Lycium barbarum glycopeptide ameliorates motor and visual deficits in autoimmune inflammatory diseases.

BACKGROUND: Lycium barbarum glycopeptide (LbGp), extracted from the traditional Chinese medicine (TCM) of Lycium barbarum (LB), provides a neuroprotective effect against neurodegenerative and neuroimmune disorders contributing to its immunomodulatory and anti-inflammatory roles. Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune-mediated central nervous system (CNS) demyelinating disease, clinically manifested as transverse myelitis (TM) and optic neuritis. However, no drug has been demonstrated to be effective in relieving limb weakness and visual impairment of NMOSD patients. PURPOSE: This study investigates the potential role of LbGp in ameliorating pathologic lesions and improving neurological dysfunction during NMOSD progression, and to elucidate the underlying mechanisms for the first time. STUDY DESIGN: We administrate LbGp in experimental NMOSD models in ex vivo and in vivo to explore its effect on NMOSD. METHODS: To evaluate motor function, both rotarod and gait tasks were performed in systemic NMOSD mice models. Furthermore, we assessed the severity of NMO-like lesions of astrocytes, organotypic cerebellar slices, as well as brain, spinal cord and optic nerve sections from NMOSD mouse models with LbGp treatment by immunofluorescent staining. In addition, demyelination levels in optic nerve were measured by G-ratio through Electro-microscopy (EM). And inflammation response was explored through detecting the protein levels of proinflammatory cytokines and NF-κB signaling in astrocytic culture medium and spinal cord homogenates respectively by Elisa and by Western blotting. RESULTS: LbGp could significantly reduce astrocytes injury, demyelination, and microglial activation in NMOSD models. In addition, LbGp also improved locomotor and visual dysfunction through preventing neuron and retinal ganglion cells (RGCs) from inflammatory attack in a systemic mouse model. Mechanistically, LbGp inhibits proinflammatory factors release via inhibition of NF-κB signaling in NMOSD models. CONCLUSION: This study provides evidence to develop LbGp as a functional TCM for the clinical treatment of NMOSD.

Vitamin D status and the risk of neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Previous studies have linked vitamin D deficiency with autoimmune diseases, and recent research has found low vitamin D levels in neuromyelitis optica spectrum disorder (NMOSD) patients. We aimed to determine the variances in serum 25(OH)D levels between NMOSD patients and healthy controls. METHODS: We searched English and Chinese databases (PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, WanFang Med, VIP) for observational studies related to serum 25(OH)D levels in NMOSD patients published up to August 24, 2023. We included studies with healthy controls and compared serum 25(OH)D levels between NMOSD patients and controls. We computed the mean difference (MD) and 95% confidence interval (CI) for continuous variables to evaluate serum 25(OH)D levels and combined odds ratios (ORs) and 95% CIs for dichotomized 25(OH)D data. RESULTS: Six papers were selected for meta-analysis, including 794 participants (347 in the NMOSD group and 447 in the healthy control group). Meta-analysis showed significantly lower serum 25(OH)D levels in the NMOSD group (MD: -7.83, 95 % CI: -10.99 to -4.68). The risk of 25(OH)D deficiency was 23.36 times higher in the NMOSD group (OR: 23.36, 95 % CI: 0.85 to 640.76, p = 0.06>0.05), with a 94 % occurrence rate. There was no significant difference in the risk of having sufficient 25(OH)D between the groups (p = 0.12>0.05). CONCLUSION: NMOSD patients have lower serum 25(OH)D levels than healthy controls. However, the current research results do not provide evidence for a causal relationship between serum 25(OH)D levels and the onset of NMOSD. Routine vitamin D supplementation may be advantageous for patients with NMOSD.

COVID-19 and the risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study.

