Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes.

BACKGROUND: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC). METHODS: 3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data. RESULTS: The sciatic nerve's MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r = - 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve's MTR peroneal NCV (r = - 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016). CONCLUSIONS: Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D. TRIAL REGISTRATION: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03022721 . 16 January 2017. RELEVANCE STATEMENT: Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes. KEY POINTS: • Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients. • Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes. • Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.

Phase angle of bioelectrical impedance analysis as an indicator for diabetic polyneuropathy in type 2 diabetes mellitus.

CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routine leading to increased morbidity and mortality. OBJECTIVE: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory and physical markers of DPN to evaluate PhA as possible diagnostic method for DPN. MATERIALS AND METHODS: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), amongst which 63 had DPN. The PhA was calculated from multi-frequency BIA. Nerve conduction studies (NCS), quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography (MRN) to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed. RESULTS: T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, p = 0.007, + 6.1%) and healthy controls (6.18 ± 0.08, p < 0.001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (ß=0.28; ß=0.31, p < 0.001) and tibial nerves (ß=0.28; ß=0.32, p < 0.001), Z-scores of QST (thermal detection ß=0.30, p < 0.05) and the FA (ß=0.60, p < 0.001). ROC analysis showed similar performance of PhA in comparison to mentioned diagnostic methods. CONCLUSION: The study shows that PhA is in comparison to other test systems used, at least an equally good and much easier to handle, investigator independent marker for detection of DPN.

Magnetic resonance neurography in spinal cord injury: Imaging findings and clinical significance.

BACKGROUND AND PURPOSE: It is unknown whether changes to the peripheral nervous system following spinal cord injury (SCI) are relevant for functional recovery or the development of neuropathic pain below the level of injury. Magnetic resonance neurography (MRN) at 3 T allows detection and localization of structural and functional nerve damage. This study aimed to combine MRN and clinical assessments in individuals with chronic SCI and nondisabled controls. METHODS: Twenty participants with chronic SCI and 20 controls matched for gender, age, and body mass index underwent MRN of the L5 dorsal root ganglia (DRG) and the sciatic nerve. DRG volume, sciatic nerve mean cross-sectional area (CSA), fascicular lesion load, and fractional anisotropy (FA), a marker for functional nerve integrity, were calculated. Results were correlated with clinical assessments and nerve conduction studies. RESULTS: Sciatic nerve CSA and lesion load were higher (21.29 ± 5.82 mm2 vs. 14.08 ± 4.62 mm2 , p < 0.001; and 8.70 ± 7.47% vs. 3.60 ± 2.45%, p < 0.001) in individuals with SCI compared to controls, whereas FA was lower (0.55 ± 0.11 vs. 0.63 ± 0.08, p = 0.022). DRG volumes were larger in individuals with SCI who suffered from neuropathic pain compared to those without neuropathic pain (223.7 ± 53.08 mm3 vs. 159.7 ± 55.66 mm3 , p = 0.043). Sciatic MRN parameters correlated with electrophysiological results but did not correlate with the extent of myelopathy or clinical severity of SCI. CONCLUSIONS: Individuals with chronic SCI are subject to a decline of structural peripheral nerve integrity that may occur independently from the clinical severity of SCI. Larger volumes of DRG in SCI with neuropathic pain support existing evidence from animal studies on SCI-related neuropathic pain.

Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.

INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A­fibers (δ) and unmyelinated C­fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN. METHODS: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (Ktrans), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp). RESULTS: The Ktrans (HC 0.031 min-1 ± 0.009, T2D 0.043 min-1 ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z­scores of thermal and mechanical detection correlated with Ktrans (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z­scores of thermal pain and Vp (r = -0.57; p = 0.015) correlated negatively. DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.

A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes. METHODS: Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST. RESULTS: Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm2; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=-0.048 [95% CI -0.091, -0.006], p=0.027; SL B=-0.062 [95% CI -0.103, -0.020], p=0.004) and CSA (MH ß=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=-0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio). CONCLUSIONS/INTERPRETATION: The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN. TRIAL REGISTRATION: ClinicalTrials.gov NCT03022721.

High-resolution MR neurography follow-up of SARS-CoV-2 vaccination-associated neuralgic amyotrophy.

