Research presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023 provides updates on pregnancy outcomes in mothers with cladribine exposure, techniques for early diagnosis of MS, biomarkers of disability progression in MS, and which patients with MOGAD will worsen without treatment. The forum was held in San Diego, California, from February 23 to 25.

Effects of Cladribine Exposure on Pregnancy Outcomes

Little is known about the risk to pregnancy outcomes in women prescribed cladribine for the treatment of multiple sclerosis (MS) 6 months prior to or after their last menstrual cycle. The results of a prospective study found that pregnancy results after cladribine exposure was associated with “generally healthy newborns” and few disease relapses, according to data presented by Karen Dost-Kovalsky and colleagues from the St. Josef-Hospital in Bochum, Germany. Preliminary findings from this study were published in Multiple Sclerosis.

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Oral cladribine was first approved by the Food and Drug Administration in 2019. Use of the agent is contraindicated in pregnancy and, thus, limited data is available on pregnancy outcomes. The findings are based on data from 55 women enrolled in the German Multiple Sclerosis and Pregnancy Registry who were exposed to cladribine after their last menstrual period (n=3), during the 6 months prior to their last menstrual period (n=18), and prior to 6 months before their last menstrual period (n=34). Outcomes were as follows:

  • 31 healthy babies born
  • 3 spontaneous abortions
  • 1 elective abortion
  • Of the 31 healthy babies, 2 babies were born with congenital malformations: 1 major atrial septum defect and 1 minor hemangioma

A total of 19 normal pregnancies were ongoing. One patient was lost to follow-up.

Most women reported a stable disease course during pregnancy. Among those who completed their pregnancy (n=35), 1 relapse was reported during pregnancy and 1 during the postpartum period.

Although the findings from this small study suggest that most newborns are born healthy to people taking cladribine during pregnancy, the study authors emphasized the need for effective contraception for at least 6 months after the last cladribine dosing.

Multiple Sclerosis Disability Progression Linked to MRI Volumetric Biomarkers

The rate of clinical disease progression in MS is associated with lower baseline brain volume and the rate of concurrent whole brain tissue atrophy, according to findings from a retrospective, longitudinal study presented by Maria Garcia-Dominguez, MD, and colleagues from the University of Massachusetts in Worcester.

Previous research suggests that a -0.4% change in longitudinal brain volume as measured using quantitative volumetric magnetic resonance imaging (MRI) is the best predictor of MS disability progression. This information can help clinicians and patients make personalized treatment decisions.

The current study was designed to investigate potential MRI volumetric biomarkers of disability progression in 212 individuals with MS (mean age, 52 years; 23.6% male). All patients were seen at a single tertiary care center. The majority of patients (79%) had relapsing MS and 18% had progressive MS. Disability progression was defined as worsening Expanded Disability Status Scale (EDSS) by 0.5 if baseline score was 4.5 or greater and worsening EDSS of 1 if baseline score was less than 4.5.

Over a median follow-up of 5.75 years, 23.11% (49 of 212) of the participants demonstrated disability progression. Annualized percent of brain volume change (odds ratio [OR], 0.42; 95% CI, 0.19-0.93; P =.033) and baseline brain volume (OR, 0.9; 95% CI, 0.90-0.99; P =.024) both were significantly associated with disability progression. Baseline deep gray areas that were significantly associated with disability progression included the caudate (P =.004), hippocampus (P =.016), and thalamus (P =.022). The analysis showed that -0.53% was the earliest cutoff for annualized brain volume loss associated with disease progression in MS. This is a smaller percent change that previously reported.

“Brain MRI characteristics such as brain volume atrophy are useful potential biomarkers to risk stratify patients [with MS] at risk of ongoing clinical deterioration,” the researchers concluded.

Artificial Intelligence Detects White Matter Lesions Faster in Early Multiple Sclerosis

A team of researchers were able to use machine learning and artificial intelligence to measure white matter lesions in early stages of MS. A novel deep learning technique effectively segmented white matter MS lesions during the early stages of MS that may otherwise be difficult to capture using current scanning methods, according to study results presented by Houman Ebrahimi and colleagues from the University of Newcastle/Cirrus, Callaghan, Australia.

