Electroneurophysiological evaluation in children and adolescents with collagen diseases

Background: Sensorimotor neuropathies have been reported in patients with known or suspected connective tissue disease. It is often difficult to diagnose early neuropathies, and the study of the peripheral neuromuscular system is often made difficult by symptoms resulting from pain in the joints and limitation of movement.Objective: We aimed to investigate the central and peripheral nervous systems involvement in patients with pediatric- onset SLE and juvenile rheumatoid arthritis through clinical assessment and neurophysiological studies (motor nerve conduction velocity (MNCV) of the tibial nerve bilaterally and somatosensory evoked potentials (SSEPs) of the median nerve bilaterally) and to study their relation to clinical data and laboratory investigations.Methods: Nineteen patients with SLE (mean age 14.47± 3.94 years)and fifteen JRA patients (mean age 13.39±3.9 years) were included in the study. Ten healthy, matched subjects served as the control group. In addition to clinical assessment, including complete neurological and psychiatric evaluation, different investigative tools needed for diagnosis as well as assessment of systemic involvement and the degree of activity, were implemented. Both patients and control groups were subjected to neurophysiological studies (Motor nerve conduction velocity (MNCV) of tibial nerve bilaterally and Somatosensory evoked potentials (SSEPs) of the median nerve bilaterally).Results: Definite manifestations of neuropsychiatric involvement attributable to SLE was diagnosed in 37% of SLE patients. Of the SLE patients, 10.5% had abnormal MNCV on the right side, while Erb-N13 interpeak latencies were prolonged in 10.5% and 31.5% of the median nerves studied on the right and left sides, respectively, and N13-N20 was prolonged in 21% and 31.5%, respectively. Neither hypertension nor renal involvement significantly affected the studied parameters; however, SLE patients with cutaneous vasculitis showed slower MNCV of tibial nerve and prolonged Erb-N13 intervals on both sides. Erb-N13 and N13-N20 (on the right side) were positively correlated to the disease activity index (SLE-DAI). Of the JRA patients, 6% had slowed nerve conduction of right tibial nerve, while the interpeak latencies of Erb-N13 were prolonged in 6.6% and 13.3% on the right and left sides, respectively and N13-N20 was prolonged in 6.6% and 20%, respectively. Erb- N13 (on the right side) was negatively correlated to the cumulative dose of steroids.Conclusion: Our study revealed that sensorimotor neuropathies are often more common than expected in patients with collagen disease. Early subclinical neuropathies may be difficult to diagnose where symptoms from joint pain may mask the diagnosis. Widespread vasculitis including  vasculitis of the vasa nervora may be the underlying pathology, which  stresses the value of steroids in treatment.Key words: Collagen disease- neuropathy- somatosensory evoked potentials

Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype–phenotype correlations in individuals with biallelic SLC18A2 variants. Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype–phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies. Results: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities. Conclusion: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders