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ObjectiveTo identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).SettingPatients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.ParticipantsPatients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.ResultsRelapsing disease was observed in 55% (42/76) of cases. Steroid treatment >1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; p<0.001). No specific factors were predictive of visual or overall disability.ConclusionsMale patients with spinal cord involvement at disease onset have a lower risk of relapsing disease and longer latency to first relapse. Steroid treatment for at least 1 month at first attack was also associated with a monophasic disease course. MOG-antibody negative seroconversion was associated with a lower risk of relapse and may help inform treatment decisions and duration.

IntroductionThe UK MS Pregnancy Register gathers pregnancy data in women with multiple sclerosis (MS) to address research gaps. We present data from >100 participants recruited since initiation in 2021.MethodsWomen with MS enter data via a dedicated online portal, completing questionnaires at 2 timepoints during pregnancy, and 3- and 12 months post-partum.ResultsOf 131 participants, most were White ethnicity (91%), and had relapsing-remitting MS (94%). 101 (89%) had ever taken DMT. Mean age at diagnosis and registration were 28.6 and 33.1 years respec- tively. Most registered in the first trimester of pregnancy (47.3%, n=62). Median EDSS was 2.5. 18 relapses were recorded in 15 patients; most relapses occurred in late pregnancy and postpartum. 78% discussed pregnancy in advance with their MS team. 86 pregnancies were exposed to DMT (62.3%), most commonly natalizumab (34.9%, n=30), glatiramer acetate (20.9%, n=18), and dimethyl fumarate (12.8%, n=11). 120 participants (91.6%) took supplements during pregnancy. Delivery gestation varied from 38 to 41 weeks, with the majority having delivered at 40 weeks. Postnatally, 58.3% of participants scored >10 on the Edinburgh PND scale.ConclusionSuch data demonstrates feasibility of large-scale, patient-orientated data gathering. Further work is required to improve postpartum data acquisition.

NMOSD is not formally recognised as a side-effect of therapy with recombinant interferon alpha. [...]we submitted requests for data on adverse events to spontaneous reporting schemes (the UK Medicines and Healthcare products Regulatory Agency's Yellow Card Scheme and VigiBase, the WHO global database of individual case safety reports) and reviewed published drug safety reports. Interferon beta therapy is widely used and moderately effective for the treatment of multiple sclerosis, but its use in people with NMOSD is associated with disease worsening8 and increasing aquaporin-4 antibody titres.9 Therefore, our findings are consistent with a growing body of evidence that suggests that activation of the type I IFN pathway causes opposing therapeutic responses in individuals with NMOSD and multiple sclerosis. Supplementary Material Supplementary appendix Recombinant interferon alpha therapy Increased endogenous IFNα Patient 1 Patient 2 Patient 3 Patient 4 Underlying disease Systemic mastocytosis Hepatitis C Monogenic interferonopathy Systemic lupus erythematosus Interferon exposure Interferon alpha (10 years) Interferon alpha (1 year) 872 fg/mL (normal 0–8 fg/mL) 815 fg/mL (normal 0–8 fg/mL) Clinical presentation Bilateral leg numbness and weakness Bilateral leg numbness and weakness Unilateral arm weakness Bilateral arm and leg numbness and weakness MRI findings LETM thoracic LETM thoracic LETM high cervical LETM high cervical Aquaporin-4 antibodies by cell-based assay Positive Positive Positive Positive Diagnostic criteria for NMOSD met Yes Yes Yes Yes Treatment Corticosteroids, azathioprine, and rituximab Corticosteroids and azathioprine Corticosteroids and ruxolitinib Corticosteroids, azathioprine, and rituximab Clinical course Relapsing transverse myelitis Relapsing transverse myelitis Single LETM Single LETM Table Patient characteristics

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low ( p o  = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher ( p o  = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.

Biologic immunotherapies have transformed the treatment landscape of multiple sclerosis. Such therapies include recombinant proteins (interferon beta), as well as monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, rituximab and ocrelizumab). Monoclonal antibodies show particular efficacy in the treatment of the inflammatory phase of multiple sclerosis. However, the immunological perturbations caused by biologic therapies are associated with significant immunological adverse reactions. These include development of neutralising immunogenicity, secondary immunodeficiency and secondary autoimmunity. These complications can affect the balance of risks and benefits of biologic agents, and 2018 saw the withdrawal from the market of daclizumab, an anti-CD25 monoclonal antibody, due to concerns about the development of severe, unpredictable autoimmunity. Here we review established and emerging risks associated with multiple sclerosis biologic agents, with an emphasis on their immunological adverse effects. We also discuss the specific challenges that multiple sclerosis biologics pose to drug safety systems, and the potential for improvements in safety frameworks.

