Treatment outcome and prognostic factors of adult glioblastoma multiforme

IntroductionThis study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM).Subjects and methodThis retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients’ follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM.ResultsThere were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI = 5.711–8.289) and 11 (95% CI = 9.304–12.696) months respectively. In univariate analysis for overall survival, age (P = 0.003), tumor size (P < 0.013), performance status (P < 0.001), the extent of surgical resection (P = 0.009), dose of radiation (P < 0.001), and adjuvant chemotherapy (P < 0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival.ConclusionThe prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival.     

Do adventitial mast cells contribute to the pathogenesis of ascending thoracic aorta aneurysm?

The precise pathogenesis of the ascending aortic aneurysm (AscAA) remains to be determined. Mast cells in the adventitia of human AscAA lesions may play a role in this pathogenesis. Adventitial mast cell density per 10 high-power fields (0.25 mm(2)) was assessed in multiple biopsy samples, from aneurysmal aortic sections (n = 41) and control (nondilated) aortic specimens (n = 50), stained by orcein-Giemsa method, an inexpensive (<$1) method. In a multivariable adjusted logistic regression model, using AscAA as the dependent variable, mast cell density was found to be an independent predictor of AscAA occurrence (odds ratio = 2.21; 95% confidence interval = 1.58-3.08; P < .001). Receiver operating characteristic curve analysis showed that the proposed cutoff value of ≥3 mast cells per 10 high-power fields was very sensitive to detect AscAA occurrence, yielding a sensitivity of 90% with a specificity of 80%. In conclusion, a significant increase in the number of mast cells in the adventitia of human ascending aortic lesions proposes a role for these cells in the pathogenesis of AscAA.     

The effects of cerebellar transcranial direct current stimulation on static and dynamic postural stability in older individuals: a randomized double‐blind sham‐controlled study

The aging population is growing rapidly. Risk of falling is higher in older people compared to young adults due to several reasons including poor posture and balance. The main aim of this study was to investigate the effect of cerebellar anodal transcranial direct current stimulation (a‐tDCS) on static and dynamic postural stability in older individuals. Twenty‐nine older adults participated in this study and were randomly allocated to two groups of active a‐tDCS (experimental; n = 14) or sham tDCS group (n = 15). Experimental group received cerebellar a‐tDCS for 20 min with intensity of 1.5 mA. Anterior–posterior and medial–lateral postural stability indices (postural sway) in addition to Berg Balance Score were measured before and after the intervention. Postural sways in static and dynamic postural tasks were significantly decreased (P < 0.05) after cerebellar a‐tDCS, in addition to Berg Balance Score that increased significantly in active cerebellar a‐tDCS group (P < 0.05). However, there were no significant changes in postural stability indices or Berg Balance Score in sham group (P > 0.05). The findings indicated immediate effect of cerebellar a‐tDCS on improvement of postural control and balance in older individuals.     

Comparison of Rossini–Rothwell and adaptive threshold‐hunting methods on the stability of TMS induced motor evoked potentials amplitudes

Several methods can be used to determine the resting motor threshold (RMT) and by that recording transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs). However, no research has compared the test retest reliability of these methods. Thus, the aim of this study was to determine intra‐ and inter‐session reliability of Rossini–Rothwell (R–R) and parameter estimation by sequential testing (PEST) methods on TMS‐induced MEPs and comparison of these two methods on RMT. Twelve healthy individuals participated in this study three times (T1, T2 and T3) over two days. TMS was applied using both R–R and PEST to estimate RMT and average of 25 MEPs were acquired at each of the three time points. The intra‐class correlation coefficient indicated high intra‐session reliability in the MEP amplitudes for both methods (0.79 and 0.88, R–R and PEST respectively). The RMT and MEP amplitudes had higher inter‐session reliability in both methods (0.99 and 0.998, R–R and PEST respectively; 0.84 and 0.76, R–R and PEST respectively). There was no significant difference between methods for RMT at both T1 (maximum stimulator output of R–R vs. PEST, 33.7% ± 7.7% vs. 33.8% ± 7.6%, p = 0.75) and T3 (maximum stimulator output of R–R vs. PEST, 33.5% ± 7.3% vs. 33.7% ± 7.3%, p = 0.19). There was a significant positive correlation between the methods' estimates of RMT, with PEST requiring significantly fewer stimuli. This study shows that the R–R and PEST methods have high intra‐and inter‐session reliability and the same precision, with PEST having the advantage over R–R in speed of estimation of RMT.     

