Identification of novel Nrf2-activating neuroprotective agents: Elucidation of structural congeners of (-)-galiellalactone and congener-based novel Nrf2 activators.

Herein, (-)-galiellalactone 1 congeners responsible for the nuclear factor erythroid 2-related factor 2 (Nrf2)-activating neuroprotective effects were elucidated. Additionally, novel congener-based Nrf2 activators were identified using a drug repositioning strategy. (-)-Galiellalactone, which comprises a tricyclic lactone skeleton, significantly activates antioxidant response element (ARE)-mediated transcription in neuroblastoma SH-SY5Y cells. Interestingly, two cyclohexene-truncated [3.3] bicyclic lactone analogs, which possess an exocyclic α-methylene-γ-butyrolactone moiety, exhibited higher Nrf2/ARE transcriptional activities than the parent (-)-galiellalactone. We confirmed that the cyclohexene moiety embedding the [3.3] bicyclic lactone congener does not play the essential role of (-)-galiellalactone for Nrf2/ARE activation. Nrf2/ARE activation by novel analogs resulted in the upregulation of downstream antioxidative and phase II detoxifying enzymes, heme oxygenase-1, and NAD(P)H quinone oxidoreductase 1, which are closely related to the cytoprotective effects on neurodegenerative diseases. (-)-Galiellalactone and its [3.3] bicyclic variants 3l and 3p increased the expression of antioxidant genes and exhibited neuroprotective effects against 6-hydroxydopamine-mediated neurotoxicity in the neuroblastoma SH-SY5Y cell line.

Ultrasound and CT findings of subcutaneous metastases in trunk and pelvis: a comprehensive analysis.

OBJECTIVE: This study aimed to describe the ultrasound, CT findings, and clinical manifestations of pathologically confirmed metastases involving the subcutaneous fat layer of the trunk and pelvis. MATERIALS AND METHODS: We included 30 patients with subcutaneous metastases in the trunk and pelvis, verified by ultrasound-guided biopsy. We comprehensively reviewed ultrasound findings of all 30 patients and contrast-enhanced CT findings of 25 patients obtained before biopsy. Medical records were reviewed, including primary malignancy type, presence of coexisting distant metastasis, and detection method leading to biopsy referral. RESULTS: Most subcutaneous metastases were heterogeneously hypoechoic (86.7%) with well-defined margins (80.0%), lobulated (46.7%) or round-to-oval (40.0%) shape, and vascularity (96.7%). Metastases frequently exhibited no contact (53.3%) or focal contact with deep peripheral fascia, resulting in acute contact angle formation (30.0%). Common CT manifestations included central low attenuation with peripheral rim-like enhancement (60.0%) or well-circumscribed lesion with heterogeneous enhancement (32.0%). Lung cancer (46.7%) was the prevalent primary malignancy. CT was the predominant detection method (56.7%). Coexisting subcutaneous metastases were present in 50.0% of cases, and distant metastases (less subcutaneous metastases) were observed in 90.0% of patients. CONCLUSION: This study describes typical imaging findings of subcutaneous metastases involving the trunk and pelvis. CT may play a crucial role in their early detection, and our results may assist radiologists in their diagnosis.

Compound Heterozygous Mutations of SACS in a Korean Cohort Study of Charcot-Marie-Tooth Disease Concurrent Cerebellar Ataxia and Spasticity.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Temporal synchronization between two Q switched pulses in a 1 × 2 array distribution inside a single YAG/Yb:YAG/Cr:YAG laser resonator.

We propose for the first time, to the best of our knowledge, a coupling method of modes guided by gain waveguides to synchronize two Q switched pulses oscillating in a 1 × 2 array distribution inside a single YAG/Yb:YAG/Cr:YAG resonator. To analyze the temporal synchronization of spatially separated Q switched pulses, the buildup time interval, spatial distribution, and longitudinal modes distribution of the two pulse beams are investigated.

Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation.

This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1-3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-ß-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

Variants of aminoacyl-tRNA synthetase genes in Charcot-Marie-Tooth disease: A Korean cohort study.

