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2 pages, 177 KiB

Open AccessEditorial

Nerve Biopsy in Peripheral Neuropathies: Not All Water Is under the Bridge

by Marco Luigetti and Andrea Di Paolantonio

Brain Sci. 2021, 11(5), 550; https://doi.org/10.3390/brainsci11050550 - 27 Apr 2021

Viewed by 1450

Abstract

Sural nerve biopsy has long been a valuable diagnostic tool for the study of peripheral neuropathies, although the recent introduction of non-invasive techniques (e.g., neuroimaging techniques, skin biopsy) and advanced genetic and immunological testing has changed the diagnostic workup of peripheral nervous system [...] Read more.

Sural nerve biopsy has long been a valuable diagnostic tool for the study of peripheral neuropathies, although the recent introduction of non-invasive techniques (e.g., neuroimaging techniques, skin biopsy) and advanced genetic and immunological testing has changed the diagnostic workup of peripheral nervous system diseases. [...] Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

Research

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11 pages, 1231 KiB

Open AccessArticle

Addressing the Need of a Translational Approach in Peripheral Neuropathy Research: Morphology Meets Function

by Laura Monza, Giulia Fumagalli, Alessia Chiorazzi and Paola Alberti

Brain Sci. 2021, 11(2), 139; https://doi.org/10.3390/brainsci11020139 - 22 Jan 2021

Cited by 8 | Viewed by 2419

Abstract

Peripheral neuropathies (PNs) are a type of common disease that hampers the quality of life of affected people. Treatment, in most cases, is just symptomatic and often ineffective. To improve drug discovery in this field, preclinical evidence is warranted. In vivo rodent models [...] Read more.

Peripheral neuropathies (PNs) are a type of common disease that hampers the quality of life of affected people. Treatment, in most cases, is just symptomatic and often ineffective. To improve drug discovery in this field, preclinical evidence is warranted. In vivo rodent models allow a multiparametric approach to test new therapeutic strategies, since they can allow pathogenetic and morphological studies different from the clinical setting. However, human readouts are warranted to promptly translate data from the bench to the bedside. A feasible solution would be neurophysiology, performed similarly at both sides. We describe a simple protocol that reproduces the standard clinical protocol of a neurophysiology hospital department. We devised the optimal montage for sensory and motor recordings (neurography) in mice, and we also implemented F wave testing and a short electromyography (EMG) protocol at rest. We challenged this algorithm by comparing control animals (BALB/c mice) with a model of mild neuropathy to grasp even subtle changes. The neurophysiological results were confirmed with neuropathology. The treatment group showed all expected alterations. Moreover, the neurophysiology matched the neuropathological analyses. Therefore, our protocol can be suggested to promptly translate data from the bench to the bedside and vice versa. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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9 pages, 1424 KiB

Open AccessCommunication

Peripheral Neuropathies Seen by Ultrasound: A Literature Analysis through Lexical Evaluation, Geographical Assessment and Graph Theory

by Daniele Coraci, Claudia Loreti, Augusto Fusco, Silvia Giovannini and Luca Padua

Brain Sci. 2021, 11(1), 113; https://doi.org/10.3390/brainsci11010113 - 16 Jan 2021

Cited by 13 | Viewed by 2475

Abstract

(1) Background: Ultrasound is a well-known tool used for the diagnosis and management of many diseases, including peripheral neuropathies. The main aim of this study was the lexical analysis of the literature on this topic considering the most cited words and the relationship [...] Read more.

(1) Background: Ultrasound is a well-known tool used for the diagnosis and management of many diseases, including peripheral neuropathies. The main aim of this study was the lexical analysis of the literature on this topic considering the most cited words and the relationship between the words and the papers. Furthermore, a geographical analysis was performed to evaluate the worldwide prevalence. (2) Methods: We performed a literature search on PubMed, and we calculated the occurrence of the words indicating nerves and the body parts. Furthermore, we calculated the number of papers for each country, considering the affiliation of the first author. Finally, to describe the relationships between the words and the papers, we used the 30 most cited words, and we built a matrix describing in which papers a word was cited. This matrix was used to create a network based on the graph theory using Gephi 0.9.2 software. (3) Results: The most cited nerves were median and ulnar ones, and the most cited body parts were hand, wrist and elbow. The United States of America was the most productive country, with 80 papers. The graph of the network showed the importance of ultrasound as support for therapy. (4) Conclusions: The study represents a lexical analysis of the literature and shows information about subjects, authors and relationships of the papers. This may be helpful for better understanding and evaluation of the situation of the current literature. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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11 pages, 1830 KiB

Open AccessArticle

Aberrant Splicing in GJB1 and the Relevance of 5′ UTR in CMTX1 Pathogenesis

by Federica Boso, Federica Taioli, Ilaria Cabrini, Tiziana Cavallaro and Gian Maria Fabrizi

Brain Sci. 2021, 11(1), 24; https://doi.org/10.3390/brainsci11010024 - 27 Dec 2020

Cited by 9 | Viewed by 3065

Abstract

The second most common form of Charcot-Marie-Tooth disease (CMT) follows an X-linked dominant inheritance pattern (CMTX1), referring to mutations in the gap junction protein beta 1 gene (GJB1) that affect connexin 32 protein (Cx32) and its ability to form gap junctions [...] Read more.

