Quantitative magnetic resonance neurography in chronic inflammatory demyelinating polyradiculoneuropathy: A longitudinal study over 6 years.

OBJECTIVE: To evaluate magnetic resonance neurography (MRN) for the longitudinal assessment of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Prospective examination of twelve CIDP patients by neurological assessment, MRN, and nerve conduction studies in 2016 and 6 years later in 2022. Imaging parameters were compared with matched healthy controls and correlated with clinical and electrophysiological markers. The MRN protocol included T2-weighted imaging, diffusion tensor imaging (DTI), T2 relaxometry, and magnetization transfer imaging (MTI). RESULTS: Nerve cross-sectional area (CSA) was increased in CIDP patients compared to controls (plexus: p = 0.003; sciatic nerve: p < 0.001). Over 6 years, nerve CSA decreased in CIDP patients, most pronounced at the lumbosacral plexus (p = 0.015). Longitudinally, changes in CSA correlated with changes in the inflammatory neuropathy cause and treatment validated overall disability sum score (INCAT/ODSS) (p = 0.006). High initial nerve CSA was inversely correlated with changes in the INCAT/ODSS over 6 years (p < 0.05). The DTI parameter fractional anisotropy (FA) showed robust correlations with electrodiagnostic testing both cross-sectionally and longitudinally (p < 0.05). MTI as a newly added imaging technique revealed a significantly reduced magnetization transfer ratio (MTR) in CIDP patients (p < 0.01), suggesting underlying changes in macromolecular tissue composition, and correlated significantly with electrophysiological parameters of demyelination (p < 0.05). INTERPRETATION: This study provides evidence that changes in nerve CSA and FA reflect the clinical and electrophysiological course of CIDP patients. Initial nerve hypertrophy might predict a rather benign course or better therapy response.

Dorsal Root Ganglia Volume-Normative Values, Correlation with Demographic Determinants and Reliability of Three Different Methods of Volumetry.

Background: Dorsal root ganglia (DRG) volume assessment by MR-Neurography (MRN) has evolved to an important imaging marker in the diagnostic workup of various peripheral neuropathies and pain syndromes. The aim of this study was (1) to assess normal values of DRG volume and correlations with demographic determinants and (2) to quantify the inter-reader and inter-method reliability of three different methods of DRG volumetry. Methods: Sixty healthy subjects (mean age: 59.1, range 23-79) were examined using a 3D T2-weighted MRN of the lumbosacral plexus at 3 Tesla. Normal values of DRG L3 to S2 were obtained after exact volumetry based on manual 3D segmentation and correlations with demographic variables were assessed. For the assessment of inter-reader and inter-method reliability, DRG volumes in a subset of 25 participants were measured by two independent readers, each applying (1) exact volumetry based on 3D segmentation, (2) axis-corrected, and (3) non-axis-corrected volume estimation. Intraclass correlation coefficients were reported and the Bland-Altman analysis was conducted. Results: Mean DRG volumes ranged from 124.8 mm3 for L3 to 323.3 mm3 for S1 and did not differ between right and left DRG. DRG volume (mean of L3 to S1) correlated with body height (r = 0.42; p = 0.0008) and weight (r = 0.34; p = 0.0087). DRG of men were larger than of women (p = 0.0002); however, no difference remained after correction for body height. Inter-reader reliability was high for all three methods but best for exact volumetry (ICC = 0.99). While axis-corrected estimation was not associated with a relevant bias, non-axis-corrected estimation systematically overestimated DRG volume by on average of 15.55 mm3 (reader 1) or 18.00 mm3 (reader 2) when compared with exact volumetry. Conclusion: The here presented normal values of lumbosacral DRG volume and the correlations with height and weight may be considered in future disease specific studies and possible clinical applications. Exact volumetry was most reliable and should be considered the gold standard. However, the reliability of axis-corrected and non-axis-corrected volume estimation was also high and might still be sufficient, depending on the degree of the required measurement accuracy.

Spatial Distribution and Long-Term Alterations of Peripheral Nerve Lesions in Schwannomatosis.

