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  • 1
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    Sciatic nerve microvascular permeability in type 2 diabetes decreased in patients with neuropathy
    Wiley ; 2022
    In:  Annals of Clinical and Translational Neurology Vol. 9, No. 6 ( 2022-06), p. 830-840
    Details
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 9, No. 6 ( 2022-06), p. 830-840
    Abstract: Clinical and histological studies have found evidence that nerve ischemia is a major contributor to diabetic neuropathy (DN) in type 2 diabetes (T2D). The aim of this study was to investigate peripheral nerve microvascular permeability using dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) to analyze potential correlations with clinical, electrophysiological, and demographic data. Methods Sixty‐five patients (35/30 with/without DN ) and 10 controls matched for age and body mass index ( BMI ) underwent DCE MRN of the distal sciatic nerve with an axial T1 ‐weighted sequence. Microvascular permeability ( K trans ), plasma volume fraction ( v p ), and extravascular extracellular volume fraction ( v e ) were determined with the extended Tofts model, and subsequently correlated with clinical data. Results K trans and v e were lower in T2D patients with DN compared to patients without DN (0.037 min −1  ± 0.010 vs. 0.046 min −1  ± 0.014; p  = 0.011, and 2.35% ± 3.87 vs. 5.11% ± 5.53; p  = 0.003, respectively). In individuals with T2D, K trans correlated positively with tibial, peroneal, and sural NCVs ( r  = 0.42; 95%CI = 0.18 to 0.61, 0.50; 95%CI = 0.29 to 0.67, and 0.44; 95%CI = 0.19 to 0.63, respectively), with tibial and peroneal CMAPs ( r  = 0.27; 95%CI = 0.01 to 0.49 and r  = 0.32; 95%CI = 0.07 to 0.53), and with the BMI ( r  = 0.47; 95%CI = 0.25 to 0.64). Negative correlations were found with the neuropathy deficit score ( r  = −0.40; 95%CI = −0.60 to −0.16) and age ( r  = −0.51; 95%CI = −0.67 to −0.31). No such correlations were found for v p . Conclusion This study is the first to find associations of MR nerve perfusion parameters with clinical and electrophysiological parameters related to DN in T2D. The results indicate that a decrease in microvascular permeability but not plasma volume may result in nerve ischemia that subsequently causes demyelination.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    URL: Article
    DOI: 10.1002/acn3.v9.6
    DOI: 10.1002/acn3.51563
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2740696-9
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  • 2
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    Neurological autoimmune diseases following vaccinations against severe acute respiratory syndrome coronavirus 2 ( SARS‐CoV ‐2): A follow‐up study
    Wiley ; 2023
    In:  European Journal of Neurology Vol. 30, No. 2 ( 2023-02), p. 463-473
    Details
    In: European Journal of Neurology, Wiley, Vol. 30, No. 2 ( 2023-02), p. 463-473
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    URL: Article
    DOI: 10.1111/ene.v30.2
    DOI: 10.1111/ene.15602
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2020241-6
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  • 3
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    82-OR: Phase Angle of Bioelectrical Impedance Analysis Correlates with Multiple Parameters of Diabetic Polyneuropathy in Patients with Type 2 Diabetes
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Background and Aims: Sensorimotor polyneuropathy (DPN) is the most common diabetic complication and a major contributor to increased morbidity and mortality in diabetic patients. With diagnostic methods still being limited, we aimed to correlate the phase angle (PhA) , a marker derived from bioelectrical impedance analysis, with determinants of DPN. In particular we used magnetic resonance neurography (MRN) together with state-of-the-art clinical and electrophysiological measurements of DPN. Materials and Methods: In this cross-sectional observational study we included 1healthy subjects and 2patients with type 2 diabetes (T2D) , amongst which 63 had DPN. The PhA was calculated using a multi-frequency bioelectrical impedance analyzer. Nerve conduction studies, quantitative sensory testing (QST) and diffusion weighted 3 Tesla MRN to determine the fractional anisotropy (FA) were performed. Results: In the group comparison lower PhA values were found in T2D patients with DPN in contrast to T2D patients without DPN (5.71+/-0.vs. 6.07+/-0.08, p=0.007) and healthy controls (5.71+/-0.vs. 6.18+/-0.08, p & lt;0.001) . Confounder-adjusted analysis among T2D patients showed positive correlations of the PhA with the FA of MRN (r=0.41, p=0.006) , with conduction velocities and action potentials of the peroneal (r=0.27, p & lt;0.001; r=0.29, p & lt;0.001) and tibial nerve (r=0.22, p=0.005; r=0.30, p & lt;0.001) and with Z-scores of QST (thermal detection r=0.31, p & lt;0.001; thermal pain r=0.20, p=0.010; mechanical pain r=0.19, p=0.015; mechanical detection r=0.19, p=0.013) . Conclusion: The close association of the PhA with the FA, a marker of structural nerve integrity of MRN, might reflect the similar physics of current or diffusion respectively being impaired by altered nerve composition. Due to correlations of the PhA with classical diagnostics of DPN it could become a novel, easily accessible and powerful marker for a quick assessment of DPN. Disclosure L.Schimpfle: None. C.Mooshage: None. D.Tsilingiris: None. Z.Kender: None. F.T.Kurz: None. J.M.E.Jende: None. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. M.Bendszus: None. S.Kopf: Board Member; Novo Nordisk, Speaker's Bureau; AstraZeneca, Recordati S.p.A. Funding The German Research Council (DFG, SFB 1158)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-82-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 4