Background: An increasing number of studies have elucidated a close nexus between COVID-19 phenotypes and neuromyelitis optica spectrum disorder (NMOSD), yet the causality between them remains enigmatic. Methods: In this study, we conducted a Mendelian randomization (MR) analysis employing summary data sourced from genome-wide association studies (GWAS) pertaining to COVID-19 susceptibility, hospitalization, severity, and NMOSD. The primary MR analysis employed the Inverse variance weighted (IVW) approach, which was supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. We implemented various sensitivity analyses including Cochran's Q test, MR-PRESSO method, MR-Egger intercept, leave-one-out analysis, and funnel plot. Results: The MR results demonstrated a nominal association between COVID-19 susceptibility and the risk of AQP4+ NMOSD, as evidenced by the IVW method (OR = 4.958; 95% CI: 1.322-18.585; P = 0.018). Conversely, no causal association was observed between COVID-19 susceptibility, hospitalization, or severity and the increased risk of NMOSD, AQP4-NMOSD, or AQP4+ NMOSD. The comprehensive sensitivity analyses further bolstered the robustness and consistency of the MR estimates. Conclusion: Our findings provide compelling evidence for a causal effect of COVID-19 phenotype on AQP4+ NMOSD, shedding new light on the understanding of the comorbidity between COVID-19 and NMOSD.

Pearls & Oy-sters: Syndrome of Inappropriate Antidiuretic Hormone Secretion Presenting as Neuromyelitis Optica Spectrum Disorder Flare.

While it was previously believed that neuromyelitis optic spectrum disorder (NMOSD) mostly affected the optic nerves and the spinal cord, it is increasingly recognized that NMOSD can involve any area of the CNS where aquaporin-4 is highly expressed. These other areas can include the hypothalamus and the circumventricular organs that surround the third and fourth ventricles, serving as osmoregulators. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia and has been associated with NMOSD due to these lesions. In this report, we present a case of a patient with known NMOSD, who presented with dizziness, fatigue, and generalized weakness and whose workup revealed hyponatremia in the setting of SIADH and hypothalamic demyelinating lesions. This case illustrates an atypical presentation of NMOSD and the importance of looking for syndromes, such as SIADH. This can guide diagnostic testing, such as getting thin MRI cuts through the hypothalamus and brainstem, as well as advanced management techniques such as immunotherapy.

High-efficacy therapies reduce clinical and radiological events more effectively than traditional treatments in neuromyelitis optica spectrum disorder.

BACKGROUND: People with neuromyelitis optica spectrum disorder (pwNMOSD) experience debilitating neurological attacks, resulting in permanent disability. OBJECTIVE: To evaluate if high-efficacy treatment was better than traditional agents at preventing disease advancement in pwNMOSD. METHODS: A retrospective study of pwNMOSD at one academic center was performed. Timelines were created for treatments subjects were exposed to along with clinical/radiological events related to disease worsening. High-efficacy treatments included eculizumab, inebilizumab, satralizumab, rituximab, ocrelizumab, tocilizumab, and sarilumab while therapies such as azathioprine, methotrexate, cyclophosphamide, and mycophenolate mofetil were classified as traditional agents. Poisson regression and mixed effects logistics models were constructed, and a subject-specific random intercept was used for intrasubject correlation. RESULTS: Of 189 pwNMOSD identified, 161 were aquaporin-4 IgG positive (AQP4 +) with 92 (77 female; median disease duration (MDD) (range) of 6.6 years (y) (1.2-18.6)) exposed only to high-efficacy therapy, 33 (28 female; 10.4 y (0.8-32.7)) only to traditional therapy, and 64 (54 female; 10.8 y (0.7-20.2)) to both. High-efficacy treatments reduced the rate of MRI advancement by 62.4% (95% CrI = [- 86.9%, - 16.8%]), relapses by 99.8% (95% CrI = [- 99.9%, - 99.6%]), and hospitalizations by 99.3% (95% CrI = [- 99.6%, - 98.8%]) when compared to traditional treatments. For AQP4 + subjects, a 655.7-fold increase in the odds of new spinal cord lesion development (95% CrI = [+ 37.4-fold, + 3239.5-fold]) was observed with traditional agents (p < 0.0001). CONCLUSION: High-efficacy treatments maximize opportunity for preventing disease advancement in newly diagnosed and established pwNMOSD.

