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In a previous work, we found that an Intracranial Elastance Index (IEI) ≥0.3 at ventricular infusion test had a high accuracy in predicting shunt response at 6 and 12 months in idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to verify the accuracy of IEI to predict response to shunt at both short- and long-term follow-up. Retrospective evaluation of 64 patients undergoing ventriculo-peritoneal shunting for iNPH between 2006 and 2015 based on a positive ventricular infusion test (IEI≥0.3). Patients were classified according to Krauss scale and mRS preoperatively, at 1-year and at last follow-up. An improvement of at least one point at Krauss score or at mRS was considered as a good outcome; unchanged or worsened patients were grouped as poor outcome. Mean follow-up was 6.6 years. Improvement at Krauss scale was seen in 62.5% and 64.3% of patients at 1-year and last follow-up, respectively. Patients in good functional status (mRS≤2) increased from 25 in the preoperative period to 57% at both 1-year and last follow-up. IEI was significantly associated with Krauss (p=0.041) and mRS (p=0.036) outcome at last follow-up. Patients with worse preoperative Krauss and mRS had higher chance to improve but higher overall scores after treatment. At ROC curves, IEI showed a good long-term prediction of change in mRS from first year to last follow-up. IEI≥0.3 predicts outcomes at both short- and long-term, with more than 50% of patients being able to look after themselves after 6 years from treatment.

Down syndrome (DS) is the most common cause of intellectual disability in infants and has a well-known relationship with the Alzheimer’s disease. The association between DS and the other pathologies of senescence, such as normal pressure hydrocephalus (NPH), has been poorly investigated. This series included two DS patients with NPH. In both cases, NPH symptoms were initially misdiagnosed as DS associated senescence. Patients were treated with ventricular-peritoneal shunt, showing a sustained improvement (1 and 4 years of follow-up). To our knowledge, this is the first description of the occurrence of NPH in adult patients with DS and surgical outcomes.

The sinking flap syndrome (SFS) is one of the complications of decompressive craniectomy (DC). Although frequently presenting with aspecific symptoms, that may be underestimated, it can lead to severe and progressive neurological deterioration and, if left untreated, even to death. We report our experience in a consecutive series of 43 patients diagnosed with SFS and propose a classification based on the possible etiopathogenetic mechanisms. In 10 years’ time, 43 patients presenting with severely introflexed decompressive skin flaps plus radiological and clinical evidence of SFS were identified. We analysed potential factors involved in SFS development (demographics, time from decompression to deterioration, type, size and cause leading to DC, timing of cranioplasty, CSF dynamics disturbances, clinical presentation). Based on the collected data, we elaborated a classification system identifying 3 main SFS subtypes: (1) primary or atrophic, (2) secondary or hydrocephalic and (3) mixed. Very large DC, extensive brain damage, medial craniectomy border distance from the midline

Background Vertebral body erosion (VBE) is commonly caused by neoplastic, inflammatory or infectious diseases: it can be rarely associated with aortic wall disorders, such as contained rupture of aortic aneurysm (CCR-AA). CCR-AA is a rare event consisting of less than 5% of all reported cases. This condition is easily undiagnosed, differential diagnosis may be challenging, and there is no consensus or recommendation that dictates guidance on management of spinal surgical treatment. Material And Methods We performed a systematic review of literature of all cases of VBE secondary to CCR-AA to identify clinical, radiological, and surgical outcome characteristics with the aim of providing a basis for future research studies. Results The search returned a total of 80 patients. All reported cases have a history of hypertension. In almost all cases the AA size reported was very high (mean diameter of 7.056 cm). The treatment of this condition involves various reported treatment strategies: a totally conservative approach, treatment of the aortic aneurysm through a minimally invasive endovascular procedure, or through open surgery and combined approach. Despite the wide variability in therapeutic strategy, the rate of good outcomes was 80%, relatively high. Conclusions ‘‘Back pain’’ and pain along the vertebral column are such frequent complaints that unusual etiologies or serious and life threatening complications may be overlooked. In addition to the common traumatic and degenerative causes of back pain, AA must also be considered. A combined approach between vascular and spine surgery could be achieved without any increased risk.

Introduction The aim of the work was to update the "Guidelines for the Management of Severe Traumatic Brain Injury" published in 2012, to reflect the new available evidence, and develop the Italian national guideline for the management of severe pediatric head injuries to reduce variation in practice and ensure optimal care to patients. Evidence acquisition MEDLINE and EMBASE were searched from January 2009 to October 2017. Inclusion criteria were English language, pediatric populations (0-18 years) or mixed populations (pediatric/adult) with available age subgroup analyses. The guideline development process was started by the Promoting Group that composed a multidisciplinary panel of experts, with the representatives of the Scientific Societies, the independent expert specialists and a representative of the Patient Associations. The panel selected the clinical questions, discussed the evidence and formulated the text of the recommendations. The documentarists of the University of Florence oversaw the bibliographic research strategy. A group of literature reviewers evaluated the selected literature and compiled the table of evidence for each clinical question. Evidence synthesis The search strategies identified 4254 articles. We selected 3227 abstract (first screening) and, finally included 67 articles (second screening) to update the guideline. This Italian update includes 25 evidence-based recommendations and 5 research recommendations. Conclusions In recent years, progress has been made on the understanding of severe pediatric brain injury, as well as on that concerning all major traumatic pathology. This has led to a progressive improvement in the clinical outcome, although the quantity and quality of evidence remains particularly low.

Severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (Covid‐19), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combatting the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was one of the earliest and hardest‐hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, FFP3 and/or PAPRs devices, goggles, full‐face visor, double gloves, water‐resistant gowns and protective caps, are mandatory. For negative patients, use of at least FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS‐CoV‐2, dura handling should be minimized. It is only through widely‐agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic. This article is protected by copyright. All rights reserved

In this paper, we propose a simplified four-step retropharyngeal approach, whose aim is getting straight to the upper cervical spine minimizing complications. While the classical retropharyngeal approach includes about 11 steps, ours is a four-step approach: patient positioning, skin-platysma incision, hyoid bone superolateral dissection and retropharyngeal blunt exposure. We avoid several steps of the classical anterior retropharyngeal approach, particularly dissection of submandibular gland, facial veins, external carotid artery and thyroid artery, bellies of the digastric muscle, hypoglossal nerve, thyrohyoid membrane and the internal branch of superior laryngeal nerve. We have adopted this technique for five patients: two patients had a C2–C3 herniated disk with myelopathy, two patients had unstable Hangman fracture with no bone fusion after 2-month treatment with rigid collar, and one patient had a C2–C3 osteophyte with dysphagia. The intraoperative time needed for reaching the retropharyngeal space was 15 (first case), 9 (second case), 7 min (third case—illustrative case—and fourth case), 8 min (fifth case). No complications occurred. Our simplification, avoiding several steps, is simple, effective, safe, and rapid and requires a simple learning curve.

