Citations

ABSTRACT Background and Aims Chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP ) is a common, treatable, autoimmune, neuropathy frequently misdiagnosed. The complex electrodiagnostic ( EDX ) criteria required for diagnosis are challenging to apply in routine practice. This study evaluates the effectiveness of a machine‐assisted EDX tool in real‐time identification of demyelinating nerve conduction studies ( NCS ) stipulated by 2021‐ EAN / PNS CIDP criteria in conjunction with an online CIDP clinical probability calculator. Methods We prospectively evaluated 100 consecutive patients with referral or EDX diagnosis of polyradiculoneuropathy beginning January 1, 2024. Fifty patients were included, each from Jacksonville and Rochester Mayo Clinics. Routine electromyography ( EMG ) reports were compared to a machine‐assisted support tool applying 2021‐ EAN / PNS CIDP EDX criteria to NCS assessing demyelination. The EDX ‐assistant performance was compared to the final clinical diagnosis and our previously reported online CIDP clinical prediction tool ( https://news.mayocliniclabs.com/cidp‐calculator/ ). Results Among 100 patients (60% male; median age 64), 30 had a final clinical CIDP diagnosis with 29 having intravenous immunoglobulin follow‐up; 27 (93%) improved and 2 (7%) stabilized. Routine EMGs reported demyelination in 14 of 30 (47%), with 46% sensitivity and 79% specificity. The EDX ‐assistant identified CIDP demyelination in 28 of 30 (93%), with 93% sensitivity and 57% specificity. The clinical calculator detected CIDP in 30 of 30 (100%) with 86% specificity, increasing to 94% after excluding false positives lacking demyelinating features on the EDX tool. Interpretation A real‐time machine‐assisted EDX support tool, used with a clinical web‐based calculator, streamlines CIDP assessment by improving standardized identification of 2021‐EAN/PNS CIDP demyelinating NCS criteria and aiding clinical decisions.

Abstract Background DNA methyltransferase 1 (DNMT1) is essential for DNA methylation and chromatin stability. DNMT1 on chromosome 19p 13.2 mutations in this gene lead to a dominantly inherited neurodegenerative phenotype with a triad of symptoms shared by all patients that includes: 1) Peripherally sensory neuropathy; 2) Sensorineural hearing loss; 3) Early on set dementia. Some patients also have seizure, narcolepsy, cerebellar ataxia, optic nerve atrophy. Importantly, almost phenotype mutations patients are can grow up until adulthood, symptoms begin at middle aged, and death typically occurs around age of 50 years. The initial clinical terms Hereditary Sensory and Autonomic Neuropathy type 1 E (HSAN1E: OMIM-614116). Aims & Objectives In DNMT1 mutations t he mutation in p.Tyr495 changing to cystaine (Y495C), the first discovard and common mutation of hereditary sensory neuropathy 1E, we producted the mutation knock-in mouse model of Y495C, verify the effect on homozygous and heterozygous mutant mice. To invastigate of impact phenotype changing the landscape of gene expression, compair wild -type littermate and tne mutant mouse. Method By using Gene knockin technichs, the process of tardeted insertion of the exogenous gene (Dnmt1 TAT>TGT) at a specific locus (Exon 19) in genomic Dnmt1, generate homozygous and heterozygouse mutant mouse. Experimental Design: To compair with wild-type littermate with mutant mouse model, parformed Rotor rod test as a neurophysiology and Nerve conduction study as a sensory test. Neuropathologically, we also parformed sciatic notch light microscopy epoxy-embedded methyl bluestained nerve. Results DNMT1 mutation knock in mouse model; Homozygous Y495C/Y495C mice were small and immatureness copaired to wt/Y495C heterozygpus one, were lethal 9.5 days during gestation. On the other hand heterozygous wt/Y495C mutant mouse catch up, give birth and grew up normally. At 9 month old Y495C mice, their sciatic notch light microscopy epoxy-embedded methyl bluestained nerve showed the characteristic fiber loss and axional degeneration. At 10-12 months and 16-18 months old, in nerve conduction study and Rotor-Rod testing, wt/Y495C mice decreased SNAP-Amplitude reduced, total running time of Rotor-Rod test dicreased with their ages. Discussion & Conclusions Heterozygous mutation in DNA metyrtransferase 1 (DNMT1) Y495C mice presented normal neural development and lifespan as well as the disease of human being (HSAN1E). Around 30's age, the patient's sensory loss become clearly present periferal sensory neuropathy. The gait disturbance is also gradually advanced with ataxia. Axonal degeneration at 9 month, deteriorating sensorimotor coordination manifested with age by Rotor-Rod test. Dementing status of DNMT1E shows FTD like symptons which advanced prominent around 40's. Reducing total ranning time by Rotre-Rod test may means loss of urge and attetion as a frontal lobe sign. Y495C homozygous mutant mice die during gestation. Homozygous genome methyration reduction cause newral hypogenesis of the fetus. The mutation in p.Tyr495 changing to cystaine (Y495C) are located in the middle part of TS domain which is hot spot mutant site, where a highly-conserved region has been identified essential for the binding of heterochromatin.