Purpose To examine the spatial distribution and long-term alterations of peripheral nerve lesions in patients with schwannomatosis by in vivo high-resolution magnetic resonance neurography (MRN). Methods In this prospective study, the lumbosacral plexus as well as the right sciatic, tibial, and peroneal nerves were examined in 15 patients diagnosed with schwannomatosis by a standardized MRN protocol at 3 Tesla. Micro-, intermediate- and macrolesions were assessed according to their number, diameter and spatial distribution. Moreover, in nine patients, peripheral nerve lesions were compared to follow-up examinations after 39 to 71 months. Results In comparison to intermediate and macrolesions, microlesions were the predominant lesion entity at the level of the proximal (p < 0.001), mid- (p < 0.001), and distal thigh (p < 0.01). Compared to the proximal calf level, the lesion number was increased at the proximal (p < 0.05), mid- (p < 0.01), and distal thigh level (p < 0.01), while between the different thigh levels, no differences in lesion numbers were found. In the follow-up examinations, the lesion number was unchanged for micro-, intermediate and macrolesions. The diameter of lesions in the follow-up examination was decreased for microlesions (p < 0.01), not different for intermediate lesions, and increased for macrolesions (p < 0.01). Conclusion Microlesions represent the predominant type of peripheral nerve lesion in schwannomatosis and show a rather consistent distribution pattern in long-term follow-up. In contrast to the accumulation of nerve lesions, primarily in the distal nerve segments in NF2, the lesion numbers in schwannomatosis peak at the mid-thigh level. Towards more distal portions, the lesion number markedly decreases, which is considered as a general feature of other types of small fiber neuropathy.

Quantitative MR-Neurography at 3.0T: Inter-Scanner Reproducibility.

BACKGROUND: Quantitative MR-neurography (MRN) is increasingly applied, however, the impact of the MR-scanner on the derived parameters is unknown. Here, we used different 3.0T MR scanners and applied comparable MR-sequences in order to quantify the inter-scanner reproducibility of various MRN parameters of the sciatic nerve. METHODS: Ten healthy volunteers were prospectively examined at three different 3.0T MR scanners and underwent MRN of their sciatic nerve using comparable imaging protocols including diffusion tensor imaging (DTI) and T2 relaxometry. Subsequently, inter-scanner agreement was assessed for seven different parameters by calculating the intraclass correlation coefficients (ICCs) and the standard error of measurement (SEM). RESULTS: Assessment of inter-scanner reliability revealed good to excellent agreement for T2 (ICC: 0.846) and the quantitative DTI parameters, such as fractional anisotropy (FA) (ICC: 0.876), whereas moderate agreement was observed for proton spin density (PD) (ICC: 0.51). Analysis of variance identified significant inter-scanner differences for several parameters, such as FA (p < 0.001; p = 0.02), T2 (p < 0.01) and PD (p = 0.02; p < 0.01; p = 0.02). Calculated SEM values were mostly within the range of one standard deviation of the absolute mean values, for example 0.033 for FA, 4.12 ms for T2 and 27.8 for PD. CONCLUSION: This study quantifies the measurement imprecision for peripheral nerve DTI and T2 relaxometry, which is associated with the use of different MR scanners. The here presented values may serve as an orientation of the possible scanner-associated fluctuations of MRN biomarkers, which can occur under similar conditions.

Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment : Longitudinal Assessment by Computed Tomography.

PURPOSE: Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose. METHODS: For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1-t4) with the following median and ranges in months: 3.1 (0.4-4.9), 6.2 (5.3-7.8), 10.4 (8.2-11.9), and 18.4 (12.8-49.8). RESULTS: DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08). CONCLUSION: CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker.

Diffusion MRI in Peripheral Nerves: Optimized b Values and the Role of Non-Gaussian Diffusion.