Treatment of intraosseous meningiomas is a two-staged procedure including tumor resection and cranial reconstruction. Several are the potential pitfall of this kind of surgery such as the conspicuous dimensions usually reached by the tumor and the peculiar involvement of irregular and deep bony structures. For these reasons, a surgical accurate virtual planning and a careful removal followed by tailored reconstruction are mandatory to achieve satisfactory results. We analyzed six patients operated on for intraosseous meningiomas between September 2014 and June 2018. Resection strategy was planned beforehand and shared with the manufacturer who provided the PEEK cranioplasty used in the reconstructive phase. Between September 2014 and April 2018, six patients affected by intraosseous meningioma were operated on. Female/male ratio was 5:1 and mean age was 54 ± 10.8 years. Mean FU was 20.3 ± 16.4 months. Mean dimension was 73.9 ± 24.8 mm × 69.2 ± 16.2 mm. Mean surgical time was 5.1 ± 1.1 h. The resection of intraosseous meningiomas requires the earliest and finest reconstructive phase. Custom-made implants should be considered the gold-standard for cranioplasty, especially in large skull and in frontal or hairless areas of the skull. The described technique is simple, accurate, and effective in achieving good results in disease control as well as cosmetic and functional restoration.

We describe the case of a 33-year-old woman with a history of over 15 years of a slow growing firm osseous-like right retroauricular mass. Surgical resection was easily performed using a sharp technique, because of a clear cleavage plane. The histologic diagnosis was a rare, unexpected, protuberant fibro-osseous lesion named "Bullough lesion." Only few cases of this benign pathologic entity have been described in English literature. Clinical differential diagnosis must be done with osteoma, periosteal chondroma, and other fibro-osseous lesions such as fibrodysplasia and ossifying fibroma. Because of the paucity of data, the natural history of this lesion is unknown and serial clinical and radiological follow-up is advised.

Decompressive craniectomy (DC) may be necessary to save the lives of patients suffering from intracranial hypertension. However, this procedure is not complication-free. Its two main complications are hydrocephalus and the sinking skin-flap syndrome (SSFS). The radiological findings and the clinical evaluation may be not enough to decide when and/or how to treat hydrocephalus in a decompressed patient. SSFS and hydrocephalus may be not unrelated. In fact, a patient affected by hydrocephalus, after the ventriculo-peritoneal shunt, can develop SSFS; on the other hand, SSFS per se can cause hydrocephalus. Treating hydrocephalus in decompressed patients can be challenging. Radiological findings and clinical evaluation may not be enough to define the most appropriate therapeutic strategy. Cerebrospinal fluid (CSF) dynamics and metabolic evaluations can represent important diagnostic tools for assessing the need of a CSF shunt in patients with a poor baseline neurologic status. Based on our experience, we propose a flow chart for treating decompressed patients affected by ventriculomegaly.

Glioblastoma (GBM) is associated with a high degree of angiogenesis. Therefore, antiangiogenic therapy could have a role in the treatment of this tumor. The currently available treatment approaches acting against angiogenesis are mainly directed toward three pathways: VEGF pathway, VEGF-independent pathways and inhibition of vascular endothelial cell migration. It has been demonstrated that antiangiogenic therapy can produce a rapid radiological response and a decrease of brain edema, without significantly influencing survival. Future studies should consider that: animal models are inadequate and cells used for animal models (mainly U87) are deeply different from patient GBM cells; GBM cells may become resistant to antiangiogenic therapy and some cells may be resistant to antiangiogenic therapy ab initio; and angiogenesis in the peritumor tissue has been poorly investigated. Therefore, the ideal target of angiogenesis is probably yet to be identified.

Objectives Glioblastoma recurs within 2 cm from the primary tumor's margins in 90–95% of cases. Natural history of recurrence is not well defined. The aim of this study was to verify if pattern of recurrence can be influenced by the extent of surgery. Patients and methods 131 patients with glioblastoma underwent tumor removal, followed by standard adjuvant radio-chemotherapy. Depending on the amount of apparently normal white matter measured around the tumor in the surgical specimen, the extent of surgery was classified into: “border resection” (BR, resection margins at the level of tumor border) or “extended resection” (ER, resection margins 1–2 cm far from tumor border). 88 patients had no residual tumor at post-operative MRI. Among these, 60 patients had a local recurrence (LR) – within 2 cm from the primary tumor's margins, 15 patients had a distant recurrence (DR), 13 patients had no recurrence. Survival curves were obtained through the Kaplan–Meier method. Dichotomous data were compared with the chi-square test. Results Patients who underwent ER presented a LR in 67% of cases. Patients who underwent BR presented a LR in 87.5% of cases (p = 0.03). Survival for 60 patients with LR was 16 months vs 35 months for 15 patients with DR (p = 0.06). PFS for patients with LR was 9 months vs 21 months for patients with DR (p = 0.05). Conclusions If tumor grows far from eloquent areas, ER may increase the probability to obtain a gross total resection, a greater number of patients with DR and, therefore, a longer survival.

Objectives Post-traumatic hydrocephalus (PTH) is commonly considered as a relative contraindication for endoscopic third-ventriculostomy (ETV). However, few studies are available on this topic. Methods An analysis of the papers published in the last ten years has been performed, in order to assess the level of evidence on which the current indication for ETV for PTH is based. References were identified by PubMed searches of clinical articles relating to both PTH and ETV. Laboratory investigations were excluded. Results Only 5 articles were selected, for a total of 15 patients with PTH treated with ETV. All these patients were described by the authors to have a communicating hydrocephalus. No complications of surgery were reported. Outcome data were not available for one patient. Thirteen out of the remaining 14 patients had a clinical improvement after the surgical procedure (93%). Direct or indirect information on pre-operative ICP was available for 11 cases. Eight of them had an elevated ICP and presented a clinical improvement after ETV. Conclusions There is no current evidence to support that PTH is a contraindication for ETV. Our data suggest that we could reconsider ETV for the treatment of PTH, especially for patients with elevated ICP. Prospective clinical trials (involving several centers, due to the difficulty of recruiting patients with PTH) are needed.

