Juvenile Patient Research Articles

Surgical treatment of spinal cord compression due to Hirayama disease: illustrative case.

BACKGROUNDHirayama disease (HD), also known as juvenile spinal muscular atrophy, is a rare condition in which flexion of the cervical neck causes compression and ischemic changes to the anterior horns of the spinal cord. Here the authors presented the first reported case of HD in North America that was successfully treated via surgical intervention.OBSERVATIONSThe patient was a 15-year boy with insidious onset upper limb weakness and atrophy. His findings were a classic presentation of HD although his complex history and relative rarity of the disease caused him to remain undiagnosed for months. After conservative management via cervical collar failed, the patient was successfully treated via C5-C7 anterior cervical discectomy and fusion. The patient’s symptoms stabilized by the 3-month follow-up.LESSONSThe diagnosis of HD is easy to miss because of the lack of reporting and widespread knowledge of this condition in North America. Thus, when presented with a case of insidious onset limb weakness in a juvenile patient, HD should be placed on the differential list and verified with cervical flexion magnetic resonance imaging. Additionally, surgical intervention should be considered a safe and effective option for HD when conservative methods have failed.

Hyaluronidase treatment of synovial fluid is required for accurate detection of inflammatory cells and soluble mediators

BackgroundSynovial fluid (SF) is commonly used for diagnostic and research purposes, as it is believed to reflect the local inflammatory environment. Owing to its complex composition and especially the presence of hyaluronic acid, SF is usually viscous and non-homogeneous. In this study, we investigated the importance of homogenization of the total SF sample before subsequent analysis.MethodsSF was obtained from the knee of 29 arthritis patients (26 rheumatoid arthritis, 2 osteoarthritis, and 1 juvenile idiopathic arthritis patient) as part of standard clinical care. Synovial fluid was either treated with hyaluronidase as a whole or after aliquoting to determine whether the concentration of soluble mediators is evenly distributed in the viscous synovial fluid. Cytokine and IgG levels were measured by ELISA or Luminex and a total of seven fatty acid and oxylipin levels were determined using LC-MS/MS in all aliquots. For cell analysis, synovial fluid was first centrifuged and the pellet was separated from the fluid. The fluid was subsequently treated with hyaluronidase and centrifuged to isolate remaining cells. Cell numbers and phenotype were determined using flow cytometry.ResultsIn all patients, there was less variation in IgG, 17-HDHA, leukotriene B4 (LTB4), and prostaglandin E2 (PGE2) levels when homogenization was performed before aliquoting the SF sample. There was no difference in variation for cytokines, 15-HETE, and fatty acids arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Between 0.8 and 70% of immune cells (median 5%) remained in suspension and were missing in subsequent analyses when the cells were isolated from untreated SF. This percentage was higher for T and B cells: 7–85% (median 22%) and 7–88% (median 23 %), respectively.ConclusionsHomogenization of the entire SF sample leads to less variability in IgG and oxylipin levels and prevents erroneous conclusions based on incomplete isolation of synovial fluid cells.

Anaesthetic management of a parturient with juvenile parkinson's disease in emergency – A case report

The association of Parkinson's disease and pregnancy is very rare. We present a case of juvenile Parkinson's disease patient who underwent emergency caesarean section. The anaesthetic considerations and management are discussed.

Analysis of microstructural changes in an X-linked juvenile retinoschisis patient harboring RS1 G668A mutation by en-face optical coherence tomography imaging

Juvenile X-linked retinoschisis (JXLR) is an X-linked recessive retinal dystrophy caused by retinoschisin (RS1) gene mutations. The current study reports and describes the cumulative findings of en-face OCT for a 7-year-old JXLR patient harboring a hemizygous pathogenic RS1 mutation (c.G668A; p.Cys223Tyr), where residue 223 is vital for cellular adhesion. Fundoscopy showed cart-wheel appearance at macula. Further, en-face OCT revealed characteristic schitic lesions in the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer. Our report adds to the Indian RS1 mutation spectrum and casts insights into the schisis microstructure using en-face imaging.

