Background

“Classical” cognitive impairment is well characterized in Multiple Sclerosis (MS), but social cognition seems to be an overlooked cognitive domain. The Reserve theory posits that baseline differences in maximal lifetime brain volume (Brain Reserve (BR)) and lifetime intellectual enrichment (Cognitive Reserve (CR)) affect cognitive performance in neurodegenerative disease.

Objectives

To investigate the effects of of BR and CR on social cognition performance, by determining if these factors moderate/attenuate the impact of grey matter (GM) atrophy.

Methods

Sixty MS patients and sixty healthy controls were enrolled. Total intracranial volume (ICV) was used has a proxy of BR and years of formal education as a proxy of CR. All participants underwent Theory of Mind (ToM) testing and 3Tesla brain MRI. Multiple linear regression analyses were performed to assess the protective effect of BR and CR on social cognition (ToM Eyes Test and ToM Videos Test). Furthermore, we investigated differences in effects according to disease duration (<10 years vs >10 years).

Results

In the linear regression analyses investigating the effect of education and ICV on social cognition, cortical GM was the only measure of brain atrophy retained for both ToM Eyes Test (R² = 0.101, p = 0.017) and Videos Test (R² = 0.098, p = 0.021), after controlling for age and sex. ICV was also an independent predictor of Eyes Test (R² = 0.079, p = 0.028) and Videos Test (R² = 0.097, p = 0.016). Moreover, an ICV x cortical GM volume interaction was significant on Eyes Test (R² = 0.158, p = 0.002) and Videos Test (R² = 0.198, p = 0.001), whereby greater ICV attenuated the negative impact of GM atrophy on social cognition tests. Conversely, education was not associated with performance on social cognition tests. Furthermore, stratification for disease duration showed that the protective effect of ICV on social cognition occurred in early stages of disease (<10 years), moderating the impact of GM atrophy. However, this effect was lost in later stages (>10 years).

Conclusions

Social cognition was associated with BR (ICV), which has a moderator effect on the negative impact of GM atrophy, while the CR (education) had no significant effect. Our results support an association between BR and social cognition which is consistent with a strong hereditability of both ICV and social cognition, suggesting that social cognition may be a cognitive domain less influenced by environmental factors, such as CR.

Background

Theory of Mind (ToM), the ability to attribute mental states to others, is an integral domain of social cognition essential to human interaction. While cognitive decline is well known to be a common and early feature of MS, research into social cognitive impairment in MS patients is scarcer. In recent years, MS has been shown to affect ToM even in the absence of impairment in other cognitive domains.

Objectives

We aimed to define the predictive value of social cognition tests to discriminate MS patients from Healthy Controls (HC), compare them with other standard neuropsychological tests, and determine the optimal cut-off points for scoring.

Methods

Sixty consecutive MS patients and 60 HC were enrolled, matched by sex, age, and education level. All participants were assessed with a standard neuropsychological battery for MS (MACFIMS), with cognitive impairment defined as a defect in two or more domains. All participants also underwent social cognition testing [Reading the Mind in the Eyes test (RMET) and Videos test (VT)].
Discriminatory power of each test was determined by Receiver Operating Characteristics curve analysis, calculating the area under the curve (AUC).

Results

As expected, HC outperformed MS patients in all cognitive domains, and 34 (56.7%) patients were classified as cognitively impaired. Compared to HC, patients had significantly lower scores on ToM testing (RMET 58.7% ± 13.8% vs 81.9% ± 10.4%, p < 0.001 and VT 75.3% ± 9.3% vs 88.1% ± 7.1%, p < 0.001). Interestingly, performance on ToM tests did not differ significantly between cognitively impaired and cognitively intact patients (RMET 56.9± 14.5% vs. 61.0± 12.7%, p=0.251 and VT 74.5± 11.2% vs. 76.3±5.9%, p=0.431).

ROC analysis yielded the highest discriminatory power for ET (AUC 0,923, 95% CI 0,859 to 0,964, p<0.001), followed by VT (AUC 0.879, 95% CI 0.807 to 0.931, p<0.001). Among standard neuropsychological tests, Symbol digit modalities test had the highest discriminatory power (AUC 0.729, 95% CI 0.640 to 0.806, p<0.001).

Youden index analysis established the optimal cutoff point at =<27 for ET (S 93.33, E 75.00, Youden index J 0.6833) and =<21 for VT (S 76.67, E 88.33, Youden index J 0.65).

Conclusions

As has been previously reported, in our patient series, ToM deficit was shown to occur independently of cognitive decline. Furthermore, ToM tests showed higher discriminatory power for the diagnosis of MS than standard neuropsychological assessment. Thus, social cognitive impairment might merit further investigation as a possivle clinical marker of disease in MS,

Background

Disease-modifying drugs (DMDs) may result in a high risk of opportunistic infections including progression of primary tuberculosis or reactivation of latent TB (LTB).

Objectives

The aim of this work is to characterize LTB in a population of patients with multiple sclerosis (MS) and to analyze its impact on MS management.

Methods

Retrospective study of MS patients who underwent QuantiFERON-TB Gold (QTF-G) in our centre between January 2015 and May 2019.

Results

Among 367 MS patients, QFT-G was negative in 323 (88%), positive in 35 (10%) and undetermined in 9 (2%). No cases of active infection were detected. Regarding patients with a positive QFT-G, the mean (SD) age was 49.1 (10.7) years, Expanded Disability Status Scale (EDSS) 3.1 (2.0), disease duration 9.7 (8.5) years, treatment duration 7.7 (7.0) years and number of previous DMDs 1.7 (2.1). Ten patients (28.6%) were DMD-naïve. Age, EDSS, disease duration, treatment duration and number of DMDs were not associated with positive QTF-G. All patients with a positive QTF-G were treated for LTB, 34 with isoniazid for 9 months and one with rifampin for 4 months. Two patients (5.7%) developed hepatic adverse effects, resolved after discontinuation of isoniazid, followed by a switch to a 4-month regimen of rifampin, which was started when liver enzymes returned to the normal range. Of the 35 patients with a positive QTF-G, 4 (11%) were started simultaneously on a DMD and LTB treatment regimen and in 31 (89%) there was a postponing of the start/switch of DMD (8 were DMD-naïve, 15 were kept on previous DMD and 8 suspended the previous DMD and were left temporarily without MS medication). The mean (SD) duration of the postponement was 3.4 (3.0) months. Four patients had relapses during the period waiting for the start/switch of DMD.

Conclusions

In our study, the treatment of LTB was effective and relatively safe. As 12.9% of patients had relapses while waiting for the start/switch of DMD, our work suggests that the start of DMDs should not be delayed beyond the 4-8 weeks recommended in the literature.