[ (11) C]-methionine positron emission tomography in the postoperative imaging and followup of patients with primary and recurrent gliomas.

We investigated the sensitivity and specificity of [(11)C]-methionine positron emission tomography ([(11)C]-MET PET) in the management of glioma patients. We retrospectively analysed data from 53 patients with primary gliomas (16 low grade astrocytomas, 15 anaplastic astrocytomas and 22 glioblastomas) and Karnofsky Performance Status (KPS) > 70. Patients underwent [(11)C]-MET PET scans (N = 249) and parallel contrast-enhanced MRI (N = 193) and/or CT (N = 113) controls. In low grade glioma patients, MRI or CT findings associated with [(11)C]-MET PET additional data allowed discrimination residual disease from postsurgical changes in 96.22% of these cases. [(11)C]-MET PET early allowed detection of malignant progression from low grade to anaplastic astrocytoma with high sensitivity (91.56%) and specificity (95.18%). In anaplastic astrocytomas, we registered high sensitivity (93.97%) and specificity (95.18%) in the postoperative imaging and during the followup of these patients. In GBM patients, CT and/or MRI scans with additional [(11)C]-MET PET data registered a sensitivity of 96.92% in the postsurgical evaluation and in the tumour assessment during temozolomide therapy. A significant correlation was found between [(11)C]-MET mean uptake index and histologic grading (P < 0.001). These findings support the notion that complementary information derived from [(11)C]-MET PET may be helpful in postoperative and successive tumor assessment of glioma patients.

Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: A phase II study.

O(6)-alkylguanine-DNA alkyltransferase (AGAT), involved in temozolomide-induced DNA damage repair, plays a key role in the efficacy of temozolomide. AGAT activity may be reduced by protracted temozolomide doses. On the basis of the preclinical findings, we treated patients with a histologically-proven diagnosis of glioblastoma (GBM) following adjuvant temozolomide failure with a low protracted dose of temozolomide (130 mg/m(2)/day, days 1-7 and 15-21, every 4 weeks). The primary endpoint of the study was 6-month progression-free survival (PFS-6 m). The secondary endpoints were overall survival (OS) from the start of temozolomide alternative schedule and toxicity. Enrolment was ceased at 27 patients due to the lack of effectiveness of this regimen. Results indicate that our schedule is well-tolerated, but ineffective in patients with GBM and further strategies are required to improve the outcome of these patients.

Vagal nerve stimulation for drug-resistant epilepsies in different age, aetiology and duration.

PURPOSE: The aim of the study was to compare the outcome with respect to age of implant, aetiology and duration of epilepsy. METHODS: One hundred thirty-five drug-resistant epileptic patients, excluded from ablative surgery, were submitted to vagal nerve stimulation (1995-2007). Aetiology was cryptogenic in 57 and symptomatic in 78 patients. Ages of implant were 0.5-6 years (18 patients), 7-12 years (32 patients), 13-18 years (31 patients) and more than 18 years (54 patients). Epilepsy types were Lennox-Gastaut (18 patients), severe multifocal epilepsy (33 patients) and partial (84 patients). Duration of epilepsy is 3 months to 57 years. Clinical outcome was determined by comparing the seizure frequency after stimulation at 3-6-12-18-24-36 months with the previous 3 months. 'Responders' were the patients experiencing a seizure frequency reduction of 50% or more during follow-up. In statistical analysis, Wilcoxon and McNemar tests, general linear model for repeated measures, logistic regression and survival analysis were used. RESULTS: The seizure frequency reduction was significant in the group as a whole between baseline and the first follow-up (Wilcoxon test). The percentage of responder increases with time (McNemar test p = 0.04). Univariate analysis showed a significant effect of the age of implant on seizure frequency reduction: Adult patient had worst clinical outcome than children (p < 0.001) and adolescents (p = 0.08). Patients with severe multifocal epilepsy had better percentage seizure reduction compared with Lennox-Gastaut and partial (p = 0.03). Lesser duration of epilepsy had positive influence on outcome. Multivariate analysis confirmed age of implant to be the strongest factor influencing prognosis. Furthermore, positive is the association between lesional aetiology and young age. CONCLUSIONS: The best responder could be a young lesional epileptic patient; after 3 years of follow-up, the percentage of responders is still in progress.

