Median Age Of Onset Research Articles

An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different ethnic groups in sub-Saharan Africa.

Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant Huntingtin (mHtt) gene to the continent; however, recent work has shown the existence of a unique Htt haplotype in South-Africa specific to indigenous Africans. We aimed to investigate the CAG trinucleotide repeats expansion in the Htt gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa. We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the mHtt. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the mHtt gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region. HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the mHTT; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6/21) were carriers for the mHTT; median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD-bar three who were juvenile onset of <21 years-were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10/19) than paternal transmission 36.8% (7/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54-16kya ago: Nilo-Sahara and Niger-Congo. This is the first study examining HD in multiple sites in sub-Saharan Africa. We demonstrated that HD is found in multiple ethnic groups residing in five sub-Saharan African countries including the first genetically confirmed HD cases from Guinea and Kenya. The prevalence of HD in the African continent, its associated socio-economic impact, and genetic origins need further exploration and reappraisal.

Evaluation of Psychiatric High and Intensive Care (EPHIC-study): monitoring innovative care from a value-based approach

IntroductionSystematic monitoring and evaluation of innovative healthcare programs are essential to develop sustainable solutions to health needs in the population (Porter &amp; Teisberg, 2006). Development of Psychiatric High and Intensive Care Units (HIC’s) in Belgium, following the Dutch Model (van Mierlo et al., 2013), is an innovative model for patients with acute and severe psychiatric illness, resulting in potential danger. HIC aims to provide intensive, need-adapted care with interventions that reduce (perceived) coercion, focusing on participative processes and continuity of care.Objectives(1) What are the clinical characteristics of admitted patients? (2) How does clinical symptomatology evolve during admission? (3) How do patients, relatives and caregivers experience the process of care and recovery? (4) What is the role of HIC’s in the reformed mental health care?MethodsThis is an explorative, hypothesis-generating study, using a mixed-method approach, consisting of qualitative and quantitative methods against a value-based framework. Data collection lasted 18 months in the first 9 HIC’s in Belgium. Results are based on validated questionnaires completed by adult patients and their HIC caregivers at admission and discharge (N=472).ResultsWe provide the first, preliminary results. Suicidality, psychotic and substance-related symptoms are the most important primary symptoms. Almost 70% have 2 or more symptoms, with psychiatric comorbidity of 50%. Substance-related- and psychotic disorders are the two most common diagnoses, followed by personality disorder cluster B and depressive disorder. 83% have been in residential care in the past, of whom 87% twice or more. The median age is 36 years, but the median age of onset of mental disorders is 21 years, which equals to 15 years in mental disorder progress and comorbidity development. Over 50% meet the criteria for Severe Mental Illness and 56% are involuntary admitted. There is a high degree of unmet needs: no outpatient care is provided for one out of five prior to admission and there is a low follow-up by mobile teams prior to and after admission (around 12% each). We found significant improvements after an average stay of 22 days for aggression, suicidality and crisis (respectively decrease of 68%, 25% and 9%); readiness to change and motivation for treatment (respectively increase of 5% and 14%) The Client Satisfaction Questionnaire scores range from 1 to 4, with an average score 3.15 out of 4.ConclusionsBased on these preliminary results we can conclude that aggression, suicidality, crisis, readiness to change and motivation for treatment all improve significantly after a short stay of 3 weeks. Despite a vulnerable, severely distressed population, patients are generally satisfied with received care. There is a high degree of unmet needs: insufficient provided outpatient care and low follow up by mobile teams.Disclosure of InterestNone Declared

Hydroa vacciniforme lymphoproliferative disorder: a retrospective study of 42 paediatric cases.

Hydroa vacciniforme lymphoproliferative disorder (HVLPD) is a rare disease related to Epstein-Barr virus (EBV), mainly in children, and is an EBV-associated cutaneous T and natural killer (NK) cell lymphoproliferative disorder. The disorder in some patients may progress to EBV-associated systemic T or NK-cell lymphoma. To summarize the characteristics of HVLPD in Chinese paediatric patients and to examine the risk factors indicating poor prognosis. We performed a retrospective analysis of patients with HVLPD from the Department of Dermatology, Beijing Children's Hospital. Based on diagnosis, medical history, examination results, and immunophenotype, we analysed HVLPD in 42 paediatric cases in order to examine the clinical features, prognoses, and risk factors. Forty-two paediatric patients were enrolled, with a median onset age of five years. All patients presented with papulovesicular lesions, and 32 systemic HVLPD (sHVLPD) patients had systemic symptoms, including fever, lymphadenopathy, hepatomegaly, splenomegaly, and liver dysfunction. Of the sHVLPD cases, 13 also had severe mosquito bite allergy (SMBA). Twenty-five cases were T-type, and nine were CD56+-dominant type. Follow-up data showed that 12 patients had complete remission, and three patients died. SMBA is a risk factor for disease progression in patients with HVLPD, and the pathological CD56+-dominant phenotype is associated with poor prognosis.

