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Nonalcoholic fatty liver disease is the most prevalent chronic liver disease globally and is linked to augmented susceptibility to type 2 diabetes mellitus (DM), cardiovascular disease, and microvascular complications inherent to DM, such as nephropathy, neuropathy, and retinopathy. The fibrosis-4 (FIB-4) scoring system, a noninvasive tool, is useful for predicting the extent of liver fibrosis across diverse pathologies. This study aimed to assess the potential predictive role of FIB-4 scores in microvascular complications associated with diabetes. The medical records of patients with type 2 DM admitted to our endocrinology clinic between February 2019 and December 2020 were retrospectively evaluated. Parameters including demographic attributes, fasting blood glucose, glycated hemoglobin, aspartate aminotransferase, alanine aminotransferase, thrombocyte levels, and microvascular complications were recorded. The FIB-4 score was computed, and patients were categorized based on these scores (<1.3 and ≥ 1.3). The analysis included 312 patients with a median age of 60 (50–68 years); 39.7 % were men. The median duration of diabetes was 10 years (5–20 years), and the median FIB-4 score was 0.93 (0.63–1.34). Neuropathy, nephropathy, and retinopathy were observed in 50.6 %, 31.4 %, and 34 % of the patients, respectively. Although the FIB-4 score did not differ significantly between patients with and without neuropathy or retinopathy, patients with nephropathy exhibited higher FIB-4 scores. Notably, patients with FIB-4 scores ≥ 1.3 demonstrated a significantly higher prevalence of nephropathy. Logistic regression analysis demonstrated that higher FIB-4 scores were significantly associated with an increased risk of nephropathy. The FIB-4 score is a cost-effective and straightforward tool with potential applicability in predicting nephropathy in individuals with type 2 DM. [ABSTRACT FROM AUTHOR]

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Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history. Plain language title: A case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaints Plain language summary: Vitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery. [ABSTRACT FROM AUTHOR]

To estimate the proportion of people with self-reported diabetes receiving eye and foot examinations in Latin America and the Caribbean (LAC). Cross-sectional analysis of national health surveys in nine countries. Adults aged 25–64 years with self-reported diabetes. We quantified the proportion who reported having an eye examination in the last two years or a foot examination in the last year. We fitted multilevel Poisson regressions to assess socio-demographic (age and sex) and clinical (oral hypoglycemic medication and insulin treatment) variables associated with having had examinations. There were 7435 people with self-reported diabetes included in the analysis. In three countries (Chile [64%; 95% CI: 56%-71%], British Virgin Islands [58%; 95% CI: 51%-65%], and Brazil [54%; 95% CI: 50%-58%]), >50% of people with diabetes reported having had an eye examination in the last two years. Fewer participants (<50% across all countries) reported having had a foot examination in the last year, with Ecuador having the lowest proportion (12%; 95% CI: 8%-17%). Older people, and those taking oral medication or insulin, were more likely to have eye/foot examinations. The proportion of eye and foot examinations in people with self-reported diabetes across nine countries in LAC is low. • There were no data on the frequency of eyes/foot examination in diabetics in LAC. • In only three countries >50% of adults with diabetes have had an eye examination. • Chile was close to having 50% of adults with diabetes who received foot examination. • Eye/foot examinations to prevent complications warrants further investment in LAC. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

One of the most common issues caused by antineoplastic agents is chemotherapy-induced peripheral neuropathy (CIPN). In patients, CIPN is a sensory neuropathy accompanied by various motor and autonomic changes. With a high prevalence of cancer patients, CIPN is becoming a major problem for both cancer patients and for their health care providers. Nonetheless, there are lacking effective interventions preventing CIPN and treating the CIPN symptoms. A number of studies have demonstrated the cellular and molecular signaling pathways leading to CIPN using experimental models and the beneficial effects of some interventions on the CIPN symptoms related to those potential mechanisms. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in mechanical and temperature sensory responses following chemotherapy such as representative bortezomib, oxaliplatin and paclitaxel. The underlying mechanisms of CIPN at cellular and molecular levels will be also discussed for additional in-depth studies needed to be better explored. Overall, this paper reviews the basic picture of CIPN and the signaling mechanisms of the most common antineoplastic agents in the peripheral and central nerve systems. A better understanding of the risk factors and fundamental mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Copyright of Revista Kiru is the property of Universidad de San Martin de Porres and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The purpose of this paper is to develop a prototype of a wearable medical device in the form of a bandage with a real-time data monitoring platform, which can be used domestically for diabetic patients to identify the possibility of foot ulceration at the early stage. Design/methodology/approach: The prototype can measure blood volumetric change and temperature variation in the forefoot area simultaneously. The waveform extracted using a pulsatile-blood-flow signal was used to assess blood perfusion-related information, and hence, predict ischemic ulcers. The temperature difference between ulcerated and the reference was used to predict neuropathic ulcers. The medical device can be used as a bandage during the application wherein the sensory module is placed inside the hollow pocket of the bandage. A platform was developed through a mobile application where doctors can extract real-time information, and hence, determine the possibility of ulceration. Findings: The height of the peaks in the pulsatile-blood-flow signal measured from the subject with foot ischemic ulcers is significantly less than that of the subject without ischemic ulcers. In the presence of ischemic ulcers, the captured waveform flattens. Therefore, the blood perfusion from arteries to the tissue of the forefoot is considerably low for the subject with ischemic ulcers. According to the temperature difference data measured over 25 consecutive days, the temperature difference of the subject with neuropathic ulcers occasionally exceeded the 4 °F range but mostly had higher values closer to the 4 °F range. However, the temperature difference of the subject who had no complications of neuropathic ulcers did not exceed the 4 °F range, and the majority of the measurements occupy a narrow range from −2°F to 2 °F. Originality/value: The proposed prototype of wearable medical apparatus can monitor both temperature variation and pulsatile-blood-flow signal on the forefoot simultaneously and thereby predict both ischemic and neuropathic diabetes using a single device. Most importantly, the wearable medical device can be used domestically without clinical assistance with a real-time data monitoring platform to predict the possibility of ulceration and the course of action thereof. [ABSTRACT FROM AUTHOR]

Copyright of Cultura, Ciencia y Deporte is the property of Cultura, Ciencia y Deporte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Minimally invasive repair of pectus excavatum (MIRPE) with intercostal nerve cryoablation (Cryo) decreases length of hospitalization and opioid use, but long-term recovery of sensation has been poorly described. The purpose of this study was to quantify long-term hypoesthesia and neuropathic pain after MIRPE with Cryo. A prospective cohort study was conducted single-institution of patients ≤21 years who presented for bar removal. Consented patients underwent chest wall sensory testing and completed neuropathic pain screening. Chest wall hypoesthesia to cold, soft touch, and pinprick were measured as the percent of the treated anterior chest wall surface area (TACWSA); neuropathic pain was evaluated by questionnaire. The study enrolled 47 patients; 87% male; median age 18.4 years. The median bar dwell time was 2.9 years. A median of 2 bars were placed; 80.9% were secured with pericostal sutures. At enrollment, 46.8% of patients had identifiable chest wall hypoesthesia. The mean percentage of TACWSA with hypoesthesia was 4.7 ± 9.3% (cold), 3.9 ± 7.7% (soft touch), and 5.9 ± 11.8% (pinprick). Hypoesthesia to cold was found in 0 dermatomes in 62%, 1 dermatome in 11%, 2 dermatomes in 17% and ≥3 dermatomes in 11%. T5 was the most common dermatome with hypoesthesia. Neuropathic symptoms were identified by 13% of patients; none required treatment. In long-term follow up after MIRPE with Cryo, 46.8% of patients experienced some chest wall hypoesthesia; the average TACWSA with hypoesthesia was 4–6%. Hypoesthesia was mostly limited to 1–2 dermatomes, most commonly T5. Chronic symptomatic neuropathic pain was rare. Level IV. • Three years following the minimally invasive repair of pectus excavatum with intercostal nerve cryoablation, pediatric patient often develop chest wall hypoesthesia, which is limited to one or two dermatomes. • The presence of chest wall hypoesthesia does not lead to significant morbidity in pediatric patients. • The presence of chronic clinically significant neuropathic is rare three years following the minimally invasive repair of pectus excavatum with intercostal nerve cryoablation [ABSTRACT FROM AUTHOR]

Superficial radial neuropathy is a purely sensory neuropathy, usually caused by nerve entrapment in the distal forearm. We report a case of superficial radial neuropathy caused by the anomalous course of the superficial radial nerve, which was found to be spirally encircling the brachioradialis tendon in the distal forearm. To the best of our knowledge, this is the first report of an anatomical variant of the superficial radial nerve that causes neuropathy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. Methods: Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. Results: Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. Conclusion: The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome (GBS) is a rare but serious condition that carries with it a high rate of morbidity and mortality. This review highlights the pearls and pitfalls of GBS, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. GBS is a rare immune-mediated neurologic disorder with peripheral nerve injury. It most commonly presents weeks after a bacterial or viral infection, though there are a variety of associated inciting events. The diagnosis is challenging and often subtle, as only 25–30% of patients are diagnosed on their initial healthcare visit. Clinicians should consider GBS in patients with progressive ascending weakness involving the lower extremities associated with hyporeflexia, but the cranial nerves, respiratory system, and autonomic system may be involved. While the ED diagnosis should be based on clinical assessment, further evaluation includes laboratory testing, cerebrospinal fluid (CSF) analysis, and potentially neuroimaging. Not all patients demonstrate albumino-cytological dissociation on CSF testing. Several criteria exist to assist with diagnosis, including the National Institute of Neurological Disorders and Stroke criteria and the Brighton criteria. Management focuses first on assessment of the patient's hemodynamic and respiratory status, which may require emergent intervention. Significant fluctuations in heart rate and blood pressure may occur, and respiratory muscle weakness may result in the need for airway protection. Neurology consultation is recommended, and definitive treatment includes PLEX or IVIG. An understanding of GBS can assist emergency clinicians in diagnosing and managing this potentially deadly disease. [ABSTRACT FROM AUTHOR]

Cryoablation during minimally invasive repair for pectus excavatum (MIRPE) reduces opioid use and hospital length of stay. Skin hypoesthesia of the chest wall also occurs. This study sought to determine the frequency, onset, duration, and location of sensory changes and neuropathic pain after cryoablation. A prospective study was conducted on patients aged ≤21 years undergoing MIRPE with cryoablation of T3 to T7 dermatomes bilaterally for 120 s at a single institution between March 2021 to December 2022. Patients underwent sensory testing of the chest wall and neuropathic pain surveys (S-LANSS) preoperatively and then postoperatively for 6 months. Incidence and duration of hypoesthesia and neuropathic pain were evaluated. Of 61 patients enrolled in the study, 45 completed evaluations at six months postoperatively. All patients had skin hypoesthesia on postoperative day (POD)1. The mean percentage of the treated anterior chest wall surface area (TACWSA) with hypoesthesia to cold stimulus was 52% (±29.3) on POD 0 and 55% (±19.7) on POD 1. Sensation returned over time, with hypoesthesia affecting 11.1% (±15.5) TACWSA at 6 months. At study completion 58% of patients (26/45) had complete return of sensation; hypoesthesia was found at: 1 dermatome 13% (2/45), 2 dermatomes 22% (11/45), and 3 dermatomes 4% (2/45). Neuropathic pain (S-LANSS ≥12) was documented in 16% (9/55) of patients at hospital discharge but decreased to 6.7% of patients at 6 months. Onset of skin hypoesthesia after cryoablation occurred on POD0 and affected 52% of the TACWSA. All patients experienced return of sensation to varying degrees, with 58% experiencing normal sensation in all dermatomes by 6 months. The etiology of persistent hypoesthesia to select dermatomes is unknown but may be related to operative technique or cryoablation. Chronic neuropathic pain is uncommon. II. Prognosis Study. [ABSTRACT FROM AUTHOR]