Background Diffusion-weighted imaging (DWI) provides specific in vivo information about tissue microstructure, which is increasingly recognized for various applications outside the central nervous system. However, standard sequence parameters are commonly adopted from optimized central nervous system protocols, thus potentially neglecting differences in tissue-specific diffusional behavior. Purpose To characterize the optimal tissue-specific diffusion imaging weighting scheme over the b domain in peripheral nerves under physiologic and pathologic conditions. Materials and Methods In this prospective cross-sectional study, 3-T MR neurography of the sciatic nerve was performed in healthy volunteers (n = 16) and participants with type 2 diabetes (n = 12). For DWI, 16 b values in the range of 0-1500 sec/mm2 were acquired in axial and radial diffusion directions of the nerve. With a region of interest-based approach, diffusion-weighted signal behavior as a function of b was estimated using standard monoexponential, biexponential, and kurtosis fitting. Goodness of fit was assessed to determine the optimal b value for two-point DWI/diffusion tensor imaging (DTI). Results Non-Gaussian diffusional behavior was observed beyond b values of 600 sec/mm2 in the axial and 800 sec/mm2 in the radial diffusion direction in both participants with diabetes and healthy volunteers. Accordingly, the biexponential and kurtosis models achieved a better curve fit compared with the standard monoexponential model (Akaike information criterion >99.9% in all models), but the kurtosis model was preferred in the majority of cases. Significant differences between healthy volunteers and participants with diabetes were found in the kurtosis-derived parameters Dk and K. The results suggest an upper bound b value of approximately 700 sec/mm2 for optimal standard DWI/DTI in peripheral nerve applications. Conclusion In MR neurography, an ideal standard diffusion-weighted imaging/diffusion tensor imaging protocol with b = 700 sec/mm2 is suggested. This is substantially lower than in the central nervous system due to early-occurring non-Gaussian diffusion behavior and emphasizes the need for tissue-specific b value optimization. Including higher b values, kurtosis-derived parameters may represent promising novel imaging markers of peripheral nerve disease. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jang and Du in this issue.

Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type 2.

PURPOSE: To examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology. METHODS: In this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3-S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14-100 months. In one patient, imaging findings were further correlated to histology. RESULTS: Follow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm2 vs. 2.15 mm2, p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified. CONCLUSION: Peripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.

Magnetization Transfer Ratio of Peripheral Nerve and Skeletal Muscle : Correlation with Demographic Variables in Healthy Volunteers.

PURPOSE: To assess the correlation of peripheral nerve and skeletal muscle magnetization transfer ratio (MTR) with demographic variables. METHODS: In this study 59 healthy adults evenly distributed across 6 decades (mean age 50.5 years ±17.1, 29 women) underwent magnetization transfer imaging and high-resolution T2-weighted imaging of the sciatic nerve at 3 T. Mean sciatic nerve MTR as well as MTR of biceps femoris and vastus lateralis muscles were calculated based on manual segmentation on six representative slices. Correlations of MTR with age, body height, body weight, and body mass index (BMI) were expressed by Pearson coefficients. Best predictors for nerve and muscle MTR were determined using a multiple linear regression model with forward variable selection and fivefold cross-validation. RESULTS: Sciatic nerve MTR showed significant negative correlations with age (r = -0.47, p < 0.001), BMI (r = -0.44, p < 0.001), and body weight (r = -0.36, p = 0.006) but not with body height (p = 0.55). The multiple linear regression model determined age and BMI as best predictors for nerve MTR (R2 = 0.40). The MTR values were different between nerve and muscle tissue (p < 0.0001), but similar between muscles. Muscle MTR was associated with BMI (r = -0.46, p < 0.001 and r = -0.40, p = 0.002) and body weight (r = -0.36, p = 0.005 and r = -0.28, p = 0.035). The BMI was selected as best predictor for mean muscle MTR in the multiple linear regression model (R2 = 0.26). CONCLUSION: Peripheral nerve MTR decreases with higher age and BMI. Studies that assess peripheral nerve MTR should consider age and BMI effects. Skeletal muscle MTR is primarily associated with BMI but overall less dependent on demographic variables.

Assessment of small fiber neuropathy in patients carrying the non-classical Fabry variant p.D313Y.

