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  • 1
    Language: English
    In: Radiology, October 2014, Vol.273(1), pp.185-93
    Description: To investigate the ability of diffusion-tensor imaging (DTI) and T2 to help detect the mildest nerve lesion conceivable, that is, subclinical ulnar neuropathy at the elbow. This prospective study was approved by the institutional ethics board. Written informed consent was obtained from all participants. Magnetic resonance neurography was performed at 3.0 T by using proton density- and T2-weighted relaxometry and DTI on elbows in 30 healthy subjects without clinical evidence of neuropathy. Quantitative analysis of ulnar nerve T2 and fractional anisotropy (FA) was performed, and T2 and FA values were correlated to electrical nerve conduction velocities (NCVs) with Pearson correlation analysis. Additional qualitative assessment of T2-weighted and FA images was performed by two readers, and sensitivity and specificity were calculated. Ten of the 30 subjects (33%) had NCV slowing across the elbow segment. Compared with subjects without NCV slowing, subjects with slowing had decreased FA values (0.51 ± 0.09 vs 0.41 ± 0.07, respectively; P = .006) and increased T2 values (64.2 msec ± 10.9 vs 76.2 msec ± 13.7, respectively; P = .01) in the proximal ulnar sulcus. FA values showed a significant correlation (P = .01) with NCV slowing over the sulcus as an electrophysiologic indicator of myelin sheath damage. Qualitative assessment of FA maps and T2-weighted images helped identify subjects with conduction slowing with a sensitivity of 80% and 55%, respectively, and a specificity of 83% and 63%. FA maps can accurately depict even mild peripheral neuropathy and perform better than the current standard of reference, T2-weighted images. DTI may therefore add diagnostic value as a highly sensitive technique for the detection of peripheral neuropathy.
    Keywords: Diffusion Tensor Imaging -- Methods ; Peripheral Nervous System Diseases -- Diagnosis
    ISSN: 00338419
    E-ISSN: 1527-1315
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  • 2
    In: Neurology, 2015, Vol.84(17), pp.1782-1787
    Description: OBJECTIVES:: To investigate whether the human sciatic nerve might have a consistent somatotopic organization according to proximal fascicle input by spinal nerves. METHODS:: Twelve patients (55.3 ± 15.5 years) with confirmed lesions of either the L5 or S1 spinal nerve root underwent magnetic resonance neurography of sciatic nerve fascicles including thigh and knee levels (T2-weighted sequence with fat saturation, repetition time/echo time 7,552/52 milliseconds, voxel size 0.27 × 0.27 × 3.0 mm). Twenty healthy subjects and 12 additional patients with an established diagnosis of peripheral polyneuropathy served as 2 separate age- and sex-matched control groups. Two blinded readers assessed patients and controls for presence of distinct lesion patterns. Spatial maps of normalized T2 signal were rendered after segmentation and coregistration of sciatic nerve voxels to detect fascicle lesion patterns. RESULTS:: A clear somatotopic distribution of nerve fascicles was observed on cross-sections along the entire course of the sciatic nerve and was distinct between patients with L5 and those with S1 lesions. Fascicles emerging from L5 were ordered in anterolateral positions within sciatic nerve cross-sections, while fascicles emerging from S1 appeared posteromedially. Visual assessment discriminated these somatotopic lesions in all cases from both healthy and polyneuropathy controls. CONCLUSION:: A distinct pattern of somatotopy was identified within the sciatic nerve according to proximal fascicle input by L5 and S1 spinal nerves. Knowledge of human nerve somatotopy may have clinically useful implications in imaging-aided diagnosis of neuropathies.
