Median Age Of Onset Research Articles

Familial occurrence of seizure disorders across MRI defined structural focal epilepsy etiology

BackgroundPrevious studies have established familial occurrence of epilepsy and seizure disorders and early age of epilepsy onset as predictors of genetic epilepsy, but have not evaluated the rate of their occurrence in patients with different epilepsy etiology. Our study determines the distribution of familial occurrence and age of epilepsy onset across structural focal epilepsy (FE) etiology in a large FE cohort. MethodsRecords of 1354 consecutive patients evaluated for epilepsy and seizure disorders in The Neurology Clinic, University Clinical Center of Serbia from 2008 to 2019 were screened for FE. Structural etiology, lobar diagnosis, familial occurrence, and age at epilepsy onset were determined. Patients with a. nonlesional focal epilepsy (NLFE), b. hippocampal sclerosis (HS) and c. congenital or perinatal etiology (CPE) were classified as NAFE, while patients with an identified acquired focal epilepsy (AFE) constituted the control group. ResultsWe identified 965 patients with FE, 329 (34.1 %) with NLFE, 213 (22.1 %) with HS, 174 (18.0 %) with CPE and 249 (25.8 %) with AFE. Familial occurrence was identified in 160 (16.6 %), 19.1 % of patients with NAFE and 9.2 % of AFE (p = 0.003). Patients with NAFE had a younger age of epilepsy onset (13 vs. 18 years, p < 0.001). The highest proportion of familial occurrence was found in patients with NLFE (23.7 %), while the youngest median age of epilepsy onset was identified in patients with HS (12 years) and CPE (11 years). ConclusionPatients with NAFE frequently have familial occurrence of epilepsy and have an earlier age of epilepsy onset than patients with AFE.

Treatment strategies and treatment-related adverse events in MG according to the age of onset.

Early-onset (EOMG) and late-onset (LOMG) are distinct groups of MG patients. It is unclear if treatment strategies and treatment-related adverse events may differ according to the age of MG onset. This single-center retrospective study includes all MG patients followed at a tertiary center since 2007. We reviewed the electronic clinical records. In total, 212 patients were identified, 142 (67.0%) females, with a median disease duration of 10 years. The median age of symptom onset was 42.0 (26.0-64.5) years, with 130 (61.3%) EOMG cases and 82 (38.7%) LOMG. EOMG were more frequently female, had longer disease duration and often more generalized MG (p < 0.001). Comorbidities were significantly more frequent in LOMG (67.1%) compared to EOMG (53.1%) (p = 0.002). Steroid-related adverse effects motivating the switch to steroid-sparing agents (82.0%) were different between groups, with hypertension, hypercholesterolemia, diabetes mellitus and malignancies being more common in LOMG. At the same time, osteoporosis and dyspepsia were more frequent in EOMG (p < 0.001). The most common first-line choice was azathioprine (45.8%), and rituximab was used in 4 patients (1.9%). Our study shows that treatment modalities are similar between EOMG and LOMG, while steroid-related adverse events appear to be distinct.

Ocular Manifestations of Multiple Sclerosis: A Population-Based Study.

To evaluate the population-based frequency and severity of multiple sclerosis (MS)-related ocular diseases. Retrospective, population-based study examining patients with MS between January 1, 1998 and December 31, 2011. Patients were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota residents. Diagnosis of MS was confirmed based on neuroimaging, cerebrospinal fluid studies, and serum studies for each patient according to the 2017 McDonald criteria. Patient data were obtained using the medical records and followed through April 1, 2018. Of the 116 patients with MS, 66% were female and the median age of onset was 36 years (interquartile range 27.5-43.5 years). About half (61/116, 53%) had MS-related neuro-ophthalmic manifestations during their disease course, and about one-fourth (33/116, 28%) had visual symptoms as their presenting symptom of MS, most commonly as optic neuritis (26/116, 22%). Optic neuritis was the leading MS-related ocular condition (37%), followed by internuclear ophthalmoplegia (16%) and nystagmus (13%). Optic neuritis was mostly unilateral (40/43, 93%), with 16% (6/43) having a visual acuity of 20/200 or worse at nadir but ultimately 95% (35/37) improving to a visual acuity of 20/40 or better. This study provides the population-based frequency of MS-related ocular disease, which demonstrates a high frequency of ocular manifestations in MS both at disease onset and during the disease course, emphasizing the utility of neuro-ophthalmologists, or collaboration between neurologists and ophthalmologists, in the care of patients with MS.