Charcot neuroarthropathy (CNA) is a progressive disease affecting the bones and joints of the foot that can lead to instability, breakdown, and collapse. Minimally invasive surgery (MIS) techniques are becoming a popular option within musculoskeletal surgery of the foot and ankle and may be an alternative to aggressive dissection seen during corrective surgery. An MIS approach minimizes vascular disruption, provides structural stability at an osteotomy or arthrodesis site, and encourages early mobilization if indicated. This retrospective study compares 17 patients who underwent an open approach for midfoot CNA reconstruction with 17 patients who underwent an MIS approach for midfoot CNA reconstruction. Preoperative and postoperative radiographic parameters were measured: lateral talus-first metatarsal, anteroposterior (AP) talus-first metatarsal, calcaneal pitch, and cuboid height. Difficulties that occurred during treatment were gathered and sorted into postoperative problems (stage I), obstacles (stage II), and complications (stage III). Changes from preoperative to postoperative radiographic lateral talus-first metatarsal and AP talus-first metatarsal angles were statistically significant (p <.001) for both the MIS and open approach. No true postoperative complications (stage III) were observed at last follow-up. The most common difficulty encountered was pin-site infection (stage I; in 23.5% of patients) in the MIS group. In the open group, the most common complications were wound development (stage I; 23.5%) and nonunions (stage II; 23.5%). Our findings suggest that midfoot CNA reconstruction with MIS methods offers similar outcomes to the open approach. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP), resulting from nerve injury, alters neural plasticity in spinal cord and brain via the release of inflammatory mediators. The remodeling of store‐operated calcium entry (SOCE) involves the refilling of calcium in the endoplasmic reticulum via STIM1 and Orai1 proteins and is crucial for maintaining neural plasticity and neurotransmitter release. The mechanism underlying SOCE‐mediated NP remains largely unknown. In this study, we found SOCE‐mediated calcium refilling was significantly higher during neuropathic pain, and the major component Orai1 was specifically co‐localized with neuronal markers. Intrathecal injection of SOCE antagonist SKF96365 remarkably alleviated nerve injury‐ and formalin‐induced pain and suppressed c‐Fos expression in response to innocuous mechanical stimulation. RNA sequencing revealed that SKF96365 altered the expression of spinal transcription factors, including Fos, Junb, and Socs3, during neuropathic pain. In order to identify the genes critical for SKF96365‐induced effects, we performed weighted gene co‐expression network analysis (WGCNA) to identify the genes most correlated with paw withdrawal latency phenotypes. Of the 16 modules, MEsalmon module was the most highly correlated with SKF96365 induced effects. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the enriched genes of MEsalmon module were significantly related to Toll‐like receptor signaling, steroid biosynthesis, and chemokine signaling, which may mediate the analgesic effect caused by SKF9636 treatment. Additionally, the SOCE antagonist YM‐58483 produced similar analgesic effects in nerve injury‐ and formalin‐induced pain. Our results suggest that manipulation of spinal SOCE signaling might be a promising target for pain relief by regulating neurotransmitter production and spinal transcription factor expression. [ABSTRACT FROM AUTHOR]

The etiology of polyneuropathies varies in the pediatric population, where hereditary or metabolic disorders are far more common than in adults. However, treatable polyneuropathies, also prevalent in these settings, are those to prioritize. Moreover, diagnosing subacute and chronic symptoms in children can be challenging compared to adults. Therefore, selecting the best and most relevant laboratory investigations and paraclinical studies is critical. This taskcan be relatively challenging in countries with limited resources or insurance coverage. This study describe the various types of polyneuropathies found in children and their characteristics and suggest an algorithm for using the best laboratory tests in the context of the Iranian healthcare system. [ABSTRACT FROM AUTHOR]

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The field of neuromuscular disorders is rapidly changing with new gene discoveries and disease modifying treatments changing the natural history of previously severe congenital disorders. The last ten years have seen new treatments move quickly into clinical practice. Early diagnosis and delivery of optimal standards of care is more crucial than ever now, so patients can get the best benefit from these new innovative treatments. This short article outlines some of the recent advances in diagnosis and treatment of congenital neuromuscular disorders including spinal muscular atrophy and Duchenne muscular dystrophy. It highlights areas of active research and the emerging therapies in limb girdle muscular dystrophies, Charcot Marie Tooth disease and congenital myasthenia syndromes. [ABSTRACT FROM AUTHOR]

The Neuropathy Score Reporting and Data System (NS-RADS) is a newly developed MR imaging-based classification that standardizes reporting and multidisciplinary communication for MR imaging diagnosis and follow-up of peripheral neuropathies. NS-RADS classification has shown to be accurate and reliable across different centers, readers' experience levels, and degrees of peripheral neuropathies, which include nerve injury, entrapment, neoplasm, diffuse neuropathy, post-interventional status, and temporal changes in muscle denervation. This article brings a practical review of NS-RADS classification, representative MR cases, and a step-by-step tutorial on how to approach this staging system. Readers can gain knowledge and apply it in their practice, aiming to standardize the communications between specialties and improve patient management. [ABSTRACT FROM AUTHOR]

