Intraoperative ultrasound and 5-ALA: the two faces of the same medal?

BACKGROUND: High Grade Gliomas (HGG) still remain the most demanding neuro-oncological challenge. Several studies have confirmed that the extent of resection (EOR) correlates with increased survival in patients with HGGs. The Gross Total Resection (GTR) of HGGs can be difficult and challenging. For this reason, technologies to improve EOR have been of interest. The aim of this paper is to analyze advantages and limitations of both intra-operative fluorescence and intra-operative ultrasound (IOUS) resection techniques. METHODS: Our work deals with the comparison of one group of 15 patients treated with both tools (study group) with a control group of 15 patients in where only fluorescence was used. Post operative outcome are valued using Karnofsky Performance Status scale (KPS) while EOR are valued with MRI within 24 h after surgery. RESULTS: The difference between the postoperative KPS and between EOR in the 2 groups resulted not statistically significant considering p<0.05. In our experience 5-ALA has a limited sensitivity before starting resection while shows it's central role in identifying the tumor remnants after its removal. Conversely, IOUS is very useful in identifying the tumor before starting resection. After the tumor removal, the sensitivity of the ultrasound in identifying tumor remnants in the margins of the cavity decreased significantly. However, in one case, at the end of resection, we have not visualized any fluorescent tissue but we detect a residual of tumor using the IOUS. CONCLUSIONS: In our preliminary experience we observe that there are no significative advantages using IOUS plus 5-ALA. However we feel that IOUS is useful in first step of resection and fluorescence in the latest steps of operation. Therefore these two technologies could be considered the two faces of the same medal because they can help the surgeon to detect the tumor in all step of tumor removal.

Postoperative Care of Patients with High-grade Glioma: Is There a Real Need for the Neurocritical ICU and Early CT Scan?

BACKGROUND: Pressure on economic resources now requires a careful rationalization of services. For adult patients with supratentorial gliomas, there is no consensus on the real need for care in a postoperative neurocritical intensive care unit (NICU) and on the timing of a postsurgical computed tomography (CT) scan. In this retrospective nonrandomized study, we assessed if and when there is a real need for NICU and if an early CT scan could be justified in the absence of neurologic worsening. METHODS: Of 264 patients, 21 were admitted to the NICU after the procedure as planned before the surgery for their clinical features (Karnofsky performance status < 70, American Society of Anesthesiologists score > 2, or Charlson Comorbidity Index > 5). RESULTS: The mean stay in the NICU was 19.7 hours. One of these patients had developed a postoperative hematoma that was subsequently removed, and died afterward. The other 243 patients were followed clinically after the procedure: 219 underwent a cerebral CT scan 24 hours after the procedure and were discharged in good condition. The other 24 patients had a cerebral CT scan within 24 hours after the procedure. The early CT showed the presence of a local edema in five cases and a hematoma surgically treated with a subsequent admission to the NICU in two cases. CONCLUSION: Considering our data, we suggest that NICU should not always be used after craniotomy for supratentorial gliomas. Clinical observation was sufficient to predict early postoperative complications. A CT scan before 24 hours after surgery is not recommended in the absence of clinical worsening.

Ultrasound guided mini-invasive tailored approach and intraoperative neurophysiological monitoring: a synergistic strategy for the removal of tumors near the motor cortex. A preliminary experience.

BACKGROUND: The aim of this paper was to evaluate the synergic strategy comprising intraoperative neurophysiological monitoring and ultrasound sonography in terms of clinical motor scores and extent of resection. METHODS: Patients harboring tumors in close relationship with the motor cortex were operated on with image-guided mini-invasive approach and multimodal neurophysiological monitoring. The peculiarity is the partial exposure of the motor cortex and the limited electrophysiological mapping used to search for negative spots. Multimodal neurophysiological monitoring comprised the electrocortical stimulation, somatosensory evoked potentials, motor evoked potentials and subcortical stimulation. Ultrasound sonography guided the tumor removal. The post-op clinical motor scores and the extent of resection were assessed. RESULTS: Twelve patients were operated on with the combined approach and were further analyzed. Six had high grade gliomas, 1 anaplastic astrocytoma, 1 oligodendroglioma, 1 pilocytic astrocytoma and three had metastasis. One out of 12 had a worsening of the motor scores at the last follow-up. The mean extent of resection was 90% ranging from 60% to 100%, but in 9 out of 12 patients, it reached or exceeded 90%. CONCLUSIONS: The synergic strategy comprising intraoperative multimodal neurophysiological monitoring and the ultrasound sonography is feasible in all surgeries. Data are promising in terms of both clinical motor scores and extent of resection. This strategy represents an alternative approach to the treatment of supratentorial tumors, although further studies are necessary to confirm the long-term efficacy of this procedure.

