Adult WHO grade II ependymomas: is Ki67 a sex-specific proliferation marker?

Ki67 is a marker for proliferation of a given cell population. Low expression of Ki67 may be associated with a favourable outcome. We investigate how the proliferation index correlates with the location, morphology and behaviour of WHO grade II ependymomas with a single-centre cohort study of adult patients admitted for surgery of WHO grade II ependymomas between 2008 and 2018. Seventeen patients were included, seven had supratentorial and 10 had infratentorial tumours. Three patients died and eight had recurrent disease. Age, gender, location, extent of resection, chemotherapy, radiotherapy and histological markers were not associated with tumour progression. Both unadjusted and adjusted analysis confirmed a higher Ki67 index in male patients. Sensitivity analysis further supported the correlation between Ki67 and male gender. Ki67 may be sex specific but does not seem to correlate with survival and time to recurrence in this series.

Low-Grade Glioma Case Series: Lessons Learned from an Evolving 10-Year Single-Institution Multidisciplinary Team Practice.

BACKGROUND: Low-grade gliomas are a heterogeneous group with significant changes in their management during the last decade. OBJECTIVE: To assess how our multidisciplinary team approach to the management of low-grade glioma has evolved over the past 10 years and its implications for outcomes. METHODS: Retrospective single-center cohort study of adult patients with a pathologically confirmed diagnosis of World Health Organization grade II glioma between 2009 and 2018. Demographic, clinical, and pathologic data were collected. RESULTS: Ninety-five patients were included. There was a statistically significant difference in the surgical approach, with more patients having gross total resection (45.7% vs. 18.4%) and fewer patients having a biopsy (21.8% vs. 49.0%) (P = 0.002) after 2014. There was a significantly better overall survival after 2014 (<2014, 16.3%; ≥2014, 0 deaths; P = 0.010) measured at the mean time of follow-up. The use of adjuvant chemotherapy (P = 0.045) and radiotherapy (P = 0.001) significantly decreased after 2014. A subgroup analysis showed that the impact of extent of surgical resection was the greatest for survival in the 1p19q noncodeleted tumors (P = 0.029) and for seizure outcomes in the 1p19q codeleted group (P = 0.018). There was no statistically significant increase in neurologic disability with more radical surgery, incorporating intraoperative neuromonitoring, as measured by modified Rankin Scale score (P > 0.05). CONCLUSIONS: More radical surgery was associated with increased survival, less need for postoperative adjuvant therapy and better seizure control, without significant morbidity. Molecular markers are useful tools for stratification of benefits after such surgery.

Reliability of Intraoperative Monitoring in Patients with a Preexisting Motor Deficit: Case Report and Literature Review.

BACKGROUND: The use of intraoperative monitoring (IOM) in glioma surgery is a widely adopted and clinically validated adjunct to define safe zones of resection for the neurosurgeon. However, the role of IOM in cases of a significant preexisting motor deficit is questionable. CASE DESCRIPTION: We describe a case of a 25-year-old with a recurrent presentation of a left paracentral glioblastoma, admitted with intratumoral hemorrhage and subsequent acute severe right-sided weakness. The patient underwent a redo left parietal craniotomy and 5-aminolevulinic acid-guided resection with IOM. The severity of the weakness was not reflected by the pre- and intraoperative cortical motor evoked potentials (MEPs) that were reassuring. The patient's hemiparesis recovered to full power postoperatively. CONCLUSIONS: Preoperative weakness is traditionally accepted as a relative contraindication to IOM and therefore its usefulness is questioned in this context. Our case challenges this assumption. We present the clinical course, review the cranial and spinal literature including the reliability of IOM in cases of preoperative motor deficit, and discuss the need for tailor-made IOM strategies.

Navigated Transcranial Magnetic Stimulation in Patient with Cranioplasty in Situ: Safe and Accurate Procedure.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a nonsurgical mapping technique used in mapping of motor and language eloquent areas within and/or surrounding brain tumors. Previous reports support this as a safe technique with minor side effects associated with minor headaches and discomfort around the stimulation area. Currently there are no published reports concerning the accuracy and safety of this procedure in patients with a titanium cranioplasty in situ. CASE PRESENTATION: A 59-year-old lady was diagnosed with a recurrent glioma in the context of increasing seizure frequency, left-sided numbness, and weakness. She was diagnosed with a World Health Organization grade 2 oligodendroglioma 10 years before her presentation, which was initially treated with radiotherapy and then surgical resection of this lesion 5 years later. The procedure was complicated with a wound infection, treated with a craniectomy and wound washout, followed by a titanium cranioplasty. Before proceeding with surgery for recurrence, nTMS was performed for motor mapping. No complications were identified. She underwent a craniotomy for tumor resection with aminolevulinic acid HCl (Gliolan), and the tumor was completely removed. Intraoperatively, the direct cortical stimulation correlated with the preoperative nTMS. The pathologic diagnosis on recurrence was an anaplastic oligodendroglioma grade III, and the patient is currently undergoing adjuvant chemotherapy. CONCLUSION: This report confirms that nTMS is a safe and accurate procedure in patients who have a titanium cranioplasty in situ.

'Noises in the head': a prospective study to characterize intracranial sounds after cranial surgery.

BACKGROUND: Patients often report sounds in the head after craniotomy. We aim to characterize the prevalence and nature of these sounds, and identify any patient, pathology, or technical factors related to them. These data may be used to inform patients of this sometimes unpleasant, but harmless effect of cranial surgery. METHODS: Prospective observational study of patients undergoing cranial surgery with dural opening. Eligible patients completed a questionnaire preoperatively and daily after surgery until discharge. Subjects were followed up at 14 days with a telephone consultation. RESULTS: One hundred fifty-one patients with various pathologies were included. Of these, 47 (31 %) reported hearing sounds in their head, lasting an average 4-6 days (median, 4 days, mean, 6 days, range, 1-14 days). The peak onset was the first postoperative day and the most commonly used descriptors were 'clicking' [20/47 (43 %)] and 'fluid moving' in the head [9/47 (19 %)]. A significant proportion (42 %, 32/77) without a wound drain experienced intracranial sounds compared to those with a drain (20 %, 15/74, p < 0.01); there was no difference between suction and gravity drains. Approximately a third of the patients in both groups (post-craniotomy sounds group: 36 %, 17/47; group not reporting sounds: 31 %, 32/104), had postoperative CT scans for unrelated reasons: 73 % (8/11) of those with pneumocephalus experienced intracranial sounds, compared to 24 % (9/38) of those without pneumocephalus (p < 0.01). There was no significant association with craniotomy site or size, temporal bone drilling, bone flap replacement, or filling of the surgical cavity with fluid. CONCLUSIONS: Sounds in the head after cranial surgery are common, affecting 31 % of patients. This is the first study into this subject, and provides valuable information useful for consenting patients. The data suggest pneumocephalus as a plausible explanation with which to reassure patients, rather than relying on anecdotal evidence, as has been the case to date.

Bradykinesia-akinesia incoordination test: validating an online keyboard test of upper limb function.

BACKGROUND: The Bradykinesia Akinesia Incoordination (BRAIN) test is a computer keyboard-tapping task that was developed for use in assessing the effect of symptomatic treatment on motor function in Parkinson's disease (PD). An online version has now been designed for use in a wider clinical context and the research setting. METHODS: Validation of the online BRAIN test was undertaken in 58 patients with Parkinson's disease (PD) and 93 age-matched, non-neurological controls. Kinesia scores (KS30, number of key taps in 30 seconds), akinesia times (AT30, mean dwell time on each key in milliseconds), incoordination scores (IS30, variance of travelling time between key presses) and dysmetria scores (DS30, accuracy of key presses) were compared between groups. These parameters were correlated against total motor scores and sub-scores from the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Mean KS30, AT30 and IS30 were significantly different between PD patients and controls (p≤0.0001). Sensitivity for 85% specificity was 50% for KS30, 40% for AT30 and 29% for IS30. KS30, AT30 and IS30 correlated significantly with UPDRS total motor scores (r = -0.53, r = 0.27 and r = 0.28 respectively) and motor UPDRS sub-scores. The reliability of KS30, AT30 and DS30 was good on repeated testing. CONCLUSIONS: The BRAIN test is a reliable, convenient test of upper limb motor function that can be used routinely in the outpatient clinic, at home and in clinical trials. In addition, it can be used as an objective longitudinal measurement of emerging motor dysfunction for the prediction of PD in at-risk cohorts.

Identifying better surgical candidates among recursive partitioning analysis class 2 patients who underwent surgery for intracranial metastases.

OBJECTIVE: The management of patients with brain metastases is typically dependent on their prognosis. Recursive partitioning analysis (RPA) is the most commonly used method for prognosticating survival, but has limitations for patients in the intermediate class. The aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this system in predicting survival for RPA class 2 patients. METHODS: Adult patient who underwent intracranial metastatic tumor surgery at an academic tertiary care institution from 1997 to 2011 were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival. The identified associations were then used to develop a grading system. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analyses. RESULTS: A total of 421 (59%) of 708 patients were RPA class 2. The preoperative factors found to be associated with poorer survival were: male gender (P < 0.0001), motor deficit (P = 0.0007), cognitive deficit (P = 0.0004), nonsolitary metastases (P = 0.002), and tumor size >2 cm (P = 0.003). Patients having 0-1, 2, and 3-5 of these variables were assigned a preoperative grade of A, B, and C, respectively. Patients with a preoperative grade of A, B, and C had a median survival of 17.0, 10.3, and 7.3 months, respectively. These grades had distinct survival times (P < 0.05). CONCLUSIONS: The present study devised a preoperative grading system that may provide prognostic information for RPA class 2 patients, which may also guide medical and surgical therapies before any intervention is pursued.

Survival and recurrence for patients undergoing surgery of skull base intracranial metastases.

Objective Skull base metastases (SBMs) are rare lesions in close proximity to critical neural and vasculature structures. This rarity and complexity have led many to only offer nonsurgical therapies. The surgical outcomes for patients with SBM therefore remain unknown. Design Retrospective, comparison analyses. Setting Johns Hopkins Hospital. Participants All patients who underwent intracranial metastatic tumor surgery. Main Outcome Measure Survival and recurrence. Results Of the 708 patients who underwent intracranial metastatic tumor surgery, 29 (4%) had SBM: 3 (10%) involved the anterior skull base, 7 (24%) the sella, 6 (21%) the orbit, 2 (7%) the sphenoid wing, 3 (10%) the clivus, 4 (14%) the petrous bone, and 4 (14%) the paranasal sinuses. Following surgery, 6 (50%) had improvements in vision and 14 (88%) had improvement and/or maintenance of their cranial nerve symptoms. Three (10%), 0(0%), and 1(3%) developed a new motor, language, and vision deficit, respectively. There were no differences in median survival (10.0 versus 9.2 months, p = 0.48) and local progression-free survival (PFS) (p = 0.52), but there was improved distal PFS (p = 0.04) between patients with and without SBM. Conclusions Patients with SBM are relatively rare. These patients can tolerate surgery with minimal morbidity and mortality, and they have similar prognoses to patients without SBM.