The impact of smoking cessation on multiple sclerosis disease progression.

The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys [median (IQR) 5.03 (3.71, 6.34)], MSWS-12 [median (IQR) 5.28 (3.62, 6.94)] and HADS-Depression [median (IQR) 0.71 (0.47, 0.96)] scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores [median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively] while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis.

Patient selection and outcome of deep brain stimulation for multiple sclerosis-associated tremor.

INTRODUCTION: Tremor is a disabling symptom of multiple sclerosis (MS), with limited treatment modalities. Thalamic ventral-intermediate-nucleus (VIM) deep brain stimulation (DBS) is a method of neuromodulation. We describe the long-term outcomes of our carefully selected patients who underwent VIM DBS for their MS-associated tremor. METHODS: Patients were referred from the regional neurology units. Pre-operative assessments included suitability for anesthesia, tremor quantification by the Fahn-Tolosa-Marin scores, and quality-of-life (EQ5D) measures. Exclusion criteria included prominent cerebellar symptoms such as ataxia and dysmetria, intracranial pathology such as ventriculomegaly, cerebellar plaques and thalamic abnormality, and comorbid psychiatric symptoms. Seven patients (3M:4F) underwent DBS for MS-associated tremor between September 2013 and February 2019. Mean age was 42 years (±SD 8 years). DBS was performed at a mean of 13 years (±SD 9 years) after diagnosis of MS. RESULTS: There were no postoperative surgical complications. All patients showed improvement in FTM tremor scores, by up to 61% at 6 months postoperatively. There was an improvement of 30-175% in quality-of-life scores at 6 months. Improvement of tremor and quality of life, over baseline, was sustained over a long period of follow-up (mean 26.6 months ± SD 20.7 months), including our longest duration at 72 months. CONCLUSION: With careful selection, DBS is a safe, efficacious intervention for MS-tremor and can positively impact on tremor and quality of life, with effects over a long period. As patients live longer with MS and the advent of new therapies, DBS should be considered for selected patients.

Neurostructural and Neurophysiological Correlates of Multiple Sclerosis Physical Fatigue: Systematic Review and Meta-Analysis of Cross-Sectional Studies.

Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic review and meta-analysis aimed to gain new insights into the neurobiology of MS fatigue. MEDLINE, ProQuest, CINAHL, Web of Science databases and grey literature were searched using Medical Subject Headings. Eligible studies compared neuroimaging and neurophysiological data between people experiencing high (MS-HF) versus low (MS-LF) levels of perceived MS fatigue, as defined by validated fatigue questionnaire cut-points. Data were available from 66 studies, with 46 used for meta-analyses. Neuroimaging studies revealed lower volumetric measures in MS-HF versus MS-LF for whole brain (-22.74 ml; 95% CI: -37.72 to -7.76 ml; p = 0.003), grey matter (-18.81 ml; 95% CI: -29.60 to -8.03 ml; p < 0.001), putamen (-0.40 ml; 95% CI: -0.69 to -0.10 ml; p = 0.008) and acumbens (-0.09 ml; 95% CI: -0.15 to -0.03 ml; p = 0.003) and a higher volume of T1-weighted hypointense lesions (1.10 ml; 95% CI: 0.47 to 1.73 ml; p < 0.001). Neurophysiological data showed reduced lower-limb maximum voluntary force production (-19.23 N; 95% CI: -35.93 to -2.53 N; p = 0.02) and an attenuation of upper-limb (-5.77%; 95% CI:-8.61 to -2.93%; p < 0.0001) and lower-limb (-2.16%; 95% CI:-4.24 to -0.07%; p = 0.04) skeletal muscle voluntary activation, accompanied by more pronounced upper-limb fatigability (-5.61%; 95% CI: -9.57 to -1.65%; p = 0.006) in MS-HF versus MS-LF. Results suggest that MS fatigue is characterised by greater cortico-subcortical grey matter atrophy and neural lesions, accompanied by neurophysiological decrements, which include reduced strength and voluntary activation. Prospero registration Prospero registration number: CRD42016017934.

Delivering an advice and guidance service in neurology.

