To determine the influence of high-efficacy disease modifying therapy (DMT) on the development of IgG SARS-CoV-2 antibody response in COVID-19 convalescent people with multiple sclerosis (pwMS).
...Seventy-four pwMS taking high-efficacy DMTs (specifically natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine and ublituximab) and diagnosed with COVID-19 and 44 healthy persons (HC) were enrolled. SARS-CoV2 antibodies were tested with Elecsys® Anti-SARSCoV-2 S assay.
pwMS taking high-efficacy DMTs had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to healthy controls (33 negative pwMS 44.6% compared to one negative HC 2.3%, p < 0.001). pwMS taking B-cell depleting therapy (ocrelizumab and ublituximab) had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to pwMS on all other DMTs (29 negative pwMS on B-cell therapy 64.4% compared to four negative pwMS on all other DMTs 13.8%, p < 0.001). Out of other DMTs, two (33.3%) pwMS taking fingolimod and two (16.7%) pwMS taking cladribine failed to develop IgG SARS-COV-2 antibodies. B-cell depleting therapy independently predicted negative titer of IgG SARS-CoV-2 antibody (ExpB =0.014, 95%CI 0.002–0.110, p < 0.001).
A significant proportion of convalescent COVID-19 pwMS on high-efficacy DMTs will not develop IgG SARS-CoV-2 antibodies. B-cell depleting therapies independently predict negative and low titer of IgG SARS-CoV-2 antibody.
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•Convalescent COVID-19 people with multiple sclerosis (pwMS) taking high-efficacy DMTs had a significantly higher chance of negative titer of SARS-CoV2 antibodies compared to healthy controls.•pwMS taking B-cell depleting therapy had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to those on other high-efficacy DMTs.•B-cell depleting therapy was an independent predictor of negative and low titer of IgG SARS-CoV-2 antibody.
We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature.
The retrospective ...observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed.
We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery.
Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.
•Inflammatory changes in the CSF are present in up to half of persons with TM following COVID-19.•Intrathecal OCB synthesis and positive serology for anti-MOG or anti AQP4 antibodies are rare.•Spinal cord MRI may be normal in up to 30% of persons with TM following COVID-19and these patients have a poorer prognosis.
Objective
So far, a limited number of real-world evidence studies about the effectiveness and safety of alemtuzumab (ALM) have been published, some of them with a relatively small number of included ...patients. We aimed to study the efficacy and safety of ALM in real-world clinical practice in two MS centers in Slovenia and Croatia.
Methods
This was a retrospective chart review of 71 consecutive patients with relapsing–remitting MS who were treated with ALM from 2015 till 2018. The following data were collected: gender, age at disease onset, disease duration at ALM initiation, previous disease modifying therapy, number of relapses, active MRI lesions, and EDSS in the year prior to ALM initiation and every year of follow-up.
Results
All patients completed the standard dosing schedule and were followed for a mean time of 3.2±1.1 years after the initiation of treatment. Complete data for the 2 years after treatment (relapses, EDSS, and MRI) were available for 48 patients, of which 14 (29.2%) achieved NEDA. Clinical NEDA was achieved in 38 out of 63 participants (60.3%). In year 1, 24 out of 57 (42.1%) patients achieved NEDA. In year 2, 26 out of 41 (63.4%) patients achieved NEDA. Lower EDSS prior to starting ALM was the only independent predictor of NEDA in a multivariable model. Adverse events occurred in 58 participants (84.1%), with no new safety signals identified.
Conclusion
According to the data from our cohort of early active RRMS patients we conclude ALM efficacy remains high in the real-world clinical practice.
More than 30 patients with multiple sclerosis (MS) and Parkinson's disease (PD) have been reported so far. Theories on the co-occurrence of MS and PD range from coincidental to causal. There has been ...only one report of MS in young onset PD in a patient heterozygous for Parkin mutation. We report a patient with MS who developed signs typical for PD and was found to be heterozygous mutation carrier in the gene for glucocerebrosidase (GBA1), a well-known risk factor for PD.
