Evolution of peripheral nerve changes in early multiple sclerosis-a longitudinal MR neurography study.

Objectives: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system. Increasing evidence indicates additional peripheral nerve involvement in early and chronic disease stages. To investigate the evolution of peripheral nerve changes in patients first diagnosed with MS using quantitative MR neurography. Materials and methods: This prospective study included 19 patients with newly diagnosed MS according to the revised McDonald criteria (16 female, mean 30.2 ± 7.1 years) and 19 age-/sex-matched healthy volunteers. High-resolution 3 T MR neurography of the sciatic nerve using a quantitative T2-relaxometry sequence was performed, which yielded the biomarkers of T2 relaxation time (T2app) and proton spin density (PSD). Follow-up scans of patients were performed after median of 12 months (range 7-16). Correlation analyses considered clinical symptoms, intrathecal immunoglobulin synthesis, nerve conduction study, and lesion load on brain and spine MRI. Results: Patients showed increased T2app and decreased PSD compared to healthy controls at initial diagnosis and follow-up (p < 0.001 each). Compared to the initial scan, T2app further increased in patients at follow-up (p = 0.003). PSD further declined by at least 10% in 9/19 patients and remained stable in another 9/19 patients. Correlation analyses did not yield significant results. Conclusion: Peripheral nerve involvement in MS appears at initial diagnosis and continues to evolve within 1 year follow-up with individual dynamics. Quantitative MRN provides non-invasive biomarkers to detect and monitor peripheral nerve changes in MS.

Microstructural changes of peripheral nerves in early multiple sclerosis: A prospective magnetic resonance neurography study.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS). However, there is increasing evidence of peripheral nerve involvement. This study aims to characterize the pattern of peripheral nerve changes in patients with newly diagnosed MS using quantitative magnetic resonance (MR) neurography. METHODS: In this prospective study, 25 patients first diagnosed with MS according to the revised McDonald criteria (16 female, mean age = 32.8 ± 10.6 years) and 14 healthy controls were examined with high-resolution 3-T MR neurography of the sciatic nerve using diffusion kurtosis imaging (DKI; 20 diffusional directions, b = 0, 700, 1200 s/mm2 ) and magnetization transfer imaging (MTI). In total, 15 quantitative MR biomarkers were analyzed and correlated with clinical symptoms, intrathecal immunoglobulin synthesis, electrophysiology, and lesion load on brain and spine MR imaging. RESULTS: Patients showed decreased fractional anisotropy (mean = 0.51 ± 0.04 vs. 0.56 ± 0.03, p < 0.001), extra-axonal tortuosity (mean = 2.32 ± 0.17 vs. 2.49 ± 0.17, p = 0.008), and radial kurtosis (mean = 1.40 ± 0.23 vs. 1.62 ± 0.23, p = 0.014) and higher radial diffusivity (mean = 1.09 ∙ 10-3 mm2 /s ± 0.16 vs. 0.98 ± 0.11 ∙ 10-3 mm2 /s, p = 0.036) than controls. Groups did not differ in MTI. No significant association was found between MR neurography markers and clinical/laboratory parameters or CNS lesion load. CONCLUSIONS: This study provides further evidence of peripheral nerve involvement in MS already at initial diagnosis. The characteristic pattern of DKI parameters indicates predominant demyelination and suggests a primary coaffection of the peripheral nervous system in MS. This first human study using DKI for peripheral nerves shows its potential and clinical feasibility in providing novel biomarkers.

Evaluation of risdiplam efficacy in 5q spinal muscular atrophy: A systematic comparison of electrophysiologic with clinical outcome measures.

