Automated whole slide morphometry of sural nerve biopsy using machine learning.

AIM: The morphometry of sural nerve biopsies, such as fibre diameter and myelin thickness, helps us understand the underlying mechanism of peripheral neuropathies. However, in current clinical practice, only a portion of the specimen is measured manually because of its labour-intensive nature. In this study, we aimed to develop a machine learning-based application that inputs a whole slide image (WSI) of the biopsied sural nerve and automatically performs morphometric analyses. METHODS: Our application consists of three supervised learning models: (1) nerve fascicle instance segmentation, (2) myelinated fibre detection and (3) myelin sheath segmentation. We fine-tuned these models using 86 toluidine blue-stained slides from various neuropathies and developed an open-source Python library. RESULTS: Performance evaluation showed (1) a mask average precision (AP) of 0.861 for fascicle segmentation, (2) box AP of 0.711 for fibre detection and (3) a mean intersection over union (mIoU) of 0.817 for myelin segmentation. Our software identified 323,298 nerve fibres and 782 fascicles in 70 WSIs. Small and large fibre populations were objectively determined based on clustering analysis. The demyelination group had large fibres with thinner myelin sheaths and higher g-ratios than the vasculitis group. The slope of the regression line from the scatter plots of the diameters and g-ratios was higher in the demyelination group than in the vasculitis group. CONCLUSION: We developed an application that performs whole slide morphometry of human biopsy samples. Our open-source software can be used by clinicians and pathologists without specific machine learning skills, which we expect will facilitate data-driven analysis of sural nerve biopsies for a more detailed understanding of these diseases.

Serial changes in regional cerebral blood flow in Gerstmann-Sträussler-Scheinker disease caused by a Pro-to-Leu mutation at codon 105 in the prion protein gene.

Gerstmann-Sträussler-Scheinker disease with a Pro-to-Leu substitution at codon 105 in the prion protein gene (GSS-P105L) is a rare variant of human genetic prion disease. Herein, we report the case of a patient with GSS-P105L, who showed serial changes in regional cerebral blood flow (rCBF) on single-photon emission computed tomography (SPECT). A 42-year-old woman, with an affected father presenting with similar symptoms, had a 1-year history of progressive gait disturbance, lower-limb spasticity, and psychiatric symptoms. Genetic analysis confirmed the diagnosis of GSS-P105L. Eleven months after disease onset, brain magnetic resonance imaging (MRI) showed bilateral frontal lobe-dominant cerebral atrophy without hyperintensity on diffusion-weighted imaging (DWI) sequences; meanwhile, SPECT revealed non-specific mild hypoperfusion. Follow-up MRI at 52 months after onset demonstrated progressive frontal lobe-dominant cerebral atrophy without hyperintensity on DWI, while SPECT revealed a marked decrease in rCBF in the bilateral right-dominant frontal lobe. Patients with GSS with a Pro-to-Leu substitution at codon 102 (GSS-P102L) have been reported to exhibit hyperintensity on DWI-MRI and a diffuse decrease in CBF with a mosaic-like pattern on SPECT, which is absent in patients with GSS-P105L, thereby possibly reflecting the differences in pathophysiology between GSS-P102L and GSS-P105L.

Usefulness of renal diffusion-weighted magnetic resonance imaging for early diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome.

A teenage girl presented with fever after aspirin use. Examination revealed no organ-specific symptoms. The serum creatinine level and urine analysis findings were normal. The drug lymphocyte stimulation test was positive for aspirin. Diffusion-weighted magnetic resonance imaging (DW-MRI) revealed hyperintensity in both kidneys although serum creatinine was only mildly elevated. A subsequent kidney biopsy confirmed acute interstitial nephritis (AIN). She later developed uveitis and the final diagnosis was tubulointerstitial nephritis and uveitis (TINU) syndrome, possibly triggered by aspirin, requiring systemic and topical corticosteroid therapies. TINU syndrome should be considered in young patients with fever of unknown origin and a history of nonsteroidal anti-inflammatory drug use. This is the first reported case suggesting the usefulness of DW-MRI, which is safe for children without exposure to ionising radiation, in detecting early-stage AIN before apparent kidney impairment.

Internal jugular vein thrombosis associated with Granulicatella adiacens.

Granulicatella adiacens, which occurs as part of the oral microflora, is an uncommon cause of infection. However, it can cause serious bloodstream infections including infective endocarditis. Although oral bacteria, most commonly the Fusobacterium spp, can cause internal jugular vein (IJV) thrombophlebitis, there are no reported cases of IJV thrombosis caused by G. adiacens Here we report a patient with septic IJV thrombosis with G. adiacens bacteraemia. A middle-aged man presented to our hospital with fever and altered mental status. Blood cultures were positive for G. adiacens, and pan-scan CT with contrast showed left IJV thrombosis, pulmonary embolism and abscesses in the gluteal muscles. The patient was successfully treated with antibiotics. When confronted with G. adiacens bacteraemia in patients with poor oral hygiene, it is necessary to be cautious of the fact that this organism can cause IJV thrombophlebitis.

Social isolation suppresses actin dynamics and synaptic plasticity through ADF/cofilin inactivation in the developing rat barrel cortex.

Exposure to a stressful environment early in life can cause psychiatric disorders by disrupting circuit formation. Actin plays central roles in regulating neuronal structure and protein trafficking. We have recently reported that neonatal isolation inactivated ADF/cofilin, the actin depolymerizing factor, resulted in a reduced actin dynamics at spines and an attenuation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor delivery in the juvenile rat medial prefrontal cortex (mPFC), leading to altered social behaviours. Here, we investigated the impact of neonatal social isolation in the developing rat barrel cortex. Similar to the mPFC study, we detected an increase in stable actin fraction in spines and this resulted in a decreased synaptic AMPA receptor delivery. Thus, we conclude that early life social isolation affects multiple cortical areas with common molecular changes.