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Background and ObjectivesPatients with multiple sclerosis (MS) may seek fertility treatment (FT)—including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse.MethodsPatients with clinically isolated syndrome (CIS) or MS aged 18–45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported.ResultsOne hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25,p= 0.37), and the IRR was 0.95 (95% CI: 0.52–1.76,p= 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS,p= 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p= 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI.DiscussionIn this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

Newly approved immunotherapies for neuromyelitis optica spectrum disorder (NMOSD) have transformed the treatment landscape and improved disability outcomes. However, there are many remaining questions regarding transitioning immunotherapies in NMOSD that have not been addressed by randomized controlled trials.This review focuses on the practical questions of managing and switching immunotherapies for NMOSD, including how to transition between immunotherapies, deciding when and if therapy should be discontinued, and transitioning during pregnancy or breastfeeding.Clinical experience and retrospective studies of real-world outcomes and complications associated with therapy, as well as therapy transitions, will help inform practice patterns moving forward. Strategies for transitioning between immunotherapies should consider the pharmacokinetics and the onset of clinical efficacy for each drug. Despite all the currently approved preventative immunotherapies, there are limited treatment options for those suffering from significant disability after their initial attack, and remyelination therapies are an important area for future research.

Bright white light therapy (LT) can improve fatigue in several disease states but has not been studied in multiple sclerosis (MS). To determine whether controlled home-based LT is feasible, tolerable, and well-adhered to in MS-associated fatigue. A randomized, controlled trial of twice-daily 1-h bright white LT (BWLT) (10,000 lx, active arm) versus dim red LT (DRLT) (

Neurogenic lower urinary tract dysfunction (LUTD) results in lower urinary tract symptoms (LUTS) that impact quality of life in people with multiple sclerosis (PwMS). The risk factors and the contribution of LUTD to multiple sclerosis (MS) disease progression are under-researched.To identify clinical and demographic predictors of LUTS in PwMS and gaps in clinical ascertainment.Participants were adults with MS enrolled in a prospective, multicenter study (SUMMIT, N=802), including a subset of N = 258 patients in the UCSF EPIC study for whom medical records were further reviewed. Demographic (age, sex, race, ethnicity), clinical (disease duration, MS type), and female-specific reproductive factors (e.g., parity) were evaluated to determine associations with bowel/bladder functional system score. Participants' medical records were analyzed to understand the patterns of LUTS ascertainment by physicians and the specific contribution of LUTS to overall bowel/bladder functional system scores.802 participants (71.3% female) contributed to these analyses. Higher bowel/bladder functional system scores, indicating worsening symptoms and function, were significantly associated with female sex (p=0.001) and progressive MS type (p≤ 0.001). In the EPIC participants, female-specific reproductive exposures (parity, menopause) were not significantly associated with worse bowel/bladder functional system scores. Most (98%) bowel/bladder functional system scores reflected the severity of LUTS (relative to bowel dysfunction). LUTS were under-ascertained clinically, and more so in women (XFemale sex and MS type are predictive of worsening LUTS. Symptoms may be less likely to be ascertained by clinicians in females compared to males.

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are chronic inflammatory demyelinating disorders of the central nervous system that often affect women during childbearing years. Therefore, issues of conception, pregnancy, and delivery are of significant importance to patients and treating physicians. The current review provides updated information regarding the effects of pregnancy on MS and NMO, as well as the available safety data on immunomodulatory MS therapies for pregnant and lactating women. Management issues of women with MS and NMO during conception, gestation, and the postpartum period also are addressed.

ObjectiveTo evaluate postpartum MRI activity in patients with MS and a completed pregnancy and to compare these results to an age-matched untreated nonpregnant MS cohort.MethodsPatient with MS from a tertiary care MS center between 2006 and 2015, with prepartum and postpartum neurologic follow-ups and MRI scans were analyzed. Clinical activity and inflammatory brain MRI activity (new T2-hyperintense or gadolinium-enhancing [Gd+] lesions) were assessed peripartum. The results were compared with untreated reproductive-age patients with MS from the placebo arm of the clinical trials.ResultsA total of 123 pregnancies in 123 women (median Expanded Disability Status Scale 1.0) were analyzed. Approximately 7.2% relapsed during pregnancy and 48.7% relapsed postpartum. Of pregnancies with prepartum and postpartum gadolinium (Gd)-enhanced MRI (n = 112), 8% had Gd+ lesions prepartum and 33% had new Gd+ lesions postpartum. Overall, 54.4% had either new T2 or Gd+ lesions postpartum. Seventy-nine percent of subjects with postpartum relapse had new MRI activity compared with 37.1% without relapse (p < 0.001). Twenty-five percent had both clinical and radiographic activity and only 24.9% maintained no evidence of disease activity status postpartum. There was no association between postpartum MRI activity and disease-modifying treatments (DMTs) (p > 0.5). MRI and clinical outcomes were also assessed for 126 nonpregnant untreated female patients with MS. Comparing pregnancy and no pregnancy groups, there was no difference in MRI activity at follow-up.ConclusionsThere was a high level of inflammatory radiographic disease activity which was related to relapses in postpartum patients with MS. Further studies are needed to determine whether hormonal fluctuations vs extended time off DMTs may be the underlying cause of our observations.