BACKGROUND: To assess compound muscle action potential (CMAP) amplitudes as electrophysiologic markers in relation to clinical outcome in adult patients with 5q-linked spinal muscular atrophy (SMA) before and during treatment with risdiplam. METHODS: In this monocentric longitudinal cohort study, CMAP of 18 adult patients with SMA type 2 or 3 were assessed at baseline (T0 ) and after 10 months (T10 ) of risdiplam treatment. CMAP amplitudes of the median, ulnar, peroneal, and tibial nerves were compared with established clinical outcome scores, and with the course of disease before start of treatment. RESULTS: During a pharmacotherapy-naive pre-treatment period of 328 ± 46 days, Revised Upper Limb Module (RULM) score and peroneal nerve CMAP amplitudes decreased, while CMAP of tibial and upper limb nerves remained unchanged. CMAP amplitudes positively correlated with clinical scores (Hammersmith Functional Motor Scale-Expanded [HFMSE], RULM) at T0 . During risdiplam treatment, HFMSE and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores increased, paralleled by marked increase of CMAP amplitudes in both median nerves (T10 -T0 ; right: Δ = 1.4 ± 1.4 mV, p = 0.0003; left: Δ = 1.3 ± 1.4 mV, p = 0.0007), but not in ulnar, peroneal, or tibial nerves. A robust increase of median nerve CMAP amplitudes correlated well with an increase in the HFMSE score (T10 -T0 ). Median nerve CMAP amplitudes at T0 were associated with subsequent risdiplam-related improvement of HFMSE and CHOP INTEND scores at T10 . CONCLUSIONS: Median nerve CMAP amplitudes increase with risdiplam treatment in adult SMA patients, and should be further evaluated as potential easy-to-use electrophysiologic markers in assessing and monitoring clinical response to therapy.

Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography.

BACKGROUND AND OBJECTIVES: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders. While peripheral nerve involvement is frequent in spastic paraplegia 7 (SPG7), the evidence of peripheral nerve involvement in SPG4 is more controversial. We aimed to characterize lower extremity peripheral nerve involvement in SPG4 and SPG7 by quantitative magnetic resonance neurography (MRN). METHODS: Twenty-six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age-/sex-matched healthy controls prospectively underwent high-resolution MRN with large coverage of the sciatic and tibial nerve. Dual-echo turbo-spin-echo sequences with spectral fat-saturation were utilized for T2-relaxometry and morphometric quantification, while two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments. RESULTS: All microstructural (proton spin density [ρ], T2-relaxation time, magnetization transfer ratio) and morphometric (cross-sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. ρ was superior in differentiating subgroups and identifying subclinical nerve damage in SPG4 and SPG7 without neurophysiologic signs of polyneuropathy. MRN markers correlated well with clinical scores and electroneurographic results. CONCLUSIONS: MRN characterizes peripheral nerve involvement in SPG4 and SPG7 as a neuropathy with predominant axonal loss. Evidence of peripheral nerve involvement in SPG4 and SPG7, even without electroneurographically manifest polyneuropathy, and the good correlation of MRN markers with clinical measures of disease progression, challenge the traditional view of the existence of HSPs with isolated pyramidal signs and suggest MRN markers as potential progression biomarkers in HSP.

Quantification and Proximal-to-Distal Distribution Pattern of Tibial Nerve Lesions in Relapsing-Remitting Multiple Sclerosis : Assessment by MR Neurography.

PURPOSE: Recent studies suggest an involvement of the peripheral nervous system (PNS) in multiple sclerosis (MS). Here, we characterize the proximal-to-distal distribution pattern of peripheral nerve lesions in relapsing-remitting MS (RRMS) by quantitative magnetic resonance neurography (MRN). METHODS: A total of 35 patients with RRMS were prospectively included and underwent detailed neurologic and electrophysiologic examinations. Additionally, 30 age- and sex-matched healthy controls were recruited. 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was conducted using dual-echo 2­dimensional relaxometry sequences with spectral fat saturation. Quantification of PNS involvement was performed by evaluating microstructural (proton spin density (ρ), T2-relaxation time (T2app)), and morphometric (cross-sectional area, CSA) MRN markers in every axial slice. RESULTS: In patients with RRMS, tibial nerve lesions at the thigh and the lower leg were characterized by a decrease in T2app and an increase in ρ compared to controls (T2app thigh: p < 0.0001, T2app lower leg: p = 0.0040; ρ thigh: p < 0.0001; ρ lower leg: p = 0.0098). An additional increase in nerve CSA was only detectable at the thigh, while the semi-quantitative marker T2w-signal was not altered in RRMS in both locations. A slight proximal-to-distal gradient was observed for T2app and T2-signal, but not for ρ. CONCLUSION: PNS involvement in RRMS is characterized by a decrease in T2app and an increase in ρ, occurring with proximal predominance at the thigh and the lower leg. Our results indicate microstructural alterations in the extracellular matrix of peripheral nerves in RRMS and may contribute to a better understanding of the pathophysiologic relevance of PNS involvement.