Impact of rituximab treatment regime on time to relapse in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder

BackgroundAquaporin-4 (AQP4) antibody associated neuromyelitis optica (NMOSD) requires long-term immunosuppression. Rituximab is increasingly used worldwide, however the optimal regime is not established. MethodsWe retrospectively examined different rituximab regimens in AQP4-NMOSD. Standard monotherapy (SM; 6 monthly infusions), SM plus oral steroids (SM+S), extended interval dosing (EID; guided by CD19 repopulation) and EID with oral steroids (EID+S) were compared. The primary outcome was time to first clinical relapse. Potential confounders including age, gender, number of previous relapses, and onset phenotype were included. Results77 patients were included: 67 females, median onset age 35.6, median DSS at rituximab initiation 5.0. 39 were on SM+S, 20 SM, 6 EID, and 12 EID+S. 25/77 patients relapsed during a median follow-up of 44.0 months. No significant difference in time to first relapse was observed between any rituximab regimen. Pooled analyses to compare regimens that use standard monotherapy (SM and SM+S) against those that use extended interval dosing (EID and EID+S) showed no significant difference. Pooled analysis of regimens using steroids with those not using steroids also showed no significant difference. Adjusted Cox proportional hazard model revealed no significant difference between rituximab regimens or influence of demographic factors. 9 significant adverse events were recorded, 5 in the SM group and 4 in SM+S. ConclusionsThis study provides some basis for further exploring EID as a viable option for long term treatment of AQP4-NMOSD. This may improve patient experience and consolidate use of hospital resources.

Autoinflammatory syndromes mimicking Behçet's disease with gastrointestinal involvement: a retrospective analysis.

This retrospective study aimed to investigate the clinical characteristics and genetic findings in paediatric patients with gastrointestinal involvement in Behçet's disease (BD), elucidating the spectrum of autoinflammatory syndromes mimicking BD in this young population. Fifty paediatric patients diagnosed with BD between January 2016 and December 2022, including 24 (48%) with gastrointestinal involvement, underwent comprehensive analysis. Clinical presentations, laboratory examinations, gastrointestinal endoscopy, and genetic tests were conducted, with patients stratified based on genetic results for rigorous comparative clinical analysis. The cohort, with a median age of disease onset at 4.0 years, predominantly manifested with recurrent oral ulcers (100%). Gastrointestinal symptoms were prevalent in 83.3%, with abdominal pain (70%) and haematochezia (16.7%) being notable. Endoscopic evaluations unveiled lesions primarily in the terminal ileum and ileocecal region, with diverse ulcers across various anatomical sites. While 70.8% initially met ICBD criteria, only 41.6% fulfilled new paediatric classification criteria. Genetic analysis in 18 patients unveiled pathogenic variants in 7, with the genetic-positive group exhibiting earlier onset and more atypical symptoms. Noteworthy cases included X-linked deficiency in ELF4, A20 haploinsufficiency, and Majeed syndrome, with two cases revealing chromosomal abnormalities such as trisomy 8 syndrome. Comparative analysis underscored earlier disease onset, heightened inflammatory markers, and distinctive gastrointestinal lesions in the genetic-positive cohort. Identification of monogenic diseases and chromosomal abnormalities resembling BD underscores the imperative of precise diagnosis for tailored treatment and genetic counselling. Expanding genetic screening initiatives holds promise for enhancing our comprehension of the genetic landscape associated with BD.

Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.