3D printing technology: Rethinking the approach to talar surgery; a literature review

Talar fractures account for less than 1% of all fractures, yet despite this low occurrence they represent a major reconstruction challenge for surgeons. While total talar replacements are seldom used, there are very few procedures that can simultaneously repair a damaged talus and allow the patient to retain adequate range of motion, joint stability, function and satisfaction. These factors have become the impetus for exploring the role of 3D printing as a relatively novel surgical intervention for reconstructing the talus. Specific indications for a 3D printed total talar replacement include severe osteoarthritis, avascular necrosis, osteomyelitis, and trauma especially in the setting of a juvenile patient. As a relatively new approach, there is still much to be explored in regards to creating a 3D printed talar prosthesis, and the utility of the technology would greatly benefit from further research and development. Based upon our initial review of seven different studies, the use of 3D printed talar implants, when surgically indicated, demonstrates promising results in increasing patient satisfaction and improving postsurgical outcomes when compared to more conventional methods of repair. Thus, 3D printed talar implants represent a potentially viable tool to be considered by surgeons for a more precise and patient outcome-driven solution following talar injury.

Comprehensive understanding of genomic profile of bone cancer by the combination of DNA and RNA detection.

e23513 Background: The diagnosis of bone tumors is mainly based on clinical manifestations, imaging examination, tissue biopsy and laboratory examination. However, most of the bone tumors have no specific clinical manifestations, which makes the diagnosis and differential diagnosis difficult. The genomic profile of bone tumor is helpful to provide molecular basis for its molecular diagnosis. Methods: A total of 357 Chinese bone cancer patients were enrolled in this study. The NGS-based YuanSu S panel which includes both DNA and RNA detection was performed by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China, for genomic alteration identification. Results: The 357 Chinese bone cancer patients were enrolled, including 206 adult patients and 151 juvenile patients, with a median age of 20 years old (ranged from 1 to 88 years). Among them, there were 214 males and 143 females. The most commonly mutated genes with a mutation frequency more than 10% were TP53 (31.65%), NCOR1 (15.69%), VEGFA (13.73%), RB1 (12.61%), CCND3 (11.76%), CDKN2A, GID4, and CCNE1 (11.48%, for each), TERT (10.64%), and MAP2K4 (10.08%). Germline mutations were detected in 28 patients, including 13 patients with HRD related mutations, such as ATM, FANCA, BRCA2, RAD50, RAD51D and FANCD2. A total of 179 gene fusions were detected in 130 bone cancer patients. Notably, 19 gene fusions such as SH2D2A-NTRK1, EMILIN1-ALK, and SZRD1-SPEN, were detected in 16 patients with the assistance of RNA detection. Statistical analysis showed that the mutations of NCOR1 (P = 1.1X10-4), VEGFA (P = 3.4X10-6), CCND3 (P = 1.0X10-5), GID4 (P = 1.1X10-6), CCNE1 (P = 3.0X10-7), RB1 (P = 0.03), and MAP2K4 (P = 1.5X10-4)were significantly associated with juvenile patient group, as well as the mutation of H3F3A (P = 7.5X10-5) was significantly associated with adult patient group. Conclusions: Here we identified the mutational characteristics of Chinese bone tumor patients. In addition, the inclusion of RNA detection effectively increased the detection of gene fusions. Our results provided the evidence for the precise treatment of bone tumors in the future.

Cover Image

Cover caption: The cover image is based on the Case Report Features of a rare peripheral primitive neuroectodermal tumour arising from the thoracic spine in a juvenile canine patient by Adrien-Maxence Hespel et al., https://doi.org/10.1002/vms3.449.

