Response to the Letter to the Editor “Lipomatosis of nerve and overgrowth syndrome: an intriguing and still unclear correlation”

Abstract

To the editor, We appreciate the letter to the editor by Vetrano et al. [11] regarding our recent paper on lipomatosis of nerve (LN) [5]. Our grouphas been interested inLNaswell as other adipose lesions of nerves for many years [3, 4, 9]. First, we agree with the authors that there is a great inconsistency in the terminology in the world’s literature of LN. Besides the term lipomatosis of nerve,which has been proposed byWHO in 2002 [2], many other terms are regularly used including fibrolipomatous hamartoma, lipofibromatous hamartoma, neural lipoma, and macrodystrophia lipomatosa, for a spectrum of pathologies.This terminologyproblemwasoneof themajor reasons that we decided to compile the world’s literature and perform the systematic review(which included the recentcasebyVetranoetal. [10]). Our systematic review is now published in JNS [6]. This study strengthened the associationofLNandnerve-territoryovergrowth. We then utilized the raw data from this large database to conduct a follow-up study to analyze the presence (or absence) of nerve-territory overgrowth between two groups of cases (i.e., LN affecting so-called predominant sensory nerves and motor (mixed) nerves.)Webelieve that the findings reported in thepaper (i.e., predominance of motor (mixed) nerve affected by LN and associated nerve territory overgrowth present) is interesting and worthy of future investigation. Second, systematic reviewsarealwayssubject to limitations,as are all studies. Yet, reviews are able to achieve synthesis of often conflicting or confusing medical literature, which was our goal. We address the specific limitations of our systematic review, including the variable amount of information about individual cases reported in the articles (ranging from the available clinical information to the imaging (e.g., MRI and/or ultrasound), and the availability of operative photographs. As stated in the materials and methods section of our discussed paper, we performed Fisher’sexact test [1] for theanalysis,usingJMPsoftware (version 13,SAS Institute Inc.,Cary,NC). Fisher’s exact test is used for the analysis of dichotomous categorical variables. It is performed in situationswhenchi-square testwouldbe lessprecise suchaswhen one or more analyzed sample sizes are small (typically 5 or less) and/or when the samples are not normally distributed [8]. To address the authors’ comment regarding the Bimbalance between (affected)median nerve and all other nerves^, we nowperformed a separate statistical analysis excluding the twomajor sites of LN in themedian nerve (and branches) at thewrist/palm and the tibial nerve (andbranches) at the ankle/foot, includingonly cases affecting nerves proximal to those sites. This analysis consisted of 17 cases in thepredominant sensorygroup (15 superficial peroneal, 1 superficial branch of the radial, and 1 sural nerves; only 1 of these cases had overgrowth); and 50 cases in the mixed (motor) group (21proximalmedian,8proximalulnar,7brachialplexus,6sciatic, 3 tibial proximal toankle, 2proximal radial, 1 lumbosacral plexus, 1 obturator, and1 femoral nerve: in this subgroup, 26 did not have overgrowth and 24 had overgrowth). Statistical analysis (Fisher’s exact test performed in JMP software) also showed a statistical significantdifference, favoring themixed(motor)nervesandpresence of the overgrowth (p= 0.0015), consistent with the 2 other statistical analyses reported in our paper [5]. Third, we strongly agree with their advocacy of advanced imaging techniques to promote diagnosing LN. In their recent case report [10], they described their experience with diffusion tensor imaging (DTI) to diagnose LN. This form of functional imaging, This article is part of the Topical Collection on Peripheral Nerves