Brain MRI volumetric changes in the follow-up of patients with anti-NMDAr encephalitis

https://doi.org/10.1016/j.clineuro.2021.106908Get rights and content

Highlights

  • A descriptive study of several structures and their changes over time in patients with antiNMDAr encephalitis is presented.

  • Significant decrease in the cerebellum and brainstem as well as global brain volume was found.

  • No significant correlation was found between the clinical phenotype and this findings.

Abstract

Introduction

Autoimmune anti-NMDAr encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by decreased consciousness, dysautonomia and seizures. The pathophysiology of the disease is related to the internalization of NR1 subtype NMDA receptors and the dysfunction of structures where they are abundant (frontotemporal and insular regions). Some reports suggest the existence of cerebral atrophy in the follow-up of these patients, with conflicting evidence regarding its presence and usefulness as a marker of prognosis.

Methods

In a longitudinal, observational study, all patients with the diagnosis of definite anti-NMDAr autoimmune encephalitis with initial and control MRI studies were included. Conventional MR Brain acquisition was performed using a 3-Tesla Skyra MRI System. Automated brain segmental analysis was performed using the Volbrain volumetry system. The differences between baseline MRI volumetric characteristics and volumetric measures at follow-up was assessed.

Results

25 patients were included (mean age 26.6, SD 9.6). 44% were females. The mean time between the studies was 24 (SD 21.4, 3–24) months. Significant volume loss was identified in the total brain volume (− 0.02%, p = 0.029), cerebellar volume (− 0.27%, p = 0.048) and brainstem volume (− 0.16%, p = 0.021).

Conclusions

This study supports previous observations regarding volume loss in several brain regions of patients with antiNMDAr encephalitis. Further analyses are required to understand the role of treatment and severe clinical forms, as well as the relationship between volume loss and functional outcome.

Introduction

Autoimmune anti NMDAr (N-methyl-D-aspartate receptor) encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by disturbances in the level of consciousness, dysautonomia, hypoventilation and epileptic seizures [1]. The pathophysiology of the disease is directly related to the internalization of the NMDA receptors of the NR1 [2] subtype and the dysfunction of the structures where they are abundant (frontotemporal and insular regions) [3], [4], [5]. The prognosis of the disease is usually good [6], with substantial recovery in the majority of patients - particularly in those who receive early immunotherapy [7]- but with about 20% presenting severe disability [8]. The estimated mortality of the disease is 7% and is related to the severity of the manifestations and associated hospital complications [9].

The objective measurement of changes in brain volume requires a longitudinal study of the patient. Brain volume loss is an unfortunate outcome in several central nervous system conditions [10], [11]. In autoimmune CNS diseases, the evidence shows that loss of brain volume is irreversible [10]. However, some exploratory studies in antiNMDAr encephalitis have demonstrated degrees of reversibility that suggest its association with a better prognosis in patients and could function as a monitoring tool for response to treatment [12].

3D MRI sequences represent a quantitative technique based on tissue segmentation according to the contrast (the difference between signal and noise) of the structures. The utility of quantitative MRI (3D) is that it allows non-invasive identification of cerebral volume loss in different diseases and the objective evaluation of these changes over time [13]. Different automated and validated software allows this analysis, highlighting VolBRAIN. Due to the main objective of documenting whether there are volumetric changes and emphasizing whether these changes correspond to specific brain areas, Volbrain open-access software was used for the segmentation of structures in the two different studies. Volbrain [14], designed by the University of Bordeaux and the University of Valencia has already demonstrated similar and even superior results to other semi-automatic segmentation programs such as Freesurfer or FIRST [15], [16], [17].

The purpose of this study was to determine if there are significant changes in the brain volume of patients with anti-NMDAr encephalitis, between the initial MRI study, obtained during the acute phase of the disease, as compared to a second MRI study, which was obtained during the clinical follow up.

Section snippets

Design

We conducted a longitudinal and observational study. The Institutional Research Committee revised and approved the protocol (Protocol # 86/19). The research project was approved by the Ethics Committee of the National Institute of Neurology of Mexico, and it conforms to the provisions of the Declaration of Helsinki in 1995 (as revised in Edinburgh 2000). All the diagnostic and therapeutic procedures were considered necessary for the clinical assistance of the patients. MRI studies were acquired

General features of the sample

25 patients that met selection criteria were included. As may be seen in Table 1, 11 patients (44%) were female and 14 (56%) were male, with a mean age of 26.64 years (16–55 years, SD 9.69). The mean hospital stay time was 49.38 days (15–200, SD 40,226).

Clinical features

Regarding the initial clinical manifestation, 11 (44%) patients presented an associated prodromal symptom (flu-like syndrome, gastrointestinal symptoms, headache). The initial clinical manifestations were psychiatric/cognitive in 15 (60%) of the

Discussion

The present study represents a descriptive analysis of the volumetric changes of patients with anti-NMDAr encephalitis in the Mexican population. As has been shown in previous studies in Latin American populations, our study included a higher percentage of males as compared to European and North American studies [19]. We provide evidence of global brain volume loss, as well as volume loss in the cerebellum and brainstem. Considering that most patients are young (mean age 26.6, SD 9.6) it is

CRediT authorship contribution statement

Enrique Gomez-Figueroa: Conception, Data collection, Drafting of article. Christian Garcia-Estrada: Drafting the article. Jorge Salado-Burbano: Editing, Drafting of article. Fernando Cortes-Enriquez: Data re analysis, Interpretation. Oscar Marrufo-Melendez: Data collection. Mariana Espinola-Nadurille: Data analysis, Interpretation. Jesus Ramirez-Bermudez: Critical revision of the article. Veronica Rivas-Alonso: Final approval. Teresita Corona: Final approval. Jose Flores-Rivera: Conception,

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