Chiari Malformation Type 1 and Syringomyelia: Why Do Patients Claim for International Guidelines? Commentary on the 2021 Chiari and Syringomyelia Consensus Document.

The diagnosis of Chiari malformation type 1 (CM1) and Syringomyelia (Syr) has become increasingly common during the past few years. Contemporarily, the body of literature on these topics is growing, although randomized controlled studies on significant case series to drive guidelines are missing in the pediatric and adult populations. As a result of the different opinions about surgical indications and techniques raised by CM1-Syr, an increasing number of well-informed but disoriented patients is emerging. To bridge this gap, an International Consensus Conference on CM1-Syr held in Milan in November 2019 aimed to find a consensus among international experts, to suggest some recommendations that, in the near future, could lead to guidelines. Here, we comment on the most relevant recommendations about the definition, diagnosis, surgical management, failures and re-intervention, and outcome. We also focus on some "wrong" indications or techniques that, although widely disapproved by the experts, and negatively experienced by many patients, are still largely in use.

Neurocognitive and Psychological Outcomes among Children and Adolescents with Brain Tumors: Development of an Observational and Longitudinal Prospective Study Protocol.

Children and adolescents affected by brain tumors are at risk for neuropsychological sequelae that need to be evaluated in order to plan adequate rehabilitation programs, and to support their development and recovery. This work aims to describe an innovative prospective observational study protocol for the early evaluation and monitoring over time of neuropsychological outcomes in this pediatric population. Pediatric patients aged 3-17 with a brain tumor diagnosis will be assessed through the use of a battery of Italian standardized neuropsychological tests, with good psychometric properties and age-appropiate, at three different time points of their clinical course: at diagnosis and before surgery (T0), after surgical removal and before the start of potential adjuvant therapies (T1), and at the one-year follow-up after potential adjuvant therapies (T2). This study will allow clinicians to support the neuropsychological development of these children by promoting appropriate and timely rehabilitation and educational programs from the early phases of their clinical course.

Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document.

BACKGROUND: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. METHODS: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). RESULTS: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." CONCLUSIONS: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

Development and application of a diagnostic and severity scale to grade post-operative pediatric cerebellar mutism syndrome.

The post-operative pediatric cerebellar mutism syndrome (CMS) affects about one-third of children and adolescents following surgical removal of a posterior fossa tumor (PFT). According to the Posterior Fossa Society consensus working definition, CMS is characterized by delayed-onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricle tumor surgery in children, and is frequently accompanied by additional features such as hypotonia and oropharyngeal dysfunction/dysphagia. The main objective of this work was to develop a diagnostic scale to grade CMS duration and severity. Thirty consecutively referred subjects, aged 1-17 years (median 8 years, IQR 3-10), were evaluated with the proposed Post-Operative Pediatric CMS Survey after surgical resection of a PFT and, in case of CMS, for 30 days after the onset (T0) or until symptom remission. At day 30 (T1), CMS was classified into mild, moderate, or severe according to the proposed scale. CMS occurred in 13 patients (43%, 95% C.I.: 25.5-62.6%), with mild severity in 4 cases (31%), moderate in 4 (31%), and severe in 5 (38%). At T1, longer symptom persistence was associated with greater severity (p = 0.01). Greater severity at T0 predicted greater severity at T1 (p = 0.0001). Children with a midline tumor location and those aged under 5 years at diagnosis were at higher risk of CMS (p = 0.025 and p = 0.008, respectively). In conclusion, the proposed scale is a simple and applicable tool for estimating the severity of CMS at its onset, monitoring its course over time, and providing an early prognostic stratification to guide treatment decisions.

Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System, Fifth Edition (WHO-CNS5), has strengthened the concept of tumor grade as a combination of histologic features and molecular alterations. The WHO-CNS5 tumor type "Diffuse midline glioma, H3K27-altered," classified within the family of "Pediatric-type diffuse high-grade gliomas," incarnates an ideally perfect integrated diagnosis in which location, histology, and genetics clearly define a specific tumor entity. It tries to evenly characterize a group of neoplasms that occur primarily in children and midline structures and that have a dismal prognosis. Such a well-defined pathological categorization has strongly influenced the pediatric oncology community, leading to the uniform treatment of most cases of H3K27-altered diffuse midline gliomas (DMG), based on the simplification that the mutation overrides the histological, radiological, and clinical characteristics of such tumors. Indeed, multiple studies have described pediatric H3K27-altered DMG as incurable tumors. However, in biology and clinical practice, exceptions are frequent and complexity is the rule. First of all, H3K27 mutations have also been found in non-diffuse gliomas. On the other hand, a minority of DMGs are H3K27 wild-type but have a similarly poor prognosis. Furthermore, adult-type tumors may rarely occur in children, and differences in prognosis have emerged between adult and pediatric H3K27-altered DMGs. As well, tumor location can determine differences in the outcome: patients with thalamic and spinal DMG have significantly better survival. Finally, other concomitant molecular alterations in H3K27 gliomas have been shown to influence prognosis. So, when such additional mutations are found, which one should we focus on in order to make the correct clinical decision? Our review of the current literature on pediatric diffuse midline H3K27-altered DMG tries to address such questions. Indeed, H3K27 status has become a fundamental supplement to the histological grading of pediatric gliomas; however, it might not be sufficient alone to exhaustively define the complex biological behavior of DMG in children and might not represent an indication for a unique treatment strategy across all patients, irrespective of age, additional molecular alterations, and tumor location.

The management of Chiari malformation type 1 and syringomyelia in children: a review of the literature.

In anticipation of the "Chiari and Syringomyelia Consensus Conference" held in Milan in 2019, we performed a systematic literature review on the management of Chiari malformation type 1 (CM1) and syringomyelia (Syr) in children.We aimed to summarize the available evidence and identify areas where consensus has not been reached and further research is needed.In accordance with PRISMA guidelines, we formulated seven questions in Patients-Interventions-Comparators-Outcomes (PICO) format. Six PICOs concerned CM1 children with/without additional structural anomalies (Syr, craniosynostosis, hydrocephalus, tethered cord, and cranio-vertebral junction anomalies), and one PICO Syr without CM1. We searched Medline, Embase, Cochrane, and NICE databases from January 1, 1999, to May 29, 2019. Cohort studies, controlled and randomized clinical trials (CCTs, RCTs), and systematic reviews were included, all pertinent only to patients ≤ 18 years of age.For CM1, 3787 records were found, 460 full texts were assessed and 49 studies (46 cohort studies, one RCT, and two systematic reviews) were finally included. For Syr, 376 records were found, 59 full texts were assessed, and five studies (one RCT and four cohort studies) were included. Data on each PICO were synthetized narratively due to heterogeneity in the inclusion criteria, outcome measures, and length of follow-up of the included studies.Despite decades of experience on CM1 and Syr management in children, the available evidence remains limited. Specifically, there is an urgent need for collaborative initiatives focusing on the adoption of shared inclusion criteria and outcome measures, as well as rigorous prospective designs, particularly RCTs.

Syringomyelia and Chiari Syndrome Registry: advances in epidemiology, clinical phenotypes and natural history based on a North Western Italy cohort.

BACKGROUND: Syringomyelia and Chiari Syndrome are classified as rare diseases, but current known occurrence in Europe is missing. The increased ability to diagnose these pathologies by magnetic resonance imaging and its widespread availability has led to an increase of reported cases, often asymptomatic, with the need to standardize definitions, diagnostic criteria and treatments. AIMS: We present shared Interregional Recommendations developed with the primary aim to estimate Syringomyelia and Chiari Syndrome prevalence and incidence in North Western Italy, with special reference to symptomatic forms. METHODS: An agreement for the standardization of definitions, classifications, diagnostic criteria and surgical Recommendations was reached by the multidisciplinary Interregional Piemonte and Valle d'Aosta Chiari-Syringomyelia Consortium (Delphi method); next, in 2011 a census for Syringomyelia and Chiari Malformation was performed through the Interregional Piemonte and Valle d'Aosta Rare Disease Registry, integrated by a dedicated form in order to estimate prevalence and incidence. RESULTS: 436 patients, 292 females, met shared interregional diagnostic criteria. Syringomyelia prevalence was estimated in 4.84:100 000; Chiari Malformation prevalence was 7.74:100 000; incidence was 0.82:100 000 and 3.08:100 000 respectively. Demographics, neuroradiological parameters and aetiology were reported (in symptomatic and asymptomatic forms). Finally, symptoms and signs, familiar and natural history were analyzed. CONCLUSIONS: First Italian epidemiological data (prevalence, incidence) on Chiari and syringomyelia was collected, according to shared diagnostic Recommendations. Future perspectives include the adoption of these Recommendations at national level to standardize the access to diagnosis and care process and promote multicenter clinical trials.