Exploring strategies to optimise outcomes in hepatitis-associated aplastic anaemia patients following haematopoietic stem cell transplantation

This study aimed to assess haematopoietic stem cell transplantation (HSCT) safety and efficacy while exploring strategies for optimising outcomes in patients with hepatitis-associated aplastic anaemia (HAAA). We retrospectively reviewed 35 HAAA patients who underwent HSCT at a large Chinese blood disease hospital between 2008 and 2022. HAAA patients receiving HSCT typically presented with severe (28.6%) and very severe (65.7%) AA. Male patients predominated (68.6%), with a median onset age of 23 years (range, 9–44). Haploidentical donor-HSCT and matched sibling donor-HSCT were in comparable proportions. The 5-year overall survival (OS) rate was 74.0%, with cumulative incidences of grade II–IV acute and chronic graft-versus-host disease (GVHD) at 37.1% and 22.4%, respectively. A diagnosis-to-HSCT interval ≥ 75 days, acute GVHD, and post-HSCT liver events (e.g., hepatic GVHD and a three-fold increase in aminotransferase or bilirubin) significantly worsened 5-year OS. In the multivariate models, recipients with sex-matched grafts had better OS, and those with younger male donors had a lower incidence of II–IV aGVHD. Higher HLA matching degree (HLA > = 7/10) was an independent prognostic factor associated with better OS and GFFS. A diagnosis-to-HSCT interval ≥ 75 days was predictive of post-transplant liver events in HAAA patients. In conclusion, HSCT was a safe and effective treatment for HAAA. Early transplantation, careful donor selection and improving post-transplant liver events were crucial to optimise outcomes.

Headache Phenotypes in Idiopathic Intracranial Hypertension and Its Short-Term Outcomes: A Retrospective Case Series Study.

Idiopathic intracranial hypertension (IIH) presents a complex physiopathology, leading into diverse manifestations, notably variable headache phenotypes. Furthermore, its frequent overlap with migraine complicates the evaluation of treatment benefit for IIH-related headache. Our aim was to investigate if there is any relationship between demographic factors, clinical patterns of headache, treatment response, and headache short-term outcome with the headache phenotype of IIH. This study was a retrospective analysis of demographic, clinical, and treatment features of patients with idiopathic intracranial hypertension presenting with headache and evaluation of headache outcomes in the first 12 months following treatment. Thirty-two patients were included (median age of onset 29.0 years (interquartile range 25.0 - 38.5), 90% females, median body mass index 32.5 kg/m2; 87.5% (n = 28) with papilledema; median cerebrospinal fluid opening pressure 36.5 cm H2O). Patients presented with migraine (n = 11, 34.4%), tension-type (n = 9, 28.1%), or a not-classifiable headache (n = 12, 37.5%). Regarding treatment and short-term follow-up (12 months), there was a failure of medical treatment in 43.8% (n = 14) and a reduction of headaches (≥ 50%) in 62.5% (n = 20) of the patients. Among headache phenotypes, there were no significant differences regarding demographics, clinical features, clinical patterns, or treatment response at baseline. Also, there were no differences regarding response to treatment or headache outcomes in 1, 3, 6, and 12 months of follow-up. In our study, migraine and unclassifiable types were the most commonly reported headache phenotypes. Headache phenotype does not appear to be an essential factor in allowing clinical distinction, treatment response, or predicting the short-term headache outcome of this intriguing entity.

Analysis of characteristics of movement disorders in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Movement disorders (MDs) are common in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis. A retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People's Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (<12 years, 12-17 years, and ≥ 18 years) and genders, and the prevalence of each MD was compared in different age and gender groups. (1) In our study there were 64 patients, of whom 76.6% (49/64) presented with MDs; the median age of onset in patients with MDs was 21 (15,35) years and 65.3% (32/49) were female. The three most common MDs were orofacial dyskinesia (OFLD) (67.3%), dystonia (55.1%), and stereotypies (34.7%). Patients <12 years were more likely to experience chorea than patients in other age groups (p = 0.003). (2) Compared with the non-MDs group, patients in the MDs group showed higher rates of prodromal manifestations, autonomic dysfunction, consciousness disorders, as well as pulmonary infection and gastrointestinal dysfunction (all p < 0.05). Peripheral blood neutrophil to lymphocyte ratio (NLR) (p = 0.014), the proportion of cerebrospinal fluid (CSF) NMDAR antibody titers ≥1:32 (p = 0.047), ICU admission rate (p = 0.04), length of stay (p = 0.007), maximum mRS score in the course of disease (p = 0.001) and mRS score at discharge (p = 0.006) in the MDs group were significantly higher than the non-MDs group. MDs associated with anti-NMDAR encephalitis were predominantly hyperkinetic. Chorea occurred more commonly in patients aged <12 years. Patients with MDs were prone to autonomic dysfunction, consciousness disorders, pulmonary infection, and gastrointestinal dysfunction; they had more intense inflammation, more severe disease, and a poorer short-term prognosis.