Charcot-Marie-Tooth disease (CMT) and related diseases are a genetically and clinically heterogeneous group of peripheral neuropathies. Particularly, mutations in several aminoacyl-tRNA synthetase (ARS) genes have been reported to cause axonal CMT (CMT2) or distal hereditary motor neuropathy (dHMN). However, the common pathogenesis among CMT subtypes by different ARS gene defects is not well understood. This study was performed to investigate ARS gene mutations in a CMT cohort of 710 Korean families. Whole-exome sequencing was applied to 710 CMT patients who were negative for PMP22 duplication. We identified 12 disease-causing variants (from 13 families) in GARS1, AARS1, HARS1, WARS1, and YARS1 genes. Seven variants were determined to be novel. The frequency of overall ARS gene mutations was 1.22% among all independent patients diagnosed with CMT and 1.83% in patients negative for PMP22 duplication. WARS1 mutations have been reported to cause dHMN; however, in our patients with WARS1 variants, CMT was associated with sensory involvement. We analyzed genotype-phenotype correlations and expanded the phenotypic spectrum of patients with CMT possessing ARS gene variants. We also characterized clinical phenotypes according to ARS genes. This study will be useful for performing exact molecular and clinical diagnoses and providing reference data for other population studies.

Discovery of new ERRγ agonists regulating dopaminergic neuronal phenotype in SH-SY5Y cells.

The discovery of small molecules that regulate specific neuronal phenotypes is important for the development of new therapeutic candidates for neurological diseases. Estrogen-related receptor γ (ERRγ), an orphan nuclear receptor widely expressed in the central nervous system (CNS), is closely related to the regulation of neuronal metabolism and differentiation. We previously reported that upregulation of ERRγ could enhance dopaminergic neuronal phenotypes in the neuroblastoma cell line, SH-SY5Y. In this study, we designed and synthesized a series of new ERRγ agonists using the X-ray crystal structure of the GSK4716-bound ERRγ complex and known synthetic ligands. Our new ERRγ agonists exhibited increased transcriptional activities of ERRγ. In addition, our molecular docking results supported the experimental findings for ERRγ agonistic activity of the potent analogue, 5d. Importantly, 5d not only enhanced the expression of dopaminergic neuronal-specific molecules, TH and DAT but also activated the relevant signaling events, such as the CREB-mediated signaling pathway. The results of the present study may provide useful clues for the development of novel ERRγ agonists for neurological diseases related to the dopaminergic nervous system.

Juxtaneural ganglia arising from the hip joint: focus on magnetic resonance imaging findings and clinical manifestations.

OBJECTIVE: To present cases of juxtaneural ganglia arising from the hip with a discussion of the magnetic resonance imaging (MRI) findings, presenting symptoms, and possible treatment option. MATERIALS AND METHODS: Two radiologists performed a consensus review of MRI scans obtained between January 2013 and March 2021 to identify patients with juxtaneural ganglia around the hip. A total of 11 patients with 11 juxtaneural ganglia were identified. Medical records and MRI findings were retrospectively reviewed. RESULTS: Eight patients had lesions involving the sciatic nerve, and three patients had lesions involving the obturator nerve. Sciatic ganglia arose from a paralabral cyst in the posteroinferior quadrant and continued through a narrow channel running along the posterior acetabulum, showing increased diameter in the sciatic foramen and intrapelvic portion. Obturator ganglia showed a J- or reverse J-shape on the coronal imaging plane and extended from a paralabral cyst in the anteroinferior quadrant via the obturator canal. Nine patients (9/11, 81.8%) had symptoms resembling those of lumbosacral radiculopathy. Four patients underwent arthroscopic surgery, and one patient underwent ultrasound-guided aspiration, all of whom showed partial improvement. Spontaneous decrease in the extent of the ganglion was observed in three patients (3/11, 27.3%). CONCLUSION: This article describes rare cases of juxtaneural ganglia arising from the hip joint and involving the sciatic and obturator nerves. The lesions share similar MRI findings, and each type of cyst (sciatic or obturator ganglia) involves a specific labral quadrant.

