Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual's diagnosis and/or help clarify risk in healthy populations.

Non-invasive real-time biopsy of intracranial lesions using short time expanded circulating tumor cells on glass slide: report of two cases.

BACKGROUND: Circulating Tumor Cells (CTCs) are promising biomarkers for monitoring solid cancer and were used to monitor brain tumors. Here we report two cases in which, for the first time, CTCs were used in cytological diagnostic evaluation to discriminate a space-occupying lesion of the brain. CASE PRESENTATION: Two cases of focal intracranial lesions, unclassified for diagnosis, untreated and apparently symptomatic, were examined after high-contrast resolution Magnetic Resonance Imaging and/or Computed Tomography scans. CTCs were seeded on chamber slides and short-time expanded under the optimized conditions as we previously reported. The first case was a focal lesion localized in the parietal-occipital area in a 67-year-old woman. The second case was a 31-year-old man with an expansive intracerebral lesion localized in the left peri-trigonal area. Both patients underwent excisional biopsy. Histopathological evaluation of the biopsy confirmed the previous cytological diagnoses, and the analysis of the clinical outcomes retrospectively validated both diagnoses. CONCLUSIONS: The cases here reported illustrate the potential for using expanded CTCs as non-invasive, real-time biopsy. Moreover, non-invasive real-time biopsy can represent an alternative diagnostic tool to be used when a functional area of the brain is at risk of injury from excisional biopsy procedures.

Abnormal pressure waves in headache sufferers with bilateral transverse sinus stenosis.

INTRODUCTION: Bilateral transverse sinus stenosis (BTSS) has been reported to be associated with idiopathic intracranial hypertension without papilloedema in headache sufferers. SUBJECTS AND METHODS: To test the accuracy of short-term cerebrospinal fluid (CSF) pressure monitoring through a lumbar needle for detection of elevated intracranial pressure in headache sufferers with BTSS, we prospectively performed lumbar puncture in order to measure lumbar CSF opening pressures and to monitor, for 1 h, the CSF pressure in 48 consecutive headache sufferers with BTSS and in 50 consecutive headache sufferers with normal appearance of transverse sinuses or stenosis of one transverse sinus. RESULTS: Of the 48 headache sufferers with BTSS, 18 (37.5%) had elevated CSF opening pressure and abnormal pressure waveforms, but short-term CSF pressure monitoring revealed abnormal pressure waves associated with elevated mean CSF pressure also in 26 (86.6%) out of 30 patients who had normal opening pressures. None of the 50 headache sufferers with normal appearance of transverse sinuses or stenosis of one transverse sinus had abnormal pressure waves and elevated CSF pressures. CONCLUSIONS: In this study, short-term CSF pressure monitoring through a lumbar needle revealed abnormal pressure waves and elevated mean CSF pressures in the majority of headache sufferers with BTSS who had normal CSF opening pressures. These findings demonstrate the accuracy of short-term CSF pressure monitoring through a lumbar needle in estimating CSF pressure; they also highlight that a single-spot opening pressure measurement has a low accuracy for recognition of increased intracranial pressure in headache sufferers with BTSS.

The upper limit of normal CSF opening pressure is related to bilateral transverse sinus stenosis in headache sufferers.

There are limited data on the relationship between normal cerebrospinal fluid (CSF) opening pressure and bilateral transverse sinus stenosis (BTSS); there are also several conflicting reports about the upper limit of normal CSF opening pressure. To evaluate the influence of BTSS on the upper limit of normal CSF opening pressure, we prospectively recorded lumbar CSF opening pressures in 217 adult patients with neurological symptoms who underwent cerebral magnetic resonance venography (MRV). The CSF opening pressures ranged between 65 and 286 mmH(2)O (mean = 149.3, s.d. = 47.5). The upper limit of opening pressure in patients with both normal appearance of transverse sinuses and unilateral transverse sinus stenosis on MRV (n = 167) was 195 mmH(2)O with a range of 65-195 mmH(2)O. All patients with BTSS were headache sufferers, and the upper limit of opening pressure in patients with BTSS (n = 50) was 286 mmH(2)O with a range of 91-286 mmH(2)O. All patients with opening pressures > 200 mmH(2)O displayed BTSS, whereas only 13% of patients with a pressure < 200 mmH(2)O displayed BTSS. Our findings demonstrate that the upper limit of normal CSF opening pressure is related to BTSS, and they also highlight that headache sufferers with opening pressures > 200 mmH(2)O should be tested for BTSS by MRV.

