Serum neurofilament light chain measurements following nerve trauma.

BACKGROUND: Optimal functional recovery following peripheral nerve injuries (PNIs) is dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in patient outcomes. Serum Neurofilament light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis, such as electromyography and/or magnetic resonance imaging assessments, but changes in serum NfL levels following traumatic PNI have not been investigated. This pre-clinical study aimed to determine whether serum NfL levels can: (1) detect the presence of a nerve trauma and (2) delineate between different severities of nerve trauma. METHODS: A rat sciatic nerve crush and common peroneal nerve crush were implemented as controlled animal models of nerve injury. At 1-, 3-, 7- and 21-days post-injury, serum samples were retrieved for analysis using the SIMOA® NfL analyser kit. Nerve samples were also retrieved for histological analysis. Static sciatic index (SSI) was measured at regular time intervals following injury. RESULTS: Significant 45-fold and 20-fold increases in NfL serum levels were seen 1-day post-injury following sciatic and common peroneal nerve injury, respectively. This corresponded with an eightfold higher volume of axons injured in the sciatic compared to the common peroneal nerve (p < .001). SSI measurements post-injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group. CONCLUSIONS: NfL serum measurements represent a promising method for detecting traumatic PNI and stratifying their severity. Clinical translation of these findings could provide a powerful tool to improve the surgical management of nerve-injured patients.

Ethylmalonic Encephalopathy: a literature review and two new cases of mild phenotype.

BACKGROUND: Ethylmalonic encephalopathy (EE) is a rare intoxication-type metabolic disorder with multisystem involvement. It is caused by mutations in ETHE1, which encodes the ETHE1 enzyme in the mitochondrial matrix that plays a key role in hydrogen sulfide (H2S) detoxification acting as a sulphur dioxygenase. RESULTS: This review focuses on the clinical, metabolic, genetic and neuroradiological features of 70 reported cases, including two new cases. The common manifestations of EE are psychomotor regression, hypotonia, developmental delay, petechia, pyramidal signs, chronic diarrhoea, orthostatic acrocyanosis and failure to thrive, respectively. A significant difference was found in EMA and C4 levels (p=0.003, p=0.0236) between classical and mild phenotypes. Urinary EMA, C4 and C5 levels were found to exhibit normal values in milder cases during attack-free periods. The most common ETHE1 gene homozygous state mutations were (p.R163Q) (c.488G>A), exon 4 deletion, (p.R163W)(c.487C>T), (p.Glu44ValfsTer62)(c.131_132delAG) and (p.M1I)(c.3G>T) mutations, respectively. Fifty-two patients underwent cranial MRI. Basal ganglia signal alterations were detected in 42 cases. Of the 70 cases, eight had a mild phenotype and slow neurological progression with low levels of ethylmalonic acid (EMA) and C4 acylcarnitine. The current age of alive patients in the published articles with mild phenotype was significantly higher than the classical phenotype. (p=0.002). Reducing the accumulation and inducing detoxification of sulfide is the main long-term treatment strategy for EE, including metronidazole, N-acetylcysteine (NAC), dietary modification, liver transplantation and continuous renal replacement therapy (CRRT). CONCLUSION: Measuring EMA and C4 acylcarnitine during metabolic attacks is critical to diagnosing EE, allowing for early treatment initiation to prevent further encephalopathic crises. Experience with liver transplantation, diet and CRRT, is currently limited. An early multidisciplinary approach with combination therapies is vital to prevent irreversible neurological damage.

Operative procedures for fissure in ano.

BACKGROUND: Reports of direct comparisons between operative techniques for anal fissure are variable in their results. These reports are either subject to selection bias (in non-randomized studies) or observer bias (in all studies) or have inadequate numbers of patients enrolled to answer the question of efficacy. OBJECTIVES: To determine the best technique for fissure surgery. SEARCH METHODS: The Cochrane Central Register of Controlled Trials and MEDLINE (1965-2011), Medline (Pubmed) and Embase were searched March to 2011. The list of cited references in all included reports and several study authors also were helpful in finding additional comparative studies.A total of four new trials were included in this update of the review. SELECTION CRITERIA: All reports in which there was a direct comparison between at least two operative techniques were reviewed and when more than one report existed for any given pair, that report was included. All studies must also be randomised. If crude data were not presented in the report, the authors were contacted and crude data obtained. DATA COLLECTION AND ANALYSIS: The two most commonly used end points in all reported studies were treatment failure and post-operative incontinence both to flatus and faeces. These are the only two endpoints included in the meta-analysis. MAIN RESULTS: Four trials, encompassing 406 patients were included in this update, with now a total of 2056 patients in the review from 27 studies that describe and analyze 13 different operative procedures. These operative techniques used by these studies include closed lateral sphincterotomy, open lateral internal sphincterotomy, anal stretch, balloon dilation, wound closure, perineoplasty, length of sphincterotomy and fissurectomy. Two new procedures in the update, similar to anal stretch were described- sphincterolysis and controlled intermittent anal dilatation. A new comparison was described, comparing the effects of unilateral internal sphincterotomy and bilateral internal sphincterotomy.Manual Anal stretch has a higher risk of fissure persistence than internal sphincterotomy and also a significantly higher risk of minor incontinence than sphincterotomy. The combined analyses of open versus closed partial lateral internal sphincterotomy show little difference between the two procedures both in fissure persistence and risk of incontinence Unilateral internal sphincterotomy was shown to be more likely to result in treatment failure compared to bilateral internal sphincterotomy, but there is no significant difference in the risk of incontinence.Sphincterotomy was less likely to result in treatment failure when compared to fissurectomy, but there was no significant difference when considering post-operative incontinence.When comparing sphincterotomy to sphincterolysis, there was no significant difference between the two procedures both in treatment failure and risk of incontinence; the same is the case when comparing sphincterotomy with controlled anal dilation. AUTHORS' CONCLUSIONS: Manual anal stretch should probably be abandoned in the treatment of chronic anal fissure in adults. For those patients requiring surgery for anal fissure, open and closed partial lateral internal sphincterotomy appear to be equally efficacious. More data are needed to assess the effectiveness of posterior internal sphincterotomy, anterior levatorplasty, wound suture or papilla excision. Bilateral internal sphincterotomy shows promise, but needs further research into its efficacy.