Paediatric Cogan´s syndrome - review of literature, case report and practical approach to diagnosis and management

Abstract Background Cogan´s syndrome is a rare, presumed autoimmune vasculitis of various vessels characterized by interstitial keratitis and vestibular impairment accompanied by sensorineural hearing loss. Due to the rarity of Cogan´s syndrome in children, therapeutic decision making may be challenging. Therefore, a literature search was performed to collect all published paediatric Cogan´s syndrome cases with their clinical characteristics, disease course, treatment modalities used and their outcome. The cohort was supplemented with our own patient. Main text Altogether, 55 paediatric Cogan´s syndrome patients aged median 12 years have been reported so far. These were identified in PubMed with the keywords “Cogan´s syndrome” and “children” or “childhood”. All patients suffered from inflammatory ocular and vestibulo-auditory symptoms. In addition, 32/55 (58%) manifested systemic symptoms with musculoskeletal involvement being the most common with a prevalence of 45%, followed by neurological and skin manifestations. Aortitis was detected in 9/55 (16%). Regarding prognosis, remission in ocular symptoms was attained in 69%, whereas only 32% achieved a significant improvement in auditory function. Mortality was 2/55. Our patient was an 8 year old girl who presented with bilateral uveitis and a history of long standing hearing deficit. She also complained of intermittent vertigo, subfebrile temperatures, abdominal pain with diarrhoea, fatigue and recurrent epistaxis. The diagnosis was supported by bilateral labyrinthitis seen on contrast-enhanced magnetic resonance imaging. Treatment with topical and systemic steroids was started immediately. As the effect on auditory function was only transient, infliximab was added early in the disease course. This led to a remission of ocular and systemic symptoms and a normalization of hearing in the right ear. Her left ear remained deaf and the girl is currently evaluated for a unilateral cochlear implantation. Conclusions This study presents an analysis of the largest cohort of paediatric Cogan´s syndrome patients. Based on the collected data, the first practical guide to a diagnostic work-up and treatment in children with Cogan´s syndrome is provided

Dog-Assisted Therapy in Neurorehabilitation of Children with Severe Neurological Impairment:An Explorative Study

Dog-assisted therapy (DAT) is increasingly applied in neurorehabilitation of patients with severe neurological impairments. To date, there are only anecdotal reports investigating its effects.; This study was aimed to evaluate the potential of DAT in pediatric inpatient neurorehabilitation for severely neurologically impaired children and adolescents, to identify characteristics of patients receiving this therapy, characteristics of the therapy sessions, and to evaluate feasibility and extent of goal achievement.; We retrospectively analyzed 850 DAT sessions performed between 2010 and 2017 at an inpatient neurorehabilitation center. The dataset included 196 children and adolescents (Md = 5.50, 0.58-20.33 years) suffering from severe neurological impairments (disorders of consciousness in 37 patients) of various etiologies. We extracted information regarding patient and session characteristics, analyzed the predefined goals with content analysis, and examined to what extent the goals were met during DAT. Data were analyzed using descriptive statistics.; Patients received an average of 4.34 therapy sessions. A total of 247 of 392 predefined goals (63%) were reached during DAT. The most frequently achieved goal was "enhancing fun" (83%), followed by "establishing contact and communication" (81%), and "relaxation" (71%). Only one critical incident regarding the dogs' safety occurred.; DAT is a feasible approach and appears to facilitate emotional, social, and psychological goals in children and adolescents with severe neurological impairment

Acetylcholine Receptor Pathway Mutations Explain Various Fetal Akinesia Deformation Sequence Disorders

Impaired fetal movement causes malformations, summarized as fetal akinesia deformation sequence (FADS), and is triggered by environmental and genetic factors. Acetylcholine receptor (AChR) components are suspects because mutations in the fetally expressed γ subunit (CHRNG) of AChR were found in two FADS disorders, lethal multiple pterygium syndrome (LMPS) and Escobar syndrome. Other AChR subunits α1, β1, and δ (CHRNA1, CHRNB1, CHRND) as well as receptor-associated protein of the synapse (RAPSN) previously revealed missense or compound nonsense-missense mutations in viable congenital myasthenic syndrome; lethality of homozygous null mutations was predicted but never shown. We provide the first report to our knowledge of homozygous nonsense mutations in CHRNA1 and CHRND and show that they were lethal, whereas novel recessive missense mutations in RAPSN caused a severe but not necessarily lethal phenotype. To elucidate disease-associated malformations such as frequent abortions, fetal edema, cystic hygroma, or cardiac defects, we studied Chrna1, Chrnb1, Chrnd, Chrng, and Rapsn in mouse embryos and found expression in skeletal muscles but also in early somite development. This indicates that early developmental defects might be due to somite expression in addition to solely muscle-specific effects. We conclude that complete or severe functional disruption of fetal AChR causes lethal multiple pterygium syndrome whereas milder alterations result in fetal hypokinesia with inborn contractures or a myasthenic syndrome later in life