Project description:ObjectiveTo describe the natural history, clinical, neurophysiological, and histological features, and outcomes of diabetic patients presenting with acute painful neuropathy associated with glycemic control, also referred to as insulin neuritis.MethodsSixteen subjects presenting with acute painful neuropathy had neurological and retinal examinations, laboratory studies, autonomic testing, and pain assessments over 18 months. Eight subjects had skin biopsies for evaluation of intraepidermal nerve fiber density.ResultsAll subjects developed severe pain within 8 weeks of intensive glucose control. There was a high prevalence of autonomic cardiovascular, gastrointestinal, genitourinary, and sudomotor symptoms in all subjects. Orthostatic hypotension and parasympathetic dysfunction were seen in 69% of subjects. Retinopathy worsened in all subjects. Reduced intraepidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results, and IENFD. Greater improvements were seen after 18 months in type 1 versus type 2 diabetic subjects in autonomic symptoms (cardiovascular p < 0.01; gastrointestinal p < 0.01; genitourinary p < 0.01) and autonomic function tests (p < 0.01, sympathetic and parasympathetic function tests).InterpretationTreatment-induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration, and autonomic dysfunction after intensive glycemic control. The neuropathy occurred in parallel with worsening diabetic retinopathy, suggesting a common underlying pathophysiological mechanism. Clinical features and objective measures of small myelinated and unmyelinated nerve fibers can improve in these diabetic patients despite a prolonged history of poor glucose control, with greater improvement seen in patients with type 1 diabetes.
Project description:Axonal peripheral neuropathy is a common complication of mitochondrial trifunctional protein (MTP) deficiency and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency that is usually considered progressive. Current treatment strategies are not able to fully prevent neuropathic symptoms in the majority of patients. We herein report three sisters with genetically proven MTP deficiency who were untreated until adolescence, when electrophysiological studies first revealed isolated axonal sensory neuropathy. Apart from mild exercise intolerance and missing deep tendon reflexes of the lower extremities, all three girls were clinically asymptomatic. A fat-reduced and fat-modified diet together with a reduction of the nocturnal fasting time resulted in complete normalisation of the electrophysiological studies after 1 year of dietary treatment. Our findings suggest that neuropathy might be responsive to dietary interventions in MTP patients at a very early stage of disease.
Project description:We investigated the lateralization of gut-innervating vagal sensory neurons and their roles in feeding behavior. Using genetic, anatomical, and behavioral analyses, we discovered a subset of highly lateralized vagal sensory neurons with distinct sensory responses to intestinal stimuli. Our results demonstrated that left vagal sensory neurons (LNG) are crucial for distension-induced satiety, while right vagal sensory neurons (RNG) mediate preference for nutritive foods. Furthermore, these lateralized neurons engage different central circuits, with LNG neurons recruiting brain regions associated with energy balance and RNG neurons activating areas related to salience, memory, and reward. Altogether, our findings unveil the diverse roles of asymmetrical gut-vagal-brain circuits in feeding behavior, offering new insights for potential therapeutic interventions targeting vagal nerve stimulation in metabolic and neuropsychiatric diseases.
Project description:BackgroundCoronary Artery Spasm (CAS) often presents in the epicardial coronary arteries. The anterior septal branch is distributed within the myocardium, and occurrences of spasms are rare. Currently, there is no available literature on this topic, and the onset of symptoms remains elusive, potentially leading to misdiagnosis.Case presentationWe present a case of acute myocardial infarction (AMI) caused by spasm in the anterior septal branch, accompanied by transient right bundle branch block (RBBB). The administration of nitroglycerin via intracoronary injection resulted in the alleviation of spasm in the anterior septal branch and the disappearance of RBBB. After the administration of anti-coronary spasm medications, the patient exhibited favorable recovery outcomes. No episodes of myocardial ischemia were observed during the six-month follow-up.ConclusionsThe presence of new RBBB in patients may warrant consideration of anterior septal coronary artery spasm, which necessitates urgent coronary angiography to clarify the underlying cause and facilitate the prompt initiation of anti-spasm treatment.