INTRODUCTION: The pathophysiological significance of the Fabry-related, non-classical variant p.D313Y still remains to be solved. This study assesses the involvement of the peripheral nervous system with respect to small fiber neuropathy and neuropathic pain in female patients carrying p.D313Y. METHODS: This study examined nine females carrying the Fabry-related p.D313Y variant by obtaining skin punch biopsies above the right lateral malleolus. Intraepidermal nerve fiber density was determined for each patient and compared to reference values matched for the patient's decade of life and sex. Moreover, each patient was characterized by a detailed neurological examination and by pain assessment via questionnaire. RESULTS: Compared to sex-matched lower fifth percentile reference values per decade, intraepidermal nerve fiber density was decreased in seven out of nine patients. Four patients reported acral paresthesias and neuropathic pain with an average visual analogue scale score of 7 out of 10 points. Two patients experienced acute pain crises. Six out of seven patients diagnosed with small fiber neuropathy had a their medical history of hypo- and/or hyperhidrosis. DISCUSSION: The diagnosis of small fiber neuropathy was made in seven out of nine females carrying the non-classical variant p.D313Y. Moreover, neuropathic pain and symptoms indicative of autonomic nervous system dysfunction seem to be common findings that may be of clinical significance and may warrant therapeutic intervention.

Assessment of Peripheral Nervous System Alterations in Patients with the Fabry Related GLA-Variant p.A143T.

Background The purpose of this study is to examine alterations of the peripheral nervous system (PNS) in oligo-symptomatic patients carrying the Fabry related GLA-gene variant p.A143T by Magnetic Resonance Neurography (MRN) and skin biopsy. This prospective study assessed dorsal root ganglia (DRG) volume L3 to S2, vascular permeability of the DRG L5, S1, and the spinal nerve L5 in five patients carrying p.A143T in comparison to patients with classical Fabry mutations and healthy controls. Moreover, skin punch biopsies above the lateral malleolus of the right foot were obtained in four patients and intraepidermal nerve fiber density (IENFD) was counted individually. Compared to controls, DRG volumes of p.A143T patients were enlarged by 30% (L3, p < 0.05), 35% (L4, p < 0.05), 29% (L5, p = 0.15), 36% (S1, p < 0.01), and 18% (S2, p < 0.05), but less pronounced compared to patients carrying a classical Fabry mutation. Compared to healthy controls, vascular permeability was decreased by 40% (L5 right), 49% (L5 left), 48% (S1 right), and 49% (S1) (p < 0.01-p < 0.001), but non-significant less than patients carrying a classical Fabry mutation. Compared to sex-matched 5% lower normative reference values per decade, IENFD was decreased in three of four patients. MRN and determination of IENFD is able to detect early alteration of the PNS segment in oligo-symptomatic patients with the disease-modifying GLA-variant p.A143T on an individual basis. This procedure might also help in further GLA-variants of uncertain significance for early identification of patients with single major organ manifestation.

MR Neurography: Normative Values in Correlation to Demographic Determinants in Children and Adolescents.

PURPOSE: To determine normative morphological and functional magnetic resonance (MR) neurography values in children and adolescents in correlation to demographic determinants. METHODS: In this study 29 healthy underage subjects (mean age 13.9 years, range 10-17 years) were examined using a standardized MR neurography protocol of the lumbosacral plexus and the right lower extremity at 3 T. Volumes of the dorsal root ganglia L3-S2, cross-sectional area of the sciatic and tibial nerves, as well as T2-weighted contrast nerve-muscle ratio and quantitative diffusion tensor imaging (DTI) values of the sciatic nerve were obtained and correlated with the demographic parameters sex, age, height and weight. RESULTS: While all obtained morphological and functional MR neurography values did not differ between male and female sex, dorsal root ganglia volume, sciatic and tibial nerve cross-sectional area correlated positively with age, height, and weight. The T2-weighted signal of the sciatic nerve was independent of demographic determinants. Negative correlation was found for fractional anisotropy (FA) with age, height, and weight, whereas radial diffusivity (RD) showed a positive correlation only with age. Mean diffusivity (MD) and axial diffusivity (AD) revealed no correlation with demographic determinants. CONCLUSION: The results of this study suggest that selection of sex-matched controls for further studies assessing peripheral nerve pathologies in underage patients may not be necessary; however, control subjects should be adapted to age, height, and weight of the patient population, especially if assessing dorsal root ganglia volume, nerve cross-sectional area and DTI.

Peripheral nervous system alterations in infant and adult neurofibromatosis type 2.

