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Purpose: Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence., Materials and Methods: Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH., Results: After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility., Conclusions: D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly., (© 2021. The Author(s).)

Purpose: During the Covid-19 pandemic every hospital has had to change its internal organization. Different institutions have highlighted the risks connected with endoscopic endonasal surgery. The goal of this paper is to illustrate the feasibility of pituitary region surgery during the SARS-CoV-2 pandemic., Methods: After two negative Covid tests were obtained, three patients with macro GH-secreting tumors, and two patients with micro ACTH-secreting tumors resistant to medical treatment underwent surgery during the pandemic. During the surgery, every patient was treated as if they were positive., Results: Neither operator, nor patient have developed Covid symptoms. The two neurosurgeons performing the operations underwent two Covid swab, which resulted negative., Conclusions: Pituitary surgery is a high risk non-urgent surgery. However, the method described has so far been effective and is safe for both patients and healthcare providers.

Introduction: Olfactory groove meningiomas (OGMs) account for 8-13 % of all intracranial meningiomas. The gold standard of treatment is generally surgery, however various approaches have been used and the literature is still uncertain about the superiority of one treatment over the others. The most debated techniques are traditional microscopic open approaches versus the endoscopic endonasal ones. The aim of this paper is to prove a valid surgical route that gathers the benefits of both endoscopic and transcranial routes., Methods: Fifty consecutive patients underwent trans-frontal sinus surgical removal of an OGM between January 2000 and January 2019 at the Neurosurgical Departments in Torino, Brescia and Legnano (Italy). The clinical features were collected in a database and compared with neuroimaging and outcomes. All patients were investigated with neuroimaging techniques. Clinical evaluations were performed 3-4 months and 1 year after surgery, together with neuroradiological follow-up., Results: All patients with OGM underwent Simpson grade I resection. The most common neurological symptom leading to neuroradiological evaluations were headaches (36 %), followed by behavioural changes (30 %), hyposmia/anosmia (12 %), visual impairments (6%) and focal deficits (6%). At 3-4 months follow-up 48 patients underwent a brain MRI (2 patients underwent a brain CT), and a complete resection was confirmed in 45 patients (94 %)., Conclusions: Despite different techniques and studies supported by good evidence, there is no consensus on the best surgical approach for OGMs. The data shown in this article suggests that the trans-frontal sinus approach is a valid alternative to an endoscopic approach and the classical transcranial routes, collecting benefits from both approaches., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Surgery for spinal metastases has undergone multiple transformations in terms of surgical technique. The need for a more aggressive surgical strategy for local control of the disease, given the advances in radiosurgery and immunotherapy, has met the incorporation of many different technological adjuncts. Separation surgery has become one of the main targets to achieve for surgeons in the treatment of spinal metastases. In this paper a prospective series of 3D endoscope-assisted transpedicular thoracic corpectomies is described. Adult patients with a diagnosis of single-level thoracic metastases requiring surgery for epidural compression were included. Data recorded for each case concerned patient demographics, surgical technique, clinical, radiological and surgical data, intra- and postoperative complications, follow-up. The goal of this study was to verify the achievement of separation surgery with this technique, while confirming the safety and feasibility of the procedure. A total number of nine patients were treated from January to April 2019 with a 3D endoscope-assisted procedure. A circumferential bilateral decompression was achieved in seven cases, while monolateral in the other two. A proper separation between the tumor and the spinal cord was achieved in all cases as confirmed by imaging. Axial pain always improved after the procedure as well as neurological functions, when compromised before surgery. No intra-operative and postoperative complications were recorded. Mean hospital stay was 4 days after surgery with early mobilization. At last follow-up no local recurrences were registered. According to preliminary results, the transpedicular 3D endoscope-assisted approach for corpectomies appeared to be a safe and effective technique to achieve proper circumferential decompression and valid separation surgery in thoracic metastases, potentially decreasing the need for costotransversectomy.