    Keywords: Repetition ; Spinal Nerves ; Sciatic Nerve ; Segmentation ; Image Processing ; N.M.R. ; Maps ; Knee ; Polyneuropathy ; Neuropathy ; Neurology & Neuropathology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 3
    Language: English
    In: 2012, Vol.7(11), p.e49742
    Description: Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. ; This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. ; In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p〈0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. ; Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Physiology ; Neurological Disorders ; Radiology And Medical Imaging
    E-ISSN: 1932-6203
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  • 4
    In: Neurology, 2016, Vol.87(18), pp.1884-1891
    Description: OBJECTIVE:: To investigate the spatial pattern of lesion dispersion in posterior interosseous neuropathy syndrome (PINS) by high-resolution magnetic resonance neurography. METHODS:: This prospective study was approved by the local ethics committee and written informed consent was obtained from all patients. In 19 patients with PINS and 20 healthy controls, a standardized magnetic resonance neurography protocol at 3-tesla was performed with coverage of the upper arm and elbow (T2-weighted fat-saturated: echo time/repetition time 52/7,020 milliseconds, in-plane resolution 0.27 × 0.27 mm). Lesion classification of the radial nerve trunk and its deep branch (which becomes the posterior interosseous nerve) was performed by visual rating and additional quantitative analysis of normalized T2 signal of radial nerve voxels. RESULTS:: Of 19 patients with PINS, only 3 (16%) had a focal neuropathy at the entry of the radial nerve deep branch into the supinator muscle at elbow/forearm level. The other 16 (84%) had proximal radial nerve lesions at the upper arm level with a predominant lesion focus 8.3 ± 4.6 cm proximal to the humeroradial joint. Most of these lesions (75%) followed a specific somatotopic pattern, involving only those fascicles that would form the posterior interosseous nerve more distally. CONCLUSIONS:: PINS is not necessarily caused by focal compression at the supinator muscle but is instead frequently a consequence of partial fascicular lesions of the radial nerve trunk at the upper arm level. Neuroimaging should be considered as a complementary diagnostic method in PINS.
    Keywords: 120 ; 181 ; Article;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 5
    In: Neurology, 2014, Vol.82(7), pp.598-606
    Description: OBJECTIVE:: We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution magnetic resonance neurography (MRN). METHODS:: In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 × 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal after segmentation of median nerve voxels. RESULTS:: In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 ± 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p 〈 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83). CONCLUSION:: It has been difficult to prove the existence of fascicular/partial nerve lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve.
    Keywords: Data Processing ; Median Nerve ; Image Processing ; Joints ; Repetition ; Classification ; Segmentation ; Peripheral Nervous System ; N.M.R. ; Elbow ; Forearm ; Neuropathy ; Topography ; Neuroanatomy, Histology & Cytology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 6
    In: Neurology, 2018, Vol.91(7), pp.e625-e634
    Description: OBJECTIVE: To detect, localize, and quantify peripheral nerve lesions in amyloid light chain (AL) amyloidosis by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS: We prospectively examined 20 patients with AL-polyneuropathy (PNP) and 25 age- and sex-matched healthy volunteers. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into mild and moderate PNP. MRN in a 3.0 tesla scanner with anatomical coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed by using T2-weighted and dual-echo 2-dimensional sequences with spectral fat saturation and a 3-dimensional, T2-weighted inversion recovery sequence. Besides evaluation of nerve T2-weighted signal, detailed quantification of nerve injury by morphometric (nerve caliber) and microstructural MRN markers (proton spin density, T2 relaxation time) was conducted. RESULTS: Nerve T2-weighted signal increase correlated with disease severity: moderate (420.2 ± 60.1) vs mild AL-PNP (307.2 ± 17.9; p = 0.0003) vs controls (207.0 ± 6.4; p 〈 0.0001). Proton spin density was also higher in moderate (tibial: 525.5 ± 53.0; peroneal: 553.6 ± 64.5; sural: 492.0 ± 56.6) and mild AL-PNP (tibial: 431.6 ± 22.0; peroneal: 457.6 ± 21.7; sural: 404.8 ± 25.2) vs controls (tibial: 310.5 ± 14.1; peroneal: 313.6 ± 11.6; sural: 261.7 ± 11.0; p 〈 0.0001 for all nerves). T2 relaxation time was elevated in moderate AL-PNP only (tibial: p = 0.0106; peroneal: p = 0.0070; sural: p = 0.0190). Tibial nerve caliber was higher in moderate (58.0 ± 8.8 mm) vs mild AL-PNP (46.5 ± 2.5 mm; p = 0.008) vs controls (39.1 ± 1.2 mm; p 〈 0.0001). CONCLUSIONS: MRN detects and quantifies peripheral nerve injury in AL-PNP in vivo with high sensitivity and in close correlation with the clinical stage. Quantitative parameters are feasible new imaging biomarkers for the detection of early AL-PNP and might help to monitor microstructural nerve tissue changes under treatment.