OBJECTIVE: To examine the involvement of dorsal root ganglia and peripheral nerves in children with neurofibromatosis type 2 compared to healthy controls and symptomatic adults by in vivo high-resolution magnetic resonance neurography. METHODS: In this prospective multicenter study, the lumbosacral dorsal root ganglia and sciatic, tibial, and peroneal nerves were examined in 9 polyneuropathy-negative children diagnosed with neurofibromatosis type 2 by a standardized magnetic resonance neurography protocol at 3T. Volumes of dorsal root ganglia L3 to S2 and peripheral nerve lesions were assessed and compared to those of 29 healthy children. Moreover, dorsal root ganglia volumes and peripheral nerve lesions were compared to those of 14 adults with neurofibromatosis type 2. RESULTS: Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in children with neurofibromatosis type 2 (L3 +255%, L4 +289%, L5 +250%, S1 +257%, and S2 +218%, p < 0.001) with an excellent diagnostic accuracy. Moreover, peripheral nerve lesions occurred with a high frequency in those children compared to healthy controls (18.89 ± 11.11 vs 0.90 ± 1.08, p < 0.001). Children and adults with neurofibromatosis type 2 showed nonsignificant differences in relative dorsal root ganglia hypertrophy rates (p = 0.85) and peripheral nerve lesions (p = 0.28). CONCLUSIONS: Alterations of peripheral nerve segments occur early in the course of neurofibromatosis type 2 and are evident even in children not clinically affected by peripheral polyneuropathy. While those early alterations show similar characteristics compared to adults with neurofibromatosis type 2, the findings of this study suggest that secondary processes might be responsible for the development and severity of associated polyneuropathy.

Amyotrophic Lateral Sclerosis versus Multifocal Motor Neuropathy: Utility of MR Neurography.

Background Differential diagnosis between amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN) relies on clinical examination and electrophysiological criteria. Peripheral nerve imaging might assist this differential diagnosis. Purpose To assess diagnostic accuracy of MR neurography in the differential diagnosis of ALS and MMN. Materials and Methods This prospective study was conducted between December 2015 and April 2017. Study participants with ALS or MMN underwent MR neurography of the lumbosacral plexus, midthigh, proximal calf, and midupper arm of the clinically more affected side using high-resolution T2-weighted sequences. Matched healthy study participants who underwent MR neurography served as a control group. Two blinded readers independently rated fascicular lesions and muscle denervation signs on a five-point scale and made an image-only diagnosis, which was compared with the clinical diagnosis to assess diagnostic accuracy (reported for ALS vs non-ALS and MMN vs non-MMN). The Kruskal-Wallis test was used to compare readers' scoring results. Results Twenty-two participants with ALS (12 men and 10 women; mean age ± standard deviation, 62.3 years ± 9.0), eight participants with MMN (seven men and one woman; mean age, 57.6 years ± 18.6), and 15 healthy participants (seven men and eight women; mean age, 59.1 years ± 10.9) were enrolled in this study. Nerves of participants with ALS either appeared normal or showed T2-weighted hyperintensities without fascicular enlargement (reader 1, 22 of 22 participants; reader 2, 21 of 22 participants). In contrast, nerves in MMN were characterized by fascicular swellings (reader 1, six of eight participants; reader 2, seven of eight participants). Muscle denervation signs were more prominent in ALS than in MMN. Inter-rater reliability for blinded diagnosis was κ of 0.82. By consensus, the sensitivity to diagnose ALS (vs MMN and healthy control participants) was 19 of 22 (86% [95% confidence interval {CI}: 67%, 95%]). The corresponding specificity was 23 of 23 (100% [95% CI: 86%, 100%]). The sensitivity to diagnose MMN (vs ALS and healthy control participants) was seven of eight (88% [95% CI: 53%, 99%]). The corresponding specificity was 37 of 37 (100% [95% CI: 91%, 100%]). Conclusion MR neurography is an accurate method for assisting in the differential diagnosis of amyotrophic lateral sclerosis and multifocal motor neuropathy. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Andreisek in this issue.

Prevalence of fascicular hyperintensities in peripheral nerves of healthy individuals with regard to cerebral white matter lesions.

