Jean-Rodolphe Vignes

Peritumoral edema and prognosis in intracranial meningioma surgery

Peritumoral brain edema (PTBE) is often associated with meningiomas. PTBE is probably implicated in the complications occurring in intracranial meningiomas. The goal of this study was to determine the exact implication of PTBE in prognosis. Thirty consecutive patients who underwent surgery for intracranial meningiomas were investigated over a 1-year period. We focused on the clinical and radiological status before and after surgery, and postoperative complications. Multiple regression analysis revealed a close correlation (p<0.05) between PTBE and symptoms, type of arterial supply, difficulty of surgical removal, and postoperative complications. PTBE is likely implicated in the morbidity of intracranial meningiomas. We suggest predictive factors for difficult surgical resection, and emphasise the importance of medical preoperative management and post-operative follow-up.

Intraorbital apocrine hidrocystoma.

A 33-year-old man reported an 18 months history of a progressive right eyelid swelling, a sensation of eye pain and headaches. He noted a visual discomfort. Physical examination showed right eyelid edema, without skin lesion. The patients acuity was unchanged from the baseline; neither exophthalmia nor deficit in the visual field was noted. Magnetic resonance image showed an intraorbital, extraconal cystic lesion. Histopathologic examination revealed apocrine hidrocystoma.

Responses of heart rate variability to acute pain after minor spinal surgery: optimal thresholds and correlation with the numeric rating scale.

Background: The autonomic nervous system is influenced by many stimuli including pain. Heart rate variability (HRV) is an indirect marker of the autonomic nervous system. Because of paucity of data, this study sought to determine the optimal thresholds of HRV above which the patients are in pain after minor spinal surgery (MSS). Secondly, we evaluated the correlation between HRV and the numeric rating scale (NRS). Methods: Following institutional review board approval, patients who underwent MSS were assessed in the postanesthesia care unit after extubation. A laptop containing the HRV software was connected to the ECG monitor. The low-frequency band (LF: 0.04 to 0.5 Hz) denoted both sympathetic and parasympathetic activities, whereas the high-frequency band (HF: 0.15 to 0.4 Hz) represented parasympathetic activity. LF/HF was the sympathovagal balance. Pain was quantified by the NRS ranging from 0 (no pain) to 10 (worst imaginable pain). Simultaneously, HRV parameters were noted. Optimal thresholds were calculated using receiver operating characteristic curves with NRS>3 as cutoff. The correlation between HRV and NRS was assessed using the Spearman rank test. Results: We included 120 patients (64 men and 56 women), mean age 51±14 years. The optimal pain threshold values were 298 ms2 for LF and 3.12 for LF/HF, with no significant change in HF. NRS was correlated with LF (r=0.29, P<0.005) and LF/HF (r=0.31, P<0.001) but not with HF (r=0.09, NS). Conclusions: This study suggests that, after MSS, values of LF>298 m2 and LF/HF>3.1 denote acute pain (NRS>3). These HRV parameters are significantly correlated with NRS.

Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of < 70 years (standard group) and 117 patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p < 0.001), including surgical resection (p < 0.001), Bevacizumab therapy (p < 0.001), and second line chemotherapy other than Temozolomide (p < 0.001). In multivariate analysis, Age ≥70 years was not an independent predictor of overall survival from recurrence (p = 0.602), RTOG-RPA classes 5–6 (p = 0.050) and KPS at recurrence <70 (p < 0.001), available in all cases, were independent significant predictors of shorter overall survival from recurrence. Initial removal of ≥ 90% of enhancing tumor (p = 0.004), initial completion of the standard combined chemoradiotherapy (p = 0.007), oncological treatment from recurrence (p < 0.001), and particularly surgical resection (p < 0.001), Temozolomide (p = 0.046), and Bevacizumab therapy (p = 0.041) were all significant independent predictors of longer overall survival from recurrence. Elderly patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

Functional variability of sacral roots in bladder control.

OBJECT Sacral roots are involved in sensory, autonomic, and motor innervation of the lower limbs and perineum. Theoretically, it can be assumed that the S-3 root level innervates the bladder; however, clinical practice shows that this distribution can vary. Few researchers have studied this variability. METHODS The authors conducted a retrospective study involving 40 patients who underwent surgery requiring an electrophysiological exploration of the sacral roots. They performed stimulations for the monitoring of muscular (3 Hz, 1 V) and bladder responses under cystomanometry (30 Hz, 10 V). RESULTS Although the S-3 roots were involved in bladder innervation in all cases, they were exclusively involved (i.e., the only nerve roots involved) in only 8 of 40 cases. In the remaining 32 cases, other sacral nerve roots were involved. The most common association was S-3+S-4 (12 cases), followed by S-2+S-3 (6 cases), S-2+S-3+S-4 (5 cases), and S-3+S-4+S-5 (2 cases). Stimulation of S-2 could sometimes induce bladder contraction (15 cases, 40%); however, the amplitude was often low. S-4 nerve roots were involved in 24 of 40 cases (60%) in the bladder motor function, whereas S-5 roots were only involved 7 times (17%). Occasionally, we noticed a horizontal asymmetry in the response, with a predominant response from the right side in 6 of 7 cases, always with a major S-3 response. CONCLUSIONS This is the first study showing a significant horizontal and vertical variability in the functional distribution of sacral roots in bladder innervation. These results show the variability of cauda equina syndromes and their forensic implications. These data should help with the monitoring of sacral roots and the performance of several tasks during surgery, including neurostimulation and neuromodulation.

