Non‐motor involvement in amyotrophic lateral sclerosis: new insight from nerve and vessel analysis in skin biopsy

Nolano, Maria; Provitera, Vincenzo; Manganelli, Fiore; Iodice, Rosa; Caporaso, Giuseppe; Stancanelli, Annamaria; Marinou, Kalliopi; Lanzillo, B.; Santoro, Lucio; Mora, Gabriele

doi:10.1111/nan.12332

Cited by 53 publications

(39 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IENFD has been reported to be reduced also in other painful conditions, such as Guillain‐Barré syndrome, meralgia paraesthestica, notalgia, Ehlers‐Danlos syndrome, and fibromyalgia and non‐painful disorders, such as Parkinson disease and related disorders, amyotrophic lateral sclerosis, critical illness, and peripheral arterial disease …”

Section: Epidemiologymentioning

confidence: 99%

“…• Expansion in knowledge on the pathophysiology of SFN will inform the development of new therapies. amyotrophic lateral sclerosis, [44][45][46] critical illness, 47 and peripheral arterial disease. 48 New techniques to determine the IENFD with indirect immunofluorescence, 49 automated PGP9.5 immunofluorescence staining (laboratory developed test), 50 and 3D analysis 51 have been reported.…”

Section: Skin Biopsymentioning

confidence: 99%

See 1 more Smart Citation

Small‐fiber neuropathy: Expanding the clinical pain universe

Sopacua

Hoeijmakers

Merkies

et al. 2019

J Peripheral Nervous Sys

104

View full text Add to dashboard Cite

Small‐fiber neuropathy (SFN) is a disorder of thinly myelinated Aδ and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life. According to international criteria, the diagnosis is established by the assessment of intraepidermal nerve fiber density and/or quantitative sensory testing. SFN is mainly associated with autoimmune diseases, sodium channel gene variants, diabetes mellitus, and vitamin B12 deficiencies, although in more than one half of patients no etiology can be identified. Recently, gain‐of‐function variants in the genes encoding for the Nav1.7, Nav1.8 and Nav1.9 sodium channel subunits have been discovered in SFN patients, enlarging the spectrum of underlying conditions. Sodium channel gene variants associated with SFN can lead to a diversity of phenotypes, including different pain distributions and presence or absence of autonomic symptoms. This suggests that SFN is part of a clinical continuum. New assessments might contribute to a better understanding of the cellular and molecular substrates of SFN and might provide improved diagnostic methods and trial designs in the future. Identification of the underlying mechanisms may inform the development of drugs that more effectively address neuropathic pain and autonomic symptoms of SFN.

show abstract

Section: Epidemiologymentioning

confidence: 99%

Section: Skin Biopsymentioning

confidence: 99%

Small‐fiber neuropathy: Expanding the clinical pain universe

Sopacua

Hoeijmakers

Merkies

et al. 2019

J Peripheral Nervous Sys

104

View full text Add to dashboard Cite

show abstract

“…Similarly, further studies have demonstrated that up to 75% of patients with ALS have small-fibre pathology, evident as a decreased density of IENFs 148 , and exhibit asymptomatic involvement of autonomic nerves and Meissner corpuscles 147 . One study suggested that loss of IENFs was only seen in patients with spinal-onset ALS 149 , but a larger study that included patients with sporadic and genetic ALS found no correlations between phenotype, genotype and disease course 148 .…”

Section: Stromamentioning

confidence: 99%

“…Beyond classic SFNs, skin biopsy can be used to identify small-fibre pathology in painless neuro degenerative disorders, such as Parkinson disease (PD) 144,145 and amyotrophic lateral sclerosis (ALS) [146][147][148] . Evidence shows that patients with PD exhibit a marked loss of IENFs and Meissner corpuscles that accompanies abnormal tactile, thermal and mechanical pain perception 144 .…”

Section: Stromamentioning

confidence: 99%

New technologies for the assessment of neuropathies

et al. 2017

View full text Add to dashboard Cite

Peripheral neuropathies are among the most common neurological disorders 1 . In routine clinical practice, diagnosis of peripheral neuropathies is typically based on clinical assessment, nerve conduction studies and needle electromyography, which can determine whether symptoms are caused by primary axonal damage or demyelinating damage. This distinction is often relevant to therapeutic choices and to prognosis, as axonal damage typically reflects an inflammatory (for example, vasculitic) or degenerative (for example, hereditary or idiopathic) process that correlates with disability, whereas demyelinating damage can reflect a hereditary neuro pathy, but more often reflects an acquired immunemediated neuropathy. Besides metabolic, inflammatory or primary degenerative neuropathies, peripheral nerves can also be damaged by compression from adjacent tissue structures, such as tendons, cysts or haematomas. In this case, proper identification of the site, nature and degree of the lesion might be challenging, but is relevant to treatment and prognosis. Moreover, some patients present with symptoms that suggest damage to small nerve fibres, which nerve conduction studies cannot be used to detect.In the past 15 years, several techniques have become available to investigate focal and diffuse peripheral neuropathies, and their reliability has widened the spectrum of diagnostic tools for clinicians and improved assessment of neuropathies. In this Review, we provide an overview of these new and emerging technologies. We first discuss peripheral nerve imaging with MRI and ultrasonography, which can provide information about the precise localization of neuro pathies and the pathological processes involved in large-fibre neuropathies, and can complement clinical and electrophysiological evaluation. We then consider techniques that can provide diagnostic information when the pathological process is restricted to small nerve fibres and is consequently not detectable with nerve conduction studies or neuroimaging. These include skin biopsy, which is established in clinical practice, and the emerging techniques of corneal confocal microscopy, laser-evoked potentials and heat-related and pain-related evoked potentials, and microneurography.Nerve imaging technology Advances in imaging techniques have made it possible to gain great insight into nerve pathology with magnetic resonance and ultrasound. Each approach offers distinct advantages, and can provide different information about damage to large myelinated fibres. Abstract | Technical advances are rapidly changing the clinical and instrumental approach to peripheral nerve diseases. Magnetic resonance neurography, diffusion tensor imaging and nerve ultrasonography are increasingly entering the diagnostic workup of peripheral neuropathies as tools that complement neurophysiology and enable investigation of proximal structures, such as plexuses and roots. Progress in the design of magnetic resonance scanners and sequences, and the development of high-frequency ultrasound probes mean th...

show abstract

“…In this issue of Neuropathology and Applied Neurobiology, Nolano and colleagues reported significant cutaneous sensory and autonomic denervation in a cohort of sporadic ALS patients, including primary lateral sclerosis (PLS), and associate these changes to a faster rate of disease progression. Specifically, nonlength‐dependent loss of intraepidermal nerve fibres along with reduced density of Meissner corpuscles and cholinergic/noradrenergic pilomotor nerve fibres was reported in both the typical ALS phenotype and PLS.…”

mentioning

confidence: 99%