OBJECTIVE: Detection and pattern analysis of fascicular nerve hyperintensities in the T2-weighted image are the backbone of magnetic resonance neurography (MRN) as they may represent lesions of various etiologies. The aim of this study was to assess the prevalence of fascicular nerve hyperintensities in healthy individuals with regard to a potential association with age or cerebral white matter lesions. METHODS: Sixty volunteers without peripheral nerve diseases between the age of 20 and 80 underwent MRN (high-resolution T2-weighted) of upper (median, ulnar, radial) and lower (sciatic, tibial) extremity nerves and a fluid-attenuated inversion recovery (FLAIR) sequence of the brain. Presence of peripheral nerve hyperintensities and degree of cerebral white matter lesions were independently rated by two blinded readers and related to each other and to age. T test with Welch's correction was used for group comparisons. Spearman's correlation coefficients were reported for correlation analyses. RESULTS: MR neurography revealed fascicular hyperintensities in 10 of 60 subjects (16.7%). Most frequently, they occurred in the sciatic nerve (8/60 subjects, 13.3%), less frequently in the tibial nerve at the lower leg and the median, ulnar, and radial nerves at the upper arm (1.7-5.0%). Mean age of subjects with nerve hyperintensities was higher than that of those without (60.6 years vs. 48.0 years, p = 0.038). There was only a weak correlation of nerve lesions with age and with cerebral white matter lesions, respectively. CONCLUSION: Fascicular nerve hyperintensities may occur in healthy individuals and should therefore always be regarded in conjunction with the clinical context. KEY POINTS: • MR neurography may reveal fascicular hyperintensities in peripheral nerves of healthy individuals. Fascicular hyperintensities occur predominantly in the sciatic nerve and older individuals. • Therefore, fascicular hyperintensities should only be interpreted as clearly pathologic in conjunction with the clinical context.

Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y.

PURPOSE: To examine dorsal root ganglia and proximal nerve segments in patients carrying the Fabry-related GLA-gene variant p.D313Y in comparison to patients with classical Fabry mutations and healthy controls by morphometric and functional magnetic resonance neurography. METHODS: This prospective multicenter study examines the lumbosacral dorsal root ganglia and sciatic nerve in 11 female p.D313Y patients by a standardized magnetic resonance neurography protocol at 3 T. Volumes of dorsal root ganglia L3 to S2, permeability of dorsal root ganglia L5 and S1, and spinal nerve L5 as well as cross-sectional area of the sciatic nerve were assessed and compared to 10 females carrying a classical Fabry mutation and 16 healthy female controls. RESULTS: Compared to healthy controls, dorsal root ganglia volumes of p.D313Y females were enlarged by 53% (L3), 48% (L4), 43% (L5), 57% (S1) (p < 0.001), and 55% (S2) (p < 0.05), but less pronounced compared to females carrying a classical Fabry mutation. Compared to healthy controls, p.D313Y patients showed no changes of dorsal root ganglia vascular permeability, while patients with a classical Fabry mutation showed a distinct decrease (p < 0.05). Sciatic nerve cross-sectional area was mildly increased by 6% in p.D313Y as well as in classical Fabry patients (p < 0.05). CONCLUSIONS: Patients carrying the GLA-gene variant p.D313Y show distinctly enlarged dorsal root ganglia, while vascular permeability remains within normal limits. Overall, these alterations partially share characteristics commonly seen in patients with a mutation causing classical FD. This suggests that p.D313Y causes a potentially treatable condition resembling an early stage of Fabry disease.

Diffusion tensor imaging in anterior interosseous nerve syndrome - functional MR Neurography on a fascicular level.

