Study Design and Setting
The study was approved by the University of Sapienza of Rome, Policlinico Umberto I Committee on Human Research.
We retrospectively reviewed a consecutive series of patients who underwent surgery for resection of AVMs between January 2016 and January 2020 in the department of Neurosurgery of Policlinico Umberto I of Rome. Data were obtained from an ongoing registry of AVM-patients treated at our institution. After enrollment, patients were divided into 2 groups according to modality of procedure performed (Group A, Asleep Surgery; Group B, Awake surgery).
Participants and Eligibility
All the patients included in the final cohort meet the following inclusion criteria:
- Patients with a neuro-radiological diagnosis of unruptured AVMs confirmed by angiographic exam and histopathological analysis.
- Preoperative KPS scale score >50%.
- Absence of major neuropsychological deficits preventing the pre and intraoperative testing
- The estimated target of the surgical procedure was the radical excision of lesion.
- Patients were included if, in the postoperative period, could undergo in a clinical and radiological follow-up program.
- Once the residual of the disease was noticed the patient and the relevant imaging were referred again to our attention, to evaluate the feasibility of a second surgery or to address the patient to an adjuvant treatment.
- Complete and correct data on clinical, radiological, surgical and follow-up records
At admission all patients underwent a general medical, a neurological, and a psychological evaluation. For all the included patients we recorded:-
- Patient-related variables: sex, age, smoking, days of recovery, pre and post-operative KPS, clinical presentation (divided in debut of seizure, focal deficit, headache or incidental, mental dizziness or acute syndrome), antiepileptic prophylaxis and treatment, incidence of post-operative seizures;
- Lesion and surgery-related variables: location and side of the lesions, S-M grade, S-M grade modified by Lawton, presence of perinidal aneurysm, signs of previously hemorrhage, presence of residual after surgery, adjuvant treatment eventually performed.
Clinical informations were obtained by the digital database of our Institution, whereas OS and KPS data were obtained by telephone-interviews. A special focus was centered on the performance status expressed as KPS results in a dichotomy data (> and < 70). In particular it was recorded in three different moments:
- Before surgery at the time of diagnosis
- At 30 days after surgery (early post-operative evaluation and
- At the end of the adjuvant treatment (the moment of the last outpatient evaluation).
We performed a descriptive analysis of all our AVMs cases, partially confirming what was reported in the literature, before focusing on the group analysis implemented to the other series.
Preoperative and Operative Protocol
All the patients included underwent a preoperative CT scanning, brain MRI scan included an high field 3 Tesla volumetric study with the following sequences: T2w, Fluid Attenuated Inversion Recovery (FLAIR), Isotropic Volumetric T1-weighted Magnetization-prepared Rapid Acquisition Gradient Echo (MPRAGE) before and after intravenous administration of paramagnetic contrast agent; diffusion tensor sequences (DTI) with 3D tractography, functional MRI (fMRI) and catheter digital subtraction angiography (DSA).
Patients with AVMs in the language cortex underwent language testing by a neuropsychologist.
Eloquent location was first identified anatomically on MRI and then confirmed by fMRI. Patients with unruptured AVMs directly in the language zone where fMRI had shown activity extremely close (<5mm) or within the nidus were not considered for surgery and referred for other non-surgical options.
All the procedures were performed with an infrared-based Neuronavigator (Brainlab, Kick® Purely Navigation), in a standard neurosurgical theatre, with a standard operative microscope. In the first postoperative day, as routine, the patients underwent a CT scan to exclude major complications and volumetric Brain MRI scan to evaluate the EOR.
General contraindications for awake procedures was uncooperative patients, patients with severe language disabilities (such as frank Wernicke's aphasia), very young patients or patients with significant language barriers. Patient’s clinical presentation is also important. Patients presenting with hemorrhage associated with hemiplegia, aphasia or a comatose state may not be good candidates for awake mapping.
Specific relative neurovascular contraindications include large and deep AVMs, posterior fossa cavernomas or AVMs and possibly patients undergoing direct bypasses for Moyamoya disease.