Would it have happened without Christmas? Thoracic emphysema and allergic bronchopulmonary aspergillosis in a juvenile cystic fibrosis patient with the G551D mutation receiving ivacaftor.

Potent CFTR modulators improve CF manifestations far beyond expectations, including reduction of risk of typical complications. This is the first report of a patient who developed life-threatening ABPA and emphysema after overwhelming improvement. https://bit.ly/2P96PTy

Late ophthalmology findings in a X-linked juvenile retinoschisis patient

X-linked juvenile retinoschisis (XLRS) is a vitreoretinal degeneration caused by mutations in the RS1 gene, generally characterized by bilateral maculopathy and peripheral retinoschisis leading to progressive visual loss during the first 2 decades of life and complications like retinal detachment and vitreous hemorrhage. Herein, we present late ophthalmology findings in a XLRS patient. Late ophthalmology findings in a X-linked juvenile retinoschisis patient

Simultaneous single lobar lung transplantation and contralateral lung volume reduction.

Lung transplantation (LTx) and lung volume reduction surgery are established therapies for end-stage chronic obstructive pulmonary disease. Although native lung hyperinflation is a well-known complication of unilateral LTx for chronic obstructive pulmonary disease, the unilateral procedure continues to be performed because of severe shortages of cadaveric donors. As native lung hyperinflation can adversely affect the graft, all possible protection should be provided for patients with one-lobe transplantation. We report an emphysematous juvenile patient who successfully underwent simultaneous living-donor, single-lobe LTx and volume reduction in the contralateral lung.

O15 Recognition of subclinical macrophage activation syndrome in an adolescent systemic juvenile idiopathic arthritis patient receiving tocilizumab: a case report

O15 Recognition of subclinical macrophage activation syndrome in an adolescent systemic juvenile idiopathic arthritis patient receiving tocilizumab: a case report

Imaging features of the initial chest high resolution CT scan in juvenile patient with coronavirus disease 2019

The coronavirus disease 2019 (COVID-19) was confirmed by nucleic acid test in 15 juvenile patients aged 4-17 years in Hangzhou Xixi Hospital from January 24 to February 10, 2020. The clinical data and the initial chest high resolution CT (HRCT) findings were retrospectively analyzed.Among 15 cases, 8 patients with a mean age of (6.5±2.3) years (4-11 year) had normal HRCT manifestations (mild disease), while 7 patients with a mean age of (11.9±3.0) years (7-17 years) showed abnormal manifestations (moderate disease). In the 7 moderate cases the CT findings included local thickening of bronchial wall in 2 cases, single lesion in 1 case, bilateral pulmonary lesions in 4 cases. There were total 11 lesions, 6 of which were ground glass and slightly high-density nodules, 5 of which were speckled ground glass and 2 with a little consolidation. There were 10 subpleural lesions, including 7 in the lower lobe of the two lungs, and 1 non-subpleural lesion; the thickened local bronchioles were observed in 3 cases. None of them had hilum and mediastinal lymph node enlargement or pleural effusion. Key words: Coronavirus infection; Coronavirus disease 2019; Minors; Tomography, X-ray computed; Diagnosis

P03-T A review of patients with possible Occipital-lobe-seizures (OLS) seen at University-Hospital-of-Wales (UHW) in 2018