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 15 ( 2022-1-24)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2022-1-24)
    Abstract: Recent studies have found that troponin T parallels the structural and functional decay of peripheral nerves at the level of the lower limbs in patients with type 2 diabetes (T2D). The aim of this study was to determine whether this finding can also be reproduced at the level of the upper limbs. Methods Ten patients with fasting glucose levels & gt;100 mg/dl (five with prediabetes and five with T2D) underwent magnetic resonance neurography of the right upper arm comprising T2-weighted and diffusion weighted sequences. The fractional anisotropy (FA), an indicator for the structural integrity of peripheral nerves, was calculated in an automated approach for the median, ulnar, and radial nerve. All participants underwent additional clinical, serological, and electrophysiological assessments. Results High sensitivity Troponin T (hsTNT) and HbA1c were negatively correlated with the average FA of the median, ulnar and radial nerve ( r = −0.84; p = 0.002 and r = −0.68; p = 0.032). Both FA and hsTNT further showed correlations with items of the Michigan Hand Outcome Questionnaire ( r = −0.76; p = 0.010 and r = 0.87; p = 0.001, respectively). A negative correlation was found for hsTNT and HbA1c with the total Purdue Pegboard Test Score ( r = −0.87; p = 0.001 and r = −0.68; p = 0.031). Conclusion This study is the first to find that hsTNT and HbA1c are associated with functional and structural parameters of the nerves at the level of the upper limbs in patients with impaired glucose tolerance and T2D. Our results support the hypothesis that hyperglycemia-related microangiopathy, represented by elevated hsTNT levels, is a contributor to nerve damage in diabetic polyneuropathy.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2021.741494
    DOI: 10.3389/fnins.2021.741494.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 5
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    Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism ( 2023-08-15)
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, ( 2023-08-15)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgad481
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 6
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    Neurological autoimmune diseases following vaccinations against SARS‐CoV‐2: a case series
    Wiley ; 2022
    In:  European Journal of Neurology Vol. 29, No. 2 ( 2022-02), p. 555-563
    Details
    In: European Journal of Neurology, Wiley, Vol. 29, No. 2 ( 2022-02), p. 555-563
    Abstract: Population‐based studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines may trigger immune‐mediated thrombotic thrombocytopenia (VITT) raising concerns for other autoimmune responses. The aim was to characterize neurological autoimmunity after SARS‐CoV‐2 vaccinations. Methods In this single‐centre prospective case study patients with neurological autoimmunity in temporal association (≤6 weeks) with SARS‐CoV‐2 vaccinations and without other triggers are reported. Clinical, laboratory and imaging data were collected with a median follow‐up of 49 days. Results In the study period 232,603 inhabitants from the main catchment area of our hospital (Rhein‐Neckar‐Kreis, county) received SARS‐CoV‐2 vaccinations. Twenty‐one cases (new onset n  = 17, flares n  = 4) diagnosed a median of 11 days (range 3–23) following SARS‐CoV‐2 vaccinations (BNT162b2 n  = 12, ChAdOx1 n  = 8, mRNA‐1273 n  = 1) were identified. Cases included VITT with cerebral venous sinus thrombosis ( n  = 3), central nervous system demyelinating diseases ( n  = 8), inflammatory peripheral neuropathies ( n  = 4), myositis ( n  = 3), myasthenia ( n  = 1), limbic encephalitis ( n  = 1) and giant cell arteritis ( n  = 1). Patients were predominantly female (ratio 3.2:1) and the median age at diagnosis was 50 years (range 22–86). Therapy included administration of steroids ( n  = 15), intravenous immunoglobulins in patients with Guillain–Barré syndrome or VITT ( n  = 4), plasma exchange in cases unresponsive to steroids ( n  = 3) and anticoagulation in VITT. Outcomes were favourable with partial and complete remissions achieved in 71% and 24%, respectively. Two patients received their second vaccination without further aggravation of autoimmune symptoms under low‐dose immunosuppressants. Conclusions In this study various neurological autoimmune disorders encountered following SARS‐CoV‐2 vaccinations are characterized. Given the assumed low incidence and mostly favourable outcome of autoimmune responses, the benefits of vaccinations outweigh the comparatively small risks.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    URL: Article
    DOI: 10.1111/ene.v29.2
    DOI: 10.1111/ene.15147
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2020241-6
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  • 7
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    Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-3-14)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-3-14)
    Abstract: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve’s FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL). Materials and methods Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage. Results Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls ( p & lt;0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p & lt;0.001 and r=0.6; p & lt;0.001) and sural sensory NCV (r=0.50; p & lt;0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p & lt;0.01 and r=0.3; p & lt;0.01) and lower (r=0.5; p & lt;0.001 and r=0.3; p = & lt;0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p & lt;0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p & lt;0.001 and r= -0.3, p = 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain. Conclusion This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    DOI: 10.3389/fendo.2023.1046690