Diagnostic performance of conventional magnetic resonance imaging for detection and grading of subscapularis tendon tear according to Yoo and Rhee classification system in patients underwent arthroscopic rotator cuff surgery.

OBJECTIVES: To assess the diagnostic accuracy of conventional MRI for detecting and grading subscapularis (SSC) tears by applying the Yoo and Rhee classification. MATERIALS AND METHODS: A total of 179 patients who underwent MRI followed by arthroscopic rotator cuff surgery were enrolled. Two musculoskeletal radiologists evaluated the SSC using axial, oblique sagittal, and oblique coronal MRI according to the Yoo and Rhee classification. Using arthroscopic findings as the reference standard, the sensitivity, specificity, accuracy, and interobserver agreement of SSC tears were analyzed. RESULTS: Arthroscopy confirmed that the numbers of type I, IIA, IIB, III, IV, and V tears were 35, 70, 35, 9, 9, and 0, respectively. The sensitivity, specificity, and accuracy of readers 1 and 2 for the detection of tears (type IIA or higher) were 85%, 75%, and 82%, and 89%, 70%, and 83%, respectively, while those for the detection of surgical candidates (type IIB or higher) were 77%, 75%, and 75%, and 77%, 83%, and 82%, respectively. The interobserver agreement for detecting SSC tear presence was substantial (κ = 0.70) for reader 1 vs. reader 2, and those for detecting the surgical candidate group was substantial (κ = 0.68) for reader 1 vs. reader 2. The interobserver agreement for grading SSC tears was excellent (κ = 0.86) for reader 1 vs. reader 2. CONCLUSION: Conventional MRI showed 82.5% and 78.5% average accuracy in detecting IIA and IIB or higher tears by applying the Yoo and Rhee classification for the diagnosis of SSC tears with an excellent interobserver agreement in tear grading.

Synthesis of 7,2'-Dihydroxy-4',5'-Dimethoxyisoflavanone, a Phytoestrogen with Derma Papilla Cell Proliferative Activity.

This paper reports a concise and scalable method for the synthesis of the phytoestrogen 7,2'-dihydroxy-4',5'-dimethoxyisoflavanone 1 via an optimized synthetic route. Compound 1 was readily obtained in 11 steps and 11% overall yield on a gram scale from commercially available 3,4-dimethoxyphenol. The key features of the synthesis include the construction of the deoxybenzoin unit through a sequence of Claisen rearrangement, oxidative cleavage, and aryllithium addition and the efficient synthesis of the isoflavanone architecture from highly functionalized 2-hydroxyketone.

Texture analysis using T1-weighted images for muscles in Charcot-Marie-Tooth disease patients and volunteers.

OBJECTIVES: To explore whether texture features using T1-weighted images correlate with fat fraction, and whether they differ between Charcot-Marie-Tooth (CMT) disease patients and volunteers. METHODS: The institutional review board approved this retrospective study, and the requirement for informed consent was waived; data of eighteen CMT patients and eighteen healthy volunteers from a previous study was used. Texture features of the muscles including mean, standard deviation (SD), skewness, kurtosis, and entropy of the signal intensity were derived from T1-weighted images. Spearman's correlation analysis was used to assess the relationship between texture features and fat fraction measured by 3D multiple gradient echo Dixon-based sequence. Mann-Whitney U test was used to compare the texture features between CMT patients and volunteers. Intraobserver and interobserver agreements for the texture features were assessed using the intraclass correlation coefficient. RESULTS: The SD (ρ = 0.256, p < 0.001) and entropy (ρ = 0.263, p < 0.001) were significantly and positively correlated with fat fraction; skewness (ρ = - 0.110, p = 0.027) and kurtosis (ρ = - 0.149, p = 0.003) were significantly and inversely correlated with fat fraction. The CMT patients showed a significantly higher SD (63.45 vs. 49.26; p < 0.001), skewness (1.06 vs. 0.56; p < 0.001), kurtosis (4.00 vs. 1.81; p < 0.001), and entropy (3.20 vs. 3.02; p < 0.001) than did the volunteers. Intraobserver and interobserver agreements were almost perfect for mean, SD, and entropy. CONCLUSIONS: Texture features using T1-weighted images correlated with fat fraction and differed between CMT patients and volunteers. KEY POINTS: • Standard deviation and entropy of muscles derived from T1-weighted images were significantly and positively correlated with the muscle fat fraction. • Mean, standard deviation, and entropy were considered highly reliable in muscle analyses. • Texture features may have the potential to diagnose early stage of intramuscular fatty infiltration.