L’hyperréflexie autonome induite par la stimulation des racines sacrées est détectée par l’analyse spectrale de l’ECG

ObjectifComparer la technique d’analyse spectrale de l’électrocardiogramme (ECG) au monitorage de la tension artérielle moyenne (TAM) et la fréquence cardiaque (FC) dans la détection de l’hyperréflexie autonome (HRA) induite par la stimulation des racines sacrées.MéthodeDix blessés médullaires candidats à l’implantation d’un stimulateur des racines sacrées pour rétention urinaire ont été inclus. Sous anesthésie iv à objectif de concentration (4 μg·mL−1 de propofol, 4 ng·mL−1 de rémifentanil), les patients étaient installés en génu-pectoral. Les racines sacrées étaient exposées par une laminectomie (L2 à S1) et leur fonction évaluée par électrostimulation sous contrôle urodynamique et cardiovasculaire. L’analyse spectrale était obtenue en temps réel grâce au logiciel (MemCalc™) d’un ordinateur connecté au moniteur d’anesthésie. L’intervalle R-R de l’ECG était décomposé, par la méthode d’entropie maximum, en spectres de fréquences sympathiques (LF: 0,04–0,15 Hz) et parasympathiques (HF: 0,15–0,4 Hz). La valeur la plus extrême de chaque paramètre était notée avant et à chaque stimulation. Une différence Δ) supérieure à 10 % était considérée comme l’expression d’HRA. La comparaison (ΔLF vs ΔTAM et ΔHF vs ΔFC) était faite par un test de concordance basé sur un coefficient kappa (k): −1 = discordance totale à 1 = concordance totale.RésultatsL’HRA était détectée chez six patients sous forme: d’augmentation de LF et TAM (n = 4); d’augmentation de LF, HF, TAM et diminution de la FC (n = 2). Le délai de détection était de 5,3 ± 1 sec pour l’ECG spectral et 10 ± 1,2 sec pour la TAM et la FC. La concordance observée était de 85 % entre LF et TAM (k = 0,7) et 90 % entre HF et FC (k = 0,8).ConclusionL’HRA induite par la stimulation des racines sacrées est détectée par l’ECG spectral de manière plus précoce que la TAM et la FC. Ces résultats demandent une confirmation par d’autres études.AbstractPurposeTo compare spectral analysis of the electrocardiogram (ECG) with mean arterial pressure (MAP) and heart rate (HR) monitoring in the detection of autonomic hyperreflexia (AHR) induced by sacral root stimulation.MethodsTen spinal cord injured patients scheduled for implantation of a sacral root stimulator for bladder retention were included. Under target controlled anesthesia with propofol 4 μg·mL−1 and remifentanil 4 ng·mL−1, the patients were placed in the knee chest position. The sacral roots were exposed by laminectomy (L2-S1) and their function assessed by electrostimulation under urodynamic and cardiovascular monitoring. Online power spectrum densities were calculated from the ECG R-R interval by the MemCalc™ software using the maximum entropy method. Low frequency (LF: 0.04–0.15 Hz) and high frequency (HF: 0.15–0.4 Hz) spectra were associated with sympathetic and parasympathetic activities respectively. The most extreme value of each variable was noted before and during each stimulation. A difference (Δ) of more than 10% signified AHR. The comparison (ΔLF vs ΔMAP and ΔHF vs ΔHR) was done by a concordance test with a kappa coefficient (k): −1 = total discordance to 1 = total concordance.ResultsAHR was detected in six patients as an increase in LF and MAP (n = 4); an increase in LF, HF, MAP with a decrease in HR (n = 2). The detection delay was 5.3 ± 1 sec (LF, HF) and 10.4 ± 1.2 sec (MAP and HR). Concordance was 85% (LF vs MAP: k = 0.7) and 90% (HF vs HR: k = 0.8).ConclusionAHR induced by sacral root stimulation is detected by spectral analysis of the ECG earlier than MAP and HR. Other studies are needed to confirm these results.PURPOSE To compare spectral analysis of the electrocardiogram (ECG) with mean arterial pressure (MAP) and heart rate (HR) monitoring in the detection of autonomic hyperreflexia (AHR) induced by sacral root stimulation. METHODS Ten spinal cord injured patients scheduled for implantation of a sacral root stimulator for bladder retention were included. Under target controlled anesthesia with propofol 4 micro g*mL(-1) and remifentanil 4 ng*mL(-1), the patients were placed in the knee chest position. The sacral roots were exposed by laminectomy (L2-S1) and their function assessed by electrostimulation under urodynamic and cardiovascular monitoring. Online power spectrum densities were calculated from the ECG R-R interval by the MemCalc(TM) software using the maximum entropy method. Low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) spectra were associated with sympathetic and parasympathetic activities respectively. The most extreme value of each variable was noted before and during each stimulation. A difference ( triangle up ) of more than 10% signified AHR. The comparison ( triangle up LF vs triangle up MAP and triangle up HF vs triangle up HR) was done by a concordance test with a kappa coefficient (k): -1 = total discordance to 1 = total concordance. RESULTS AHR was detected in six patients as an increase in LF and MAP (n = 4); an increase in LF, HF, MAP with a decrease in HR (n = 2). The detection delay was 5.3 +/- 1 sec (LF, HF) and 10.4 +/- 1.2 sec (MAP and HR). Concordance was 85% (LF vs MAP: k = 0.7) and 90% (HF vs HR: k = 0.8). CONCLUSION AHR induced by sacral root stimulation is detected by spectral analysis of the ECG earlier than MAP and HR. Other studies are needed to confirm these results.