It is increasingly common for secondary care to provide advice to primary care without an outpatient appointment. Even before the increased telemedicine during COVID-19, many hospital services gave advice alone for some referrals, yet there are few published data about patient outcomes. Does advice and guidance alter outpatient numbers or simply mean that patients are seen later? Which neurological conditions can we manage at a distance? Do complaints increase from either primary care or patients? Do clinics become more complex and time consuming? Our department has developed an advice and guidance service embedded within the English electronic referral system since 2017, allowing detailed analysis of the outcome of 6500 patients over 2.5 years. We suggest ways to set up and run a neurology advice and guidance service, looking at the potential benefits and the barriers.

Assessing the long-term effectiveness of interferon-beta and glatiramer acetate in multiple sclerosis: final 10-year results from the UK multiple sclerosis risk-sharing scheme.

BACKGROUND: Because multiple sclerosis (MS) is a chronic disease causing disability over decades, it is crucial to know if the short-term effects of disease-modifying therapies reported in randomised controlled trials reduce long-term disability. This 10-year prospective observational study of disability outcomes (Expanded Disability Status Scale (EDSS) and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue. METHODS: The outcomes of the UK treated patients were compared with a modelled untreated control based on the British Columbia MS data set to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multilevel model (MLM) and a continuous Markov model. RESULTS: 4862 patients with MS were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years). EDSS worsening was reduced by 28% (MLM), 7% (Markov) and 24% time-adjusted Markov in the total cohort, and by 31% (MLM) and 14% (Markov) for relapsing remitting patients. The utility worsening was reduced by 23%-24% in the total cohort and by 24%-31% in the RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4-year (CI 2.7 to 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores. CONCLUSIONS: This study supports a beneficial effect on long-term disability with first-line MS disease-modifying treatments, which is clinically meaningful. However the waning effect noted requires further study.

Late Peripheral Thoracic Aneurysms following Aortic Root Surgery in Patients with Loeys-Dietz Syndrome.

The Loeys-Dietz syndrome is a multisystem connective tissue disorder characterized by aortopathy, arterial tortuosity, peripheral aneurysms, and skeletal features. The peripheral arteriopathy is an important cause of morbidity and potential mortality. This report presents 2 cases: the first demonstrating a 5-cm pseudoaneurysm of the right internal mammary artery and the second demonstrating a 2.3-cm aneurysm of the left internal mammary artery, each following aortic root surgery. These were successfully treated with percutaneous techniques. No complications were seen at follow-up as long as 2 years. Patients with Loeys-Dietzs syndrome require comprehensive long-term vascular follow-up and are likely to require percutaneous vascular interventions.

Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation.

OBJECTIVE: To define changes in phenotype and functional responses of reconstituting T cells in patients with aggressive multiple sclerosis (MS) treated with ablative chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). METHODS: Clinical and brain magnetic resonance imaging measures of disease activity were monitored serially in patients participating in the Canadian MS HSCT Study. Reconstitution kinetics of immune-cell subsets were determined by flow cytometry, whereas thymic function was assessed using T-cell receptor excision circle analyses as well as flow cytometry measurements of CD31+ recent thymic emigrants (RTEs). Functional assays were performed to track central nervous system-autoreactive antigen-specific T-cell responses, and the relative capacity to generate Th1, Th17, or Th1/17 T-cell responses. RESULTS: Complete abrogation of new clinical relapses and new focal inflammatory brain lesions throughout the 2 years of immune monitoring following treatment was associated with sustained decrease in naive T cells, in spite of restoration of both thymic function and release of RTEs during reconstitution. Re-emergence as well as in vivo expansion of autoreactive T cells to multiple myelin targets was evident in all patients studied. The reconstituted myelin-specific T cells exhibited the same Th1 and Th2 responses as preablation myelin-reactive T cells. In contrast, the post-therapy T-cell repertoire exhibited a significantly diminished capacity for Th17 responses. INTERPRETATION: Our results indicate that diminished Th17 and Th1/17 responses, rather than Th1 responses, are particularly relevant to the abrogation of new relapsing disease activity observed in this cohort of patients with aggressive MS following chemoablation and HSCT.

Transition to secondary progressive multiple sclerosis: The consequences for patients and healthcare systems, a healthcare professional survey.

