Alessandro Agnoletti

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.

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.

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. Patients 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.

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.

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.

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.

Are acute subdural hematomas possible without head trauma

Acute subdural hematomas (ASDHs) are rarely reported in the literature. In general, it is due to head trauma, but if the traumatic event is very mild, it is inadequate to explain the ASDH occurrence. Risk factors for the development of spontaneous ASDH include hypertension, vascular abnormalities and deficit of coagulation. We present two cases of ASDH in patients with the coagulation deficit and review of the literature to understand the coagulation factors role and platelet role in the management of ASDHs.

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.

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.

P08.10SINGLE BRAIN METASTASIS 9 YEARS AFTER ORTHOTOPIC LIVER TRANSPLANT WITH HISTOLOGICAL NEGATIVE EXPIANTED LIVER: CASE REPORT

We describe the case of a 67 years old man, that underwent orthotopic liver transplant (OLT) in 2004 for cirrhosis. Native liver hystological examination was negative for focal hepatocarcinoma (HCC) areas. In 2008, during regular follow up, pulmonary lesions were found and diagnosed as hepatocarcinoma metastasis.In 2013, patient accused vertigo and dizziness: neuroimaging showed a cerebellar lesion. Hystological diagnosis was HCC metastases. The peculiarity is the onset of lung metastasis after transplant, with negative analysis on native liver, and brain metastasis after stable disease. This case is also relevant due to long survival related to the unavailability of many oncologic therapies in transplanted patients.