Longitudinal Brain Atrophy Present in Clinically Inactive NMOSD, MS


Patients with AQP4+NMOSD with long cord lesion showed higher annualized atrophy rate of normalized grey matter volume compared with those without long cord lesion.

Satoshi Kuwabara, MD

Satoshi Kuwabara, MD

Recently published data from a longitudinal study found that patients with aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) have silent progression of brain atrophy, even amongst those with clinically inactive age-matched cases.

The clinical records of 114 patients with AQP4+NMOSD and 283 with relapsing-remitting MS at Chiba University Hospital were reviewed in a trio of study groups. Senior author Satoshi Kuwabara, MD, professor of neurology, Chiba University Graduate School of Medicine, and colleagues then included patients who received 2 MRI scans using the same scanner for at least a 1-year interval into study 1. In study 2, only those without clinical relapses and disability progression between MRI-1 and MRI-2 were included to compare clinically stable patients. Lastly, an age-matched study was performed as study 3.

Statistical parametric mapping-12 was used to calculate brain volume and assess the longitudinal brain atrophy rate in the overall cohort of 36 patients with AQP4+ NMOSD and 60 patients with MS. The retrospective cohort study compared the annualized atrophy rate of patients with AQP4– NMOSD with or without clinical features including the history of optic neuritis, myelitis brain stem lesion, and long cord lesion.

Age and Expanded Disability Status Scale (EDSS) score at MRI-1 were significantly higher in patients with AQP4+ NMOSD compared with those with MS. On the other hand, patients with AQP4+ NMOSD showed lower oligoclonal band positivity compared with patients with MS (18.5% vs 67.3%, respectively). No other items, including the men-to-women ratio, disease duration, annualized relapse rare (ARR) from disease onset, and months from disease-modifying drug (DMD) initiation, were different between the 2 groups.

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Despite a higher normalized white matter (NWV) volume at baseline MRIs in patients with AQP4+ NMOSD, investigators observed no difference between the 2 patient groups on annualized atrophy rate of normalized grey matter (NGV) and normalized brain volume (NBV). Among patients without clinical relapse and disability progression, Intracranial volume (ICV) at MRI-1 and normalized lesion volume (NLV) at MRI-1 and MRI-2 in patients with AQP4+ NMOSD compared with those with MS. Additionally, NWV was higher in the AQP4+ NMOSD group than in patients with MS at both MRI-1 and MRI-2. On the other hand, annualized atrophy rates of NGV, NWV, and NBV were not different between the 2 groups.

Patients with AQP4+ NMOSD with long cord lesion also showed a higher annualized atrophy rate of NGV compared with those without long cord lesion (median, 0.79% vs 0.41%; P = .046). Investigators noted no differences in annualized atrophy of NBV and NWV regardless of length of cord lesion (P = .047 for both). These patients also showed higher annualized atrophy of NGV compared with those without long cord lesion in study 2 (median, 0.92% vs 0.41%; P = .005), and study 3 (median, 0.90% vs 0.41%; P <.001).

Investigators referenced previous findings from 2 other studies which found combined ganglion cell and inner plexiform layer loss to be independent of optic neuritis attacks in NMOSD, as well as subclinical neurodegeneration among this patient population using otpical coherence tomography. Kuwabara et al wrote, "therefore, subclinical neurodegeneration may occur not only in the retina, but also in the brain in patients with AQP4+NMOSD. Our data suggest dying back degeneration after the long cord lesion could cause the grey matter atrophy in the brain in patients with AQP4+ NMOSD."

They also noted that future studies should shed light on brain atrophy not only for patients with MS, but also in patients with AQP4+ NMOSD. To exclude the treatment effect, longer follow-up MRI duration and health controls may also be used in prospective studies to compare the brain atrophy rate between those on steroids and more efficacious medications.

Masuda H, Mori M, Hirano S, et al. Silent progression of brain atrophy in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. J Neurol Neurosurg Psychiatry. Published online August 6, 2021. doi: 10.1136/jnnp-2021-326386
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