The purpose of our study was to compare the 1-year revision surgery rates and outcomes of open versus endoscopic carpal tunnel release. Our hypothesis was that, compared to open release, endoscopic carpal tunnel release was an independent risk factor for revision surgery within 1-year. This was a retrospective cohort study of 4338 patients undergoing isolated endoscopic or open carpal tunnel release. Demographic data, medical comorbidities, surgical approach, need for revision surgery, hand dominance, history of prior injection, and Patient Reported Outcomes Measurement Information System upper extremity (UE), pain interference (PI) and physical function scores were analyzed. Multivariable analysis was used to identify the risk factors for revision surgery within one year of the index procedure. In total, 3280 patients (76%) underwent open and 1058 (24%) underwent endoscopic carpal tunnel release. Within one year of the index procedure, 45 patients required revision carpal tunnel release. The average time to revision was 143 days. The rate of revision carpal tunnel release in the open group was 0.71% compared to 2.08% in the endoscopic group. Multivariable analysis demonstrated that endoscopic surgery, male sex, cubital tunnel syndrome, tobacco use, and diabetes were associated independently with revision surgery. In this study, we found that endoscopic carpal tunnel release was associated independently with a 2.96 times greater likelihood of requiring revision carpal tunnel release within one year, compared to open carpal tunnel release. Male sex, concurrent cubital tunnel syndrome, tobacco use, and diabetes also were associated independently with greater risk of needing revision carpal tunnel release within one year. Prognostic II. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The incidence of microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy has increased in newly diagnosed diabetes patients. The aim of this study was to determine the factors affecting the incidence of microvascular complications in newly diagnosed patients with type 2 diabetes. PATIENTS AND METHODS: This study was conducted on 97 newly diagnosed type 2 DM patients who applied to Malatya Training and Research Hospital Endocrinology outpatient clinic between September 2021 and July 2022. The patient files were reviewed retrospectively and their age, height, weight, body mass index (BMI), fasting/postprandial blood glucose measurements, serum HDL cholesterol, LDL cholesterol, total cholesterol, triglyceride, HbA1c levels, glomerular filtration rate (GFR) and complications of retinopathy, nephropathy, and neuropathy were recorded. Mann-Whitney U, t-test, Kruskal-Wallis, Binary logistic regression analysis, and Chi-square analysis were used to analyze the data. RESULTS: The mean age of the patients included in the study was 47.40±7.78 (min: 23 - max: 62). Non-proliferative retinopathy was observed in 74.2% of patients, proliferative retinopathy in 25.8%, diffuse neuropathy in 49.5% and mononeuropathy was detected in 9.3% of them. Fasting blood glucose, postprandial blood glucose and HbA1c values were found to be higher in patients with proliferative retinopathy than in patients without retinopathy. Fasting blood glucose, postprandial blood glucose and HbA1c values were found to be higher in patients with neuropathy than in patients without neuropathy. In addition, patients with mononeuropathy had statistically significantly higher HbA1c values than patients with diffuse-type neuropathy. It was found that the urine protein values of patients with mononeuropathy were significantly higher than those without neuropathy and those with diffuse neuropathy. Each 0.677-unit increase in HbA1c increases the risk of proliferative retinopathy 1.98-fold, and every 1.018-unit increase increases the risk of neuropathy 2.76-fold. Proliferative retinopathy and mononeuropathy rates were discovered to be higher in patients with a family history. CONCLUSIONS: Microvascular complications are common in newly diagnosed T2DM patients and an increase in HbA1c is a significant risk factor. Every newly diagnosed T2DM patient should be screened for microvascular complications. [ABSTRACT FROM AUTHOR]

Charcot neuroarthropathy adversely affects the quality of life of diabetic patients with peripheral neuropathy and therefore early diagnosis is essential. The midfoot is the commonest site for Charcot deformity and can lead to ulceration, deep infection and amputation. The goal of treatment in Charcot arthropathy is to achieve a stable, plantigrade foot without infection and ulceration to allow for ambulation in the long term. The aim of this article is to review the classification of Charcot midfoot deformity and assess the role of non-operative and surgical measures in the management of these patients. We specifically reviewed the indications and literature around surgical exostectomy. [ABSTRACT FROM AUTHOR]

Mutations in the neurofilament light polypeptide gene (NEFL) are an uncommon cause of Charcot-Marie-Tooth disease (CMT). The aim of this study is to elucidate the clinical characteristics and genetic spectrum of NEFL -related neuropathy in a Taiwanese CMT cohort. Mutational analysis of the coding regions of NEFL was performed by Sanger sequencing or targeted resequencing. Twenty-one patients from nine CMT pedigrees, identified from a cohort of 508 unrelated CMT patients, were found to have a NEFL mutation. Genetic, clinical and electrophysiological features were analyzed. Six NEFL mutations were identified, including two novel ones (p.P8S, p.N98Y). NEFL p.E396K was the most common mutation, accounting for 33.3% of the patients in our cohort. All patients manifested sensorimotor polyneuropathy with a mean age of disease onset of 13.5 ± 9.6 (1–40) years. Their motor nerve conduction velocities (MNCVs) of the ulnar nerve ranged from 22.1 to 48.7 m/s. Seventy percent of the patients could be classified as intermediate CMT with ulnar MNCVs between 25 and 45 m/s. Six of the 21 patients (28.6%) had additional features of central nervous system (CNS) involvement, including motor developmental delay, spasticity, cerebellar signs, neuropathic pain and scoliosis. NEFL mutations account for 1.8% (9/508) of the CMT patients in Taiwan. The present study delineates the clinical and genetic characteristics of NEFL -related neuropathy in Taiwan, and highlights that ulnar MNCV above 25 m/s and CNS involvement may serve as diagnostic clues for NEFL -related neuropathy. [ABSTRACT FROM AUTHOR]

