Median Nerve Shear Wave Elastography is Associated With the Neurophysiological Severity of Carpal Tunnel Syndrome.

OBJECTIVES: This study examines the associations between the median nerve (MN) shear wave elastography (SWE), the MN cross-sectional area (CSA), patient's symptoms, and the neurophysiological severity of carpal tunnel syndrome (CTS). The most appropriate site to perform SWE was also tested. METHODS: This prospective study comprised 86 wrists of 47 consecutive patients who volunteered for MN ultrasound after an electrodiagnostic study. The neurophysiological severity of CTS was assessed according to the results of a nerve conduction study (NCS). The MN CSA was measured at the carpal tunnel inlet (wCSA) and the forearm (fCSA). SWE was performed on the MN in a longitudinal orientation at the wrist crease (wSWE), at the forearm (fSWE), and within the carpal tunnel (tSWE). RESULTS: The wCSA and wSWE correlated positively with the neurophysiological severity of CTS (r = .619, P < .001; r = .582, P < .001, respectively). The optimal cut-off values to discriminate the groups with normal NCS and with findings indicating CTS were 10.5 mm2 for the wCSA and 4.12 m/s for the wSWE. With these cut-off values, wCSA had a sensitivity of 80% and specificity of 87% and wSWE a sensitivity of 88% and specificity of 76%. Neither tSWE nor fSWE correlated with the neurophysiological severity of CTS or differed between NCS negative and positive groups (P = .429, P = .736, respectively). CONCLUSION: Shear wave velocity in the MN at the carpal tunnel inlet increases in CTS and correlates to the neurophysiological CTS severity equivalently to CSA measured at the same site.

Median nerve ultrasound cross sectional area and wrist-to-forearm ratio in relation to carpal tunnel syndrome related axonal damage and patient age.

Objective: Primary objective was to retrospectively examine the effects of patient age and carpal tunnel syndrome (CTS) related axon loss on median nerve (MN) high resolution ultrasound (HRUS) in younger and older patients. HRUS parameters evaluated in this study were MN cross sectional area at the wrist (CSA) and wrist-to-forearm ratio (WFR). Methods: The material comprised 467 wrists of 329 patients. The patients were categorized into younger (<65 years) and older (≥65 years) groups. Patients with moderate to extreme CTS were included in the study. Axon loss of the MN was assessed by needle EMG and graded by the interference pattern (IP) density. The association between axon loss and CSA and WFR was studied. Results: The older patients had smaller mean CSA and WFR values compared to the younger patients. CSA correlated positively to the CTS severity only in the younger group. However, WFR correlated positively to CTS severity in both groups. In both age groups, CSA and WFR correlated positively with IP reduction. Conclusions: Our study complemented recent findings on the effects of patient age on the CSA of the MN. However, although the MN CSA did not correlate with the CTS severity in older patients, the CSA increased in respect to the amount of axon loss. Also, as a new result, we presented the positive association of WFR with CTS severity among older patients. Significance: Our study supports the recently speculated need for different MN CSA and WFR cut-off values for younger and older patients in assessing the severity of CTS. With older patients, WFR may be a more reliable parameter to assess the CTS severity than the CSA. CTS related axonal damage of the MN is associated to additional nerve enlargement at the carpal tunnel intel site.

Inter-operator and inter-device reproducibility of shear wave elastography in healthy muscle tissues.

PURPOSE: The study aimed to assess whether the more limiting factor in reproducibility of shear wave elastography (SWE) would be the operator dependency or the incompatibility of different ultrasound (US) devices. The interrater agreement with less experienced operators was studied. METHODS: A total of 24 healthy volunteers participated in the study (18 females, 6 males; range of age 27-55 years). SWE of biceps brachii (BB) and tibialis anterior (TA) muscles was performed on both sides from all participants in both longitudinal and transverse orientation of the transducer in respect to muscle fibers. Two operators repeated the SWE with two different US devices from different manufacturers (scanners 1 and 2). RESULTS: Intraclass correlation coefficient between the two operators was 0.91 (CI 0.88-0.93) for scanner 1 and 0.81 (CI 0.74-0.86) for scanner 2, respectively. Instead, there were significant differences in the SWE measurements between the two scanners, emphasizing in transverse orientation of the transducer. In the transverse transducer orientation, the mean shear wave velocity (SWV) in TA was 1.45 m/s (standard deviation [SD] ± 0.35 m/s) with scanner 1 and 2.35 m/s (SD ± 0.83 m/s) with scanner 2 (p < 0.001). In BB, the mean transverse SWV was 1.49 m/s (SD ± 0.35 m/s) with scanner 1 and 2.29 m/s (SD ± 0.63 m/s) with scanner 2 (p < 0.001). In longitudinal transducer orientation, the mean SWV in TA was 3.00 m/s (SD ± 0.73 m/s) with scanner 1 and 3.26 m/s (SD ± 0.42 m/s) with scanner 2 (p = 0.050). In BB, the mean longitudinal SWV was 3.60 m/s (SD ± 0.77 m/s) with scanner 1 and 3.96 m/s (SD ± 0.62 m/s) with scanner 2 (p = 0.019). The presented mean values were obtained by operator 1, there were no significant differences in the SWE measurements performed by the two operators. CONCLUSION: The results implicate that the reproducibility of the SWE measurements depends rather on the used US device than on the operator. It is recommendable that clinics collect reference values with their own US device and consider threshold values presented in previous studies only directional.

Large Intraneural Ganglion Cyst in the Peroneal Nerve.

A 23-year-old previously healthy male was referred to the clinical neurophysiology unit due to a relatively fast-onset paralysis of muscles of the anterior right leg. Electroneuromyography (ENMG) revealed a total denervation of the muscles innervated by the deep peroneal nerve, diminished sensory response of the superficial peroneal nerve, and partial denervation of the peroneus longus muscle. Ultrasound and magnetic resonance imaging (MRI) revealed a large fluid collection inside the common peroneal nerve, primarily suspected to be an intraneural ganglion cyst. The cyst was surgically excised, and the function of the muscles innervated by the peroneal nerve was recovering at the control ENMG 6 months later. We describe a case of a large intraneural ganglion cyst of the peroneal nerve in an otherwise healthy young male, diagnosis by ENMG, ultrasound, and MRI, as well as subsequent operative treatment. This report demonstrates the utility of nerve ultrasound in differentiating between different causes of peroneal nerve dysfunction.

Reduction in median nerve cross-sectional area at the forearm correlates with axon loss in carpal tunnel syndrome.

OBJECTIVE: To explore the relationship between axon loss and measured cross-sectional areas of the median nerve (MN) in severe carpal tunnel syndrome (CTS). METHODS: In this retrospective study of 158 examined wrists, we compared axon loss to the ultrasound parameters MN cross-sectional area at the wrist (wCSA), MN cross-sectional area at the forearm (fCSA) and wrist-to-forearm ratio (WFR), in patients with moderate to extreme CTS. Axon loss was evaluated by needle electromyography (EMG) of the abductor pollicis brevis muscle (spontaneous activity and reduction of interference pattern). RESULTS: Both the spontaneous activity and interference pattern reduction correlated negatively to fCSA (r = -0.189, p = 0.035; r = -0.210, p = 0.019; respectively). In moderate CTS, both the spontaneous activity and interference pattern reduction correlated positively to WFR (r = 0.231, p = 0.048; r = 0.232, p = 0.047; respectively). The WFR was highest when slight spontaneous activity was detected. Neither wCSA nor WFR correlated with axon loss in severe and extreme CTS. CONCLUSIONS: The fCSA is smaller when axon loss in CTS is more prominent. The WFR is highest when CTS is associated with slight axon loss of the MN. SIGNIFICANCE: CTS might cause retrograde axonal atrophy detected as small fCSA. Prominent axon loss in CTS may reduce the diagnostic value of WFR.

The Neurophysiological Severity of Carpal Tunnel Syndrome Cannot Be Predicted by Median Nerve Cross-Sectional Area and Wrist-to-Forearm Ratio.

PURPOSE: The median nerve cross-sectional area at the wrist (CSA) and the wrist-to-forearm ratio of the cross-sectional areas (WFR) are ultrasound parameters used in the diagnosis and grading of carpal tunnel syndrome. This study aimed to determine the diagnostic accuracy of the CSA and WFR as well as to compare their diagnostic value. METHODS: A retrospective evaluation was conducted of a cohort of 218 patients who had undergone nerve conduction studies (NCSs) and an ultrasound of the median nerve. The examined wrists were classified into an NCS negative and three NCS positive (mild, moderate, and severe) categories. The CSA and WFR were compared across the categories. RESULTS: The CSA and WFR were significantly smaller in the NCS negative category than in the NCS positive categories. The WFR was significantly smaller in the mild category than in the moderate category. The CSA could not be used to differentiate across the NCS positive categories. CONCLUSIONS: The CSA and WFR are satisfactorily reliable in detecting carpal tunnel syndrome, but they cannot be considered as surrogate indicators of electrophysiological severity.

Twist predicts poor outcome of patients with astrocytic glioma.

AIMS AND METHODS: Epithelial-mesenchymal transition (EMT) has previously been linked to glioma invasion and progression. To determine whether EMT regulators, Twist and Zeb1, had clinical significance in astrocytic gliomas, the association of Twist and Zeb1 with clinicopathological and molecular factors was studied in 269 astrocytoma samples. RESULTS: Twist and Zeb1 were widely expressed in astrocytic gliomas, but the expression of the former did not correlate with that of the latter. Stronger Twist expression levels were associated with higher WHO grades (p=0.001), whereas Zeb1 did not correlate with WHO grades. We found no association between Twist and proliferation activity (Ki67/MIB-1), p53 status, epidermal growth factor receptor (EGFR) amplification or neural cell adhesion molecule (NCAM) expression. There was no significant difference in Twist or Zeb1 expression when primary and secondary gliomas were analysed. Tumours with high Twist expression were IDH1 negative (p=0.009). High hypoxia-inducible factor-1α expression correlated significantly with positive Twist expression (p<0.001), whereas it was not associated with Zeb1 expression. Zeb1 expression did not correlate with proliferation, EGFR or IDH1. Nevertheless, we did find a correlation between high Zeb1 expression and low p53 expression levels (p=0.027). Positive NCAM expression was significantly associated with Zeb1 positivity (p=0.022). Zeb1 had no association with patient survival, whereas positive Twist expression predicted poor survival for patients in both univariate (p<0.001) and multivariable analyses (p=0.027). CONCLUSIONS: EMT regulators, Twist and Zeb1, are common features of infiltrating astrocytomas, and Twist is upregulated in glioblastomas in particular. Twist may be a novel marker for poor prognosis in glioma patients.

