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massimo cossu

massimo.cossu@ospedaleniguarda.it

Journal articles

2008
 
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Cossu, Chabardès, Hoffmann, Lo Russo (2008)  Presurgical evaluation of intractable epilepsy using stereo-electro-encephalography methodology: Principles, technique and morbidity.   Neurochirurgie 54: 3. 367-373 May  
Abstract: In the stereo-electro-encephalography (SEEG) methodology developed by Talairach and Bancaud in Sainte-Anne Hospital in Paris, France, the objective of placing depth electrode recordings in presurgical evaluation is to study the spatial and temporal organization of a seizure. This defines for each patient the cortical onset zone, the propagation pattern of the seizure, and the possible involvement of eloquent areas of the cortex. This methodology requires a meticulous stereotactic surgical technique. We report here the SEEG methodology, surgical technique, and morbidity.
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Massimo Cossu, Giorgio Lo Russo, Stefano Francione, Roberto Mai, Lino Nobili, Ivana Sartori, Laura Tassi, Alberto Citterio, Nadia Colombo, Manuela Bramerio, Carlo Galli, Laura Castana, Francesco Cardinale (2008)  Epilepsy surgery in children: results and predictors of outcome on seizures.   Epilepsia 49: 1. 65-72 Jan  
Abstract: PURPOSE: To retrospectively analyze the results on seizures of surgery in children with drug-resistant focal epilepsy. To identify the factors predicting seizure control among several presurgical, surgical, and postsurgical variables. METHODS: One hundred thirteen patients (67 male, 46 female), younger than 16 years, operated on from 1996 to 2004 and followed-up for at least 2 years were identified. Individualized microsurgical resections, aimed at removal of the epileptogenic zone, were performed according to the results of tailored presurgical evaluations, which included stereo-electroencephalographic recording with intracerebral electrodes when needed. Risk of seizure recurrence was assessed for the considered variables by bivariate and multivariate analysis. RESULTS: Mean age at surgery was 8.8 years, mean duration of epilepsy was 5.7 years, and mean age at seizure onset was 3.1 years. One hundred eight patients (96%) had an abnormal magnetic resonance imaging. At postoperative follow-up (mean duration 55.1 month), 77 patients (68%) were in Engel's class I, with 68 patients (60%) being seizure free (Engel's classes Ia and Ic). At multivariate analysis, variables associated with a significantly lower risk of seizure recurrence were unifocal lesion at MRI and older age at seizure onset (presurgical variables), temporal unilobar resection and complete lesionectomy (surgical variables), diagnosis of glial-neuronal tumors (postsurgical variables). CONCLUSIONS: Surgery is a valuable option for children with drug-resistant focal epilepsies which may provide excellent results in a considerable amount of cases. Since results of surgery for epilepsy strongly depend on the presurgical identification of the Epileptogenic Zone, future work should be focused on refinement and implementation of diagnostic strategies.
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Michele Terzaghi, Ivana Sartori, Roberto Mai, Laura Tassi, Stefano Francione, Francesco Cardinale, Laura Castana, Massimo Cossu, Giorgio LoRusso, Raffaele Manni, Lino Nobili (2008)  Coupling of minor motor events and epileptiform discharges with arousal fluctuations in NFLE.   Epilepsia 49: 4. 670-676 Apr  
Abstract: PURPOSE: We recently demonstrated that in nocturnal frontal lobe epilepsy (NFLE) highly stereotyped minor motor events (MMEs, in the form of short-lasting stereotyped movements involving the limbs, the axial musculature, and/or the head), could occur in either the presence or absence of an epileptiform discharge (ED). In lack of a systematic analysis, both MMEs and EDs were frequently observed to occur in association with arousal fluctuations. Hereby, in the same group of refractory NFLE subjects, we report a methodical neurophysiolgical investigation set out to investigate whether, and how, the arousal mechanism, monitored through visual scoring of the cyclic alternating pattern, modulates the expression of MMEs and EDs. METHODS: The relationship of MMEs, EDs and arousal fluctuation was assessed in subjects explored using implanted electrodes. RESULTS: The occurrence of both EDs and MMEs was associated with higher level of arousal (p < 0.0001). Multivariate logistic regression analysis shows a significant effect of interaction of EDs and MMEs during CAP sleep (p < 0.001). CONCLUSIONS: Both MMEs and EDs are associated with arousal. We suggest that recurrence of EDs in itself can induce an increase in arousal level, which in turn, through a gate effect, facilitate the occurrence of MMEs. Thus, MMEs wouldn't be a direct effect of EDs, but rather originate from an indirect effect related to loss of cortical inhibition, which is secondary to arousal. In this perspective MMEs may be regarded as the result of aspecific dishinibition, triggered by internal epileptiform stimuli, of innate motor patterns generated by central pattern generators (CPGs). The CPG system might represent, through arousal facilitation, the substrate of the heterogeneous expression of MMEs in NFLE.
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2007
 