BACKGROUND AND AIMS: Transition to secondary progressive multiple sclerosis (SPMS) from relapsing-remitting MS (RRMS) is an expected part of the disease trajectory for most patients. However, the transition is challenging to identify due to the gradual nature of progression, and the complications of superimposed relapses, comorbidities, and natural variability in symptoms. This healthcare professional (HCP) survey sought to characterize the transition to and management of SPMS in UK clinical practice. METHODS: Telephone interviews with 20 neurologists and MS specialist nurses from England and Scotland gathered quantitative and qualitative responses. Numerical analyses and theoretical thematic methods were used to identify key emerging themes. RESULTS: The burden SPMS imposes on patients and caregivers was a major theme; discharge from specialist services is common, leading to a sense of abandonment. Respondents acknowledged substantial hesitancy toward identifying SPMS, predominantly due to restricted options of licensed and reimbursed disease-modifying therapies (DMTs) for SPMS compared with RRMS. Currently, HCPs continue DMTs under a label of RRMS, even after recognition of progression. This survey identified MS to be unusual in comparison with other disease areas in that reimbursement guidelines have a direct impact on clinicians' decisions around disease staging. Respondents suggested reimbursed DMTs proven to slow disability progression in SPMS will create a step-change in identifying SPMS, providing rationale to acknowledge progression earlier while removing key obstacles to identification. To aid this change, respondents identified a need for SPMS-specific diagnostic guidance, despite substantial divergence in implementation of current guidance. CONCLUSIONS: In contrast to the current heterogeneity, a more structured and standardized approach to the identification of SPMS, along with guidelines on treatment, will ensure patients can maximally benefit as treatment options for SPMS evolve.

Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis.

Early intervention with high-efficacy disease-modifying therapy (HE DMT) may be the best strategy to delay irreversible neurological damage and progression of multiple sclerosis (MS). In European healthcare systems, however, patient access to HE DMTs in MS is often restricted to later stages of the disease due to restrictions in reimbursement despite broader regulatory labels. Although not every patient should be treated with HE DMTs at the initial stages of the disease, early and unrestricted access to HE DMTs with a positive benefit-risk profile and a reasonable value proposition will provide the freedom of choice for an appropriate treatment based on a shared decision between expert physicians and patients. This will further optimize outcomes and facilitate efficient resource allocation and sustainability in healthcare systems and society.

Results from SPECTRUM: A survey of healthcare professionals to understand current diagnosis and management practices for secondary progressive multiple sclerosis in the United Kingdom.

BACKGROUND: Recognising the transition from relapsing remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) in clinical practice can be challenging. With disease-modifying therapies (DMTs) commonly used for RRMS accepted to be less efficacious once progression has occurred, treatment options for progressive forms of MS have been limited. Emergence of new DMTs in SPMS are changing the treatment landscape. There is a need to better understand current practice and the factors underlying it, to facilitate consensus on the overall management of SPMS and optimise diagnostic and management decisions. This survey project aimed to assess current practices for the diagnosis and management of patients with SPMS in the UK. METHODS: Healthcare professionals (HCPs) involved in the management of patients with SPMS from geographically distributed MS neurology centres in the UK participated in face-to-face or telephone interviews, facilitated by a semi-structured questionnaire. The survey data were descriptively analysed using quantitative and qualitative methods. RESULTS: Fifty-nine HCPs (41 neurologists, 15 specialist nurses and 3 'other'), from 59 UK centres took part. Sixty-one percent (n = 36/59) of respondents applied a specific definition for SPMS, although only 6% of these (2/36) used the Lublin 2014 phenotype criteria. Expanded Disability Status Scale (EDSS) score increase with an absence of relapses was an important consideration for SPMS diagnosis for 83% (n = 49/59) of respondents, and 36% (n = 21/59) considered this to be the most important piece of evidence that they look for when they suspect a patient is transitioning from RRMS to SPMS. The median (interquartile range [IQR]) estimated time between first suspicion and diagnosis of SPMS was 12 months (12-24 [n = 45/59]), with concerns over withdrawing DMTs and the psychological impact of a diagnosis on patients the most commonly reported reasons for reluctance to diagnose. Seventy-three percent (n = 43/59) of respondents followed specific guidelines for DMT management of patients transitioning from RRMS to SPMS, with most (86%, n = 37/43) using the NHS England algorithm. Ninety-eight percent (n = 58/59) use DMTs to treat patients they suspect may be transitioning to SPMS, and 51% (n = 30/59) reported using DMTs for newly diagnosed SPMS patients. Approximately 1 in 5 HCPs may consider continuing DMTs beyond EDSS 7.0 in certain circumstances. CONCLUSION: The survey highlighted variation across the UK in SPMS definition, diagnosis and reported real-world management. Disparity in practice may result in unnecessary variations in treatment patterns and consequently outcomes. HCPs should be equipped to make timely and accurate decisions, which will be important in improving access to appropriate therapies for patients with SPMS.

