Background

Italy was strongly hit by COVID-19 pandemic, therefore the Italian Government decreed urgent measures promoting social distancing in order to limit the spread of the virus. In fact, since March 11^th, all not indispensable work, social, sporting, retail and recreational activities were suspended or, where possible, converted to the so-called smart-working. Fear of getting sick from COVID-19, government’s lockdown and the imposed social distancing might have an impact on anxiety, depression and quality of life (QoL) in people with Multiple Sclerosis (pwMS).

Objectives

The aim of our study was to investigate anxiety, depression and QoL changes in pwMS during SARS-CoV-2 outbreak and lockdown in Italy.

Methods

Sixty-seven pwMS with a previous (less than 6 months) neuropsychological evaluation before SARS-CoV-2 outbreak (T0) were re-evaluated at the time of the outbreak and lockdown in Italy (T1). They underwent a clinical and neurological evaluation (at T0) and completed the State-Trait Anxiety Inventory (STAI-Y1), the Beck Depression Inventory second edition (BDI-II), and Multiple Sclerosis Quality of Life-54 (MsQoL-54) at T0 and T1. Bonferroni correction for multiple comparisons was applied.

Results

BDI-II and STAI-Y1 scores did not change between T0 and T1, whereas the satisfaction on sexual function subscale of MsQoL-54 was significantly higher at T1 (p<0.001).

Conclusions

Despite the tight Italian lockdown due to the COVID-19 pandemic and the fear of getting sick, we did not observe a relevant negative impact on anxiety, depression and QoL of our sample of pwMS. Contrariwise, we were even able to detect some positive effects on specific aspects of QoL, such as sexual satisfaction.

Background

The cerebellum plays a relevant role in both motor and cognitive function due to the high number of cerebellar connections with the brain and spinal cord. Alterations in cerebellar functional connectivity may modulate the relationship between brain structural damage and clinical impairment in multiple sclerosis.

Objectives

To investigate whether resting-state functional connectivity changes of the sensorimotor cerebellum represent adaptive neuroplastic mechanisms to reduce the effects of structural damage on physical disability in patients with multiple sclerosis and no disability.

Methods

A total of 144 multiple sclerosis patients with a score of ≤1.5 on the Expanded Disability Status Scale and 98 healthy subjects were selected from the Italian Neuroimaging Network Initiative database and included in this study. Both patients and healthy subjects underwent multimodal 3T-MRI including functional MRI at rest. After parcellation of the cerebellum, the sensorimotor cerebellum (lobules I-V + VIII) was identified and used as a seed for resting-state functional connectivity analysis.

Results

In patients, brain areas with decreased and increased sensorimotor cerebellar functional connectivity were found to coexist with respect to healthy subjects. Areas of decreased cerebellar functional connectivity, i.e. the lingual gyrus, insula, and precentral and postcentral gyri, negatively correlated with T2 lesion load and white matter atrophy. Areas of increased cerebellar functional connectivity, i.e. the posterior cerebellum, nucleus accumbens, prefrontal cortex, cingulate/paracingulate gyri, and precuneus, positively correlated with T2 lesion load and cerebellar and thalamic atrophy. Areas of increased cerebellar functional connectivity with the cingulate gyrus and precuneus negatively correlated with global grey and white matter atrophy.

Conclusions

In patients with multiple sclerosis, the sensorimotor cerebellum extensively reorganizes its functional links with other brain regions. Areas of decreased cerebellar functional connectivity related to white matter damage are present even in the absence of clinical manifestations and may represent a preclinical condition. Areas of increased cerebellar functional connectivity related to both lesion burden and thalamic or cerebellar atrophy likely represent a compensative reorganization of brain circuits. Lastly, global atrophy may influence functional connectivity changes in posterior cortical areas.

Background

Despite the high prevalence and debilitating nature of fatigue and depression in Relapsing-Remitting Multiple Sclerosis (RRMS), the underlying pathophysiology is still far from being fully understood. While several findings highlighted the contribution of white matter lesion load (WMLL) and brain atrophy, the role of cortical lesions (CL) has been only marginally assessed.