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.

Mixed connective tissue disease with juvenile onset: results of a retrospective single-center study

Mixed connective tissue disease (MCTD) is one of the very rare systemic autoimmune diseases; it accounts for 0.1–0.6% of cases in pediatric rheumatologists' practices. MCTD is characterized by a broad spectrum of clinical manifestations and a high frequency of extremely unspecific symptoms at the onset, with the overall picture of the disease forming slowly and gradually. The diagnosis is often delayed and confirmed only at an advanced stage of organ dysfunction with the development of irreversible changes.Objective: to identify a group of patients fulfilling the criteria for MCTD in an open, single-center, continuous retrospective study among anti-ribonucleoprotein (anti-RNP) antibody-positive patients and to analyze their demographic, clinical and laboratory characteristics and therapy.Material and methods. All anti-RNP-positive patients admitted to the pediatric department of V.A. Nasonova Research Institute of Rheumatology from 2019 to 2023 and meeting at least one of the variants of the MCTD criteria (Kasukawa, Alarcуn-Segovia, Kahn and Sharp criteria) were included in the study.Results and discussion. 18 (56.25%, 17 girls and 1 boy) of 32 anti-RNP-positive patients fulfilled criteria for MCTD. Patients most frequently fulfilled a combination of criteria – Sharp and Kahn (n=8) or Alarcуn-Segovia and Kahn (n=8). The median age of onset of MCTD was 12.2 [9.7; 13.9] years. The most common clinical manifestations were arthritis (100%), various skin lesions (94.4 %), Raynaud's phenomenon (88.9%), lymphadenopathy (72.2%) and general constitutional disorders (50%). Sjögren's syndrome (SS) was diagnosed in 17 (94.4%) patients. All patients had antinuclear factor (ANF) 1/1280, and the anti-RNP level was &gt;200 U/ml. There were also antibodies against double-stranded DNA (n=5), Ro- (n=4) and Sm- (n=5) antigens. An IgM rheumatoid factor was detected in 6 patients and hypergammaglobulinemia in 10 patients. Capillaroscopic changes in the nailfold with predominant scleroderma type were found in 77.8% of patients. The most common combination was of Raynaud's phenomenon, arthritis, SS, lymphadenopathy and hypergammaglobulinemia (50%). All patients received glucocorticoids, 9 – hydroxychloroquine, 8 – methotrexate, 3 – mycophenolate mofetil, 1 – cyclophosphamide, 1 – azathioprine. Biologic DMARDs (bDMARDs) were prescribed to 12 (66.7%) patients: 3 – rituximab, 8 – abatacept, 1 – belimumab, with an acceptable safety profile and initial efficacy.Conclusion. Most patients in the study met the Kahn criteria. Only 2 patients met all variants of the criteria, which indicates the need to use a combination of criteria when a MCTD is suspected. A combination of Raynaud's phenomenon, arthritis, SS, lymphadenopathy and hypergammaglobulinemia was observed in half of patients with MCTD. The presence of Raynaud's phenomenon and high ANF titer in children with rheumatic diseases, especially with a polymorphic clinical picture, requires the inclusion of MCTD in differential diagnosis. Preliminary results indicate the safety of the use of biologic drugs in children with MCTD.

Febrile infection-related epilepsy syndrome with claustrum lesion: an underdiagnosed inflammatory encephalopathy.

To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C). Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis. Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5years. All patients developed seizures after fever, with a median interval of 5days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3months). The median follow-up was 11.5months;60% of patients were diagnosed with refractory epilepsy. Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome.

Variant and clinical landscape of Leber hereditary optic neuropathy based on 1516 families with mtDNA variants in a tertiary centre

AimsTo investigate the clinical characteristics of Leber hereditary optic neuropathy (LHON) with mtDNA primary mutations to better understand features associated with prognosis.MethodsThis study enrolled 1540 LHON patients from 1516 unrelated...