Spontaneous intestinal perforation among very preterm infants in China: a multicenter cohort study.

Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Factors Associated with the Myopia Degree in Students

Purpose: to identify the most significant factors associated with myopic refraction in medical university students, which can be used for early prediction and prevention of myopia.Materials and methods. The survey data of students of 1–6 courses of Kazan State Medical University and the data on refraction of patients’ eyes obtained from the “Medical record of a patient receiving medical care on an outpatient basis” (registration form No. 025/y) were used. The refraction of the eye in each of the participants was calculated as the average value of the spherical equivalent of the right and left eyes.Results. According to the ophthalmologist’s examination, myopia was detected in 219 (69 %) of the surveyed students. 134 (42 %) students had mild myopia, 66 (21 %) had moderate myopia, 19 (6 %) were highly myopic. Among myopes, 73 % of students wear glasses (160/219), contact lenses — 41 % of respondents (90/219). The median age of onset of spectacle wear was 13 years (Q1–Q3 = 10–26). The median refraction of the right eye (D) was -2.50 D (Q1–Q3 = -1.5…-4.0), the left eye -2.75 D (Q1–Q3 = -1.6…-4.0). The early age of onset of spectacle wear is the factor most significantly associated with myopic refraction (+0.23 D/year, p = 1.30×10-11), and an important prognostic sign of the development of high myopia. Factors associated with stronger myopic refraction are high height and low weight, as well as less physical activity.Conclusion. It is necessary to take into account the anthropometric and behavioral features of the patient when developing an individual plan for the prevention and treatment of myopia, in order to avoid the development of complications leading to vision loss.

Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study

Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR). We excluded multiple births, deaths within the first month of life, individuals who could not be linked to MGR, or individuals with contradictory information on sex. Information on diagnoses of type 1 diabetes was retrieved by linkages to the National Diabetes Register and National Patient Register (1982-2020). Individuals with inconsistent records of diabetes type were excluded. We estimated the cumulative incidence and hazard ratios (HRs) of type 1 diabetes in adults (aged 19-30 years) and children (aged 0-18 years) by family history of type 1 diabetes and the heritability of adult-onset and childhood-onset type 1 diabetes based on tetrachoric correlations, using sibling pairs. 2 943 832 individuals were born in Sweden during the study period, 2 832 755 individuals were included in the analysis of childhood-onset type 1 diabetes and 1 805 826 individuals were included in the analysis of adult-onset type 1 diabetes. 3240 cases of adult-onset type 1 diabetes (median onset age 23·4 years [IQR 21·1-26·2]; 1936 [59·7%] male and 1304 [40·2%] female) and 17 914 cases of childhood-onset type 1 diabetes (median onset age 9·8 years [6·2-13·3]; 9819 [54·8%] male and 8095 [45·2%] female) developed during follow-up. Having a first-degree relative with type 1 diabetes conferred an HR of 7·21 (95% CI 6·28-8·28) for adult-onset type 1 diabetes and 9·92 (9·38-10·50) for childhood-onset type 1 diabetes. The HR of developing type 1 diabetes before the age 30 years was smaller if a first-degree relative developed type 1 diabetes during adulthood (6·68 [6·04-7·39]) rather than during childhood (10·54 [9·92-11·19]). Similar findings were observed for type 1 diabetes in other relatives. Heritability was lower for adult-onset type 1 diabetes (0·56 [0·45-0·66]) than childhood-onset type 1 diabetes (0·81 [0·77-0·85]). Adult-onset type 1 diabetes seems to have weaker familial aggregation and lower heritability than childhood-onset type 1 diabetes. This finding suggests a larger contribution of environmental factors to the development of type 1 diabetes in adults than in children and highlights the need to identify and intervene on such factors. Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Swedish Diabetes Foundation, and the China Scholarship Council.