Scalp Metastasis from Glioblastoma Multiforme: A Case Report and Literature Review.

Glioblastoma multiforme (GBM) is a common malignant brain tumor that rarely metastasizes extracranially, despite its aggressive clinical course. This report details the case of a young man presenting with a single subcutaneous localization of GBM that arose six months after initial surgery and recurred after excision. Only six other cases of scalp metastasis of GBM following surgery have been described in the literature, each with peculiar features. Whenever feasible, surgery is the most effective way to obtain local control of disease. However, a correct approach must be carefully planned to minimize the risks of recurrence and wound dehiscence.

Role of nitric oxide and mechanisms involved in cerebral injury after subarachnoid hemorrhage: is nitric oxide a possible answer to cerebral vasospasm?

Cerebral vasospasm represents the most critical event that could occur after subarachnoid hemorrhage (SAH). Therapy is only partially effective because cerebral arterial constriction is not fully understood yet. One of the most important biological messenger associated to SAH is nitric oxide (NO), that is considered local regulator of cerebral blood flow. Different nitric oxide synthase (NOS) forms play a role in different biological processes, one of which is to link neuronal activity to blood flow in cerebral cortex. We performed a reassessment of the literature to summarize the role of NO as the main inflammatory pathway activated after SAH to clarify its importance for treatment of vasospasm.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.

Say "no" to spinal cord injury: is nitric oxide an option for therapeutic strategies?

PURPOSE: a literature review was made to investigate the role of nitric oxide (NO) in spinal cord injury, a pathological condition that leads to motor, sensory, and autonomic deficit. Besides, we were interested in potential therapeutic strategies interfering with NO mechanism of secondary damage. MATERIALS: A literature search using PubMed Medline database has been performed. RESULTS: excessive NO production after spinal cord injury promotes oxidative damage perpetuating the injury causing neuronal loss at the injured site and in the surrounding area. CONCLUSION: different therapeutic approaches for contrasting or avoiding NO secondary damage have been studied, these include nitric oxide synthase inhibitors, compounds that interfere with inducible NO synthase expression, and molecules working as antioxidant. Further studies are needed to explain the neuroprotective or cytotoxic role of the different isoforms of NO synthase and the other mediators that take part or influence the NO cascade. In this way, it would be possible to find new therapeutic targets and furthermore to extend the experimentation to humans.

Surgery in cerebral metastases: are numbers so important?

BACKGROUND: The prognosis of cerebral metastases (MTS) is linked to progression of both systemic and local disease. The importance of MTS resection has been already pointed out. The observation of a high mortality for not-neurological causes confirms that the modern treatments allow a significant control of the disease within the nervous system. Nevertheless, management difficulties increase with multiple lesions and in these cases the role of surgery has still to be defined. MATERIALS AND METHODS: We collected the clinical data of patients operated in two centers for cerebral MTS from lung carcinoma during 8 years. Patient selection for surgery followed definite criteria; the limit for multiple MTS was three. We analyzed the functional and survival outcomes of the cohort. RESULTS AND CONCLUSIONS: Our series included 242 patients: 105 had multiple MTS. Statistical analysis did not show significant differences in mean survival and outcomes between patients with single and multiple lesions. The decease occurred for neurological causes in 15.7% of cases. The selection of candidates for surgery requires several considerations and entails the success rate of this treatment. In patients with the multiple lesions who fulfilled the selection criteria we observed a nevertheless satisfying success after the operation. Our results imply that surgery may be applied also in selected patients with more diffuse intracranial disease. A pre-operative accurate patient selection is related to acceptable quality-of-life following the operation even in cases of multiple MTS.

A retrospective two-center study of antiepileptic prophylaxis in patients with surgically treated high-grade gliomas.

