Unique Finding of a Primary Central Nervous System Neuroendocrine Carcinoma in a 5-Year-Old Child: A Case Report.

Neuroendocrine tumors (NETs) are rare neoplasms predominantly arising in the gastrointestinal-tract or the lungs of adults. To date, only ten cases of primary central nervous system (CNS) NETs have been reported, with just three of them describing a neuroendocrine carcinoma (NECA) and none occurring in a child. We report on a previously healthy 5-year-old boy, who presented with headaches, nausea and vomiting, and was diagnosed with a left cerebellar solid mass with a cystic component. After gross-total resection, histology revealed a neuroendocrine carcinoma. Molecular analysis of the tumor tissue showed a KRAS-splice-site mutation (c451-3C > T). The KRAS-mutation was discovered to be a maternal germline mutation, previously described as likely benign. After extensive search for an extracranial primary tumor, including Ga-68 DOTANOC-PET-CT, the diagnosis of a primary CNS NECA was established, and proton irradiation was performed. Unfortunately, the patient developed an in-field recurrence just 5 weeks after the end of radiotherapy. The tumor was re-resected with vital tumor tissue. Six cycles of chemotherapy were initiated, consisting of cisplatin, carboplatin, etoposide and ifosfamide. The patient remains disease free 22 months after the end of treatment, supporting the beneficial effect of platinum- and etoposide-based chemotherapy for this tumor entity.

Influence of socioeconomic status on cognitive outcome after childhood arterial ischemic stroke.

AIM: To determine whether socioeconomic status (SES) is a stronger predictor for cognitive outcome after childhood arterial ischemic stroke compared to clinical factors. METHOD: We investigated perceptual reasoning, executive functions, language, memory, and attention in 18 children and adolescents (12 males, six females, median age at testing 13y 4mo, range 7y-17y 5mo) after arterial ischemic stroke; collected sociodemographic information (education of parents, household income); and used clinical information (initial lesion volume, residual lesion volume, age at stroke, time since stroke). Linear regression models were used to investigate the potential influence of SES and clinical parameters on cognitive abilities. RESULTS: SES had a moderate effect on all cognitive outcome parameters except attention by explaining 41.9%, 37.9%, 38.0%, and 22.5% of variability in perceptual reasoning, executive functions, language, and memory respectively. Initial lesion volume was the only clinical parameter that showed moderate importance on cognitive outcome (33.1% and 25.6% of the variability in perceptual reasoning and memory respectively). Overall, SES was a stronger predictor of cognitive outcome than clinical factors. INTERPRETATION: Future paediatric studies aiming at clinical predictors of cognitive outcome should control their analyses for SES in their study participants. The findings of the present study further point to the need for more attention to the treatment of children with low SES. WHAT THIS PAPER ADDS: Socioeconomic status (SES) explains up to 42% of variance in cognitive outcome after childhood arterial ischemic stroke. SES is a stronger predictor of outcome than clinical factors.

An adolescent with herpes simplex encephalitis, presenting with mild symptoms and rapid deterioration: A case report.

Headaches in children are a common, but unspecific symptom that can have many underlying causes, ranging from unspecific tension headache through migraine and up to encephalitis and intracranial hypertension. We present the case of a 14-year-old boy who presented to our emergency department with headache, nausea as well as vomiting and developed seizures later on. The initial diagnosis was complicated by a magnetic resonance imaging which did not show any signs of inflammation, but was of limited informative value due to orthodontic appliances. Despite the unremarkable imaging, prophylactic antiviral and antibiotic treatment was started after lumbar puncture. Herpes simplex virus as well as human herpes virus 7 were confirmed in the cerebrospinal fluid. Although both viruses are ubiquitous, severe infections are a rare complication. Immunodeficiency syndromes are predisposing factors for serious complications and genetic analysis of UNC93B and TLR-3 might be helpful for decision-making. No genetic or immunologic predisposition was found in our patient. The patient's condition deteriorated rapidly, so he had to be admitted to the pediatric intensive care unit, where he was intubated and his antiviral treatment with acyclovir was extended by foscarnet. After prolonged mechanical ventilation, he slowly improved. With intensive neurorehabilitation, he could finally return to his daily life activities 3 months after diagnosis. Despite headaches being an unspecific symptom, the possibility of a herpes simplex virus encephalitis should always kept in mind, especially in patients presenting with additional symptoms such as vomiting, altered mental status and/or focal neurological deficits. An initial magnetic resonance imaging might be misleading if orthodontic appliances are in place. Initiation of treatment without delay is crucial for neurologic outcome of herpes simplex virus encephalitis.

Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors.

