Diabetic visceral neuropathy of gastroparesis: Gastric mucosal innervation and clinical significance.

BACKGROUND AND PURPOSE: The pathogenesis of diabetic gastroparesis due to visceral neuropathy involves multidimensional mechanisms with limited exploration of gastric mucosal innervation. This study aimed to examine quantitatively this topic and its relationship with gastroparesis symptoms and gastric emptying in diabetes. METHODS: We prospectively enrolled 22 patients with type 2 diabetes and gastroparesis symptoms and 25 age- and gender-matched healthy controls for comparison. The assessments included: (i) neuropathology with quantification of gastric mucosal innervation density (MID) on endoscopic biopsy; (ii) clinical manifestations based on the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire; and (iii) functional tests of gastric emptying scintigraphy (GES). RESULTS: In patients with diabetes, stomach fullness, bloating and feeling excessively full after meals constituted the most common GCSI symptoms. Seven patients with diabetes (32%) had prolonged gastric emptying patterns. In diabetes, gastric MID was significantly lower in all the regions examined compared with the controls: antrum (294.8 ± 237.0 vs. 644.0 ± 222.0 mm/mm3 ; p < 0.001), body (292.2 ± 239.0 vs. 652.6 ± 260.9 mm/mm3 ; p < 0.001), and fundus (238.0 ± 109.1 vs. 657.2 ± 332.8 mm/mm3 ; p < 0.001). Gastric MID was negatively correlated with gastroparesis symptoms and total scores on the GCSI (p < 0.001). Furthermore, gastric MID in the fundus was negatively correlated with fasting glucose and glycated hemoglobin levels. Gastric emptying variables, including half emptying time and gastric retention, were prolonged in patients with diabetes, and gastric retention at 3 h was correlated with fasting glucose level. CONCLUSION: In diabetes, gastric MID was reduced and GES parameters were prolonged. Both were correlated with gastroparesis symptoms and glycemic control. These findings provide pathology and functional biomarkers for diabetic visceral neuropathy of gastroparesis and underlying pathophysiology.

Maladaptive motor cortical excitability and connectivity in polyneuropathy with neuropathic pain.

BACKGROUND AND PURPOSE: Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain. METHODS: This cross-sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging. RESULTS: Thirty-three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short-latency afferent inhibition at an interstimulus interval of 20 ms was associated with structural connectivity of left M1 with brain areas associated with pain perception. CONCLUSIONS: Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy.

Skin nerve pathology: Biomarkers of premanifest and manifest amyloid neuropathy.

OBJECTIVE: Small-fiber sensory and autonomic symptoms are early presentations of familial amyloid polyneuropathy (FAP) with transthyretin (TTR) mutations. This study aimed to explore the potential of skin nerve pathologies as early and disease-progression biomarkers and their relationship with skin amyloid deposits. METHODS: Skin biopsies were performed in patients and carriers to measure intraepidermal nerve fiber (IENF) density, sweat gland innervation index of structural protein gene product 9.5 (SGII[PGP9.5]) and peptidergic vasoactive intestinal peptide (SGII[VIP]), and cutaneous amyloid index. These skin pathologies were analyzed with clinical disability assessed by FAP stage score (stage 0-4) and compared to neurophysiological and psychophysical tests. RESULTS: There were 70 TTR-mutant subjects (22 carriers and 48 patients), and 66 cases were TTR-A97S. Skin nerve pathologies were distinct according to stage. In carriers, both skin denervation and peptidergic sudomotor denervation were evident: (1) IENF density was gradually reduced from stage 0 through 4, and (2) SGII(VIP) was markedly reduced from stage 1 to 2. In contrast, SGII(PGP9.5) was similar between carriers and controls, but it declined in patients from stage 2. Skin amyloids were absent in carriers and became detectable from stage 1. Cutaneous amyloid index was correlated with SGII(PGP9.5) and stage in a multivariate mixed-effect model. When all tests were compared, only IENF density, SGII(PGP9.5), and cutaneous amyloid index were correlated with stage, and IENF density had the highest abnormal rate in carriers. INTERPRETATION: Biomarkers of sensory and sudomotor innervation exhibited a stage-dependent progression pattern, with sensory nerve degeneration as the early skin nerve pathology. Ann Neurol 2019;85:560-573.

Occurrence and genotype of Giardia cysts isolated from faecal samples of children and dogs and from drinking water samples in an aboriginal area of central Taiwan.

To investigate some aspects of Giardia infection, we performed a cross-sectional study on schoolchildren from an aboriginal area of Nantou County in central Taiwan. Faecal samples from 209 participants and samples of dog faeces and of water from mountain springs found in the area were collected. The participants also filled a questionnaire pertaining to demographic data. Giardia duodenalis was detected in eight of the 209 participants, and all positive isolates belonged to assemblage A. In addition, assemblage A isolates were obtained from four of the 22 water samples, and assemblage C or D isolates were obtained from four of the 42 canine faecal samples. Our results suggest that the risk of Giardia transmission is greater from waterborne than canine transmission in this study area.