Peripheral Nerve Involvement at First Diagnosis of Multiple Sclerosis: A Prospective MR Neurography Study.

OBJECTIVES: The aim of this study was to assess peripheral nerve involvement in patients with multiple sclerosis (MS) at first clinical presentation using quantitative magnetic resonance (MR) neurography in correlation with clinical, laboratory, electrophysiological, and central nervous MR imaging data. MATERIALS AND METHODS: In this prospective monocentric study, 30 patients first diagnosed with MS according to the McDonald criteria (19 women; mean age, 32.4 ± 8.8 years) and 30 age- and sex-matched healthy volunteers were examined with high-resolution 3 T MR neurography using a dual-echo T2-relaxometry sequence covering the tibial and peroneal nerves from proximal thigh to distal calf. Magnetic resonance biomarkers of T2 relaxation time (T2 app ), proton spin density (PSD), and nerve cross-sectional area (CSA) were correlated with clinical symptoms, intrathecal immunoglobulin (Ig) synthesis, nerve conduction study, and lesion load on brain and spine MR imaging. The diagnostic accuracy of MR biomarkers was assessed using receiver-operating characteristic curves. RESULTS: Diffuse nerve changes were detected along the tibial and peroneal nerves in MS patients, who showed decreased PSD ( P < 0.001), increased T2 app ( P < 0.001), and smaller tibial nerve CSA ( P < 0.001) compared with healthy subjects. Tibial PSD was identified as best parameter separating patients from controls (area under the curve = 0.876). Intrathecal IgG and IgM synthesis correlated with PSD values ( r = -0.44, P = 0.016, and r = -0.42, P = 0.022). Contrast-enhancement of brain or spine lesions was related to larger tibial and peroneal CSA ( P < 0.001, P = 0.033). Abnormal electrophysiology correlated with higher tibial and peroneal T2 app ( P < 0.001 and P = 0.033), lower tibial and peroneal PSD ( P = 0.018 and P = 0.002), and smaller peroneal CSA ( P < 0.001). CONCLUSIONS: Quantitative MR neurography reveals peripheral nerve changes in patients with initial diagnosis of MS. Correlation of imaging findings with intrathecal immunoglobulin synthesis may indicate a primary coaffection of the peripheral nervous system in MS.

Quantitative magnetic resonance neurographic characterization of peripheral nerve involvement in manifest and pre-ataxic spinocerebellar ataxia type 3.

BACKGROUND AND PURPOSE: Knowledge about the exact underlying pathophysiological changes involved in the genesis and progression of spinocerebellar ataxia type 3 (SCA3) is limited. Lower extremity peripheral nerve lesions in clinically, genetically and electrophysiologically classified ataxic and pre-ataxic SCA3 mutation carriers were characterized and quantified by magnetic resonance neurography (MRN). METHODS: Eighteen SCA3 mutation carriers and 20 age-/sex-matched healthy controls were prospectively enrolled. All SCA3 mutation carriers underwent detailed neurological and electrophysiological examinations. 3 T MRN covered the lumbosacral plexus and proximal thigh to the tibiotalar joint by using T2-weighted inversion recovery sequences, dual-echo relaxometry sequences with spectral fat saturation, and two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse. Detailed quantification of nerve lesions by morphometric and microstructural MRN markers, including T2 relaxometry and magnetization transfer contrast imaging, was conducted in all study participants. RESULTS: MRN detected peripheral nerve damage in ataxic and pre-ataxic SCA3. The quantitative markers proton spin density (ρ), T2 relaxation time, magnetization transfer ratio and cross-sectional area were decreased in SCA3, indicating chronic axonopathy. MTR and ρ identified early, subclinical nerve damage in pre-ataxic SCA3 and in SCA3 mutation carriers without polyneuropathy and were superior in differentiating between all subgroups. Additionally, microstructural markers correlated well with clinical symptom scores and electrophysiological results. CONCLUSIONS: Our data provide a comprehensive characterization of peripheral nerve damage in SCA3 and assist in understanding the mechanisms of the multisystemic disease evolution. Evidence of peripheral nerve involvement prior to the onset of clinically overt ataxia might have important implications for designing early intervention studies.