Pediatric intracranial ependymoma: correlating signs and symptoms at recurrence with outcome in the second prospective AIEOP protocol follow-up.

PURPOSE: The aims of patients' radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. METHODS: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. RESULTS: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5-104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. CONCLUSIONS: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI.

Prevention and management of hearing loss in syndromic craniosynostosis: A case series.

OBJECTIVE: To assess the audiological profile in a cohort of children affected by syndromic craniosynostosis. METHODS: Eleven children with Apert syndrome (n=4), Saethre-Chotzen syndrome (n=3), Muenke syndrome (n=2), Crouzon syndrome (n=1) and Pfeiffer syndrome type 1 (n=1) were submitted to a complete audiologic evaluation including otoscopy, pure-tone audiometry, tympanometry and acoustic reflex testing, ABR, otoacustic emissions, temporal bone High Resolution CT (HRCT) scan. The main outcome measures were prevalence, type and severity of hearing loss, prevalence of chronic otitis media, correlation with the time of first surgical correction. RESULTS: Seven of 11 patients (64%) presented hearing loss (HL), conductive in 3/7 patients (43%) and mixed in 4/7 (57%). No patients showed a purely sensorineural HL. All hearing impaired patients displayed middle ear disorders: the patients with conductive HL had otitis media with effusion (OME) and 3/4 patients with mixed HL showed tympanic alterations or cholesteatoma. A bilateral vestibular aqueduct enlargement was detected by HRCT scan in one normal hearing patient. The ABRs resulted normal in all cases. CONCLUSION: Our study confirms the high prevalence of otologic diseases in such patients. In contrast with previous studies, middle ear disorders were responsible for the hearing impairment also in patients with mixed HL due to secondary inner ear damage. These findings restate the necessity of a close audiologic follow-up. We did not detect the specific ABR abnormalities previously reported, possibly because of an early correction of the cranial vault malformations.

Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma.

BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.

End-of-life care in pediatric neuro-oncology.

BACKGROUND: The management of children with cancer during the end-of-life (EOL) period is often difficult and requires skilled medical professionals. Patients with tumors of the central nervous system (CNS) with relapse or disease progression might have additional needs because of the presence of unique issues, such as neurological impairment and altered consciousness. Very few reports specifically concerning the EOL period in pediatric neuro-oncology are available. PROCEDURE: Among all patients followed at our center during the EOL, we retrospectively analyzed data from 39 children and adolescents with brain tumors, in order to point out on their peculiar needs. RESULTS: Patients were followed-up for a median time of 20.1 months. Eighty-two percent were receiving only palliative therapy before death. Almost half the patients (44%) died at home, while 56% died in a hospital. Palliative sedation with midazolam was performed in 58% of cases; morphine was administered in 51.6% of cases. No patient had uncontrolled pain. CONCLUSIONS: The EOL in children with advanced CNS cancer is a period of active medical care. Patients may develop complex neurological symptoms and often require long hospitalization. We organized a network-based collaboration among the reference pediatric oncology center, other pediatric hospitals and domiciliary care personnel, with the aim to ameliorate the quality of care during the EOL period. In our cohort, palliative sedation was widely used while no patients died with uncontrolled pain. A precise process of data collection and a better sharing of knowledge are necessary in order to improve the management of such patients.