Obesity is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m2, early onset and a family history of being overweight. Candidate genes were screened by direct sequence analysis to search for rare genetic variations. The common LEP -2548 G/A polymorphism was also evaluated for its influence on the BMI (in obesity patients) and for obesity risk, using a case-control study involving 117 healthy individuals. Two different non-synonymous alterations in MC4R were found in two patients: the p.(Thr112Met), previously described in the literature as a probable gene involved in the obesity phenotype, and the novel p.(Tyr302Asp) variant, predicted to be pathogenic by in silico evaluations and family segregation studies. The LEP -2548 G/A polymorphism was not associated with the BMI or obesity risk. In conclusion, we have reported a novel mutation in MC4R in a family of Italian patients with severe obesity. Screening for MC4R could be important for directing the carriers of mutations towards therapy including partial agonists of the MC4R that could normalize their appetite and inhibit compulsive eating. Next-generation sequencing could be used to clarify the genetic basis of obesity in the future.

Hemorrhagic contusions (HC) represent a common consequence of traumatic brain injury (TBI) and usually evolve during the first 12 h after trauma. The relationship between decompressive craniectomy (DC) and evolution of the post-traumatic HC is still unclear. The aim of the present study was to evaluate the impact of DC on HC evolution. Fifty-seven patients with the evidence of at least one HC at admission CT scan were analyzed. Twenty-five patients (Group 1) underwent DC and 32 patients underwent medical therapy alone (Group 2). Fisher's exact test was used to compare categorical variables. Logistic regression model was used to assess the independent contribution of predictive factors (age, ≤50 years; treatment received, DC vs. medical; anticoagulant/antiplatelet drugs intake; Rotterdam CT score, 1-3 vs. 4-6) to the evolution/new appearance of an HC. A significant increase (≥2 cc) of any HC during the observation period was detected in 8 patients (14%): 4/25 patients (16%) of Group 1 and 4/32 patients (12.5%) of Group 2 (Fisher exact test two-sided p=0.72). Univariate and multivariate analyses showed that none of the analyzed factors was associated with increased or de novo appearance of any HC. DC does not seem to constitute a risk factor for the evolution of HC.

The enzyme poly(ADP-ribose) polymerase (PARP-1, EC 2.4.2.30) is activated by DNA strand breaks caused by several agents and utilizes NAD to form polyADPR, bound to acceptor proteins. The involvement of PARP-1 in autoimmune diseases has been suggested: antiPARP autoantibodies are described in systemic lupus erythematosus (SLE), DNA strand breaks have been evidenced in systemic sclerosis (SSc). We tested poly(ADP-ribosyl)ation activity and NAD concentration in PMC from patients affected by SLE or SSc and from controls. Lower PARP-1 activity and higher NAD concentration were observed in pathological conditions than controls, supporting the role of PARP-1 activation in modulating NAD concentration.

The activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) is virtually absent in Lesch-Nyhan disease (LND), an X-linked genetic disorder characterized by uric acid accumulation and neurodevelopmental dysfunction. The biochemical basis for the neurological and behavioral abnormalities have not yet been completely explained. Prior studies of cells from affected patients have shown abnormalities of NAD metabolism. In the current studies, NAD metabolism was evaluated in HPRT gene knock-out mice. NAD content and the activities of the enzymes required for synthesis and breakdown of this coenzyme were investigated in blood, brain and liver of HPRT(-) and control mice. NAD concentration and enzyme activities were found to be significantly increased in liver, but not in brain or blood of the HPRT(-) mice. These results demonstrate that changes in NAD metabolism occur in response to HPRT deficiency depending on both species and tissue type.

Background and purpose Reports on the safety and efficacy of intraventricularly administered (IVT) colistin for the treatment of Acinetobacter baumannii ventriculomeningitis in adults are limited and no comparative studies of IVT colistin versus intravenous (IV) therapy alone have been published. This study compared outcomes of patients with postneurosurgical ventriculomeningitis caused by extensively drug-resistant A. baumannii treated with IV colistin or IV plus IVT colistin. Methods In an 11-year period, information on 18 consecutive patients with extensively drug-resistant A. baumannii ventriculomeningitis was collected. Infection was defined on the basis of (i) isolation of A. baumannii from the cerebrospinal fluid (CSF); (ii) laboratory evidence of CSF infection; (iii) signs/symptoms of central nervous system (CNS) infection. Patients were divided into group 1 (nine patients, IV colistin alone) and group 2 (nine patients, IV plus IVT colistin). Results Cerebrospinal fluid sterilization was documented for 12 of 18 patients (66.6%). The CSF sterilization rate was 33.3% in group 1 and 100% in group 2 (P = 0.009). The mean time to CSF sterilization was 21 days (range 8–48). Five patients died due to A. baumannii CNS infection (all in group 1), and five deaths were unrelated to A. baumannii ventriculomeningitis. Intensive care unit mean length of stay was shorter in group 2 (20.7 vs. 41.6 days, P = 0.046). Crude relative risk ratio of cumulative incidence of persistent CNS infection in group 1 versus group 2 was 13. No cases of chemical meningitis due to intrathecal colistin administration were encountered. Conclusions Intraventricular colistin administration is much more effective than IV therapy alone and does not seem to add further toxicity.

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency always causing hyperuricemia presents various degrees of neurological manifestations, the most severe which is Lesch–Nyhan syndrome. The HPRT gene is situated in the region Xq26-q27.2 and consists of 9 exons. At least 300 different mutations at different sites in the HPRT coding region from exon 1 to exon 9 have been identified. A new mutation in the HPRT gene has been determined in one patient with complete deficiency of erythrocyte activity, with hyperuricemia and gout but without Lesch–Nyhan disease. Analysis of cultured fibroblasts revealed minimal residual HPRT activity mainly when guanine was the substrate. Genomic DNA sequencing demonstrated patient's mother heterozygosity for the mutation and no mutation in her brother. The mutation consists in a C→T transversion at cDNA base 463 (C463T) in exon 6, resulting in proline to serine substitution at codon 155 (P155S). This mutation had not been reported previously and has been designated HPRTSardinia. The mutation identified in this patient allows some expression of functional enzyme in nucleated cells such as fibroblasts, indicating that such cell type may add further information to conventional blood analysis. A multicentre survey gathering patients with variant neurological forms could contribute to understand the pathophysiology of the neurobehavioral symptoms of HPRT deficiency.

