Neurophysiologic cut off values for safe resection of patients with supratentorial gliomas.

BACKGROUND: Gliomas have infiltrative nature and tumor volume has direct prognostic value. Optimal resection limits delineated by high-frequency monopolar stimulation with multipulse short train technique is still a matter of debate for safe surgery without (or with acceptable) neurological deficits. It is also an enigma whether the same cut-off values are valid for high and low grades. We aimed to analyze the value of motor mapping/monitoring findings on postoperative motor outcome in diffuse glioma surgery. METHODS: Patients who were operated on due to glioma with intraoperative neuromonitorization at our institution between 2017 and 2021 were analyzed. Demographic information, pre- and post-operative neurological deficit, magnetic resonance images, resection rates, and motor evoked potential (MEP) findings were analyzed. RESULTS: Eighty-seven patients of whom 55 had high-grade tumors were included in the study. Total/near-total resection was achieved in 85%. Subcortical motor threshold (ScMTh) from resection cavity to the corticospinal tract was ≤ 2mA in 17; 3 mA in 14; 4 mA in 6; 5 mA in 7, and ≥5mA in 50 patients. On the 6th month examination, six patients (5 with high-grade tumor) had motor deficits. These patients had changes in MEP that exceeded critical threshold during monitoring. Receiver operating characteristic analysis revealed 2.5 mA ScMTh as the cut-off point for limb paresis after awakening and 6 months for the groups. CONCLUSIONS: Subcortical mapping with MEP monitoring helps to achieve safe wider resection. The optimal safe limit for SCMTh was determined as 2.5 mA. Provided that safe threshold values are maintained in MEP, surgeon may force the functional limits by lowering the SCMTh to 1 mA, especially in low-grade gliomas.

Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability.

BACKGROUND: Aetiological diagnosis in non-syndromic intellectual disability (NSID) still poses a diagnostic challenge to clinicians. METHODS: Screening is currently achieved by chromosomal microarrays followed by whole-exome sequencing (WES). In search for the aetiological yield of WES in patients with NSID, 59 unrelated patients were studied. RESULTS: Among the 59 patients, 44 (74.6%) were from consanguineous unions. Epilepsy was present in 11 (37.9%), behavioural problems in 12 (41.4%) and autistic features in 14 (48.3%). WES analysis resulted in molecular diagnosis in 29 patients (49.2%). Some of the genes were specific for nervous system functioning, like HERC1, TBC1D7, LINS, HECW2, DEAF1, HNMT, DLG3, NRXN1 and HUWE1. Others were ubiquitously expressed genes involved in fundamental cellular processes, like IARS, UBE3A, COQ4, TAF1, SETBP1, ARV1, ZC4H2, KAT6A, ASXL3, THOC6, HNRNPH2, TUBA8 and KIF1A. Twenty-two (75.8%) were consanguineously married; however, only 12 (41.4%) of the detected genes caused autosomal recessive phenotypes. CONCLUSIONS: This cohort suggests that recessive genes probably represent an actually smaller subgroup of NSID, even among families with consanguinity. Although in societies with high consanguinity rates, considering the recessive inheritance first seems to be an advantageous strategy, de novo mutations in autosomal dominantly expressed genes represent the major aetiological group in patients with NSID, even among those patients from consanguineous families.

Genetic IGF1R defects: new cases expand the spectrum of clinical features.

PURPOSE: We aimed to identify the phenotypic variability of IGF1R defects in a cohort of short children with normal GH secretion gathered through the last decade. PATIENTS AND METHODS: Fifty children (25 girls) with short stature and a basal/stimulated growth hormone (GH) over 10 ng/ml having either a low birth weight or microcephaly were enrolled. MLPA and then Sanger sequence analysis were performed to detect IGF1R defects. The auxological and metabolic evaluation were carried out in index cases and their first degree family members whenever available. RESULTS: A total of seven (14%) IGF1R defects were detected. Two IGF1R deletions and five heterozygous variants (one frameshift, four missense) were identified. Three (likely) pathogenic, one VUS and one likely benign were classified by using ACMG. All children with IGF1R defects had a height < - 2.5SDS, birth weight < - 1.4SDS, and head circumference < - 1.36SDS. IGF-1 ranged from - 2.44 to 2.13 SDS. One child with a 15q terminal deletion had a normal phenotype and intelligence, whereas low IQ is a finding in a case with missense variant. Two parents who carried IGF1R mutations had diabetes mellitus, hypertension and hyperlipidemia, one of whom also had hypergonadotropic hypogonadism. CONCLUSION: We found a deletion or variant in IGF1R in 14% of short children. Birth weight, head circumference, intelligence, dysmorphic features, IGF-1 levels and even height are not consistent among patients. Additionally, metabolic and gonadal complications may appear during adulthood, suggesting that patients should be followed into adulthood to monitor for these late complications.