Impact of direct epispinal stimulation on bladder and bowel functions in pigs: A feasibility study

This study assesses the potential of epispinal (subdural) stimulation application in the treatment of urinary and bowel neurological disorders. Acute experiments were performed on a large animal model — the domestic pig — to develop a new methodology facilitating future results and technology transfers to human.

An intermediate animal model of spinal cord stimulation

Spinal cord injuries (SCI) result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self-) catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.

A cost-utility analysis of sacral anterior root stimulation (SARS) compared with medical treatment in patients with complete spinal cord injury with a neurogenic bladder

BACKGROUND CONTEXT Sacral anterior root stimulation (SARS) and posterior sacral rhizotomy restores the ability to urinate on demand with low residual volumes, which is a key for preventing urinary complications that account for 10% of the causes of death in patients with spinal cord injury with a neurogenic bladder. Nevertheless, comparative cost-effectiveness results on a long time horizon are lacking to adequately inform decisions of reimbursement. PURPOSE This study aimed to estimate the long-term cost-utility of SARS using the Finetech-Brindley device compared with medical treatment (anticholinergics+catheterization). STUDY DESIGN/SETTINGS The following study design is used for the paper: Markov model elaborated with a 10-year time horizon; with four irreversible states: (1) initial treatment, (2) year 1 of surgery for urinary complication, (3) year >1 of surgery for urinary complication, and (4) death; and reversible states: urinary calculi; Finetech-Brindley device failures. PATIENT SAMPLE The sample consisted of theoretical cohorts of patients with a complete spinal cord lesion since ≥1 year, and a neurogenic bladder. OUTCOME MEASURES Effectiveness was expressed as quality adjusted life years (QALYs). Costs were valued in EUR 2013 in the perspective of the French health system. METHODS A systematic review and meta-analyses were performed to estimate transition probabilities and QALYs. Costs were estimated from the literature, and through simulations using the 2013 French prospective payment system classification. Probabilistic analyses were conducted to handle parameter uncertainty. RESULTS In the base case analysis (2.5% discount rate), the cost-utility ratio was 12,710 EUR per QALY gained. At a threshold of 30,000 EUR per QALY the probability of SARS being cost-effective compared with medical treatment was 60%. If the French Healthcare System reimbursed SARS for 80 patients per year during 10 years (anticipated target population), the expected incremental net health benefit would be 174 QALYs, and the expected value of perfect information (EVPI) would be 4.735 million EUR. The highest partial EVPI is reached for utility values and costs (1.3-1.6 million EUR). CONCLUSIONS Our model shows that SARS using Finetech-Brindley device offers the most important benefit and should be considered cost-effective at a cost-effectiveness threshold of 30,000 EUR per QALY. Despite a high uncertainty, EVPI and partial EVPI may indicate that further research would not be profitable to inform decision-making.

Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0–86) and 8.0 months (mean, 8.5; range, 0–56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03–2.08]; p = 0.032), RTOG–RPA V–VI classes (aHR, 1.38; 95% CI [1.11–1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10–5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44–0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31–0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG–RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG–RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.