Updated cerebrospinal fluid total protein reference values improve chronic inflammatory demyelinating polyneuropathy diagnosis

Abstract

Introduction Recent literature has concluded that cerebrospinal fluid total protein (CSF‐TP) upper reference limits (URL) should be higher than 45 mg/dl and stratified by age. Methods Data‐driven URLs were applied to the analysis of a cohort of patients with correctly and incorrectly diagnosed chronic inflammatory demyelinating polyneuropathy (CIDP). Descriptive statistics were calculated, and exploratory analyses were used to test the impact of different CSF‐TP URLs on sensitivity and specificity of CIDP diagnosis. Results The adoption of higher and age‐dependent CSF‐TP URLs reduced the sensitivity of CSF analysis slightly (from 95% to 84%‐86%); however, the overall CIDP detection rate was unchanged. Twelve of 36 (33%) false‐positive diagnoses occurred with CSF‐TP elevation as the sole supportive criteria. By applying updated CSF‐TP URLs, the specificity of CSF analysis increased from 39% to 57%‐64%. Discussion Implementation of data‐driven CSF‐TP URLs improves CIDP diagnostic specificity without compromising sensitivity, thereby lessening CIDP misdiagnosis. Muscle Nerve 60: 180–183, 2019

Does cerebrospinal fluid analysis have a meaningful role in the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy?

“…To understand why the CIDP detection rate did not change with the higher URLs, it is important to appreciate the limited role that elevated CSF protein has in the EFNS/PNS criteria for CIDP. All of the patients in whom CIDP had been correctly-diagnosed in the Breiner et al 9 study met clinical and electrodiagnostic criteria, which are mandatory for all 3 diagnostic categories-definite, probable, and possible CIDP. Elevated CSF protein is considered a supportive criterion for CIDP.…”

“…The Breiner et al 9 study informs the discussion about the misdiagnosis of CIDP. Cerebrospinal fluid analysis is probably overused in the routine evaluation of CIDP and may contribute more to the misdiagnosis than to the correct diagnosis of CIDP.…”

“…In this issue of Muscle & Nerve , Breiner et al . applied different sets of criteria with higher protein URLs to patient cohorts that were either correctly or incorrectly diagnosed with CIDP.…”

“…In the EFNS/PNS criteria, the presence of elevated CSF protein can move a patient from possible to probable or probable to definite CIDP. In the study by Breiner et al ., 43 patients in whom CIDP had been correctly diagnosed underwent CSF analysis. Within this cohort, an elevated CSF protein level was the sole supportive criterion in only 1 case.…”

“…Although most clinical laboratories use an upper reference limit (URL) of 45 mg/dl to define elevated protein, there is emerging evidence to suggest that higher, age-matched URL should be implemented (50 mg/dl for patients of <50 years and 60 mg/dl for patients ≥50 years). 8 In this issue of Muscle & Nerve, Breiner et al 9 applied different sets of criteria with higher protein URLs to patient cohorts that were either correctly or incorrectly diagnosed with CIDP.…”