MEFV mutations in systemic onset juvenile idiopathic arthritis.

OBJECTIVES: Autoinflammatory diseases constitute a large spectrum of monogenic diseases like FMF or cryopyrin-associated periodic syndromes (CAPS) and complex genetic trait diseases such as systemic onset juvenile idiopathic arthritis (SoJIA). An increased rate of MEFV mutations has been shown among patients with PAN and HSP, in populations where FMF is frequent. The aim of the study is to search for MEFV mutations in our patients with SoJIA and see whether these mutations had an effect on disease course or complications. METHODS: Thirty-five children with the diagnosis of SoJIA were screened for 12 MEFV mutations. The control data were obtained from a previous study of our centre determining the carrier frequency in Turkish population. RESULTS: Two patients were homozygous and three patients were heterozygous for the M694V mutation. One patient was a compound heterozygote for the M680I/V726A mutations. Heterozygous V726A mutation was found in one patient. The overall mutation frequency of patients was 14.28%. This figure had been compared with the previously published rate of disease-causing mutations in this country, which is 5%. Disease-causing mutations were found to be significantly more frequent in the SoJIA patients than the population (P < 0.01). Among these, M694V was the leading mutation with a frequency of 10% in SoJIA. Six patients carrying MEFV mutations were among the most resistant cases requiring biological therapy. CONCLUSION: SoJIA patients had a significantly higher frequency of MEFV mutations but clinical studies with large number of patients are needed to confirm the association of MEFV mutations with SoJIA and its course.

A cross-sectional analysis of sagittal knee laxity and isokinetic muscle strength in soccer players.

In this cross-sectional study, sagittal knee laxity and isokinetic strength of knee extensor and flexor muscle groups were measured and differences related to leg dominance were evaluated. A total of 44 healthy male soccer players (who had trained regularly at least for the last five years) and 44 sedentary people as their control counterparts were involved in this study. All participants were tested using a KT-1000 knee arthrometer for knee laxity. Isokinetic concentric knee peak torque and hamstring/quadriceps (H/Q) ratio were also measured at 60, 180, 300 degrees/s through a Cybex 2 - 340 dynamometer. Posterior laxity in the non-dominant side of soccer players was significantly higher than in the dominant side (p < 0.005) while there were no significant anterior and total anteroposterior (total AP) laxity differences in both groups. Soccer players had significantly lower anterior and total AP laxity values than controls (p < 0.0001) while there was no significant difference between posterior laxity values in both sides. Dominant extremity demonstrated significantly higher knee flexor peak torque and H/Q ratio at 180 degrees /s in soccer players (p < 0.05). Similarly in sedentary controls, H/Q ratio at 60 degrees /s of the dominant side was significantly higher than that in the non-dominant side (p < 0.05). Soccer players had significantly higher extensor and flexor peak torque values and H/Q ratios than sedentary subjects for both extremities. In both groups, there were no significant correlations between knee laxity and isokinetic knee extensor and flexor strength and H/Q ratios except weak negative correlation between posterior knee laxity and isokinetic extensor peak torque at 60, 180 and 300 degrees /s (p < 0.005, r = - 0.43, p < 0.05, r = - 0.39, p < 0.05, r = - 0.32 respectively) in the non-dominant side of soccer players and at 300 degrees /s (p < 0.05, r = - 0.32) in the non-dominant side of controls. Soccer players demonstrated significantly less sagittal knee laxity and higher isokinetic strength of the knee flexors and extensors compared to sedentary controls. Isokinetic strength difference was found to be higher for the flexor muscle group. Further prospective studies are needed to explain whether the increased H/Q ratio decreases the risk of ligamentous injury.

Effect of the vastus medialis obliquus on the patellofemoral joint.

