Background and Aims:

To define post-acute cognitive and behavioural features in a large cohort of subjects with confirmed COVID-19.

Methods:

49 subjects with confirmed COVID-19 underwent a comprehensive neuropsychological assessment and a brain MRI scan within two months from hospital discharge. Frequencies of cognitive and behavioural alterations, according to the normative data, were reported. Total brain volumes were obtained. In all patients, correlations were performed between neuropsychological performances, brain volumes and the severity of acute-phase respiratory symptoms at the time of hospital admission.

Results:

At the time of the visit, 16% of patients presented with depressive symptoms and 18% reported post-traumatic stress disorder. 45% of the total sample showed executive dysfunctions, 30% visuospatial difficulties, and 25% long-term verbal and nonverbal memory problems. The youngest patients (age<50) showed the most severe profile with 75% of patients showing executive dysfunctions, 50% pure visuospatial dysfunctions and 40% primary long-term memory problems. The total sample showed a negative relationship between frontal executive performances and the severity of acute-phase respiratory symptoms at the hospital admission (R=-0.347; p<0.01). No significant relationship was observed between cognitive performances and brain volume.

Conclusions:

Cognitive and behavioural alterations are associated with COVID-19 infection within two months from hospital discharge and were more severe in the youngest patients. The patient cognitive/behavioural disturbances were independent of their brain structural integrity.

Further studies are needed to determine whether these alterations are directly linked with the infection itself or with its related consequences, and whether they are reversible or part of a neurodegenerative process.

Background and Aims:

Given the evidence of long-term neurological complications following COVID-19, including cognitive impairment¹, we aimed at assessing EEG cortical source densities (CSD) and linear lagged connectivity (LLC) values and their clinical, structural brain MRI and neuropsychological correlates in patients with recent COVID-19.

Methods:

We enrolled 49 adult patients with recent COVID-19, good recovery and cognitive disturbances, observed at 2-months post-discharge evaluation. Same-day 19-channel EEG and neuropsychological testing battery were performed; 36/49 patients underwent also 3T MRI. Thirty-three retrospective, age-/sex-matched healthy controls were selected, having no history of neurological or cognitive disturbances. Using low-resolution brain electromagnetic tomography (eLORETA) solutions at fixed frequencies², EEG lobar CSD and LLC values of COVID-19 and healthy subjects were investigated. Correlations with cognitive scores, recent and past medical history and white matter hyperintensities (WMH) volume were explored.

Results:

Patients showed pathological scores in memory, executive and visuo-spatial functions. 14/49 patients had symptoms suggestive of reactive depression. Analysis at delta frequency band (1.5-4.0 Hz) revealed higher CSD within bilateral frontal-temporal regions and greater LLC values between right frontal lobe and bilateral temporal and parietal-occipital lobes in COVID-19 patients. Delta CSD and LLC values positively correlated with executive performances, whereas no significant correlations were found with WMH, past and recent medical history.

Conclusions:

Differently from our acute-phase study³, EEG alterations after COVID-19 might be at least partially independent of acute infection severity and suggest instead a link with ongoing neuro-psychiatric symptoms. 8-months follow-up data will confirm the reversibility and/or evolution of our findings.

Background and Aims:

The COVID-19 pandemic and related restrictions has been disruptive for healthcare systems, especially for time-sensitive emergencies. During the viral outbreak, a reduction of stroke patients’ volume in hospitals in Italy and worldwide has been extensively reported, as well as a severe delay in all integrated steps of hyperacute treatments and management.

Methods:

This was a single-centre, observational cohort study performed in Careggi University Hospital, a Tertiary Stroke Center with endovascular facilities of the integrated “Hub and Spoke” stroke organisation in Area Vasta Centro of Tuscany. We retrospectively analysed system processes timings, treatment and clinical variables between early pandemic phase (from 1^st of March to 30^th of April 2020) and pre-pandemic (the same period of 2019), to evaluate the impact of COVID-19 related restrictions on performance metrics and overall stroke care efficiency at our center.

