Author Of 4 Presentations
LB1261 - Resting-state neural activity, cognitive functioning and reserve in relapsing-remitting multiple sclerosis: a microstates EEG study. (ID 2157)
In multiple sclerosis (MS) the prevalence of cognitive impairment (CI) ranges 40–65%. Besides, high level of cognitive reserve (CR) is strongly associated with better cognitive functioning in patients with MS (PwMS). How the cognitive performance and the CR level in PwMS can be associated to the fluctuations of spontaneous EEG is not completely understood.
To compare scalp voltage maps (microstates) during resting between PwMS and healthy controls (HCs) and to investigate how the temporal parameters of microstates and the level of CR can predict the cognitive performance.
50 relapsing-remitting multiple sclerosis (RRMS) patients and 25 HCs, matched for age and sex, were enrolled. For PwMS, we administrated the Brief International Cognitive Assessment (BICAMS) and the Cognitive Reserve Index questionnaire (CRIq). All participants underwent to 15-min of high-density EEG recording (256ch), closed-eyes. EEG data were filtered 1-40Hz, ICA-corrected for artifacts and downsampled to 256Hz. Microstates analysis identified a set of voltage maps representing the EEG activity for all participants that were fitted on the corrected-EEGs to quantify: global explained variance (GEV), mean duration (MD), time coverage (TC) and occurrence (Frequ). Repeated Two-Way ANOVA (Bonferroni comparisons) was used to compare groups and microstates; stepwise multiple linear regression was performed to study the cognitive performance in correlation to the microstates and level of CR; alpha=0.05.
24% of PwMS had CI and 34% reported a low level of CR. Microstates analysis found 4 maps in both groups and PwMS showed a significant increase in Map-A (GEV/TC/Frequ) and Map-B (GEV), while Map-C (MD) and Map-D (MD/TC) were significantly decreased with respect to HCs. Multiple linear regression analysis showed two strong predicted models (p<0.001), respectively, for Brief Visual-Spatial Memory Test (BVMT) and Symbol Digit Memory Test (SDMT). BVMT was predicted by GEV of Map-C improved by CRI_L, reaching 44% of explained variance. SDMT was predicted by Frequ of Map-A and CRI_Edu.
Microstate analysis reveled altered fluctuations of EEG topographies in RRMS patients with low disability and at the first stage of disease. In particular, Map-C (salience network) and leisure as well as Map-A (auditory processing) and education, respectively, predicted BVMR and SDMT scores.
P0688 - Area postrema syndrome and longitudinally extensive transverse myelitis in a patient with prostatic adenocarcinoma and Aquaporin-4 antibodies. (ID 1872)
Neuromyelitis optica spectrum disorder (NMOSD) is not defined as a “classical” paraneoplastic neurological syndrome (PNS), however there are growing evidences that NMOSD may be associated with cancer.
The aim of the present report is to describe the clinical presentation of a patient with NMOSD of probable paraneoplastic origin.
A 79-years old man presented with acute onset of mild dysphagia associated with intractable hiccups and vomiting one month after radiotherapy for prostatic adenocarcinoma (cT2N0M). Two weeks later, he developed subacute lower-limb weakness and hypoesthesia that rapidly spread involving the trunk and upper limbs. MRI showed an extensive T2 hyperintense, tumefactive spinal cord lesion, extending from C2 to the conus and similar lesion in the area postrema. Cerebrospinal fluid analysis showed increased cell count (mononuclear cells) and protein concentration. He resulted positive for Aquaporin-4-IgG (AQP4) antibodies on serum. He was treated with intravenous steroids with mild improvement.
Our patient fulfills the criteria for a “probable PNS”, according to PNS diagnostic criteria, since NMOSD is a “non-classical” PNS and cancer occurred within two years from the diagnosis. It has been recently highlighted that older male patients (>45 years) presenting with longitudinally extensive transverse myelitis or patient with an “area postrema” syndrome at onset have higher risk for neoplasm associated NMOSD. Appropriate tumor screening should be always performed in patients with the aforementioned clinical features.
Since prostatic cells express AQP4, we hypothesize that AQP4-IgG could be part of the immune response against cancer cells or alternatively that radiotherapy could have led to a break of tolerance against AQP4, given the close temporal relationship with disease onset.
