JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM

Vitamin D levels do not correlate with severity of idiopathic peripheral neuropathy
Morrison AH, Hoke M, Thomas S, Chaudhry V, Polydefkis M, and Höke A
Peripheral neuropathy (PN) is a common neurological condition in elderly adults. Vitamin D deficiency has been associated with diabetic and chemotherapy-induced neuropathy, but its role in idiopathic PN, in which no underlying cause of neuropathy can be identified, has not been investigated.
Long-term safety and tolerability of hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: Results from the ADVANCE-CIDP 3 trial
Hadden RDM, Andersen H, Bril V, Basta I, Rejdak K, Duff K, Greco E, Hasan S, Anderson-Smits C and Ay H
Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) consists of subcutaneous human immunoglobulin G (IgG) 10% with recombinant human hyaluronidase (rHuPH20) and can be administered at the same dose and interval as intravenous IgG (IVIG). fSCIG recently received US approval as maintenance therapy for adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and European approval for adults and children with CIDP after stabilization with IVIG.
Physical exercise halts further functional decline in an animal model for Charcot-Marie-Tooth disease 1X at an advanced disease stage
Klein D, Yépez MG and Martini R
Charcot-Marie-Tooth (CMT) type 1 neuropathies are the most common inherited diseases of the peripheral nervous system. Although more than 100 causative genes have been identified so far, therapeutic options are still missing. We could previously identify that early-onset physical exercise (voluntary wheel running, VWR) dampens peripheral nerve inflammation, improves neuropathological alterations, and clinical outcome in Cx32def mice, a model for CMT1X. We here investigate the clinical and histopathological effect of late-onset exercise in Cx32def mice at an advanced disease stage.
Assessing corneal dendritic cells in glucose dysregulation small-fibre neuropathy
Idiaquez JF, Barnett-Tapia C, Perkins BA and Bril V
Small-fibre neuropathy (SFN) is associated with glucose dysregulation, including impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Corneal confocal microscopy (CCM) offers a non-invasive tool to assess corneal nerve damage and dendritic cell density (DCD). In this study, we investigated corneal DCD in patients with SFN and glucose dysregulation, defined as IGT or T2D.
Reply to "Nerve ultrasound as a screening tool for inherited sensory neuronopathy"
Salvalaggio A, Cacciavillani M, Tierro B and Briani C
Nerve ultrasound as a screening tool for inherited sensory neuronopathy
Pelosi L and Roxburgh R
Neuralgic amyotrophy presentation of acute intermittent porphyria: A case report
Theuriet J, Gerfaud-Valentin M, Durel CA, Gouya L and Pegat A
Porphyrias are inherited metabolic disorders caused by mutations in genes encoding enzymes involved in the heme biosynthetic pathway, leading to the accumulation of heme precursors. Acute hepatic porphyrias (AHP), including acute intermittent porphyria (AIP), can present with predominant peripheral neurological manifestations, often leading to a misdiagnosis as Guillain-Barré syndrome.
Paclitaxel alters the microvascular network in the central and peripheral nervous system of rats with chemotherapy-induced painful peripheral neuropathy
Zippo AG, Rodriguez-Menendez V, Pozzi E, Canta A, Chiorazzi A, Ballarini E, Monza L, Alberti P, Meregalli C, Bravin A, Coan P, Longo E, Saccomano G, Paiva K, Tromba G, Cavaletti G and Carozzi VA
Chemotherapy-induced peripheral neurotoxicity (CIPN), with paraesthesia, numbness, dysesthesia and neuropathic pain ranks among the most common dose-limiting toxicity of several widely used anticancer drugs. Recent studies revealed the microvascular angiogenesis as a new important actor, beside peripheral neurons, in the neurotoxicity and neuropathic pain development and chronicisation. The aim of this work is to elucidate the role of vascular alterations in CIPN.
Glucose-lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes
Ponirakis G, Al-Janahi I, Elgassim E, Hussein R, Petropoulos IN, Gad H, Khan A, Zaghloul HB, Siddique MA, Ali H, Mohamed FFS, Ahmed LHM, Dakroury Y, El Shewehy AMM, Saeid R, Mahjoub F, Al-Thani SN, Ahmed F, Homssi M, Mahmoud S, Hadid NH, Obaidan AA, Salivon I, Mahfoud ZR, Zirie MA, Al-Ansari Y, Atkin SL and Malik RA
Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN.
Knowledge gaps in diagnosing chronic polyneuropathy: Review of national guidelines
Wiersma M, van der Star GM, Notermans NC, van Doorn PA, Vrancken AFJE and
The prevalence of chronic polyneuropathy will increase due to the aging population, and therefore, it becomes ever so important to optimize the diagnostic process. However, it is uncertain which blood tests are required and when nerve conduction studies (NCS) should be done in the workup of chronic polyneuropathy. We aimed to investigate the methodology used to develop national polyneuropathy guidelines and to provide an overview and strength of evidence of the recommendations. We searched PubMed and websites of national neurological associations as listed on the website of the World Federation of Neurology to identify national guidelines pertaining to the workup of chronic polyneuropathy by neurologists in an outpatient clinic setting. We identified three national guidelines in the United States and seven national guidelines in Denmark, France, Germany, the Netherlands, Norway, Spain, and Turkey. The methodology used to develop the guidelines differed greatly. All guidelines recommend a series of blood tests. Some guidelines advise to conduct NCS in all patients, while other guidelines advise to conduct NCS when certain symptoms are present. There is variation in recommendations about the extensiveness of NCS, but all mention measuring the sural nerve and the motor peroneal nerve. The evidence for the recommendations is graded as low. Despite some overlap, there are disparities between guidelines regarding the workup that is advised to do in patients with chronic polyneuropathy. It remains unclear which combination of blood tests are to be strongly recommended. Furthermore, it is undetermined whether NCS are always necessary.