Results:

In 2020 the number of acute stroke patients admitted to our Hospital and those receiving tPA showed a mild decline (114vs94 stroke patients and 22%vs20% receiving rtPA), while the proportion receiving EVT raised (from 23% to 31%, p=0.190). A slight delay in patients’ shipment and treatment administration was generally detected in 2020 (an increase of 45min p=0.484 in symptom onset to 1st_Hospital_door_time, 19min p=0.192 in door_to_needle and 18min p=0.220 in door_to_groin_puncture), but some intrahospital parameters improved regarding during pandemic: mean door to neurological evaluation and to CT Scan timings were significantly lower in 2020 (12minvs0 min, p=0.005 and 93vs58, p=0.01, respectively).

Conclusions:

Overall quality of care performance at our comprehensive stroke center was not affected during lockdown period.

Background and Aims:

The number of cases of encephalitis in COVID-19 pandemic is increasing. We describe characteristics and outcome of encephalitis in COVID-19 (COV-ENC) patients in one of the most affected regions by COVID-19 of the world, Lombardia, during the first pandemic wave.

Methods:

A multi-center observational study on neurological complications in COVID-19 patients was conducted by the Italian society of Hospital Neuroscience (SNO). Adult patients admitted to 20 Neurological Departments in Lombardia between February-April 2020 with COV-ENC have been included.

Results:

30 COV-ENC patients had a mean age of 66.5 years and male frequency of 56.6%. Altered consciousness was characterized by confusion in 86%, coma in 30%, delirium in 37.9% and alteration of personality traits in 27.6%. Epileptic seizures occurred in 74% of cases. One third of cases had hyperproteinorrachia, one third pleocytosis/hyperproteinorrachia, and remaining third had a normal CSF. PCR for SARS-CoV-2 was negative in all tested patients. EEG was altered in 82.7% of patients. Brain CT and MRI were normal in 9 patients, and among abnormal findings 9 patients had mesial temporal lesions, one of which confirmed with PET imaging. The course was favorable in 39.2% of patients, sequelae were few in 26.6% and moderate in 19.2%, while 20% of patients died.

Conclusions:

The outcome tends to be worse in male patients. PCR negativity seems to confirm an autoimmune etiology more than a direct invasion of the virus. However, a temporal lobe involvement, detected in 30% of patients with COV-ENC, suggests usual sites of encephalitis due to herpes virus.

Background and Aims:

Persistent hyposmia represents one of the most common neurological complications of coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. To date, however, its neural bases remain poorly understood.

Methods:

Sixty-two patients (mean age 64 ± 10.5 years, range 35-79) underwent whole-body [18]F-FDG-PET including a dedicated brain acquisition following their recovery after SARS-Cov2 infection. Patients that previously required mechanic ventilation or showed severe respiratory distress syndrome due to SARS-CoV-2 infection were excluded given the potential independent effect of these clinical scenarios on brain metabolism. The presence of isolated persistent hyposmia was assessed with the smell diskettes olfaction test. Voxelwise analyses were used to compare hyposmic and non-hyposmic patients and controls (61 subjects, age 61.1 ± 11.1 years), as well as to correlate regional metabolism with quantitative performance at the olfaction test.

Results:

Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in hyposmic patients with respect to controls and in the orbitofrontal cortex in hyposmic patients compared to non-hyposmic patients. In the hyposmic group, quantitative performance at the olfaction test correlated with regional metabolism in the cingulate gyrus, in the bilateral thalami and in the right temporal gyrus.

Conclusions:

Isolated persistent hyposmia hyposmia after SARS-Cov2 infection without an history of severe respiratory distress is associated with significant metabolic alterations in regions beyond those involved in primary olfactory processing.

Background and Aims:

Ocrelizumab (OCZ) has been approved in 2018 in Italy for the treatment of patients with multiple sclerosis (MS), but real-world data about its use are limited.

Aims: To evaluate effectiveness and safety of OCZ for primary progressive MS (PPMS), active secondary progressive (SPMS) and relapsing remitting MS (RRMS) patients recruited at the MS Center of Bari, Italy

Methods:

Patients with ≥3 infusions were retrospectively recruited. Clinical and demographic data were collected (Tab 1). Wilcoxon paired test was used to evaluate the EDSS changes over time. We assessed relapse incidence after treatment start and adverse events (AE).