Object. A modified technique of open-door laminoplasty for cervical stenotic myelopathy (CSM) is described, and the role of evoked potential monitoring in selecting patients for surgery and evaluating results is discussed. Methods. Between October 1992 and October 1996, 33 patients with CSM underwent open-door laminoplasty. After surgery, in 27 patients (81.8%) different levels of clinical improvement were demonstrated, and in five of them (15%) full recovery was observed. The Japanese Orthopaedic Association score increased from 5 to 12 (mean 9.8) preoperatively to 8 to 14 (mean 11.6) postoperatively. At 1-year follow up, the N13 cervical response was restored in nine (75%) of 12 patients with isolated presurgical abnormality and in 57.1% of those with combined abnormalities of both N13 and P14 response. Although significant clinical improvement was observed in 82% of the cases, in 24 of 33 patients MEP abnormalities persisted at least at one explored level. Conclusions. Of several laminoplasty techniques, the one described here offers some advantages: preservation of biomechanical function of posterior muscular—ligamentous complex, prevention of laminar collapse, smaller degrees in reduction of range of cervical motion, stabilization of the spine with no postoperative malalignment, and maintenance of decompressive effect that avoids recurrent stenosis. Neurophysiological studies sometimes clarified neurological disorders that were only suspected on the basis of history and/or clinical examination, leading to early diagnosis.

Purine and pyridine metabolism were studied in ten Lesch-Nyhan patients, with virtually no hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in erythrocytes. Increased NAD erythrocyte concentrations were found in all patients. Raised activities of two enzymes catalysing NAD synthesis from nicotinic acid (nicotinic acid phosphoribosyltransferase: NAPRT, and NAD synthetase: NADs) was found in erythrocyte lysates from all patients. The two enzymes had normal apparent Km for their substrates and increased Vmax. The rate of synthesis of pyridine nucleotides from nicotinic acid by intact erythrocytes in vitro was also increased in most patients. These findings suggest that raised NAD concentrations in HPRT- erythrocytes are due to enhanced synthesis as a result of increased enzyme activities.

✓ Chronic subdural hematomas (SDHs) generally occur in elderly patients. Its pathogenesis is usually related to head trauma with tearing and rupture of the bridging veins, although in some cases a history of trauma is not recognizable. There are many reports regarding the association between spontaneous chronic SDHs and an alteration in coagulative parameters. A coagulative disorder should be suspected when an unexplained hemorrhage occurs, especially in a young patient. The authors report on three young men with a deficiency in coagulation factor XIII (FXIII) who underwent surgery for chronic SDHs. The role of FXIII in the pathogenesis of chronic SDH is emphasized. In patients with unexplained chronic SDH all coagulation parameters and factors should be screened to identify an eventual coagulative disorder.

Background and purposeIn the last decade there has been an increasing use of antiplatelet/anticoagulant agents in the elderly. The aim of the study was to evaluate the association between exposure to anticoagulant/antiplatelet therapy and chronic subdural haematoma-CSDH.MethodsSingle institution case-control study involving 138786 patients older than 60 years who visited our academic tertiary care Emergency Department from January 1st 2001 to December 31st 2010. 345 patients with CSDH (cases) were identified by review of ICD-9 codes 432.1 and 852.2x. Case and controls were matched with a 1:3 ratio for gender, age (± 5 years), year of admission and recent trauma. A conditional logistic model was built. A stratified analysis was performed with respect to the presence (842 patients) or absence (536 patients) of recent trauma.ResultsThere were 345 cases and 1035 controls. Both anticoagulant and antiplatelet agents were associated with an increased risk of CSDH with an OR of 2.46 (CI 95% 1.66-3.64) and 1.42 (CI 95% 1.07-1.89), respectively. OR was 2.70 (CI 95% 1.75-4.15), 1.90 (CI 95% 1.13-3.20), and 1.37(CI 95% 0.99-1.90) for patients receiving oral anticoagulants, ADP-antagonists, or Cox-inhibitors, respectively. History of recent trauma was an effect modifier of the association between anticoagulants and CSDH, with an OR 1.71 (CI 95% 0.99-2.96) for patients with history of trauma and 4.30 (CI 95% 2.23-8.32) for patients without history of trauma.ConclusionsAnticoagulant and antiplatelet therapy have a significant association with an increased risk of CSDH. This association, for patients under anticoagulant therapy, appears even stronger in those patients who develop a CSDH in the absence of a recent trauma.

OBJECTIVE: To assess the role of surgery on survival of patients with grade II gliomas of the cerebral hemispheres. METHODS: One hundred and thirty one low grade hemispheric gliomas surgically treated (biopsied patients excluded) between 1978 and 1989 were retrospectively reviewed. Thalamic, basal ganglia, callosal, or ventricular location were not considered. All tumours were World Health Organisation (WHO) grade II gliomas: 42 fibrillary and 11 gemistocytic astrocytomas, 49 oligodendrogliomas, and 29 oligoastrocytomas. Patients' ages ranged from 14 to 63 (mean 32.9, median 34) years, Karnofsky performance from 0.50 to 0.90 (mean 80.7, median 80), and postsurgical follow up of the living patients from 24 to 190 (mean 97.02, median 93) months. Postoperative external radiotherapy was performed in 49 cases. RESULTS: The overall survival probability at five years was 97.1%, at eight years 76.1%, and at 10 years 62.7% (median survival time 144 months). The impact on survival of the following variables was analysed: age (< 20, 21-40, and > 40 years), Karnofsky score (80-100, 70 < or = 70), histology, tumour extension (T1 < 3 cm, T2 3-5 cm, T3 > 5 cm maximum diameter), extent of surgical resection (S1 radical, S2 subtotal < 10% residual tumour, S3 partial-10%-50% residual tumour), and radiotherapy (either performed or not). A significant positive association with survival at univariate analysis was found for the age group < 20 years (P = 0.003), for total and subtotal surgical resections (S1 and S2; P < 0.001) and for the non-irradiated patients (P = 0.0049), whereas a shorter survival probability was noticed for gemistocytic astrocytomas (P < 0.001) and for tumour extension > 5 cm (T3; P = 0.0193). Karnofsky performance did not show any significant association with survival. The most relevant factor affecting survival at the multivariate analysis was the extent of surgical resection, which resulted as the only variable retaining a significant value (P = 0.001, risk factor = 2.20). CONCLUSIONS: The data strongly support the role of a surgical removal as extensive as possible in the treatment of these tumours.