Paraneoplastic NMOSD is a rare disease that is becoming more frequently recognized. Further studies should elucidate the immunological relationship between cancer and AQP4-IgG.
P0883 - MRI activity and extended interval of Natalizumab dosing: a multicenter Italian study (ID 1269)
- M. Clerico
- S. De Mercanti
- A. Signori
- M. Iudicello
- C. Cordioli
- E. Signoriello
- G. Lus
- S. Bonavita
- L. Lavorgna
- G. Maniscalco
- E. Curti
- L. Lorefice
- E. Cocco
- V. Nociti
- M. Mirabella
- D. Baroncini
- G. Mataluni
- D. Landi
- M. Petruzzo
- R. Lanzillo
- I. Gandoglia
- A. Laroni
- R. Frangiamore
- A. Sartori
- P. Cavalla
- G. Costantini
- M. Sormani
- R. Capra
Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML) without efficacy reduction.
To evaluate the non-inferiority of the efficacy of an extended interval dosing (EID) regimen compared with the standard interval dosing (SID) of natalizumab regarding the multiple sclerosis (MS) MRI activity.
It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and eight patients were enrolled. Median dose interval (MDI) following 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks).
Two hundred and sixteen patients were in the SID group (MDI = 4.4 weeks) and 144 in the EID group (MDI 6 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 2.98% (95% CI: 0.56-5.40) vs 3.32% (95% CI: 0.00-6.65%) [p=0.88] and 6.65% (95% CI: 3.02-10.29) vs 5.67% (95% CI: 1.76-9.58%) [p=0.73]. The EID regimen does not increase the occurrence of MRI activity after 6 and 12 months.
There is no evidence of a reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation confirms previous clinical results and together with the increasing evidence of a reduced risk of PML associated to an EID regimen, supports the need of a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, in order to better manage JCV-positive patients after 24 doses of natalizumab.
P1086 - Botulinum toxin injections in multiple sclerosis versus post-stroke spasticity (ID 1888)
Botulinum toxin (BTX) is an effective and safe treatment for spasticity both in multiple sclerosis (MS) and post-stroke spasticity (PSS).
The aim of our single-centre retrospective study was to compare the sites of injection and the dosages of BTX used for the treatment of spasticity in MS and PSS.
We enrolled 33 patients with MS and 55 patients with PSS that were treated with BTX in our outpatient spasticity clinic. Clinical and demographic data were collected. Total BTX dosage, upper and lower limb dosage, pattern of injected muscles, and their respective dosage were recorded. We performed a statistical analysis to compare BTX treatment dosage in the two conditions and to investigate any predictor of total BTX dosage.
MS patients received a significant lower total BTX dosage compared to PSS (p<0.001): they were treated with lower BTX dosage in the lower limbs (p=0.005), but not in the upper limbs (p=0.30). Patients with MS were rarely injected in the upper limbs. Proximal upper limbs muscles were more frequently injected in MS, while patients with PSS were more frequently treated in distal muscles (fingers). In the lower limbs MS patients were more frequently injected in adductor muscles and rectus femoris while PSS patients were treated in soleus and tibialis posterior. EDSS was the only variable correlated to total BTX dosage (rho=0.399, p=0.021).
In our experience, MS spasticity requires a lower BTX dosage than PSS. This observation could be explained both by a different pattern of muscles affected by spasticity in these two diseases and also by different clinical management (e.g. the need of maintaining a greater residual function in MS, especially in lower limbs).
Presenter Of 2 Presentations
LB1258 - SARS-CoV-2 pandemic lockdown: perceived consequences on multiple sclerosis patients (ID 2154)
SARS-CoV-2 pandemic implied a prolonged lockdown phase, which may have deep consequences for mental and physical health. The effects may be particularly severe for people with chronic diseases such as multiple sclerosis (MS).
The aim of the present study was to evaluate the self-reported possible consequences on MS patients of lockdown phase during SARS-CoV-2 pandemic.