Living with secondary progressive multiple sclerosis in Europe: perspectives of multiple stakeholders.

The transition from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS) remains a clinical challenge owing to the heterogeneous course of the disease, indistinct disease progression and lack of availability of validated biomarkers and diagnostic tools. This article summarizes the outcomes from an international expert group meeting conducted to validate the preliminary research findings gathered through interviews with primary healthcare stakeholders and pharmaceutical representatives, and to understand the current and future patient journey of SPMS across seven European countries. We highlight the uncertainty in SPMS diagnosis and management and, consequently, the need for uniform assessment guidelines, enhanced awareness and a collaborative effort between the stakeholders associated with SPMS patient care and the pharmaceutical industry.

COVID-19 is associated with new symptoms of multiple sclerosis that are prevented by disease modifying therapies.

BACKGROUND: Infections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS. METHODS: The COVID-19 and MS study is an ongoing community-based, prospective cohort study conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms. RESULTS: Fifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection. CONCLUSION: COVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection.

Translumbar Embolization of Type II Endoleaks: 12 Years of Experience at a Regional Vascular Centre.

BACKGROUND AND AIMS: The management of persistent type II endoleaks (T2E) is often problematic for the endovascular specialist, with a lack of clear evidence for the best approach for embolization. The aim of this study was to evaluate the safety and efficacy of translumbar embolization (TLE) for T2E following endovascular aneurysm repair (EVAR). METHODS: This retrospective review included 27 embolizations performed on 23 patients with a median age of 78 (range 67-94 years; male: female 15:9), during the period September 2006 to July 2018. Primary outcome was freedom from aneurysm sac growth defined as <2 mm sac diameter increase on subsequent computed tomography. RESULTS: The initial technical success rate was 100%, with complete "on table" embolization of the T2E on fluoroscopy; however, 4 (15%) patients needed repeat TLE due to persistent endoleak identified on follow-up computed tomography or because of further sac expansion. Satisfactory stasis was achieved in these 4 cases following a second embolization. The mean volume of embolic injected was 7.4 mL per case. Feeding vessels were identified on angiography in all cases; the nidus was supplied by lumbar branches in 21 cases, by the inferior mesenteric artery in 1 case and by both in a further 5 cases. Freedom from aneurysm sac growth (defined as < 2 mm) following 1 or 2 separate TLE was achieved in 18 (78%) and 20 (86%) patients, respectively. The major complication rate was <5% with one case of psoas abscess presenting 7 months following embolization; there were 2 minor complications in the form of intraprocedural transient abdominal pain. CONCLUSION: The translumbar approach is a safe and effective technique to treat T2E, as evidenced by the low complication and reintervention rate.

Abdominal Aortic Aneurysm Repair in Renal and Liver Transplant Recipients.