χ-Separation Imaging for Diagnosis of Multiple Sclerosis versus Neuromyelitis Optica Spectrum Disorder.

Background Use of χ-separation imaging can provide surrogates for iron and myelin that relate closely to abnormal changes in multiple sclerosis (MS) lesions. Purpose To evaluate the appearances of MS and neuromyelitis optica spectrum disorder (NMOSD) brain lesions on χ-separation maps and explore their diagnostic value in differentiating the two diseases in comparison with previously reported diagnostic criteria. Materials and Methods This prospective study included individuals with MS or NMOSD who underwent χ-separation imaging from October 2017 to October 2020. Positive (χpos) and negative (χneg) susceptibility were estimated separately by using local frequency shifts and calculating R2' (R2' = R2* - R2). R2 mapping was performed with a machine learning approach. For each lesion, presence of the central vein sign (CVS) and paramagnetic rim sign (PRS) and signal characteristics on χneg and χpos maps were assessed and compared. For each participant, the proportion of lesions with CVS, PRS, and hypodiamagnetism was calculated. Diagnostic performances were assessed using receiver operating characteristic (ROC) curve analysis. Results A total of 32 participants with MS (mean age, 34 years ± 10 [SD]; 25 women, seven men) and 15 with NMOSD (mean age, 52 years ± 17; 14 women, one man) were evaluated, with a total of 611 MS and 225 NMOSD brain lesions. On the χneg maps, 80.2% (490 of 611) of MS lesions were categorized as hypodiamagnetic versus 13.8% (31 of 225) of NMOSD lesions (P < .001). Lesion appearances on the χpos maps showed no evidence of a difference between the two diseases. In per-participant analysis, participants with MS showed a higher proportion of hypodiamagnetic lesions (83%; IQR, 72-93) than those with NMOSD (6%; IQR, 0-14; P < .001). The proportion of hypodiamagnetic lesions achieved excellent diagnostic performance (area under the ROC curve, 0.96; 95% CI: 0.91, 1.00). Conclusion On χ-separation maps, multiple sclerosis (MS) lesions tend to be hypodiamagnetic, which can serve as an important hallmark to differentiate MS from neuromyelitis optica spectrum disorder. © RSNA, 2022 Supplemental material is available for this article.

Neuromyelitis optica spectrum disease coexisting with subacute combined degeneration: a case report.

BACKGROUND: Subacute combined degeneration (SCD) is a demyelinating disease characterized by vitamin B12 deficiency related segmental degeneration of the dorsal or lateral columns of the spinal cord. However, few cases have been reported as a comorbidity of SCD and neuromyelitis optica spectrum disease (NMOSD). CASE PRESENTATION: Herein, we describe a female patient (61-year-old) who had sensory deficits, paresthesia, and weakness of the distal extremities for over 2 months. She then received an initial diagnosis of SCD with typical inverted "V-sigh" hyperintensities over the posterior aspect of the spinal cord in magnetic resonance imaging (MRI - T2-weighted imaging), as well as megaloblastic anaemia in blood examinations. From the past history, there was no evidence of a dietary deficiency or gastric abnormalities. However, traditional treatment with vitamin B12 supplementation was ineffective. Hence, a demyelinating antibody examination showed that she had antibodies targeting aquaporin 4 (AQP4) in both the cerebrospinal fluid and serum, leading to the diagnosis of NMOSD. Her clinical symptoms were obviously improved after treatment with intravenous glucocorticoids. CONCLUSION: People who have nutritional deficiency or altered gastrointestinal function are more likely to develop SCD. This case raises the awareness that the poor therapeutic effects of simple vitamin B12 supplementation could be explained by immunoreactions against AQP4. A better recognition will be of great importance for the correct diagnosis of the comorbidity, as well as for essential treatment and even a better prognosis.

Effective connectivity within the corticothalamic circuit in the neuromyelitis optica patients: A comparative study using resting-state fMRI.