Little is known about the value of high-resolution follow-up imaging in patients with neuralgic amyotrophy (NA) and the question of the best treatment algorithm remains unclear. Three patients (one female, two male) with the clinical presentation of SARS-CoV-2-vaccination-associated NA underwent initial magnetic resonance neurography (MRN) imaging and follow-up examinations. All patients showed a marked clinical improvement, independent of treatment, including an almost full recovery of motor function over the course of 8-12 months which was accurately mirrored by imaging findings on MRN. MRN imaging is a valuable tool for monitoring the further clinical course of patients suffering from vaccination-associated NA.

Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes.

CONTEXT: Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals. OBJECTIVE: The aim of this study was to demonstrate the feasibility of a noninvasive assessment of human muscle microcirculation via dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of skeletal muscle in patients with type 2 diabetes (T2D). METHODS: A total of 56 participants (46 with T2D, 10 healthy controls [HC]) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated. RESULTS: In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; P = 0.042) while the homeostasis model assessment (HOMA) index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; P = .011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, P = .018) and HOMA index (r = -0.38, P = .020). CONCLUSION: The results signify that skeletal muscle DCE-MRI can be employed as a noninvasive technique for the assessment of muscle microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regard to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.

Neurological autoimmune diseases following vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A follow-up study.

BACKGROUND AND PURPOSE: Population-based studies suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger neurological autoimmunity including immune-mediated thrombotic thrombocytopenia. Long-term characterization of cases is warranted to facilitate patient care and inform vaccine-hesitant individuals. METHODS: In this single-center prospective case study with a median follow-up of 387 days long-term clinical, laboratory and imaging characteristics of patients with neurological autoimmunity diagnosed in temporal association (≤6 weeks) with SARS-CoV-2 vaccinations are reported. RESULTS: Follow-up data were available for 20 cases (central nervous system demyelinating diseases n = 8, inflammatory peripheral neuropathies n = 4, vaccine-induced immune thrombotic thrombocytopenia n = 3, myositis n = 2, myasthenia n = 1, limbic encephalitis n = 1, giant cell arteritis n = 1). Following therapy, the overall disability level improved (median modified Rankin Scale at diagnosis 3 vs. 1 at follow-up). The condition of two patients worsened despite immunosuppressants possibly related to their autoimmune diagnoses (limbic encephalitis n = 1, giant cell arteritis n = 1). At 12 months' follow-up, 12 patients achieved complete clinical remissions with partial responses in five and stable disease in one case. Correspondingly, autoimmune antibodies were non-detectable or titers had significantly lowered in all, and repeat imaging revealed radiological responses in most cases. Under vigilant monitoring 15 patients from our cohort underwent additional SARS-CoV-2 vaccinations (BNT162b2 n = 12, mRNA-1273 n = 3). Most patients (n = 11) received different vaccines than prior to diagnosis of neurological autoimmunity. Except for one short-lasting relapse, which responded well to steroids, re-vaccinations were well tolerated. CONCLUSIONS: In this study long-term characteristics of neurological autoimmunity encountered after SARS-CoV-2 vaccinations are defined. Outcome was favorable in most cases. Re-vaccinations were well tolerated and should be considered on an individual risk/benefit analysis.

Diametrical Effects of Glucose Levels on Microvascular Permeability of Peripheral Nerves in Patients With Type 2 Diabetes With and Without Diabetic Neuropathy.

Clinical studies investigating the benefit of glucose control on the progression of diabetic neuropathy (DN) have come to controversial results in patients with type 2 diabetes (T2D). This study aimed to assess associations of HbA1c levels with parameters of nerve perfusion in patients with T2D with and without DN using dynamic contrast-enhanced magnetic resonance neurography (DCE-MRN) at 3 Tesla. A total of 58 patients with T2D (20 with DN and 38 without DN) took part in this cross-sectional single-center study. Groups were matched for age, BMI, HbA1c, duration of T2D, and renal function. All patients underwent DCE-MRN with subsequent electrophysiologic and serologic testing. The extended Tofts model was used to quantify the sciatic nerve's microvascular permeability (Ktrans), volume fraction of the extracapillary extracellular space, and volume fraction of the plasma space. As a main result, we found that Ktrans correlated positively with HbA1c in patients with DN, while a negative correlation between the two parameters was found in patients without DN. Our results indicate that the effect of glucose control on the capillary permeability of peripheral nerves differs between patients with T2D with and without DN.