The Impact of Highly Effective Treatment in Pediatric-Onset Multiple Sclerosis: A Case Series.

INTRODUCTION: Pediatric-onset multiple sclerosis (POMS) is characterized by high inflammatory disease activity. Our aim was to describe the treatment sequencing and report the impact highly effective disease-modifying treatment (HET) had on disease activity. MATERIALS AND METHODS: Five consecutive patients with POMS were administered HET following lower efficacy drug or as initial therapy. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. RESULTS: Our patients had an average age of 13.8 years (range 9-17) at diagnosis and 13.4 years (range 9-16) at disease onset, and 2/5 (40%) POMS were female. The pre-treatment average annualized relapse rate was 1.6 (range 0.8-2.8), and the average follow-up length was 5 years (range 3-7). A total of 2/5 (40%) patients were stable on HET at initial therapy, and 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2-5). CONCLUSION: It has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.

A "Post-mortem" of COVID-19-associated stroke: a case-control study.

OBJECTIVES: To assess whether COVID-19 could be a concurrent factor in the genesis and/or worsening of stroke and to provide data on COVID-19 -associated stroke patients during the first pandemic wave and comparative data on COVID-19 negative stroke patients in the same period. MATERIALS AND METHODS: This is a retrospective, observational, case-control, single centre study, carried out in a General Hospital in northern Italy. Sixty-three consecutive stroke patients were included, COVID-19-associated stroke was classified as cases and non COVID-19-associated stroke as controls. RESULTS: A total of 19/63 (28.8%) had a COVID-19-associated stroke, 11 /63 (17.5%) were haemorrhagic and 52/63 (82.5%) ischaemic. COVID-19-associated strokes were more severe (p-value 0.019) and had a higher risk of severe disability and/or death (OR 3.79, CI 95%: 1.21-11.93, p-value 0.19). The COVID-19-associated stroke patients with onset during hospitalization for COVID-19 had a more severe stroke than patients with COVID-19 onset during hospitalization for stroke (p-value 0.019). CONCLUSION: Although no relationship was observed between the stroke aetiology and COVID-19, intriguingly, COVID-associated stroke turned out to be more severe and disabling. Hopefully, further studies will provide more data and help in the management of this emerging population.

Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach.

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population.

Secondary cluster headache due to a contralateral demyelinating periaqueductal gray matter lesion.

OBJECTIVES/BACKGROUND: Tension-type headache and migraine without aura are the most common primary headaches occurring in people with demyelinating diseases, whereas cluster headache (CH) can be considered exceptional. The location of demyelinating lesions could be strategic in these cases, involving areas interacting with the trigeminovascular system. METHODS AND RESULTS: We report a case of a 54-year-old woman with right-sided CH as the initial manifestation of multiple sclerosis and showing a left dorsal brainstem lesion on magnetic resonance imaging, in the region of the dorsal longitudinal fasciculus (DLF). CONCLUSION: Our case seems to suggest a possible role of the DLF in the process that leads to CH attacks. Because neuroimaging clearly showed a lesion contralateral to CH pain, we hypothesize that some fibers from periaqueductal gray matter project to the contralateral side, besides the known ipsilateral connections.

Copper deficiency-associated myelopathy in cryptogenic hyperzincemia: a case report.

Copper deficiency syndrome is an underestimated cause of posterior myelitis. We describe the case of a 41-year-old woman, who developed a subacute ataxic paraparesis associated with low back pain. Her 3T spine MRI showed a thin hyperintense FS-Echo T2 longitudinally extensive lesion involving the posterior columns of the cervical cord (from C2 to C6). An extensive diagnostic work-up excluded other causes of myelopathy and blood tests pointed out hypocupremia and mild hyperzincemia. Patients affected by this rare form of oligoelement deficiency typically develop progressive posterior column dysfunction with sensory ataxia and spasticity, sometimes associated with sensori-motor polyneuropathy. Clinical and radiological characteristics of posterior myelopathy due to copper deficiency are briefly reviewed. Physicians should be aware of this condition since a prompt introduction of copper supplementation can avoid progression of the neurological damage.

Five- and seven-year prognostic value of new effectiveness measures (NEDA, MEDA and six-month delayed NEDA) in relapsing-remitting multiple sclerosis.

The concept of 'no evidence of disease activity' (NEDA) has been proposed as a surrogate marker for treatment response in relapsing-remittent multiple sclerosis (MS). However, there is no agreement regarding its prognostic value, nor about the starting time for evaluation of drug effectiveness. Aim of this study was to investigate if the status preservation of two-year NEDA, 'minimal evidence of disease activity' (MEDA) and six-month delayed NEDA (6md-NEDA, with a "rebaseline" six months after the treatment start) predicts the achievement of long-term disability outcomes (EDSS score ≥ 4.0 or 6.0, 3-month confirmed disability progression (CDP) or conversion to secondary progressive MS) after five and seven years of disease. A total of 271 treatment courses (TCs) were analyzed in this retrospective study, involving all TCs started with any disease-modifying treatments (DMT). Overall, 72 (27%), 77 (28%) and 92 (34%) TCs maintained NEDA, MEDA and 6md-NEDA status after a two-year treatment. NEDA, MEDA and 6md-NEDA TCs had a lower risk of attaining all disability outcomes, compared to 'evidence of disease activity' (EDA) TCs. NEDA status determined a lower risk of CDP after five (OR 0.18, 95% CI 0.07-0.45, p < .0001) and seven years of disease (OR 0.15, 95% CI 0.05-0.44, p < .0001), with high positive (90%) and low negative (42%) predictive value, good specificity and low sensitivity. NEDA TCs had a lower risk of CDP compared to MEDA TCs after seven years (OR 0.30, 95% CI 0.10-0.91, p = .04). 6md-NEDA had a small impact on the improvement of NEDA prognostic value.

Spinal cord lesions are frequently asymptomatic in relapsing-remitting multiple sclerosis: a retrospective MRI survey.

BACKGROUND: Spinal cord (SC) involvement correlates with poor prognosis in patients with multiple sclerosis (MS). Nevertheless, there is no consensus on the use of SC-MRI at follow-up, mainly because of the belief that SC lesions are nearly always symptomatic. OBJECTIVES: The aim of the present study was to investigate the frequency of asymptomatic SC combined unique activity (CUA, new/enlarging T2 or gadolinium-positive [Gd+] lesions) on MRI in a cohort of patients diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). METHODS: We retrospectively investigated all scans showing SC-CUA in patients with CIS or RRMS referred to a single Italian MS centre. We determined whether they were symptomatic and whether they had associated brain radiological activity. RESULTS: In 340 SC-MRI scans with SC-CUA (230 patients), SC-CUA was asymptomatic in 31.2%; 12.1% of SC-CUA had neither clinical activity nor brain radiological activity (44.5% and 25.4%, respectively, considering only follow-up SC-CUA). At multivariate analysis asymptomatic SC-CUAs were associated with older age at onset (34.0 ± 10.37 vs 31.0 ± 9.99 years, p = 0.006), non-spinal onset (76.4 vs 47.4%, p < 0.001), lower EDSS score at MRI (1.8 ± 0.93 vs 2.4 ± 1.28, p = 0.001) and lower number of Gd+ SC lesions (0.1 ± 0.33 vs 0.3 ± 0.54, p = 0.04), compared to symptomatic SC-CUAs. CONCLUSIONS: A substantial proportion of our patients had SC-CUA without clinical symptoms and/or without concomitant brain MRI activity. In these patients, SC-CUA was the only sign of disease activity, suggesting that regular SC-MRI follow-up is required for reliable assessment of radiological activity and may improve the management of patients with MS.