Introduction: Central diabetes insipidus (CDI) is a frequent complication of pituitary surgery, but its diagnosis lacks standardized criteria. Copeptin, a surrogate marker of arginine vasopressin release, is triggered by psycho-physical stresses such as pituitary surgery. Low postoperative copeptin could predict CDI onset. The aims of this study were the validation of copeptin as a predictor of post-neurosurgical CDI and the identification of the optimal timing for its determination., Methods: Sixty-six consecutive patients operated for a hypothalamic-pituitary lesion were evaluated. Copeptin was determined preoperatively and at 1, 6, 12, 24 and 48 h post-extubation. Fifty-eight patients were reassessed after 3-6 months post-surgery to confirm transient (3 cases) or permanent CDI (5 cases) diagnosis., Results: A marked copeptin peak was identified at 1 h after extubation, when a value below or equal to 12.8 pmol/L had a good accuracy in identifying CDI cases (AUC 0.866, 95% CI 0.751-0.941). Moreover, a copeptin peak above 4.2 pmol/L excluded permanent forms (AUC 1, 95% CI 0.629-1). Regression analysis identified copeptin as the only significant predictor of CDI (OR 0.86, 95% CI 0.75-0.98, p = 0.02). A copeptin T1/T0 ratio below or equal to 1.47 identified patients at risk of isolated biochemical alterations even in the absence of an overt CDI., Conclusions: A prompt increase of copeptin is expected at 1 h after extubation. The absence of this peak is a reliable predictor of post-neurosurgical CDI., (© 2019 S. Karger AG, Basel.)

The first step of glioma treatment is surgery. Extent of resection (EOR) improves patient survival if surgery does not negatively impair a patient's neurological status. However, how surgery affects the patient's quality of life (QOL) has been less studied, especially as regards cognitive aspects. In our study, we retrospectively analyzed our cases with awake surgery. In all patients, surgical excision was stopped when active functions were intraoperatively identified. A neuropsychological assessment was performed both before and after surgery (5 days and 1 month after). Writing, motor speech, comprehension, expression, reading, pragmatics, attention, memory, problem solving and visuoperceptive functions were evaluated and scored with the NOMS scale. We found no differences in the median values of writing and motor speech, while there was a difference in the following variables: comprehension, expression, reading, pragmatics, attention, memory, problem solving and visuoperceptive functions. Moreover, the Dunn test did not show any difference between preoperative evaluation and evaluation performed 30 days after surgery regarding comprehension, expression, reading, pragmatics, attention, problem solving and visuoperceptive functions. However, there was a difference between preoperative and postoperative evaluation for memory. This retrospective study shows that awake surgery could be a reasonable possibility to preserve a patient's QOL achieving an EOR >82% of the Total Tumor Volume (Fluid-attenuated inversion recovery (FLAIR) hyperintense region in low-grade gliomas and enhancing nodules plus FLAIR hyperintense region in high-grade gliomas). In this series memory was the only aspect that had an impairment after surgery without a complete recovery at one month after surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Cortical bone trajectory (CBT) screw is an attractive technique in terms of fixation strength and less invasiveness. However, the insertion of a pedicle screw penetrating cortical bone on the ideal trajectory is technically demanding. The use of 3-dimensional (3D) patient-matched guides may facilitate the use of this technique. In this technical note and case series, the use of a patient-matched 3D targeting guide for a circumferential fixation with CBT screws is described., Methods: Eleven patients with a mean age of 49 years were treated. The MySpine MC (Medacta International SA, Castel San Pietro, Switzerland) technology was used to place CBT screws. A computed tomography (CT) scan-derived 3D model of the patient vertebra was created after the surgeons planned the best custom CBT screw trajectory. Then, scaffolds were printed and used during surgery to guide the screw through the patient pedicle. An intersomatic arthrodesis was also performed., Results: The images of the planned trajectory were superimposed on the postoperative CT scan, confirming the accuracy of the trajectory. The mean deviation from the planned pedicle midpoint was 0.91 mm; 85.2% of the screws were placed within 2° from the planned trajectory. There were 2 grade A (<2 mm) and no grade B or C perforations. The actual entry point was always within 2 mm from the planned entry point., Conclusions: This technical note and case series is the first clinical description on the use of a patient-matched guide for posterior CBT screw placement. The use of these devices could also improve placement accuracy and decrease the risk of nerve damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Syringobulbia is an uncommon lesion that occurs in the central nervous system; it is often defined as a pathologic cavitation in the brainstem. The cases with partial blockage of the cerebrospinal fluid pathways at the level of the foramen magnum are more common and the most important group. The most common treatment of syringobulbia is craniovertebral decompression., Case Description: This paper reports a case of a symptomatic syringobulbia in which an urgent endoscopic endonasal approach to the craniovertebral junction (CVJ) was done to limit bulbo-medullary compression and rapid neurologic deterioration. A 69-year-old man was admitted to the hospital because of acute onset of dysphonia, dysphagia, imbalance, and vomiting. Magnetic resonance imaging revealed a cystic lesion in the brainstem, suggestive of a syringobulbia in Klippel Feil syndrome with CVJ stenosis., Conclusions: This case report details the successful use of endoscopic endonasal anterior decompression to treat syringobulbia, and adds to the growing literature in support of the endonasal endoscopic approach as a safe and feasible means for decompressing the craniocervical junction, even in the setting of urgency. However, prudent patient selection, combined with sound clinical judgment, access to instrumentation, and intraoperative imaging cannot be overemphasized., (Copyright © 2019. Published by Elsevier Inc.)