Characterization and quantification of alcohol-related polyneuropathy by magnetic resonance neurography.

BACKGROUND: We characterized and quantified peripheral nerve damage in alcohol-dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS: Thirty-one adult patients with a history of excessive alcohol consumption and age-/sex-matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol-related polyneuropathy (ALN) and without ALN (Non-ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual-echo 2-dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross-sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ], apparent T2-relaxation-time [T2app ]) was conducted in all study participants. RESULTS: MRN detected nerve damage in ADP with and without ALN. A proximal-to-distal gradient was identified for nerve T2-weighted (T2w)-signal and T2app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN (p < 0.0001) and in Non-ALN (p = 0.0052) versus controls, and T2app was higher in ALN versus controls (p < 0.0001) and also in ALN versus Non-ALN (p = 0.0214). T2w-signal and CSA were only higher in ALN versus controls. CONCLUSIONS: MRN detects and quantifies peripheral nerve damage in ADP in vivo even in the absence of clinically overt ALN. Microstructural markers (T2app , ρ) are most suitable for differentiating between ADP with and without manifest ALN, and may help to elucidate the underlying pathomechanism in ALN.

Dual-Echo Turbo Spin Echo and 12-Echo Multi Spin Echo Sequences as Equivalent Techniques for Obtaining T2-Relaxometry Data: Application in Symptomatic and Asymptomatic Hereditary Transthyretin Amyloidosis as a Surrogate Disease.