As a standard protocol adopted at our center  For Asleep group a standard total intravenous anesthesia protocol with Propofol (1 mg/kg) and Remifentanil (0.5 mg/kg/min) has been used and maintained until the end of surgery. For Awake group, a standard Full Awake Surgery protocol was routinely performed with the aid of Intraoperative Neuromonitoring realized with use of bi- and monopolar stimulating probes respectively for the cortical and subcortical mapping. During craniotomy and surgical exposure for awake cases, patients were sedated with intravenous agents that included propofol (50-100 mg/kg/min) and remifentanil (0.05-0.2 mg/kg/min). Local anesthesia with lidocaine was used for scalp and temporal muscle. Before mapping, sedatives were discontinued and patients were awakened under the care of the anesthesiologist.
In general, it was intraoperatively judged necessary to stop malformation excision when:
- despite a directly visualized or a Navigation proven remnant, neuromonitoring or intraoperative neuropsychological testing outlined a risk for postoperative motor morbidity,
- white matter appeared free of tangling vases.
Data sources and Quantitative variables
The presence of residual was determined through a comparison between the MR images and angiography obtained before surgery and the first early angiography after surgery.
In case of residual, we signaled if patient follow a wait-and see follow-up or another surgery/adjuvant treatment with radiosurgery.
A close range dedicated neuro-imaging follow-up program was routinely performed in our Institution. This program included:
- A standard early (maximum 24 hours after surgery) postoperative volumetric brain MRI and angiography.
- At approximately one month from surgery (25-35 days) a angio-CT scan was repeated for a first step follow-up control;
- At 6 month/1 year from surgery with CT-Angiography scan;
At every radiological reevaluation we performed a complete outpatient clinical and neurological outpatient re-evaluation.
Size, statistical power of the study and potential source of Bias
The study size is given by selection of the inclusion criteria. As previously stated, we addressed no missing data because incomplete records were an exclusion criterion. A potential source of bias is expected from exiguity of the sample, nevertheless it presents an excellent post hoc statistical estimated power 1-b. 0.87 (for a. 0.05; effect size, 0.74). The sample was analyzed with SPSS v18 (SPSS Inc., Released 2009, PASW Statistics for Windows, Version 18.0, Chicago, Illinois, USA) to outline potential correlations between the investigated variables.
Comparison between nominal variables have been made with Chi2 test. Threshold of statistical significance was considered p<.05.
The informed consent was approved by the Institutional Review Board of our Institution. Before surgical procedure, all the patients gave informed written explicit consent after appropriate information. Data reported in the study have been completely anonymized. No treatment randomization has been performed. This study is perfectly consistent with Helsinki declaration of Human Rights in medical Research.
Neurological outcome was assessed using the Karnofsky performance scale (KPS). A single clinical nurse, under the supervision of a neurologist, performed all clinical assessments before any treatment, preoperatively, at 1 months postoperatively, and during the follow-up period. All patients had follow-up data within 1 year of analysis.
AVM-related seizures that interfered with daily activities (working, school, driving, etc) were assigned a score lower than 70.
Research Strategy for Awake series on AVMs
We performed a review of the literature by analyzing all reported cases of AVM treated with awake surgery and mapping with the aim of identifying the clinical features, operative strategies, surgical results, outcome and rate of complications. We adopted PRISMA criteria for clinical research.
Therefore, while screening the literature, we adopted the following inclusion and exclusion criteria:
Meta-analysis, Case series, Clinical study or Clinical image reporting cases of patients who suffered from intracranial AVM for which an awake surgical approach was adopted;
Conversely, we excluded the following:
Cases reported without detailed clinical features of patients; cases reported without description of radiological images, or summaries and book chapters; papers that report other pathologies or in circumstantial mode (out of topic) and papers written in languages other than English.
Information Sources and Search
The English literature was systematically investigated using MEDLINE, the NIH Library, Pubmed and Google Scholar. The last search date was 15 May 2021. The following search terms were used:
Arterio-venous malformation or AVM AND Awake surgery or Awake mapping. Duplicated articles are removed after the first investigation trough the libraries.