Neurophysiological monitoring is of undoubted value for the intraoperative safety of neurosurgical procedures. Widely developed and used for cranial surgery, it is equally as effective, though perhaps less commonly employed, for spinal pathology. The most frequently used techniques for intraoperative monitoring during spinal surgery include somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs) and electromyography, which can either be spontaneous free-running (sEMG) or triggered (tEMG). The knowledge of the benefits and limitations of each modality is essential in optimising the value of intraoperative monitoring during spinal procedures. This review will analyse the single techniques, their anatomical and physiological basis, their use in spinal surgery as reliable indicators of functional injury, their limits and their application to specific procedures in minimally invasive surgery, such as the lateral transpsoas access for interbody fusion and the divergent trajectory for cortico-pedicular screws. In these particular techniques, because of reduced visual exposure, neuromonitoring is indeed essential to exploit the full potential of minimally invasive surgery, while avoiding damage to nervous structures.

Background: Among the posterior techniques, the use of cervical interfacet spacers (CISs) represents a promising technology whose potentialities are still being studied. The purpose of the present review was to assess the available data on CISs., Methods: A search on PubMed was performed. The search terms were "cervical interfacet spacers," "facet spacers," "DTRAX facet system," "Goel facet spacer," "pseudarthrosis," "cervical lordosis," "iatrogenic kyphosis," "cervical foraminal decompression," "cervical biomechanics," "atlantoaxial instability," and "subaxial instability.", Results: Mechanical studies have shown that stand-alone CISs promoted stiffness in all directions, except for extension. Foraminal distraction was recorded in 86% of the cases. Clinical studies have shown that the use of CISs could promote successful arthrodesis, given the large surface area affected by fusion and decreasing the need for autografts. The effectiveness for the treatment of radiculopathy has been confirmed by several clinical studies. In a series of 154 levels of implanted CISs, no evidence of significant loss of cervical lordosis was identified. CISs could help in enhancing fusion in C1-C2 fixation., Conclusions: Biomechanical studies on specimens showed a positive trend in increasing stiffness of the cervical spine, despite some controversial results. In clinical studies, facet distraction was shown to be a safe and valid option for clinical indirect decompression, although longer follow-up is required for confirmation. No evidence of the loss of cervical lordosis has been recorded. The long-term effects and CIS use in revision procedures as adjuvant implants to treat pseudarthrosis or atlantoaxial instability are currently under investigation, and further studies are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pedicle screw instrumentation is a standard procedure in lumbar spinal fusion. The cortical bone trajectory (CBT) screw is an alternative technique, less invasive but harder to perform. The identification of the entry point and the appropriate direction can be tricky especially to the surgeons just at the beginning. Therefore, the aim of this study is to evaluate the reliability of preoperative computed tomography (CT) planning in the CBT screw placement., Methods: We retrospectively evaluated 82 patients who underwent a single-level posterior lumbar arthrodesis with CBT screws. The correct entry point and the best trajectory were identified on a 3-dimensional (3D) multiplanar reconstruction CT view. The concordance between achieved and planned trajectories was assessed on a postoperative CT., Results: A total of 328 screws was positioned. The average entry point distance from the target was 1.1 mm (standard deviation, ±0.15 mm). In 301 screws (91.8%), the obtained trajectory differed no more than 2° from the planned one. No screws misplaced or new neurological deficit was recorded., Conclusions: The CBT screw placement is a great alternative to the pedicle screw. Accurate preoperative 3D planning is useful to predict the entry point and the direction with accuracy similar to navigation systems, avoiding its costs and technical difficulties. The 3D CT planning is helpful in the customization of spine surgery, and the results underline the radiological reliability of this technique., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Endoscopic transnasal transsphenoidal surgery has become the standard procedure for the majority of skull base diseases, including sellar, parasellar, and clival pathologies. The aim of this study was the objective evaluation of nasal airflow resistances and olfactory function in 3-dimensional (3D) endoscopic transnasal transsphenoidal surgery., Methods: One hundred patients who underwent 3D transnasal endoscopic surgery for sellar, parasellar, and clival diseases were enrolled. Active anterior rhinomanometry and Sniffin' Sticks tests were performed before endoscopic surgery and at 3 and 6 months postoperatively., Results: No significant difference about nasal airflow resistance and olfactory function was observed between preoperative and postoperative subjective and objective scores. In the group of patients with sellar and parasellar diseases, a worst nasal respiratory function was seen when crusting was present, and a worst olfactory function was observed in patients with synechiae. Nasal functions returned to previous levels when crusting or synechiae solved. No statistically significant correlation was observed between the evaluated nasal functions and the reconstruction with flaps., Conclusions: The 3D endoscopic transnasal transsphenoidal surgery represents a more and more important tool in skull base surgery. It does not determine nasal respiratory and olfactory alterations after the treatment, without an increase in nasal complaints that could worsen quality of life.