Introduction Patients having experienced OLS describe their seizures as featuring bright colours, and severe blurring of their vision, occasionally ictal vomiting, deviation of the eyes, and hypersalivation with or without impairment of consciousness. OLS are thought to account for between 5% and 10% of epilepsies with photo-sensitive epilepsies occurring in 1–5% of epilepsies. Method EEG’s including prolonged, sleep deprived and video monitoring EEG’s including (where appropriate) hyperventilation and photic-stimulation were reviewed in 929 patients referred at the UHW during 2017–2018. Results Four patients were found to have evidence of occipital lobe seizures. One was a juvenile patient with suspected idiopathic occipital lobe epilepsy. One patient was found to have posterior temporal/occipital lobe abnormality on Magnetic Resonance Imaging as a result of childhood injury. MELAs and concordant occipital stroke were thought to be the cause of the third patient. The final patient has been treated intensively because of injury due to collapse. Vomiting was not a feature of any seizure semiology. Hypersalivation and spitting were observed late into the seizure of one patient (spread temporally with secondary generalization). All described visual disturbance ranging from simple colored 2-dimensional shapes in the vision to more complex kaleidoscopic manifestations. Electrographic correlate was similar comprising repetitive sharp wave discharges. Conclusion Although thought to account for 5–10% of epilepsies, we at UHW (the largest teaching hospital in Wales) found OLS accounted for a very small percentage of confirmed epilepsies.

The periosteal flap augmentation technique in chronic lateral ankle instability

Anatomic repair of the lateral ligament complex of the ankle joint and augmentation with an autologous pedicled periosteal flap of the distal fibula following identification and concomitant treatment of intra-articular pathologies. Symptomatic chronic mechanical lateral ankle instability. As amodular step in the treatment of osteochondral lesions in conjunction with lateral ankle instability. Higher degree osteoarthritis of the ankle joint (>Kellgren/Lawrence2 and 4 or Outerbridge3 and 4) and/or hindfoot deformity; mechanical incompetence of both the fibulotalar anterior ligament and the fibulocalcaneal ligament preventing anatomical reinsertion; general risk factors. Diagnostic arthroscopy for identification and treatment of intraarticular pathologies; verification and grading of ligamentous instability (medial, lateral, combined). Open exposure of the distal fibula and the ruptured components of the lateral ankle ligament complex. Anatomic reinsertion of the original ligaments and assessment of their mechanical competence. Apart from the situation in the juvenile patient with athick periosteal layer adoubled and pedicled periosteal strip of the distal fibular periosteum will suffice for the augmentation in one ligamentous component, only. Fixation in the talus or calcaneus is achieved via suture anchors, screws with awasher or transosseous fixation via interference screw. Postoperative immobilization in alower leg split cast or asplint until wound healing (5-8days), mobilization in awalker or an ankle orthosis with consecutive full weight-bearing for further 4-5weeks. Proprioceptive and pronator muscle training, optionally insole or lateral wedge at the shoe sole for 6months postoperatively. Avoidance of contact sports for 4-6months. Several studies have reported reliable restoration of ligamentous ankle stability with overall success rates >90% and good to excellent total results in >90% of patients with limited minor complications. In view of the heterogeneous data from previous studies, some recent studies have demonstrated that the outcome after periosteal augmentation is comparable to that after techniques employing free tendon graft for anatomic restoration of ligamentous ankle stability. The technique has been applied successfully in cases of poor mechanical properties of the formerly ruptured ligaments and in patients with ahigh functional demand.

Description of a novel RyR2 mutation in a juvenile patient with symptomatic catecholaminergic polymorphic ventricular tachycardia in sleep and during exercise: a case report