Multi-session anodal tDCS enhances the effects of postural training on balance and postural stability in older adults with high fall risk: Primary motor cortex versus cerebellar stimulation

Background

Postural control impairment is a key target for rehabilitation of older adults with high fall risk.

Mechanosensitivity of the median nerve and mechanically produced motor responses during Upper Limb Neurodynamic Test 1

Objectives

In spite of the widespread use and recognised importance of the Upper Limb Neurodynamic Test 1 (ULNT1) in clinical practice, controversy remains about the neurophysiological basis for sensory and motor responses to the test. The aims of this study were to determine the effects of two limb positions (neutral and ULNT1) on mechanosensitivity of the median nerve, and to investigate the mechanisms underlying muscle stiffness and loss of range during the elbow extension component of the ULNT1.

Design

In both limb positions, a KIN-COM^® dynamometer controlled passive elbow extension at 3°/second, and recorded both elbow extension range of movement and elbow flexor resistive torque.

Setting

Electrophysiology laboratory, School of Physiotherapy, University of South Australia.

Participants

Twenty-six asymptomatic subjects.

Main outcome measures

Range of elbow extension and elbow flexor resistive torque. Surface electrodes placed over 10 upper limb muscles recorded electromyographic (EMG) activity. Using a hand-held micro-switch, participants indicated occurrence of pain onset and pain that limited further movement.

Results

The median nerve was more sensitive to mechanical longitudinal stresses during passive elbow extension in the ULNT1 position than in the neutral position, as demonstrated by increased EMG activity and increased mean elbow flexor resistive torque (neutral position, 0.8 Nm, 95% confidence interval 0.7-0.9 Nm; ULNT1 position, 3.9 Nm, 95% confidence interval 3.8-4.0 Nm). Pain onset and pain limit occurred earlier in range in the ULNT1 position (pain onset, 45°, 95% confidence interval 40-50°) than in the neutral position (3°, 95% confidence interval 0-6°). In the ULNT1 position, EMG activity was greater in muscles responsible for an antalgic posture in the upper limb, although some EMG activity was evident prior to pain onset.

Conclusions

The mechanosensitivity of the median nerve was greater during elbow extension in the ULNT1 position than in the neutral position. The increased EMG activity that occurred primarily in muscles contributing to an antalgic posture with concurrent changes in resistive torque and range of movement may be explained by a flexor withdrawal response to pain that acts to reduce the stretch on the median nerve. Muscle activity prior to pain onset is probably due to mechanoreceptor activation following preferential stretch of the median nerve.     

Facilitation of cortically evoked potentials with motor imagery during post-exercise depression of corticospinal excitability

This study examined whether muscle fatigue alters the facilitatory effect of motor imagery on corticospinal excitability. We aimed to determine if post-exercise depression of potentials evoked magnetically from the motor cortex is associated with alterations in internally generated movement plans. In experiment 1, motor-evoked potentials (MEPs) were recorded from two right hand and two right forearm muscles, at rest and during motor imagery of a maximal handgrip contraction, in eight neurologically normal subjects, before and after a 2-min maximal voluntary handgrip contraction. Resting MEP amplitude was facilitated by motor imagery in three of the four muscles, but consistently only in two. Motor imagery also reduced the trial-to-trial variability of resting MEPs. Following the exercise, resting MEP amplitude was depressed reliably in only one muscle engaged in the task, although two other muscles exhibited some depression. Motor imagery MEPs were smaller after exercise, but the degree of facilitation compared to the rest MEP was unchanged. In experiment 2, TMS intensity was increased after exercise-induced MEP depression so that the MEP amplitude matched the pre-exercise baseline. The amplitude of the MEP facilitated with motor imagery was not altered by MEP depression, nor was it increased when the TMS intensity was increased. These results suggest, at least with a simple motor task, that while post-exercise depression reduces corticospinal excitability, it does not appear to significantly affect the strength of the input to the motor cortex from those areas of the brain responsible for the storage and generation of internal representations of movement.     

