RESUMEN
Peripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage pancreatic islet ß cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth and increased levels of mitochondrial reactive oxygen species. hIAPP-transgenic mice, which have elevated plasma hIAPP levels without hyperglycemia, developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intraepidermal nerve fiber (IENF) density. Similarly, hIAPP Ob/Ob mice, which have hyperglycemia in combination with elevated plasma hIAPP levels, had signs of neuropathy, although more aggravated. In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density. Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects. T2DM patients had reduced IENF density and more hIAPP oligomers in the skin compared with non-T2DM controls. Thus, we provide evidence that hIAPP aggregation is neurotoxic and mediates peripheral neuropathy in mice. The increased abundance of hIAPP aggregates in the skin of T2DM patients supports the notion that hIAPP is a potential contributor to T2DM neuropathy in humans.
Asunto(s)
Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Hiperglucemia , Islotes Pancreáticos , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 2/patología , Islotes Pancreáticos/patología , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/patología , Polipéptido Amiloide de los Islotes Pancreáticos/genética , Ratones Transgénicos , Hiperglucemia/patología , Dolor/patología , AmiloideRESUMEN
BACKGROUND: Ultrasound is widely used in the diagnosis of peripheral nerve compressions. Nevertheless, the role of ultrasound, and in particular the cross-sectional area (CSA) measurements, in the diagnosis of cubital tunnel syndrome (CuTS) is debatable, especially in patients who have had previous surgeries. We evaluated the diagnostic value of ultrasound and CSA measurements in a heterogenous group of CuTS patients suffering from persisting or recurrent CuTS after a previous surgical intervention. METHODS: All patients with persisting or recurrent CuTS after previous surgery, who received a nerve ultrasound with or without CSA measurements in a tertiary referral center between 2015 and 2022, were included. Median CSA was calculated at five locations from the upper arm to the wrist. The sensitivity of ultrasound and electrodiagnostic studies and the correlation between both diagnostic tools were calculated. RESULTS: Thirty-seven nerves from 35 patients who received nerve ultrasound, of which 21 nerves from 19 patients who received additional CSA measurements, were included. Ultrasound indicated signs of persisting or recurrent compression in 73.0% of patients, and ulnar swelling based on CSA measurements was found in 71.4% of patients. Electrodiagnostic testing was positive in 40.7% of patients. CuTS diagnosis was supported by both electrodiagnostic studies and CSA in only 34.6% of patients. CONCLUSIONS: CSA and electrodiagnostic testing in patients with persistent or recurrent symptoms after previous surgery did not correlate well, and the sensitivity of both tests was lower than in diagnostic accuracy studies. Ultrasound was found to be useful in evaluating ulnar nerves after previous surgery.
Asunto(s)
Síndrome del Túnel Cubital , Humanos , Síndrome del Túnel Cubital/diagnóstico por imagen , Síndrome del Túnel Cubital/cirugía , Muñeca , Nervio Cubital/diagnóstico por imagen , Nervio Cubital/cirugía , Codo , UltrasonografíaRESUMEN
BACKGROUND: Neuropathic pain caused by adhesions or neuroma formation of the superficial branch of the radial nerve (SBRN) is difficult to treat. The authors evaluated the effectiveness of different routinely used surgical techniques for SBRN neuralgia to provide a basis for future studies on SBRN neuralgia and explored the prognostic value of a preoperative diagnostic nerve block. METHODS: The authors performed a retrospective cohort study by reviewing surgical records for procedures to treat SBRN neuralgia. Patient satisfaction was scored as satisfied or unsatisfied, and pain intensity was scored with a numeric rating scale. RESULTS: The authors included 71 patients who had 105 surgeries on the SBRN. Patients with a neuroma ( n = 43) were most satisfied after proximal denervation with burying into the brachioradialis muscle compared with burying elsewhere (53 versus 0 percent; p < 0.001). Adhesions of the SBRN ( n = 28) were treated with neurolysis (39 percent satisfied). If neurolysis or denervation did not suffice, an additional denervation of the lateral antebrachial cutaneous nerve or posterior interosseous nerve led to satisfaction in 38 percent. A decrease of less than 3.5 points on the numeric rating scale score after diagnostic nerve block led to higher postoperative pain scores (4.0 versus 7.5; p = 0.014). The authors found that the outcome of the diagnostic nerve block can predict the outcome of SBRN denervation and burying into brachioradialis muscle. CONCLUSIONS: The most effective burying technique is burying the SBRN into the brachioradialis muscle. Future studies on the treatment of SBRN neuralgia should therefore compare newer techniques, with burying the SBRN into the brachioradialis muscle as the control group.