Patients with high-grade glioma (HGG) still have a very poor prognosis. The infiltrative nature of the tumor and the inter- and intra-tumoral cellular and genetic heterogeneity, leading to the acquisition of new mutations over time, represent the main causes of treatment failure. Radioimmunotherapy represents an emerging approach for the treatment of HGG. Radioimmunotherapy utilizes a molecular vehicle (monoclonal antibodies) to deliver a radionuclide (the drug) to a selected cell population target. This review will provide an overview of preclinical and clinical studies to date and assess the effectiveness of radioimmunotherapy, focusing on possible future therapies for the treatment of HGG.

Objective The management of post-traumatic ventriculomegaly (PTV) is controversial. This is due to the difficulty to determine whether PTV is related to an atrophic process or to a true “active” hydrocephalus. The purpose of this study is to analyze the CSF-dynamics in patients with PTV and, possibly, to identify parameters that correlate with prognosis. Methods 15 patients with PTV were treated following this protocol: 1-frontal ventriculostomy (with Rickham reservoir); 2-CSF-dynamics evaluation; 3-ventriculo-peritoneal shunt. CSF dynamics evaluation was based on an intraventricular infusion test (performed three to five days after ventriculostomy). Outflow Resistance (R-out) and Intracranial Elastance Index (EI, i.e. the reciprocal of intracranial compliance) were calculated. Patients were classified according to response to shunt into: 1-fast responders: rapid clinical improvement, i.e. within days/one month from surgery; 2-slow responders: patients presenting little clinical improvement occurring after months (despite neurorehabilitation); 3-non responders: no clinical improvement. Results Seven patients (46.7%) were classified as fast-responders, three patients were classified as slow-responders (20%) and five patients were classified as non-responders (33.3%). Opening CSF pressure was less than 15 mmHg for all patients. R-out (cut-off >10 mmHg/ml/min) had 100% sensitivity, 50% specificity, 100% negative predictive value and 63.6% positive predictive value. EI (cut-off value >0.3) had 100% specificity, 42.4% sensitivity, 100% positive predictive value and 66.7% negative predictive value. Conclusions Based on these considerations, we can suggest that, for patients with normal pressure PTV, analysis of CSF dynamics could be of help in selecting patients for CSF-shunt. A combination of Intracranial Elastance and of R-out could help predicting shunt responsiveness.

Patients aged 65 years or older represent half of all patients with glioblastoma. Nonetheless, this older cohort is often excluded from trials. The NOA-08 Phase III trial compared radiotherapy (RT) (60 Gy) versus temozolomide (TMZ; 100 mg/m(2)) in the elderly patients (65 years and older) with high-grade glioma. Median overall survival was comparable between the two groups (8.6-RT- and 9.6-TMZ-months). Resection extent was the only independent prognostic factor for overall survival. Several concerns arise: the inclusion of patients with a very low Karnofsky Performance Status (KPS; KPS = 20), the lack of an analysis of the impact of KPS and comorbidities on outcome, the salvage therapy administered at tumor progression (RT in the TMZ group and TMZ in the RT group), which could have balanced the effects of primary treatments, the absence of information on spread of disease/tumor site, the mixture of grade III and grade IV histologies. Ongoing trials evaluating RT plus TMZ, RT plus bevacizumab and other treatment modalities in the elderly population are going to change clinical practice in the near future.

Background Decompressive craniectomy (DC) is a known risk factor for the development of post-traumatic hydrocephalus. The occurrence of subdural hygroma (SH) was also reported in 23–56% of patients after DC and it seemed to precede hydrocephalus in more than 80% of cases. We analyzed the relationship among DC, SH and hydrocephalus. Methods From 2007 to 2011, 64 patients underwent DC after head trauma. Variables we analyzed were: intaventricular hemorrhage, age, GCS, distance of craniectomy from the midline, evacuation of a hemorrhagic contusion (HC) and infection. Logistic regression was used to assess the independent contribution of the predictive factors to the development of hydrocephalus. Results Nineteen patients (29.7%) developed hydrocephalus. Interhemispheric SH was present in 8/19 patients with hydrocephalus and temporally preceded the occurrence of ventricular enlargement. Moreover, most patients who developed a interhemispheric SH had been undergone DC whose superior margin was close to the midline. Logistic regression analysis showed that craniectomy closer than 25 mm to the midline was the only factor independently associated with the development of hydrocephalus. Conclusion Craniectomy close to the midline can predispose patients to the development of hydrocephalus. SH could be generated with the same mechanism, and these three events could be correlated on a timeline.

Reconstruction of calvarial bone defects can be achieved using utologous bone or awide range of prostheticmaterials [1].Macroorous hydroxyapatite (MH) has histologically proven its potential steointegration in animal models [2–4]. Recent radiological and linical data in human subjects are in favour of good osteointegraion of MH cranioplasty [5,6]. However, the MH implant has weak echanic stability and is prone to fractures [7]. Furthermore, it is ot known how fast and to which extent the implant is ossified n vivo. We report a case with limited ossification of a MH prosthesis our years after implantation.

Evaluation of: Stupp R, Wong ET, Kanner AA et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised Phase III trial of a novel treatment modality. Eur. J. Cancer 48(14), 2192–2202 (2012).Glioblastoma (GBM) is the most common primary malignant cerebral tumor in adults, with a poor prognosis despite several therapeutic efforts. Electric fields (EFs) have shown promising results as a new anticancer treatment. Stupp et al. report on the first Phase III trial comparing EF versus chemotherapy in patients with recurrent GBM. The study was designed for superiority; although well conducted, it might not have shown it for a limited compliance in the EF group. Even with this limitation, the trial has shown at least equivalence of EF to chemotherapy, with a decreased toxicity and increased quality of life favoring EF. Further basic and clinical studies are warranted to increase knowledge, efficacy, compliance and cost–effectiveness. This trial has opened a new promising field...