Background. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nervous system disease associated with polyautoimmunity. Case. We report a previously healthy 13-year old boy who was referred to our outpatient clinic with gait disturbance and distal lower limb weakness that had been increasing for six months. The patient had decreased deep tendon reflexes in the upper extremities and absence in the lower extremities, reduced muscle strength in the distal and proximal lower extremities, muscle atrophy, drop foot, and normal pinprick sensations. The patient was diagnosed with CIDP as a result of clinical findings and electrophysiological studies. Autoimmune diseases and infectious agents were investigated in terms of triggering CIDP. Although there was no clinical sign other than polyneuropathy, he was also diagnosed with Sjögren's syndrome due to positive antinuclear antibodies and antibodies against Ro52, and with autoimmune sialadenitis. After six months of monthly intravenous immunoglobulin and oral methylprednisolone treatments, the patient was able to dorsiflex his left foot and walk without support. Conclusions. To our knowledge, our case is the first pediatric case with the coexistence of Sjögren's syndrome and CIDP. Therefore, we suggest investigating children with CIDP in terms of underlying autoimmune diseases such as Sjögren's syndrome. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates still vary across centers.Methods: Patients with a suspected hereditary NMD were referred to neuromuscular specialists at the National Taiwan University Hospital. Molecular diagnoses were performed by employing a capture panel containing 194 genes associated with NMDs.Results: Among the 50 patients referred, 43 had a suspicion of myopathy, and seven had polyneuropathy. The overall diagnostic rate was 58%. Pathogenic variants in 19 genes were observed; the most frequent pathogenic variant found in this cohort (DYSF) was observed in only four patients, and 10 pathogenic variants were observed in one patient each. One case of motor neuron disease was clinically mistaken for myopathy. A positive family history increased the diagnostic rate (positive: 72.7% vs. negative: 56.3%). Fourteen patients with elevated plasma creatine kinase levels remained without a diagnosis.Conclusion: The application of NGS in this single-center study proves the great diversity of hereditary NMDs. A capture panel is essential, but high-quality clinical and laboratory evaluations of patients are also indispensable. [ABSTRACT FROM AUTHOR]

OBJECTIVE: PSMD9 is a ubiquitous protein present at high concentrations in eukaryotic cells. It contributes to the degradation of intracellular proteins in the immune system. It is part of the 26S proteasome complex, and its regulatory role on proteasomal activity as well as its effect on genetic transcription have been recognized. PSMD9 has been related with insulin secretion, and it regulates the ligand-dependent retinoid-target genes transcription. Importantly, PSMD9 rs74421874 (IVS3+nt460-G>A), rs3825172 (IVS3+nt437-C>T), and rs14259 SNPs have been previously linked to type 2 diabetes (T2D), maturity-onset diabetes of the young 3 (MODY3), overweight status and waist circumference, hypertension, hypercholesterolemia, cardiovascular disease, microvascular disease (retinopathy, neuropathy, and nephropathy), carpal tunnel syndrome, depression, anxiety, insomnia, and sleep hours. MATERIALS AND METHODS: In this study, we analyzed the above-mentioned PSMD9 rs74421874 (IVS3+nt460-G>A), rs3825172 (IVS3+nt437-C>T), and rs14259 SNPs for linkage to the T2D quantitative traits of T2D age of onset, duration in years of combined oral hypoglycemic agents and insulin therapy and only insulin therapy, stress, and the birth weight of the subjects’ children; and with the T2D qualitative phenotypes of irregular menses, couple infertility, and menopausal hot flashes. RESULTS: We found that PSMD9 was linked to irregular menses of reproductive age, menopausal hot flashes, T2D age of onset, years of combined oral and insulin therapy and of insulin therapy; we also found that it shows only a tendency towards linkage to stress, birthweight, and couple infertility. CONCLUSIONS: This is the first time that this gene is implicated with irregular menses of reproductive age (a trait of polycystic ovarian syndrome), hot flashes, T2D onset age, and duration years of combined oral and insulin therapy and only insulin therapies. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An 8-y-old Labrador Retriever dog had mild ataxia of the hindlimbs 4 mo after lumbosacral dorsal laminectomy for intervertebral disk disease. Ataxia of the hindlimbs gradually worsened over the next 6 y. On autopsy, gross lesions were not recognized in the spinal cord. Histopathology revealed an intradural extraparenchymal cholesterol granuloma in the cauda equina associated with remnant nerve roots. Nerves associated with the cholesterol granuloma had axonal degeneration, myelin vacuolation, and edema. In those foci, macrophages were increased in number between nerve fibers. Immunohistochemistry for neurofilament protein and Luxol fast blue staining highlighted the presence of remnant axons and myelin sheaths within the granuloma. Inflammatory cell infiltrates in the granuloma were mainly macrophages and CD3- or CD20-immunopositive T or B lymphocytes, respectively. We conclude that the cholesterol granuloma likely formed subsequent to degenerative neuropathy in the cauda equina. [ABSTRACT FROM AUTHOR]

Chronic elbow pain can be osseous, soft tissue, cartilaginous, and nerve related in etiology. Imaging plays an important role in differentiating between these causes of chronic elbow pain. This document provides recommendations for imaging of chronic elbow pain in adult patients. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]

Episodic weakness is typically associated with a group of disorders so called periodic paralyses. Their major causes are mutation of ion channels, and have rarely been linked to mitochondrial disorders. We report a 20-year-old man with episodic weakness and axonal sensorimotor neuropathy since the age of 10 years. Analysis of the next generation sequencing data of the entire mitochondrial genome extracted from the blood revealed a homoplasmic m.9185T > C variant in MT-ATP6. Acetazolamide may be responsive for episodic weakness, and supplements with l-carnitine with coenzyme-Q10 seem to be beneficial as well. To the best of our knowledge, this is the first report in Taiwan which reveals episodic weakness and sensorimotor polyneuropathy as a unique phenotype of MT-ATP6 mutations. [ABSTRACT FROM AUTHOR]