BackgroundCatecholaminergic polymorphic ventricular tachycardia is an inherited disease presenting with arrhythmic events during physical exercise or emotional stress. If untreated, catecholaminergic polymorphic ventricular tachycardia is a highly lethal condition: About 80% of affected individuals experience recurrent syncope, and 30% experience cardiac arrest. Catecholaminergic polymorphic ventricular tachycardia is caused by mutations in genes encoding ryanodine receptor type 2 (RyR2) and cardiac calsequestrin (CASQ2). In cases of sympathoadrenergic activation, both mutations result in a spontaneous Ca2+ release in cardiac cells, facilitating ventricular arrhythmias.Case presentationWe present a case of a 17-year-old Caucasian boy who survived sudden cardiac death caused by ventricular fibrillation while performing running exercise in a fitness center. The diagnostic workup included blood tests, coronary angiography, electrophysiological testing, and cardiac magnetic resonance imaging, but all results were normal. Because the patient’s medical history included recurrent syncope during physical and emotional stress, we strongly suspected catecholaminergic polymorphic ventricular tachycardia as the underlying disease. Genetic screening was performed and confirmed the diagnosis, revealing a new heterozygous point mutation in the gene for RyR2, c.12520T>A (p.F4174 l, exon 90, RyR2 gene). The patient was discharged from our hospital after undergoing implantation of an implantable cardioverter defibrillator for secondary prevention. Shortly after implantation, the implantable cardioverter defibrillator terminated a sustaining ventricular tachycardia episode by antitachycardic pacing. This episode occurred early in the morning while the patient was asleep.ConclusionsWe present a case of catecholaminergic polymorphic ventricular tachycardia associated with a novel single point mutation in the RyR2 gene, which, to the best of our knowledge, has not been described in the literature so far. Our patient experienced arrhythmic events under both resting conditions and physical activity, an uncommon finding in patients with catecholaminergic polymorphic ventricular tachycardia. This novel mutation may cause arrhythmias independent of sympathoadrenergic stimulation, but further evidence is needed to prove causality.

Whole‐exome sequencing and microRNA profiling reveal PI3K/AKT pathway’s involvement in juvenile myelomonocytic leukemia

BackgroundClinical studies and genetic analyses have revealed that juvenile myelomonocytic leukemia (JMML) is caused by somatic and/or germline mutations of genes involved in the RAS/MAPK signalling pathway. Given the vastly different clinical prognosis among individual patients that have had this disease, mutations in genes of other pathways may be involved.MethodsIn this study, we conducted whole‐exome and cancer‐panel sequencing analyses on a bone marrow sample from a 2‐year old juvenile myelomonocytic leukemia patient. We also measured the microRNA profile of the same patient’s bone marrow sample and the results were compared with the normal mature monocytic cells from the pooled peripheral blood.ResultsWe identified additional novel mutations in the PI3K/AKT pathway and verified with a cancer panel targeted sequencing. We have confirmed the previously tested PTPN11 gene mutation (exon 3 181G>T) in the same sample and identified new nonsynonymous mutations in NTRK1, HMGA2, MLH3, MYH9 and AKT1 genes. Many of the microRNAs found to be differentially expressed are known to act as oncogenic MicroRNAs (onco‐MicroRNAs or oncomiRs), whose target genes are enriched in the PI3K/AKT signalling pathway.ConclusionsOur study suggests an alternative mechanism for JMML pathogenesis in addition to RAS/MAPK pathway. This discovery may provide new genetic markers for diagnosis and new therapeutic targets for JMML patients in the future.

Management of youth psoriatic arthritis with etanercept: a case report

Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease of the skin and joints still poorly understood in pediatric patients. It has been reported a case report of PsA in a male infant patient in Paraiba state, Northeast Brazil. The goal of this study was describing a rare case of juvenile PsA and its management upon using classical and biologic treatment based on the drug etanercept. The patient was diagnosed with scales on the scalp, knees and other parts of the body and joint inflammation besides social behavior deficit since he was aged 5. Classical therapy to PsA including acitretrin and topical glucocorticoids did not ameliorate the illness symptoms. Then, the patient received the anti-TNF-α drug etanercept used to treat moderate to severe psoriasis and juvenile rheumatoid arthritis. Before the week 16 of the treatment was observed a strong remission of the symptoms which is related to the inhibition of the inflammatory response into skin and joints. Besides no side effects was observed during etanercept administration. This study indicates that anti-TNF-α therapy might be used to treat immune-mediated inflammation likely to PsA in pediatric patients.   Keywords: Juvenile patient, psoriatic arthritis, biologic therapy