Neuromyelitis Optica, which is known as NMO, is a demyelination syndrome and inflammatory condition of the central nervous system that affects the optic nerves. Since structural imaging approaches cannot adequately describe the brain disorders in patients with NMO, functional magnetic resonance imaging (fMRI) can be used. Resting-state fMRI was performed on 25 healthy subjects and 26 NMO patients. After preprocessing the data, the time series belonging to the regions of the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precuneus (PRE), thalamus (THA), and middle temporal gyrus (MTG) were extracted as components of the corticothalamic circuit. The obtained time series were statistically analyzed as the input of dynamic causal modeling (DCM) in order to evaluate the effective connectivity within the corticothalamic circuit. The statistical analyses showed that the mean of effective connectivity power was significantly higher in the healthy subjects than in the NMO patients. For the healthy subjects, there was no significant difference in effective connectivity power between the two groups of males and females at the significance level of 0.05. In the NMO patients, there was a significant difference between the effective connectivity levels of the male and female groups only for IFG â†’ MFG, in which it was greater in males than in females. The results of our studies showed that resting-state fMRI could exhibit the difference between healthy and NMO subjects.

Effects of Vitamin D and Dexamethasone on Lymphocyte Proportions and Their Associations With Serum Concentrations of 25-Hydroxyvitamin D3In Vitro in Patients With Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder.

Background: Clear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate. Objective and Methods: Patients with MS (N=12) and neuromyelitis optica spectrum disorder (NMOSD; N=12) were enrolled along with 15 healthy controls. Changes in lymphocyte subset proportions during stimulation of their peripheral blood mononuclear cells (PBMCs) with the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and correlations with serum concentrations of the vitamin D precursor 25-hydroxyvitamin D3 (serum 25(OH)D3) were explored. The impact of 1,25(OH)2D3 stimulation on the expression of vitamin-D-responsive genes in immune cells was also investigated. Results: In both MS and NMOSD, stimulation of PBMCs with 1,25(OH)2D3 followed by steroid suppressed the proliferation of total lymphocytes and T cells. The ratio of CD19+CD27+ memory B cells (Bmem) to all B cells after stimulation with 1,25(OH)2D3 was negatively correlated with serum 25(OH)D3 in MS (Spearman's ρ=-0.594, p=0.042), but positively correlated in NMOSD (Pearson's r = 0.739, p=0.006). However, there was no relationship between the ratio of Bmem to CD19+CD24+CD38+ regulatory B cells and serum 25(OH)D3 in either MS or NMOSD. In addition, the level of 1,25(OH)2D3-induced CYP24A1 mRNA expression in PBMCs was significantly and negatively correlated with serum 25(OH)D3 (for ΔCT, r=0.744, p=0.014) in MS. Conclusion: These findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D3 and the proportion of Bmem under immune-cell stimulation differed between MS and NMOSD. Further investigations are warranted with larger patient populations.

Hypothalamic lesions in neuromyelitis optica spectrum disorders: exploring a scoring system based on magnetic resonance imaging.

PURPOSE: We propose a scoring system for early diagnosis of sleep abnormalities in neuromyelitis optica spectrum disorders (NMOSD) with hypothalamic lesions based on magnetic resonance imaging (MRI). MATERIALS AND METHODS: We evaluated MRI features of 45 patients with hypothalamic lesions identified from two cohorts. Univariate logistic regression analysis identified factors associated with sleepiness, which were subsequently used to develop a scoring system. Interrater reliability was determined using intraclass correlation coefficient (ICC). Correlations between scores and clinical features were analyzed. RESULTS: In total, 48.9% of 45 patients with hypothalamic lesions exhibited sleepiness. The number of involved slices, maximum width/length of hypothalamic lesions, and boundaries extending beyond the hypothalamus were associated with sleepiness (all p < 0.05). The sensitivity and specificity of the scoring system were 68.2% and 87.0%, respectively. The ICC values for the maximum width and length measurement of hypothalamic lesions were 0.82 and 0.81, respectively. Daily sleep time and Epworth sleepiness scale scores were positively correlated with MRI-based scores (p < 0.05, 95% confidence interval (CI) 0.69-0.93 and p < 0.05, 95% CI 0.55-0.88, respectively). CONCLUSION: A scoring system based on MRI features was developed to provide diagnosis of sleepiness in NMOSD with hypothalamic lesions earlier than other measures.

