Emmanuel Mandonnet

Continuous growth of mean tumor diameter in a subset of grade II gliomas

Serial magnetic resonance images of 27 patients with untreated World Health Organization grade II oligodendrogliomas or mixed gliomas were reviewed retrospectively to study the kinetics of tumor growth before anaplastic transformation. Analysis of the mean tumor diameters over time showed constant growth. Linear regression, using a mixed model, found an average slope of 4.1mm per year (95% confidence interval, 3.8–4.4mm/year). Untreated low‐grade oligodendrogliomas or mixed gliomas grow continuously during their premalignant phase, and their pattern of growth can be predicted within a relatively narrow range. These findings could be of interest to optimize patients management and follow‐up. Ann Neurol 2003;53:524–528

Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of WHO grade II gliomas: Towards a "minimal common brain"

Despite recent advances in non-invasive brain mapping imaging, the resectability of a given area in a patient harboring a WHO grade II glioma cannot be predicted preoperatively with high reliability, due to mechanisms of functional reorganization. Therefore, intraoperative mapping by direct electrical stimulation remains the gold standard for detection and preservation of eloquent areas during glioma surgery, because it enables to perform on-line anatomo-functional correlations. To study potentials and limitations of brain plasticity, we gathered 58 postoperative MRI of patients operated on for a WHO grade II glioma under direct electrical cortico-subcortical stimulation. Postoperative images were registered on the MNI template to construct an atlas of functional resectability for which each voxel represents the probability to observe residual non-resectable tumor, that is, non-compensable area. The resulting atlas offers a rigorous framework to identify areas with high plastic potential (i.e. with probabilities of residual tumor close to 0), with low compensatory capabilities (i.e. probabilities of residual tumor close to 1) and with intermediate level of resectability (probability around 0.5). The resulting atlas highlights the utmost importance of preserving a core of connectivity through the main associative pathways, namely, it supports the existence of a minimal common brain among patients.

Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas

A consecutive series of 143 unselected adult patients with histologically proved World Health Organization grade II gliomas was reviewed to assess the prognostic value of growth rates of mean tumor diameters on successive magnetic resonance images before treatment. There is an inverse correlation between growth rates and survival (p < 0.001; median survival at 5.16 years for a growth rate of 8mm/year or more; median survival >15.0 years for a growth rate <8mm/year). Thus, individual magnetic resonance imaging tumor growth rates should be incorporated in the planning of the initial therapeutic strategy of grade II gliomas. Ann Neurol 2006;60:380–383

Simulation of anisotropic growth of low-grade gliomas using diffusion tensor imaging

A recent computational model of brain tumor growth, developed to better describe how gliomas invade through the adjacent brain parenchyma, is based on two major elements: cell proliferation and isotropic cell diffusion. On the basis of this model, glioma growth has been simulated in a virtual brain, provided by a 3D segmented MRI atlas. However, it is commonly accepted that glial cells preferentially migrate along the direction of fiber tracts. Therefore, in this paper, the model has been improved by including anisotropic extension of gliomas. The method is based on a cell diffusion tensor derived from water diffusion tensor (as given by MRI diffusion tensor imaging). Results of simulations have been compared with two clinical examples demonstrating typical growth patterns of low‐grade gliomas centered around the insula. The shape and the kinetic evolution are better simulated with anisotropic rather than isotropic diffusion. The best fit is obtained when the anisotropy of the cell diffusion tensor is increased to greater anisotropy than the observed water diffusion tensor. The shape of the tumor is also influenced by the initial location of the tumor. Anisotropic brain tumor growth simulations provide a means to determine the initial location of a low‐grade glioma as well as its cell diffusion tensor, both of which might reflect the biological characteristics of invasion. Magn Reson Med, 2005.

Epileptic seizures in diffuse low-grade gliomas in adults

Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.

Dynamic history of low‐grade gliomas before and after temozolomide treatment

To evaluate the natural progression and the impact of temozolomide in low‐grade gliomas and to correlate these changes with the profile of genetic alterations.

Extension of paralimbic low grade gliomas: toward an anatomical classification based on white matter invasion patterns

ObjectLow grade gliomas are both proliferative and diffusive tumors, as recently modelized. When proliferation is predominant, the tumor is rather bulky and its main locations are the supplementary motor area and the paralimbic system. Diffusion occurs preferentially along white matter tracts. Recent anatomo-functional studies, performed both inxa0vitro and inxa0vivo, have described the fiber tracts centered around the insula. We thus propose to analyze the extension of paralimbic low grade gliomas in terms of invaded subcortical pathways.MethodsWe retrospectively reviewed the MRIs of patients followed for a WHO grade II glioma at the Salpêtrière Hospital between 1991 and 2003. We selected patients with tumors centered on the insula and extending in temporal and frontal lobes (Type 2b-2c-3 of Yasargil’s classification). We then analyzed on FLAIR sequences the extension (tracked on successive examinations before any treatment) along two main fasciculi in that area: the uncinate and arcuate fasciculi.ResultsA total of 40 patients fulfilled the inclusion criteria. The uncinate fasiculus was invaded in 28 cases, the arcuate fasciculus in 9 cases, and both fasciculi in 3 cases. Longitudinal follow-up was available in 16 cases, and confirmed the preferential extension along these fasciculi.ConclusionThis kinetic analysis of extension of paralimbic low grade gliomas confirms that these tumors spread along distinct subcortical fasciculi. Due to the functional role of these pathways, this classification could be useful to elaborate therapeutic strategy (prognosis index, pre- and intra-operative neuropsychological testing, functional outcome).

Natural history of incidental world health organization grade II gliomas

Seizure is the presenting symptom in most of World Health Organization grade II gliomas (GIIGs). Rarely, a GIIG is discovered incidentally on imaging. Little is known about the natural course and prognosis of incidental GIIGs. The aim of the present study is to characterize their natural history and to investigate whether their clinical and radiological behaviors differ from those of symptomatic GIIGs.

Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations

BackgroundWhile the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time.MethodHere, we critically review exactly what DES can tell us about cerebral function.ResultsFirst, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms.ConclusionIn brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

Computational modeling of the WHO grade II glioma dynamics: principles and applications to management paradigm

The advent of magnetic resonance imaging (MRI) has allowed the follow-up of tumor growth by precise volumetric measurements. Such information about tumor dynamics is, however, usually not fully integrated in the therapeutic management, and the assessment of tumor evolution is still limited to qualitative description. In parallel, computational models have been developed to simulate in silico tumor growth and treatment efficacy. Nevertheless, direct clinical interest of these models remains questionable, and there is a gap between scientific advances and clinical practice. In this paper, WHO grade II glioma will serve as a paradigmatic example to illustrate that computational models allow characterizing tumor dynamics from serial MRIs. The role of these dynamics for both therapeutic management and biological research will be discussed.