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2D linear measures of ventricular enlargement may be relevant markers of brain atrophy and long-term disability progression in multiple sclerosis

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Abstract

Objectives

Aim of this study was to investigate the reliability and validity of 2D linear measures of ventricular enlargement as indirect markers of brain atrophy and possible predictors of clinical disability.

Methods

In this retrospective longitudinal analysis of relapsing-remitting MS patients, brain volumes were computed at baseline and after 2 years. Frontal horn width (FHW), intercaudate distance (ICD), third ventricle width (TVW), and 4th ventricle width were obtained. Two-dimensional measures associated with brain volume at correlation analyses were entered in linear and logistic regression models testing the relationship with baseline clinical disability and 10-year confirmed disability progression (CDP), respectively. Possible cutoff values for clinically relevant atrophy were estimated via receiver operating characteristic (ROC) analyses and probed as 10-year CDP predictors using hierarchical logistic regression.

Results

Eighty-seven patients were available (61/26 = F/M; 34.1 ± 8.5 years). Moderate negative correlations emerged between ICD and TVW and normalized brain volume (NBV; p < 0.001) and percentage brain volume change per year (PBVC/y) and FHW, ICD, and TVW annual changes (p ≤ 0.005). Baseline disability was moderately associated with NBV, ICD, and TVW (p < 0.001), while PBVC/y predicted 10-year CDP (p = 0.01). A cutoff percentage ICD change per year (PICDC/y) value of 4.38%, corresponding to − 0.91% PBVC/y, correlated with 10-year CDP (p = 0.04). These estimated cutoff values provided extra value for predicting 10-year CDP (PBVC/y: p = 0.001; PICDC/y: p = 0.03).

Conclusions

Two-dimensional measures of ventricular enlargement are reproducible and clinically relevant markers of brain atrophy, with ICD and its increase over time showing the best association with clinical disability. Specifically, a cutoff PICDC/y value of 4.38% could serve as a potential surrogate marker of long-term disability progression.

Key Points

• Assessment of ventricular enlargement as a rapidly accessible indirect marker of brain atrophy may prove useful in cases in which brain volume quantification is not practicable.

• Two-dimensional linear measures of ventricular enlargement represent reliable, valid, and clinically relevant markers of brain atrophy.

• A cutoff annualized percentage brain volume change of − 0.91% and the corresponding annualized percentage increase of 4.38% for intercaudate distance are able to discriminate patients who will develop long-term disability progression.

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Abbreviations

4VW:

4th ventricle width

AUC:

Area under the receiver operating characteristic curve

CDP:

Confirmed disability progression

EDSS:

Expanded Disability Status Scale

FHW:

Frontal horn width

FU:

Follow-up

ICC:

Intraclass correlation coefficient

ICD:

Intercaudate distance

MS:

Multiple sclerosis

NBV:

Normalized brain volume

NEDA:

No evidence of disease activity

P4VWC/y:

Percentage 4th ventricle width change per year

PBVC/y:

Percentage brain volume change per year

PFHWC/y:

Percentage frontal horn width change per year

PICDC/y:

Percentage intercaudate distance change per year

PTVWC/y:

Percentage third ventricle width change per year

ROC:

Receiver operating characteristic

TSD:

Total skull diameter

TVW:

Third ventricle width

WM:

White matter

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Author notes

  1. Mario Quarantelli and Maria Petracca contributed equally to this work.

Authors and Affiliations

  1. Department of Advanced Biomedical Sciences, University “Federico II”, Via Pansini, 5, 80131, Naples, Italy

    Giuseppe Pontillo, Sirio Cocozza, Martina Di Stasi, Chiara Paolella, Maria Brunella Cipullo, Teresa Perillo, Elena Augusta Vola, Camilla Russo, Enrico Tedeschi, Andrea Elefante & Arturo Brunetti

  2. Department of Neurosciences and Reproductive and Odontostomatological Sciences, University “Federico II”, Naples, Italy

    Antonio Carotenuto, Marco Masullo, Marcello Moccia, Roberta Lanzillo, Vincenzo Brescia Morra & Maria Petracca

  3. Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy

    Mario Quarantelli

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Corresponding author

Correspondence to Sirio Cocozza.

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Guarantor

The scientific guarantor of this publication is Mario Quarantelli.

Conflict of interest

S.C. and C.R. received fees for speaking from Genzyme.

M.M. has received research grants from ECTRIMS-MAGNIMS and from Merck.

The remaining authors have no conflict of interest to declare.

The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors (M.Q.) has significant statistical expertise.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional review board approval was obtained.

Methodology

• Retrospective

• Observational

• Performed at one institution

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Pontillo, G., Cocozza, S., Di Stasi, M. et al. 2D linear measures of ventricular enlargement may be relevant markers of brain atrophy and long-term disability progression in multiple sclerosis. Eur Radiol 30, 3813–3822 (2020). https://doi.org/10.1007/s00330-020-06738-4

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