A 55-year-old woman presented with conjunctival congestion, retro-orbital pain, and diplopia. She had received her first vaccine against SARS-CoV-2—ChAdOx1 nCoV-19—10 days before admission. Both on ...the night after the vaccination and 7 days later, the patient reported marked flu-like symptoms and a fever. She had no medical history of visual problems, autoimmune disorders, stroke, thrombosis, thrombocytopenia, neurological disorders, or arterial disease risk factors—including hypertension, diabetes, or smoking.On examination, she had binocular diplopia at vertical and right lateral gaze, and her visual acuity was 0·85 in both eyes. MRI showed superior ophthalmic vein thrombosis (SOVT) with no contrast filling (figure) and bilateral high T2 signal intensity of the superior ophthalmic vein (figure).
Although the understanding of secondary progressive multiple sclerosis (SPMS) is evolving, early detection of relapse-independent progression remains difficult. This is further complicated by ...superimposed relapses and compensatory mechanisms that allow for silent progression. The term relapsing multiple sclerosis (RMS) subsumes relapsing-remitting multiple sclerosis (RRMS) and SPMS with relapses. The latter is termed ‘active’ SPMS, for which disease-modifying therapies (DMTs) approved for either RMS or active SPMS can be used. However, the level of evidence supporting efficacy and safety in SPMS differs between drugs approved for RMS and SPMS. Our review aims to identify current evidence from published clinical trials and European public assessment reports from the marketing authorization procedure on the efficacy, especially on progression, of DMTs approved for RMS and SPMS. To identify relevant evidence, a literature search has been conducted and European public assessment reports of DMTs approved for RMS have been screened for unpublished data specific to SPMS. Only two clinical trials demonstrated a significant reduction in disability progression in SPMS study populations: the EXPAND study for siponimod, which included a typical SPMS population, and the European study for interferon (IFN)-beta 1b s.c., which included patients with very early and active SPMS. Both DMTs also achieved significant reductions in relapse rates. Ocrelizumab, cladribine, ofatumumab, and ponesimod are all approved for RMS – ocrelizumab, ofatumumab, and ponesimod based on an RMS study, cladribine based on an RRMS study. Data on efficacy in SPMS are only available from post hoc analyses of very small subgroups, representing only up to 15% of the total study population. For these DMTs, approval for RMS, including active SPMS, was mainly based on the assumption that the reduction in relapse rate observed in patients with RRMS can also be applied to SPMS. Based on that, the potential of these drugs to reduce relapse-independent progression remains unclear.
Management of multiple sclerosis (MS) requires a high level of communication between health care professionals (HCPs) and people with MS (pwMS) including profound investigation and discussion of ...symptoms to identify therapeutic needs. For treatment decisions, monitoring of disease activity is important, in this respect self-monitoring devices and apps, as well as magnetic resonance imaging are important tools.
MS Perspectives is a cross-sectional online survey conducted in Germany which was designed to collect data, among others, on the communication between pwMS and HCPs regarding treatment goals, symptom assessment, usage of devices and apps to self-monitor health functions, as well as to identify patients' attitude toward the role of magnetic resonance imaging (MRI). Between December 2021 and February 2022, 4,555 pwMS completed the survey.
In total, 63.7% of participants reported that treatment goals have been discussed with their HCPs. Symptoms worsening in the past 12 months independent of relapses was more often reported by pwMS than inquired by HCPs, according to patients' report. Devices or apps for health monitoring were used by less than half of participants. Frequency of MRI controls was much lower in participants with longer compared to shorter disease duration (47.5 vs. 86.3%). The proportion of patients with annual or semiannual scans was highest among pwMS receiving infusion therapy (93.5%), followed by oral medication (82.5%) and injectables (73.4%), and lowest for pwMS without immunotherapy (58.2%).
MS Perspectives identified a rather low patient involvement regarding treatment goals and symptom assessment in clinical practice. Regarding this and our findings for health self-monitoring and MRI usage, strategies for improving patient-HCP communication and disease monitoring may be considered.
Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in ...multiple sclerosis (MS), infections have been reported more frequently in alemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeria meningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication.
Vertebral artery (VA) involvement in giant cell arteritis (GCA) has rarely been reported. We aimed to evaluate the prevalence, patients' characteristics, and immunotherapies used in patients with GCA ...and VA involvement at diagnosis and 1 year follow-up, retrospectively including patients being diagnosed between January 2011 and March 2021 in our department. Clinical features, laboratory data, VA imaging, immunotherapy, and 1 year follow-up data were analyzed. Baseline characteristics were compared to GCA patients without VA involvement. Among all 77 cases with GCA, 29 patients (37.7%) had VA involvement, as diagnosed by imaging and/or clinical signs and symptoms. Gender distribution and erythrocyte sedimentation rate (ESR) were significantly different in the groups with and without VA involvement, with more women being affected (38/48 patients, 79.2%) and a significantly higher median ESR in patients without VA involvement (62 vs. 46 mm/h;
= 0.012). MRI and/or CT showed vertebrobasilar stroke at GCA diagnosis in 11 cases. 67/77 patients (87.0%) received high-dose intravenous glucocorticosteroids (GCs) at diagnosis, followed by oral tapering. Six patients were treated with methotrexate (MTX), one with rituximab, and five with tocilizumab (TCZ). 2/5 TCZ patients achieved clinical remission after 1 year, vertebrobasilar stroke within the first year occurred in 2/5 patients. Diagnosis of VA involvement might be underrecognized in GCA patients. VA imaging should be performed in elderly patients with vertebrobasilar stroke presenting with GCA symptoms, not to miss GCA as the etiology of stroke. Efficacy of immunotherapies in GCA with VA affection and long-term outcomes need to be investigated further.