Cingulate epilepsy in a child with a low-grade glioma.

INTRODUCTION: Anterior cingulate epilepsy is a peculiar epileptic syndrome with a broad range of clinical manifestations, depending on the numerous projections of anterior cingulate into motor systems. Its diagnosis is often delayed, as seizures mostly occur during sleep and are typically misdiagnosed as parasomnias. Moreover, most focal anterior cingulate epilepsies are believed to be cryptogenic or idiopathic, even if there are some reports of anterior cingulate cortical dysplasia, while anterior cingulate neoplasms underlying epilepsy are rare. CASE REPORT: Here, we report a 30-month-old boy who developed, at the age of 20 months, cingulate epilepsy associated with a low-grade oligodendroglial tumor. It must outlined that the clinical presentation was characterized by very frequent and disabling seizures as the only symptom of the disease, while the results of several neuropsychological tests suggested intact intellectual and behavioral abilities. DISCUSSION AND CONCLUSION: Seizures disappeared completely after surgical removal of the lesion and neuropsychological child's performances remained completely normal. Long-term follow-up and observation are essential for evaluating the future clinical course.

Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors.

Previous studies suggest the expression of UbcH10 gene, that codes for a protein belonging to the ubiquitin-conjugating enzyme family, as a valid indicator of the proliferative and aggressive status of tumors of different origin. Therefore, to look for possible tools to be used as diagnostic markers in astrocytic neoplasias, we investigated UbcH10 expression in normal brain, gliosis and low-grade and high-grade astrocytic tumors by immunohistochemistry. UbcH10 expression was observed in low-grade astrocytoma and in glioblastoma. Our data indicate a clear correlation between UbcH10 expression and the histological grade of the astrocytic tumors. Moreover, the analysis of UbcH10 expression allows the differentiation between gliotic and malignant tissues. Finally, since proteasome inhibitors have recently been considered as possible drugs in the chemotherapy of various tumors, our results would suggest new perspectives for the treatment of brain malignancies based on the suppression of the UbcH10 function.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

Relationship between high prolactin levels and migraine attacks in patients with microprolactinoma.

The pathophysiology of pituitary-associated headache is unknown, although structural and functional features of the tumour are proposed mechanisms. The objective of this study was to evaluate whether headache in a population with pituitary micro-adenomas was related to hyperprolactinemia. We recruited 29 patients with microprolactinoma and headache: 16 with migraine (group A) and 13 with tension-type-headache (group B). The prolactin (PRL) levels measured during attacks of headache were significantly higher in nine patients (56%) of group A and in one patient (8%) of group B. In four of the nine patients of group A, PRL increased after thyrotropin-releasing-hormone (TRH) test and induced severe attacks. After dopamine-agonist (DA) treatment, the headache improved in seven (44%) patients of the group A and in two (15%) patients of the group B. Three of the four patients in whom the TRH-test induced headache attacks, improved after DA treatment. We suggest that hyperprolactinemia may contribute to development of pain in migraine subgroups and further TRH-test could be used to predict which patients could benefit by DA therapy.

Indications and limits of intraoperative cortico-subcortical mapping in brain tumor surgery: an analysis of 101 consecutive cases.

AIM: Here we report our recent experience in supratentorial cortico-subcortical stimulation mapping during surgery for cerebral lesions closely related to sensorimotor and language areas. METHODS: We retrospectively analyzed clinical data of 101 consecutive patients operated on with the aid of electrical stimulation mapping (ESM). Patients harbored a mass lesion situated in or near language (Group A, 30 patients) and sensorimotor (Group B, 71 patients) areas. RESULTS: A macroscopically complete removal of the tumor was carried out in 22 cases out of 28 of group A and in 57 out of 73 of group B. In the first group there was one postoperative death due to a pulmonary embolism. At a mean follow-up of 24.3 months, 15 patients are still alive, 12 out of them are recurrence free and hold a useful language function, while the other 12 patients had a mean survival time of 19.3 months, with a mean high quality survival period (KPS?70) of 17.8 months. In the second group there was no postoperative death. At a mean follow-up of 24.8 months, 55 patients are alive and 47 maintain a useful motor function. Eighteen patients died for tumor progression, with a mean survival time of 18.7 months. Their median high-quality survival period (KPS ? 70), with preservation of a useful motor function, was 16.5 months. CONCLUSION: When properly indicated and correctly carried out, ESM for language and motor functions allows to enhance resection of lesions in eloquent areas with a surgical permanent morbidity comparable to that for lesion in non eloquent areas.