Clinical symptoms, biochemistry, and liver histology during the native liver period of progressive familial intrahepatic cholestasis type 2

BackgroundProgressive familial intrahepatic cholestasis type 2 (PFIC2) is an ultra-rare disease caused by mutations in the ABCB11 gene. This study aimed to understand the course of PFIC2 during the native liver period.MethodsFrom November 2014 to October 2015, a survey to identify PFIC2 patients was conducted in 207 hospitals registered with the Japanese Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Investigators retrospectively collected clinical data at each facility in November 2018 using pre-specified forms.ResultsBased on the biallelic pathogenic variants in ABCB11 and/or no hepatic immunohistochemical detection of BSEP, 14 Japanese PFIC2 patients were enrolled at seven facilities. The median follow-up was 63.2 [47.7–123.3] months. The median age of disease onset was 2.5 [1–4] months. Twelve patients underwent living donor liver transplantation (LDLT), with a median age at LDLT of 9 [4–57] months. Two other patients received sodium 4-phenylbutyrate (NaPB) therapy and survived over 60 months with the native liver. No patients received biliary diversion. The cases that resulted in LDLT had gradually deteriorated growth retardation, biochemical tests, and liver histology since the initial visit. In the other two patients, jaundice, growth retardation, and most of the biochemical tests improved after NaPB therapy was started, but pruritus and liver fibrosis did not.ConclusionsJapanese PFIC2 patients had gradually worsening clinical findings since the initial visit, resulting in LDLT during infancy. NaPB therapy improved jaundice and growth retardation but was insufficient to treat pruritus and liver fibrosis.

536 - Association between pediatric BMI and vitiligo distribution: an observational cohort study

Abstract Background No articles have ever addressed the relationship of BMI with the location of disease in pediatric vitiligo patients. Objective We aimed to explore the relationship between birthweight, reported BMI classifications, and pediatric vitiligo disease characteristics. Methods We explored 232 consecutive pediatric vitiligo patients. Patients’ parents self-reported height, weight, and disease localization. The body mass index classifications were divided into underweight for body mass index (BMI) &amp;lt;18.5, normal for BMI of 18.5 or greater and &amp;lt;25, and overweight for a BMI of 25. Results Exploring birthweight and age of onset, there was a trend towards decreasing median age of onset with weight increases, but it is not statistically significant when we group the patients by BMI class. There is a trend towards older age for children with higher BMI classes (p-value = 0.06). For kids under the age of 12, duration of disease was 4.6 years, vs. 7.7 years for kids over the age of 12 years (p&amp;lt;0.001). When further broken down into kids under 6 years, &amp;gt;6 and less than 12 years, &amp;gt;12 years, and less than 14 years, and 14-17 years, years of disease jumped from 1.3 to 4, to 6.6, and to 7.5 years respectively, demonstrating increased years of disease burden (P&amp;lt;0.001). There is a positive trend in locations and age when looked at for self-reported BSA of 1-25% vs. &amp;gt;25%: (p-value = 0.044). Wrists, hands, hips, legs, ankles, and feet were statistically more likely to be involved by 14-17 years, over 0-6 years (p&amp;lt;0.05 for each site). BSA was 1-25% in 79% of kids under 12 years of age and 75% for kids&amp;gt; 12 years of age. For those with a BSA of 26%+ all anatomical regions explored were statistically significant (p&amp;lt;0.05) other than the specific locations of the scalp, eyelids, lips or mouth. Limitations The cohort does not address long-term weight fluctuations. There are some limitations to self-reported data. Conclusion and Relevance Long-term disease in children and adolescents is associated with increasing years of disease burden and extension of disease to highly visible acral locations. BMI was not directly associated with disease extent in this cohort.

Neurological function and drug-refractory epilepsy in Sturge-Weber syndrome children: a retrospective analysis.

Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy. Conclusion:The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30-57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. •In SWS,stroke-like episodes and seizure clusters are risk factors of DRE,the occurrence of status epilepticus impacts the neurological function.

Abstract TP96: Association Between Infarct Volume, Neighborhood-Level Deprivation, and Outcomes in Pediatric Stroke

Introduction: Recent studies in adults have reported an association between neighborhood-level deprivation, infarct volume and outcome. However, this is yet to be investigated in pediatric arterial ischemic stroke (AIS). Our study aimed to assess the relationship between neighborhood-level deprivation, infarct volume, and neurological outcome in children diagnosed with AIS. Methods: We conducted a study of a consecutive cohort of children aged &amp;gt; 28 days-18 years and diagnosed with AIS between 2004 and 2019 at a comprehensive stroke center. Patient demographic, clinical characteristics and neighborhood material deprivation data including household income, parental educational attainment, the proportion of single-parent families, and housing quality were collected. Lesion volumes were determined by conducting semi-automatic segmentation of diffusion-weighted MRI brain scans at stroke presentation. Neurological outcome was assessed using the Pediatric Stroke Outcome Measure Severity Classification System wherein poor outcome was defined as moderate-to-severe deficit at 18 months post-stroke. Wilcoxon rank sum test was conducted. Results: Seventy-two patients were included in the study (62% male, median age of stroke onset 6.1 years [IQR 1.0-12.7]). 39% of patients were White, 72% lived in an urban region, and 64% in highly deprived neighborhoods. 70% of patients arrived within 6 hours from onset of stroke. Cardiac disease and other risk factors including infection and head trauma represented the most common risk factor. 55% presented with moderate stroke severity (as per the PedNIHSS). Median lesion volume was 14 cm 3 (IQR 2-51) and a mean infarct volume of 3% was reported. Race, rurality, and neighborhood-level material deprivation were not significantly associated with either percent infarct volume or neurological outcome; however, percent infarct volume was significantly associated with neurological outcome at 18 months post-stroke (W = 79, p = 0.025). Conclusion: Our study findings confirm the relationship between infarct volume and pediatric AIS outcomes. Future multi-center studies are warranted to further understand the interplay between material deprivation, infarct volume, and post-AIS neurological outcomes in children.

Neonatal hemophagocytic lymphohistiocytosis: A meta-analysis of 205 cases.

Neonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH. The objective of this study was to perform a meta-analysis of published cases of nHLH. A comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30days. Up to 70 variables were extracted from each case. A total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0-11, n=141). Median age at diagnosis was day of life 15 (IQR: 6-27, n=87). Causes of HLH included familial HLH (48%, n=99/205), infection (26%, n=53/205), unknown (17%, n=35/205), macrophage activation syndrome/rheumatologic (2.9%, n=4/205), primary immune deficiency (2.0%, n=5/205), inborn errors of metabolism (2.4%, n=5/205), and malignancy (2.0%, n=4/205). Fever was absent in 19% (n=28/147) of all neonates and 39% (n=15/38) of preterm neonates. Bicytopenia was absent in 26% (n=47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases (n=64/102). Liver injury (68%, n=91/134) and/or liver failure (24%, n=32/134) were common. Flow cytometry was performed in 22% (n=45/205) of cases. Many patients (63%, n=121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time. Evaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.

Predictors of relapsing disease course following index event in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disease that can present as a monophasic or relapsing disease course. Here, we investigate the predictors of developing relapsing disease with a focus on the index event. MethodsMOGAD patients followed at Massachusetts General Hospital and Brigham and Women's Hospital were included. Data on demographic, clinical, and laboratory features were collected. Time-to-event survival analysis was performed using a Cox proportional hazards model. Univariate and multivariate regression analyses were performed. ResultsWe included 124 patients with a diagnosis of MOGAD of which 62.1% (n = 77) were female. The median (IQR) onset age and follow-up time were 31 (16, 45), and 4.08 (2.2, 7.9) years respectively. In total, 40.3% (n = 50) of patients remained monophasic and, 59.7% (n = 74) developed a relapsing course. The median (IQR) time between the index event and the second attack was 3(2, 13.7) months. Starting maintenance therapy following the index event was associated with decreased risk of relapsing disease (HR:0.26; 95%CI: 0.12, 0.54; P < 0.001). Maintenance therapy with intravenous immunoglobulin (HR:0.1; 95% CI:0.01, 0.78, P = 0.02), rituximab (HR: 0.21; 95%CI: 0.08, 0.55; P = 0.001), and mycophenolate mofetil (HR: 0.27; 95%CI: 0.09, 0.77; P = 0.01) was associated with a decreased risk of relapsing disease course. A polyphasic first attack (HR:2.4; 95%CI:1.31, 4.4; P = 0.004) and high CSF protein (HR:2.06; 95%CI: 1.01, 4.16; P = 0.04) were associated with a relapsing course. ConclusionsIn MOGAD patients, starting maintenance therapy following the index event reduces the risk of relapsing disease regardless of age, sex, and onset phenotype, while polyphasic first attack, and elevated CSF protein predict relapsing disease course.