Background: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented. Thus, we decided to perform a multicenter study among Italian neurosurgical centers performing pituitary surgery to provide an actual depiction from the neurosurgical standpoint., Methods: On behalf of the SINch (Società Italiana di Neurochirurgia), a survey was undertaken with the participants to explore the activities in the field of pituitary surgery within 41 public institutions., Results: Of the 41 centers, 37 participated in the present study. The total number of neurosurgical procedures performed in 2016 was 1479. Most of the procedures were performed using the transsphenoidal approach (1320 transsphenoidal [1204 endoscopic, 53 microscopic, 53 endoscope-assisted microscopic] vs. 159 transcranial). A multidisciplinary tumor board is convened regularly in 32 of 37 centers, and a research laboratory is present in 18 centers., Conclusions: Diagnosing pituitary/hypothalamus disorders and treating them is the result of teamwork, composed of several diverse experts. Regarding neurosurgery, our findings have confirmed the central role of the transsphenoidal approach, with preference toward the endoscopic technique. Better outcomes can be expected at centers with a multidisciplinary team and a full, or part of a, residency program, with a greater surgical caseload., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Giant pituitary adenomas are rare tumors that can have a devastating impact on a patient's life. They require a well-studied therapeutic approach that often combines different strategies., Case Description: A 29-year-old woman was diagnosed with the largest GH-secreting pituitary adenoma reported in the literature, to the best of the author's knowledge. The tumor was removed with a combined approach: endoscopic endonasal transsphenoidal and transcortical transventricular. All available acromegaly drugs were used. After 2 surgeries, a large part of the tumor was removed. Both postoperative courses were uneventful. Because the disease was still active, medical therapy was initiated. The combination of pasireotide, pegvisomant, and cabergoline permitted satisfactory control of hormonal levels., Conclusions: Giant adenomas, >4 cm, are rare pituitary tumors. Therefore in order to achieve the best clinical results, they require complex management that involves a multidisciplinary team of ear, nose, and throat surgeons; endocrinologists; radiation therapists; ophthalmologists; and neurosurgeons., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Olfactory groove meningiomas (OGMs) represent approximately 10% of all intracranial meningiomas. They arise in the olfactory fossa, a variable depression delimited by the lateral lamella and perpendicular plate. The cribriform plate with the lateral lamella and ethmoidal and orbital roof could be viewed as a 'canyon' with the frontal sinus as the main entrance., Methods: Between January 2000 and December 2013, 32 consecutive patients underwent removal of OGMs through this 'canyon' at the Department of Neurosurgery of Brescia and Turin. Complete removal was achieved in all patients with this trans-frontal sinus subcranial approach (Simpson grade I; mean lesion volume, 46.6 cm3)., Results: Five patients (15.6%) experienced nasal CSF leakage, treated with external lumbar drain positioning for 4 days and resolved in all cases but one, which was re-operated. Two patients (6.2%) during the CSF leakage experienced meningitis at day 7 after surgery, both successfully treated by intravenous antibiotic therapy. After one month, one patient developed hydrocephalus, treated with a ventricular peritoneal shunt. In one patient, traction on the OGM caused bleeding of the callosomarginal artery, which was coagulated with superior frontal gyrus ischemia without neurological consequences. Glasgow Outcome Scale Score at 6 months was V in 29 patients, IV in one patient, and I in two patients., Conclusions: Advantages with this approach may include easy and early control of blood supply from its insertion in the skull base, minimal frontal lobe retraction, preservation of the frontal veins draining to the sagittal sinus, and a satisfactory aesthetic outcome.

