d-2-hydroxyglutaric aciduria is a neurometabolic disorder with both a mild and a severe phenotype and with unknown etiology. Recently, a novel enzyme,
d-2-hydroxyglutarate dehydrogenase, which ...converts
d-2-hydroxyglutarate into 2-ketoglutarate, and its gene were identified. In the genes of two unrelated patients affected with
d-2-hydroxyglutaric aciduria, we identified disease-causing mutations. One patient was homozygous for a missense mutation (c.1331T→C; p.Val444Ala). The other patient was compound heterozygous for a missense mutation (c.440T→G; p.Ile147Ser) and a splice-site mutation (IVS1-23A→G) that resulted in a null allele. Overexpression studies in HEK-293 cells of proteins containing the missense mutations showed a marked reduction of
d-2-hydroxyglutarate dehydrogenase activity, proving that mutations in the
d-2-hydroxyglutarate dehydrogenase gene cause
d-2-hydroxyglutaric aciduria.
Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 ...inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA.
Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers.
Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (
= 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (
= 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (
= 0.038) and when distinguishing according to adverse events (AEs) occurrence (
= 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 CI: 1.341-8.406,
= 0.01) and those experiencing AEs (HR = 2.970 CI: 1.186-7.435,
= 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (
= 0.0002).
Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.
Abstract Background: Optic perineuritis is a rare form of orbital inflammatory pseudotumor in which the specific target tissue is the optic nerve sheath. Patients are mainly represented by adult ...women. Differential diagnosis with demyelinating optic neuritis is essential in terms of prognosis and treatment. Case presentation: An 8-year-old Caucasian girl presented with bilateral loss of vision, disc edema, eye movement impairment, and diplopia. Brain MRI findings were suggestive of optic perineuritis. The patient received steroid pulse therapy followed by prolonged course of oral steroid therapy. The visual acuity recovered dramatically within 2 days. Two months later, a new MRI investigation was normal. No clinical relapse was observed at the follow-up. Discussion: We first report on a child affected by optic perineuritis. Our observation suggests that optic perineurits should be considered in the differential diagnosis of children presenting with visual loss and disc edema. An early and correct diagnosis may lead to an appropriate therapeutic approach with very good outcome.
Objective
Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic ...Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome.
Methods
This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries.
Results
A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems.
Conclusions
The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on
https://clinicaltrials.gov
NCT 05200715.
Abstract Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are degenerative disorders of muscle. Although the mechanisms underlying muscle degeneration are still uncertain, ...oxidative-damage has been proposed to play a key role. Isoprostanes are markers of free radical-catalyzed lipid peroxidation; the aim of our study was to evaluate plasma isoprostane levels in group of patients affected by Duchenne and Becker muscular dystrophies. PF2 -isoprostane levels were measured by colorimetric enzyme immunoassay in the plasma of 17 patients with DMD and 24 with BMD. When compared to a group of healthy controls, affected patients showed significantly higher plasma levels of isoprostanes ( p = 0.001). When patients were stratified according to the clinical diagnosis, isoprostane levels were not statistically different between DMD and BMD patients. In conclusion whether the condition of oxidative stress found in plasma depends on the degenerative process occurring in muscles or on different mechanisms, such as the release of myoglobin in the blood, should be ascertained. However, our study confirms that oxidative stress findings in DMD/BMD patients are effectively present at the plasma levels. The condition of oxidative stress might act as an adjunctive cause of extra-muscular cell damage to which these patients are exposed for their entire life.
Background:
This study aims at describing the therapeutic outcome of patients carrying the R92Q variant in the TNFRSF1A gene treated with anakinra (ANA) or canakinumab (CAN) and identifying any ...factors predictive of complete response to IL-1 inhibition.
Methods:
Clinical data of patients treated with ANA or CAN for recurrent inflammatory attacks due to the presence of the R92Q variant were retrospectively collected and analysed.
Results:
Data about 20 treatment courses with IL-1 inhibitors (16 with ANA and 4 with CAN) from 19 patients were collected. Mean age at disease onset was 20.2 ± 14.8 years. In 5 cases (26%) the R92Q variant was found in a family member affected by recurrent fever. The therapeutic response was complete in 13(68%) and partial in 2 patients (11%); treatment failure was observed in 4 cases (21%). Median AIDAI decreased from 10 (interquartile range IQR = 28) to 0 (IQR = 1) at the 12-month follow-up visit (p < 0.001). Mean ESR and median CRP dropped respectively from 40.8 ± 24.8 to 9.1 ± 4.5 mm/h (p < 0.001) and from 3.0 (IQR = 1.9) to 0.3 (IQR = 0.3) mg/dl (p < 0.001) after 12 months of treatment. A steroid-sparing effect was observed from the third month of treatment (p < 0.01). Thirteen patients (65%) were still on treatment at the last follow-up visit (median duration of treatment 17 (IQR = 38) months). The presence of R92Q mutation in a symptomatic relative (p = 0.022), the relapsing remitting disease course (p < 0.001) and the presence of migratory erythematous skin rashes during fever attacks (p = 0.005) were associated with complete efficacy of IL-1 inhibitors.