We perform a randomized trial to test the impact of electronic pill bottles with audiovisual reminders on oral disease modifying therapy (DMT) adherence in people with MS (PwMS).Adults with multiple sclerosis (MS) taking an oral DMT were randomized 1:1 for 90 days to remote smartphone app- and pill bottle-based (a) adherence monitoring, or (b) adherence monitoring with audiovisual medication reminders. Optimal adherence was defined as the proportion of doses taken ±3 h of the scheduled time. Numbers of missed pills and pills taken early, on time, late, and extra were recorded. A multivariable regression model tested possible associations between optimal adherence and age, MS duration, cognitive functioning, and number of daily prescription pills.85 participants (66 female; mean age 44.9 years) took dimethyl/diroximel fumarate (n = 49), fingolimod (n = 26), or teriflunomide (n = 10). Optimal adherence was on average higher in the monitoring with reminders arm (71.4%) than the monitoring only arm (61.6%; p = 0.033). In a multivariable model, optimal adherence was less likely in younger participants (p 0.001) and those taking more daily prescription pills (p 0.001). In the monitoring only arm, 4.0% of doses were taken early, 61.6% on time, 5.6% late, 4.4% in excess, and 24.4% were missed. In the reminders arm, these proportions were 3.4%, 71.4%, 3.7%, 8.7%, and 12.8%, respectively.We map real-world oral DMT adherence patterns using mHealth technology. PwMS who received medication reminders had higher optimal adherence. Nonadherence was more nuanced than simply missing pills. Developing strategies to improve adherence remains important in longitudinal MS care.

Background Alcohol and in particular red wine have both immunomodulatory and neuroprotective properties, and may exert an effect on the disease course of multiple sclerosis (MS). Objective To assess the association between alcohol and red wine consumption and MS course. Methods MS patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) who completed a self-administered questionnaire about their past year drinking habits at a single time point were included in the study. Alcohol and red wine consumption were measured as servings/week. The primary outcome was the Expanded Disability Status Scale (EDSS) at the time of the questionnaire. Secondary clinical outcomes were the Multiple Sclerosis Severity Score (MSSS) and number of relapses in the year before the questionnaire. Secondary MRI outcomes included brain parenchymal fraction and T2 hyperintense lesion volume (T2LV). Appropriate regression models were used to test the association of alcohol and red wine intake on clinical and MRI outcomes. All analyses were controlled for sex, age, body mass index, disease phenotype (relapsing vs. progressive), the proportion of time on disease modifying therapy during the previous year, smoking exposure, and disease duration. In the models for the MRI outcomes, analyses were also adjusted for acquisition protocol. Results 923 patients (74% females, mean age 47 ± 11 years, mean disease duration 14 ± 9 years) were included in the analysis. Compared to abstainers, patients drinking more than 4 drinks per week had a higher likelihood of a lower EDSS score (OR, 0.41; p = 0.0001) and lower MSSS (mean difference, − 1.753; p = 0.002) at the time of the questionnaire. Similarly, patients drinking more than 3 glasses of red wine per week had greater odds of a lower EDSS (OR, 0.49; p = 0.0005) and lower MSSS (mean difference, − 0.705; p = 0.0007) compared to nondrinkers. However, a faster increase in T2LV was observed in patients consuming 1–3 glasses of red wine per week compared to nondrinkers. Conclusions Higher total alcohol and red wine intake were associated with a lower cross-sectional level of neurologic disability in MS patients but increased T2LV accumulation. Further studies should explore a potential cause-effect neuroprotective relationship, as well as the underlying biological mechanisms.

Objective To evaluate the effect of pregnancy loss (PL) on MS disease activity. Methods Eleven women with first-trimester PLs were identified through a reproductive questionnaire. MS activity (MRI lesions and/or clinical relapses) was compared for the 12 months before conception and after PL. Results There was MS activity in 7/11 participants after, compared with 3/11 before PL (McNemar's test, p = .29), including MRI activity in 7/11 after, compared with 2/11 before PL (McNemar's test, p = .13). Conclusion Larger studies are needed to confirm this observed trend of increased MS activity following PL.