    Keywords: Adult–Pathology ; Aged–Complications ; Analysis of Variance–Diagnostic Imaging ; Case-Control Studies–Etiology ; Evoked Potentials, Motor–Etiology ; Female–Etiology ; Ganglia, Spinal–Etiology ; Humans–Etiology ; Imaging, Three-Dimensional–Etiology ; Immunoglobulin Light-Chain Amyloidosis–Etiology ; Magnetic Resonance Imaging–Etiology ; Male–Etiology ; Middle Aged–Etiology ; Polyneuropathies–Etiology ; Protons–Etiology ; Severity of Illness Index–Etiology ; Protons;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 7
    In: Neurology, 2017, Vol.89(5), pp.475-484
    Description: OBJECTIVE:: To detect and quantify lesions of the small-caliber sural nerve (SN) in symptomatic and asymptomatic transthyretin familial amyloid polyneuropathy (TTR-FAP) by high-resolution magnetic resonance neurography (MRN) in correlation with electrophysiologic and histopathologic findings. METHODS:: Twenty-five patients with TTR-FAP, 10 asymptomatic carriers of the mutated transthyretin gene (mutTTR), and 35 age- and sex-matched healthy controls were prospectively included in this cross-sectional case-control study. All participants underwent 3T MRN with high-structural resolution (fat-saturated, T2-weighted, and double-echo sequences). Total imaging time was ≈45 minutes per patient. Manual SN segmentation was performed from its origin at the sciatic nerve bifurcation to the lower leg with subsequent evaluation of quantitative microstructural and morphometric parameters. Additional time needed for postprocessing was ≈1.5 hours per participant. Detailed neurologic and electrophysiologic examinations were conducted in the TTR group. RESULTS:: T2 signal and proton spin density (ρ) reliably differentiated between TTR-FAP (198.0 ± 13.3, 429.6 ± 15.25), mutTTR carriers (137.0 ± 16.9, p = 0.0009; 354.7 ± 21.64, p = 0.0029), and healthy controls (90.0 ± 3.4, 258.2 ± 9.10; p 〈 0.0001). Marked differences between mutTTR carriers and controls were found for T2 signal (p = 0.0065) and ρ (p 〈 0.0001). T2 relaxation time was higher in patients with TTR-FAP only (p = 0.015 vs mutTTR carriers, p = 0.0432 vs controls). SN caliber was higher in patients with TTR-FAP vs controls and in mutTTR carriers vs controls (p 〈 0.0001). Amyloid deposits were histopathologically detectable in 10 of 14 SN specimens. CONCLUSIONS:: SN injury in TTR-FAP is detectable and quantifiable in vivo by MRN even in asymptomatic mutTTR carriers. Differences in SN T2 signal between controls and asymptomatic mutTTR carriers are derived mainly from an increase of ρ, which overcomes typical limitations of established diagnostic methods as a highly sensitive imaging biomarker for early detection of peripheral nerve lesions. CLASSIFICATION OF EVIDENCE:: This study provides Class III evidence that MRN accurately identifies asymptomatic mutTTR carriers.
    Keywords: Adult–Diagnostic Imaging ; Aged–Genetics ; Amyloid Neuropathies, Familial–Pathology ; Case-Control Studies–Genetics ; Cross-Sectional Studies–Diagnostic Imaging ; Disability Evaluation–Injuries ; Early Diagnosis–Pathology ; Female–Pathology ; Heterozygote–Pathology ; Humans–Pathology ; Image Processing, Computer-Assisted–Pathology ; Magnetic Resonance Imaging–Pathology ; Male–Pathology ; Middle Aged–Pathology ; Neural Conduction–Pathology ; Prealbumin–Pathology ; Prodromal Symptoms–Pathology ; Prospective Studies–Pathology ; Sural Nerve–Pathology ; Abridged ; Prealbumin;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 8
    In: Annals of Neurology, November 2017, Vol.82(5), pp.676-685
    Description: To detect and quantify peripheral nerve lesions in multiple sclerosis (MS) by magnetic resonance neurography (MRN). Thirty-six patients diagnosed with MS based on the 2010 McDonald criteria (34 with the relapsing-remitting form, 2 with clinically isolated syndrome) with and without disease-modifying treatment were compared to 35 healthy age-/sex-matched volunteers. All patients underwent detailed neurological and electrophysiological examinations. Three Tesla MRN with large anatomical coverage of both legs and the lumbosacral plexus was performed by using 2-dimensional (2D) fat-saturated, T2-weighted (T2w) and dual echo turbo spin echo sequences as well as a 3D T2-weighted, fat-saturated SPACE sequence. Besides qualitative visual nerve assessment, a T2w signal quantification was performed by calculation of proton spin density and T2 relaxation time. Nerve diameter was measured as a morphometric criterion. T2w hyperintense nerve lesions were detectable in all MS patients, with a mean lesion number at thigh level of 151.5 ± 5.7 versus 19.1 ± 2.4 in controls (p 〈 0.0001). Nerve proton spin density was higher in MS (tibial/peroneal: 371.8 ± 7.7/368.9 ± 8.2) versus controls (tibial/peroneal: 266.0 ± 11.0/276.8 ± 9.7, p 〈 0.0001). In contrast, T2 relaxation time was significantly higher in controls (tibial/peroneal: 82.0 ± 2.1/78.3 ± 1.7) versus MS (tibial/peroneal: 64.3 ± 1.0/61.2 ± 0.9, p 〈 0.0001). Proximal tibial and peroneal nerve caliber was higher in MS (tibial: 52.4 ± 2.1mm , peroneal: 25.4 ± 1.3mm ) versus controls (tibial: 45.2 ± 1.4mm , p 〈 0.0015; peroneal: 21.3 ± 0.7mm , p = 0.0049). Peripheral nerve lesions could be visualized and quantified in MS in vivo by high-resolution MRN. Lesions are defined by an increase of proton spin density and a decrease of T2 relaxation time, indicating changes in the microstructural organization of the extracellular matrix in peripheral nerve tissue in MS. By showing involvement of the peripheral nervous system in MS, this proof-of-concept study may offer new insights into the pathophysiology and treatment of MS. Ann Neurol 2017;82:676-685.