BACKGROUND: Median survival time of recurrent embryonal brain tumors is short regardless of salvage chemotherapy used. An evolving alternative approach to conventional chemotherapy is to target neovascularization by interfering with tumor angiogenesis at various levels. PROCEDURE: From November 2006 to December 2010, 16 patients (median age: 9 years) with recurrent (9 first, 7 multiple) embryonal brain tumors were treated with an antiangiogenic multidrug combination regimen (bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide, and cyclophophamide) and additional intraventricular therapy (etoposide and liposomal cytarabine). RESULTS: At a median of 33 months, 10/16 patients are alive. 4/4 patients with CNS primitive neuroectodermal tumors (CNS PNET) and 1/7 patients with medulloblastoma (MB) died of tumor progression during the first year. Another patient with MB died of an accident after 23 months, the remaining five patients with MB are alive for 12, 33, 33, 37, and 58 months. For the seven patients with MB, both overall survival (OS) and event free survival (EFS) after 6 months was 100%, after 12 months 85.7 ± 13%, and after 24 months 68.6 ± 19%. In contrast, for patients with CNS PNET, both OS and EFS after 6 months was 75.0 ± 22% and 0.0% and all patients had died by 12 months. Low-dose oral etoposide and cyclophosphamide was reduced after a median of 2 months and discontinued after a median of 11 months. Toxicities were manageable and therapy was generally well tolerated. CONCLUSION: Our results suggest that the chosen antiangiogenic drug combination is particularly beneficial for patients with MB and warrants further investigation.

Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily.

Dasatinib is considered an effective drug in imatinib-resistant chronic myeloid leukemia. Although reported to be well-tolerated, severe events such as pleural or pericardial effusion have been reported at 140 mg daily. We examined our chronic myeloid leukemia patients treated with dasatinib at 100 mg or 50 mg daily and identified 4 of 13 patients who developed marked effusion formation. In 2 patients, grade III/IV pleural and/or pericardial effusions were recorded. All 4 patients had received previous anti-leukemia therapy but none had pre-existing cardiac or pulmonary diseases. In 3 patients, dasatinib had to be discontinued despite treatment with diuretics and glucocorticosteroids. In conclusion, dasatinib-treated chronic myeloid leukemia patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at 100 mg or 50 mg daily. Therefore, all patients should be examined for pre-existing comorbidity and risk factors before starting dasatinib and all should have repeated chest X-rays during long-term dasatinib therapy.

CT-MR image data fusion for computer-assisted navigated surgery of orbital tumors.

PURPOSE: To demonstrate the value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative assessment of orbital tumors, and to present, particularly, CT and MR image data fusion for surgical planning and performance in computer-assisted navigated surgery of orbital tumors. MATERIALS AND METHODS: In this retrospective case series, 10 patients with orbital tumors and associated complaints underwent MDCT and MRI of the orbit. MDCT was performed at high resolution, with a bone window level setting in the axial plane. MRI was performed with an axial 3D T1-weighted (w) gradient-echo (GE) contrast-enhanced sequence, in addition to a standard MRI protocol. First, MDCT and MR images were used to diagnose tumorous lesions compared to histology as a standard of reference. Then, the image data sets from CT and 3D T1-w GE sequences were merged on a workstation to create CT-MR fusion images that were used for interventional planning and intraoperative image guidance. The intraoperative accuracy of the navigation unit was measured, defined as the deviation between the same landmark in the navigation image and the patient. Furthermore, the clinical preoperative status was compared to the patients' postoperative outcome. RESULTS: Radiological and histological diagnosis, which revealed 7 benign and 3 malignant tumors, were concordant in 7 of 10 cases (70%). The CT-MR fusion images supported the surgeon in the preoperative planning and improved the surgical performance. The mean intraoperative accuracy of the navigation unit was 1.35mm. Postoperatively, orbital complaints showed complete regression in 6 cases, were ameliorated notably in 3 cases, and remained unchanged in 1 case. CONCLUSION: CT and MRI are essential for the preoperative assessment of orbital tumors. CT-MR image data fusion is an accurate tool for planning the correct surgical procedure, and can improve surgical results in computer-assisted navigated surgery of orbital tumors.

Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, lipiodol, and cyanoacrylate.

We performed a retrospective analysis of 46 patients with histologically confirmed hepatocellular carcinoma (HCC) who were treated with transarterial embolization (TAE) of the hepatic arteries. To induce permanent embolization, microspheres (Embosphere; 100 to 700 micron) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was injected. A total of 106 TAE procedures were performed. Cumulative survival rates were calculated. No patient died during embolization or within the first 24 hours. Severe procedure-related complications were observed in 2 patients. At the time of analysis, 38 of 46 patients were alive. The 180-, 360-, 520-, and 700-day cumulative survival rates for the total study population were 80.6%, 70.7%, 70.7%, and 47.1%, respectively, with a median survival of 666 days. TAE with the use of microspheres and Lipiodol and cyanoacrylate for unresectable HCC is a feasible treatment modality. Bland embolization with the use of microspheres can be used in patients for whom chemoembolization is not desired.