A survey of Italian cases of dystonia treated by deep brain stimulation.

AIM: The aim of this study was to report on Italian cases of dystonia treated by deep brain stimulation up to the end of 2005. METHODS: Retrospective survey. Presentation of data collection among all Italian neurosurgical institutions. RESULTS: Seven out of 123 Italian neurosurgical centres were enrolled. Sixty-nine patients were operated. According to different classification criteria, cases were grouped as follows: 37 primary and 32 secondary dystonia; 61 generalized and 8 focal dystonia; 16 patients aged at onset <2 years, 22 aged 3-12 years, 14 aged 13-20 years, 17 aged >20 years. Primary dystonia (DYT) mutation 1 was identified in 21% of primary generalized dystonia. Age at surgery was <15 years in 21.7% of cases (N.=15). Mean time between clinical onset and surgery was 17 years. Globus pallidus internus (GPi) was chosen for implantation in all cases. Type of anesthesia, method of target localization, lead and implanted pulse generator (IPG) model differed among centres. Surgical complications occurred in 19% of patients, but at a higher rate (33%) in the pediatric subgroup. Stimulation parameters varied among centres, but the main scheme was 90-120 micros and 130 Hz. Follow-up duration ranged from 3 to 84 months (longer than 24 months in 50% of patients). Mean Burke-Fahn-Marsden scale (BFM) improvement was 42% for both severity and disability score, ranging from 0% to 92%. Improvement of at least 50% in BFM severity score has been reached by 45% of primary and 37% of secondary dystonia. Clinical results were better in the DYT1 subgroup, with 60% of cases improving more than 50%. Among secondary dystonia, the drug-induced group had very good results too. On the contrary delayed surgery and presence of comorbidity were negatively correlated to the outcome. CONCLUSION: In this series, primary generalized dystonia has a better outcome, especially if associated to DYT1 mutation. Among secondary dystonia, the drug-induced group has very good RESULTS: Correlation analysis of time to surgery and associated comorbidity suggests that earlier surgery is advisable.

Bilateral transverse sinus stenosis predicts IIH without papilledema in patients with migraine.

BACKGROUND: The headache profile of patients with idiopathic intracranial hypertension without papilledema (IIHWOP) may be indistinguishable from that of migraine. Bilateral transverse sinus stenosis (BTSS) has been found in the majority of patients with IIHWOP. The frequency of BTSS associated with IIHWOP in patients with migraine is unknown. OBJECTIVE: To detect the frequency of BTSS in adult patients with migraine and to investigate whether the presence of BTSS identifies patients with IIHWOP. METHODS: In a prospective study from December 2000 to November 2005, 724 consecutive patients with recurrent headaches who fulfilled International Headache Society diagnostic criteria for migraine underwent cerebral MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 70 age-matched control subjects. RESULTS: Six hundred seventy-five of the 724 patients with migraines had normal MRV. Seventy of these 675 patients underwent LP, and all of them had normal CSF pressure. Forty-nine (6.7%) of the 724 patients with migraine had BTSS. Twenty-eight of these 49 patients with BTSS underwent LP, and 19 (67.8%) had IIHWOP. The headache profiles of patients with BTSS and IIHWOP did not differ from those of patients with normal MRVs and CSF pressures within normal limits. CSF pressure was normal in both patients and controls with normal MRV. CONCLUSIONS: Of patients with migraine, 6.7% had bilateral transverse sinus stenosis; 67.8% of these patients had idiopathic intracranial hypertension without papilledema (IIHWOP). These results suggest that patients with migraine who present bilateral transverse sinus stenosis on cerebral MR venography should undergo lumbar puncture to exclude IIHWOP.

Transverse sinus stenoses persist after normalization of the CSF pressure in IIH.

BACKGROUND: Bilateral transverse sinus (TS) stenosis has been found in more than 90% of patients with idiopathic intracranial hypertension (IIH). OBJECTIVE: To evaluate whether TS stenosis changed after normalization of CSF pressure in patients with IIH during medical treatment. METHODS: Fourteen consecutive patients with IIH with bilateral TS stenosis on cerebral MR venography (MRV) during the medical treatment were studied. Patients were followed for over a 6-year period. During the follow-up, patients underwent repeated lumbar punctures (LPs) and cerebral MRV. MRV was always performed before each LP. RESULTS: TS stenosis persisted in all the patients during the follow-up. In 9 of 14 (64%) patients with IIH, CSF pressure normalized during medical treatment. CONCLUSIONS: Transverse sinus (TS) stenoses, as revealed by MR venography, persist in patients with idiopathic intracranial hypertension after normalization of CSF pressure, suggesting the lack of a direct relationship between the caliber of TS and CSF pressure.

Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and first results by the study group of the Italian neurosurgical society.

The preliminary results obtained by the Study Group for Treatment of Involuntary Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian Neurosurgical Society, are reported. The series includes 16 cases of very advanced Parkinson's Disease (PD), aged 46-81; 15 of them were not eligible for Deep Brain Stimulation. Ten cases have been evaluated at 3-30 months after implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2 8 Volt, 100-400 microsec., 20-120 Hz) by chronically implanted electrodes, relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia are reduced. Standing, gait, motor performance, speech and swallowing are improved. Benefit is marked as far as axial symptoms is concerned. Also the symptoms of Long Term Dopa Syndrome -dyskinesias, motor fluctuations - and other secondary effect of levodopa administration psychiatric symptoms - are improved. Levodopa dosage may be reduced by 50%. The effect seems persistent and does not fade away with time. Improvement ranged, on the basis of the UPDRS scale, from <25% to 75%. There was only one case of complete failure. Quality of life is markedly improved in patients who were absolutely incapable of walking and unable arise out of chair. After stimulation they could walk, even if assistance was necessary. Improvement was observed also in those with disabling motor fluctuation and dyskinesias which could be abolished.

Use of chronic sacral nerve stimulation in neurological voiding disorders.

AIM: Neurogenic low urinary tract dysfunctions unresponsive to medical and conservative therapy are difficult to manage. Nowadays they can be treated with Sacral Nerve Stimulation (SNS), even if clinical experiences reported in literature are still limited. METHODS: We performed SNS in 6 patients with neurogenic bladder: 3 patients had incontinence-urgency (1 myelitis, 1 multiple sclerosis, 1 autonomic polineuropathy) and 3 patients had urinary retention (1 incomplete spinal cord lesion, 1 operation for discal hernia T5-T6, 1 hysterectomy). RESULTS: Among cases with incontinence-urgency we achieved complete control of the bladder in 2 patients while in 1 patient the number of urinary losses was reduced of the 80%. In 2 patients with urinary retention we obtained complete recovery of the bladder function, while in 1 patient the number of cateterisms/die reduced of 50%, the urinary volume for micturion increased and residual urinary volume decreased. Results were unchanged during the follow-up (maximum 26 months), except for 1 patient in which a partial loss of effectiveness occurred. CONCLUSIONS: Chronic electric stimulation of S3 sacral roots via an implanted neuroprotesis is therefore an effectiveness, save and promising therapeutic option in treatment of neurogenic bladder dysfunctions.

Effects of Ginko Biloba and caspase inhibitors on brain ischemia in the Mongolian Gerbil.

AIM: Data reported in previous studies and our own previous experience have led us to explore the mechanism of and the degree of protection afforded by Ginko Biloba in a model of cerebral ischemia in the Mongolian Gerbil evaluating histological and neurological effects in this rodent. METHODS: Mongolian Gerbils were divided into experimental groups: Group A consisted of animals subjected only to experimental ischemia; 5 minutes occlusion of the carotid arteries. Group B consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately before the surgical procedure. Group C consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately after the surgical procedure. Group D consisted of animals subjected to experimental ischemia and to a dose of the caspase inhibitors z-VAD.FMK and z-DEVD.FMK injected intracerebroventricularly through the right hemisphere before the surgical procedure. Group E consisted of animals subjected to experimental ischemia and to a dose of caspase inhibitors injected after the surgical procedure. Group F consisted of Sham-operated animals. Histological controls were done by H and E and the TUNEL method in the frontal cortex and caudate-putamen. RESULTS: The percentage of normal cells was not statistically significant at analysis with H and E, whereas the TUNEL method showed good protection with Ginko Biloba and caspase inhibitors, when the latter is given in the reperfusion phase. These data were in agreement with data obtained at neurological examination. CONCLUSION: We could say that cellular morphology is in itself an untrustworthy tool for judging the effects of ischemia and protective drugs; the TUNEL method may add important information about the different components of cellular death; the reperfusion phase may be critical for apoptotic phenomena; Ginko Biloba might protect neurons of the frontal cortex from both necrotic and apoptotic death in this model of ischemia.