A two-step non-radioactive method that uses reverse-phase high-performance liquid chromatography (RP-HPLC) is described for the determination of phosphoribosylpyrophosphate synthetase (EC 2.7.6.1) activity in human erythrocytes. The method is accurate and easily reproducible in different chromatographic systems; it is based on the quantification of phosphoribosylpyrophosphate by conversion into orotidine monophosphate and uridine monophosphate. Phosphoribosylpyrophosphate synthetase activity was determined in the erythrocytes of healthy adults and children, the latter showing significantly higher activity than the former. The enzyme activity assayed in children with different neurological disorders was significantly lower in patients with Rett syndrome than in control children or in autistic or mentally retarded patients.

In general, cranioplasty is viewed as a straightforward surgical procedure, and for many years the complications associated with the procedure have been underestimated. We reviewed our 5-year experience consisting of 218 cranioplasties. Study outcomes focused specifically on the occurrence of complications after cranioplasty. Autologous bone-assisted and prosthetic cranioplasties were considered. Variables described by other authors to be associated with complications were studied, including history of previous cranioplasty, wider craniectomy size, bifrontal craniectomy, and delayed cranioplasty. We also analyzed the influence of material used for craniectomy on the occurrence of complications. The overall complication rate was 19.7%. Nineteen cases of infection (8.7%), 5 cases of postoperative wound dehiscence (2.3%), 6 cases of epidural hemorrhage (2.8%), and 13 cases of cranioplasty dislocation (5.9%) were observed. Bifrontal cranioplasties were more frequently associated with complications (p=0.01; Fisher's exact test) and infection (p0.0001; Fisher's exact test). Postoperative wound dehiscence was more frequently observed with hand-made or custom-made cranioplasties compared with autologous cranioplasties (p=0.02). Early cranioplasty (3 months from craniectomy) was significantly associated with cranioplasty dislocation (p=0.03). Logistical regression analysis showed that the only factor independently associated with complication was the site of cranioplasty (p=0.01). In particular, patients with a bifrontal cranioplasty had a 2-fold increased risk of complication (CI 95 1.1-3.6, p=0.017) and a 2.5-fold increased risk of developing infection (CI 95 1.3-4.9, p=0.009) compared with hemispheric/bihemispheric cranioplasty. Our analysis confirms that cranioplasty is burdened by a significant complication rate. In this context, bifrontal cranioplasty is related to a higher risk of complication and, in particular, infection.

We describe the case a spinal cord localization of neurological toxoplasmosis in a HIV-positive patient with Burkitt lymphoma, previously treated with chemotherapy and immunotherapy. This complication occurred while patient was in complete remission of lymphoma, with CD4+ T cell count of 270 /ml, undetectable HIV viremia, and despite the trimethoprim/ sulfamethoxazole prophylaxis. Indeed, we hypothesize that in our patient neurologic toxoplasmosis has been fostered more by previous immuno-chemotherapy than by HIV- related immunodeficiency. On the whole, this case suggests that parameters usually employed to predict the risk for opportunistic infections in HIV-positive people might not apply to patients with HIV-related lymphomas.

Background It is a prevalent myth that a postoperative infection may actually confer a survival advantage in patients with malignant glioma. This contention is based largely on anecdotal reports. Recently, a single-center study showed there was no survival advantage in those patients who had glioblastoma with postoperative infection. Objective To examine the impact of postoperative infections on outcome in patients with glioblastoma treated at our center. Methods This study included 197 patients with newly diagnosed primary glioblastoma treated from January 2001 to January 2008. Of the 197 patients, 10 (5.08%) had postoperative bacterial infection. The Kaplan-Meier method, log-rank test, and Breslow test were used in the univariate approach; Cox regression was used in the multivariable approach. Results The median survival was 16 months (95% confidence interval [CI], 14-18 mo). The infection group had a significant advantage in the median survival: 30 months (95% CI, 21-39) vs 15 months (95% CI, 13-17) for patients without postoperative infection. This advantage was also confirmed by Cox regression; in fact, patients not developing a postoperative infection showed an adjusted hazard ratio for death of 2.3 (95% CI, 1-5.3). Conclusion The association between infection and prolonged survival is not definitive; we acknowledge the considerable difficulties in undertaking this type of study in a retrospective manner. Our results can instead stimulate further multicentric studies (to increase the number of patients) or experimental studies using genetically modified bacteria for treatment of glioblastoma.

Decompressive craniectomy (DC) has been regarded as an ultima ratio measure in the treatment of refractory intracranial hypertension after brain injury. Most discussion about its benefits is based on studies performed in patients who are65 years of age. The aim of this study was to identify patients aged ≥66 years who underwent DC after traumatic brain injury (TBI), in order to assess patient outcome and to correlate the values of potential predictors of survival on prognosis. From January 2002 to December 2009, 44 patients aged ≥66 underwent DC (follow-up, 12-102 months). Potential predictors of outcome were analyzed, including age, post-resuscitation Glasgow Coma Scale (GCS) score, presence of mass lesion, Simplified Acute Physiology Score (SAPS) II, Injury Severity Score (ISS), and timing of surgical decompression. Mortality was 48% at discharge from the intensive care unit (ICU), 57% at hospital discharge, and 77% at 1-year follow-up and at last follow-up. A bad outcome Glasgow Outcome Scale Dead-Vegetative State-Severely Disabled (GOS D-VS-SD) was observed in 36/44 patients both at hospital discharge and at 1-year follow-up. Mean SAPS II was 45.2 for patients who survived and 57.3 for patients who had died (p=0.0022). Patients who survived had a higher mean post-resuscitation GCS score (p=0.02). Logistical regression analysis indicated post-resuscitation GCS score as the only independent predictive factor for outcome. None of the 22 patients with a post-resuscitation GCS score of 3-5 had a good outcome, 2/10 (20%) patients with a post-resuscitation GCS score of 6-8 and 6/12 patients (50%) with a post-resuscitation GCS score ≥9 had a good outcome.