The second most common form of Charcot-Marie-Tooth disease (CMT) follows an X-linked dominant inheritance pattern (CMTX1), referring to mutations in the gap junction protein beta 1 gene (GJB1) that affect connexin 32 protein (Cx32) and its ability to form gap junctions in the myelin sheath of peripheral nerves. Despite the advances of next-generation sequencing (NGS), attention has only recently also focused on noncoding regions. We describe two unrelated families with a c.-17+1G>T transversion in the 5′ untranslated region (UTR) of GJB1 that cosegregates with typical features of CMTX1. As suggested by in silico analysis, the mutation affects the regulatory sequence that controls the proper splicing of the intron in the corresponding mRNA. The retention of the intron is also associated with reduced levels of the transcript and the loss of immunofluorescent staining for Cx32 in the nerve biopsy, thus supporting the hypothesis of mRNA instability as a pathogenic mechanism in these families. Therefore, our report corroborates the role of 5′ UTR of GJB1 in the pathogenesis of CMTX1 and emphasizes the need to include this region in routine GJB1 screening, as well as in NGS panels. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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12 pages, 4536 KiB

Open AccessArticle

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

by Marco Luigetti, Marina Romozzi, Giulia Bisogni, Davide Cardellini, Tiziana Cavallaro, Andrea Di Paolantonio, Gian Maria Fabrizi, Silvia Fenu, Luca Gentile, Marina Grandis, Gianluca Marucci, Sara Massucco, Anna Mazzeo, Davide Pareyson, Angela Romano, Massimo Russo, Angelo Schenone, Matteo Tagliapietra, Stefano Tozza, Giuseppe Vita and Mario Sabatelli Show full author list Hide full author list

Brain Sci. 2020, 10(11), 780; https://doi.org/10.3390/brainsci10110780 - 26 Oct 2020

Cited by 29 | Viewed by 2765

Abstract

Pathological evidence of amyloid on nerve biopsy has been the gold standard for diagnosis in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) for a long time. In this article, we reviewed the pathological findings of a large series of sural nerve biopsies from a cohort [...] Read more.

Pathological evidence of amyloid on nerve biopsy has been the gold standard for diagnosis in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) for a long time. In this article, we reviewed the pathological findings of a large series of sural nerve biopsies from a cohort of hATTR-PN patients, collected by different Italian referral centers. Patients and Methods: We reviewed clinical and pathological data from hATTR-PN patients, diagnosed and followed in five Italian referral centers for peripheral neuropathies. Diagnosis was formulated after a positive genetic test for transthyretin (TTR) mutations. Sural nerve biopsy was performed according to standard protocols. Results: Sixty-nine sural nerve biopsies from hATTR-PN patients were examined. Congo red positive deposits were found in 73% of cases. Only the Phe64Leu mutation failed to show amyloid deposits in a high percentage of biopsies (54%), as already described. Unusual pathological findings, such as myelin abnormalities or inflammatory infiltrates, were detected in occasional cases. Conclusions: Even if no longer indicated to confirm hATTR-PN clinical suspicion, nerve biopsy remains, in expert hands, a rapid and inexpensive tool to detect amyloid deposition. In Italy, clinicians should be aware that a negative biopsy does not exclude hATTR-PN, particularly for Phe64Leu, one of the most frequent mutations in this country. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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15 pages, 12509 KiB

Open AccessArticle

Pathological Findings in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Single-Center Experience

by Marco Luigetti, Angela Romano, Andrea Di Paolantonio, Giulia Bisogni, Salvatore Rossi, Amelia Conte, Francesca Madia and Mario Sabatelli

Brain Sci. 2020, 10(6), 383; https://doi.org/10.3390/brainsci10060383 - 17 Jun 2020

Cited by 10 | Viewed by 3670

Abstract

Objective: Segmental demyelination is the pathological hallmark of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but other elementary lesions are frequently observed, configuring a series of different pathological pictures. In this article, we review the pathological findings of a large series of sural nerve biopsies [...] Read more.

Objective: Segmental demyelination is the pathological hallmark of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but other elementary lesions are frequently observed, configuring a series of different pathological pictures. In this article, we review the pathological findings of a large series of sural nerve biopsies from our cohort of CIDP patients. Patients and Methods: Patients with CIDP who underwent nerve biopsy were retrospectively selected from those referred to the Institute of Neurology of the “Università Cattolica del Sacro Cuore” in Rome, Italy, from 1982 to February 2020. Sural nerve biopsy was performed according to standard protocols. Results: Sural nerve biopsy was performed in 43/130 CIDP patients. Demyelinating abnormalities and axonal loss were found in 67.4% and 83.7% of biopsies, respectively. Conversely, onion bulbs and inflammatory infiltrates were rare (18.6% and 4.7%, respectively). In three cases, we observed normal pathological findings. Conclusions: A pathognomonic pathological finding of CIDP cannot be established, but we confirm the utility of nerve biopsy in this setting to confirm the diagnosis (also in atypical phenotypes) and to elucidate pathogenic mechanisms. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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Review