PURPOSE: By applying diffusor tensor imaging (DTI) in patients with anterior interosseous nerve syndrome (AINS), this proof of principle study aims to quantify the extent of structural damage of a peripheral nerve at the anatomical level of individual fascicles. METHODS: In this institutional review board approved prospective study 13 patients with spontaneous AINS were examined at 3 Tesla including a transversal T2-weighted turbo-spin-echo and a spin-echo echo-planar-imaging pulse sequence of the upper arm level. Calculations of quantitative DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for median nerve lesion and non-lesion fascicles as well as ulnar and radial nerve were obtained. DTI values were compared to each other and to a previously published dataset of 58 healthy controls using one-way Analysis of Variance with Bonferroni correction and p-values <.05 were considered significant. Receiver operating characteristic (ROC) curves were performed to assess diagnostic accuracy. RESULTS: FA of median nerve lesion fascicles was decreased compared to median nerve non-lesion fascicles, ulnar nerve and radial nerve while MD, RD, and AD was increased (p < .001 for all parameters). Compared to median nerve values of healthy controls, lesion fascicles showed a significant decrease in FA while MD, RD, and AD was increased (p < .001 for all parameters). FA of median nerve non-lesion fascicles showed a weak significant decrease compared to healthy controls (p < .01) while there was no difference in MD, RD, and AD. ROC analyses revealed an excellent diagnostic accuracy of FA, MD and RD in the discrimination of median nerve lesion and non-lesion fascicles in AINS patients as well as in the discrimination of lesion fascicles and normative median nerve values of healthy controls. CONCLUSION: By applying this functional MR Neurography technique in patients with AINS, this proof of principle study demonstrates that diffusion tensor imaging is feasible to quantify structural nerve injury at the anatomical level of individual fascicles.

Magnetic Resonance Neurography : Normal Values and Demographic Determinants of Nerve Caliber and T2 Relaxometry in 60 healthy individuals.

PURPOSE: To establish normal values and to identify demographic determinants of quantitative biomarkers in magnetic resonance neurography (MRN). METHODS: In this study 60 healthy individuals (5 men and 5 women of every decade between 20 and 80 years) were examined according to a standardized MRN protocol at 3 T, including multiecho T2 relaxometry. Nerve cross-sectional area (CSA), transverse relaxation time (T2), and proton spin density (PSD) were assessed for the sciatic, tibial, median, ulnar, and radial nerves. Correlation with demographic variables, such as height, weight, body mass index (BMI), and age was expressed by Pearson coefficients and t­tests were used to compare MRN biomarkers between men and women with and without normalization to body weight and BMI by linear regression. RESULTS: The average nerve CSA correlated moderately with height (r = 0.28, p = 0.04), weight (r = 0.40, p = 0.002), and BMI (r = 0.35, p = 0.008), but not with age (r = 0.23, p = 0.09). While T2 did not correlate with demographic parameters, PSD was strongly inversely associated with BMI (r = -0.64, p < 0.001) and weight (r = -0.557, p < 0.001). Sex-dependent differences in imaging marker values were found for CSA but became negligible after normalization to body weight. CONCLUSION: Quantitative biomarkers of MRN co-vary with demographic variables. As particularly important determinants, we identified body weight for nerve CSA and BMI for PSD. The presented normal values and demographic determinants may assist investigations into the potential of MRN biomarkers in further disease-specific studies.

Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease.

PURPOSE: To examine dorsal root ganglia and the proximal nerve segments in female patients with Fabry disease by functional and morphometric magnetic resonance neurography. METHODS: In this prospective multicenter study the lumbosacral dorsal root ganglia and proximal sciatic nerve were examined in ten female patients with Fabry disease by a standardized magnetic resonance neurography protocol at 3 T. Volumes of dorsal root ganglia L3-S2, permeability of dorsal root ganglia L5 and S1 and the spinal nerve L5 as well as the cross-sectional area of the proximal sciatic nerve were compared to 16 gender-matched healthy controls. RESULTS: Dorsal root ganglia were symmetrically enlarged by 54% (L3), 79% (L4), 60% (L5), 94% (S1), and 106% (S2) (p < 0.001). Additionally, permeability of the blood-tissue interface was decreased by 47% (p < 0.001). This finding was most pronounced in the peripheral zone of the dorsal root ganglia, where the cell bodies of the primary sensory neurons are located (p < 0.001). While spinal nerve permeability showed no differences compared to healthy controls, proximal sciatic nerve cross-sectional area was mildly increased by 6% (p < 0.01). CONCLUSION: Although heterozygous, Fabry females show severe enlarged dorsal root ganglia with a concomitant dysfunctional perfusion, even in patients with minor disease progression and in patients who are not considered for enzyme replacement therapy yet. Alterations in dorsal root ganglia volume and perfusion might serve as a very early in vivo marker for involvement of the peripheral nervous system in Fabry disease, even in patients with residual enzyme activity.

