Processing of nerve biopsies: A practical guide for neuropathologists

Weis, Joachim; Brandner, Sebastian; Lammens, Martin; Sommer, Claudia; Vallat, Jean‐Michel

doi:10.5414/np300468

Cited by 59 publications

(40 citation statements)

References 67 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For detailed phenotyping of individuals with identified MME mutations, we re-assessed diagnostic sural nerve biopsies and studied skin biopsies for evaluation of intra-epidermal free nerve endings using established protocols. [15][16][17] Subcutaneous adipose tissue biopsies and blood samples were obtained from seven individuals with MME mutations and from 25 control individuals without known neuropathies (mean age 67 years, range 49 to 87 years). The study was approved by the ethics committee of the Medical University of Vienna.…”

Section: Study Participantsmentioning

confidence: 99%

Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies

Auer‐Grumbach

Toegel

Schabhüttl

et al. 2016

The American Journal of Human Genetics

View full text Add to dashboard Cite

Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.

show abstract

Section: Study Participantsmentioning

confidence: 99%

Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies

Auer‐Grumbach

Toegel

Schabhüttl

et al. 2016

The American Journal of Human Genetics

View full text Add to dashboard Cite

show abstract

“…The biopsies were processed following standard procedures (Weis et al. ). Semithin sections were stained with toluidine blue and both light and electron microscopic studies were performed.…”

Section: Methodsmentioning

confidence: 99%

Underestimated associated features in CMT neuropathies: clinical indicators for the causative gene?

et al. 2016

Self Cite

View full text Add to dashboard Cite

IntroductionCharcot–Marie–Tooth neuropathy (CMT) is a genetically heterogeneous group of peripheral neuropathies. In addition to the classical clinical phenotype, additional features can occur.MethodsWe studied a wide range of additional features in a cohort of 49 genetically confirmed CMT patients and performed a systematic literature revision.ResultsPatients harbored a PMP22 gene alteration (n = 28) or a mutation in MPZ (n = 11), GJB1 (n = 4), LITAF (n = 2), MFN2 (n = 2), INF2 (n = 1), NEFL (n = 1). We identified four novel mutations (3 MPZ, 1 GJB1). A total of 88% presented at least one additional feature. In MPZ patients, we detected hypertrophic nerve roots in 3/4 cases that underwent spinal MRI, and pupillary abnormalities in 27%. In our cohort, restless legs syndrome (RLS) was present in 18%. We describe for the first time RLS associated with LITAF or MFN2 and predominant upper limb involvement with LITAF. Cold‐induced hand cramps occurred in 10% (PMP22,MPZ,MFN2), and autonomous nervous system involvement in 18% (PMP22,MPZ, LITAF,MFN2). RLS and respiratory insufficiency were mostly associated with severe neuropathy, and pupillary abnormalities with mild to moderate neuropathy.ConclusionsIn CMT patients, additional features occur frequently. Some of them might be helpful in orienting genetic diagnosis. Our data broaden the clinical spectrum and genotype–phenotype associations with CMT.

show abstract

“…To perform the morphological evaluation, nerve samples were fixed for 2 h in 2.5% glutaraldehyde (Weis et al., ) and stored at 4°C in 2.5% glutaraldehyde – 4% paraformaldehyde in cacodylate buffer 0.08 m, pH 7.4 (Sandell and Peters, ).…”

Section: Methodsmentioning

confidence: 99%

“…From each sample, using the ultramicrotome, semithin sections (0.80 μ m) were obtained and stained with toluidine blue and toluidine blue polychrome (Fig. b) (Weis et al., ).…”

Section: Methodsmentioning

confidence: 99%

Spontaneous Age‐related Changes of Peripheral Nerves in Cattle: Morphological and Biochemical Studies

Biasibetti

Bisanzio

Mioletti

et al. 2015

Anat Histol Embryol

View full text Add to dashboard Cite

Peripheral nerve function is significantly affected by ageing. During ageing process, multiple changes occur on tissue cells and extracellular matrix. The aim of this work was to study the ageing-associated changes of peripheral nerves in adult and old regularly slaughtered cattle compared with young calves, and correlate them to the features reported in humans and laboratory animals. Samples of axial dorsal metacarpal nerves from 44 cows were collected immediately after slaughtering. Each nerve was dissected and divided into two fragments: one used for morphological evaluation (n = 43) and the other one for biochemical analysis (n = 31). Axonal degeneration, demyelination, thickness of perineurium and endoneurium and increase of mast cells were the most important features detected. The mean amount of glycosaminoglycan quantitative content recorded in the samples increased with the age. Axonal degeneration, demyelination and thickness of endoneurium were positively and significantly correlated with biochemistry. The presence of changes affecting the different elements of the peripheral nerves, similar to that reported in humans and in laboratory species, the easy availability of the nerve tissue in this species, the considerable size of the samples and the life conditions more similar to humans than to laboratory animals, allows the authors to consider cattle as a potential good model for the comparative study of spontaneous ageing nerve lesions.

show abstract

Processing of nerve biopsies: A practical guide for neuropathologists

Cited by 59 publications

References 67 publications

Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies

Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies

Underestimated associated features in CMT neuropathies: clinical indicators for the causative gene?

Spontaneous Age‐related Changes of Peripheral Nerves in Cattle: Morphological and Biochemical Studies

Contact Info

Product

Resources

About