Intravoxel incoherent motion magnetic resonance imaging in the assessment of brain microstructure and perfusion in idiopathic normal-pressure hydrocephalus.

PURPOSE: To determine the relationship between intravoxel incoherent motion (IVIM) MRI parameters and clinical changes post-tap test (TT) in idiopathic normal-pressure hydrocephalus (iNPH) patients. METHODS: Forty-four probable iNPH patients underwent 3 T MRI before and after TT. IVIM parameters were calculated from eight different bilateral regions of interest in basal ganglia, centrum semiovale, and corona radiata. Patients were categorized based on TT response into positive (group 1) and negative (group 2) groups. A Welch two-sample t-test was used to compare differences in D, D*, f, and ADC between the two groups, while a paired t-test was employed to assess the changes within each group before and after TT. These parameters were then correlated with clinical results. RESULTS: In the lenticular and thalamic nuclei, D value was significantly lower in the group 1 compared to group 2 both pre- and post-TT (p = 0.002 and p = 0.007 respectively). Post-TT, the positive response group exhibited a notably reduced D* value (p = 0.012) and significantly higher f values (p = 0.028). In the corona radiata and centrum semiovale, a significant post-TT reduction in D* was observed in the positive response group (p = 0.017). Within groups, the positive response cohort showed a significant post-TT increase in ADC (p < 0.001) and a decrease in D* (p = 0.007). CONCLUSION: IVIM permits the acquisition of important non-invasive information about tissue and vascularization in iNPH patients. Enhanced perfusion in the lenticular and thalamic nuclei may suggest the role of re-established microvascular and glymphatic pathways, potentially elucidating the functional improvement in motor function after TT in iNPH patients.

Clinical applicability of arterial spin labeling magnetic resonance imaging in patients with possible idiopathic normal pressure hydrocephalus: A prospective preliminary study.

PURPOSE: idiopathic Normal Pressure Hydrocephalus (iNPH) patients have a global reduction of cerebral blood flow (CBF) and Arterial Spin Label (ASL) MRI allows a global evaluation of CBF without the injection of contrast agents. This work aims to assess the qualitative evaluation agreement of ASL CBF colored maps between different neuroradiologists and by correlating these data to the Tap Test. METHODS: Thirty - seven patients with the diagnosis of possible iNPH were consecutively submitted to a diagnostic MRI on a 1.5 Tesla Magnet before and after the lumbar infusion test and the Tap Test. Twenty - seven patients improved after the Tap Test and were addressed to surgery while 10 patients did not improve. All the MRI examinations included a 3D-Pulsed ASL sequence. Two different neuroradiologists independently reviewed all ASL images. They were asked to give a score (0 not improved; 1 improved) to global perfusion image quality by comparing ASL images obtained after the Tap Test to those obtained before. Comparison between inter- and intra-reader qualitative scores were performed with Cohen's kappa. RESULTS: Inter-reader agreement between the two neuroradiologists showed that qualitative scores were attributed similarly by two readers (k = 0.83). This technique has a good PPV (90.5 %; CI 95 %, 72.7-97.1 %), NPV (50 %; CI 95 %, 34.1-65.6 %), SN (70.37 %; CI 95 %, 49.8-86.2 %) SP (80 %; CI 95 %, 44.4-97.5 %) and accuracy (73 %; CI 95 %, 55.9-86.2 %) when considered in the setting of possible iNPH patients. CONCLUSION: ASL-MRI seems to be a promising non-invasive technique in the preoperative selection of patients affected by possible iNPH.

MDS-UDPRS-III in the diagnosis of idiopathic Normal Pressure Hydrocephalus and identification of candidates for Ventriculo-Peritoneal Shunting surgery. Results from a retrospective large cohort of patients.

OBJECTIVES: To evaluate the entity of extrapyramidal signs, characterize them and evaluate the dynamics of change by the mean of MDS-UPDRS-III in iNPH patients after the TT to determine if this tool may help the diagnosis of iNPH and the identification of candidates for Ventriculo-Peritoneal Shunting. MATERIALS AND METHODS: We retrospectively collected data from 120 patients with the initial diagnosis of possible iNPH; they underwent neurological examination by the means of MDS-UPDRS-III and other scales before and after Tap Test (TT). They were then classified as defined iNPH (57), probable iNPH (35), and NOT-iNPH (28) based on the clinical response after the Tap Test and VPS. RESULTS: After the Tap Test, defined and probable iNPH groups improved by 3.35 (2.57-4.12, p < 0.001) and 3.43 (2.43-4.4, p < 0.001) points on MDS-UPDRS-III respectively; NOT-iNPH did not improve significantly on MDS-UPDRS-III and on any other variable studies. Defined iNPH also shifted significantly from asymmetric prevalence of symptoms to a more symmetric form (from 70% before to 57% after). CONCLUSION: extrapyramidal signs improved significantly after the Tap Test in definite and probable iNPH patients. MDS-UPDRS-III may be a useful complementary tool in the diagnosis of iNPH and identification of candidates for Ventriculo-Peritoneal Shunting.