In this study, the effect of dynamic stabilizers on the patellofemoral (PF) joint was investigated in normal volunteers (group I) and in patients with patellar pain (group II) or instability (group III) by using computed tomography (CT) analysis and integrated electromyography (iEMG) of the quadriceps muscle. Nine subjects (16 knees) from group I, 10 patients (12 knees) from group II and 8 patients (12 knees) from group III were included in the study. CT scans of the PF joint with quadriceps contracted (QC) and uncontracted (QU) and iEMG of vastus medialis obliquus (VMO), vastus lateralis (VL) and rectus femoris (RF) were obtained with the aid of a specially designed jig at 0 degree, 15 degrees, 30 degrees and 45 degrees of knee flexion. The same muscle contraction pattern simulating closed kinetic chain exercise was used for both CT and iEMG. The difference between the congruence angles (CA) and tilt angles (PTA) in QC and QU positions and VMO:VL ratio from the iEMG were calculated separately for each flexion angle. CA was increased in all groups with quadriceps contraction at 0 degree and 15 degrees of flexion. PTA was decreased in group I and increased in groups II and III with quadriceps contraction at the same flexion angles. This difference was statistically significant in group III at 0 degree and 15 degrees of flexion. Quadriceps contraction did not affect the patellar position significantly even in the instability group at 45 degrees of flexion. In all flexion angles the balanced VMO:VL activity ratio was observed only in group I. In the other groups, VL activity was higher than VMO activity except at 45 degrees of flexion. These findings do not support the hypothesis of dominant centralizing effect of VMO on the patella in extension, but the effect of the VMO may be more clearly demonstrated by measuring PTA in both QC and QU positions.

Articular cartilage homeostasis after anterior cruciate ligament reconstruction.

Several factors may be responsible for osteoarthritis after anterior cruciate ligament (ACL) reconstruction. The detrimental effect of the surgical technique may explain part of the progression of the pathologic process. In this study, the effect of ACL reconstruction on articular cartilage was investigated by measuring proteoglycan fragments (PF) in synovial fluid collected from patients who had undergone this operation. Synovial samples were obtained from 44 patients with chronic ACL deficiency aged 26 +/- 7 years preoperatively, and from some of them, samples were collected for monitoring at 1 month (n = 22), 3 months (n = 17), 6 months (n = 18) and 12s month (n = 18). Synovial fluid taken from 12 contralateral asymptomatic knees of 12 patients (not necessarily opposite knees of ACL-deficient cases) served as controls. Preoperative values were significantly larger than controls (P < 0.05). PF level reached its maximum value in the 1st month (P < 0.05) and then gradually decreased. It was significantly lower than preoperative values at 6 and 12 months but still greater than controls (P < 0.05). It seems that surgical trauma affects cartilage metabolism for the first 3 months postoperatively. Although reconstruction of the ACL contributes to articular cartilage homeostasis, a complete return to normal values cannot be achieved in 1st postoperative year at least in knees with chronic ACL deficiency. Long-term monitoring is needed to see whether these findings are early signs of osteoarthritis. Further studies may more clearly demonstrate the effect of the surgical procedure on knees with acute and subacute ACL deficiency.

Effect of tibial tubercle elevation on patellofemoral compressive force in patellofemoral arthrosis.

In this study, the effect of tibial tubercle elevation on the patellofemoral compressive force (PFCF) was investigated in patients with patellofemoral arthrosis. Fifteen (11 women and 4 men) patients who had undergone tibial tubercle elevation were included in the study. The average follow-up was 4.5 years. The mean age of the patients was 59 years (range 34-71 years). They were able to maintain a normal pain-free daily life. Maximal isometric quadriceps force (Q) was calculated by equating the moment generated by this force to the moment of the force measured at the ankle by a modified hand dynamometer. PFCF was calculated from the quadriceps and patellar tendon forces. Statistical analyses were then applied to the measured and calculated quantities. The mean quadriceps force in the operated knee decreased by 20%. Likewise, the mean PFCF was found to be reduced by 30% in the operated knees as compared with the asymptomatic contralateral knees. The above differences in Q and PFCF between the operated knee and the asymptomatic knee were statistically significant (P < 0.05). Therefore, the results of this study do not agree with the previously held view that Q and PFCF increase due to the removal of pain after the elevation operation. It is our contention that comparison of the forces measured preoperatively in a painful joint with the forces that can be attained postoperatively in the pain-free joint can lead to errors in biomechanical evaluations.

