Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

ObjectiveTo investigate cross-sectional associations of CSF levels of neurofilament light chain (NfL) and of the newly emerging marker chitinase 3–like protein 1 (CHI3L1) with brain and spinal cord atrophy, which are established MRI markers of disease activity in MS, to study CHI3L1 and NfL in relapsing (RMS) and progressive MS (PMS), and to assess the expression of CHI3L1 in different cell types.MethodsIn a single-center study, 131 patients with MS (42 RMS and 89 PMS) were assessed for NfL and CHI3L1 concentrations in CSF, MRI-based spinal cord and brain volumetry, MS subtype, age, disease duration, and disability. We included 42 matched healthy controls receiving MRI. CHI3L1 expression of human brain cell types was examined in 2 published single-cell RNA sequencing data sets.ResultsCHI3L1 was associated with spinal cord volume (B = −1.07, 95% CI −2.04 to −0.11, p = 0.029) but not with brain volumes. NfL was associated with brain gray matter (B = −7.3, 95% CI −12.0 to −2.7, p = 0.003) but not with spinal cord volume. CHI3L1 was suitable to differentiate between progressive or relapsing MS (p = 0.015, OR 1.0103, CI for OR 1.002–1.0187), and its gene expression was found in MS-associated microglia and macrophages and in astrocytes of MS brains.ConclusionsNfL and CHI3L1 in CSF were differentially related to brain and spinal cord atrophy. CSF CHI3L1 was associated with spinal cord volume loss and was less affected than NfL by disease duration and age, whereas CSF NfL was associated with brain gray matter atrophy. CSF NfL and CHI3L1 measurement provides complementary information regarding brain and spinal cord volumes.Classification of evidenceThis study provides Class II evidence that CSF CHI3L1 is associated with spinal cord volume loss and that CSF NfL is associated with gray matter atrophy.

P111 Successful treatment of type 1 spinal dural arteriovenous fistula results in reduction of spinal cord volume

ObjectivesTo examine the utility of standardised volumetric spinal cord measurement as an indicator of successful disconnection of a Type 1 spinal dural arteriovenous fistula.DesignRetrospective analysis at a tertiary neuroscience centre.SubjectsPatients with symptomatic Type 1 spinal dAVFs presenting to the senior author and neurovascular MDT (June 2009 – December 2017). Inclusion based on availability of appropriate cross-sectional imaging. DAVFs arising below T12 excluded: 18 patients with a total 19 dAVFs identified.MethodsType 1 fistulation demonstrated on TRICKS MR angiography and spinal catheter angiography. Sagittal volumes evaluated using Horos (Purview, Annapolis, USA) and wireframe models created. Measurement arbitrarily standardised at ±2 levels from the origin of the fistulous draining vein. Pre- and post-operative clinical outcomes assessed using the Aminoff-Logue Scale. Wilcoxon test employed for between-group comparisons and Spearman’s rank test for clinico-radiological correlation (Prism 7, GraphPad Software, Inc. California).ResultsCord volumes reduced by a mean of 0.854 cm3 (p=0.0181; 95% CI=−1.55,–0.16; SD=1.44). Volume change was not related to gait (r=0.037, p=0.8812, 95% CI=−0.44, 0.49) or micturition scores (r=−0.24, p=0.3165, 95% CI=−0.64, 0.25).ConclusionsSurgical disconnection of type 1 dAVF resulted in a reduction in spinal cord volume. This was not predictive of change in clinical indices in this small series but perhaps merits investigation of this as a surrogate marker in a larger series.

Spinal cord volume loss

ObjectiveCross-sectional studies have shown that spinal cord volume (SCV) loss is related to disease severity in multiple sclerosis (MS). However, long-term data are lacking. Our aim was to evaluate SCV loss as a biomarker of disease progression in comparison to other MRI measurements in a large cohort of patients with relapse-onset MS with 6-year follow-up.MethodsThe upper cervical SCV, the total brain volume, and the brain T2 lesion volume were measured annually in 231 patients with MS (180 relapsing-remitting [RRMS] and 51 secondary progressive [SPMS]) over 6 years on 3-dimensional, T1-weighted, magnetization-prepared rapid-acquisition gradient echo images. Expanded Disability Status Scale (EDSS) score and relapses were recorded at every follow-up.ResultsPatients with SPMS had lower baseline SCV (p < 0.01) but no accelerated SCV loss compared to those with RRMS. Clinical relapses were found to predict SCV loss over time (p < 0.05) in RRMS. Furthermore, SCV loss, but not total brain volume and T2 lesion volume, was a strong predictor of EDSS score worsening over time (p < 0.05). The mean annual rate of SCV loss was the strongest MRI predictor for the mean annual EDSS score change of both RRMS and SPMS separately, while correlating stronger in SPMS. Every 1% increase of the annual SCV loss rate was associated with an extra 28% risk increase of disease progression in the following year in both groups.ConclusionSCV loss over time relates to the number of clinical relapses in RRMS, but overall does not differ between RRMS and SPMS. SCV proved to be a strong predictor of physical disability and disease progression, indicating that SCV may be a suitable marker for monitoring disease activity and severity.

Preferential spinal cord volume loss in primary progressive multiple sclerosis

Background: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). Objective: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. Methods: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). Results: PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS. Conclusion: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

184 Effect of Cervical Deformity Correction on Spinal Cord Volume and Stenosis

INTRODUCTION There persists a debate on whether simple isolation of points of stenosis is sufficient or whether certain deformities must also be mitigated to restore neurologic concerns in patients with spinal deformity. Despite indications that cervical kyphosis has a significant effect on spinal cord volume, there remains no studies examining pre- and post-operative effect of deformity corrections on spinal cord volume and number of stenotic levels. METHODS Cervical deformity patients with pre-operative and 1-year MRI’s available were assessed for spinal canal volume at each interspace and at each body from C2-C7/T1. Stenotic vertebral levels were measured using Pavlov's method from C2-T1. Changes in spinal cord volume and number of stenotic levels from baseline to 1-year according to decompression technique used (laminectomy, foraminotomy, discectomy, or corpectomy) and type of pre-operative cervical deformity were measured using t-tests, and improvement in radiographic alignment and myelopathy scores using bivariate correlation tests. RESULTS >14 patients were evaluated. 11 received an osteotomy, 8 a decompression procedure, 6 received a posterior-only approach while the remaining received anterior-then-posterior approach. Patients presented with an average canal volume of 272.4 mm2 and 4.6 stenotic levels. At 1-year, average canal volume was 343.8 (29% increase), and average stenotic levels was 2.9. Patients with deformity apices in the cervical spine had less baseline canal volume (cervical apex: 231.6 mm2 vs. lower apex: 303.6 mm2, P = 0.022) as well as more stenotic levels cervical apex: 6.0 vs. lower apex: 3.4, P = 0.049). There was no significant relationship between decompressive techniques and volume (with decompression: ? +75mm2, w/o: ? +64mm2, P = 0.591). CONCLUSION This analysis shows a 29% increase in canal volume and correction of stenosis in cervical deformity patients. Realignment resulted in an increase in canal volume irrespective of decompression procedure. This preliminary analysis highlights a need for further investigation of spinal cord changes in deformity cases.