BACKGROUND: Abdominal aortic aneurysm (AAA) repair in patients with organ transplant remains a challenge. We looked at AAA repair in patients with organ transplants at our tertiary liver and kidney transplant unit. METHODS: A retrospective analysis of a prospectively maintained database was undertaken from January 2008 to July 2018. We looked at patient demographics, type of repair, and technical success including reinterventions, perioperative transplant organ function, and 30-day and 1-year survival rate. Eight of 662 patients who underwent AAA repair had a solid organ transplant. Of these, 5 were kidney transplants, 2 liver transplants, and 1 had kidney and liver transplant; 75% were male; and average age was 63.4 (range: 49-83). All patients had asymptomatic AAAs, and 6 were treated with standard endovascular repair, 1 standard repair with iliac branch device, and 1 open repair. Adjunctive techniques such as CO2 angiograms, deployment of main body through contralateral iliac, low-profile sheaths, custom-made stent grafts, and temporary axillo-femoral shunting were used to protect transplant organs. Thirty-day survival was 100% with 1 death at 5 months from liver failure, and 1 patient has a persistent type-2 endoleak 3 years after the procedure. CONCLUSION: Abdominal aortic aneurysm repair in patients with organ transplants can be undertaken using adjunctive endovascular and open surgical techniques.

Cell-free mitochondrial DNA in progressive multiple sclerosis.

Recent studies have linked cell-free mitochondrial DNA (ccf-mtDNA) to neurodegeneration in both Alzheimer's and Parkinson's disease, raising the possibility that the same phenomenon could be seen in other diseases which manifest a neurodegenerative component. Here, we assessed the role of circulating cell-free mitochondrial DNA (ccf-mtDNA) in end-stage progressive multiple sclerosis (PMS), where neurodegeneration is evident, contrasting both ventricular cerebral spinal fluid ccf-mtDNA abundance and integrity between PMS cases and controls, and correlating ccf-mtDNA levels to known protein markers of neurodegeneration and PMS. Our data indicate that reduced ccf-mtDNA is a component of PMS, concluding that it may indeed be a hallmark of broader neurodegeneration.

Safety and Outcomes of Ipsilateral Antegrade Angioplasty for Femoropopliteal Disease.

PURPOSE: Previous reports have suggested higher periprocedural complications after ipsilateral antegrade femoral arterial access (AA). We looked at a contemporary series comparing complication rates between AA and contralateral retrograde femoral arterial access (RA) for femoropopliteal angioplasty. METHOD: A prospective review of all cases between 2010 and 2015 in a United Kingdom tertiary vascular center. Demographical and procedural data were obtained for those undergoing percutaneous femoropopliteal angioplasty. The primary outcome looked at periprocedural complications including retroperitoneal hematoma, pseudoaneurysm, hematoma requiring transfusion, arteriovenous fistulation, and surgical intervention. Secondary outcomes included contrast and radiation doses in addition to procedural failure leading to major amputation. RESULTS: A total of 556 (66% male) patients underwent femoropopliteal angioplasty, 461 (82%) via AA. Groups were of comparable age, sex, comorbidity, and symptomatology. AA patients had a lower body mass index, 26 versus 29 ( P = .005). No significant difference was seen in periprocedural (15.8% AA vs 11.6% RA; P = 0.292) or access site complications (3.7% AA vs 1.1% RA; P = 0.186). There was less need for a closure device, 40.3% AA vs 73% RA ( P < .01), less contrast, 94 mL AA: 114 mL RA ( P < .001), and less radiation, 3487 cGy cm2 AA: 9697 cGy cm2 RA ( P < .001). Arterial access was also associated with greater technical success of 83.8%: 73.3% RA ( P = .002). CONCLUSIONS: Arterial access is associated with higher technical success and reduced contrast/radiation doses with no significant difference in complications compared to RA contrary to previous reports.

Seizures and Encephalitis in Myelin Oligodendrocyte Glycoprotein IgG Disease vs Aquaporin 4 IgG Disease.

Importance: Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non-multiple sclerosis-related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)-related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease. Objective: To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG-positive and MOG-IgG-positive patients. Design, Setting, and Participants: Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England. Main Outcomes and Measures: The difference in seizure frequency between the AQP4-IgG-positive and MOG-IgG-positive patient groups was determined. Results: Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG-positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG-positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG-positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only AQP4-IgG-positive patient with seizures had a diagnosis of complex partial epilepsy preceding the onset of NMO by several years and experienced no encephalitic illness; her magnetic resonance imaging results demonstrated no cortical, subcortical, or basal ganglia involvement. Conclusions and Relevance: Patients with MOG-IgG-associated disease were more likely to have seizures and encephalitis-like presentation than patients with AQP4-IgG-associated disease.