Differences in Gray Matter Structure May Help Distinguish Multiple Sclerosis From NMOSD

In a recently published retrospective, comparative study, investigators found significant gray matter differences, with the thalamus consistently smaller in patients with multiple sclerosis (MS) as compared to those with neuromyelitis optica spectrum disorder (NMOSD). While not groundbreaking, these findings further emphasized the importance of advanced imaging technologies in differentiating the 2 disorders, which may also have implications for diagnosis and treatment strategies.¹

The study, which took place at King Saud University Medical City, Saudia Arabia, comprised of 24 patients with NMOSD and 25 patients with MS who were both on immunomodulatory treatments. To be included, subjects must have had at least 2 MRI scans, including T1-weighted FSEGE sequences, with follow-ups performed at least 6 months apart. During the study, investigators examined temporal changes between the 2 cohorts, including analyses of anatomical T1-weighted MRI scans using the CAT12 toolbox.

Led by Salman Aljarallah, MBBS, assistant professor at King Saud University in Saudi Arabia and serves on the medical advisor board at The Sumaira Foundation, results showed that cerebral white matter (excluding infratentorial white matter) was significantly larger in patients with MS compared with those with NMOSD (69.3 [±10.3] vs 62.8 [±9.3]; P = .02). More notably, between the 2 groups, there was smaller thalamic size volume in patients with MS compared with NMOSD at baseline (MS average: 6.8 [±3.0]; NMOSD: 9.2 [2.6]; P = .004).

When parsing patients with NMOSD by subtype, results showed that those with seronegative NMOSD (n = 5) had the largest thalamic volume (average, 10.96 mL [±2.18]) followed by MOG-positive NMOSD (average 9.1 mL [±2.3]) and aquaporin-4-positive patients (8.6 mL [±2.8]). This difference between average thalamic volume between MS and NMOSD groups persisted in follow-up MRI (6.8 [±3.2] and 8.7 [±2.6], P = 0.03).

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"This study identified that, indeed, significant differences do exist between MS and NMOSD, even if clinical presentations are more or less similar,” Aljarallah et al wrote.¹ "While some of these differences, including gross abnormalities such as plaques, can be easily visually seen in routine MRI, we identify more subtle differences in the deep gray matter volume that help differentiate MS from NMOSD, which helps in the management. The most consistent finding in this study was that a smaller thalamic volume in patients with MS was a strong predictor for the diagnosis of multiple sclerosis and is a good marker to differentiate MS from NMOSD."

Receiver under the curve (ROC) analyses revealed differentiated thalamic volume between the 2 groups, with a 70.6% sensitivity, 64.3% specificity, and an area under the operating curve of 0.73, thus identifying a volume less than 7.06 mL as favoring MS. Cerebral white matter volume was larger in MS (OR, 0.9; P = .03), but this lost significance after adjusting for age (OR, 0.97; P = 0.4). Furthermore, caudate volume was smaller in MS on follow-up scans, with reduced volume linked to higher odds of MS (OR, 2.5; 95% CI, 1.03-6.25; P = .04).

At the 6-month follow-up, on average, both patients with MS and NMOSD demonstrated some reduction in gray matter volume, caudate volume, and cerebellar volume; however, these differences were not statistically significant. Overall, patients with MS had lower whole brain volume, cerebral white matter volume, and hippocampal at follow-up, while patients with NMOSD had lower cerebrospinal fluid volume and thalamic volumes at follow-up compared with baseline. At baseline, all patients with MS had optic neuritis, compared with 75% of those with NMOSD. In addition, patients with MS more often had transverse myelitis (64% vs 41%) and cerebral or brainstem symptoms.

The study had a small number of limitations, including the fact that the sample size was not large in size and the study was single-centered. While the study excluded patients who had MRIs done using different protocols, this may have made the results more representative of a real-world population. Also, the study did not include patients with MOG antibodies who did not fulfill the criteria of NMOSD.

REFERENCE
1. Alosaimi M, Alkanhal H, Aldeligan S, et al. Thalamic volume differentiates multiple sclerosis from neuromyelitis optica spectrum disorder: MRI-based retrospective study. Front Neurol Multiple Sclerosis and Neuroimmunology. 2025;2(15). doi:10.3389/fneur.2024.1491193