Neuropsychology intervention for managing invisible symptoms of MS (NIMIS-MS) group: A pilot effectiveness and acceptability study.

BACKGROUND: People with MS (pwMS) commonly experience a range of hidden symptoms, including cognitive impairment, anxiety and depression, fatigue, pain, and sensory difficulties. These "invisible" symptoms can significantly impact wellbeing, relationships, employment and life goals. We developed a novel bespoke online group neuropsychological intervention combining psychoeducation and cognitive rehabilitation with an Acceptance and Commitment Therapy (ACT)-informed approach for pwMS in an acute tertiary hospital. This 'Neuropsychological Intervention for Managing Invisible Symptoms' in MS (NIMIS-MS) consisted of 6 sessions, each with a psychoeducation and ACT component. The content included psychoeducation around managing cognitive difficulties, fatigue, pain, sleep and other unpleasant sensations in MS with the general approach of understanding, monitoring, and recognising patterns and potential triggers. Specific cognitive rehabilitation and fatigue management strategies were introduced. The ACT-informed component focussed on three core ACT areas of the 'Triflex' of psychological flexibility (Harris, 2019): Being Present, Opening Up, and Doing What Matters. METHODS: 118 pwMS attended the NIMIS-MS group intervention which was delivered 14 times in six-week blocks over an 18-month period. To evaluate the effectiveness and acceptability, participants completed measures of depression and anxiety (HADS), functional impairment (WSAS), Values- Progress (VQ) and Values- Obstruction (VQ), and Acceptance of MS (MSAS) pre and post NIMIs-MS group intervention. Qualitative feedback was obtained during focus groups after the final session and via online feedback questionnaires RESULTS: Pre-post analysis showed that symptoms of depression and anxiety were significantly lower and acceptance of MS was significantly higher following completion of the NIMIS-MS group. Qualitative feedback showed that participants reported that they felt more equipped to manage the "invisible" symptoms of MS following completion of the group, and benefited from using ACT-based strategies and techniques. Participants highly valued the peer support that evolved during the NIMIS-MS groups. The online format was considered more accessible than in-person groups, due to less concerns of travel time, cost, fatigue, and comfort and infection. CONCLUSION: Evaluation suggests that our novel NIMIS-MS groups is an acceptable, beneficial and feasible approach for providing neuropsychological interventions to individuals with MS.

Autoimmune central nervous system disorders: Antibody testing and its clinical utility.

A rapidly expanding repertoire of neural antibody biomarkers exists for autoimmune central nervous system (CNS) disorders. Following clinical recognition of an autoimmune CNS disorder, the detection of a neural antibody facilitates diagnosis and informs prognosis and management. This review considers the phenotypes, diagnostic assay methodologies, and clinical utility of neural antibodies in autoimmune CNS disorders. Autoimmune CNS disorders may present with a diverse range of clinical features. Clinical phenotype should inform the neural antibodies selected for testing via the use of phenotype-specific panels. Both serum and cerebrospinal fluid (CSF) are preferred in the vast majority of cases but for some analytes either CSF (e.g. N-methyl-D-aspartate receptor [NMDA-R] IgG) or serum (e.g. aquaporin-4 [AQP4] IgG) specimens may be preferred. Screening using 2 methods is recommended for most analytes, particularly paraneoplastic antibodies. We utilize murine tissue-based indirect immunofluorescence assay (TIFA) with subsequent confirmatory protein-specific testing. The cellular location of the target antigen informs choice of confirmatory diagnostic assay (e.g. blot for intracellular antigens such as Hu; cell-based assay for cell surface targets such as leucine-rich glioma inactivated 1 [LGI1]). Titers of positive results have limited diagnostic utility with the exception of glutamic acid decarboxylase (GAD) 65 IgG autoimmunity, which is associated with neurological disease at higher values. While novel antibodies are typically discovered using established techniques such as TIFA and immunoprecipitation-mass spectrometry, more recent high-throughput molecular technologies (such as protein microarray and phage-display immunoprecipitation sequencing) may expedite the process of antibody discovery. Individual neural antibodies inform the clinician regarding the clinical associations, oncological risk stratification and tumor histology, the likely prognosis, and immunotherapy choice. In the era of neural antibody biomarkers for autoimmune CNS disorders, access to appropriate laboratory assays for neural antibodies is of critical importance in the diagnosis and management of these disorders.

Final analysis of 379 pregnancy outcomes after exposure to dimethyl fumarate in a prospective international registry.

BACKGROUND: Dimethyl fumarate (DMF) has a favorable benefit-risk profile treating people with multiple sclerosis and should be used in pregnant women only if the potential benefits outweigh potential risks to the fetus. OBJECTIVE: Assess pregnancy outcomes in a completed international registry (TecGistry) of women with MS exposed to DMF. METHODS: TecGistry included pregnant women with MS exposed to DMF, with data collected at enrollment, 6-7 months gestation, 4 weeks after estimated due date, and at postpartum weeks 4, 12, and 52. Outcomes included live births, gestational size, pregnancy loss, ectopic/molar pregnancies, birth defects, and infant/maternal death. RESULTS: Of 397 enrolled, median (range) age was 32 years (19-43). Median (range) gestational week at enrollment was 10 (0-39) and at first DMF exposure was 1 (0-13). Median (range) duration of gestational DMF exposure was 5 weeks (0-40). Fifteen (3.8%) spontaneous abortions occurred. Of 360 (89.1%) live births, 323 were full term and 37 were premature. One neonatal death and no maternal deaths occurred. Adjudicator-confirmed EUROCAT birth defects were found in 2.2%. CONCLUSION: DMF exposure during pregnancy did not adversely affect pregnancy outcomes; birth defects, preterm birth, and spontaneous abortion were in line with rates from the general population.