A 58-year-old woman presented to the emergency department with progressive memory deficits, odd behavior, and recurrent falls.

Neuromyelitis optica spectrum disorders are a group of relapsing, inflammatory, demyelinating neurologic syndromes involving the central nervous system associated with antibodies against aquaporin-4. Although most commonly an idiopathic autoimmune condition, neuromyelitis optica may occur as a paraneoplastic syndrome in rare instances. We report a case of transverse myelitis caused by paraneoplastic neuromyelitis optica as the presenting clinical syndrome in a patient with esophageal adenocarcinoma.

Multiple sclerosis (MS) is thought to be an autoimmune disease of the central nervous system (CNS). Initial presentations of MS typically occur between ages 20 and 40 and include symptoms such as monocular visual impairment, double vision, numbness, paresthesias, or weakness. Fatigue, cognitive impairment, and bowel/bladder symptoms are also common. The pathologic hallmark of the disease is the presence of glial scars (or sclerosis) in the CNS. MS is diagnosed on the basis of clinical findings and supporting evidence from magnetic resonance imaging (MRI). Ancillary tests such as evoked potentials and lumbar puncture are not routinely performed but aid in diagnostic evaluation.

Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) are chronic inflammatory disorders of the central nervous system that often affect women during their childbearing years. Therefore, many patients and providers navigate pregnancy-related management decisions. The current review provides updated information on the clinical effects of pregnancy on MS and NMO course, as well as the available data on safety of immunomodulatory MS treatments for pregnant and lactating women. We also address broader management issues of women with MS and NMO during conception, gestation and the postpartum period.

The Neurology Video Primer breaks down and illustrates difficult and dense topics in short concise concept videos, providing an overview of the most common neurologic symptoms and diseases, including stroke, epilepsy, headache, neurologic emergencies, demyelinating diseases, neurodegenerative disease, exploring pertinent clinical findings, epidemiology, disease mechanisms, pathophysiology, differential diagnoses, key steps in making the diagnosis and important concepts in treatment.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, predominantly affecting women of childbearing age. Therefore, issues of conception, pregnancy, and delivery are of significant importance to patients and treating physicians. We discuss immunologic and clinical effects of pregnancy on the course of MS including both immunosuppression on a local level and a heightened state of immunocompetence on a global level. Clinical outcomes of the Pregnancy in Multiple Sclerosis trials are reported. We analyze and update the available data on safety and efficacy of immunomodulating MS treatments and symptomatic treatments for pregnant and lactating women, and address specific issues of MS management at the time of pregnancy. We review the data related to estrogen-based MS therapies currently or previously in trials. Pregnancy does not appear to be associated with adverse outcomes in MS patients. Some evidence suggests possible beneficial effects, although clear prospective data of sufficient length and quality are limited. Long-term relapse rates or disability progression do not seem to be affected by pregnancy in MS patients. The use of immunosuppressive or immunomodulatory agents in pregnancy is not routinely advisable but could be considered under special circumstances.

Basilar artery occlusion can cause locked-in syndrome, which is characterized by quadriplegia, anarthria, and limited communication via eye movements. Here, we describe an uncommon stroke syndrome associated with endovascular recanalization of the top of the basilar artery: “reverse locked-in syndrome.” We report the case of a patient with atypical neurological deficits caused by acute ischemic stroke of the midbrain tegmentum. We perform neuroanatomic localization of the patient’s infarcts by mapping the magnetic resonance imaging (MRI) data onto a brainstem atlas. A 61-year-old man presented with acute coma and quadriplegia due to top of the basilar artery occlusion. He underwent emergent endovascular thrombectomy, with successful recanalization of the basilar artery at 4 h and 43 min post-ictus. The patient regained consciousness and purposeful movement in all four extremities, but the post-procedure neurological examination demonstrated bilateral ptosis with complete pupillary and oculomotor paralysis. MRI revealed infarction of the bilateral oculomotor nuclei in the midbrain tegmentum. At 9-month follow-up, he had anisocoria and dysconjugate gaze, but was living at home and required minimal assistance in performing all activities of daily living. Since the patient’s deficits were the exact opposite of those described in locked-in syndrome, we propose the term “reverse locked-in syndrome” to describe this neurological entity characterized by bilateral ptosis, non-reactive pupils, and ophthalmoplegia with preservation of consciousness and extremity motor function.

Neuromyelitis optica spectrum disorders (NMOSD) belong to a group of relapsing neurological syndromes characterized by significant morbidity and mortality due to central nervous system (CNS) inflammation and necrosis. Most patients are seropositive for pathogenic antibodies targeting Aquaporin-4, and while this water channel is mostly expressed on the foot processes of astrocytes, it is also expressed in placental tissues. On planning a pregnancy, patients should be well informed about the increased risk of preeclampsia and miscarriages, and that most medications used to treat NMOSD have potentially severe toxicities to the fetus. There is also increased risk of relapses in the postpartum period, and immunosuppressive agents are the mainstream method of preventing attacks.