Concise syntheses and anti-inflammatory effects of isocorniculatolide B and corniculatolide B and C.

The first total syntheses of isocorniculatolide B, corniculatolide B, and corniculatolide C, consisting of isomeric corniculatolide skeletons, have been accomplished in a divergent manner. The key features of the synthesis involve the construction of diaryl ether linkages by nucleophilic aromatic substitution, installation of a C14-substituted alkyl side chain via a sequence of Baeyer-Villiger reaction and Claisen rearrangement, and efficient construction of corniculatolide and isocorniculatolide frameworks, including 17-membered (exterior) macrolactone skeletons from a versatile diaryl ether intermediate by Mitsunobu macrolactonization. Moreover, we prepared the structural congeners of isomeric corniculatolides via diverted total synthesis approach including desmethyl analogues and related dimeric macrolides. The anti-inflammatory activities of the synthesized natural products, analogues and synthetic intermediates were also investigated. In particular, corniculatolide B significantly inhibited the protein expression of COX-2 and the mRNA expressions of TNF-α, IL-1ß and IL-6 by inhibiting of NF-κB signaling in intestinal epithelial cells induced by lipopolysaccharide treatment. It also significantly inhibited the promoter activity and the phosphorylation of subunits p50 and p65 of NF-κB to the same extent as Bay 11-7082, a potent IκB kinase inhibitor. These results suggest that corniculatolide B might have therapeutic potential in inflammatory bowel disease via NF-κB signaling pathway.

Facile and Rapid Isolation of Oxypeucedanin Hydrate and Byakangelicin from Angelica dahurica by Using [Bmim]Tf2N Ionic Liquid.

Ionic liquids (ILs) have sparked much interest as alternative solvents for plant materials as they provide distinctive properties. Therefore, in this study, the capacity of ILs to extract oxypeucedanin hydrate and byakangelicin from the roots of Angelica dahurica (A. dahurica) was investigated. The back-extraction method was examined to recover target components from the IL solution as well. Herein, [Bmim]Tf2N demonstrated outstanding performance for extracting oxypeucedanin hydrate and byakangelicin. Moreover, factors including solvent/solid ratio, extraction temperature and time were investigated and optimized using a statistical approach. Under optimum extraction conditions (solvent/solid ratio 8:1, temperature 60 °C and time 180 min), the yields of oxypeucedanin hydrate and byakangelicin were 98.06% and 99.52%, respectively. In addition, 0.01 N HCl showed the most significant ability to back-extract target components from the [Bmim]Tf2N solution. The total content of both oxypeucedanin hydrate (36.99%) and byakangelicin (45.12%) in the final product exceeded 80%. Based on the data, the proposed approach demonstrated satisfactory extraction ability, recovery and enrichment of target compounds in record time. Therefore, the developed approach is assumed essential to considerably reduce drawbacks encountered during the separation of oxypeucedanin hydrate and byakangelicin from the roots of A. dahurica.

An Efficient Ionic Liquid-Mediated Extraction and Enrichment of Isoimperatorin from Ostericum koreanum (Max.) Kitagawa.

Ionic liquids (ILs) have attracted significant interest because of their desirable properties. These characteristics have improved their application to overcome the shortcomings of conventional separation techniques for phytochemicals. In this study, several ILs were investigated for their capacity to extract isoimperatorin, a bioactive furanocoumarin, from the roots of Ostericum koreanum. Herein, 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) was selected as a promising IL for separating isoimperatorin. A central composite design was applied to optimize the extraction conditions. Under the optimal conditions, the yield of isoimperatorin reached 97.17 ± 1.84%. Additionally, the recovery of isoimperatorin from the [Bmim][BF4] solution was successfully achieved (87.73 ± 2.37%) by crystallization using water as an antisolvent. The purity of the isoimperatorin was greatly enhanced, from 0.26 ± 0.28% in the raw material to 26.94 ± 1.26% in the product, in a one-step crystallization process. Namely, an enhancement of approximately 103-folds was reached. The developed approach overcomes the shortcomings of conventional separation methods applied for gaining isoimperatorin by significantly reducing the laboriousness of the process and the consumption of volatile organic solvents. Moreover, the simplicity and effectiveness of the method are assumed to be valuable for producing isoimperatorin-enriched products and for promoting its purification. This work also confirms the efficiency of ILs as a promising material for the separation of phytochemicals.

