Background

So-called low-grade gliomas are most often revealed by a seizure occurring in a young adult who had no previous symptoms. This is a very slowly progressive tumor (approximately 4 mm/year); this slow growth allows the brain to adapt to the tumor’s presence and reorganize its circuits to compensate for tumor areas that have become non-functional.

Prof. Mandonnet has specialized for over 20 years in the management of low-grade gliomas. He has developed a personalized, patient-centered approach. Throughout the care pathway, support is provided by the best specialists in the field. The entire care process is coordinated by a dedicated medical assistant, Ms. Chadia Draou (01-49-95-81-46; chadia.draou@aphp.fr)

1. At the Time of Diagnosis

The first consultation takes place during the neurosurgery appointment with Prof. Mandonnet. All necessary time is taken to get to know the patient and their lifestyle, to explain the disease and what is known about its progression, as well as the available means to prevent its advancement. The benefits and risks of each option are discussed, namely surgical treatment, chemotherapy (Temodal or PCV), radiotherapy, and targeted therapy (Vorasidenib or Ivosidenib).
Most often, a surgical resection is proposed as first-line treatment, due to its proven benefit. The principles of functionally maximal resection are then explained in detail—that is, a resection whose goal is to remove as much of the tumor as possible while maximizing the chances of recovery to a “normal” life. In particular, the procedure for awake surgery is presented, as well as the risk of transient brain function disorders appearing in the immediate postoperative period. These disorders recover remarkably thanks to brain plasticity, enhanced by specialized cognitive rehabilitation care in the Physical Medicine and Rehabilitation department of Prof. Beaudreuil. Thus, after a rehabilitation period of a few months (3 to 6 months), the vast majority of patients can resume their professional life (see article https://pubmed.ncbi.nlm.nih.gov/38372820/). It is also explained that patients nevertheless experience significant fatigue (see article https://pubmed.ncbi.nlm.nih.gov/35462205/), which may require a therapeutic part-time return to work for a few months.

2. Preparation for Awake Surgery

A complete assessment will include:
– a language and cognitive evaluation with a speech therapist from the Lariboisière team (Isabelle Poisson, Marion Barberis, Cécile Prevost, Sophie Bouteloup). This evaluation is fundamental, as subtle impairments may be revealed, although previously unnoticed in daily life. These areas of vulnerability will require particular attention (during surgery and rehabilitation), as they indicate that the brain has reached its compensation limits for these functions.
– specialized functional and anatomical imaging. The objective is notably to confirm that language functions are indeed lateralized to the left side (99% of right-handers and 90% of left-handers). Here too, it is essential to identify patients with atypical language lateralization, in order to select the appropriate tests for monitoring during the awake phase of surgery.
– an electroencephalogram (EEG). Epilepsy is a distinct issue in the management of diffuse low-grade glioma. EEGs will allow optimal adjustment of anti-epileptic treatments.
– a consultation with the anesthesiologist to prepare medically for the procedure and with the nurse anesthetist to prepare for the hypno-sedation technique used by the Lariboisière team.

3. During Surgery

Awake surgery is one of the most reliable methods for removing these tumors as extensively as possible while preserving patient functionality. This is cutting-edge surgery, requiring a dedicated multidisciplinary team. The procedure lasts approximately 5 to 6 hours, including 2 hours of wakefulness during which the patient participates by performing various tasks under the speech therapist’s direction. The entire operating room team assists and encourages the patient throughout the procedure.

4. After Surgery

A brain MRI is performed the day after the procedure to ensure the absence of complications and verify the quality of the resection. Corticosteroid treatment for anti-edema purposes is prescribed for a few weeks. Anti-epileptic treatment is reinforced for a few weeks (or initiated if there was none). The hospital stay lasts a few days. Before discharge, the patient undergoes a complete cognitive and language assessment, which will enable a personalized rehabilitation strategy to be proposed. If the disorders are minor, the speech therapist refers the patient directly to a colleague in private practice. If the disorders are more significant, the patient is referred to the rehabilitation physician, who will decide on the optimal rehabilitation plan (day hospital if the patient is fully autonomous, full hospitalization if lacking autonomy).
The patient is seen again 4 months after surgery, with a new complete clinical, electrophysiological, cognitive, language, and radiological evaluation. It is during this follow-up consultation that the various options for subsequent treatment are discussed, based on multiple parameters.

5. Subsequent Treatment

In the vast majority of cases, a period of clinical and radiological surveillance is proposed. Only in cases of progression and/or signs of aggressiveness (histological grade 3, high growth rate on MRI, size of any residual tumor, etc.) is adjuvant treatment proposed. The case is then discussed in a multidisciplinary team meeting (MDT). The discussion involves the neuro-oncologist, radiotherapist, radiologist, pathologist, molecular biologist, and neurosurgeon. Together, they converge on the best recommendation for each case.
Treatment may consist of:
– Chemotherapy, most often using a combination of three drugs (PCV protocol = procarbazine – CCNU – vincristine)
– Radiotherapy
– Targeted therapy against the IDH mutation
– Repeat surgery

Research

Development of digital tools for optimizing cognitive assessments.
This theme is being developed within LABCOM Cog-Toolkit, a joint laboratory between Frontlab at the Brain Institute (where Prof. Mandonnet conducts his research) and the company Humans Matter. The Cog-Surg platform, dedicated to awake surgery, is currently under development.

Prediction of cognitive functions after surgery.
We are still far from knowing everything about the brain and its capacity to remodel after surgery. The goal is therefore to advance our ability to anticipate deficits in complex cognitive functions based on the extent of resection. Several works by Prof. Mandonnet have enabled major progress in understanding functions such as cognitive flexibility (https://pubmed.ncbi.nlm.nih.gov/35245898/) or creativity (https://pubmed.ncbi.nlm.nih.gov/38593576/). Other functions are still under study, such as motivation, social cognition, working memory, etc.

Elucidation of plasticity mechanisms by MRI and PET
The principles of brain network reorganization during the recovery phase remain very poorly understood. A collaborative project with Orsay Hospital, a site historically involved in positron emission tomography (PET), aims to describe the neural bases of this reorganization. The hope is to identify new methods to facilitate and optimize reorganization.