Repetitive 1.6 ATA hyperbaric oxygen therapy for bilateral ARCO Stage II steroid-associated osteonecrosis of the femoral head.

Hyperbaric oxygen (HBO2) therapy has been demonstrated to have beneficial effects on the early stages of steroid-associated osteonecrosis (SAON) of the femoral head. Since high HBO2 pressure (e.g., 2.4-2.5 atmospheres absolute/ATA) has been commonly considered to have a greater ability to restore tissue oxygenation in the femoral head than low pressure (e.g., 1.6 ATA), the latter HBO2 protocol is rarely used for SAON treatment. In this paper, we present the case of a 36-year-old female diagnosed with bilateral early stage (Association for Research on Osseous Circulation, ARCO stage II) SAON caused by steroid therapy for neuromyelitis optica spectrum disorder (NMOSD). Because the patient could not endure high HBO2 pressures, the treatment pressure was adjusted to 1.6 ATA, which was the highest pressure the patient could withstand. After 20 treatment sessions, her symptoms were relieved significantly. Her visual analog score (VAS: using a 0-10 score) decreased from 7 to 2, and after 50 treatment sessions her symptoms disappeared almost completely. A significant improvement was also observed radiologically by computed tomography (CT) and magnetic resonance imaging (MRI) examinations. This case study provides a potential HBO2 treatment protocol with reduced pressure for early-stage femoral head necrosis. Further research is needed to validate this finding and explore the potential mechanism of HBO2 on SAON.

Acute bilateral cerebral infarction in the presence of neuromyelitis optica spectrum disorder: A case report.

RATIONALE: Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory demyelinating disorders of the central nervous system; they are characterized by severe optic neuritis and transverse myelitis. Intravenous methylprednisolone pulse (IVMP) therapy is an effective treatment that is administered to patients in the acute phase of NMOSD; this therapy has achieved remarkable results in clinical practice. However, there are no reports on NMOSD patients who have experienced an acute bilateral cerebral infarction while undergoing IVMP treatment. PATIENT CONCERNS: We report on a 62-yr-old woman who was undergoing IVMP therapy for the primary diagnosis of NMOSD. Unexpectedly, the patient's existing limb weakness worsened, and she developed motor aphasia on the second day of IVMP treatment. Additionally, brain magnetic resonance imaging revealed acute bilateral cerebral infarction. DIAGNOSIS: The patient's clinical manifestations, medical imaging results, and laboratory test results were taken into consideration; the final diagnosis was acute bilateral cerebral infarction in the presence of NMOSD. INTERVENTIONS: Subsequent to the onset of acute cerebral infarction, the patient was immediately treated with oral aspirin, atorvastatin, and intravenous butylphthalide. The hormone dose was adjusted to an oral 60-mg/d dose for maintenance; this was followed by immunoadsorption plasmapheresis for 3 days, and double-filtration plasmapheresis for 2 days. OUTCOMES: Following treatment onset, the patient's ocular symptoms significantly improved, and her limb muscle strength gradually recovered. Two months after discharge, the patient's husband reported that she was able to walk with the help of others and take care of herself, and that there was no recurrence. LESSONS: Medical professionals must be aware of the possibility of NMOSD patients with cerebrovascular risk factors suffering an acute cerebral infarction while undergoing high-dose IVMP therapy, as this therapy can exacerbate existing problems.

Biotinidase deficiency presenting as Neuromyelitis Optica Spectrum Disorder.