Resting-state functional-MRI in iNPH: can default mode and motor networks changes improve patient selection and outcome? Preliminary report.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant. METHODS: We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded. RESULTS: At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038). CONCLUSIONS: Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.

Primary Leptomeningeal Medulloblastoma in Adults: A Diagnostic Challenge-Case Report and Systematic Review.

Primary leptomeningeal medulloblastoma (PL-MB) in adults is a rare disease with a severe prognosis. A 35-year-old woman presented with headaches, diplopia, and gait ataxia, with triventricular hydrocephalus and descent of the cerebellar tonsils beyond the foramen magnum. Endoscopic third ventriculostomy was performed. Six months later, headaches recurred. Dilatation of the supratentorial ventricular system and massive cerebellar swelling without contrast-enhancing nodularities were reported. Occipitocervical decompression with duraplasty was performed. A bioptic diagnosis of PL-MB was made. Craniospinal irradiation and chemotherapy were administered. After 18 months, no recurrence was observed. Few cases of PL-MB have been reported: patients die before treatment or within a few days after surgery. Our long-term survival could be ascribable to a slow clinical presentation and an early diagnosis that allowed surgical treatment and the administration of a combined chemoradiotherapy protocol. Cerebellar swelling, even without associated enhancing lesions, with or without hydrocephalus, should be a neuroradiological alarm sign, and PL-MB should be considered.

Image-guided LINAC radiosurgery in hypothalamic hamartomas.

Introduction: Hypothalamic hamartomas (HH) are developmental malformations that are associated with mild to severe drug-refractory epilepsy. Stereotactic radiosurgery (SRS) is an emerging non-invasive option for the treatment of small and medium-sized HH, providing good seizure outcomes without neurological complications. Here, we report our experience treating HH with frameless LINAC SRS. Materials and methods: We retrospectively collected clinical and neuroradiological data of ten subjects with HH-related epilepsy that underwent frameless image-guided SRS. Results: All patients underwent single-fraction SRS using a mean prescribed dose of 16.27 Gy (range 16-18 Gy). The median prescription isodose was 79% (range 65-81 Gy). The mean target volume was 0.64 cc (range 0.26-1.16 cc). Eight patients experienced complete or near complete seizure freedom (Engel class I and II). Five patients achieved complete seizure control within 4 to 18 months after the treatment. Four patients achieved Engel class II outcome, with stable results. One patient had a reduction of seizure burden superior to 50% (Engel class III). One patient had no benefit at all (Engel class IV) and refused further treatments. Overall, at the last follow-up, three patients experience class I, five class II, one class III and one class IV outcome. No neurological complications were reported. Conclusions: Frameless LINAC SRS provides good seizure and long-term neuropsychosocial outcome, without the risks of neurological complications inherently associated with microsurgical resection.

Long-Standing Overt Ventriculomegaly in Adults (LOVA): Diagnostic Aspects, CSF Dynamics with Lumbar Infusion Test and Treatment Options in a Consecutive Series with Long-Term Follow-Up.

BACKGROUND: Long-standing overt ventriculomegaly in adults is a chronic form of hydrocephalus without a clear pathophysiological description and a consensus about the treatment. We present the results of endoscopic third ventriculostomy (ETV) in a consecutive series with a mean follow-up of 79 ± 23 months, highlighting how the preoperative lumbar infusion test could facilitate understanding the pathophysiology of the disease. METHODS: We retrospectively collected data regarding clinical assessment, neuroradiological findings, and preoperative lumbar infusion tests in 22 symptomatic patients. RESULTS: In the majority of cases, patients reported imbalance and gait disorders, and 8 subjects had headaches. The preoperative lumbar infusion test demonstrated a mean opening pressure of 13.95 ± 2.88 mm Hg, with plateau values ranging from 22 to 39 mm Hg. The resistance to outflow was 11.21 ± 2.00 mm Hg/mL/min. After the procedure, all patients reported improvement or halted progression in their presenting symptoms, whereas no significant reduction was demonstrated in Evans' index. One subject underwent a second ETV procedure after more than 2 years because of the failure of the endoscopic approach. CONCLUSIONS: A progressive exhaustion of brain compliance plays an important role in explaining the dichotomy between severe ventriculomegaly and mild clinical symptoms in patients with long-standing overt ventriculomegaly in adults. The role of the aqueductal stenosis as a diagnostic criterion might be reconsidered. The preoperative infusion test data support this observation. Preoperative assessment should include not only clinical and neuroradiological evaluation but also the study of cerebrospinal fluid dynamics. ETV should be considered the treatment of choice because of its safety and efficacy. Long-term follow-up is mandatory.