Co-occurrence of schwannomatosis and rhabdoid tumor predisposition syndrome 1.

BACKGROUND: The clinical phenotype associated with germline SMARCB1 mutations has as yet not been fully documented. It is known that germline SMARCB1 mutations may cause rhabdoid tumor predisposition syndrome (RTPS1) or schwannomatosis. However, the co-occurrence of rhabdoid tumor and schwannomas in the same patient has not so far been reported. METHODS: We investigated a family with members harboring a germline SMARCB1 deletion by means of whole-body MRI as well as high-resolution microstructural magnetic resonance neurography (MRN). Breakpoint-spanning PCRs were performed to characterize the SMARCB1 deletion and its segregation in the family. RESULTS: The index patient of this family was in complete continuous remission for an atypical teratoid/rhabdoid tumor (AT/RT) treated at the age of 2 years. However, at the age of 21 years, she exhibited paraparesis of her legs and MRI investigations revealed multiple intrathoracic and spinal schwannomas. Breakpoint-spanning PCRs indicated that the germline deletion segregating in the family encompasses 6.4-kb and includes parts of SMARCB1 intron 7, exons 8-9 and 3.3-kb located telomeric to exon 9 including the SMARCB1 3' UTR. The analysis of sequences at the deletion breakpoints showed that the deletion has been caused by replication errors including template-switching. The patient had inherited the deletion from her 56-year-old healthy mother who did not exhibit schwannomas or other tumors as determined by whole-body MRI. However, MRN of the peripheral nerves of the mother's extremities revealed multiple fascicular microlesions which have been previously identified as indicative of schwannomatosis-associated subclinical peripheral nerve pathology. CONCLUSION: The occurrence of schwannomatosis-associated clinical symptoms independent of the AT/RT as the primary disease should be considered in long-term survivors of AT/RT. Furthermore, our investigations indicate that germline SMARCB1 mutation carriers not presenting RTs or schwannomatosis-associated clinical symptoms may nevertheless exhibit peripheral nerve pathology as revealed by MRN.

[Improved diagnostics and therapeutic decision making in traumatic peripheral nerve lesions using MR-neurography]. / Gezielte Therapieplanung bei traumatischen Nervenläsionen mittels MR-Neurographie.

INTRODUCTION: The correct diagnosis of peripheral nerve injuries is essential for choosing the correct treatment in nerve surgery. Especially, nerve defects require early diagnosis to provide quick surgical reconstruction and prevent long-term disabilities. Recent developments in MR-neurography provide surgeons with a diagnostic tool delivering precise information on the structure and possibly function of nerves. Here we describe a series of cases, that benefited from preoperative MR-neurography to identify the correct type of injury. MATERIAL AND METHODS: We demonstrate five traumatic nerve injuries which were evaluated using high-resolution MR-neurography imaging for therapeutic planning, combined with standard clinical, electrophysiological and sonography diagnostics. We show the clinical feasibility, benefit of this new technique for nerve surgery and the correlation of preoperative MR-neurography images to the intraoperative situation (in surgically managed cases). RESULTS: Two cases were successfully treated without surgery based on the intact nerve-integrity found in the MR-neurography, despite pathological electrophysiology and inconclusive sonography. In three cases, the MR-Neurography enabled a precise diagnosis and localization of the nerve lesion. Thereby, a precise surgical reconstruction of the nerve lesion was achieved, confirming the matching of MR-neurography findings and intraoperative situs. DISCUSSION: Although, systematic clinical analyses are not available yet, our data suggest that MR-neurography can help surgeons to correctly define the type of nerve injury and thus identify the appropriate treatment preoperatively. In the presented cases, MR-neurography correctly diagnosed the type of injury and therefore allowed adequate planning and decision making between non-surgical treatment, neurolysis or nerve reconstruction. We believe that MR-neurography is an emerging tool for nerve surgeons to improve the treatment of nerve injuries. CONCLUSION: MR-neurography delivers decisive information on the nerve lesion and helps to identify the necessity to operate and the correct surgical treatment.