Biotinidase deficiency disorder is a rare inherited metabolic disorder with typical neurological manifestations of hypotonia, developmental delay, rashes, seizures, hearing and vision impairment. We present two cases with different and unusual clinical profiles, whose neuroimaging resembled Neuromyelitis Optica Spectrum Disorder. Case 1 was initially treated with immunomodulation with steroids and intravenous immunoglobulins, with partial improvement. However reinvestigation for worsening of symptoms showed more extensive changes on spine magnetic resonance imaging. Raised lactate and alanine levels on repeat cerebrospinal fluid testing resulted in further investigations that revealed a biotinidase deficiency. Case 2 presented mainly with respiratory symptoms: a barium swallow suggested bulbar dysfunction. Neuroimaging of brain and spine was similar to that in case 1 and the child was promptly investigated for and confirmed to have biotinidase deficiency. Both cases responded to biotin supplementation. It is important to be cognisant of atypical neurological presentations of biotinidase deficiency including those that mimic immune mediated neurodemyelination disorders, as biotinidase deficiency is potentially treatable.

Cannabis extract for the treatment of painful tonic spasms in a patient with neuromyelitis optica spectrum disorder: A case report.

Painful tonic spasm (PTS) is a common yet debilitating symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), especially those with longitudinally extensive transverse myelitis. Although carbamazepine is an effective treatment, it poses the risk of severe adverse reactions, such as Steven-Johnson syndrome (SJS). In this case report, we describe an NMOSD patient with severe PTS suffering from carbamazepine-induced SJS who responded well to cannabis extract. Since cannabinoids can ameliorate spasticity in an experimental autoimmune encephalomyelitis model through cannabinoid 1 (CB1) receptor activation, cannabis extract which includes delta-9-tetrahydrocannabinol (THC) is a potential treatment option for PTS in NMOSD patients.

Bone health in neuromyelitis optica: Bone mineral density and fractures.

BACKGROUND: The bone health in neuromyelitis optica spectrum disorder with aquaporin-4 immunoglobulin G antibodies (NMOSD-AQP4) have not been fully evaluated. To evaluate the prevalence of fractures and bone loss in patients with NMOSD-AQP4 compared to healthy controls and patients with multiple sclerosis (MS) and to identify the risk factors associated with fractures and low bone mineral density (BMD) in patients with NMOSD-AQP4. METHODS: Seventy-one patients with NMOSD-AQP4 were included. The two control groups consisted of 213 age-, sex-, menopause-, and body mass index (BMI)-matched healthy participants from the Korean National Health and Nutrition Examination Survey (healthy controls) and 41 patients with multiple sclerosis (disease controls). We collected demographic and clinical data related to bone health including BMD and FRAX score. RESULTS: Patients with NMOSD-AQP4 had a higher prevalence of fractures than the healthy control group (OR = 5.40, CI = 2.004-14.524, p = 0.001), with falling, but not steroid use, being associated with an increased risk of fractures after diagnosis with NMOSD-AQP4 (OR = 24.902, CI = 3.086-200.947, p = 0.003). They also had significantly lower BMD than controls (femur neck, p = 0.044; total hip, p < 0.001), which was more prominent in young participants. The BMD in the NMOSD-AQP4 group was associated with cumulative dose of oral steroids, age, sex, BMI, and partly with the prophylactic calcium supplements. Though the patients with NMOSD-AQP4 did not differ significantly from patients with MS in terms of fracture rate and BMD, they had higher risk of fractures as measured by the Fracture Risk Assessment Tool (for major osteoporotic fractures, (p = 0.001; for hip fractures, p = 0.018). CONCLUSION: Patients with NMOSD-AQP4 had a significantly higher risk of fractures that could mostly be attributed to falling. Additionally, low BMD was observed in these patients; it was more prominent among young patients, associated with steroid use, and may partially prevented by the use of prophylactic calcium supplements.

Scrambler therapy improves pain in neuromyelitis optica: A randomized controlled trial.

