JNNP: Asymptomatic progression of brain atrophy in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory disease of the central nervous system (CNS)
.

It mainly affects the optic nerve and spinal cord, but brain damage may also occur

Unlike AQP4+NMOSD, MS has a progressive stage in the course of the disease
.

Brain atrophy, especially cortex and gray matter atrophy, is associated with worsening cognition and disability

Only one study so far has reported longitudinal brain atrophy in patients with NMOSD

The study retrospectively analyzed the clinical data of 114 AQP4+NMOSD patients and 283 RRMS patients admitted to the Chiba University Affiliated Hospital
.

The patient registration process and study design are shown

Diagnosis and as mentioned earlier, the AQP4 antibody was positive by cell-based analysis

Flow chart and research design

First, all patients who meet the above inclusion criteria are included in the study1
.

In Study 2, only patients with no clinical recurrence and disability progression between MRI-1 and MRI-2 were included to compare only clinically stable patients

Young patients with AQP4+NMOSD were matched by selecting MS patients whose age difference was less than 5 years old

Percentage change of brain volume between MRI-1 and MRI-2 in patients with AQP4+NMOSD and MS

The demographic characteristics (including the sex ratio and age of MRI-1) and clinical characteristics (including the course of MRI-1, the EDSS score of MRI-1, the annualized recurrence rate (ARR) from onset to MRI-1, and finally The number of months of an attack, the number of months since the baseline treatment, and the positive rate of oligoclonal bands (OCB) were investigated
.

Isoelectric focusing method detects the positive rate of cerebrospinal fluid (CSF) OCB

Compared with MS patients, AQP4+NMOSD patients have significantly higher age and EDSS score on MRI-1
.

On the other hand, the positive rate of OCB in AQP4+NMOSD patients is lower than that in MS patients (18.

On the other hand, 26, 22, 5, and 2 MS patients were treated with interferon-β, fengolimod, dimethyl fumarate, or natalizumab, respectively

Age-matched AQP4+NMOSD patients had higher NGV, NWV, and NBV in MRI-1 and MRI-2 than age-matched MS patients
.
On the other hand, compared with age-matched MS patients, age-matched AQP4+NMOSD patients have lower NLVs for MRI-1 and MRI-2
.
However, there was no difference in the annual shrinkage rates of NGV, NWV, and NBV between the two groups
.
All other items, including ΔEDSS, the number of years from MRI-1 to MRI-2, and the ICV of MRI-1 and MRI-2, were not different between the two groups
.
There is no significant difference in the annual shrinkage rate of NBV, NGV and NWV
.

Clinical features and brain volume of age-matched AQP4+NMOSD and MS patients in MRI-1 and MRI-2

The results showed that there was no difference in ΔEDSS (EDSS at MRI-2 minus EDSS at MRI-1) and ARR between MRI-1 and MRI-2
.
The time between MRI-1 and MRI-2 in AQP4+NMOSD patients is longer than that in MS patients
.
Compared with MS patients, ICV patients with AQP4+NMOSD have lower NLVs of MRI-1, MRI-1 and MRI-2
.
The NWV of MRI-1 and MRI-2 in AQP4+NMOSD patients was higher, but there was no difference in the annual atrophy rate of NGV, NWM and NBV between the two patient groups
.
The annualized atrophy rate of NGV, NWV and NBV with or without sustained prednisolone was compared
.
The results showed that the annualized atrophy rate of NBV and NWV of patients without persistent prednisolone (n=5) was significantly higher than that of patients with persistent prednisolone (n=31) (p=0.
008 and 0.
003, respectively )
.
There was no difference in the annual shrinkage rate of NGV (p=0.
45)
.
The age and EDSS score of AQP4+NMOSD patients in Study 1 were higher than those of MS patients
.

The positive rate of OCB in MS patients is higher than that in AQP4+NMOSD patients
.
On MRI-1, there was no difference in the proportion of women between the two groups, the duration of the disease, the ARR after the onset, the number of months after the last episode, and the number of months after the onset of DMD
.
A total of 24 patients with AQP4+NMOSD were treated on MRI-1 (prednisolone only, n=20; prednisolone plus azathioprine, n=3; and prednisolone plus egualizumab , N=1)
.
On the other hand, 41 MS patients received MRI-1 treatment
.
Studies have shown that longitudinal brain atrophy may occur even in clinically stable AQP4+NMOSD patients
.
The median annual atrophy rate of NBV in MS patients was 0.
46 in Study 1, 0.
42 in Study 2, and 0.
44 in Study 3.
These values ​​are within the previously reported brain atrophy rate of healthy controls (0.
1% to 0.
3%) and MS The median value between patients (0.
6% to 1.
35%)
.
The pathological range of brain atrophy rate in MS patients is >0.
46%, the specificity is 90%, the specificity is >0.
40%, and the specificity is 80%
.

The positive rate of OCB in MS patients is higher than that in AQP4+NMOSD patients
.
On MRI-1, there was no difference in the proportion of women between the two groups, the duration of the disease, the ARR after the onset, the number of months after the last episode, and the number of months after the onset of DMD
.
A total of 24 patients with AQP4+NMOSD were treated on MRI-1 (prednisolone only, n=20; prednisolone plus azathioprine, n=3; and prednisolone plus egualizumab , N=1)
.
On the other hand, 41 MS patients received MRI-1 treatment
.

In conclusion, longitudinal brain atrophy may occur even in clinically stable AQP4+NMOSD patients
.
Data show that in patients with AQP4+NMOSD, death degeneration after spinal cord injury may lead to gray matter atrophy
.
Future research should reveal not only the brain atrophy of MS patients, but also the brain atrophy of AQP4+NMOSD patients
.
 

Death and degeneration after spinal cord injury may lead to atrophy of gray matter in the brain
.
Future research should reveal not only the brain atrophy of MS patients, but also the brain atrophy of AQP4+NMOSD patients
.
 Death and degeneration after spinal cord injury may lead to atrophy of gray matter in the brain
.
Future research should reveal not only the brain atrophy of MS patients, but also the brain atrophy of AQP4+NMOSD patients
.
 Masuda  H ,  Mori  M ,  Hirano  S Masuda  H Masuda Mori  M Mori Hirano  S Hirano , et al Silent progression of brain atrophy in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder Journal of Neurology, Neurosurgery & Psychiatry  Published Online First:  06 August 2021 .
  Published Online First: doi:  10.
1136/jnnp-2021-326386doi: leave a message here