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14 pages, 3017 KiB

Open AccessFeature PaperReview

Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

by Chiara Briani, Sergio Ferrari, Marta Campagnolo, Matteo Tagliapietra, Francesca Castellani, Alessandro Salvalaggio, Sara Mariotto, Andrea Visentin and Tiziana Cavallaro

Brain Sci. 2021, 11(2), 132; https://doi.org/10.3390/brainsci11020132 - 20 Jan 2021

Cited by 11 | Viewed by 3490

Abstract

Despite the introduction of non-invasive techniques in the study of peripheral neuropathies, sural nerve biopsy remains the gold standard for the diagnosis of several neuropathies, including vasculitic neuropathy and neurolymphomatosis. Besides its diagnostic role, sural nerve biopsy has helped to shed light on [...] Read more.

Despite the introduction of non-invasive techniques in the study of peripheral neuropathies, sural nerve biopsy remains the gold standard for the diagnosis of several neuropathies, including vasculitic neuropathy and neurolymphomatosis. Besides its diagnostic role, sural nerve biopsy has helped to shed light on the pathogenic mechanisms of different neuropathies. In the present review, we discuss how pathological findings helped understand the mechanisms of polyneuropathies complicating hematological diseases. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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19 pages, 16781 KiB

Open AccessReview

Contribution of Skin Biopsy in Peripheral Neuropathies

by Maria Nolano, Stefano Tozza, Giuseppe Caporaso and Vincenzo Provitera

Brain Sci. 2020, 10(12), 989; https://doi.org/10.3390/brainsci10120989 - 15 Dec 2020

Cited by 25 | Viewed by 4670

Abstract

In the last three decades the study of cutaneous innervation through 3 mm-punch-biopsy has provided an important contribution to the knowledge of small fiber somatic and autonomic neuropathies but also of large fiber neuropathies. Skin biopsy is a minimally invasive technique with the [...] Read more.

In the last three decades the study of cutaneous innervation through 3 mm-punch-biopsy has provided an important contribution to the knowledge of small fiber somatic and autonomic neuropathies but also of large fiber neuropathies. Skin biopsy is a minimally invasive technique with the advantage, compared to sural nerve biopsy, of being suitable to be applied to any site in our body, of being repeatable over time, of allowing the identification of each population of nerve fiber through its target. In patients with symptoms and signs of small fiber neuropathy the assessment of IntraEpidermal Nerve Fiber density is the gold standard to confirm the diagnosis while the quantification of sudomotor, pilomotor, and vasomotor nerve fibers allows to evaluate and characterize the autonomic involvement. All these parameters can be re-evaluated over time to monitor the disease process and to evaluate the effectiveness of the treatments. Myelinated fibers and their receptors can also be evaluated to detect a “dying back” neuropathy early when nerve conduction study is still normal. Furthermore, the morphometry of dermal myelinated fibers has provided new insight into pathophysiological mechanisms of different types of inherited and acquired large fibers neuropathies. In genetic neuropathies skin biopsy has become a surrogate for sural nerve biopsy, no longer necessary in the diagnostic process, to study genotype–phenotype correlations. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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Other

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8 pages, 213 KiB

Open AccessOpinion

Neuropathic Pain Related to Peripheral Neuropathies According to the IASP Grading System Criteria

by Giulia Di Stefano, Andrea Di Lionardo, Giuseppe Di Pietro and Andrea Truini

Brain Sci. 2021, 11(1), 1; https://doi.org/10.3390/brainsci11010001 - 22 Dec 2020

Cited by 15 | Viewed by 3239

Abstract

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system. Neuropathic pain represents a broad category of pain conditions, common complications of peripheral neuropathies, which are characterized by a combination of positive symptoms, including paresthesia and/or dysesthesia [...] Read more.

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system. Neuropathic pain represents a broad category of pain conditions, common complications of peripheral neuropathies, which are characterized by a combination of positive symptoms, including paresthesia and/or dysesthesia and sensory deficits in the painful area. In the present paper, we aimed to assess neuropathic pain frequency and clinical characteristics of peripheral neuropathies due to different aetiologies according to grading system criteria of the International Association for the Study of Pain for a definitive diagnosis of neuropathic pain. Epidemiological studies applying these criteria have been conducted in patients with diabetes, brachial plexus injury, and other traumatic nerve injuries. Neuropathic pain was diagnosed in 37–42% of patients with diabetic peripheral neuropathy, 56% of patients with brachial plexus injury, and 22% of patients with intercostobrachial neuropathy. The most frequent neuropathic pain type was ongoing pain (described as burning or pressing), followed by paroxysmal pain (electric shock-like sensations) and allodynia (pain evoked by brushing and pressure). By providing information on the frequency, clinical signs, and variables associated with neuropathic pain due to different aetiologies, these studies contribute to improving the clinical management of this condition. Full article

(This article belongs to the Special Issue Pathology of Peripheral Neuropathies )

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