Mycobacterium leprae causes leprosy and can impair peripheral nerves. If nerve function is damaged and is not treated immediately and effectively, it can cause disability. Hence, early detection of peripheral neuropathy is critical. Toronto Clinical Scoring System (TCSS) is a simple neuropathy assessment instrument for diabetic neuropathy, chemotherapy-induced peripheral neuropathy, and human immunodeficiency virus neuropathy. Therefore, TCSS is expected to be an alternative tool for diagnosing leprosy neuropathy. This study aims to determine the diagnostic value of TCSS in leprosy neuropathy. This is a cross-sectional observational study with 40 participants. The TCSS and Semmes–Weinstein Monofilament tests were used to assess neuropathy. The diagnostic analysis showed that the sensitivity was 85.7%, specificity was 84.2%, positive predictive value was 85.7%, negative predictive value was 84.2%, positive likelihood ratio (LR+) was 5.42, negative (LR-) was 0.17, accuracy was by 85%, and area under curve value of 93.2%. The optimal cut-off point score of TCSS is ≥6. It can be concluded that TCSS is an alternative diagnostic tool with a high accuracy value and can be used as a routine examination for the early detection of leprosy neuropathy. [ABSTRACT FROM AUTHOR]

Intraoperative fluorescence angiography with indocyanine green or fluorescein is used in ophthalmology and neurosurgery. However, there are few reports on the use of fluorescence angiography for peripheral neuropathy. This study aimed to assess the validity of fluorescein angiography (FAG) for peripheral nerve entrapment neuropathy. We used an established model of chronic nerve compression (CNC) neuropathy in C57BL/6 mice by entrapping their left sciatic nerve with a silastic tube. Mice were assigned to the uninjured group (control), two-week CNC neuropathy group, four-week CNC neuropathy group, or six-week CNC neuropathy group. We then performed FAG to assess neural blood flow and quantified the peak of the luminance at the compression site with luminance analysis software. Following FAG, histological examinations using an anti-fluorescein antibody and Masson's trichrome staining were performed to evaluate the area of fluorescein distribution and epineural fibrosis. The luminance in the CNC neuropathy groups was significantly lower than that in the control group. Histological analysis revealed the fluorescein positive areas in the CNC neuropathy groups were significantly smaller than that in the control group, and the epineural fibrosis areas in the CNC neuropathy groups were significantly larger than that in the control group. We observed a significant decline of luminance in the CNC neuropathy groups, and the histological assessment was consistent with this result. FAG was found to be a valid method for assessing CNC neuropathy in mice. [ABSTRACT FROM AUTHOR]

It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with type 1 diabetes. To investigate bladder function using non-invasive urodynamics as a potential indicator of autonomic neuropathy in adolescents with type 1 diabetes. This involved examining the association between urinary flow disturbances, reported symptoms, and results from other autonomic tests. Cross-sectional study enrolling 49 adolescents with type 1 diabetes and 18 control subjects. All participants underwent uroflowmetry and ultrasound scanning, completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire, and were instructed to record their morning urine volume and voiding frequencies and report them back. Cardiovascular reflex tests (CARTs) and the quantitative sudomotor axon reflex test (QSART) were performed. The main results are shown in the Summary figure. In this study, urological abnormalities were not significantly more frequent in adolescents with diabetes, however, urological issues were observed. This is supported by previous findings of Szabo et al. who found that adolescents with type 1 diabetes had reduced flow acceleration and time to maximum flow compared to control subjects. In our study, we observed cases with reduced acceleration and prolonged uroflow curves, possibly indicating detrusor underactivity. People with diabetes had a higher risk of nocturia than healthy controls, which our results supported. Some adolescents reported urination twice per night. Based on these findings, it is considered beneficial to ask about urological symptoms annually to determine if more examinations (frequency-volume charts and uroflowmetry) are necessary and/or if any opportunities for treatment optimization exist. However, uroflowmetry has limitations, as bladder filling and emptying is a complex process involving multiple pathways and neurological centers, making it difficult to standardize and evaluate. Another limitation of this study was that our control group was smaller and consisted of fewer males than females, which could affect the results due to differences in anatomy and physiology in the lower urinary tract system. In conclusion, adolescents with type 1 diabetes, as well as healthy adolescents, frequently experience urological symptoms. Although urological abnormalities were not significantly more frequent in adolescents with diabetes in this study, the focus on nocturia and risk for bladder dysfunction seems relevant, even in adolescents without any other tests indicating autonomic dysfunction. [Display omitted] [ABSTRACT FROM AUTHOR]

Optic neuropathies were estimated to affect 115 in 100,000 population in 2018. Leber's Hereditary Optic Neuropathy (LHON) as one of such optic neuropathy diseases that was first identified in 1871 and can be defined as a hereditary mitochondrial disease. LHON is associated with three mtDNA point mutations which are G11778A, T14484, and G3460A that affect the NADH dehydrogenase subunits of 4, 6, and 1, respectively. However, in most cases, only one point mutation is involved. Generally, in manifestation of the disease, there are no symptoms until the terminal dysfunction in the optic nerve is observed. Due to the mutations, nicotinamide adenine dinucleotide (NADH) dehydrogenase or complex I is absent and thus ATP production is stopped. This further causes the generation of reactive oxygen species and retina ganglion cells apoptosis. Aside from the mutations, there are several environmental factors such as smoking and alcohol consumption that can be pointed out as the risk factors of LHON. Nowadays, gene therapy has been intensively studied for LHON treatment. Disease models using human induced pluripotent stem cells (hiPSCs) have been utilized for LHON research. [ABSTRACT FROM AUTHOR]