Risk Factors of Persistent Hydrocephalus in Children with Brain Tumor: A Retrospective Analysis.

OBJECT: Hydrocephalus is one of the main complications of brain tumors in children, being present in about 50% of cases at the time of the tumor diagnosis and persisting up to 10-40% of cases after surgical resection. This is a single-institution retrospective study on the variables that may predict the need for treatment of persistent hydrocephalus in pediatric patients presenting with a brain tumor. METHODS: Retrospective case note review of 43 newly diagnosed brain tumors in children referred between April 2012 and January 2018 to our regional pediatric neuro-oncology service was carried out. Diagnosis of hydrocephalus was carried out using both preoperative and postoperative MRI to determine Evans' index (EI) and the fronto-occipital horn ratio (FOHR) from each scan. Simple logistic regression was used to analyze categorical variables as appropriate. A p value <0.05 was considered significant. RESULTS: Forty-three children were analyzed, 26 males and 17 females with a median age at diagnosis 10.4 years (IQR: 5.2-13.5). Hydrocephalus was present in 22/43 children (51%) preoperatively; in 8/22 children (36%) with hydrocephalus undergoing tumor resection, hydrocephalus persisted also in the postoperative period. An EI >0.34 (p = 0.028) and an FOHR >0.46 (p = 0.05) before surgery were associated with a higher prevalence of persistent hydrocephalus and therefore to the need for a cerebrospinal fluid drain device in the postoperative phase. CONCLUSION: Preoperative identification of children at risk for developing persistent hydrocephalus would avoid delays in planning the permanent cerebrospinal fluid drain devices. This study finds that an EI >0.34 and an FOHR >0.46 at diagnosis could impact on the therapeutic management of children with hydrocephalus associated with brain tumors. Prospective and larger-scale studies are needed to standardize this approach.

Late-onset occlusion of the Monro foramina after endoscopic third ventriculostomy in adults: Case discussion and review of the literature.

BACKGROUND: Few cases of adult idiopathic occlusion of the foramen of Monro (AIOFM) are described in the literature. The diagnosis of AIOFM after an endoscopic procedure is even more infrequent. CASE DESCRIPTION: We described the case of a 50-year-old woman who developed bilateral membranous occlusion of both Monro foramina 20 years after an endoscopic third ventriculostomy (ETV) for triventricular hydrocephalus due to an aqueductal stenosis. The patient underwent an endoscopic treatment (left foraminoplasty and septostomy) to check the patency of the stoma on the floor of the third ventricle. After the endoscopic procedure, the symptoms improved and the postoperative magnetic resonance imaging (MRI) demonstrated the resolution of the biventricular hydrocephalus. CONCLUSION: Bilateral occlusion of both FM with consequent bilateral lateral ventricles enlargement is an extremely rare condition, especially if we consider the cases of biventricular hydrocephalus after endoscopic procedures. In our opinion, an endoscopic approach should be attempted as first choice procedure, avoiding any intraventricular stent or shunt placement.

Computer-Guided In-House Cranioplasty: Establishing a Novel Standard for Cranial Reconstruction and Proposal of an Updated Protocol.