BACKGROUND: The effectiveness of antiepileptic prophylaxis in patients with newly diagnosed high-grade glioma is debated. Craniotomy, surgical manipulation and bleeding are believed to favor the onset of seizures and, therefore, perioperative antiepileptic drugs (AEDs) are generally used. Nevertheless, evidence to initiate preoperative AED prophylaxis are weak. AIM: Aim of this paper was to evaluate the need for AED prophylaxis in surgically-treated malignant glioma patients without history of seizures. MATERIALS AND METHODS: We conducted a retrospective, two-center cohort study to assess the effectiveness of preoperative AED prophylaxis. Patients were divided in two groups: one with AED preoperative administration and the other without. Because of its non-hepatic metabolism, levetiracetam (LEV) was chosen. Logistic regression models were used to investigate the odds ratio for each group. The explanatory variables included the treatment received, sex, age, and site of lesion. The outcome measure of successful LEV prophylaxis was seizure vs. no seizure post-operatively, at three and six months after surgery. RESULTS: Our results showed that LEV prophylaxis was not a significant predictor of seizure occurrence, although the regression coefficient indicated a slight reduction in seizure risk following LEV administration. Patient's age was a significant predictor of seizure occurrence. Younger patients had a higher risk of seizure in the six months post-surgery. CONCLUSIONS: We conclude that AEDs prophylaxis does not provide a substantial benefit to surgically treated high-grade glioma patients and should not be administered routinely. Further investigations are required to detect subgroups of patients at higher risk of developing seizures in order to selectively administer AED.

Recovery after delayed surgery in a case of spinal subdural hematoma.

Spinal chronic subdural hematoma (SCSH) is a rare pathology usually associated with trauma or hematological alterations or is due to iatrogenic causes; rarely SCSH can be spontaneous. We report a case of a 79-year-old female who underwent a surgical evacuation of a spontaneous SCSH one year after diagnosis. She presented with a severe paraparesis and showed a considerable improvement in sensory-motor performances after surgery. The treatment of spontaneous SCSH is not well defined and universally accepted. Early surgery is mandatory in cases presenting with severe deficits. To the best of our knowledge, this is the first case showing a good outcome in a case of SCSH following a delayed surgery. In our opinion, an aggressive approach should be considered as a viable option in cases of spontaneous SCSH even after a lasting spinal cord compression.

Multiple cavernomas of the brain: simultaneous hemorrhage of two lesions in a non-familial form.

BACKGROUND: Cavernomas of the brain are congenital lesions clinically divided into hereditary and a sporadic forms. Multiple lesions are usually observed in the familial form, whereas the sporadic variant generally shows a single cavernoma. In this case we describe the simultaneous bleeding of two lesions in a patient with a non-familial cavernomatosis. CASE DESCRIPTION: A 46-year-old woman presented with slight hyposthenia involving the left arm and cervical stiffness. Examinations revealed two cavernomas with recent signs of bleeding. The lesions were surgically removed achieving a total excision. The patient was discharged after 10 days with slight left hyposthenia. DISCUSSION: Simultaneous hemorrhage of multiple cavernomas is rare. To the best of our knowledge, this is the first case showing a sporadic form presenting with two hemorrhagic lesions. We suggest an aggressive approach in order to avoid the risk of rebleeding, which is particularly high in case of hemorrhagic cavernomatosis.

5-aminolevulinic acid and neuronavigation in high-grade glioma surgery: results of a combined approach.

In high-grade glioma surgery, several techniques are used to achieve the maximum cytoreductive treatment preserving neurological functions. However, the effectiveness of all the methods used alone is reduced by specific limitations of each. We assessed the reliability of a multimodal strategy based on 5-aminolevulinic acid (5-ALA) and neuronavigation. We prospectively studied 18 patients with suspected, non eloquent-area malignant gliomas amenable for complete resection. Conventional illumination was used until the excision appeared complete. The cavity was then systematically inspected in violet-blue light to identify any residual tumour. Multiple biopsies of both fluorescent and non-fluorescent tissue were performed in all cases. Each specimen was labelled according to the sampling location (inside or outside the boundary set by the neuronavigator). The samples were analysed by a neuropathologist blinded to the intraoperative classification. We reviewed the results of both methods, either singly or in combination. Individual analysis showed higher 5-ALA reliability compared to neuronavigation. However, several false-negative fluorescent specimens were detected. With the combined use of fluorescence and neuroimaging, only 1 sample (negative for both 5-ALA and navigation) was tumoral tissue. In our experience, the combined approach showed the best sensitivity and it is recommended in cases of lesions involving non-eloquent areas.