Patient-reported disease burden in the Accelerate Clinical Trials in Charcot-Marie-Tooth Disease Study
Rehbein T, Purks J, Dilek N, Behrens-Spraggins S, Sowden JE, Eichinger KJ, , Burns J, Pareyson D, Scherer SS, Reilly MM, Shy ME, McDermott MP, Heatwole CR and Herrmann DN
The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden.
The NCX1 calcium exchanger is implicated in delayed axotomy after peripheral nerve stretch injury
Wilhelmy B, Gerzanich V, Simard JM and Stokum JA
After peripheral nerve stretch injury, most degenerating axons are thought to become disconnected at the time of injury, referred to as primary axotomy. The possibility of secondary axotomy-a delayed and potentially reversible form of disconnection-has not been evaluated. Here, we investigated secondary axotomy in a rat model of sciatic nerve stretch injury. We also evaluated whether axon sparing and functional improvement results from pharmacological blockade of the sodium-calcium exchanger 1 (NCX1), which is widely believed to contribute to traumatic axon degeneration but was previously only investigated in vitro.
Focal slowing of nerve conduction velocity in leprosy patients unveiled through multisegmented nerve analysis
Daccach V, Tomaselli PJ, Algemiro JS, Toscano P, Dos Santos ACJ, Frade MAC and Marques W
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of M. leprae, particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols.
Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study
Burgess J, Marshall A, Rapteas L, Hamill KJ, Marshall A, Malik RA, Frank B and Alam U
To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings.
Peripheral neuropathy, an independent risk factor for falls in the elderly, impairs stepping as a postural control mechanism: A case-cohort study
Kohle F, Stark C, Klünter HD, Wernicke D, Wunderlich G, Fink GR, Klussmann JP, Schroeter M and Lehmann HC
Peripheral neuropathies perturbate the sensorimotor system, causing difficulties in walking-related motor tasks and, eventually, falls. Falls result in functional dependency and reliance on healthcare, especially in older persons. We investigated if peripheral neuropathy is a genuine risk factor for falls in the elderly and if quantification of postural control via posturography is helpful in identifying subjects at risk of falls.
Nerve ultrasound in CANVAS-spectrum disease: Reduced nerve size distinguishes genetically confirmed CANVAS from other axonal polyneuropathies
Salvalaggio A, Cacciavillani M, Tierro B, Coraci D, Currò R, Ferrarini M, Pegoraro E, Bello L, Fabrizi GM, Filla A, Padua L, Manganelli F, Cortese A and Briani C
Ultrasound nerve cross-sectional area (CSA) of patients affected with axonal neuropathy usually shows normal value. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) seems to represent an exception, showing smaller CSA, but previous reports did not test for biallelic RFC1 gene repeat expansions.
Clinical and genetic features of CMT2T in Italian patients confirm the importance of MME pathogenic variants in idiopathic, late-onset axonal neuropathies
Geroldi A, La Barbera A, Mammi A, Origone P, Gaudio A, Ponti C, Sanguineri F, Matà S, Sperti M, Carboni I, Bellone E, Gotta F, Gemelli C, Massucco S, Valeria G, Marinelli L, Grandis M, Bisogni G, Sabatelli M, Piscosquito G, Esposito G, Schenone A, Manganelli F, Mandich P, Tozza S and Luigetti M
Since 2016, biallelic mutations in the membrane metalloendopeptidase (MME) gene have been associated with late-onset recessive CMT2 (CMT2T). More recently, heterozygous mutations have also been identified in familial and sporadic patients with late-onset axonal neuropathy, ranging from subclinical to severe. This indicates that the heterozygous MME variants may not be fully penetrant, or alternatively, that they may be a potential risk factor for neuropathy. Here, we describe the clinical, neurophysiological, and genetic findings of 32 CM2T Italian patients.
Correction to "Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study"
Oxygen matters: Unraveling the role of oxygen in the neuronal response to cisplatin
Crugeiras J, Calls A, Contreras E, Alemany M, Navarro X, Yuste VJ, Casanovas O, Udina E and Bruna J
Cell culture is a fundamental experimental tool for understanding cell physiology. However, translating these findings to in vivo settings has proven challenging. Replicating donor tissue conditions, including oxygen levels, is crucial for achieving meaningful results. Nevertheless, oxygen culture conditions are often overlooked, particularly in the context of chemotherapy-induced neurotoxicity.
Association of dynamic hepatic metabolism with clinical outcomes in patients with severe Guillain-Barré syndrome: A prospective cohort study from multi-centers in China
Xie J, Yu H, Lv W, Li K, Li H, Ji Y, Cai Y, Cheng Y, Luo L, Wu C, Xu Y, Du L, Chen Y, Pang C and Deng B
Little is known about the ability of serological biomarkers to monitor clinical outcomes in patients with Guillain-Barré syndrome (GBS). The objective of this study was to determine the associations of liver function, easily available and convenient biomarkers, with the clinical course and outcome of severe GBS in patients.
Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy
Vittert AB, Daniel M, Svientek SR, Risch MJ, Nelson NS, Donneys A, Dehdashtian A, Sacks GN, Buchman SR and Kemp SWP
Radiation-induced peripheral neuropathy is a rare, but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation-induced peripheral neuropathy has not been established. The purpose of the present study was to examine neuropathic pain, sensorimotor impairment, and muscle force parameters following the administration of a clinically relevant radiation dose in a rat model.