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Objective: To assess the diagnostic and prognostic potential of serum neurofilament light chain (sNfL) in children with first acquired demyelinating syndrome (ADS). Methods: We selected 129 children with first ADS including 19 children with myelin oligodendrocyte glycoprotein (MOG)-antibody associated disease (MOGAD), 36 MOG/AQP4-seronegative ADS, and 74 with multiple sclerosis (MS) from the BIOMARKER study cohort. All children had a complete set of clinical, radiological, laboratory data and serum for NfL measurement using a highly sensitive digital ELISA (SIMOA). A control group of 35 children with non-inflammatory neurological diseases was included. sNfL levels were compared across patient groups according to clinical, laboratory, neuroradiological features and outcome after 2 years. Results: sNfL levels were significantly increased in MOGAD, seronegative ADS and MS compared to controls (p-value < 0.001), in particular in children with an acute disseminated encephalomyelitis (ADEM)-like magnetic resonance imaging (MRI) pattern (p < 0.001) or longitudinally extensive myelitis (p < 0.01). In pediatric MS, elevated sNfL levels were significantly associated with higher numbers of cerebral (p < 0.001) and presence of spinal (p < 0.05) MRI lesions at baseline and predicted a higher number of relapses (p < 0.05). Conclusion: sNfL levels are significantly elevated in all three studied pediatric ADS subtypes indicating neuroaxonal injury. In pediatric MS high levels of sNfL are associated with risk factors for disease progression., publishedVersion

Contains fulltext : 287938.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Neuroimmunological diseases such as autoimmune encephalitis (AE) or acquired demyelinating syndromes (ADS), can present with neurological symptoms and imaging features that are indistinguishable from mitochondrial diseases (MD) in particular at initial presentation. METHODS: Retrospective analysis of the clinical, laboratory and neuroimaging features of five patients who presented with signs of a neuroimmunological disease but all had pathological pathogenic variants in genes related to mitochondrial energy metabolism. RESULTS: Four patients presented with an acute neurological episode reminiscent of a possible AE and one patient with a suspected ADS at initial presentation. MRI findings were compatible with neuroimmunological diseases in all patients. In two children cerebrospinal fluid (CSF) studies revealed a mildly elevated cell count, two had elevated CSF lactate, none had oligoclonal bands (OCBs). All patients improved rapidly with intravenous steroids or immunoglobulins. Four patients had one or more relapses. Three patients showed worsening of their neurological symptoms with subsequent episodes and one patient died. Relapses in conjunction with new and progressive neurological symptoms, led to additional work-up which finally resulted in different genetic diagnosis of MD in all patients (MT-TL1, MT-ND5, APOA1-BP, HPDL, POLG). DISCUSSION: We would like to draw attention to a subset of patients with MD initially presenting with signs and symptoms mimicking neuroimmunological. Absence of CSF pleocytosis, elevated CSF lactate and progressive, relapsing course should trigger further (genetic) investigations in search of a MD even in patients with good response initially to immunomodulating therapies.

Background and ObjectivesAcute disseminated encephalomyelitis (ADEM) is the most common phenotype in pediatric myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease. A previous study demonstrated impaired brain growth in ADEM. However, the effect of MOG antibodies on brain growth remains unknown. Here, we performed brain volume analyses in MOG-positive and MOG-negative ADEM at onset and over time.MethodsIn this observational cohort study, we included a total of 62 MRI scans from 24 patients with ADEM (54.2% female; median age 5 years), of which 16 (66.7%) were MOG positive. Patients were compared with healthy controls from the NIH pediatric MRI data repository and a matched local cohort. Mixed-effect models were applied to assess group differences and other relevant factors, including relapses.ResultsAt baseline and before any steroid treatment, patients with ADEM, irrespective of MOG antibody status, showed reduced brain volume compared with matched controls (median [interquartile range] 1,741.9 cm3 [1,645.1–1,805.2] vs 1,810.4 cm3[1,786.5–1,836.2]). Longitudinal analysis revealed reduced brain growth for both MOG-positive and MOG-negative patients with ADEM. However, MOG-negative patients showed a stronger reduction (−138.3 cm3[95% CI −193.6 to −82.9]) than MOG-positive patients (−50.0 cm3[−126.5 to −5.2]), independent of age, sex, and treatment. Relapsing patients (all MOG positive) showed additional brain volume loss (−15.8 cm3[−68.9 to 37.3]).DiscussionPatients with ADEM exhibit brain volume loss and failure of age-expected brain growth. Importantly, MOG-negative status was associated with a more pronounced brain volume loss compared with MOG-positive patients.