Vagus nerve stimulation (VNS) is effective in treating catastrophic 1 epilepsy in very young children.

The objective of this study is to evaluate the safety and efficacy of vagus nerve stimulation (VNS) in very young children suffering from catastrophic epilepsy and status epilepticus. We reviewed files of 60 VNS-implanted children at our institution and we selected six very young patients, less than 3 years old (mean age at implant 1.6 years). All patients suffered from severe cognitive impairment and catastrophic epilepsy with underlying diagnosis of hemimegalencephaly (1), hypoxic-ischemic encephalopathy (1), tuberous sclerosis complex (1), and malignant migrating partial epilepsy of infancy (3). Three patients were VNS-implanted during admission at intensive care unit (ICU) after developing life-threatening status epilepticus. The mean follow-up time was 41.6 months. The VNS was implanted using a single cervical incision. No surgery-related complications were observed. Four of six children have shown a significant, persistent improvement in seizure control (range, 60-90%). In patients with status, insertion of the vagal nerve stimulator allowed early cessation of status and discharge from ICU. Quality of life and parental satisfaction improved and for three children there was some milestone evolution. Catastrophic epilepsy in infancy can be devastating and difficult to treat with drugs and surgery. If resective surgery is inappropriate or refused, VNS can be considered as a well-tolerated and effective procedure even in toddlers affected by severe epilepsy and multiple developmental disabilities.

Vagus nerve stimulation: clinical experience in drug-resistant pediatric epileptic patients.

INTRODUCTION: Vagus nerve stimulation (VNS) is an effective alternative treatment for patients with partial refractory epilepsy. Nevertheless, information regarding VNS in children is still limited. MATERIALS AND METHODS: The clinical efficacy, safety and neuropsychological effects of VNS in 34 children (mean age 11.5 years) with drug-resistant epilepsy were studied. Mean follow-up was 30.8 months. Nine patients have been diagnosed with Lennox-Gastaut Syndrome, nine patients were affected by severe partial epilepsy with bisynchronous EEG and drop attacks, and 16 patients suffered from partial epilepsy without bisynchronous EEG and fall seizures. Forms were designed for prospective data collection on each patient's history, seizures, implants, device settings, quality of life (QOL), neuropsychological assessment and adverse events. Surgical technique was performed both by standard two incisions and single neck incision. RESULTS: Mean reduction in total seizures was 39% at 3 months, 38% at 6 months, 49% at 12 months, 61% at 24 months and 71% at 36 months. Significant better results were obtained in partial epilepsy, with and without drop attacks, than in Lennox-Gastaut syndrome--three patients being seizure-free. No operative morbidity was reported. Side-effects were minor and transient--the most common were voice alteration and coughing during stimulation. In two patients, electrode breakage occurred 3 years after surgical procedure; in both cases, a new device was implanted after removing the vagal electrode coils and generator. CONCLUSION: VNS can be considered an appropriate strategy as an add-on treatment in children affected by drug-resistant partial epilepsy and ineligible for resective epilepsy surgery.

Bobble head doll syndrome in a child with a third ventricular cyst and hydrocephalus.

INTRODUCTION: The bobble head doll syndrome, mainly affecting children under 10 years of age, is a rare and surgically treatable movement disorder characterized by head bobbing occurring at a rate of 2-3 times/s. Its pathophysiological mechanism is not well known but two main factors are commonly associated with the condition: a dilatation of the third ventricle and, more frequently, a cystic lesion rather than a solid mass in the region of the third ventricle. ILLUSTRATIVE CASE: The illustrative case concerns a child with a third ventricular cystic lesion and hydrocephalus who had experienced abnormal head movements since the age of 1 year as well as ataxia and tremor of the arms. Contrast cranial MRI, at the age of 3, demonstrated enlargement of the third and lateral ventricles, a ballooned cyst inside the third ventricle with compression of all the diencephalic structures, a funnel dilation of the cranial part of the aqueduct, and a cyst in the septum pellucidum. A ventriculoperitoneal shunt (Hakim-Cordis) was placed and the head bobbing, tremor of the arms, and ataxia disappeared immediately. CONCLUSION: The good and immediate clinical result in our case emphasizes the opinion that the reduction of CSF pressure is the best therapeutical option in the bobble head doll syndrome.