Multiple sclerosis (MS) often affects women of childbearing age. There are many issues to consider when counseling women about their disease and treatment during this time. The Pregnancy in Multiple Sclerosis (PRIMS) study, published in 1998, is the best large-scale prospective study published to date. Based on this trial, and those that followed, it is recognized that the rate of relapse in MS decreases during pregnancy, especially during the third trimester, but there is a significant increase in relapse rate in the first three months postpartum. If relapses do occur during pregnancy, women are often treated with methylprednisolone, but this is generally avoided in the first trimester. Disease-modifying therapies (DMTs) are usually discontinued during preconception, pregnancy, and while breast-feeding. DMTs are classified under different FDA pregnancy categories based on human and animal data. Breast-feeding may influence postpartum relapse rate, but the true effect continues to be debated.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system most often characterized by clinical relapses and periods of remission. The past decade has seen a dramatic increase in disease-modifying therapies for MS. Fourteen FDA-approved immunomodulatory drugs are currently available, and more medications are in development. A growing number of reported opportunistic infections, including progressive multifocal leukoencephalopathy (PML), highlight the serious complications of these new drugs and the need for specific screening guidelines. Using data from Phase II and III randomized controlled trials, case reports, drug manufacturing data, and clinical experience, we outline the most common and serious infections associated with novel MS therapies.

Multiple sclerosis (MS) can affect cardiovascular function in a variety of ways leading to abnormalities in blood pressure response, heart rate, heart rhythm, left ventricular systolic function, and may cause pulmonary edema or cardiomyopathy. Cardiovascular dysfunction in MS is incompletely understood and likely underrecognized.The clinical presentation and pathophysiology of cardiovascular dysfunction in MS are reviewed, as are the cardiovascular toxicities of MS therapies, fingolimod and mitoxantrone. Cardiovascular dysfunction in MS can be caused by brainstem lesions affecting autonomic pathways in the medulla, overall plaque burden, and clinical severity of the disease.Cardiovascular abnormalities may be clinical or subclinical, and can lead to sudden death in some cases. Neurologists should be aware of the clinical presentation and pathophysiology of cardiovascular dysfunction in MS so as to ameliorate cardiovascular symptoms, prevent cardiovascular complications, and choose therapeutic agents that do not worsen underlying cardiovascular disease.

A 19-year-old man developed a severe upper respiratory infection. His chest X-ray was normal and the infection was presumed to have been viral. One week after his respiratory symptoms had resolved, he developed numbness of his entire left side. He reported no weakness, headache, changes in vision, seizures or right-sided symptoms during this period. His MR scan of brain showed an isolated symmetrical, non-expansile lesion in the splenium of the corpus callosum, characterised by diffusion restriction (figure 1A, B) and fluid attenuated inversion …

Herpes simplex virus (HSV) encephalitis can induce an autoimmune encephalitis mediated by autoantibodies against the N-methyl-D-aspartate receptor (NMDAR). Post-HSV NMDAR encephalitis and de novo NMDAR encephalitis have been more commonly described in children and young adults. We describe the case of a 67-year-old woman with post-HSV NMDAR encephalitis and review the relevant literature. Clinical, serological, neurophysiological, and imaging evaluations were undertaken in the evaluation of this patient. A literature review was performed. Nearly 2 months after a typical course of HSV encephalitis confirmed by HSV polymerase chain reaction studies from the spinal fluid and treated with intravenous acyclovir, a 67-year-old woman suffered neurological deterioration. There was no evidence of active HSV infection, but NMDAR antibodies were found in her serum and spinal fluid. The patient improved after initiation of immunosuppressive therapy. All patients who experience new or recurrent neurological symptoms following recovery from HSV encephalitis should be evaluated for post-infectious autoimmune encephalitis, including NMDAR encephalitis.

Introduction Immune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine. Case presentation Case 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels. Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects were observed in either patient. Conclusions In our two case reports, we found an association between vitamin D deficiency and immune thrombocytopenia where platelet levels responded to vitamin D treatment and hydroxychloroquine but not to prednisone. We believe there may be synergism between vitamin D supplementation and hydroxychloroquine. The mechanism by which high-dose vitamin D results in increased platelet counts in immune thrombocytopenia patients is unknown. However, vitamin D has long been thought to play an immunomodulatory role, which may include a dampened immune response in patients with immune thrombocytopenia or other autoimmune diseases.