Soft tissue sarcoma: DWI and DCE-MRI parameters correlate with Ki-67 labeling index.

OBJECTIVES: To examine the correlation of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) parameters with Ki-67 labeling index (LI) in soft tissue sarcoma (STS). METHODS: The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Thirty-six patients with STS who underwent 3.0-T MRI, including diffusion-weighted and dynamic contrast-enhanced MRI, between July 2011 and February 2018, were included in this study. The mean and minimum apparent diffusion coefficients (ADCs) (ADCmean and ADCmin, respectively), volume transfer constant, reflux rate, and volume fraction of the extravascular extracellular matrix of each lesion were independently analyzed by two readers. Their relationship with the Ki-67 LI was examined using Spearman's correlation analyses. Differences between low- and high-proliferation groups based on Ki-67 LI were evaluated statistically. Optimal cut-off points were determined using the area under the curve analysis for significant parameters. Interobserver agreement was assessed with the intraclass correlation coefficient. RESULTS: ADCmean (ρ = - 0.333, p = 0.047) was significantly and inversely correlated with Ki-67 LI. The high-proliferation group showed a significantly lower ADCmean than did the low-proliferation group (median, 1.08 vs. 1.20; p = 0.048). When a cut-off ADCmean value of 1.16 × 10-3 mm2/s was used, the sensitivity, specificity, and area under the curve for differentiating low- and high-proliferation groups were 75.0%, 60.0%, and 0.712, respectively. Interobserver agreements between the two readers were almost perfect for all parameters. CONCLUSIONS: ADCmean was correlated with Ki-67 LI and could help differentiate between STS with low and high proliferation potential. KEY POINTS: • ADC meanwas significantly and inversely correlated with Ki-67 labeling index in soft tissue sarcoma. • In the high-proliferation group, ADC meanvalues were significantly lower than those of the low-proliferation group.

Collective Syntheses of Guaiane Sesquiterpenes: Stereoselective Syntheses of (+)-Dysodensiol F, (+)-10ß,14-Dihydroxy-allo-aromadendrane, and (-)-Dendroside C Aglycon.

A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10ß,14-dihydroxy-allo-aromadendrane, and (-)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis-fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (-)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10ß,14-dihydroxy-allo-aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (-)-dendroside C aglycon is also disclosed via our synthesis.

N-terminal pro-B-type natriuretic peptide levels in children: comparison in cardiac and non-cardiac diseases.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP), a well-known marker of cardiac disease, may be elevated in acute infections and other non-cardiac diseases. The aim of this study was to evaluate NT-proBNP levels in cardiac and non-cardiac diseases and found out the patient's clinical status that affects the NT-proBNP levels. METHODS: NT-proBNP levels were measured in three groups of children: a cardiac disease group, an infectious disease group, and a non-cardiac, non-infectious disease group. RESULT: In total, 348 children were enrolled, including 134 patients (38.5%) with cardiac disease, 170 patients (48.9%) with infectious disease, and 44 patients (12.6%) with non-cardiac, non-infectious disease. The NT-proBNP level of the cardiac disease group (median: 548 pg/mL; range: 5-35,000 pg/mL) was significantly higher than that of the infectious disease group (median: 193 pg/mL; range: 10-35,000 pg/mL) and the non-cardiac, non-infectious disease group (median: 280 pg/mL; range: 6-35,000 pg/mL). Regarding clinical status, the NT-proBNP levels were significantly higher in patients who needed mechanical ventilation support, oxygen therapy, or inotropic medication or had a change in mental status than in other patients. However, the systemic inflammatory response syndrome and mortality were not related to the NT-proBNP level. CONCLUSION: Among heterogeneous group of children, NT-proBNP level can be a useful marker of cardiac disease. Furthermore, the NT-proBNP levels were related to patients' clinical deteriorations, such as shock rather than the inflammatory status of patients.

