Objective:

To find clinically relevant CSF biomarkers which are altered in Hereditary spastic paraplegia.

Background:

Hereditary spastic paraplegia (HSP) is a group of inherited disorders characterized by progressive stiffness and contraction in the lower limbs. Cerebrospinal fluid (CSF) biomarkers in HSP are substances found in the spinal fluid that can indicate disease presence, progression, or response to therapy. The identification of specific CSF biomarkers is crucial for diagnosing HSP, monitoring its progression, and evaluating therapeutic responses, given the heterogeneity and overlap of symptoms with other neurological conditions.

Design/Methods:

A thorough systematic search was conducted in the databases: PubMed/MEDLINE, Cochrane, EMBASE, and ClinicalTrials.gov databases to identify observational studies that focused on CSF biomarkers in HSP. The search included trials from the earliest available date up to September 2024

Results:

Three cross-sectional studies analyzed cerebrospinal fluid (CSF) biomarkers in hereditary spastic paraplegia (HSP). The first study on HSP5 patients found mean CSF 27-hydroxycholesterol at 10 ng/mL and neurofilament light chain (NfL) at 529 pg/mL. The second study showed higher CSF NfL in HSP patients (919 pg/mL) than in controls (386.5 pg/mL). The third study reported elevated CA4-7α,x-diol-3-one levels in SPG5 patients (0.92 ng/mL vs. 0.3 ng/mL in controls), suggesting its potential as a diagnostic biomarker. Studies were excluded for lacking quantifiable biomarker data or focusing on non-HSP conditions.

Conclusions:

This review highlights cerebrospinal fluid (CSF) biomarkers, including 27-hydroxycholesterol, neurofilament light chain (NfL), and CA4-7α,x-diol-3-one, for diagnosing hereditary spastic paraplegia (HSP). Elevated NfL and CA4-7α,x-diol-3-one in SPG5 suggest diagnostic potential, but further research with standardized methods is needed to confirm their clinical utility.