Polysialic acid is associated with better prognosis and IDH1-mutation in diffusely infiltrating astrocytomas.

BACKGROUND: The aim of the study was to assess the localization of Polysialic acid (polySia) and Neural cell adhesion molecule (NCAM) in grade I-IV astrocytomas by confocal microscopy, and also to clarify and compare their relationship to conventional clinicopathological features in these tumors. METHODS: Study material was stained immunohistochemically for polySia, NCAM and IDH1-R132H point mutation. Confocal microscopy of polySia and NCAM staining was performed on tissue micro-array samples (TMA) of 242 diffusely infiltrating astrocytomas (grade II: 28; grade III: 33; grade IV: 181) and 82 pilocytic astrocytomas. The results were statistically correlated to clinicopathological factors and survival data. RESULTS: PolySia was observed in 45 cases (19%) and NCAM positivity in 92 cases (38%). All 45 tumors with polySia positivity were also positive for NCAM whereas there were 47 tumors which contained positive staining for NCAM but not for polySia. The simultaneous expression was concomitant and colocalized suggesting polysialyated NCAM (polySia-NCAM). PolySia expression was significantly stronger in IDH1 mutated tumors than in IDH1 non-mutated (p = 0.001, chi-square test). There were no significant differences in polySia-NCAM between primary tumors or recurrences (p = n.s., chi-square test). PolySia positivity was associated with longer patient survival in relation to total tumor material (p = 0.020, log-rank test). Furthermore, when only glioblastomas were assessed, patients with positive polySia had significantly better prognosis (p = 0.006, log-rank test). In multivariate survival analysis, polySia was found to be an independent prognostic factor. PolySia was nearly absent in grade I pilocytic astrocytomas (1 immunopositive tumor of 82). CONCLUSIONS: Expression of polySia is common in adult grade II-IV astrocytomas, whereas it is nearly absent in pediatric grade I pilocytic astrocytomas. PolySia positivity is associated with longer survival rates in patients with a grade II-IV astrocytomas and also grade IV glioblastomas assessed separately. The results of this study suggest that IDH1 mutation may be associated with polySia expression pathways in malignant gliomas.

Hsp27 and its expression pattern in diffusely infiltrating astrocytomas.

AIMS: Heat shock protein 27 (Hsp27) is induced by cell stress conditions. In the presence of oxidative stress it functions as an antioxidant. To study the putative expression patterns and clinical significance of Hsp27, we assessed the associations between Hsp27, R132H mutation of Isocitrate dehydrogenase1 (IDH1-R132H), Hypoxia-inducible factor subunit alpha (HIF-1 alpha), Carbonic anhydrase IX (CA IX), and patient prognosis in astrocytic gliomas. METHODS: Tissue micro-array samples of 295 grade II-IV astrocytomas were stained immunohistochemically for Hsp27, IDH1-R132H, HIF-1 alpha, and CA IX. We tested their relationship with clinicopathological features and patient survival. RESULTS: There was a significant correlation between Hsp27 expression and increasing WHO grade (p<0.001). Hsp27 expression correlated significantly with IDH1 mutation when studied within the entire cohort (p<0.001) as well as separately in WHO grade II and III tumors (p=0.006 and 0.002, respectively). IDH1 mutation and HIF-1 alpha positive staining were detected simultaneously (p<0.001). In IDH1 mutated tumors, positive HIF-1 alpha staining correlated with CA IX expression (p=0.027), whereas no such correlation was found in IDH1 non-mutated tumors. IDH1 mutation was associated with a low cell proliferation index (p=0.001) and HIF-1 alpha with increasing proliferation (p = 0.003). Hsp27 expression was associated with a shorter rate of patient survival in univariate survival analysis (p=0.001). In multivariate survival analysis, patient age, IDH1 mutation and HIF-1 alpha appeared as independent prognostic factors (p<0.000, <0.000 and 0.011 respectively) CONCLUSIONS: Hsp27 expression is associated with increasing WHO grade and patient prognosis in astrocytic gliomas. The results suggest that IDH1 mutation may have an effect on the expression pathways of Hsp27 and CA IX.

Complement activation in astrocytomas: deposition of C4d and patient outcome.

BACKGROUND: C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. METHODS: Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. RESULTS: The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann-Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). CONCLUSION: The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement.