Michael Murek

Gross total resection rates in contemporary glioblastoma surgery: results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping

BACKGROUND Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery. OBJECTIVE To evaluate the impact of using 5-aminolevulinic acid and intraoperative mapping and monitoring on the rate of complete resection of enhancing tumor (CRET), gross total resection (GTR), and new neurological deficits as part of an institutional protocol. METHODS One hundred three consecutive patients underwent resection of glioblastoma from August 2008 to November 2010. Eligibility for CRET was based on the initial magnetic resonance imaging assessed by 2 reviewers. The primary end point was the number of patients with CRET and GTR. Secondary end points were volume of residual contrast-enhancing tissue and new postoperative neurological deficits. RESULTS Fifty-three patients were eligible for GTR/CRET (n = 43 newly diagnosed glioblastoma, n = 10 recurrent); 13 additional patients received surgery for GTR/CRET-ineligible glioblastoma. GTR was achieved in 96% of patients (n = 51, no residual enhancement >0.175 cm); CRET was achieved in 89% (n = 47, no residual enhancement). Postoperatively, 2 patients experienced worsening of preoperative hemianopia, 1 patient had a new mild hemiparesis, and another patient sustained sensory deficits. CONCLUSION Using 5-aminolevulinic acid imaging and intraoperative mapping/monitoring together leads to a high rate of CRET and an increased rate of GTR compared with the literature without increasing the rate of permanent morbidity. The combination of safety and resection-enhancing intraoperative technologies was likely to be the major drivers for this high rate of CRET/GTR.

Decompressive Hemicraniectomy in Patients With Supratentorial Intracerebral Hemorrhage

Background and Purpose— Decompressive craniectomy (DC) lowers intracranial pressure and improves outcome in patients with malignant middle cerebral artery stroke. Its usefulness in intracerebral hemorrhage (ICH) is unclear. The aim of this study was to analyze feasibility and safety of DC without clot evacuation in ICH. Methods— We compared consecutive patients (November 2010–January 2012) with supratentorial ICH treated with DC without hematoma evacuation and matched controls treated by best medical treatment. DC measured at least 150mm and included opening of the dura. We analyzed clinical (age, sex, pathogenesis, Glasgow Coma Scale, National Institutes of Health Stroke Scale), radiological (signs of herniation, side and size of hematoma, midline shift, hematoma expansion, distance to surface), and surgical (time to and indication for surgery) characteristics. Outcome at 6 months was dichotomized into good (modified Rankin Scale 0–4) and poor (modified Rankin Scale 5–6). Results— Twelve patients (median age 48 years; interquartile range 35–58) with ICH were treated by DC. Median hematoma volume was 61.3mL (interquartile range 37–83.5mL) and median preoperative Glasgow Coma Scale was 8 (interquartile range 4.3–10). Four patients showed signs of herniation. Nine patients had good and 3 had poor outcomes. Three patients (25%) of the treatment group died versus 8 of 15 (53%) of the control group. There were 3 manageable complications related to DC. Conclusions— DC is feasible in patients with ICH. Based on this small cohort, DC may reduce mortality. Larger prospective cohorts are warranted to assess safety and efficacy.

Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome

OBJECT Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. METHODS The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. CONCLUSIONS A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.

Early Re-Do Surgery for Glioblastoma Is a Feasible and Safe Strategy to Achieve Complete Resection of Enhancing Tumor

Background Complete resection of enhancing tumor as assessed by early (<72 hours) postoperative MRI is regarded as the optimal result in glioblastoma surgery. As yet, there is no consensus on standard procedure if post-operative imaging reveals unintended tumor remnants. Objective The current study evaluated the feasibility and safety of an early re-do surgery aimed at completing resections with the aid of 5-ALA fluorescence and neuronavigation after detection of enhancing tumor remnants on post-operative MRI. Methods From October 2008 to October 2012 a single center institutional protocol offered a second surgery within one week to patients with unintentional incomplete glioblastoma resection. We report on the feasibility of the use 5-ALA fluorescence guidance, the extent of resection (EOR) rates and complications of early re-do surgery. Results Nine of 151 patients (6%) with glioblastoma resections had an unintentional tumor remnant with a volume >0.175 cm3. 5-ALA guided re-do surgery completed the resection (CRET) in all patients without causing neurological deficits, infections or other complications. Patients who underwent a re-do surgery remained hospitalized between surgeries, resulting in a mean length of hospital stay of 11 days (range 7-15), compared to 9 days for single surgery (range 3-23; p=0.147). Conclusion Our early re-do protocol led to complete resection of all enhancing tumor in all cases without any new neurological deficits and thus provides a similar oncological result as intraoperative MRI (iMRI). The repeated use of 5-ALA induced fluorescence, used for identification of small remnants, remains highly sensitive and specific in the setting of re-do surgery. Early re-do surgery is a feasible and safe strategy to complete unintended subtotal resections.

Diskogenic microspurs as a major cause of intractable spontaneous intracranial hypotension

Objective: To visualize and treat spinal dural CSF leaks in all patients with intractable spontaneous intracranial hypotension (SIH) who underwent spinal microsurgical exploration. Methods: Patients presenting between February 2013 and July 2015 were included in this consecutive case series. The workup included spinal MRI without and with intrathecal contrast, dynamic myelography, postmyelography CT, and microsurgical exploration. Results: Of 69 consecutive patients, 15 had intractable symptoms. Systematic imaging revealed a suspicious single location of the leak in these 15 patients. Fourteen patients underwent microsurgical exploration; 1 patient refused surgery. Intraoperatively, including intradural exploration, we identified the cause of the CSF leaks as a longitudinal dural slit (6.1 ± 1.7 mm) on the ventral (10), lateral (3), or dorsal (1) aspect of the dura. In 10 patients (71%), a ventral, calcified microspur originating from the intervertebral disk perforated the dura like a knife. Three patients (22%) had a lateral dural tear with an associated spinal meningeal diverticulum, and in 1 patient (7%), a dorsal osteophyte was causal. The microspurs were removed and the dural slits sutured with immediate cessation of CSF leakage. Conclusion: The nature of the CSF leak is a circumscribed longitudinal slit at the ventral, lateral, or dorsal dura mater. An extradural pathology, diskogenic microspurs, was the single cause for all ventral CSF leaks. These findings challenge the notion that CSF leaks in SIH are idiopathic or due to a weak dura. Microsurgery is the treatment of choice in cases with intractable SIH.

Impact of early-onset seizures on grading and outcome in patients with subarachnoid hemorrhage.

OBJECT After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. METHODS This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I-III) and poor (WFNS IV-V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0-3 was considered a good outcome and an mRS score of 4-6 was considered a poor outcome. RESULTS Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14-7.46; p=0.03) and good outcome (OR 4.01, 97.5% CI 1.63-10.53; p=0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p<0.001), and poor WFNS grade (p<0.001) were associated with poor outcome. CONCLUSIONS Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.

Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage.

Background Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. Methods More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. Results Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Δ at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). Conclusions Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift.

Polymorphous oligodendroglioma of Zülch revisited: a genetically heterogeneous group of anaplastic gliomas including tumors of bona fide oligodendroglial differentiation.

A polymorphous variant of oligodendroglioma was described by K.J. Zülch half a century ago, and is only very sporadically referred to in the subsequent literature. In particular, no comprehensive analysis with respect to clinical or genetic features of these tumors is available. From a current perspective, the term polymorphous oligodendroglioma (pO) may appear as contradictory in terms, as nuclear monotony is a histomorphological hallmark of oligodendrogliomas. For the purpose of this study, we defined pO as diffusely infiltrating gliomas felt to be of oligodendroglial rather than astrocytic differentiation and characterized by the presence of multinucleate tumor giant cells and/or nuclear pleomorphism. In a total of nine patients, we identified tumors consistent with this working definition. All tumors were high‐grade. We characterized these with respect to clinical, histomorphological and genetic features. Despite clinical and genetic heterogeneity, we identified a subset of tumors of bona fide oligodendroglial differentiation as characterized by combined loss of heterozygosity of chromosome arms 1p and 19q (LOH 1p19q). Those tumors that lacked LOH 1p19q showed a high frequency of IDH1 mutations and loss of alpha thalassemia/mental retardation syndrome X‐linked gene (ATRX) immunoreactivity, indicating a possible phenotypic convergence of true oligodendrogliomas and gliomas of the alternative lengthening of telomeres (ALT) pathway. p53 alterations were common irrespective of the 1p19q status. Histomorphologically, the tumors featured interspersed bizarre multinucleate giant tumor cells, while the background population varied from monotonous to significantly pleomorphic. Our findings indicate, that a rare polymorphous – or “giant cell” – variant of oligodendroglioma does indeed exist.

Feasibility and Safety of Repeat Instant Endovascular Interventions in Patients with Refractory Cerebral Vasospasms

BACKGROUND AND PURPOSE: For patients with cerebral vasospasm refractory to medical and hemodynamic therapies, endovascular therapies often remain the last resort. Data from studies in large cohorts on the efficacy and safety of multiple immediate endovascular interventions are sparse. Our aim was to assess the feasibility and safety of multiple repeat instant endovascular interventions in patients with cerebral vasospasm refractory to medical, hemodynamic, and initial endovascular interventions. MATERIALS AND METHODS: This was a single-center retrospective study of prospectively collected data on patients with cerebral vasospasm refractory to therapies requiring ≥3 endovascular interventions during the course of treatment following aneurysmal subarachnoid hemorrhage. The primary end point was functional outcome at last follow-up (mRS ≤2). The secondary end point was angiographic response to endovascular therapies and the appearance of cerebral infarctions. RESULTS: During a 4-year period, 365 patients with aneurysmal subarachnoid hemorrhage were treated at our institution. Thirty-one (8.5%) met the inclusion criteria. In 52 (14%) patients, ≤2 endovascular interventions were performed as rescue therapy for refractory cerebral vasospasm. At last follow-up, a good outcome was noted in 18 (58%) patients with ≥3 interventions compared with 31 (61%) of those with ≤2 interventions (P = .82). The initial Hunt and Hess score of ≤2 was a significant independent predictor of good outcome (OR, 4.7; 95% CI, 1.2–18.5; P = .03), whereas infarcts in eloquent brain areas were significantly associated with a poor outcome (mRS 3–6; OR, 13.5; 95% CI, 2.3–81.2; P = .004). CONCLUSIONS: Repeat instant endovascular intervention is an aggressive but feasible last resort treatment strategy with a favorable outcome in two-thirds of patients with refractory cerebral vasospasm and in whom endovascular treatment has already been initiated.

A mathematical model describes the malignant transformation of low grade gliomas: Prognostic implications

Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose a mathematical model describing the spatio-temporal transition of LGGs into HGGs. Our modelling approach is based on two cellular populations with transitions between them being driven by the tumour microenvironment transformation occurring when the tumour cell density grows beyond a critical level. We show that the proposed model describes real patient data well. We discuss the relationship between patient prognosis and model parameters. We approximate tumour radius and velocity before malignant transformation as well as estimate the onset of this process.