Prolonged-release fampridine (PR-FAM), a potassium channel blocker, is approved for improving walking ability in patients with multiple sclerosis (MS). Beyond this, positive effects on other MS ...symptoms like fatigue, cognition, and tremor have been described. To our knowledge, a positive effect of PR-FAM on spinal myoclonus has not been described so far. Here, we report a 32-year-old female with myoclonus after cervical myelitis affecting both hands which markedly improved after administration of PR-FAM. Treatments used before such as carbamazepine or levetiracetam had to be withdrawn because of intolerable side effects or lack of efficacy. The positive effect of PR-FAM could be confirmed by transient suspension. PR-FAM may be considered as a treatment option in refractory spinal myoclonus after myelitis in selected cases.
Background:
Symptomatic and asymptomatic delayed non-ischemic cerebral enhancing (NICE) lesions in magnetic resonance imaging (MRI) have been reported as a rare complication after endovascular ...therapy (EVT) in recent years with incidence rates between 0.05% and 0.9% in most studies. Information on long-term clinical course and immunotherapies is scarce or has not been reported in detail in the literature.
Objective:
Aims of our study were to assess the incidence of NICE lesions in patients after cerebral EVT over a period of more than 12 years, describe clinical and EVT characteristics, and immunotherapies applied.
Methods:
A retrospective chart review of all patients treated by endovascular therapy for symptomatic or asymptomatic aneurysms at the University Hospital of Augsburg from May 1, 2008 to December 31, 2020 was performed. Patients were identified retrospectively and followed-up prospectively where appropriate. In addition, one case treated at another institution was included.
Results:
Five out of 746 patients, 0.67%, developed NICE lesions after EVT, all with non-ruptured aneurysms and all symptomatic upon detection of NICE lesions by MRI. In total, the disease course of 6 female patients is reported. Symptoms occurred after a mean time of 15 days (±13.42, SD) after EVT with headache (6/6 patients), focal neurological signs (6/6 patients), epileptic seizures (2/6 patients) and cognitive deficits (3/6 patients). All 6 patients received glucocorticosteroids (GCS), 1/6 azathioprine (AZA), 4/6 mycophenolate mofetil (MMF), 1/6 methotrexate (MTX), 1/6 rituximab (RTX), 2/6 cyclophosphamide (CYC) and 3/6 tocilizumab (TCZ). A treatment response could be observed for GCS, TCZ and MMF (in two of four cases), RTX and AZA did not result in disease stabilization.
Conclusions:
Delayed NICE lesions are a rare complication after EVT, requiring immunotherapies in all patients reported here. Physicians should be aware of this disorder in case of new symptoms or contrast enhancing lesions after EVT.
Autoimmune encephalitis associated with antibodies against the metabotropic glutamate receptor type 1 is a rare autoimmune disease with only 18 cases being described in the literature so far. Most ...patients present with subacute cerebellar ataxia. In more than one third of cases a paraneoplastic aetiology has been suspected. Here we report a case of a 45-year-old man without known malignancy, who presented with progressive dysarthria and subsequently developed subacute cerebellar ataxia. Immunotherapy with glucocorticoids, i.v. immunoglobulins and rituximab improved clinical symptoms and resulted in a stable disease course up to the present. The article describes the clinical course of the patient with a follow-up-period of approximately 24 months and reviews the cases reported in the literature so far.
Infectious diseases are an important consideration in autoimmune conditions such as multiple sclerosis. Infective episodes may trigger relapses and significantly deteriorate the course of the ...disease. Some immunotherapies may cause increased rates of infection-related adverse events. Thus, infection and vaccine-related issues should be included in the individualized patient-specific treatment strategy and counseling before starting therapy and regularly on treatment. Clinical and epidemiological studies as well as pharmacovigilance data repeatedly demonstrated the safety of the great majority of vaccines in multiple sclerosis patients. Moreover, studies have shown that vaccinations with killed/inactivated vaccines do not increase the short-term risk of relapse or deterioration in multiple sclerosis, whereas infections have been shown to provoke relapses. The available evidence indicates reduced humoral vaccination efficacy on treatment with MS drugs acting on the S1P receptor, natalizumab, and B-cell depleting therapies. Recent data for cladribine tablets suggest the potential of effective immunization in the interval of the two treatment courses and after completion of therapy. Regardless of treatment, vaccine efficacy may be optimized with proper timing of application. Multiple sclerosis patients receiving highly effective therapies should be vaccinated according to general recommendations for healthy adults. Immunization against COVID-19 is highly recommended for all multiple sclerosis patients regardless of age and comorbidities. Preliminary data show the potential of adequate responses in patients treated with cladribine tablets.
We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients.
In a multicentre ...prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up.
Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (RRMS2010 and CIS2010). After reclassification of CIS2010 patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS2017 than RRMS2017 patients (9.1 pg/ml, IQR 6.2–13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4–20.1 pg/ml, n = 213; p = 0.036). sNfL levels correlated with number of T2 and Gd+ lesions at baseline and future clinical relapses. Patients receiving disease-modifying therapy (DMT) during the first four years had higher baseline sNfL levels than DMT-naïve patients (11.8 pg/ml, IQR 7.5-20.7 pg/ml, n = 726; 9.7 pg/ml, IQR 6.4–15.3 pg/ml, n = 88). Therapy escalation decisions within this period were reflected by longitudinal changes in sNfL levels.
Assessment of sNfL increases diagnostic accuracy, is associated with disease course prognosis and may, particularly when measured longitudinally, facilitate therapeutic decisions.
Supported the German Federal Ministry for Education and Research, the German Research Council, and Hertie-Stiftung.
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