Selected highlights from the American Academy of Neurology annual meeting, Boston, MA, 22-27 April 2023.
April 26 Edition
April 25 Edition
Combining sNfL and cGFAP improves prognostic value
NfL/GFAP changes during anti-CD20 treatment
How is JC virus transmitted?
Does body weight affect B cell kinetics?
Hyperglycemia medications and MS risk
CONGRESS HIGHLIGHTS – MONDAY EDITION
Combining sNfL and cGFAP improves prognostic value
A study at the University of Ottawa examined fluid biomarkers collected from 60 MS patients over a mean of 15.8 years (Thebault et al. AAN 2023; S9.001). During the observation period, 40% of patients developed progressive disease and 43% reached EDSS ≥4.0. The prediction of progressive MS was improved with the combination of serum neurofilament-light chain (sNfL) and glial fibrillary acid protein in CSF (cGFAP) compared to either measure alone. NfL generally reflects neuroaxonal damage due to disease activity; GFAP is a marker of astrocyte activation and neurodegeneration. Patients in the highest quintiles of both measures had a 5.5-fold higher risk of reaching EDSS ≥4.0 and a 3.6-fold increased risk of developing progressive MS compared to those in the lowest quintile.
NfL/GFAP changes during treatment
A small study (N=37) examined changes in plasma levels of NfL and GFAP during treatment with ocrelizumab in patients with RMS and PMS (Gross et al. AAN 2023;P1.010). Samples were obtained at baseline and after 3-12 months. Age-adjusted NfL and GFAP levels were comparable in RMS and PMS patients at baseline. Following ocrelizumab initiation, NfL levels decreased 27.6% (from 6.8 to 4.9) in RMS patients but were unchanged in PMS patients. GFAP levels were unchanged in RMS patients but increased (from 52.4 to 60.8) in PMS patients. The results suggest that ocrelizumab is primarily effective in reducing inflammatory activity in RMS patients.
A separate study examined sNfL changes during treatment with cladribine (Moser et al. AAN 2023;P1.006). Fourteen patients (mean age 35.9 years, median EDSS 1.75) were followed up for 39 months. Treatment significantly reduced sNfL levels (mean 24.7 to 8.75 pg/mL). However, sNfL level at baseline or at 12 months was not correlated with long-term disease control. During the observation period, 36% of patients had breakthrough disease activity. The authors concluded that sNfL levels after the first treatment cycle were not predictive of long-term response.
How is JC virus transmitted?
Masking and social distancing substantially reduced the spread of seasonal influenza during the COVID-19 pandemic. The Centers for Disease Control reported that the seropositivity rate was 0.2% of samples tested in 2020/2021 vs. 26-30% pre-pandemic (https://www.cdc.gov/flu/season/faq-flu-season-2020-2021.htm). The same does not appear to be the case for JC virus transmission. An analysis of the TOUCH database (N=22,375) found that during the period of masking and social distancing (2020 to 2022), anti-JCV antibody serostatus changed in about 7.2% of Tysabri patients (Krieger et al. AAN 2023;P12.007). This was comparable to the rate seen prior to the pandemic (7.7% in 2017-2018). These findings suggest that JCV virus transmission was largely unaffected by masking and social distancing, leaving open the question of how Tysabri patients acquire the virus.
Does body weight affect B cell kinetics?
A retrospective study examined the impact of body-mass index (BMI) on B cell repopulation in 381 MS patients receiving ocrelizumab (Loeffler et al. AAN 2023;P7.016). Mean age was 48.6 years, 61.5% were female and 58.5% had a BMI >25 (overweight/obese). There was no significant difference in the rate of B cell repopulation in patients with BMI >25 vs. BMI ≤25. A prior study in 108 MS patients reported that a higher BMI was associated with faster B cell repopulation (Signoriello et al. Mult Scler Relat Disord 2020;43:102186). A post-hoc analysis of the OPERA/ORATORIO trials recently reported that patients with higher BMI obtain less benefit from ocrelizumab (Hauser et al. Neurol Neuroimmunol Neuroinflamm 2023;10:e200094).
Hyperglycemia medications and MS risk
A novel health claims database analysis reported that exposure to anti-hyperglycemia medications was associated with a lower risk of developing MS in younger individuals (Branigan et al. AAN 2023;P9.007). Patient records were examined for an MS diagnosis in the 1-6 years after a diagnosis of Type 2 diabetes. In subjects aged < 45 years, there was a significantly lower risk of MS (RR 0.22). The opposite was seen in individuals aged >45 years, where exposure to diabetes medications was associated with a higher risk of MS in women (RR 1.53) and men (RR 1.17). The metabolic syndrome (diabetes, obesity) can be associated with neuropathological changes, such as a pro-inflammatory milieu and blood-brain barrier permeability (Van Dyken et al. Front Neurosci 2018;12:930). Also noteworthy is the finding of impaired insulin sensitivity in MS patients (Penesova et al. Metab Brain Dis 2015;30:895-901). Oral hypoglycemic agents (e.g. metformin) are currently being investigated in MS, ostensibly for their anti-inflammatory and antioxidant effects (Dziedzic et al. Int J Mol Sci 2020;21:5957). The authors concluded that additional research is needed to clarify the interactions between endocrinal factors and neuropathological changes in MS.
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