Researchers developed an automated algorithm architecture based on GoogleNet trends that used 6 convolutional layers containing 256 filters in the first layer and incrementally decreasing in filter size from 128 down to 8 filters as the last layer. This is known as a convolutional neural network (CNN) as opposed to fully connected (FC) layers, which current scanning methods use.

The researchers also capitalized on preprocessing techniques that allowed for cleaner images and greater pixel diversity prior to processing the images with the main algorithm.

The findings are based on 171 MRI scans from 3 different tesla MRI scanners. The first 61 scans were used to train the algorithm and the remaining 110 scans were used to test the validity of the algorithm.

The researchers discovered that the new automated algorithm increased overall average accuracy of detection of active white matter lesions from 88% to 92%. They also confirmed the robustness of the new algorithm when it was applied to different scanners with varying deep learning parameters, suggestive of its effective performance during real-world application.

In addition, the new algorithm was faster, analyzing between 200 to 300 image slices in an average time of 2 minutes, saving neurologists time in obtaining a more precise MS diagnosis in the early stages of the disease, they noted. 

This automated algorithm will help neurologists to diagnose MS at an early stage when treatment is most efficacious, they concluded.

Which Patients With MOGAD Will Worsen Without Treatment?

While patients with anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD)-optic neuritis can improve without any management, patients with MOGAD-myelitis will worsen without intervention with high-dose steroids, according to findings presented by Natalia Kosior and colleagues from the University of Western Ontario, London, Canada. 

Researchers assessed the efficacy of no treatment vs high-dose steroids on disability outcomes in patients with MOGAD-optic neuritis and MOGAD-myelitis. In patients with NMOSD, the researchers also examined the effects of high-dose corticosteroid treatment alone vs with plasmapheresis.

Of the 65 patients included in the study, 23 had MOGAD (myelitis, n=11; optic neuritis, n=12) and 42 had NMOSD (myelitis, n=30; optic neuritis, n=12). The number needed to treat (NNT) and number needed to harm (NNH) for each group depending on treatment were as follows:

  • MOGAD-myelitis. Treatment with high-dose steroids: NNT=1.32 (P =.002) vs NNH=3.6 (P =not significant)
  • MOGAD-optic neuritis. Treatment with high-dose steroids vs no treatment: NNT=1.02 (P <.001) vs NNT=2.08 (P =.09), respectively
  • NMOSD-myelitis. Treatment with high-dose steroids vs plasmapheresis plus high-dose steroids: NNT=2.29 (P =.002) vs NNT=2.33 (P =.03), respectively

In addition to a lack of significant difference in outcome with the addition of plasmapheresis to high-dose steroid treatment in the NMOSD group, after adjusting for group differences (such as severity), the use of high-dose corticosteroids was linked to a greater likelihood of improvement (NNT=1.73, P =.002) as compared with the group using high-dose corticosteroids plus plasmapheresis (NNT=1.98, P =0.02).

The researchers concluded that while patients with MOGAD-optic neuritis improve without any management, they do show a marked improvement when using high-dose steroids. “Patients with MOGAD-myelitis are also very responsive to steroids, however, as opposed to MOGAD-optic neuritis, they worsened if not treated,” the researchers said. Patients with NMOSD did not experience any improvement through the use of plasmapheresis in addition to high-dose steroids.

More multiple sclerosis news from ACTRIMS Forum is available here.


Dost-Kovalsky K, Thiel S, Ciplea AI, Gold R, Hellwig K. Cladribine and pregnancy in women with multiple sclerosis – a cohort study. Presented at: ACTRIMS Forum 2023; February 23-25; San Diego, CA. Poster 478.

Garcia-Dominguez MA, Hemond C. Brain atrophy rate is associated with disability progression in multiple sclerosis. Presented at: ACTRIMS Forum 2023; February 23-25; San Diego, CA. Poster 050.

Ebrahimi H, Afzal H, Ramadan S, Lechner Scott J. Artificial intelligence is helping to predict multiple sclerosis by detecting active lesions. Presented at: ACTRIMS Forum 2023; February 23-25; San Diego, CA. Poster 005.

Kosior N, Perrier RL, Casserly C, Morrow SA, Racosta JM. New insights into the use of high dose of steroids and plasmapheresis in MOGAD and NMOSD patients. Presented at: ACTRIMS Forum 2023; February 23-25; San Diego, CA. Poster 327.