Annegret Quade

Pathogenic variants in voltage-gated sodium channels (VGSCs) may cause disturbed sensory function, including small fiber neuropathy (SFN) in adults, but little is known about their role in children and adolescents.A total of 39 prospectively enrolled children (age 12.03 ± 4.61 years) with abnormal pain sensation underwent detailed diagnostics including quantitative sensory testing (QST, if >5 years old), quality of life assessment, and genetic studies for VGSC variants and further etiologies.QST results were consistent with Aẟ- und C-fiber damage, including increased cold, warmth, and mechanical detection thresholds, higher thermal sensory limen, and allodynia. Intraepidermal nerve fiber densities were low in 9/18 children. This resulted in a great impact on physical quality of life and pain scales but not on social life. Five children showed heterozygous variants of unknown significance (VUS) in genes encoding VGSC (SCN9A, n = 2; SCN10A, n = 3) with maternal or paternal inheritance in two and one patients, respectively. Three further patients showed likely disease-associated variants in the HUWE1, TRIO, and PYGM genes.Despite a high disease burden and small fiber damage indicated by QST and skin histology, only VUS in VGSC and additional monogenic causes of pain symptoms outside of VGSC genes were identified. Genetic studies in affected children should therefore be comprehensive, not restricted to VGSC variants and be supplemented by a detailed clinical workup. In silico modeling and future functional studies might help to identify VUS that play a role in altered pain perception.

Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy. Here, we report 15 patients (age range 3 months to 15 years) who suffered from autoimmune encephalitis with autoantibodies to NMDAR1 following Herpes encephalitis, presenting with movement abnormalities (young children) or neuropsychiatric symptoms (older children) as major complaints, respectively. The diagnosis was based on positive cerebrospinal fluid (CSF) and/or serum anti-NMDAR-antibodies with two children showing only positive CSF antibody findings. The time lag between first symptoms and diagnosis of autoimmune encephalitis was significantly longer than between first symptoms and diagnosis of HSVE (p <0.01). All patients improved during immunosuppressive treatment, during which plasmapheresis or rituximab treatments were applied in 11 patients, irrespective of their age. Despite immunotherapy, no patients relapsed with HSVE. Early diagnosis and treatment of autoimmune encephalitis after HSVE may be associated with a better outcome so that high clinical awareness and routine testing for anti-NMDAR-antibodies after HSVE seems advisable. If autoimmune encephalitis is suspected, antibody testing should also be performed on CSF if negative in serum.

Background: Cancer therapy-induced bone loss (CTIBL) is well-known sequela of adjuvant endocrine therapy in postmenopausal patients (pts) with primary breast cancer (PBC). Pts exposed to chemotherapy (Ctx) with alkylators for lymphoma/leukemia own a high risk of premature CTIBL which as in premenopausal PBC pts may be mainly an indirect endocrine effect of Ctx. In contrast, data on direct effects of modern perioperative Ctx on bone metabolism are limited. This retrospective study was initiated to gain more detailed insights into the influence of perioperative anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of pts with pre- and postmenopausal PBC.