The common non-synonymous variant G38S of the KCNE1-(minK)-gene is not associated to QT interval in Central European Caucasians: results from the KORA study

Aims The QT interval in the general population is a complextrait with 30–50% heritability. QT prolongation is associatedwith an increased risk of sudden death. A recent family-basedstudy found an association between QT interval and the commonnon-synonymous Glycin 38 Serine variant (G38S, rs1805127) ofthe KCNE1 gene coding for the minK-potassium channel subunit.We intended to replicate this finding in a large populationsample of central European Caucasian ancestry as part of ourongoing search for genetic variants predisposing to arrhythmias. Methods and results We studied 3966 unrelated individuals fromthe KORA S4 population-based study without atrial fibrillation,pacemaker implant, or pregnancy. Individuals were genotypedby MALDI-TOF mass spectrometry. We did not detect any significantassociation between the genotypes of the G38S variant and theQT interval in the entire population or in any gender. Conclusion Unlike the common Lysine 897 Threonine variant ofKCNH2 (K897T, rs1805123) the G38S variant of KCNE1 does notappear to have a strong modifying effect on QT interval. However,we cannot rule out an effect of G38S on QT in other ethnic groups,under exercise or medications or on the risk for arrhythmiasand sudden death.     

Treatment results of tonsillar lymphoma: a 10-year experience

Primary extranodal non-Hodgkins lymphomas of the head and neck account for 10–20% of all non-Hodgkins lymphomas. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies, although the tonsil is the most common primary extranodal site of head and neck non-Hodgkins lymphomas. In this study we analyzed our cases of tonsillar lymphoma treated in our institution during the last 10 years to compare the finding of this study with those of previous studies. We reviewed the cases of tonsillar lymphoma treated in the Radiation Oncology Department of Shiraz University from 1992 to 2002. Clinical data were obtained from patients files. The patients were treated by combined chemotherapy [a median of six cycles of a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone)] and radiation therapy (40–50 Gy to the primary site and neck). Chemotherapy mainly preceded radiotherapy, although the sequence of radiotherapy and chemotherapy was determined by individual physicians and patients choice. Surgery was used mainly to establish the diagnosis, and tonsillectomy was performed for localized small lesions. Between 1992 and 2002, 19 patients with stage IE (10), IIE (7), and IIIE (2) disease were treated. Median and mean age was 48 and 44 years (range: 22–76 years), respectively, at the time of diagnosis, with a male to female ratio of 1.2:1. The vast majority of patients presented in early stages with aggressive histology. High-grade tumors seemed to affect mainly young people (p=0.226). Diffuse large B-cell lymphomas were the most prevalent. Male patients were significantly younger than females (p=0.021). The patients were treated by combined chemotherapy and radiation therapy. All patients achieved and maintained complete remission with a median of 60 months relapse-free survival and a 5-year cause-specific survival rate of 100%. All patients developed some degree of oropharyngeal mucositis. Three patients (16%) experienced grade 3 or 4 neutropenia. Mild (grade I) xerostomia remained persistently in four patients (21%). A late fatal side effect was observed in one patient who developed radiation-induced sarcoma 7 years after initial diagnosis and died 8 months later without evidence of recurrent lymphoma. Complete follow-up was obtained in all patients. The follow-up period ranged from 18 to 141 months with a median of 60 and a mean of 60.4 months. At the time of last follow-up, all patients but one were alive. Age, sex, stage, bulk of disease, performance status, number of chemotherapy cycles, number of involved sites, histologic subtypes, and radiation dose were analyzed as prognostically significant for disease-specific survival in our cases. Significant prognostic factors were not identified by multivariate analysis. Combined chemotherapy and radiation therapy is safe, highly effective, and probably curative for most patients with primary tonsillar lymphoma.An erratum to this article can be found at