LEUCINE-RICH ALPHA 2 GLYCOPROTEIN: A USEFUL BIOMARKER TO DISCRIMINATE SMALL INTESTINAL MUCOSAL HEALING IN C-REACTIVE PROTEIN-NEGATIVE CROHN’S DISEASE

Abstract BACKGROUND The treatment goals for inflammatory bowel disease, including Crohn's disease (CD), have shifted from clinical remission to mucosal healing. However, frequent endoscopies burden patients. Leucine-rich alpha 2 glycoprotein (LRG), produced by hepatocytes, neutrophils, and the intestinal epithelium, is more gut-specific than C-reactive protein (CRP). We examined whether LRG, as a biomarker, can detect small intestinal mucosal healing in CD patients, especially in those who are CRP-negative. METHOD 1) This study examined CD patients who visited our department from May 2021 to April 2023, had LRG measured, and underwent image evaluation using capsule endoscopy or balloon-assisted endoscopy. We analyzed their clinical background, looked for a correlation between LRG and CRP, assessed the ROC-AUC of LRG and CRP for mucosal healing, and measured the LRG and CRP cutoff values to determine mucosal healing. 2) Next, in CRP-negative CD patients, we analyzed the ROC-AUC of LRG for mucosal healing and LRG cutoff value to determine mucosal healing. Endoscopic evaluation was done within 3 months before and after LRG measurement. Absent open ulcers indicated mucosal healing. The upper limit of normal CRP value was &amp;lt;3 mg/L. We used the Spearman correlation coefficient to determine the correlation. RESULTS 1) Here, 67 CD patients were analyzed; 43 (64%) were men. The median age (range) of onset was 25.6 (3-57) years. The median disease duration (range) was 7.6 (0-27) years. B1, B2, and B3 of Montreal Classification were established in 31 (46.2%), 21 (31.3%), and 15 (22.3%) patients, respectively. The median (range) of LRG was 21.7 (7.6-67.4) μg/mL. The median (range) of CRP was 10.8 (0.0-86.9) mg/L. LRG and CRP were strongly correlated (r=0.878, p&amp;lt;0.001). The ROC-AUC of LRG for mucosal healing was 0.839 (95% confidence interval [CI] 0.760-0.918). LRG cutoff value for discriminating mucosal healing was 15.5 μg/mL (sensitivity 77%, specificity 75%). The ROC-AUC of CRP for mucosal healing was 0.811 (95% CI 0.721-0.900). The CRP cutoff value to differentiate mucosal healing was 0.9 mg/L (sensitivity 55%, specificity 90%). 2) Forty CRP-negative CD patients were analyzed; 23 (57%) were men. The median age (range) of onset was 21.9 (3-57) years. The median disease duration (range) was 7.0 (0-27) years. B1, B2, and B3 of Montreal Classification were established in 17 (42.5%), 12 (30.0%), and 11 (27.5%) patients, respectively. The median (range) of LRG was 12.3 (7.6-23.5) μg/mL. The ROC-AUC of LRG for mucosal healing was 0.817 (95% CI 0.696-0.938). The LRG cutoff value to differentiate mucosal healing was 14.1 μg/mL (sensitivity 61%, specificity 76%). CONCLUSION LRG may be a better biomarker than CRP for assessing endoscopic remission of the small intestinal mucosa in CD. In CRP-negative CD patients, LRG level of ≥14.1 μg/mL could indicate small intestinal ulcers.