Multidimensional outcome measure of selective dorsal rhizotomy in spastic cerebral palsy.

BACKGROUND: One of the treatment option to reduce spasticity in cerebral palsy children is selective dorsal rhizotomy. Several studies have demonstrated short and long term improvements in gait and other activities after rhizotomy but this surgery still remains a controversial procedure and patient outcome indicators measures are not uniform. AIMS: To describe our assessment and outcome evaluation protocol and to verify by this protocol short term results of rhizotomy. METHODS: We recruited 9 cerebral palsy children (mean age 7.9 years ± 3.2) affected by mild to moderate spastic diplegia and operated by rhizotomy. Patients were studied preoperatively and at 12 months after surgery by the following clinical and instrumental measures correlated to the International Classification of Functioning: modified Ashworth Scale, passive Range of Motion, Medical Research Council Scale, Selective Motor Control Scale, 3D-motion analysis and energy cost of locomotion measurements (indicators of "body functions"); Gross Motor Functional Measure and Motor Functional Independence Measure (indicators of "activities and participation"). RESULTS: Our data showed, after rhizotomy, reduction of spasticity specially in plantarflexors muscles (p < 0.01), increase of strength of knee flexors/extensors and foot plantar/dorsiflexion muscles (p < 0.01), improvement of selective motor control (p < 0.05), more similar spatio-temporal parameters of gait analysis to healthy subjects, reduced equinus foot and knees hyperflexion as energy cost. CONCLUSION: The complementary use of multiple indicators may improve the evaluation of the results of dorsal rhizotomy. A beneficial outcome measured by these indicators has been found in our spastic diplegic children one year after rhizotomy.

Relevance of intraoperative D wave in spine and spinal cord surgeries.

PURPOSE: The combined recordings of epidural-(D wave) and muscle motor evoked potentials (m-MEPs) have been proposed in many studies in intramedullary spinal cord tumour (IMSCT) surgery, although not all agree. Furthermore, the usefulness of the intraoperative monitoring of motor systems using these methods in other types of spine surgery has not yet been clearly confirmed. The aim of this study is to test the impact of intraoperative D wave on the monitorability and motor outcome in spine surgery. METHODS: Intraoperative recording of posterior tibial nerve somatosensory potentials, lower limb m-MEPs (LLm-MEPs) and epidurally recorded D wave caudally to the surgical level was attempted in a total of 103 spine and spinal cord surgeries (23 IMSCT, 55 extramedullary spinal cord tumours and 25 myelopathies). RESULTS: There was a 97.1 %, overall monitorability where at least 1 of the 3 modalities was applicable in 100 surgical procedures. Baseline LLm-MEPs were recorded bilaterally in 85 cases and unilaterally in 11. A caudal D wave was recorded in 97 cases. Transient, or persistent intraoperative modifications occurred in 14/23 IMSCT, 5/55 extramedullary spinal cord tumours and in 2/25 myelopathies. The presence of a persistent stable caudal D wave was predictive of a good motor outcome even when the LL-MEPs were absent and/or when lost during surgery. CONCLUSIONS: Not only is intraoperative D wave recording to be considered mandatory in IMSCT surgery but it should also be attempted in other types of spine/spinal cord surgeries.

Surveillance study of healthcare-associated infections in a pediatric neurosurgery unit in Italy.

BACKGROUND: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit. METHODS: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0-18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs. RESULTS: The study included 260 patients, with a mean age of 4.3 ± 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs. CONCLUSION: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management.

Infant ependymoma in a 10-year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) experience with omitted or deferred radiotherapy.