The introduction of modern endoscopy in neurosurgery brought light to one of the darkest areas: the skull base. In particular, the trans-nasal route allowed skull base surgeons to visualize and dominate the entire midline skull base. We analyzed our surgical series of 199 patients that were affected by several pathologies (pituitary adenomas, clivalchordomas, craniopharyngioma, Rathke's cleft cysts, tuberculum sellaemeningiomas, and craniovertebral junction pathologies with bulbar compression) and treated each by using a 3D-HD endoscope between December 2012 and December 2015 and reviewed the literature. We present our results in terms of tumor resections and decompression inpatients affected by craniovertebral junction pathologies. Analyzing our direct experience, as well as the literature, we can assert that the amount and accuracy of necessary movements in order to achieve a determined target are affected by the screen clarity and image resolution of the device. Additionally, the experience of the surgeon has an important role in the surgical outcome. Moreover, depth perception is critical in order to obtain precise and accurate movements. Our observations and the experts' opinion indicate that this modality provides improved surgical dexterity by affording the surgeon with depth perception while manipulating tissue and maneuvering the endoscope in the endonasal corridor, which is especially crucial in reducing the learning curve of young neurosurgeons.

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.

Purpose: The exposure of the third segment of the extracranial vertebral artery (V3) is an important step in the extreme lateral inferior transcondylar-transtubercular exposure (ELITE) approach. The muscular suboccipital triangle provides one of the landmarks to identify the V3 segment; however, identification of this triangle and dissection of the V3 segment is not always straightforward in the actual surgery. Blind dissection below the level of the foramen magnum can lead to vertebral artery injury. While the surgeon may be able to readily define the V3 segment of the vertebral artery by feeling its pulse, it is important to have a safe systematic approach to finding the V3 segment when the vessel is illusive. We propose a simple method to identify the V3 segment avoiding accidental injury of the vertebral artery., Methods: Sixteen cadaver heads (using both sides) were prepared by injecting red- or blue-coloured silicone into their arteries and veins, respectively. We performed an ELITE bilaterally on each cadaver head following four key bony landmarks. A postauricular lazy S-shaped skin incision was made centered just behind the mastoid tip. The posterior neck muscles were cut along the line of the skin incision behind the attachment of the sternocleidomastoid muscle to expose the occipital bone. All the incised muscles were reflected anteriorly as the ELITE is a dorsolateral approach. A suboccipital craniotomy was made exposing the posterior half of the sigmoid sinus up to the inferior retrosigmoid point (point A). The foramen magnum was opened after the craniotomy was completed. The dura on the foramen magnum was followed posteriorly in order to identify the occipital midline dural point (point B) that is identified by the bony ridge at the junction of the posterior fossa dura on the foramen magnum and the posterior most aspect of the spinal dura. The posterior tubercle of C1 (point C) was identified directly inferior to Point B. The posterior arch of C1 was followed anteriorly from the tubercle to find the "J-groove", which cradles the vertebral artery (point D). The V3 segment lies above this groove, covering the paravertebral venous plexus. We measured the distances between the landmarks introduced above after completion of the exposure., Results: The distance between points A and B was 30.5 +/- 5.6 mm, points B-C was 10.4 +/- 2.3 mm, points C-D was 19.1 +/- 3.8 mm. The V3 segment was identified using the anatomical relationships described above in all heads. In no cadaver specimen was the artery injured., Conclusions: Identification of the V3 segment of the vertebral artery by systematically detecting the four anatomical points defined above is simple and much safer than a direct dissection below the foramen magnum.

Posttraumatic epileptic seizures have an incidence of about 10% in series of severe head injuries. Control of "early seizures", i.e. those occurring in the first week after injury, is mandatory. Attacks, especially if recurrent, may add secondary damage to the injured brain: intravenous phenythoin with therapeutic plasma level allows control of the attacks. Seizures occurring months or years after injury are called "late seizures": recurring "late seizures" make up the clinical syndrome of "posttraumatic epilepsy". "Prophylaxis" should mean that drug treatment, given for a more or less prolonged period of time, blocks permanently the ripening of the epileptogenic foci avoiding the occurrence of seizures. In animal "prophylaxis" by antiepileptic drugs seems efficacious in many experimental models including iron induced epilepsy which is considered a model of posttraumatic epilepsy and vice versa. In the human being "prophylaxis" has been attempted with: phenytoin, phenobarbital, carbamazepine, valproate but without success. During treatment period the occurrence of seizures is prevented but, after discontinuation of the drug, seizures occur just as in non treated patients. The ripening of the epileptic focus in posttraumatic epilepsy, as in iron induced epilepsy, seems to be due to a cascade of events beginning with haemorrhage, haemolysis, iron or heme compound liberation, free radical formation, peroxidation and cell death. Experimentally free radical scavengers and antiperoxidants have marked prophylactic effect. Some of them (phosphate diester of vitamin E and C, melatonin, vanillyl alcohol) may be employed in clinical practice, but up to date there is no controlled study in human beings.