Conclusions:
R92Q patients showed a favourable response to ANA and CAN, particularly when the mutation segregated in a family member and when a relapsing-remitting disease course or TNF-α receptor-associated periodic syndrome (TRAPS) typical skin rash were observed. In the subgroup of patients not taking advantage of IL-1 blockage different molecular mechanisms underlying the autoinflammatory picture are likely to exist.
Recurrent Miller Fisher Syndrome in Children Grosso, Salvatore, MD PhD; Verrotti, Alberto, MD; Tei, Monica, MD ...
Pediatric neurology,
03/2014, Volume:
50, Issue:
3
Journal Article
Peer reviewed
Abstract Background Miller Fisher syndrome is usually a monophasic disorder. Recurrent Miller Fisher syndrome is extremely rare, and all patients with recurrences have been adults. Although the ...optimal treatment for Miller Fisher syndrome has yet to be established, the typical therapy includes intravenous immunoglobulin or plasma exchange. The efficacy of steroids is still debated. Patients We describe two children with recurrent Miller Fisher syndrome. Episodes occurred at the age of 11.5 and 13 years in patient 1 and at the age of 8 and 13 years in patient 2. Results Clinical patterns of the first and recurrent episodes of Miller Fisher syndrome were overlapping. In both patients, steroids were effective in controlling clinical deterioration of Miller Fisher syndrome recurrences. Conclusions Recurrent Miller Fisher syndrome is a rare disorder that may occur in children. Our observations and a review of the literature suggest that there may be a small group of patients in whom steroids may be a therapeutic option when intravenous immunoglobulin fails to control clinical symptoms.
The worldwide incidence and prevalence of cystic echinococcosis have fallen dramatically over the past several decades. Nonetheless, infection with Echinococ- cus granulosus （E. granulosus） remains a ...major public health issue in several countries and regions, even in places where it was previously at low levels, as a result of a reduction of control programmes due to economic problems and lack of resources. Geographic distribution differs by country and region depending on the pres- ence in that country of large numbers of nomadic or semi-nomadic sheep and goat flocks that represent the intermediate host of the parasite, and their close con- tact with the final host, the dog, which mostly provides the transmission of infection to humans. The greatest prevalence of cystic echinococcosis in human and ani- mal hosts is found in countries of the temperate zones, including several parts of Eurasia （the Mediterranean regions, southern and central parts of Russia, central Asia, China）, Australia, some parts of America （espe- cially South America） and north and east Africa. Echi- nococcosis is currently considered an endemic zoonotic disease in the Mediterranean region. The most frequent strain associated with human cystic echinococcosis ap- pears to be the common sheep strain （G1）. This strain appears to be widely distributed in all continents. The purpose of this review is to examine the distribution of E, granulosus and the epidemiology of a re-emerging disease such as cystic echinococcosis.
Background
Epilepsy associated with Prader-Willi syndrome (PWS) represents an early and important complication, often not clearly reported and described in the literature. Consequently, there are ...controversial data about the clinical characteristics of epilepsy and electroencephalographic (EEG) abnormalities found in these patients.
Data sources
Based on recent original publications, we have reviewed the different types of seizures and EEG findings in PWS patients, the response to antiepileptic treatment, and the prognosis of epilepsy.
Results
The frequency of epilepsy in PWS patients ranges from 4% to 26%. The types of seizure include generalized tonic-clonic seizures, complex partial seizures, atypical absence, staring spells, and myoclonic, tonic and hemiclonic seizures, but the most frequent type is focal epilepsy. Status epilepticus has never been reported. EEG abnormalities are not typical but variable in different patients. However, generalized and focal discharges are the most frequently reported findings. There is no evidence of relationship between the course of epilepsy and frequency, morphology and spread of EEG discharges. However, epilepsy in PWS patients is usually responsive to antiepileptic monotherapy with rapid seizure control and a good outcome.
Conclusions
The frequency of epilepsy is higher in PWS patients than in general populations and this complication can be a challenge for the clinicians of these patients. Prospective studies are needed to confirm the good long-term prognosis.
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