    Keywords: Multiple Sclerosis, Relapsing-Remitting -- Pathology ; Peripheral Nerves -- Pathology;
    ISSN: 0364-5134
    E-ISSN: 1531-8249
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  • 9
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 01 July 2010, Vol.77(3), pp.670-676
    Description: To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m ), maintenance TMZ starting at 150 mg/m using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). The median follow-up interval was 21.7 months. Grade 4 hematologic toxicity was observed in 15 patients (36.6%). Treatment-related nonhematologic Grade 4-5 toxicity was reported for 2 patients (4.9%). The median progression-free survival was 7.6 months (95% confidence interval, 6.2–10.4). The 1-year survival rate was 73.2% (95% confidence interval, 56.8–84.2%). The presence of gene promoter methylation in the tumor tissue was associated with significantly superior progression-free survival. The dose-dense regimen of TMZ administered in a 1-week on/1-week off schedule resulted in acceptable nonhematologic toxicity. Compared with data from the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981-22981/CE.3, patients with an unmethylated gene promoter appeared not to benefit from intensifying the TMZ schedule regarding the median progression-free survival and overall survival. In contrast, data are promising for patients with a methylated promoter.
    Keywords: Glioblastoma ; Indomethacin ; O6-Methylguanine-DNA Methyltransferase ; Mgmt ; Radiotherapy ; Temozolomide ; Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
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  • 10
    Language: English
    In: BMC Neurology, 01 July 2017, Vol.17(1), pp.1-9
    Description: Abstract Background Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism resulting in multifaceted neurological, hepatic, and psychiatric symptoms. The objective of the study was to comparatively assess two clinical rating scales for WD, the Unified Wilson’s Disease Rating Scale (UWDRS) and the Global Assessment Scale for Wilson’s disease (GAS for WD), and to test the feasibility of the patient reported part of the UWDRS neurological subscale (termed the “minimal UWDRS”). Methods In this prospective, monocentric, cross-sectional study, 65 patients (median age 35 [range: 15–62] years; 33 female, 32 male) with treated WD were scored according to the two rating scales. Results The UWDRS neurological subscore correlated with the GAS for WD Tier 2 score (r = 0.80; p 〈 0.001). Correlations of the UWDRS hepatic subscore and the GAS for WD Tier 1 score with both the Model for End Stage Liver Disease (MELD) score (r = 0.44/r = 0.28; p 〈 0.001/p = 0.027) and the Child-Pugh score (r = 0.32/r = 0.12; p = 0.015/p = 0.376) were weak. The “minimal UWDRS” score significantly correlated with the UWDRS total score (r = 0.86), the UWDRS neurological subscore (r = 0.89), and the GAS for WD Tier 2 score (r = 0.86). Conclusions The UWDRS neurological and psychiatric subscales and the GAS for WD Tier 2 score are valuable tools for the clinical assessment of WD patients. The “minimal UWDRS” is a practical prescreening tool outside scientific trials.
    Keywords: Copper Metabolism ; German Network of Hereditary Movement Disorders (Genemove) ; Global Assessment Scale for Wilson’s Disease (GAS for Wd) ; Unified Wilson’s Disease Rating Scale (Uwdrs) ; Wilson Disease ; Medicine
    E-ISSN: 1471-2377
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