The diagnosis and treatment of breast cancer can involve a series of life-altering, traumatic experiences, leading to distress, reduced quality of life, and long-standing fears of recurrence. Distress may exacerbate physical symptoms, impair coping, impact health behaviors, and reduce compliance with cancer treatment. Psychological treatments have focused on alleviating distress and improving quality of life. Given the growing evidence of the role of stress and behavior on cancer outcomes, a biobehavioral approach to treatment may serve to achieve these traditional treatment goals while also impacting disease course. Shapiro's (2001) eye movement desensitization and reprocessing (EMDR) protocol for illness and somatic disorders was greatly informed by her interest in mind-body approaches to health and the newly emerging (1992) field of psychoneuroimmunology. The protocol includes first identifying and addressing the realistic fears and challenges a woman faces. Once appropriate, EMDR therapy turns to the reprocessing of past memories, present triggers, and the development of positive future templates of health. This article focuses on situations, usually in the early diagnosis and intensive phases of cancer treatment, when the reprocessing phases of EMDR therapy need to be delayed because of the demands of cancer treatment or insufficient client stability. Resourcing interventions that are compatible with biobehavioral goals are provided, with brief clinical examples.

BackgroundThere is limited evidence to guide DMT prescribing prior to and during pregnancy, leading to wide variation in practice. In 2019, ABN consensus guidelines were published to address this. We set out to establish what impact these have had.MethodsAn online questionnaire was cascaded to UK MS neurologists. Individuals completed the ques- tionnaire anonymously.Results85 responses were obtained; 76 from DMT prescribers in a variety of settings. 74/76 (97%) were aware of the ABN guidelines. 74% reported a recent change in prescribing IFN-B and 70% in prescribing natalizumab around pregnancy, compared to 5% for alemtuzumab and 1% for teriflunomide and fingoli- mod. The ABN guidelines were the most commonly cited reason for change (58 individuals), followed by SmPC changes and influence from peers.There was significant variation in natalizumab prescribing - 51% ‘normally continue to prescribe’ until 34/40, 12% stop when pregnancy confirmed and 11% stop prior to conception. 58% encourage breastfeeding on natalizumab whilst 34% discourage this.ConclusionsThere remains significant variation in advice given to women with MS considering pregnancy. This is most marked with higher efficacy DMT, where risk-benefit decision making is complex. Additional data and resources for women with MS, including a UK MS Pregnancy register, are urgently needed.ruth.dobson@qmul.ac.uk

Neurologists increasingly use anti-CD20 therapies, including for women of childbearing age, despite these medications being unlicensed for use in pregnancy. Current evidence suggests that women can safely conceive while taking anti-CD20 therapy. Women should not be denied treatment during pregnancy when it is clinically indicated, although they should be counselled regarding live vaccinations for their infant. Women receiving regular ocrelizumab for multiple sclerosis should preferably wait 3 months before trying to conceive. There are few data around ofatumumab in pregnancy, and while there is probably a class effect across all anti-CD20 therapies, ofatumumab may need to be continued during pregnancy to maintain efficacy. We recommend that anti-CD20 therapies can be safely given while breast feeding. It is important to make time to discuss treatments with women of childbearing age to help them choose their most suitable treatment. Outcomes should be monitored in pregnancy registries.

BackgroundWe present baseline data on the first 50 participants recruited to the UK MS Pregnancy Register.MethodsData collected via questionnaires from consenting participants until 20th December 2021 were included.Results50 participants (all with relapsing remitting MS; mean age at diagnosis 28.0 years; mean age at recruitment 33.0 years) were included. Median EDSS was 2.5 (n=16). Gestation at recruitment ranged from 2 to 40 weeks. 78% had discussed their pregnancy in advance with their MS team. 90% of patients had ever taken DMT. Of the patients that stopped DMT (n=23), 16 reported stopping for pregnancy-related reasons. Of these, 39% stopped before pregnancy and 30% following conception. 15 women are continuing DMT during their current pregnancy, taking the following DMT: Glatiramer acetate (n=5), natalizumab (n=7), Peginterferon beta-1a (n=2), not recorded (n=1). In those with prior pregnancies, 61% (14/23) reported pregnancy loss with 1 case of a rare genetic condition in the baby. None of the prior pregnancy losses happened whilst on DMT. One participant reported previous PPH and foetal macrosomia and another reported previous pre-eclampsia.ConclusionsThese results show that a patient-facing pregnancy MS registry is feasible and can collect previous adverse pregnancy outcomes. Future results will inform clinicians and women about the safety of DMT and adjunctive medication during pregnancy and postpartum.

The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs. We provide recommendations for eligibility, starting, monitoring, switching and stopping of DMTs; pregnancy; equitable access to DMT; autologous haemopoietic stem-cell transplantation; and use of generics. We highlight best practice where it exists and discuss future priorities.