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Coronal plane hindfoot malalignment produces abnormal compensatory forces within the midfoot and forefoot. The primary aim of this study is to compare radiographic hindfoot alignment in patients with a midfoot Charcot event, and identify patterns associated with breakdown. A retrospective review of 43 patients (48 limbs) with midfoot Charcot neuroarthropathy were compared between the coronal hindfoot alignments and Charcot joint involvement. Coronal hindfoot alignment was classified as neutral (n = 15), valgus (n = 16), and varus (n = 17) utilizing the Saltzman hindfoot alignment radiograph. Charcot joint breakdown was classified as isolated tarsometatarsal joint (n = 8), combination of tarsometatarsal and naviculocuneiform joints (n = 22), and midtarsal joints including talonavicular and calcaneocuboid joints (n = 18). Patients exhibiting varus hindfoot alignment had 5.8 times greater risk of breakdown at the tarsometatarsal and naviculocuneiform joints (odds ratio 5.8, 95% confidence interval 1.7-22.9, p <.01). Hindfoot varus induces external rotation of the talus, resulting in compensation through the naviculocuneiform and tarsometatarsal joint, which correlates with our findings of a 6-fold increase in naviculocuneiform and tarsometatarsal joint collapse. Patients exhibiting valgus hindfoot alignment had 27 times greater risk of breakdown at the midtarsal joint (odds ratio 27.0; 95% confidence interval 5.6-207.0, p <.01). Hindfoot valgus induces internal rotation of the talonavicular joint, which correlates with our findings of a 27-fold increase in midtarsal joint breakdown. Varus and valgus hindfoot alignment are associated with different midfoot injury patterns, which may have implications in surgical management and allow for focused surveillance in neuropathic patients presenting with early-stage clinical findings consistent with Charcot neuroarthropathy. [ABSTRACT FROM AUTHOR]

Submuscular transposition (SMT) of the ulnar nerve is frequently performed as secondary procedure in patients with persistent or recurrent cubital tunnel syndrome (CuTS) despite previous surgery. Good results have been reported for this surgical strategy, but mainly in small retrospective case series. The goal of the present study is therefore to analyze the results prospectively using a patient-reported outcome measure (PROM): patient-rated ulnar nerve evaluation (PRUNE). SMT of the ulnar nerve was performed in 30 consecutive patients who were referred because of persistent or recurrent CuTS despite previous surgery. Objective outcome was measured in the outpatient clinic using the Likert scale. The PRUNE questionnaire was obtained pre-operatively, 6 weeks, 3 months, 6 months, and 12 months after the surgery. Simultaneously, 20 patients with primary surgery for CuTS, that underwent simple decompression, were followed. Good outcome (Likert 1 or 2) was obtained in 67% after SMT for persistent/recurrent CuTS and 85% after decompression as primary surgical treatment. PRUNE scores were significantly decreased in both groups at all follow-up moments after surgery compared with pre-operative for the total questionnaire and subscales "pain," "sensory/motor symptoms," and "specific activities." In both groups, PRUNE score remained stable until 12 months of follow-up. This prospective study confirms previous results from retrospective studies showing that SMT is an effective surgical option for persistent or recurrent CuTS. Prospective (randomized controlled) trials are needed to compare the effectiveness of SMT to the surgical alternative of subcutaneous transposition of the ulnar nerve. [ABSTRACT FROM AUTHOR]

The present aim was to estimate direct health care costs of patients suffering from post-traumatic trigeminal neuropathy (PTTN) and to compare the use of health care services, medications, and costs between temporary and persistent (>3 months) PTTN cohorts. A pre-existing clinical dataset of PTTN patients visiting a tertiary orofacial pain clinic in Belgium was utilized, including symptoms and quality of life measurements. Cost and resource utilization data were obtained by Belgium's largest health insurance provider for a period of 5 years after onset. Data from 158 patients was analyzed. The average cost per patient in the first year after injury was €2353 (IQR 1426–4499) with an out-of-pocket expense of 25% of the total cost. Hospitalization and technical interventions were the main drivers of cumulative costs, followed by consultation costs. For each cost category, expenditure was significantly higher in patients with persistent PTTN than in those with temporary PTTN (median 5-year total costs in persistent PTTN patients yielded €8866 (IQR 4368–18191) versus €4432 (IQR 2156–9032) in temporary PTTN, p <0.001) PTTN patients received repeated and frequent head and neck imaging (mean number of imaging investigations per patient was 10 ± 12). Medication consumption was high, with an unwarranted higher use of opioids and antibiotics in persistent PTTN patients. Within the limitations of this study, it seems there is a need for informing patients in detail on the inherent risks of nerve damage during dental and oromaxillofacial procedures. Every surgery should be preceded by a risk-benefit assessment in order to avoid unnecessary nerve damage. [ABSTRACT FROM AUTHOR]