Juvenile Myasthenia Gravis in North Texas: Clinical Features, Treatment Response, and Outcomes

BackgroundJuvenile myasthenia gravis (JMG) is a rare autoimmune disease that causes fatigable muscle weakness in children aged <18 years. There is currently no curative treatment or internationally accepted standard of care for JMG. The objective is to investigate relationships between clinical presentation, antibody status, severity of disease onset, electrodiagnostic evaluation, and response to therapy in JMG. MethodsThis study was a retrospective chart review. Congenital myasthenic syndromes were excluded. Data on demographics, treatments, and outcomes were collected. Disease severity was evaluated using Myasthenia Gravis Foundation of America (MGFA) clinical classifications. ResultsWe identified 84 patients with JMG at Children's Medical Center Dallas between January 2014 and February 2022. It was found that 52% of patients presented with ocular JMG (median onset age 4.5 years) and 48% with generalized JMG (median onset age 11.5 years); 81% tested positive for acetylcholine receptor antibodies. Patients were 17% non-Hispanic white, 29% Hispanic, 39% black, and 12% Asian. There was a significant difference in average MGFA scores between ethnicities (P = 0.047) and age groups (P = 0.004), with postpubertal patients having higher average MGFA scores than prepubertal patients. Seventy-one percent of patients who underwent thymectomy experienced a decrease in MGFA scores postprocedure. ConclusionsOur study showed that there were significant differences in disease severity between ethnicities and age groups and that most patients who underwent thymectomy showed clinical improvement. These outcomes highlight the need for additional therapies in the treatment of JMG and the importance of extending clinical trials to the pediatric population.

Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

Cardiopulmonary exercise testing on adaptive equipment in children and adults with Friedreich ataxia.

Traditional exercise is often difficult for individuals with Friedreich ataxia (FRDA), and evidence is limited regarding how to measure exercise performance in this population. We evaluated the feasibility, reliability, and natural history of adaptive cardiopulmonary exercise test (CPET) performance in children and adults with FRDA. Participants underwent CPET on either an arm cycle ergometer (ACE) or recumbent leg cycle ergometer (RLCE) at up to four visits (baseline, 2 weeks, 4 weeks, and 1 year). Maximum work, oxygen consumption (peak VO2), oxygen (O2) pulse, and anaerobic threshold (AT) were measured in those who reached maximal volition. Test-retest reliability was assessed with intraclass coefficients, and longitudinal change was assessed using regression analysis. In our cohort (N = 23), median age was 18 years (interquartile range [IQR], 14-23), median age of FRDA onset was 8 years (IQR 6-13), median Friedreich Ataxia Rating Scale score was 58 (IQR 54-62), and GAA repeat length on the shorter FXN allele (GAA1) was 766 (IQR, 650-900). Twenty-one (91%) completed a maximal CPET (n = 8, ACE and n = 13, RLCE). Age, sex, and GAA1 repeat length were each associated with peak VO2. Preliminary estimates demonstrated reasonable agreement between visits 2 and 3 for peak work by both ACE and RLCE, and for peak VO2, O2 pulse, and AT by RLCE. We did not detect significant performance changes over 1 year. Adaptive CPET is feasible in FRDA, a relevant clinical trial outcome for interventions that impact exercise performance and will increase access to participation as well as generalizability of findings.

Seizures as Initial Presentation and Enduring Predisposition to Seizures in Autoimmune Encephalitis

Purpose. This retrospective study is aimed at investigating the clinical characteristics of autoimmune encephalitis (AE) and long-term prognosis of patients who initially present with seizures as well as risk factors for enduring predisposition to seizures in AE. Methods. From January 1, 2013, to October 31, 2021, a total of 343 AE patients from a single center diagnosed with autoimmune encephalitis (AE) were enrolled in this study, including 198 antibody-positive AE and 145 antibody-negative but probable AE. According to initial symptoms, AE patients were divided into two groups: onset with seizure group and onset with nonseizure group. The clinical characteristics were retrospectively reviewed. Patients were clinically evaluated at onset and at 6, 12, and 24 months of follow-up. Modified Rankin Scale (MRS) score, Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score, and seizure-related information were assessed. Results. In AE, patients with seizures as the first presentation were younger, with a median-onset age of 28 years old. Compared with other types of antibody-positive AE, anti-GABABR AE more frequently began with seizures, while anti-CASPR2, anti-AMPAR, and anti-DPPX encephalitis usually began with symptoms other than seizures. The most common type of initial seizures in AE was focal to bilateral seizure (67.6%), with a significant prevalence in antibody-positive AE (P=0.001). In addition, compared with nonseizure group, patients with seizures as an initial presentation had higher MRS and CASE scores at 24 months of follow-up. Older age at onset and focal nonmotor seizure type were independent risk factors for an enduring predisposition to seizures in AE patients. Conclusion. The younger and anti-GABABR-positive AE patients are more prone to onset with seizures. AE patients who initially presented with seizures had worse long-term neurological recovery. Onset age and seizure type should be highly appreciated when formulating the strategy for therapy at post-AE status.

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.