Concise Synthesis of Catechin Metabolites 5-(3',4'-Dihydroxyphenyl)-γ-valerolactones (DHPV) in Optically Pure Form and Their Stereochemical Effects on Skin Wrinkle-Reducing Activities.

A concise and scalable synthetic route for optically pure (4S) and (4R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactones (DHPVs), catechin metabolites, has been developed via the efficient construction of a γ-valerolactone moiety from hexenol. Noticeably, the different skin wrinkle-reducing activities of each metabolite were revealed via our unique syntheses of DHPVs in an enantiomerically pure form.

Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells.

Despite numerous reports on the beneficial effects of catechin or epicatechin contained in tea and cacao extract on human health, a conclusive and precise molecular mechanism has not been elucidated. Metabolism of chemical compounds in gut microbiota recently gained significant attention, and extensive studies have been devoted in this field. In conjunction with these results, our group focused on the anti-inflammatory effects of both enantiomers of DHPV (5-(3',4'-dihydroxyphenyl)-γ-valerolactone), produced in the intestine by microbiota metabolism, on IEC-6 cells. Divergent and efficient enantioselective synthesis of (S)- and (R)-DHPV was efficiently achieved by cross-metathesis and Sharpless asymmetric dihydroxylation as a key reaction for four steps in 16% and 14% overall yields, respectively. The anti-inflammatory effects of two enantiomers were tested on IEC-6 cells, and we found that (S)-DHPV was more active than (R)-DHPV. This result implicates that the metabolite produced in the gut has beneficial effects on IEC-6 cells of rat intestines, and the chirality of the metabolite is important for its anti-inflammatory activity. This also provided information for the future discovery of novel small molecular therapeutics for the treatment of inflammatory bowel disease.

Diffusion tensor imaging of the sciatic nerve in Charcot-Marie-Tooth disease type I patients: a prospective case-control study.

OBJECTIVES: This study aimed to evaluate whether diffusion tensor imaging (DTI) parameters and cross-sectional area (CSA) can differentiate between the sciatic nerve of Charcot-Marie-Tooth (CMT) disease type I (demyelinating form) patients and that of controls. METHODS: This prospective comparison study included 18 CMT type I patients and 18 age/sex-matched volunteers. Magnetic resonance imaging including DTI and axial T2-weighted Dixon sequence was performed for each subject. Region of interest analysis was independently performed by two radiologists on each side of the sciatic nerve at four levels: hamstring tendon origin (level 1), lesser trochanter of the femur (level 2), gluteus maximus tendon insertion (level 3), and mid-femur (level 4). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated. The CSA of the sciatic nerve bundle was measured using axial water-only image at each level. Comparisons of DTI parameters between the two groups were performed using the two-sample t test and Mann-Whitney U test. Interobserver agreement analysis was also conducted. RESULTS: Interobserver agreement was excellent for all DTI parameter analyses. FA was significantly lower at all four levels in CMT patients than controls. RD, MD, and CSA were significantly higher at all four levels in CMT patients. AD was significantly higher at level 2 in CMT patients. CONCLUSION: DTI assessment of the sciatic nerve is reproducible and can discriminate the demyelinating nerve pathology of CMT type I patients from normal nerves. The CSA of the sciatic nerve is also a potential parameter for diagnosing nerve abnormality in CMT type I patients. KEY POINTS: • Diffusion tensor imaging parameters of the sciatic nerve at proximal to mid-femur level revealed significant differences between the Charcot-Marie-Tooth disease patients and controls. • The cross-sectional area of the sciatic nerve was significantly larger in the Charcot-Marie-Tooth disease patients. • Interobserver agreement was excellent (intraclass coefficient > 0.8) for all diffusion tensor imaging parameter analyses.