The utility of electrodiagnostic tests (EDx) for patients with a high pretest probability of idiopathic median neuropathy at the carpal tunnel (IMNCT) based on characteristic symptoms and signs is debated. Decision-making and care strategies could be informed by a better understanding of factors associated with surgeon recommendations for electrodiagnostic testing. Ninety-one upper-extremity surgeons participated in an online, survey-based experiment. Participants viewed 7 vignettes of patients with carpal tunnel syndrome, with the following factors randomized in each vignette: patient age, gender, magnitude of incapability, symptom intensity and the presence of nocturnal symptoms, palmar abduction weakness, and positive provocative tests results. We sought patient and surgeon factors associated with ordering EDx and surgeon-rated comfort with performing carpal tunnel release (CTR) without EDx. Surgeons recommended EDx for over half of the patient vignettes, with notable variation (median, 57%; interquartile range, 14–100), and felt relatively neutral, on average, offering CTR without EDx. Twenty-six (29%) out of 91 surgeons ordered EDx for all patient scenarios, and 18 surgeons (20%) did not order testing for any scenario. A lower likelihood of EDx was associated with older age and positive provocative tests results. Greater surgeon comfort offering CTR without EDx was associated with older patients, the presence of nocturnal symptoms, palmar abduction weakness, and positive provocative tests results. Upper-extremity surgeons are neutral regarding diagnosing IMNCT based on electrodiagnostic evidence of pathology and are relatively more comfortable offering surgery without EDx in older patients that present with key aspects of carpal tunnel syndrome. There is notable variation in care, with half of all surgeons always or never ordering EDx. Future studies can investigate whether a treatment strategy offering surgery to patients with a high pretest probability of IMNCT and only using EDx in intermediate probability scenarios can limit use of testing without affecting patient health. [ABSTRACT FROM AUTHOR]

Copyright of Nosileftiki is the property of Hellenic Nurses' Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Hypertriglyceridemia is a risk factor for the development of small fibre damage. • Patients with hypertriglyceridemia had a higher neuropathy disability score (NDS). • Patients with hypertriglyceridemia had lower of CCM parameters compared to control. • Subjects with metabolic syndrome showed lower CCM parameters compared to control. Hypertriglyceridemia has been identified as a risk factor for diabetic neuropathy. Patients with hypertriglyceridemia underwent assessment of neuropathy and corneal confocal microscopy. 24 patients with severe hypertriglyceridemia defined as a triglyceride level more than 5.5 mmol/L (485 mg/dL) with no history of diabetes and 19 age-matched controls underwent assessment of HbA1c, blood pressure, fasting lipid profile, neuropathy disability score (NDS) and corneal confocal microscopy (CCM). Patients with hypertriglyceridemia had a significantly higher NDS (P<0.001) and lower CNFD (no./mm2) (27.1 [25.0-29.9] Vs 35.9 [31.2-40.6], p<0.001), CNBD (no./mm2) (55.4±22.3 Vs 91.6±30.8, p<0.001), CNFL (mm/mm2) (19.2±4.3 Vs 26.7±4.4, p<0.001) and IWL (mm/mm2) (24.3±6.9 Vs 36.6±10.0, p<0.001) compared to control subjects. In subjects with hypertriglyceridemia serum triglyceride levels correlated with CNFD (rho= -0.473, p=0.002), CNBD (rho= -0.341, p=0.043), CNFL (rho= -0.446, p=0.006) and IWL (rho= -0.408, p=0.034), no correlation was found between triglycerides and CCM parameters in subjects without hypertriglyceridemia. Subjects with metabolic syndrome had a lower CNFD (32.3 [29.2-37.5] Vs 27.1 [20.8-30.2] no./mm2, p=0.003), CNBD (20.1±6.0 Vs 23.9±5.3 no./mm2, p=0.036), CNFL (57.7±26.9 Vs 79.2±32.6 mm/mm2, p=0.037) and IWL (25.4±7.1 Vs 32.9±11.2 mm/mm2, p=0.036) compared to subjects without metabolic syndrome. Hypertriglyceridemia and metabolic syndrome are associated with small nerve fibre damage and clinical neuropathy. Elevated serum triglycerides may be a potential therapeutic target for the treatment of peripheral neuropathy. [ABSTRACT FROM AUTHOR]

This article examines the history of the policy concerning a class of diseases called intractable diseases in Japan with a particular focus on the roles of patient support groups in firstly legitimizing the grouping of such diseases and then shaping the nature of the support that the Japanese Ministry of Health and Welfare provided to the patients and their families affected by them. The Ministry started its policy on intractable diseases in 1972, predating the enactment of the 1983 Orphan Drug Act in the United States, which is known to be one of the most important events for the international rare diseases community. This policy decision was triggered by the emergence of subacute myelo-optic neuropathy (SMON) as a social problem in the country in the late 1960s. The Ministry first made its support available to patients with this particular disease and, as a result of a series of actions from patient support groups and their medical and political supporters, the same support was made available to those considered to be in similarly difficult circumstances. The way in which the support was arranged, however, turned out to be structurally divisive, inviting the patient groups to negotiate with the national and local governments separately depending on subject matters, and for about three decades since the start of the policy, they struggled to present their unified voice in the country. The governmental support for intractable diseases was finally revised in the mid-2000s, but as this article demonstrates, that became possible only after the patient groups came to realize the need of presenting a unified voice in their effort to improve the lives of those affected. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its different subtypes are linked to mutations in dozens of different genes. Mutations in gangliosideinduced differentiation-associated protein 1 (GDAP1) cause two types of CMT, demyelinating CMT4A and axonal CMT2K. The GDAP1-linked CMT genotypes are mainly missense point mutations. Despite clinical profiling and in vivo studies on the mutations, the etiology of GDAP1-linked CMT is poorly understood. Here, we describe the biochemical and structural properties of the Finnish founding CMT2K mutation H123R and CMT2K-linked R120W, both of which are autosomal dominant mutations. The disease variant proteins retain close to normal structure and solution behavior, but both present a significant decrease in thermal stability. Using GDAP1 variant crystal structures, we identify a side-chain interaction network between helices ⍺3, ⍺6, and ⍺7, which is affected by CMT mutations, as well as a hinge in the long helix ⍺6, which is linked to structural flexibility. Structural analysis of GDAP1 indicates that CMT may arise from disruption of specific intra- and intermolecular interaction networks, leading to alterations in GDAP1 structure and stability, and, eventually, insufficient motor and sensory neuron function. [ABSTRACT FROM AUTHOR]