G. Cantore

Choroid plexus papillomas: Consideration of a surgical series of 33 cases

SummaryWith the aim of understanding better the behaviour of an uncommon lesion such as the choroid plexus papilloma, we have analysed a surgical series of 33 cases operated on at the Neurosurgical Department, University of Rome “La Sapienza”, between 1955 and 1992 and have reviewed the relevant literature. Our results support the view that a radical resection of these lesions, which if removed entirely, carry a very good prognosis. The hydro-cephalus should be treated only if persistent.Adjuvant treatment such as radiotherapy and chemotherapy should be reserved for specific cases.

KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo

Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high infiltration in the brain parenchyma rendering the tumor difficult to eradicate by neurosurgery. Efforts to identify molecular targets involved in the invasive behavior of GBM suggested ion channel inhibition as a promising therapeutic approach. To determine if the Ca2+-dependent K+ channel KCa3.1 could represent a key element for GBM brain infiltration, human GL-15 cells were xenografted into the brain of SCID mice that were then treated with the specific KCa3.1 blocker TRAM-34 (1-((2-chlorophenyl) (diphenyl)methyl)-1H-pyrazole). After 5 weeks of treatment, immunofluorescence analyses of cerebral slices revealed reduced tumor infiltration and astrogliosis surrounding the tumor, compared with untreated mice. Significant reduction of tumor infiltration was also observed in the brain of mice transplanted with KCa3.1-silenced GL-15 cells, indicating a direct effect of TRAM-34 on GBM-expressed KCa3.1 channels. As KCa3.1 channels are also expressed on microglia, we investigated the effects of TRAM-34 on microglia activation in GL-15 transplanted mice and found a reduction of CD68 staining in treated mice. Similar results were observed in vitro where TRAM-34 reduced both phagocytosis and chemotactic activity of primary microglia exposed to GBM-conditioned medium. Taken together, these results indicate that KCa3.1 activity has an important role in GBM invasiveness in vivo and that its inhibition directly affects glioma cell migration and reduces astrocytosis and microglia activation in response to tumor-released factors. KCa3.1 channel inhibition therefore constitutes a potential novel therapeutic approach to reduce GBM spreading into the surrounding tissue.

Malignant monstrocellular brain tumours. A study of 42 surgically treated cases.

SummaryA series of 42 cases of monstrocellular brain tumour (MBT) who received surgery over a 34 year period is reviewed with the aim of gaining more understanding of the biology of this oncotype. A case of benign pleomorphic xanthoastrocytoma was identified among the cases and is discussed in another paper. In this series, as in most others taken from the literature, MBTs were more frequent in young subjects (55% were under 50 years of age and 17% were children) and presented as a superficially located (63%), often sharply circumscribed (42%) mass. The mean survival time for 24 patients treated by surgery and radiotherapy (RT) was 57 weeks compared to 32 weeks for 12 treated by surgery alone (p < 0.02). Patients younger and older than 50 years showed the same survival and the slightly better course of children did not reach statistical significance. Besides postoperative RT, the only other factor that showed a significantly positive influence on survival was the presence of a definite lymphocytic infiltration (LI) in the tumour (p < 0.05). This result confirms our previous study on the prognostic influence of LI in glioblastoma (GB). Actually, we noted that the prolonged survival of both MBT and GB patients exhibiting a definite LI (67% and 11.5%, respectively, in the two series) was strikingly similar. We conclude that MBT is a peculiar oncotype with a probably better prognosis than GB in the majority of cases. Lymphocytes seem to play a major prognostic role and giant-monstrous cells are indirectly implicated, reasonably enhancing the hosts immune response by magnifying the antigenic stimulus.

Transsphenoidal adenomectomy for GH-, PRL- and ACTH-secreting pituitary tumours: outcome analysis in a series of 125 patients

Transsphenoidal surgery (TSS) is a well recognised treatment for secreting pituitary adenomas, however a very wide variation of clinical outcomes and recurrence rates has been reported, depending on the different criteria used to define the cure. We reported the clinical outcome of a large series of patients operated on for a secreting pituitary adenoma according to the most recent stringent criteria of biochemical remission nowadays accepted. One hundred and twenty-five consecutive patients with a secreting pituitary adenoma (42 PRL-, 67 GH- and 16 ACTH-secreting adenomas) who were operated on by the two same neurosurgeons were considered for the study. Biochemical remission of disease was achieved in 56% of patients; 78% for patients with microadenoma and 47% for patients with macroadenomas, respectively. No cases of mortality or major immediate postoperative complications were observed. Tumour size, high hormone levels and dural invasion were significantly correlated to a poor surgical outcome. The recurrence rates ranged between 0 and 24%, being higher for PRL-secreting tumours. In conclusion, TSS is safe and effective in secreting pituitary tumours. It is still the first treatment for GH- and ACTH-secreting adenomas, whereas in patients with prolactinomas, surgery should be reserved for cases of resistance or intolerance to dopamine agonists.