Project description:IntroductionCombined nutritional deficiency is an uncommon cause of vision loss in the USA. Notably, vitamin A deficiency can produce nyctalopia but rarely causes bilateral central vision loss. The combination of these symptoms is unusual, although likely underreported.Case presentationWe report an exceptionally rare case of bilateral central vision loss and nyctalopia caused by combined vitamin A, zinc, and copper deficiency, likely following bariatric surgery and alcohol use. Following mineral and vitamin supplementation, the patient's vision improved significantly and returned to baseline within 1 month. Vision loss resulting from this specific multicombination of vitamin and mineral deficiency has never been reported previously in the English-language ophthalmic literature.ConclusionGiven rising rates of bariatric surgery and alcohol use in the USA and abroad, clinicians should be aware that the combination of progressive nyctalopia and bilateral central vision loss may be produced by combined nutritional deficiency. Screening and supplementation of both vitamin and mineral deficiency may result in dramatic reversal of visual loss in such cases.
Project description:In rats and guinea pigs, sensory innervation of the airways is derived largely from the vagus nerve, with the extrapulmonary airways innervated by Wnt1+ jugular neurons and the intrapulmonary airways and lungs by Phox2b+ nodose neurons; however, our knowledge of airway innervation in mice is limited. We used genetically targeted expression of enhanced yellow fluorescent protein-channelrhodopsin-2 (EYFP-ChR2) in Wnt1+ or Phox2b+ tissues to characterize jugular and nodose-mediated physiological responses and airway innervation in mice. With optical stimulation, Phox2b+ vagal fibers modulated cardiorespiratory function in a frequency-dependent manner while right Wnt1+ vagal fibers induced a small increase in respiratory rate. Mouse tracheae contained sparse Phox2b-EYFP fibers but dense networks of Wnt1-EYFP fibers. Retrograde tracing from the airways showed limited tracheal innervation by the jugular sensory neurons, distinct from other species. These differences in physiology and vagal sensory distribution have important implications when using mice for studying airway neurobiology.
Project description:Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem's dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that parasympathetic vagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.
Project description:Extensive intrathoracic tumors are rarely diagnosed radiologically without pre-existing symptoms. If located in the posterior mediastinum, it is most probably a neurogenic tumor. Schwannoma is the most frequent neurogenic neoplasia in this location, and most schwannomas are benign. To specify the diagnosis, a thoracic computed tomography must be done; if the growth is close to the medullary canal, a magnetic resonance tomography of the spinal column is necessary to detect neuroforamen infiltration. Our surgical goal was complete excision of the tumor, although many authors favor a minimally invasive approach. In our patient we performed open, en bloc removal of the tumor; removal of parts of the intraforamen was also necessary, which necessitated revision of the affected neuroforamen. Histologically this was a very rare case of vagal schwannoma (which has an incidence of less than 6% of all neurogenic tumors). This patient has a very promising prognosis following complete tumor resection.
Project description:Vagal flexibility describes the ability to modulate cardiac vagal responses to fit a dynamic range of challenges. Extant theory on vagal function implies that vagal flexibility is a mediating mechanism through which resting vagal activity, a putative individual difference related to self-regulation, affects adaptive behavior and cognition. Nevertheless, little research has directly tested this hypothesis, thereby leaving fundamental mechanisms of vagal function and adaptability unclear. To this end, 47 healthy subjects completed a 5 min baseline followed by Stroop tasks combined with concurrent auditory distractors. There were four different Stroop task conditions that varied the social and emotional content of the auditory distractors. Electrocardiogram was continuously recorded to assess vagal responses to each condition as heart rate variability [root mean square of successive differences (RMSSDs)] reactivity. Vagal flexibility significantly mediated the association between resting vagal activity and stability of inhibition performance (Stroop interference) scores. In particular, higher resting RMSSD was related to higher standard deviation of RMSSD reactivity scores, reflecting greater differences in RMSSD reactivity between distractor conditions (i.e., greater vagal flexibility). Greater vagal flexibility was in turn related to more stability in Stroop interference across the same conditions. The mean of RMSSD reactivity scores across conditions was not significantly related to resting RMSSD or stability in Stroop performance, and mean RMSSD reactivity did not mediate relations between resting RMSSD and stability in Stroop performance. Overall, findings suggest that vagal flexibility may promote the effects of resting vagal activity on stabilizing cognitive inhibition in the face of environmental perturbations.