016/j.jns.2024.123368

A spectrum of neurological diseases with elevated cerebrospinal fluid adenosine deaminase levels

J Neurol Sci. 2024 Dec 26:469:123368. doi: 10.1016/j.jns.2024.123368. Online ahead of print.

Authors

Hideo Handa¹, Akiyuki Uzawa², Atsuhiko Sugiyama¹, Hajime Yokota³, Manato Yasuda¹, Akio Kimura⁴, Takayoshi Shimohata⁴, Satoshi Kuwabara¹

Affiliations

¹ Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
² Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: [email protected].
³ Department of Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁴ Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan.

PMID: 39754823
DOI: 10.1016/j.jns.2024.123368

Abstract

Objectives: This study aimed to investigate cerebrospinal fluid (CSF) adenosine deaminase (ADA) levels in various neurological disorders and examine the relationships between CSF ADA levels and immunological parameters.

Methods: Overall, 276 patients whose CSF ADA levels were measured for suspected tuberculous meningitis (TBM) were evaluated. Data on baseline characteristics, final diagnoses, CSF ADA levels, and other laboratory parameters were collected. Thereafter, CSF ADA levels were compared based on final diagnoses, and correlations between CSF ADA levels and other CSF and blood laboratory parameters were evaluated.

Results: Five diseases exhibited a significant increase in CSF ADA levels relative to the noninflammatory disease control group (n = 40): (1) TBM (n = 15, p < 0.0001), (2) fungal meningitis (n = 7, p = 0.0400), (3) autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A, n = 7, p < 0.0001), (4) neurosarcoidosis (n = 7, p = 0.0028), and (5) lymphoproliferative disorders (n = 18, p = 0.0001). Strong positive correlations were observed between CSF ADA and CSF parameters, including soluble IL2 receptor (r_s = 0.7566, p < 0.0001), albumin (r_s = 0.6693, p < 0.0001), lactate dehydrogenase (r_s = 0.6452, p < 0.0001), white blood cell count (r_s = 0.6035, p < 0.0001), protein (r_s = 0.6334, p < 0.0001), and lymphocytes (r_s = 0.5954, p < 0.0001).

Discussion: CSF ADA levels were elevated in various inflammatory neurological diseases, especially in TBM, fungal meningitis, GFAP-A, neurosarcoidosis, and lymphoproliferative disorders. CSF ADA levels may reflect T-cell hyperactivation in the central nervous system.

Keywords: Adenosine deaminase; Autoimmune glial fibrillary acidic protein astrocytopathy; Lymphoproliferative disorders; Neurosarcoidosis; Tuberculous meningitis.