BACKGROUND: Restoring the ideal geometry of the skull vault can be a challenging task. This is especially true for complex cases when cranial reconstruction is associated with concomitant cranial resection in a one-stage procedure. Oftentimes, cranioplasty designing and production are delegated to external companies, with a significant increase in time and cost to fabricate an alloplastic implant. This case series collects and critically examines previous experiences in the field of in-house cranial reconstruction providing an updated protocol to establish a novel standard for cranial reconstruction with a substantial reduction of costs. MATERIALS AND METHODS: A virtual craniotomy was digitally designed by the surgeon and transferred in the operating room using navigation and a surgical guide. Cranial reconstruction was planned using interpolation functions, recreating the ideal shape of the skull vault. Molds were designed, and 3D printed to intra-operatively shape polymethyl methacrylate (PMMA) according to the pre-operative plan. For validating the accuracy of reconstruction, as well as the restoration of the appropriate skull thickness, software-encoded color maps and root-mean-square error (RMSE), were calculated. RESULTS: All surgeries were uneventful. No adverse reactions to PMMA were observed. Accuracy of the procedure was validated, showing a submillimetric deviation from the original planning and a plate thickness value similar to the adjoining bone. All steps of design and production were performed by the surgical team, and costs were seven to ten times less than the past. CONCLUSION: We discussed and improved previous reports in the field of computer-guided in-house cranioplasty, particularly when complex one-stage resective and reconstructive procedures are planned. The use of three-dimensional analyses provides a validation of the accuracy of the resulting cranial reconstruction. The authors hope that the results might inspire other colleagues to consider computer-guided in-house cranioplasty, giving surgeons the mastery of each planning phase with a substantial decrease in costs.

The evolution of craniofacial resection: A new workflow for virtual planning in complex craniofacial procedures.

Complex craniofacial surgery has been later to take advantage of computerized planning than traditional maxillofacial procedures. Virtual reality, 3D model navigation, and bioengineering analyses have changed our approach to the surgical planning of craniofacial resection, increasing the benefits of surgery in terms of accuracy while decreasing complication rate. This study introduces a new workflow for 3D reconstruction, virtual model navigation, and alignment analyses, and demonstrates its successful application in a sample of four patients. A case of squamous cell carcinoma of the maxillary and ethmoid sinus in a 62-year-old patient is presented to evaluate the application of the workflow for a combined transfacial and transcranial resection. Results demonstrate that virtual surgical planning was successfully translated into navigational coordinates and reproduced in the operating room. While the literature provides a wide range of applications of virtual planning for traditional maxillofacial procedures, its introduction for complex craniofacial procedures remains difficult. The presented case shows that it is worth investigating the correlation between virtual reality planning and surgical accuracy for craniofacial resection, and related advantages in terms of surgical safety and improved prognosis.

A novel approach to skull-base and orbital osteotomies through virtual planning and navigation.

OBJECTIVE: Computer-assisted planning of osteotomy lines, coupled with navigation-guided performance of planned osteotomies, is a highly innovative approach to skull-base and orbital surgery. The aim of this pilot study is to provide an assessment of the accuracy of this novel approach in guiding the correct positioning of osteotomy lines in frontal, temporal, and orbital regions, defining the agreement between the spatial position of the planned and performed osteotomies. METHODS: Fifteen patients with orbital, frontal sinus, and lateral skull-base diseases underwent virtual surgical planning. Osteotomies to access the orbit, frontal sinus, and lateral skull base were planned on computer tomography-based three-dimensional models. The planned osteotomies were reproduced on the operating field using a navigation system. The positions of the performed and planned osteotomies were compared. The results were described as the mean positional difference between planned and performed osteotomies and as Lin's concordance coefficient, and Bland-Altman limits of agreement were also defined. RESULTS: The overall mean difference was 0.719 mm (95% confidence interval [CI]: 0.472 to 0.965 mm). Overall, Lin's concordance coefficient was 0.997 (95% CI: 0.996 to 0.998), and overall Bland-Altman limits of agreement ranged from -1.407 to 2.844 mm. The smallest mean difference (0.587 mm, 95% CI: 0.244 to 0.931 mm) was calculated in the orbit group, whereas the highest mean difference (0.904 mm, 95% CI: 0.428 to 1.379 mm) was described in the lateral skull-base group. CONCLUSION: This study's results support the use of this novel planning and navigation protocol for guiding osteotomy in anterior and lateral skull-base surgery, providing a clinical validation of this technique. LEVEL OF EVIDENCE: 4 Laryngoscope, 00:1-9, 2018 Laryngoscope, 129:823-831, 2019.

Supratentorial Cavernous Malformations Involving the Corticospinal Tract and Sensory Motor Cortex: Treatment Strategies, Surgical Considerations, and Outcomes.