Atypical presentation of progressive multifocal leukoencephalopathy in a multiple myeloma patient after auto-SCT successfully treated with combination therapy

BACKGROUND:: Placing of sewing needles in the brain through the anterior fontanelle was first described in Germany in 1914. Forty cases have been reported in the scientific literature; most of them were identified in Turkey and Iran, with only a few cases in the Far East, North and Eastern Europe, and the United States. The only case observed in Italy was recorded in 1987. In nonmedical literature, this practice was frequently described in Persian novels, and it has been thought that this ritual could have been diffused with the Persian Empire domination over the centuries. OBJECTIVE:: We report on a new Italian case of an 82-year-old woman admitted for progressive right hemiparesis and gait disturbance. METHODS:: Brain computed tomography scan showed a left frontoparietal chronic subdural haematoma and, surprisingly, three 4-cm-long sewing needles inserted through the region of the anterior fontanelle. The patient and her friends and family did not remember any event justifying their presence. RESULTS:: Subdural collection was evacuated by craniotomic approach, and the sewing needles were left in place and followed up. CONCLUSION:: The rare cases of intracranial needling reported in the literature may represent only the tip of the iceberg. The phenomenon is usually reported as an incidental finding in asymptomatic adults, whereas many babies could not have been diagnosed because they died. The therapy remains controversial, although many authors suggest only follow-up for asymptomatic patients. In this article, all the pertinent literature is reviewed and the most important clinical aspects are discussed, along with a historical assessment of the problem. Language: en

Purines and pyrimidines, regarded for a long time only as building blocks for nucleic acid synthesis and intermediates in the transfer of metabolic energy, gained increasing attention since genetically determined aberrations in their metabolism were associated clinically with various degrees of mental retardation and/or unexpected and often devastating neurological dysfunction. In most instances the molecular mechanisms underlying neurological symptoms remain undefined. This suggests that nucleotides and nucleosides play fundamental but still unknown roles in the development and function of several organs, in particular central nervous system. Alterations of purine and pyrimidine metabolism affecting brain function are spread along both synthesis (PRPS, ADSL, ATIC, HPRT, UMPS, dGK, TK), and breakdown pathways (5NT, ADA, PNP, GCH, DPD, DHPA, TP, UP), sometimes also involving pyridine metabolism. Explanations for the pathogenesis of disorders may include both cellular and mitochondrial damage: e.g. deficiency of the purine salvage enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase are associated to the most severe pathologies, the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to impairment of mitochondrial functions. This review gathers the presently known inborn errors of purine and pyrimidine metabolism that manifest neurological syndromes, reporting and commenting on the available hypothesis on the possible link between specific enzymatic alterations and brain damage. Such connection is often not obvious, and though investigated for many years, the molecular basis of most dysfunctions of central nervous system associated to purine and pyrimidine metabolism disorders are still unexplained.

The incidence of post-traumatic hydrocephalus (PTH) has been reported to be 0.7-51.4%, and we have frequently observed the development of PTH in patients undergoing decompressive craniectomy (DC). For this reason we performed a retrospective review of a consecutive series of patients undergoing DC after traumatic brain injury (TBI). From January 2006 to December 2009, 41 patients underwent DC after closed head injury. Study outcomes focused specifically on the development of hydrocephalus after DC. Variables described by other authors to be associated with PTH were studied, including advanced age, the timing of cranioplasty, higher score on the Fisher grading system, low post-resuscitation Glasgow Coma Scale (GCS) score, and cerebrospinal fluid (CSF) infection. We also analyzed the influence of the area of craniotomy and the distance of craniotomy from the midline. Logistic regression was used with hydrocephalus as the primary outcome measure. Of the nine patients who developed hydrocephalus, eight patients (89%) had undergone craniotomy with the superior limit25 mm from the midline. This association was statistically significant (p = 0.01 - Fisher's exact test). Logistic regression analysis showed that the only factor independently associated with the development of hydrocephalus was the distance from the midline. Patients with craniotomy whose superior limit was25 mm from the midline had a markedly increased risk of developing hydrocephalus (OR = 17). Craniectomy with a superior limit too close to the midline can predispose patients undergoing DC to the development of hydrocephalus. We therefore suggest performing wide DCs with the superior limit25 mm from the midline.

Differentiating a pyogenic cerebral abscess from a cystic brain tumor can be a challenge when using morphological and functional imaging techniques. Several studies on MRI perfusion-weighted imaging (PWI) have demonstrated that enhancing abscess capsules have lower cerebral blood volume ratios (rCBV) than the enhancing rims of necrotic tumors. We report a 67-year-old male with a Nocardia cerebral abscess showing restricted diffusion in the necrotic center, but high values for rCBV in the enhancing capsule on PWI, therefore mimicking a high-grade necrotic tumor. Differential diagnosis between cerebral abscesses and necrotic tumors is greatly improved by the adjunct of diffusion-weighted imaging (DWI) and PWI to the morphological magnetic resonance findings; yet there is still overlap. That an abscess may show increased rCBV along the capsule, therefore mimicking a hypervascular brain tumor on PWI, should be considered when attempting a radiological diagnosis of a ring-enhancing brain lesion.

Glioblastoma multiforme is the most common primary brain tumor in adults. Median survival from the time of diagnosis is 14 months, with less than 5% of patients surviving 5 years. Despite advances in deciphering the complex biology of these tumors, the overall prognosis has only slightly improved in the past three decades. The clinical failure of many therapeutic approaches can be explained by the following considerations: the location of tumors within the brain presents a special set of challenges, including ability of drugs to cross the BBB; cancer cells have unstable genetic structures, very susceptible to mutations; cancer cells have an amalgam of different genetic defects that respond in different ways to any given treatment agent; and, infiltrating and apparently normal but 'activated' cells are evident in the brain surrounding the main tumor. In this way, the biologic phenomena of the 'normal brain' adjacent to the enhanced tumor could allow us to understand the first steps of cancerogenesis and, consequently, to interfere with the pathways responsible for tumor growth and recurrence.