Tensile properties of the superior glenohumeral and coracohumeral ligaments.

Recent evidence has shown that the superior glenohumeral ligament (SGHL) and coracohumeral ligament (CHL) are important static stabilizers. To clarify the function of these two ligaments, we studied their tensile properties with bone-ligament-bone complexes from fresh-frozen shoulders, 10 SGHLs and 10 CHLs. Each ligament's cross-sectional area was measured, and uniaxial tensile testing of each complex was performed. The stiffness, ultimate load, percent elongation, and energy absorbed to failure of each bone-ligament-bone complex were derived from its load-elongation curve. The cross-sectional area of the coracohumeral ligament was significantly greater than that of the superior glenohumeral ligament of their midportions (CHL, 53.7 +/- 3.2 mm2 vs. SGHL, 11.3 +/- 1.6 mm2, p < 0.05). Results also reveal significant differences between the tensile properties for the two ligaments, with the coracohumeral ligament possessing greater stiffness (CHL, 36.7 +/- 5.9 N/mm vs. SGHL, 17.4 +/- 1.5 N/mm, p < 0.05) and ultimate load (CHL, 359.8 +/- 40.3 N vs. SGHL, 101.9 +/- 11.5 N, p < 0.05) than the superior glenohumeral ligament. Our findings confirm that the coracohumeral ligament is an important capsuloligamentous structure of the glenohumeral joint.

A biomechanical analysis of rotator cuff deficiency in a cadaveric model.

We conducted this cadaveric study to define a biomechanical rationale for rotator cuff function in several deficiency states. A dynamic shoulder testing apparatus was used to examine change in middle deltoid muscle force and humeral translation associated with simulated rotator cuff tendon paralyses and various sizes of rotator cuff tears. Supraspinatus paralysis resulted in a significant increase (101%) in the middle deltoid force required to initiate abduction. This increase diminished to only 12% for full glenohumeral abduction. The glenohumeral joint maintained ball-and-socket kinematics during glenohumeral abduction in the scapular plane with an intact rotator cuff. No significant alterations in humeral translation occurred with a simulated supraspinatus paralysis, nor with 1-, 3-, and 5-cm rotator cuff tears, provided the infraspinatus tendon was functional. Global tears resulted in an inability to elevate beyond 25 degrees of glenohumeral abduction despite a threefold increase in middle deltoid force. These results validated the importance of the supraspinatus tendon during the initiation of abduction. Glenohumeral joint motion was not affected when the "transverse force couple" (subscapularis, infraspinatus, and teres minor tendons) remained intact. Significant changes in glenohumeral joint motion occurred only if paralysis or anatomic deficiency violated this force couple. Finally, this model confirmed that rotator cuff disease treatment must address function in addition to anatomy.

Mechanical properties of the long head of the biceps tendon.

In this study, the geometric and mechanical properties of the long head of the biceps tendon were determined in order to elucidate its role in shoulder stability. We used a laser-micrometer system to measure the cross-sectional area and shape of seven fresh-frozen tendons at three levels: proximal, middle, and distal levels. The cross-sectional areas were found to be 22.7 +/- 9.3 mm2, 22.7 +/- 3.5 mm2, and 10.8 +/- 2.7 mm2, respectively. While statistically significant differences could not be demonstrated between the magnitudes of the areas, a consistent difference in shape was noted between the proximal and middle levels, the tendon being flatter as it progressed over the humeral head and more triangular as it passed through the bicipital groove. We then performed cyclic relaxation tests and uniaxial tensile testing of the tendons which revealed a cyclic stress relaxation of 18 +/- 4% over ten cycles. All tensile failures occurred within the mid-portion of the tendon substance. Additionally, the modulus was calculated between 3% and 6% strain and found to be 421 +/- 212 MPa, while the ultimate tensile strength, ultimate strain, and strain energy density were 32.5 +/- 5.3 MPa, 10.1 +/- 2.7 %, and 1.9 +/- 0.4 MPa, respectively. These mechanical properties of the long head of the biceps tendon are of the same order of magnitude as tendons from other joints. The high stiffness of this tendon indicates that it has an ability to support the large load transferred to it by the muscle and to act as a humeral head depressor.