Fragestellung: Längen- und Dickenwachstum der Knochen werden durch biologische und mechanische Faktoren moduliert. Dadurch können pathologische Belastungen eine Ursache von Fehlstellungen sein. Computersimulationen können Spannungen im Knocheninneren und die sich daraus ergebenden Wachstumsreize [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Familial hypocalciuric hypercalcemia (FHH, [OMIM #145980]) is recognized as a benign endocrine condition affecting PTH and calcium levels due to heterozygous inactivating mutations in the calcium sensing receptor (\(\it CaSR\)). The condition is often un- or misdiagnosed but may have a prevalence as high as 74 in 100.000. Here, the neonatal courses of two brothers with paternally inherited FHH (\(\it {CaSR_c.554}\)G>A; p.(\(\it {Arg185Gln}\))) are described. The older brother was born preterm at 25 weeks gestation with hypercalcemia and hyperparathyroidism. The younger brother, born full-term, had severe hyperparathyroidism, muscular hypotonia, thrombocytopenia, failure to thrive and multiple metaphyseal fractures. Treatment with cinacalcet was initiated, which resulted in subsequent reduction of PTH levels and prompt clinical improvement. While it is known that homozygous mutations in \(\it CaSR\) may lead to life-threatening forms of neonatal severe hyperparathyroidism (NSHPT), few reports have described a severe clinical course in neonates with FHH due to heterozygous mutations. However, based on the pathophysiological framework, in \(\textit {de novo}\) or paternally transmitted FHH the differing calcium needs of mother and fetus can be expected to induce fetal hyperparathyroidism and may result in severe perinatal complications as described in this report. In summary, FHH is a mostly benign condition, but transient neonatal hyperparathyroidism may occur in affected neonates if the mutation is paternally inherited. If severe, the condition can be treated successfully with cinacalcet. Patients with FHH should be informed about the risk of neonatal disease manifestation in order to monitor pregnancies and neonates.

Das Tolosa-Hunt-Syndrom (THS) ist eine schmerzhafte Entzundung der Orbitalregion, welche unterschiedliche Strukturen, wie Augenmuskeln und -nerven, betreffen kann. In der klinischen Prasentation stehen daher oft schmerzhafte Augenmotilitatsstorungen im Vordergrund. Es wird von einem 16-jahrigen Madchen mit der Diagnose eines THS berichtet, welches sich mit einer akuten schmerzlosen Schwellung des linken Augenlides, einer Lidheberschwache sowie einem Abweichen der Sehachse des linken Auges nach unten und zur Seite vorstellte. Magnetresonanztomographische (MRT-)Untersuchungen mit Kontrastmittel zeigten einen inflammatorischen Pseudotumor im Apex der Orbita links mit Beteiligung des Sinus cavernosus. Eine Stostherapie mit Kortikosteroiden fuhrte zur vollstandigen Erholung der Patientin. Anhand unserer Fallbeschreibung lasst sich festhalten, dass sich ein THS im Jugendalter auch atypisch ohne das Leitsymptom Schmerz prasentieren kann. Zukunftige Datenerhebungen konnten neue Informationen zu Pravalenz und klinischem Spektrum des THS zeigen.

A 6-year-old girl developed sudden onset painless loss of vision with swelling of both optic discs. Brain MRI demonstrated bilateral extensive optic nerve involvement with perineural enhancement (figure). Her vision recovered completely after treatment with IV methylprednisolone.1 Serum myelin oligodendrocyte glycoprotein (MOG) antibodies tested positive.

ObjectiveTo describe the presentations, radiologic features, and outcomes of children with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs).MethodsIdentification of children fulfilling the diagnostic criteria for possible autoimmune encephalitis (AE) and testing positive for serum MOG abs. Chart review and comprehensive analysis of serum MOG abs using live cell assays and rat brain immunohistochemistry.ResultsTen children (4 girls, 6 boys) with AE and serum MOG abs were identified. The median age at onset was 8.0 years (range: 4–16 years). Children presented with a combination of encephalopathy (10/10), headache (7/10), focal neurologic signs (7/10), or seizures (6/10). CSF pleocytosis was common (9/10, median 80 white cell count/μL, range: 21–256). Imaging showed cortical and deep gray matter involvement in all in addition to juxtacortical signal alterations in 6/10 children. No involvement of other white matter structures or contrast enhancement was noted. MOG abs were detected in all children (median titer 1:640; range: 1:320–1:10,540). Nine children had a favorable outcome at discharge (modified Rankin scale of < 2). Five of 10 children had up to 3 additional demyelinating relapses associated with persisting MOG abs. One child had NMDA receptor (NMDAR) abs at initial presentation. A second child had a third demyelinating episode with MOG abs with overlapping NMDAR encephalitis.DiscussionAE associated with serum MOG abs represents a distinct form of autoantibody-mediated encephalitis in children. We therefore recommend including MOG abs testing in the workup of children with suspected AE.

Bilateral optic neuritis (bilON) is a rare clinical presentation often thought to be associated with relapsing disorders such as neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS).To characterize the clinical, radiological phenotype and antibody status of children presenting with bilON.Retrospective multicenter study on children with bilON age18 years with a first episode aquired demyelinating syndrome (ADS), cMRI, AQP4- and serum MOG-antibody status and follow-up data were collected.30 patients (f:m = 15:15, median age 8.0y) with bilON met the inclusion criteria. 22/30 (73%) were MOG-positive (median: 1:1280, range: 1:160-1:1520). No patient showed AQP4-abs. 4/30 patients (13%), all with high MOG-abs titers, had recurrent episodes. No patient developed MS. Improvement after IVMP was observed in most patients (26/30; 87%). Outcome was favorable with no sequelae in 22/30 patients. Serial MOG-abs titers tested in 15/22 patients decreased to a median of 1:160 (range: 0-1:640) over a period of 31 months (range: 2-141 months) in 14/15 (93%) patients. MR imaging showed a predominantly anterior affection of the visual system in seropositive patients with bilateral intraorbital lesions in 68% (15/22), compared to 25% in MOG-negative patients (2/8).Pediatric bilON is associated with high MOG-abs titers in combination with anterior involvement of the visual system. Despite severe loss of vision, the majority of patients shows distinct recovery after IVMP.

We present a boy with a genetically proven congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. While massively elevated 17-hydroxyprogesterone (17-OHP) concentrations after birth led to the diagnosis, 17-OHP concentrations became immeasurable starting with the second year of life even though the dose of hydrocortisone was continuously decreased to ∼7 mg/m2/day. Furthermore, 17-OHP levels were immeasurable during the ACTH test and after withdrawing hydrocortisone medication. In contrast, ACTH levels increased after cessation of hydrocortisone treatment suggesting complete primary adrenal cortex failure. We discuss this case based on the differential diagnosis of complete adrenal cortex failure including other genetic causes in addition to CAH, prednisolone treatment, autoimmune adrenalitis, adrenoleukodystrophy, CMV infection, and adrenal hemorrhage infarction. The most likely disease in our boy is autoimmune adrenalitis, which is difficult to prove years after the onset of the disease. Treatment of CAH had masked the classical symptoms of complete adrenal cortex insufficiency leading to delayed diagnosis in this case.

Hintergrund und Fragestellung Bildgebende Diagnostik ist wichtig fur die Klarung von Missbrauchsfallen. Ihre Anwendung und Ergebnisse bei entsprechenden Verdachtsfallen in einer der grosten medizinischen Kinderschutzeinrichtungen in Deutschland zu betrachten, war Ziel dieser Untersuchung.

N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare antibody-mediated autoimmune encephalitis often associated with an ovarian teratoma in adolescent females. Here we present a 17-year-old girl with only and unusual psychiatric symptoms as part of her NMDAR encephalitis in combination with a very small ovarian teratoma suspected by magnetic resonance (MR) imaging and finally histologically confirmed. We further review the literature of NMDAR encephalitis in combination with an ovarian teratoma and discuss the recommended radiological workup in children with a suspected ovarian tumor.

PURPOSE: Sonographic evaluation of the infant hip joint according to the method of Graf has proven to be an important pediatric investigative instrument. Our goal was to investigate quantitatively whether (and in what ways) the clinically relevant infant hip joint structures visualize differently when utilizing trapezoidal as opposed to linear transducers. Our approach was both theoretical via a mathematical model and practical with in-vivo measurements in neonates. MATERIALS AND METHODS: In a prospective study: 1. theoretical and computed analyses were performed for both linear and trapezoidal transducers regarding their respective accuracy for demonstrating the anatomic geometry of the infant hip, assuming not only correctly centered transducer positioning but also cases with off-centered displacement in the cranial or caudal direction; 2. both hip joints in 97 infants were examined by experienced investigators with comparison of the results for parallel vs. trapezoidal transducers. RESULTS: Theoretical mathematical error analysis reveals no intrinsic systemic deviations between trapezoidal vs. parallel transducers in US scanning of the infant hip and furthermore no inherent disadvantages in the trapezoidal technique. Even when off-center transducer alignments of 1.5 cm are employed in the mathematical models, there is no significant relative distortion of the required anatomic structures when comparing the characteristics of both transducers. The practical in-vivo data from our 97 neonates confirmed the theoretical considerations. CONCLUSION: No loss of accuracy or other negative factors are evident when trapezoidal transducers are used to visualize the infant hip joint in comparison with the customary parallel technique. There are no significantly measurable differences between the two approaches.

PURPOSE: To examine the diagnostic advantages of an asymmetric film-screen system (a-FSS) compared to a conventional 200-speed FSS with and without anatomical lung filter. METHODS: Standard radiographs were obtained from an anthropomorphic chest phantom with simulated pulmonary nodules. The existence or non-existence of nodules was assessed in 7344 individual observations. The results were evaluated using ROC analysis. RESULTS: In an overall evaluation the a-FSS with an ROC area of 0.873 +/- 0.018 was not significantly superior (p > 0.05) to the lung filter but significantly superior (p 0.05), whereas the lung filter was rated significantly lower (p < 0.05). CONCLUSIONS: Asymmetric FSS improves chest diagnostics, because it yields significantly more diagnostic information in the mediastinum using equivalent x-ray exposure without reducing the image quality in the lung areas in respect of simulated pulmonary nodules.

Sonographic evaluation of the infant hip joint according to the method of Graf has proven to be an important pediatric investigative instrument. Our goal was to investigate quantitatively whether (and in what ways) the clinically relevant infant hip joint structures visualize differently when utilizing trapezoidal as opposed to linear transducers. Our approach was both theoretical via a mathematical model and practical with in-vivo measurements in neonates.In a prospective study: 1. theoretical and computed analyses were performed for both linear and trapezoidal transducers regarding their respective accuracy for demonstrating the anatomic geometry of the infant hip, assuming not only correctly centered transducer positioning but also cases with off-centered displacement in the cranial or caudal direction; 2. both hip joints in 97 infants were examined by experienced investigators with comparison of the results for parallel vs. trapezoidal transducers.Theoretical mathematical error analysis reveals no intrinsic systemic deviations between trapezoidal vs. parallel transducers in US scanning of the infant hip and furthermore no inherent disadvantages in the trapezoidal technique. Even when off-center transducer alignments of 1.5 cm are employed in the mathematical models, there is no significant relative distortion of the required anatomic structures when comparing the characteristics of both transducers. The practical in-vivo data from our 97 neonates confirmed the theoretical considerations.No loss of accuracy or other negative factors are evident when trapezoidal transducers are used to visualize the infant hip joint in comparison with the customary parallel technique. There are no significantly measurable differences between the two approaches.