Object It is generally believed that the outcome of traumatic brain injury is not improved by decompressive craniectomy in patients older than 30–50 years. A literature search was performed to assess the level of evidence with respect to the effect of age on outcome in these cases. Methods References were identified by PubMed searches of journal articles published between 1995 and December 2008. The inclusion criteria were as follows: 1) clinical series including adults; and 2) focus on age as a prognostic factor. Technical notes and laboratory investigations were excluded. Results Fourteen English-language articles were finally selected. In 5 of the 14 studies, the authors performed no statistical analysis. In 6 studies they concluded that age was not significantly related to outcome (with 1 of these studies showing a correlation between age and outcome only after 65 years). Three studies showed a correlation between age and outcome. Conclusions With respect to age and effectiveness of decompressive craniectomy, there are no robust data to establish any degree of core evidence and the referred age thresholds are arbitrary.

Subdural empyema represents a loculated suppuration between the dura and the arachnoid. It has been described either intracranially or in the spinal canal, the latter localization being quite rare. It is a rare but serious illness with a declining mortality rate but rather frequent neurological sequelae. Morbidity and mortality in intracranial and spinal subdural empyema directly relate to the delay in diagnosis and therapy. The epidemiology, etiology, pathophysiology and symptoms of spinal subdural empyema and cranial subdural empyema are somewhat different, but brain and spinal subdural empyema are not always two different entities. An adequate treatment strategy should be selected on a case-by-case basis, especially for patients with a massive CNS involvement, where management represents a challenge.

Dermoid cysts account for less than 1% of all intracranial neoplasms and these are principally situated close to the midline. Those located at the petrous apex are generally in the intradural, and less frequently in the interdural, compartment. We report a 37-year-old woman with a giant interdural dermoid cyst of the petrous apex, associated with erosion of the middle fossa floor, and review the relationships of these dysembryogenic lesions, the dura mater and the neurovascular structures of this complex anatomical region, along with the relevant literature.

The aim of this study is to investigate the role of poly(ADP-ribose) polymerase (PARP), involved in DNA repair and in autoimmune pathologic conditions such as systemic lupus erythematosus (SLE) and both limited systemic sclerosis (lSSc) and diffuse systemic sclerosis (dSSc), to assess its possible implication in the pathogenetic processes. The relationship between PARP activity and the intracellular concentration of its substrate nicotinamide adenine dinucleotide (NAD) is also investigated. Peripheral mononuclear cells (PMC) from controls and patients with SLE, lSSc, and dSSc were irradiated with ultraviolet light (UV) and PARP activity was assayed by a radiochemical method. Pyridine nucleotide concentrations were assayed by a high-performance liquid chromatography-linked method. PARP activity was detectable in nonirradiated cells and showed similar values in all groups. The activity significantly increased after UV irradiation in control, SLE, and lSSc cells, but not in dSSc cells. Irradiated PMC from both SLE and dSSc showed lower enzyme activity with respect to irradiated controls. Higher intracellular NAD content was found in all of the pathologic conditions in comparison to values in the control; this difference was statistically significant in dSSc. Our data demonstrate a lower PARP activity in response to UV damage in PMC from patients affected by the above pathologic conditions compared with controls. An inverse relationship between PARP activity and NAD content was also observed.

Background Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoreticular proliferation, which usually involves the lungs, but may also involve the central nervous system (CNS). Unique involvement of the CNS has been reported rarely. We report our experience with LYG confined to the brain and review the pertinent literature. Patients and Methods From January 1995 to September 2007, we identified patients with isolated brain LYG through a search of the histopathology database of the Catholic University of Rome; medical and radiological data were analyzed. Immunophenotype, in situ hybridization analysis of EBV-encoded small RNAs (EBER ISH) and immunoglobulin rearrangement studies were performed on the pathological specimens. Results Four patients with brain-LYG (male/female 1:1, mean age 44 years) underwent surgery in the study period. Subsequent therapy was tailored according to LYG grading. At the latest follow-up (range from 18 to 221 months), patient conditions had improved in all cases. EBER ISH was negative in all cases. Study of the IgH chain gene documented a monoclonal pattern in two cases. Conclusions CNS-LYG is a rare disease that should be considered in the differential diagnosis of both diffuse and space-occupying cerebral lesions. Primary cerebral LYG seems not to be associated with EBV and appears to have a better prognosis than systemic LYG with CNS localization, which is frequently EBV positive.

Chemotherapy including high-dose methotrexate (HD-MTX), with or without radiotherapy, is standard treatment for primary cerebral nervous system lymphoma (PCNSL). It remains controversial whether addition of other drugs will add to therapeutic efficacy. We report here on 41 patients with PCNSL treated using a combined treatment modality, including HD-MTX (3.5 g/m2 for 2 cycles) prior to whole brain radiotherapy (WBRT). In 22 patients, the chemotherapy was intensified by adding high-dose cytosine arabinoside (HD-AraC) (2g/m2 for 4 doses for 2 cycles). Complete remission was obtained in 23 of 34 assessable patients (67%), and overall and disease-free survival rates were 24% and 46%, respectively, without differences between treatment groups. The addition of HD-AraC was complicated by severe infections in 17/22 (77%) patients, resulting in 3 toxic deaths. Our study indicates that addition of HD-AraC may not improve clinical outcome in PCNSL, while it increases toxicity. More targeted and less toxic therapies are warranted.

A 64-year-old man was referred to us for suspected normal pressure hydrocephalus (NPH), according to the clinical history of gait disturbance and urge incontinence, and radiologic evidence of a supratentorial hydrocephalus, with enlarged pericephalic spaces (figure 1). A new MRI revealed a 4-cm prepontine arachnoid cyst …

BACKGROUND AND PURPOSE Subdural empyema represents a loculated infection between the dura and the arachnoid. It has been described either intracranially or in the spinal canal, the latter localization being quite rare. While treatment guidelines for a single (either brain or spinal) localization of a subdural empyema are more or less established, its management when a massive involvement of CNS is evident represents a challenge. METHODS The authors describe a unique case of a 65-year-old woman having a massive involvement of the entire CNS with multiple localizations, both intracranial and spinal. Early diagnosis was obtained through brain CT scans followed by cranio-spinal contrast enhanced MRI scans. Patient was treated with external ventricular drainage and suboccipital craniectomy, while on antibiotic therapy. RESULTS Patient's neurological condition gradually improved. By the end of the eighth hospital week, she was discharged without any neurological deficit. CONCLUSIONS Spinal subdural empyema and brain subdural empyema are not always, as in our case, two different entities. Prompt diagnosis and treatment constitute the major variables affecting outcome.