Results:

Our cohort of 133 patients included 35 PPMS, 22 SPMS and 76 RRMS patients. The median (IQR) follow-up after the first DMT start were 2,09 (0,6-3,3), 1,8 (0.08-4.02), 1.63 (1.17-3.10) years for PPMS, RRMS and SPMS patients respectively. The last available EDSS after OCZ start significantly increased compared to the baseline values only in the PPMS group (p= 0.01), but it remained stable in SP and RR groups. No clinical relapses and no evidence of radiological activity were found in RRMS patients during follow up. AEs reported were mostly infusion-related reactions in all groups, 1 Dengue fever and 2 Herpes Zoster infections. Seven of our cases reported COVID-19 infection during pandemic, one of them died.

Conclusions:

Our real-world data indicate that OCZ stabilized disability progression and disease activity in RR and SP patients. The safety profile was quite favorable in this cohort.

Background and Aims:

To compare serum Neurofilament light chain (sNfL) levels in patients with Multiple Sclerosis (MS), MOG-Antibody Disease (MOGAD) and Neuromyelitis Optica Spectrum Disorders (NMOSD).

Methods:

We performed a propensity score (PS)-based nearest-neighbor matching within a caliper of 0.05 to select patients with homogeneous baseline characteristics. Using ultrasensitive single-molecule array assays (SIMOA), we measured sNfL in the sera of adult patients with MS (n=17), MOGAD (n=15), NMOSD with AQP4-Ab (n=16) and Healthy Controls (HCs) (n=24). MOG-IgG and AQP4-IgG were analysed by a semiquantitative ratiometric method. SNfL levels were compared among the different disease groups. Spearman test was used to evaluate the correlation between sNfL and EDSS score in each group and to estimate the correlation between MOG-IgG titer and sNFL levels.

Results:

MOGAD patients showed a significant lower sNFL levels compared to MS (median 16,47pg/mL range 5,10-71,78 vs 7,34 range 2,43-115,43; p=0.01) and NMOSD adult patients (median 16,46pg/mL range 4,2-196,47; p=0.02)[Fig.1]. All groups had an increased sNFL value compared to HCs (median 5,64pg/mL range 2,47-8,84; p<0.0001). A positive significant correlation was found between sNfL and EDSS scores in MOGAD (r=0.636; p=0.005), NMO-AQP4 (r=0.908; p<0.0001) and MS patients (r=0.534; p = 0.014) [Fig.2]. No correlation was found between MOG-IgG titers and sNfL levels (p=0.294).

Conclusions:

Our results confirm the value of sNfL as a clinically meaningful blood biomarker of disability levels in different demyelinating diseases. In MOGAD patients MOG-IgG titers are not correlated with the sNfL levels, suggesting that they are more related to inflammatory processes.

Background and Aims:

Clinically isolated syndrome (CIS) characterizes the first episode of multiple sclerosis (MS). IgG oligoclonal bands (OCBs) and high levels of inflammatory factors in CSF represent promising biochemical markers of CIS and MS. Here we evaluated the levels of a complex panel of CSF inflammatory mediators in CIS and relapsing-remitting MS (RRMS) patients at time of diagnosis, both with and without OCB, compared with a control group.

Methods:

Patients with CIS (n=22), RRMS (82 OCB+; 36 OCB-) and controls (n=29) with other neurological diseases, wereenrolled at diagnosis and followed for two years. Mann-Whitney tests were used to compare CSF levels of 20 inflammatory mediators between groups.

Results:

CIS patients showed higher levels of CXCL13 (P<0.01), IFN-γ (P<0.001), CCL25, chitinase-3 L1, IFN-α2 (all P-values<0.05) than the control group, whereas showed increased levels of BAFF (P<0.01) and decreased levels of IFNλ2 (P<0.01) compared to RRMS patients. RRMS group presented higher levels of several molecules, including CXCL13 (p<0.001), IFN-γ (p<0.001), IFN-α2 (p<0.001), IFNλ2 (p<0.001), MMP2 (p<0.05) than the control group. In particular, OCB(+) RRMS patients, showed increased levels of CXCL13 (P<0.001), sCD163 (P<0.01), and decreased levels of BAFF (P<0.01), IFNλ2 (P<0.05), and IL10 (P<0.05) compared to OCB(-).

Conclusions:

Since early CIS episode, abnormal, specific CSF inflammatory profile, mainly pro-inflammatory immune response linked to both B- and T-cells, confirms the crucial role played by intrathecal CSF inflammation in the disease pathogenesis, even before the MS diagnosis. In particular, CSF BAFF levels, possibly mediating B-cell and T-cell activation, may represent an early candidate marker specific of CIS.