PURPOSE: The protocols of the 1990s omitted or delayed irradiation, using upfront chemotherapy to spare the youngest children with ependymoma the sequelae of radiotherapy (RT). We treated 41 children under the age of 3 years with intracranial ependymoma between 1994 and 2003. PATIENTS AND METHODS: After surgery, chemotherapy was given as follows: regimen I with four blocks of vincristine, high-dose methotrexate 5 g/m(2), and cyclophosphamide 1.5 g/m(2) alternating with cisplatin 90 mg/m(2) plus VP16 450 mg/m(2) for 14 months; subsequently, regimen II was used: VEC (VCR, VP16 300 mg/m(2), and cyclophosphamide 3 g/m(2)) for 6 months. Radiotherapy was planned for residual tumor after the completion of chemotherapy or for progression. RESULTS: We treated 23 boys and 18 girls who were a median 22 months old; 14 were given regimen I, 27 were given regimen II; 22 underwent complete resection, 19 had residual tumor. Ependymoma was Grade 2 in 25 patients and Grade 3 in 16; tumors were infratentorial in 37 patients and supratentorial in 4. One child had intracranial metastases; 29 had progressed locally after a median 9 months. Event-free survival was 26% at 3 and 5 years and 23% at 8 years. One child died of sepsis, and another developed a glioblastoma 72 months after RT. Progression-free survival was 27% at 3, 5, and 8 years, and overall survival was 48%, 37%, and 28% at 3, 5, and 8 years, respectively. Of the 13 survivors, 6 never received RT; their intellectual outcome did not differ significantly in those children than in those without RT. CONCLUSIONS: Our results confirm poor rates of event-free survival and overall survival for up-front chemotherapy in infant ependymoma. No better neurocognitive outcome was demonstrated in the few survivors who never received RT.

Long-term results of a second endoscopic third ventriculostomy in children: retrospective analysis of 40 cases.

OBJECTIVE: To evaluate retrospectively the operative findings and long-term results of a repeat endoscopic third ventriculostomy (ETV) in pediatric hydrocephalic patients readmitted after the first procedure with symptoms and/or signs of intracranial hypertension and/or radiological evidence of increased ventricular dilation and/or occluded stoma on follow-up radiological examinations. METHODS: We analyzed a series of 482 ETVs in pediatric patients from 2 Italian departments of pediatric neurosurgery. The clinical charts of 40 patients undergoing a second ETV were selected and reviewed retrospectively. The pre- and postoperative radiological findings and operative films were analyzed retrospectively. RESULTS: Forty patients underwent a total of 82 ETVs. Thirty-eight patients were operated on twice and 2 were operated on 3 times. During the second procedure, the stoma was found to be closed in 28 patients without underlying adhesions, to be open but with significant arachnoid adhesions in the prepontine cistern in 8 patients, to be open without adhesions in 2 patients, to have a pinhole orifice in 1 patient, and to be closed with underlying adhesions in 1 patient. The second procedure allowed reopening of the stoma or lysis of the arachnoid adhesions in 35 patients and was abandoned in 3 patients because of extensive arachnoid adhesions or because the stoma was found to be wide open (2 patients). In 30 patients (75%), the second ETV was effective, and the 2 patients who underwent a third ETV remained shunt free. In 10 patients (25%), a ventriculoperitoneal shunt was eventually placed. Age younger than 2 years at the time of the first procedure and arachnoid adhesions in the subarachnoid cisterns observed during the second procedure are the main negative prognostic factors for the success of a second ETV. CONCLUSION: A second ETV can be performed with a reasonable chance of restoring patency of the stoma and avoiding placement of an extrathecal shunt. Every effort should be made to detect subarachnoid adhesions in the cistern on preoperative imaging study to select potential candidates and avoid unnecessary procedures.

Immunohistochemical and proteomic profile of melanotic medulloblastoma.

We present the case of a 6-year-old male affected by an infratentorial tumor. Histological diagnosis was melanotic medulloblastoma. Immunohistochemistry showed in the melanin rich areas positive cells for HMB45. We performed a proteomic study to compare protein profiles in melanotic versus non-melanotic areas. Protein profiles of different areas of the tumor displayed similarity, with the exception of seven proteins. In accordance with the hypothesis that melanotic medulloblastomas produce oculo-cutaneous melanin, proteomic analysis showed melanocytic-associated antigens and epidermal autoantigen 450K in the pigmented nodule; both these proteins have a significant role as markers of melanotic elements.