BACKGROUND: Cavernous malformations (CMs) are congenital malformations and may be located anywhere in the brain. We present a series of CMs located close to or inside of the motor-sensory cortex or corticospinal tract (CST) with clinical onset due to hemorrhage or mass effect. In such cases, surgery becomes an acceptable option. OBJECTIVE: To evaluate the role of diffusion tensor imaging (DTI), functional-magnetic-resonance imaging (fMRI), intraoperative neurophysiological monitoring, neuronavigation, and brain-mapping and the clinical results of surgical treatment of CMs in this critical location. METHODS: The study included 54 patients harboring 22 cortical and 32 deep locations. This series was distinct because in group I, where the DTI was not obtained, and in the group II, where this evaluation was performed. RESULTS: The postoperative permanent morbidity rate was 4% in the historical group for the deeper CMs, and there was no morbidity in the second group. DTI and fMRI permitted us to estimate the distance between the CMs and both the cortical activation cluster and the pyramidal tract. These data, in addition to intraoperative mapping and monitoring, made it necessary for us to perform a partial resection in 2 cases in the second series. CONCLUSION: CMs are congenital lesions and CST fibers can run directly on their surface. Integration of fMRI and DTI data with intraoperative functional monitoring and direct cortical and subcortical mapping are mandatory to accomplish an optimal resection, tailoring the best surgical approach to the acceptable morbidity. A subtotal resection could be considered an option for deep locations.

The role of perfusion and diffusion MRI in the assessment of patients affected by probable idiopathic normal pressure hydrocephalus. A cohort-prospective preliminary study.

BACKGROUND: Invasive tests measuring resistance to cerebral spinal fluid (CSF) outflow and the effect of temporary drainage of CSF are used to select candidates affected by idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. Neither test, however, completely excludes patients from treatment. Perfusion and diffusion magnetic resonance imaging (MRI) are non-invasive techniques that might be of value in selecting patients for surgical treatment and understanding brain changes in iNPH patients. The aim of this study was to understand the role of perfusion and diffusion MRI in selecting candidates for shunt surgery and to investigate the relationship between cerebral perfusion and possible microstructural changes in brain tissue before and after invasive tests, and after ventricular-peritoneal (VP) shunt implantation, to better clarify pathophysiological mechanisms underlying iNPH. METHODS: Twenty-three consecutive patients with probable iNPH were included in this study. Patients underwent a clinical and neuroradiological evaluation before and after invasive tests, and after surgery. Only patients who showed a positive result in at least one of the invasive tests were submitted for VP shunt implantation. Perfusion and diffusion magnetic resonance imaging (MRI) was performed before and after invasive tests and after shunt surgery. RESULTS: Thirteen patients underwent surgery and all showed clinical improvement after VP shunt implantation and a significant increase in perfusion in both periventricular white matter (PVWM) and basal ganglia (BG) regions. The 10 patients that did not have surgery showed after invasive tests, a significant reduction in perfusion in both PVWM and BG regions. Comparing the changes in perfusion with those of diffusion in positive patients we found a significant positive correlation in BG and a significant inverse correlation in PVWM area. CONCLUSIONS: Perfusion MRI is a non-invasive technique that could be useful together with invasive tests in selecting patients for surgical treatment. Furthermore, the relationship between perfusion and diffusion data could better clarify pathophysiological mechanisms underlying iNPH. In PVWM area we suggest that interstitial edema could reduce microvascular blood flow and interfere with the blood supply to these regions. In BG regions we suggest that a chronic hypoxic insult caused by blood hypo-perfusion produces a chronic cytotoxic edema. Both in PVWM and in BG regions, pathophysiological mechanisms could be modified after VP-shunt implantation.

Comparison of the molecular profile of brain metastases from colorectal cancer and corresponding primary tumors.

AIM: Little is known about molecular biology of brain metastasis (BM) from colorectal cancer and its concordance with matched primary tumors. MATERIALS & METHODS: We identified 56 consecutive colorectal cancer patients who underwent neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and PIK3CA. The molecular profile of the brain lesion was compared with the corresponding primary tumor. RESULTS: The molecular profile concordance rate was 95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median overall survival was 24.0 months (95% CI: 15.6-32.4). CONCLUSION: In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.

MGMT promoter methylation status in brain metastases from colorectal cancer and corresponding primary tumors.

BACKGROUND: Brain metastases (BM) from colorectal cancer are usually associated with poor prognosis. The aim of this retrospective study is to evaluate MGMT promoter methylation in BM and their corresponding primary colorectal cancer tumors. MATERIALS & METHODS: MGMT promoter methylation status was assessed by pyrosequencing in 53 consecutive patients resected for BM. A concordance analysis between BM and matched primary tumor was performed in 39 cases. RESULTS: MGMT methylation was found in 34 (64.2%) BM and in 25 corresponding primary tumors (64.1%). Median survival after neurosurgery was independent from MGMT promoter methylation (163 days for those with methylated MGMT versus 193 days for the unmethylated). CONCLUSION: Epigenetic MGMT promoter methylation was common and the concordance between primary and secondary lesions was high.

HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series.

Brain metastases (BM) from colorectal cancer (CRC) are a rare but increasing event. Surgical resection of oligometastatic disease, including BM, may produce a survival benefit in selected patients. Previous studies described the HER-2 expression patterns in CRC patients, but its prognostic role still remains controversial. Information on the HER-2 expression in BM from CRC is currently lacking. Among the over 500 patients treated at our Department of Neurosurgery in the last 13 years (1999-2012), we identified a cohort of 50 consecutive CRC patients resected for BM. Clinical data were retrospectively reviewed using electronic hospital charts and surgical notes. Formalin-fixed, paraffin-embedded tissue samples were retrieved and histologically reviewed. HER-2 status was assessed on 4-µm sections by HerceptTest™, and scored by two pathologists according to gastric cancer HER-2 status guidelines. In score 2+ cases HER-2 gene copy number was analyzed by FISH, performed using the PathVysion HER-2 DNA Probe Kit. Median age at time of BM resection was 65 years (35-82); most patients were males (60%) with a good performance status. The majority of the BM were single (74%) and sited in the supratentorial area (64%); 2-4 lesions were diagnosed in 9 patients (18%), and >4 in 3 patients (6%). The rate of HER-2 positivity (defined as IHC score 3+ or IHC score 2+ and FISH gene amplification) was 8.1% for the primary CRC tumors and 12% for their corresponding BM. The concordance rate between primary tumors and matched BM was 89%. Median overall survival after neurosurgery was 6.5 months for HER-2 IHC score 0 vs. 4.6 months for HER-2 IHC score 1+/2+/3+; the difference was statistically significant (p = 0.01, Log-rank test). HER-2 positivity of our case cohort was low but comparable to literature. Concordance rate of HER-2 expression between BM and corresponding primary tumors is high and similar to those reported for breast and gastric cancers. Our data suggest a potential negative prognostic value of HER-2 expression in brain lesions from CRC.

Delayed Positivization of Cerebral Angiography in Reversible Cerebral Vasoconstriction Syndrome (RCVS) Presenting with Recurrent Subarachnoid Haemorrhage.

Benign angiopathy of the central nervous system is a clinical syndrome with evidence of reversible cerebral vasoconstriction (RCVS). Haemorrhagic stroke, either subarachnoid or intracerebral is an unusual presentation of RCVS. We describe a case of RCVS presenting with a subarachnoid haemorrhage (SAH), with rebleeding and onset of hydrocephalus during the first week, and, notably, delayed evidence of typical angiographic features after two negative prior exams. Normalization of the angiographic vasculitic-like lesions was documented at month +6. Repeated cerebral angiograms are mandatory to exclude this kind of disease, and the uncommon presentation of this case reinforces this concept.

Treatment of recurrent high-grade gliomas with GliaSite brachytherapy: a prospective mono-institutional Italian experience.

AIMS AND BACKGROUND: The present study evaluated toxicity, local control, and survival in patients with relapsed high-grade glioma after surgery and external beam radiation therapy and treated with re-operation and GliaSite brachytherapy. METHODS: Between 2006 and 2008, 15 patients with recurrent high-grade glioma underwent re-operation and GliaSite brachytherapy. Ten patients were males and 5 females. Median age was 40 years (range, 20-71). Karnofsky performance status was ≥70. All patients but one received GliaSite irradiation of the surgical cavity wall at the dose of 4500 cGy at a depth of 1 cm. RESULTS: No severe acute side effects were observed during GliaSite brachytherapy. Pathologically documented, symptomatic late radiation necrosis was observed in 3 patients (20%); 2 subsequently died of further complications. Two patients were alive at a median follow-up 13 months (range, 1-30). Median overall survival after GliaSite brachytherapy was 13 months. CONCLUSIONS: Patients with recurrent high-grade glioma can be treated with additional surgery and GliaSite brachytherapy, delivering 4500 cGy at 1 cm depth without significant acute side effects but with a significant rate (20%) of late radiation necrosis, resulting in 13% of treatment-related deaths. Compared with the literature, survival results in our study appear to be satisfactory, but they may be related to patient selection criteria. Re-intervention followed by GliaSite brachytherapy should not be offered as a standard treatment for recurrent high-grade glioma, because of the high rate of late complications, treatment-related deaths, and high treatment costs.