A 40‐year‐old woman with difficulty going down stairs in high‐heeled shoes

Scripko, Patricia D.; Oaklander, Anne Louise; Koeppen, Arnulf H.; Frosch, Matthew P.; Schmahmann, Jeremy D.

doi:10.1002/ana.24301

Cited by 2 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The median and ulnar nerves of MMN patients were 25–30 % larger than those in the healthy controls and ALS patients. The diffuse rather than focal nerve enlargements are in line with high resolution ultrasound studies of peripheral nerves [ 26 , 27 ] and the brachial plexus [ 9 , 28 ]. Pathogenic mechanisms underlying MMN therefore seem to affect significant lengths of motor nerves rather than patchy and focal involvement, as suggested by the observed patterns of weakness and conduction block [ 1 , 5 ].…”

Section: Discussionsupporting

confidence: 63%

See 1 more Smart Citation

MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

et al. 2016

View full text Add to dashboard Cite

ObjectivesTo study disease mechanisms in multifocal motor neuropathy (MMN) with magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) of the median and ulnar nerves.MethodsWe enrolled ten MMN patients, ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls (HCs). Patients underwent MRI (in a prone position) and nerve conduction studies. DTI and fat-suppressed T2-weighted scans of the forearms were performed on a 3.0T MRI scanner. Fibre tractography of the median and ulnar nerves was performed to extract diffusion parameters: fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivity. Cross-sectional areas (CSA) were measured on T2-weighted scans.ResultsForty-five out of 60 arms were included in the analysis. AD was significantly lower in MMN patients (2.20 ± 0.12 × 10-3 mm2/s) compared to ALS patients (2.31 ± 0.17 × 10-3 mm2/s; p < 0.05) and HCs (2.31± 0.17 × 10-3 mm2/s; p < 0.05). Segmental analysis showed significant restriction of AD, RD and MD (p < 0.005) in the proximal third of the nerves. CSA was significantly larger in MMN patients compared to ALS patients and HCs (p < 0.01).ConclusionsThickening of nerves is compatible with changes in the myelin sheath structure, whereas lowered AD values suggest axonal dysfunction. These findings suggest that myelin and axons are diffusely involved in MMN pathogenesis.Key Points• Diffusion magnetic resonance imaging provides quantitative information about multifocal motor neuropathy (MMN). • Diffusion tensor imaging allows non-invasive evaluation of the forearm nerves in MMN. • Nerve thickening and lowered diffusion parameters suggests myelin and axonal changes. • This study can help to provide insight into pathological mechanisms of MMN. Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-016-4575-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 63%

“…It is a consistent feature of both genetic and acquired demyelinating polyneuropathies, i.e. Charcot-Marie-Tooth type 1 and chronic inflammatory demyelinating polyneuropathy [ 28 , 29 ]. This is further supported by the occasional pathological observation of onion bulb formation in nerve biopsy studies in MMN [ 7 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Polygenic inheritance of common variants has been shown to be associated with early-onset PD (4). There is also evidence that multiple rare variants in Mendelian genes may increase the risk of some diseases in a non-Mendelian fashion in amyotrophic lateral sclerosis (5) and schizophrenia (6). Here, we define Known Mutation-PD as PD cases carrying a recognised high penetrance pathogenic mutation regardless of family history.…”

Section: Introductionmentioning

confidence: 99%

Additional rare variant analysis in Parkinson’s disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance

et al. 2016

View full text Add to dashboard Cite

Oligogenic inheritance implies a role for several genetic factors in disease etiology. We studied oligogenic inheritance in Parkinson’s (PD) by assessing the potential burden of additional rare variants in established Mendelian genes and/or GBA, in individuals with and without a primary pathogenic genetic cause in two large independent cohorts totaling 7,900 PD cases and 6,166 controls. An excess (≥30%) of cases with a recognised primary genetic cause had ≥1 additional rare variants in Mendelian PD genes, as compared with no known mutation PD cases (17%) and unaffected controls (16%), supporting our hypothesis. Carriers of additional Mendelian gene variants have younger ages at onset (AAO). The effect of additional Mendelian variants in LRRK2 G2019S mutation carriers, of which ATP13A2 variation is particularly common, may account for some of the variation in penetrance. About 10% of No Known Mutation-PD cases harbour a rare GBA variant compared to known pathogenic mutation PD cases (8%) and controls (5%), with carriers having earlier AAOs. Together, the data suggest that the oligogenic inheritance of rare Mendelian variants may be important in patient with a primary pathogenic cause, whereas GBA increases risk across all forms of PD. This study highlights the potential genetic complexity of Mendelian PD. The identification of potential modifying variants provides new insights into disease mechanisms by potentially separating relevant from benign variants and by the interaction between genes in specific pathways. In the future this may be relevant to genetic testing and counselling of patients with PD and their families.

show abstract

A 40‐year‐old woman with difficulty going down stairs in high‐heeled shoes

Abstract: A 40-year-old woman was seen in the outpatient neu-View this article online at wileyonlinelibrary.com.

Cited by 2 publications

References 37 publications

MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

Additional rare variant analysis in Parkinson’s disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance

Contact Info

Product

Resources

About