Prawo pacjenta małoletniego do informacji medycznej

THE RIGHT OF A JUVENILE PATIENT TO MEDICAL INFORMATIONFirst of all, the right of a juvenile patient to medical information belongs to constitutional rights because it is derived from Article 30 of the Polish Constitution which refers to the inherent and inalienable dignity of a person and a citizen. Pursuant to Article 9 of the Act of 06.11.2008 on Patient’s Rights and the Ombudsman for Patient’s Rights, a patient is entitled to information about his or her health. Furthermore, a patient, including a juvenile one who is at least 16 years old, or his/her statutory representative have a right to receive from a doctor comprehensible information about the patient’s health, diagnosis, suggested and possible diagnostic and treatment methods, predictable consequences of their use or abandonment, results of treatment and prognosis. The binding legal regulations are aimed at ensuring proper communication between a doctor and a patient, which is obviously indispensable for correct progress of medical treatment.

Application of Low-dose Stereoradiography in In Vivo Vertebral Morphologic Measurements: Comparison With Computed Tomography.

Though computed tomography (CT) and 3 dimensional (3D) reconstruction of the spine and ribcage are powerful techniques for detailed monitoring of spinal growth and surgical planning of patients, drawbacks can arise. We explored the application of low-dose stereoradiography of the spine to calculate distinct morphologic parameters of the vertebral body in a juvenile patient population with early-onset scoliosis or congenital scoliosis. This study compares the 3D vertebral morphology measurements using low-dose stereoradiography with the currently accepted imaging modality for such measurements, CT scans. A total of 86 vertebrae of 6 patients with early-onset scoliosis and 3 patients with congenital scoliosis, age ranged between 7.8 and 12.5 years, who had both thoracic spine CT scan and low-dose stereoradiography of the spine were included. 3D reconstructions of CT and low-dose stereoradiography were generated. Using previously validated image processing techniques, vertebral anterior (A), posterior (P), left (L), and right (R) heights, superior and inferior endplates depth and width (S-D, I-D, S-W, I-W) were measured on the CTs' 3D reconstructions and were compared with the same parameters measured on low-dose stereoradiography reconstructions using a postprocessing custom code. The agreement between the 2 techniques in measurement of the vertebral morphology was assessed using the Bland-Altman plots. No significant difference was observed in the A, P, L, R, S-W, and I-W between the stereoradiography and CT measurements (P>0.05). S-D and I-D were significantly greater in low-dose stereoradiography measurements P<0.05. Bland-Altman plots showed an agreement between the stereoradiography and CT techniques in vertebral height measurements (A, P, L, R); however, larger measurement bias and greater limits of agreement in S-D, I-D, S-W, and I-W measurements were shown. In vivo measurements of the vertebral heights using low-dose stereoradiography 3D reconstructions were comparable with CT measurements except for the superior and inferior vertebral depths. The low-dose stereoradiography imaging modality and the postprocessing platform can be used for assessment of the vertebral heights and monitoring asymmetric growth in patients undergoing growth-sparing treatment except for the vertebral levels with congenital deformities. Level IV.

Spontaneous regression of Epstein-Barr virus-associated lymphoproliferative disorder in a juvenile idiopathic arthritis patient after the discontinuation of methotrexate and etanercept.

A case of a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) since the age of 4 years is reported here. This patient also suffered from multiple congenital anomalies. On long-term treatment with oral methotrexate (MTX) and etanercept, multiple subcutaneous nodules were detected, which were accompanied by increased lactate dehydrogenase and uric acid levels. A biopsy of the largest nodule revealed Epstein-Barr (EB) virus-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified as clinical stage IIIA due to a mediastinal lesion. Immunosuppressive treatment was discontinued immediately, which led to regression of the remaining nodules and normalization of the lactate dehydrogenase levels. The patient was considered to have an iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the World health organization (WHO). To our knowledge, this is the first case report of a JIA patient with EBV-positive DLBCL following the administration of etanercept and methotrexate and spontaneous regression of lymphoproliferation after the discontinuation of antirheumatic treatment.