•We report a case of MS patient who developed PD and was found to be heterozygous carrier of GBA1 gene mutation.•MS might increase the chances of PD development in GBA1 gene mutation carriers.•The mechanisms by which GBA1 mutations increase the risk of development PD in the setting of MS are not known.
At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and ...burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.
Few reports in the literature describe isolated peripheral neuropathies in relation to Mycoplasma pneumoniae infection without concurrent damage to the central nervous system. To our knowledge only a ...single case of mononeuritis multiplex with brachial plexus neuropathy coincident with M. pneumoniae has been documented until now. Here we present the first clinical case of lobar M. pneumoniae pneumonia in a 19-year-old female patient, where coincident neurological complications manifested as unilateral brachial plexus neuropathy, affecting axillar and suprascapular nerves. Isolated M. pneumoniae from sputum belonged to P1 type 2 and to MLVA type 3-6-6-2. No mutation associated with macrolide resistance in domain V of the 23S rRNA gene was detected. Serological testing of a GM1 antibody showed positive results, which might support the role of immunologic mechanisms in the pathogenesis of peripheral neuropathies related to M. pneumoniae infection.
Infusion-associated reactions (IARs) occur in >90% patients with multiple sclerosis (MS) treated with alemtuzumab. We aimed to study the frequency of IARs at 2 sites using 5 days of steroids (1g/day ...of IV methylprednisolone), but otherwise distinct protocols.
This was retrospective chart review of 38 consecutive MS patients who were treated with alemtuzumab from June 2015 till February 2017 at Department of Neurology, University Hospital Center Zagreb, Croatia and Department of Neurology, University Medical Center Ljubljana, Slovenia.
Seventeen patients (44.7%) did not experience IARs. Skin reactions and fever were the most common IARs attributed to alemtuzumab infusions and they were most frequent on Day 5 and Day 1, respectively. We have observed significant differences in the occurrence of fever (p = 0.005) depending on the site of alemtuzumab administration which could be explained by different antipyretics used; fever was absent in the Slovenian cohort because high dose intravenous metamizole was administered. Two out of 9 treatment naïve, and 19 out of 29 patients who previously received immunomodulatory treatment had IARs (χ2 = 5.208, p = 0.022).
Modified premedication scheme consisting of 1g/day of IV methylprednisolone throughout all 5 days of alemtuzumab treatment may reduce overall IARs. Intravenous administration of antipyretics may work better than oral administration.
•Skin reactions and fever were the most common IARs attributed to alemtuzumab infusions.•Modified premedication scheme may reduce overall IARs associated with alemtuzumab.•Intravenous compared to oral administration of antipyretics significantly reduces the occurrence of fever.
•There was no association between IVIG/no-IVIG and ARR one year after the delivery.•We found no predictors of postpartum relapses in women with RRMS.•We observed a similar curve of ARR associated ...with pregnancy as previously reported.
To evaluate the effect of intravenous immunoglobulins (IVIG) on prevention of postpartum relapses in women with relapsing-remitting multiple sclerosis (RRMS).
This was a retrospective study performed in Ljubljana, Slovenia where the practice for all pregnant women with RRMS is to receive IVIG after the delivery (10 g monthly, during first 6 months after delivery) and in Zagreb, Croatia where no such practice exists. The following data were collected: date of delivery, maternal age at delivery, year of the RRMS diagnosis, EDSS, disease modifying therapy prior to pregnancy, relapses in the year prior, during and in the period of one year after pregnancy.
Data on 132 pregnancies from 112 women (mean age at delivery 31.70±4.10, average disease duration 6.34±4.33) were analyzed. There was no association between the IVIG treatment and annualized relapse rate one year after the delivery (0.27 vs 0.38, rate ratio 1.409, 95% CI 0.764–2.598, p = 0.272). No risk factors for the postpartum relapse were identified (age at delivery, duration of RRMS, EDSS prior pregnancy, disease modifying therapy prior pregnancy, relapses in the year prior pregnancy, IVIG).
This study provides no evidence of benefit for postpartum administration of IVIG in women with RRMS.
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