At the end of lockdown phase we performed a telephonic interview on MS patients of our clinic. All patients underwent neurological tele-consult during lockdown phase. We collected demographic and clinical characteristics of the patient. Symptoms of SARS-CoV-2 infection, worsening of anxiety, depression, fatigue, spasticity, changes in physical activity, weight, and change in eating habits were investigated.
Ninety-five patients were enrolled in the study (F 71,3%), with a mean age of 50,3±10,8 years. Median disease duration was 163 months (0-459) and median EDSS at last in-person visit was 2 (0-8,5). Median PDDS was 2 (2-8). The distribution of patients according to disease form was the following: RR 77,7%, SP 13,8%, PP 8,5%. Twenty-two patients reported symptoms suggestive of possible SARS-CoV-2 infection (11,7% fever, 7% cough, 6,4% sore throat, 11,7% cold, 1,1% dyspnoea, 1,1% hyposmia). An increase in spasticity was reported by 18,1% of patients. Fatigue, anxiety and depression were increased in 27,7%, 37,2% and 35,1% of patients, respectively. Fifty-five patients reported worries for SARS-CoV-2 pandemic, with 43,6% of patients believing that the infection could have a particular impact on them compared to general population. The reported aspects on which pandemic and lockdown had a particular impact were: restrictions of personal freedom (27,7%), social retirement (22,3%), work-relate issues (19,1%), reduction of physical activity (7,4%), worries for relatives’ health (6,4%). Forty-six patients had an increase in weight (median increase 2kg, range 1-8), 63,8% reduced their physical activity and 35,1% of them increased the food intake.
Compared to pre-lockdown phase, a high percentage of MS patients report an increase in anxiety, depression, fatigue and spasticity, reduced exercise and increased weight. These aspects could impact particularly on MS patients with high disability.
LB1260 - Optic neuritis in long standing clinically stable secondary progressive multiple sclerosis after SARS-CoV-2 infection: a mere coincidence? (ID 2156)
The spread of SARS-CoV-2 raised concern of infection susceptibility in patients with autoimmune diseases, multiple sclerosis (MS) in particular. The effects of SARS-CoV-2 on MS disease activity are still unknown. To our knowledge, no increased risk of relapses during or after the infection has been reported.
The aim of the present report is to describe the case of a woman with longstanding secondary progressive MS presenting with optic neuritis 4 weeks after SARS-CoV-2 infection.
A 60-year-old patient was diagnosed with MS in 1999. Her first symptom (diplopia) dated back to 10 years earlier. In the following 10 years she reported 3 episodes of paraparesis. She was treated with interferon beta from 2000. She had no relapses nor new T2 lesions during treatment, but she developed a disease progression. In 2012 a diagnosis of secondary progressive diseases was made and treatment was stopped.
In the following years the EDSS remained stable at 6.5, without relapses. Her 2016 MRI scan revealed 2 new small brain lesions compared to the previous one (2012).
On 19th March 2020 the patient developed fever and hypogeusia, resolved spontaneously in 3 days. Seven days earlier she had made contact with her mother, who was diagnosed with COVID-19 infection. On 21th her orofaringeal swab resulted positive for SARS-CoV-2.
On 7th May a sudden reduction of visual acuity in the left eye (20/50) was reported. Left eye visual evoked potentials showed increased latency, with preserved amplitude. A diagnosis of optic neuritis was made. Visual acuity improved in less than a week. A brain MRI performed 20 days later and did not unveil any new lesion or contrast enhancement.
Inflammatory response via cytokine storm is a key feature in SARS-CoV-2 infection. Some immunomodulating drugs such as tociliziumab, an IL-6 receptor blocker, seem to be effective in this condition. Cytokine storm could also be a trigger for CNS autoimmunity: the increased frequency of acute disseminated encephalomyelitis and the reports of “probable” or seropositive autoimmune encephalitides in SARS-CoV-2 patients further suggest this hypothesis. As far as we know, this is the first report of a relapse after SARS-CoV-2 infection. Intriguingly, the relapse occurred in stabile non active progressive MS.
In conclusion, we report the case of acute ON in a secondary progressive MS patient 50 days after SARS-CoV-2 confirmed infection. We hypothesize a possible role of the infection in MS immune activity resurgence.