Reports about the prognostic value of
IDH
mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated ...the prognostic value of
IDH
mutations and methylation of the promoter region of the
MGMT
gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for
IDH
mutations by direct sequencing, and, for promoter status of
MGMT
gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an
IDH
mutation was 4 years, which is significantly longer than in patients with wild-type
IDH
(1.2 years,
p
= 0.009). Patients’ survival was not significantly influenced by the tumors’
MGMT
promoter status, both in Group 1— 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (
p
= 0.330)—as well as in Group 2—1.5 years vs. 1.6 years, methylated versus unmethylated promoter (
p
= 0.829). In our population, the
IDH
mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and
IDH
mutation had a significantly improved outcome. In addition,
IDH
mutations are a more powerful prognostic marker concerning both PFS and MS than the
MGMT
promoter status in those patients.
Recent studies have reported mutations in the telomerase reverse transcriptase promoter (
p) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene ...alterations in a cohort of patients with progressive/higher-grade meningiomas.
We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III). The tumor samples were screened for
p and
mutations, and
rearrangements. Additionally,
p was sequenced in a separate cohort of 19 patients with radiation-associated meningiomas. We examined the impact of mutational status on patients' progression and overall survival.
Somatic
p mutations were detected in six patients (6/26 = 23%). Regional intratumoral heterogeneity in
p mutation status was noted. In 4 patients,
p mutations were detected in recurrent specimens but not in the available specimens of the first surgery. Additionally, a
gene fusion (
) was found in one sample. In contrary, none of the investigated samples harbored an
or
mutation. In the cohort of radiation-induced meningiomas,
p mutation was detected in two patients (10.5%). Importantly, we found that patients with emergence of
p mutations had a substantially shorter OS than their
p wild-type counterparts (2.7 years, 95% CI 0.9 - 4.5 years versus 10.8 years, 95% CI 7.8 -12.8 years, p=0.003).
In progressive/higher-grade meningiomas,
p mutations are associated with poor survival, supporting a model in which selection of this alteration is a harbinger of aggressive tumor development. In addition, we observe spatial intratumoral heterogeneity of
p mutation status, consistent with this model of late emergence in tumor evolution. Thus, early detection of
p mutations may define patients with more aggressive meningiomas. Stratification for
alterations should be adopted in future clinical trials of progressive/higher-grade meningiomas.
The influence of the degree of resection on survival in patients with glioblastoma multiforme is still under discussion. The highly controlled 5-aminolevulinic acid study provided a unique platform ...for addressing this question as a result of the high frequency of "complete" resections, as revealed by postoperative magnetic resonance imaging scans achieved by fluorescence-guided resection and homogeneous patient characteristics.
Two hundred forty-three patients with glioblastoma multiforme per protocol from the 5-aminolevulinic acid study were analyzed. Patients with complete and incomplete resections as revealed by early magnetic resonance imaging scans were compared. Prognostic factors that might cause bias regarding resection and influence survival (e.g., tumor size, edema, midline shift, location, age, Karnofsky Performance Scale score, National Institutes of Health Stroke Scale score) were used for analysis of overall survival. Time to reintervention (chemotherapy, reoperation) was analyzed further to exclude bias regarding second-line therapies.
Treatment bias was identified in patients with complete (n = 122) compared with incomplete resection (n = 121), i.e., younger age and less frequent eloquent tumor location. Other factors, foremost preoperative tumor size, were identical. Patients without residual tumor survived longer (16.7 versus 11.8 mo, P < 0.0001). In multivariate analysis, only residual tumor, age, and Karnofsky Performance Scale score were significantly prognostic. To account for distribution bias, patients were stratified for age (>60 or <or=60 yr) and eloquent location. Survival advantages from complete resection remained significant within subgroups, and age/eloquent location were no longer unevenly distributed. Reinterventions occurred marginally earlier in patients with residual tumor (6.7 versus 9.5 mo, P = 0.0582).
Treatment bias was demonstrated regarding resection and second-line therapies. However, bias and imbalances were controllable in the cohorts available from the 5-aminolevulinic acid study so that the present data now provide Level 2b evidence (Oxford Centre for Evidence-based Medicine) that survival depends on complete resection of enhancing tumor in glioblastoma multiforme.
OBJECTIVE Direct stimulation of the peroneal nerve by the ActiGait implantable drop foot stimulator is a potent therapy that was described previously for stroke-related drop foot. The authors report ...here successful long-term application of the ActiGait implantable drop foot stimulator in patients with multiple sclerosis (MS). METHODS Six patients with MS and 2 years of persisting central leg paresis received an implantable ActiGait drop foot stimulator after successful surface test stimulation. Ten weeks and 1 year after surgery, their gait speed, endurance, and safety were evaluated. Patient satisfaction was assessed with a questionnaire. RESULTS In the 20-m gait test, stimulation with the ActiGait stimulator significantly reduced the time needed, on average, by approximately 23.6% 10 weeks after surgery, and the time improved further by 36.3% after 1 year. The median distance covered by patients with the stimulator after 6 minutes of walking increased significantly from 217 m to 321 m and remained stable for 1 year; the distance covered by patients after surface stimulation was 264 m. Patients with an implanted ActiGait stimulator noticed pronounced improvement in their mobility, social participation, and quality of life. CONCLUSIONS The ActiGait implantable drop foot stimulator improved gait speed, endurance, and quality of life in all patients over a period of 1 year. It may serve as a new therapeutic option for patients with MS-related drop foot.
Objective To present midterm to long-term results obtained in carpal tunnel release, in situ decompression, and anterior transposition of the ulnar nerve using the retractor integrated endoscope. ...Methods During the period 2000–2010, 145 patients underwent endoscopic carpal tunnel releases ( n = 47), endoscopic in situ decompression of the ulnar nerve ( n = 55), and endoscopic anterior transposition of the ulnar nerve ( n = 52). Bilateral surgery was performed in 9 patients. Independent examinations at 24 months after surgery were used for objective results (Bishop score). Subjective results were procured using a questionnaire. Results After endoscopic carpal tunnel release, 59.6% of patients showed excellent results, 21.2% showed good results, 12.8% showed fair results, and 6.4% showed poor results according to objective scoring. In 85% of patients, subjective improvement was noted after surgery; symptoms were the same as before surgery in 12.8% of patients and were worse in 2.1% of patients after surgery. After endoscopic in situ decompression, 56.4% of patients showed excellent results on objective scoring, 32.7% showed good results, 9.1% showed fair results, and 1.8% showed poor results. On subjective questioning, 72.7% of patients reported improvement, 20% reported no change in symptoms, and 7.3% reported worse symptoms. After endoscopic anterior transposition of the ulnar nerve, 48.1% of patients showed excellent results on objective scoring, 26.9% showed good results, 23.1% showed fair results, and 1.9% showed poor results. Subjectively, 65.4% of patients reported improvement, 26.9% reported no change in symptoms, and 7.7% reported worse symptoms. Patients with symptom duration of <9 months before surgery showed better results than patients with symptom duration of >9 months. Conclusions The retractor-endoscopic technique provides good long-term results after carpal tunnel release, in situ decompression, and anterior subcutaneous transposition of the ulnar nerve. Outcomes showed some correlation to the duration of preoperative symptoms.
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