Ependymoma of the filum terminale: Treatment and prognostic factors in a series of 28 cases

SummaryA series of 28 ependymomas arising in the filum terminale was divided into two groups based on the presence/absence of connections with the conus medullaris and/or roots of the cauda equina. Group A comprised ependymomas having no connections with the contiguous structures and group B those either infiltrating or adhering to such structures.Factors having a positive influence on the prognosis (risk of recurrence) were: 1) clinical history under one year (p<0.01); 2) confinement of tumour to the filum terminale (p<0.01); 3) total tumour removal (p<0.05). Postoperative radiotherapy had no appreciable effect on outcome. The combination of significant factors was in turn significantly influenced by the mode of tumour growth, which proved to be the cardinal factor in prognosis. This point is examined in the light of the pulished work.

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol

Aim: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on “anatomo–electro–clinical correlations”. Methods: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. “Tailored” surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. Results: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a “hippocampal sclerosis/cryptogenic” group (n = 57) and a “tumours/cortical organisation disorders” group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. Conclusions: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo–electro–clinical data and can be treated effectively and safely with tailored surgery.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmanns area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

Fractionated stereotactic conformal radiotherapy for large benign skull base meningiomas

Purposeto assess the safety and efficacy of fractionated stereotactic radiotherapy (FSRT) for large skull base meningiomas.Methods and MaterialsFifty-two patients with large skull base meningiomas aged 34-74 years (median age 56 years) were treated with FSRT between June 2004 and August 2009. All patients received FSRT for residual or progressive meningiomas more than 4 centimeters in greatest dimension. The median GTV was 35.4 cm3 (range 24.1-94.9 cm3), and the median PTV was 47.6 cm3 (range 33.5-142.7 cm3). Treatment volumes were achieved with 5-8 noncoplanar beams shaped using a micromultileaf collimator (MLC). Treatment was delivered in 30 daily fractions over 6 weeks to a total dose of 50 Gy using 6 MV photons. Outcome was assessed prospectively.ResultsAt a median follow-up of 42 months (range 9-72 months) the 3-year and 5-year progression-free survival (PFS) rates were 96% and 93%, respectively, and survival was 100%. Three patients required further debulking surgery for progressive disease. Hypopituitarism was the most commonly reported late complication, with a new hormone pituitary deficit occurring in 10 (19%) of patients. Clinically significant late neurological toxicity was observed in 3 (5.5%) patients consisting of worsening of pre-existing cranial deficits.ConclusionFSRT as a high-precision technique of localized RT is suitable for the treatment of large skull base meningiomas. The local control is comparable to that reported following conventional external beam RT. Longer follow-up is required to assess long term efficacy and toxicity, particularly in terms of potential reduction of treatment-related late toxicity.

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA phasic receptors

A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease.

Gangliogliomas of the cerebral hemispheres. Report of 14 cases with long-term follow-up and review of the literature

SummaryThis retrospective study focuses on 14 patients with ganglioglioma of the cerebral hemispheres who received surgical treatment in the Neurosciences Department/Neurosurgery of “La Sapienza” University of Rome between 1953 and 1990. The data are analyzed together with those on 98 published cases of ganglioglioma confined to the cerebral hemispheres. These tumours have no sex preference but a decided preference for the young (mean age 18 years). They are characterized by a history of epilepsy often of long standing and sometimes refractory to drugs. The most frequent site is the temporal lobe (61%). At operation the tumour proved to be solid in 52% of cases and the satellite cyst at the tumour wall in 48%. Removal was total in 65% of cases. Even after subtotal removal, the prognosis is good in terms both of survival and of seizure control. Radiotherapy seems to have no role in the treatment of these tumours.