5-aminolevulinic acid and neuronavigation in high-grade glioma surgery: results of a combined approach

In high-grade glioma surgery, several techniques are used to achieve the maximum cytoreductive treatment preserving neurological functions. However, the effectiveness of all the methods used alone is reduced by specific limitations of each. We assessed the reliability of a multimodal strategy based on 5-aminolevulinic acid (5-ALA) and neuronavigation. We prospectively studied 18 patients with suspected, non eloquent-area malignant gliomas amenable for complete resection. Conventional illumination was used until the excision appeared complete. The cavity was then systematically inspected in violet-blue light to identify any residual tumour. Multiple biopsies of both fluorescent and non-fluorescent tissue were performed in all cases. Each specimen was labelled according to the sampling location (inside or outside the boundary set by the neuronavigator). The samples were analysed by a neuropathologist blinded to the intraoperative classification. We reviewed the results of both methods, either singly or in combination. individual analysis showed higher 5-ALA reliability compared to neuronavigation. However, several false-negative fluorescent specimens were detected. With the combined use of fluorescence and neuroimaging, only 1 sample (negative for both 5-ALA and navigation) was tumoral tissue. in our experience, the combined approach showed the best sensitivity and it is recommended in cases of lesions involving non-eloquent areas (AU)

En la cirugía de gliomas de alto grado se utilizan diversas técnicas para lograr el máximo tratamiento citoreductivo y la conservación de las funciones neurológicas. Sin embargo, la efectividad de todos los métodos utilizados en solitario queda reducida por las limitaciones específicas de cada uno de estos métodos. Evaluamos la fiabilidad de una estrategia multimodal basada en el ácido 5-aminolevulínico (5-ALA) y la neuronavegación. Estudiamos de modo prospectivo a 18 pacientes con una zona sospechosa y no elocuente de gliomas malignos, susceptibles de resección completa. Se utilizó iluminación convencional hasta que la extirpación nos pareció completa. Se inspeccionó entonces sistemáticamente la cavidad con luz azul violeta para identificar cualquier tumor residual. En todos los casos se realizaron biopsias múltiples tanto del tejido fluorescente como del no fluorescente. Se etiquetó cada muestra conforme al emplazamiento de cada una de ellas (interior o exterior a los límites del neuronavegador). Las muestras fueron analizadas por un neuropatólogo, quien se atuvo a la clasificación intraoperatoria. Revisamos los resultados de ambos métodos, tanto de manera individual como combinada. El análisis individual mostró una mayor fiabilidad del 5-ALA en comparación a la neuronavegación. Sin embargo, se detectaron diversas muestras fluorescentes falso-negativas. Con el uso combinado de la fluorescencia y la neuroimagen, únicamente 1 muestra (negativa para el 5-ALA y la navegación) constituía tejido tumoral. En nuestra experiencia, la técnica combinada mostró una mejor sensibilidad, recomendándose para los casos de lesiones que impliquen zonas no elocuentes (AU)

Fluorescence and image guided resection in high grade glioma.

The extent of resection in high grade glioma is increasingly been shown to positively effect survival. Nevertheless, heterogeneity and migratory behavior of glioma cells make gross total resection very challenging. Several techniques were used in order to improve the detection of residual tumor. Aim of this study was to analyze advantages and limitations of fluorescence and image guided resection. A multicentric prospective study was designed to evaluate the accuracy of each method. Furthermore, the role of 5-aminolevulinc acid and neuronavigation were reviewed. Twenty-three patients harboring suspected high grade glioma, amenable to complete resection, were enrolled. Fluorescence and image guides were used to perform surgery. Multiple samples were obtained from the resection cavity of each lesion according to 5-ALA staining positivity and boundaries as delineated by neuronavigation. All samples were analyzed by a pathologist blinded to the intra-operative labeling. Decision-making based on fluorescence showed a sensitivity of 91.1% and a specificity of 89.4% (p<0.001). On the other hand, the image-guided resection accuracy was low (sensitivity: 57.8%; specificity: 57.4%; p=0.346). We observed that the sensitivity of 5-ALA can be improved by the combined use of neuronavigation, but this leads to a significant reduction in specificity. Thus, the use of auxiliary techniques should always be subject to critical skills of the surgeon. We advocate a large-scale study to further improve the assessment of multimodal approaches.