OBJECTIVE: To determine whether Scrambler therapy is an effective, acceptable, and feasible treatment of persistent central neuropathic pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and to explore the effect of Scrambler therapy on co-occurring symptoms. METHODS: We conducted a randomized single-blind, sham-controlled trial in patients with NMOSD who have central neuropathic pain using Scrambler therapy for 10 consecutive weekdays. Pain severity, pain interference, anxiety, depression, and sleep disturbance were assessed at baseline, at the end of treatment, and at the 30- and 60-day follow-up. RESULTS: Twenty-two patients (11 per arm) were enrolled in and completed this trial. The median baseline numeric rating scale (NRS) pain score decreased from 5.0 to 1.5 after 10 days of treatment with Scrambler therapy, whereas the median NRS score did not significantly decrease in the sham arm. Depression was also reduced in the treatment arm, and anxiety was decreased in a subset of patients who responded to treatment. These symptoms were not affected in the sham arm. The safety profiles were similar between groups. CONCLUSIONS: Scrambler therapy is an effective, feasible, and safe intervention for central neuropathic pain in patients with NMOSD. Decreasing pain with Scrambler therapy may additionally improve depression and anxiety. CLINICALTRIALSGOV IDENTIFIER: NCT03452176. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that Scrambler therapy significantly reduces pain in patients with NMOSD and persistent central neuropathic pain.

Neuromyelitis optica spectrum disorder with severe orthostatic hypotension due to hypothalamic lesions.

BACKGROUND: Rare cases of neuromyelitis optica spectrum disorder (NMOSD) occur with only hypothalamic lesions as the initial lesion, and such cases can present with hypersomnia, endocrinopathy, and autonomic failure. However, orthostatic hypotension (OH) caused by hypothalamic lesions due to NMOSD has not been reported. CASE REPORT: We report the case of a patient with NMOSD who presented with severe OH due to hypothalamic lesions. CONCLUSION: We suggest that clinicians should be aware that NMOSD with hypothalamic lesions can present with OH.

Epidemiology of pediatric multiple sclerosis, neuromyelitis optica, and optic neuritis in Taiwan.

BACKGROUND AND OBJECTIVE: The epidemiology of pediatric acquired demyelinating disorders remains to be clarified in many parts of Asia. We carry out this study to depict the epidemiology of pediatric multiple sclerosis (MS), neuromyelitis optica (NMO), and optic neuritis (ON) in Taiwan. METHODS: We conducted a retrospective nationwide population-based study using data from Taiwan's National Health Insurance Research Database. Prevalent cases of pediatric MS and NMO during 2001-2015, and incident cases of pediatric MS, NMO, and ON during 2003-2015 were identified. The demographic features and comorbidities were investigated. RESULTS: We identified 403 MS, 42 NMO, and 1496 ON incident cases under the age of 20 during 2003-2015. The majority of pediatric MS (86.1%) and NMO (90.5%) patients were 10 years old or above. The incidence of MS and ON was relatively steady, while that of NMO increased prominently later during the study period. The average incidence of pediatric MS and NMO during 2011-2015 was 0.52 and 0.11 per 100,000 person-years, respectively. The female preponderance was evident for pediatric MS and NMO, and less so for pediatric ON. The most common autoimmune comorbidities for pediatric MS were thyrotoxicosis (1.0%) and systemic lupus erythematosus (0.7%). CONCLUSION: The epidemiology of pediatric MS was largely stationary in Taiwan during 2001-2015, while the prevalence of pediatric NMO rose steeply during this period, probably reflecting better recognition of this clinical entity. Autoimmune comorbidities were uncommon for pediatric MS and NMO in Taiwan.

Secondary hypersomnia as an initial manifestation of neuromyelitis optica spectrum disorders.

The identification of AQP4-IgG, a specific and pathogenic antibody of NMO/SD has led to a broadening of the clinical spectrum of manifestations of NMO/SD including the presence of encephalic symptoms. Lesions are often distributed on peri­ependymal area and sometimes affected the diencephalon leading to sleep disorders. We report a case of hypersomnia with polysomnographic documentation during the first attack of NMO/SD. Brain MRI revealed bilateral hypothalamic lesions around the third ventricle, whereas optic nerves and spinal cord were intact. The record of the nocturnal video-polysomnography followed by multiple sleep latency tests (MSLT) revealed an abnormal shortened sleep period with a single sleep onset in REM allowing secondary central hypersomnia diagnosis. The recovery of hypersomnia was complete within few months without psychostimulant treatment and the diencephalic lesion disappeared. Thus, diencephalic form of NMO/SD seems to cause narcolepsy or non-narcoleptic central hypersomnia and have a good recovery.