Objectives

To investigate: i) the contribution of CL volume to fatigue and depression; ii) the relative role of total CL volume (tCLV), intracortical lesion volume (ICLV) and juxtacortical lesion volume (JCLV).

Methods

Sixty-five RRMS patients underwent: i) clinical evaluation including the Expanded Disability Status Scale (EDSS), ii) assessment of fatigue and depression trough the Modified Fatigue Impact Scale (MFIS) and the Beck Depression Inventory (BDI), iii) a 3T–MRI protocol including Double-Echo (DE) and 3D–Double Inversion Recovery (DIR) imaging to identify WMLL and CL. Correlation analyses were run between WMLL, CL and MFIS, and BDI. A multiple linear regression model was applied to evaluate the contribution of CL to MFIS and BDI, controlling for clinico-demographic data and WMLL.

Results

The correlation analysis showed that tCLV and JCLV correlated with MFIS (rho= 0.31, p=0.007; rho= 0.28, p=0.01 rispectively) and BDI (rho= 0.24, p=0.03 and rho= 0.23, p=0.04, rispectively), while ICLV or WMLL did not correlate with neither MFIS nor BDI. Regression analysis did not reveal any CL volume as a significant predictor of fatigue or depression.

Conclusions

Although CL volume is not a significant independent predictor of fatigue and depression, our study shows a significant role of CL volume in determining these symptoms in RRMS.

Background

Cognitive deterioration affects a large proportion of multiple sclerosis (MS) patients, but it occurs also with healthy aging. The effects of aging on cognitive performance in MS have not been fully investigated yet.

Objectives

By evaluating a large multicentric cohort of healthy controls (HC) and MS patients, we compared the age-related decline of cognitive functions occurring in HC and MS patients.

Methods

Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was evaluated in 301 healthy controls (HC) (150 females, age 18-76 years, mean education=14.9 years) and 664 MS patients (421 females; age 18-77 years; mean education=13.3 years; 536 relapsing-remitting and 128 progressive MS) recruited from 3 centers of the Italian Neuroimaging Network Initiative (INNI, www.inni-ms.org). BRB-N allowed to assess verbal memory (Selective Reminding Test [SRT]), visuospatial memory (10/36 Spatial Recall Test [SPART] and delayed-recall), information processing speed (Symbol Digit Modalities Test [SDMT], Paced Auditory Serial Addition Test [PASAT] 3” and 2”) and verbal fluency (Word List Generation [WLG]). Raw scores of each test were converted to Z-scores, based on HC’s cohort by running linear models to regress out the effects of sex, age, education and center. The residuals for both HC and MS patients were then divided by the HC’s error term. Linear models were built for investigating the association of standardized scores with age in MS patients.

Results

In HC, scores of all the BRB-N tests except PASAT 3” and WLG declined significantly with aging (p from <0.0001 to 0.003). Compared to HC, MS patients showed significant worse estimated mean performances already from the age of 20 years in all BRB-N tests (p from <0.0001 to 0.003), except for SPART, SPART delayed-recall and PASAT 3”, whose estimated mean scores significantly worsened later in age (p from 0.03 to 0.04). MS patients showed also a steeper age-related decline of SPART, SPART delayed-recall, SDMT, PASAT 3”, PASAT 2” performances compared to HC (p from <0.0001 to 0.008). No differential effect of age compared to HC was detected in MS patients for WLG and SRT.

Conclusions

Cognitive deficits already affect young adult MS patients and progress faster during patients’ lifespan compared to healthy aging. A different susceptibility to age-effect exists in the cognitive tests currently used to assess cognition in MS patients. The accumulation of MS-related damage combined with brain aging may have synergic detrimental effects on cognitive performances of MS patients.

Funding. This project has been supported by a research grant from the Fondazione Italiana Sclerosi Multipla (FISM2018/S/3), and financed or co-financed with the ‘5 per mille’ public funding.