OBJECTIVES: Multi spin echo (MSE) sequences are often used for obtaining T2-relaxometry data as they provide defined echo times (TEs). Due to their time-consuming acquisition, they are frequently replaced by turbo spin echo (TSE) sequences that in turn bear the risk of systematic errors when analyzing small structures or lesions. With this study, we aim to test whether T2-relaxometry data derived from either dual-echo TSE or 12-echo MSE sequences are equivalent for quantifying peripheral nerve lesions. Hereditary transthyretin (ATTRv) amyloidosis was chosen as a surrogate disease, as it allows the inclusion of both asymptomatic carriers of the underlying variant transthyretin gene (varTTR) and symptomatic ATTRv amyloidosis patients. MATERIALS AND METHODS: Overall, 50 participants with genetically confirmed varTTR (20 clinically symptomatic ATTRv amyloidosis; 4 females, 16 males; mean age, 61.8 years; range, 33-76 years; and 30 asymptomatic varTTR-carriers; 18 females, 12 males; mean age, 43.1 years; range, 21-62 years), and 30 healthy volunteers (13 females, 17 males, mean age 41.3 years, range 22-73) were prospectively included and underwent magnetic resonance neurography at 3 T. T2-relaxometry was performed by acquiring an axial 2-dimensional dual-echo TSE sequence with spectral fat saturation (TE1/TE2, 12/73 milliseconds; TR, 5210 milliseconds; acquisition time, 7 minutes, 30 seconds), and an axial 2-dimensional MSE sequence with spectral fat saturation and with 12 different TE (TE1, 10 milliseconds to TE12, 120 milliseconds; ΔTE, 10 milliseconds; TR, 3000 milliseconds; acquisition time, 11 minutes, 23 seconds) at the right mid to lower thigh. Sciatic nerve regions of interest were manually drawn in ImageJ on 10 central slices per participant and sequence, and the apparent T2-relaxation time (T2app) and proton spin density (ρ) were calculated individually from TSE and MSE relaxometry data. RESULTS: Linear regression showed that T2app values obtained from the dual-echo TSE (T2appTSE), and those calculated from the 12-echo MSE (T2appMSE) were mathematically connected by a factor of 1.3 throughout all groups (controls: 1.26 ± 0.02; varTTR-carriers: 1.25 ± 0.02; symptomatic ATTRv amyloidosis: 1.28 ± 0.02), whereas a factor of 0.5 was identified between respective ρ values (controls: 0.47 ± 0.01; varTTR-carriers: 0.47 ± 0.01; symptomatic ATTRv amyloidosis: 0.50 ± 0.02). T2app calculated from both TSE and MSE, distinguished between symptomatic ATTRv (T2appTSE 66.38 ± 2.6; T2appMSE 84.6 ± 3.3) and controls (T2appTSE 58.1 ± 1.0, P = 0.0028; T2appMSE 72.8 ± 0.7, P < 0.0001), whereas differences between varTTR-carriers (T2appTSE 61.8 ± 1.5; T2appMSE 76.7 ± 1.3) and ATTRv amyloidosis were observed only for T2appMSE (P = 0.0082). The ρ value differentiated well between healthy controls (ρTSE 365.1 ± 7.2; ρMSE 170.4 ± 3.8) versus varTTR-carriers (ρTSE 415.7 ± 9.8, P = 0.0027; ρMSE 193.7 ± 5.3, P = 0.0398) and versus symptomatic ATTRv amyloidosis (ρTSE 487.8 ± 17.9; ρMSE 244.7 ± 13.1, P < 0.0001, respectively), but also between varTTR-carriers and ATTRv amyloidosis (ρTSEP = 0.0001; ρMSEP < 0.0001). CONCLUSIONS: Dual-echo TSE and 12-echo MSE sequences provide equally robust and reliable T2-relaxometry data when calculating T2app and ρ. Due to their shorter acquisition time and higher resolution, TSE sequences may be preferred in future magnetic resonance imaging protocols. As a secondary result, ρ can be confirmed as a sensitive biomarker to detect early nerve lesions as it differentiated best among healthy controls, asymptomatic varTTR-carriers, and symptomatic ATTRv amyloidosis, whereas T2app might be beneficial in already manifest ATTRv amyloidosis.

Chemotherapy-induced peripheral neuropathy: longitudinal analysis of predictors for postural control.

Impaired postural control is often observed in response to neurotoxic chemotherapy. However, potential explanatory factors other than chemotherapy-induced peripheral neuropathy (CIPN) have not been adequately considered to date due to primarily cross-sectional study designs. Our objective was to comprehensively analyze postural control during and after neurotoxic chemotherapy, and to identify potential CIPN-independent predictors for its impairment. Postural control and CIPN symptoms (EORTC QLQ-CIPN20) were longitudinally assessed before, during and three weeks after neurotoxic chemotherapy, and in three and six months follow-up examinations (N = 54). The influence of peripheral nerve function as determined by nerve conduction studies (NCS: compound motor action potentials (CMAP) and sensory action potentials (SNAP)), physical activity, and muscle strength on the change in postural control during and after chemotherapy was analyzed by multiple linear regression adjusted for age and body mass index. Postural control, CIPN signs/symptoms, and CMAP/SNAP amplitudes significantly deteriorated during chemotherapy (p < .01). During follow-up, patients recovered from postural instabilities (p < .01), whereas CIPN signs/symptoms and pathologic NCS findings persisted compared to baseline (p < .001). The regression model showed that low CMAP and high SNAP amplitudes at baseline predicted impairment of postural control during but not after chemotherapy. Hence, pre-therapeutically disturbed somatosensory inputs may induce adaptive processes that have compensatory effects and allow recovery of postural control while CIPN signs/symptoms and pathologic peripheral nerve function persist. Baseline NCS findings in cancer patients who receive neurotoxic chemotherapy thus might assist in delineating individual CIPN risk profiles more precisely to which specific exercise intervention programs could be tailor-made.

Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis.

OBJECTIVE: To quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular changes. METHODS: Twenty-five patients with symptomatic ATTRv-PNP, 30 asymptomatic carriers of the mutant transthyretin gene (mutTTR), and 20 age-/sex-matched healthy controls prospectively underwent magnetization transfer contrast imaging at 3 Tesla. Two axial three-dimensional gradient echo sequences with and without an off-resonance saturation rapid frequency pulse were conducted at the right distal thigh. Sciatic nerve regions of interest were manually drawn on 10 consecutive axial slices in the images without off-resonance saturation, and then transferred to the corresponding slices that were generated by the sequence with the off-resonance saturation pulse. Subsequently, the MTR and cross-sectional area (CSA) of the sciatic nerve were evaluated. Detailed neurologic and electrophysiologic examinations were conducted in all ATTRv-PNP patients and mutTTR-carriers. RESULTS: Sciatic nerve MTR and CSA reliably differentiated between ATTRv-PNP, mutTTR-carriers, and controls. MTR was lower in ATTRv-PNP (26.4 ± 0.7; P < 0.0001) and in mutTTR-carriers (32.6 ± 0.8; P = 0.0005) versus controls (39.4 ± 2.1), and was also lower in ATTRv-PNP versus mutTTR-carriers (P = 0.0009). MTR correlated negatively with the NIS-LL and positively with CMAPs and SNAPs. CSA was higher in ATTRv-PNP (34.3 ± 1.7 mm3 ) versus mutTTR-carriers (26.0 ± 1.1 mm3 ; P = 0.0005) and versus controls (20.4 ± 1.2 mm3 ; P < 0.0001). CSA was also higher in mutTTR-carriers versus controls. INTERPRETATION: MTR is a novel imaging marker that can quantify macromolecular changes in ATTRv-PNP and differentiate between symptomatic ATTRv-PNP and asymptomatic mutTTR-carriers and correlates with electrophysiology.

Quantitative MR neurography biomarkers in 5q-linked spinal muscular atrophy.

OBJECTIVE: To characterize and quantify peripheral nerve lesions and muscle degeneration in clinically, genetically, and electrophysiologically well-classified, nonpediatric patients with 5q-linked spinal muscular atrophy (SMA) by high-resolution magnetic resonance neurography (MRN). METHODS: Thirty-one adult patients with genetically confirmed 5q-linked SMA types II, IIIa, and IIIb and 31 age- and sex-matched healthy volunteers were prospectively investigated. All patients received neurologic, physiotherapeutic, and electrophysiologic assessments. MRN at 3.0T with anatomic coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed with dual-echo 2D relaxometry sequences with spectral fat saturation and a 3D T2-weighted inversion recovery sequence. Detailed quantification of nerve injury by morphometric and microstructural MRN markers and qualitative classification of fatty muscle degeneration were conducted. RESULTS: Established clinical scores and compound muscle action potentials discriminated well between the 3 SMA types. MRN revealed that peroneal and tibial nerve cross-sectional area (CSA) at the thigh and lower leg level as well as spinal nerve CSA were markedly decreased throughout all 3 groups, indicating severe generalized peripheral nerve atrophy. While peroneal and tibial nerve T2 relaxation time was distinctly increased at all analyzed anatomic regions, the proton spin density was clearly decreased. Marked differences in fatty muscle degeneration were found between the 3 groups and for all analyzed compartments. CONCLUSIONS: MRN detects and quantifies peripheral nerve involvement in SMA types II, IIIa, and IIIb with high sensitivity in vivo. Quantitative MRN parameters (T2 relaxation time, proton spin density, CSA) might serve as novel imaging biomarkers in SMA to indicate early microstructural nerve tissue changes in response to treatment.