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 8
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    High‐resolution MR neurography follow‐up of SARS‐CoV ‐2 vaccination‐associated neuralgic amyotrophy
    Wiley ; 2023
    In:  Annals of Clinical and Translational Neurology
    Details
    In: Annals of Clinical and Translational Neurology, Wiley
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Article
    DOI: 10.1002/acn3.51916
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2740696-9
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  • 9
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2021
    In:  Frontiers in Neuroscience Vol. 15 ( 2021-3-3)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2021-3-3)
    Abstract: Nerve damage in diabetic neuropathy (DN) is assumed to begin in the distal legs with a subsequent progression to hands and arms at later stages. In contrast, recent studies have found that lower limb nerve lesions in DN predominate at the proximal sciatic nerve and that, in the upper limb, nerve functions can be impaired at early stages of DN. Materials and Methods In this prospective, single-center cross-sectional study, participants underwent diffusion-weighted 3 Tesla magnetic resonance neurography in order to calculate the sciatic nerve’s fractional anisotropy (FA), a surrogate parameter for structural nerve integrity. Results were correlated with clinical and electrophysiological assessments of the lower limb and an examination of hand function derived from the Purdue Pegboard Test. Results Overall, 71 patients with diabetes, 11 patients with prediabetes and 25 age-matched control subjects took part in this study. In patients with diabetes, the sciatic nerve’s FA showed positive correlations with tibial and peroneal nerve conduction velocities ( r = 0.62; p & lt; 0.001 and r = 0.56; p & lt; 0.001, respectively), and tibial and peroneal nerve compound motor action potentials ( r = 0.62; p & lt; 0.001 and r = 0.63; p & lt; 0.001, respectively). Moreover, the sciatic nerve’s FA was correlated with the Pegboard Test results in patients with diabetes ( r = 0.52; p & lt; 0.001), prediabetes ( r = 0.76; p & lt; 0.001) and in controls ( r = 0.79; p = 0.007). Conclusion This study is the first to show that the sciatic nerve’s FA is a surrogate marker for functional and electrophysiological parameters of both upper and lower limbs in patients with diabetes and prediabetes, suggesting that nerve damage in these patients is not restricted to the level of the symptomatic limbs but rather affects the entire peripheral nervous system.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2021.642589
    DOI: 10.3389/fnins.2021.642589.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
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    Magnetic Resonance Neurography Reveals Smoking-Associated Decrease in Sciatic Nerve Structural Integrity in Type 2 Diabetes
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 15 ( 2022-2-15)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2022-2-15)
    Abstract: It is controversially discussed in how far smoking contributes to diabetic polyneuropathy (DPN) in type 2 diabetes (T2D). Diffusion-weighted magnetic resonance neurography (MRN) at 3 Tesla has been shown to provide objective values for structural nerve integrity in patients with T2D. The aim of this study was to investigate the contribution of cigarette smoking on structural nerve integrity in T2D. Methods This cross-sectional prospective cohort study investigated the structural integrity of the sciatic nerve in 10 smokers, 40 never-smokers, and 20 ex-smokers with T2D and 10 healthy control subjects, using diffusion tensor imaging MRN at 3 Tesla and semi-automated nerve fiber tracking. Results were correlated with clinical, electrophysiological, and serological data. Results The sciatic nerve’s fractional anisotropy (FA), a parameter for structural nerve integrity, was significantly lower in smokers with T2D when compared to controls ( p = 0.002) and never-smokers ( p = 0.015), and lower in ex-smokers when compared to controls ( p = 0.015). In addition, sciatic nerve radial diffusivity, a marker of myelin damage, was increased in smokers versus controls and never-smokers ( p = 0.048, p = 0.049, respectively). Furthermore, FA in T2D patients was negatively correlated with clinical and electrophysiological markers of DPN. FA also showed negative correlations with the pulse wave velocity, a marker of arterial stiffness and associated microangiopathy, in controls ( r = −0.70; p = 0.037), never-smokers ( r = −0.45; p = 0.004), ex-smokers ( r = −0.55; p = 0.009), and a similar trend in smokers ( r = −0.63; p = 0.076). Negative correlations were found between FA and skin auto-fluorescence, a marker of tissue advanced glycation end product accumulation and therefore long-term glycemic stress in T2D, in never-smokers ( r = −0.39; p = 0.020) and smokers ( r = −0.84; p = 0.004), but not in ex-smokers ( r = −0.07; p = 0.765). Conclusion The findings indicate that smoking contributes to sciatic nerve damage in T2D, potentially worsening DPN due to glycemic stress and less microangiopathy-associated myelin damage in active smokers, while angiopathic effects predominate in ex-smokers. To stop smoking may therefore pose a promising preventive measure to slow the progression of DPN in T2D.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    DOI: 10.3389/fnins.2021.811085
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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