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L Nobili, S Francione, R Mai, F Cardinale, L Castana, L Tassi, I Sartori, G Didato, A Citterio, N Colombo, C Galli, G Lo Russo, M Cossu (2007)  Surgical treatment of drug-resistant nocturnal frontal lobe epilepsy.   Brain 130: Pt 2. 561-573 Feb  
Abstract: Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.
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Christian R Baumann, Nicola Acciarri, Helmut Bertalanffy, Orrin Devinsky, Christian E Elger, Giorgio Lo Russo, Massimo Cossu, Uli Sure, Anuradha Singh, Hermann Stefan, Tilo Hammen, Dimitrios Georgiadis, Ralf W Baumgartner, Frederick Andermann, Adrian M Siegel (2007)  Seizure outcome after resection of supratentorial cavernous malformations: a study of 168 patients.   Epilepsia 48: 3. 559-563 Mar  
Abstract: PURPOSE: The optimal management of cerebral cavernous malformations (CCMs) with epileptic seizures is still a matter of debate. The aim of our study was to examine seizure outcome in the largest published series of surgically treated patients with epilepsy due to a supratentorial CCM, and to define predictors for good surgical outcome. METHODS: We retrospectively studied 168 consecutive patients with a single supratentorial CCM and symptomatic epilepsy in a multicenter study. Pre- and postoperative clinical examinations, age at epilepsy onset, age at operation, type of symptoms due to the CCM (seizures, headache, hemorrhage, focal deficits), type and frequency of epileptic seizures, and the localization and size of the CCM were assessed. Seizure outcome was determined in the first, second, and third postoperative years. RESULTS: The CCM was completely resected in all patients. More than two thirds of the patients were classified as seizure free in the first 3 postoperative years. Predictors for good seizure outcome were age older than 30 years at the time of surgery, mesiotemporal CCM localization, CCM size <1.5 cm, and the absence of secondarily generalized seizures. No mortality occurred in our series, but only mild postoperative neurologic deficits in 12 (7%) patients. CONCLUSIONS: Considering the natural history of CCMs, the favorable neurologic and seizure outcome, surgical resection of CCMs should be considered in all patients with supratentorial CCMs and concomitant epilepsy, irrespective of the presence or absence of predictors for a favorable seizure outcome.
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Michele Terzaghi, Ivana Sartori, Roberto Mai, Laura Tassi, Stefano Francione, Francesco Cardinale, Laura Castana, Massimo Cossu, Giorgio LoRusso, Raffaele Manni, Lino Nobili (2007)  Sleep-related minor motor events in nocturnal frontal lobe epilepsy.   Epilepsia 48: 2. 335-341 Feb  
Abstract: PURPOSE: Nocturnal frontal lobe epilepsy (NFLE) is characterized by a wide spectrum of sleep-related motor manifestations of increasing complexity, ranging from major episodes to brief motor events (minor motor events, MMEs). NFLE patients may exhibit a large quantity of MMEs in the form of short-lasting stereotyped movements. Whereas major episodes are considered epileptiform manifestations, it remains unclear whether the MMEs are related to epileptiform discharges (EDs). METHODS: To study the relation between EDs and the occurrence of MMEs, we report a detailed neurophysiolgical evaluation in NFLE subjects explored by using implanted electrodes. RESULTS: The median value of ED-related movements was 71.8%. Motor expression in relation to epileptiform discharge was surprisingly variable; no peculiar expression of MMEs could be attributed to the presence of EDs. CONCLUSIONS: Our data suggest that ED-associated MMEs are extremely polymorphous, and no univocal relation to EDs can be identified. We hypothesize that MMEs are not a direct effect of epileptiform discharge (i.e., not epileptic in origin), but the result of aspecific disinhibition of innate motor patterns. We warn clinicians that the epileptic nature of minimal motor phenomena in NFLE cannot be established on the clinical phenomenology of the event.
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Fabio Moroni, Lino Nobili, Giuseppe Curcio, Fabrizio De Carli, Fabiana Fratello, Cristina Marzano, Luigi De Gennaro, Franco Ferrillo, Massimo Cossu, Stefano Francione, Giorgio Lo Russo, Mario Bertini, Michele Ferrara (2007)  Sleep in the human hippocampus: a stereo-EEG study.   PLoS ONE 2: 9. 09  
Abstract: BACKGROUND: There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. CONCLUSIONS/SIGNIFICANCE: Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonance may have a supportive role for the processing/consolidation of memory.
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2006
 
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Christian R Baumann, Bernhard Schuknecht, Giorgio Lo Russo, Massimo Cossu, Alberto Citterio, Frederick Andermann, Adrian M Siegel (2006)  Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed.   Epilepsia 47: 3. 563-566 Mar  
Abstract: PURPOSE: Considering the epileptogenic effect of cavernoma-surrounding hemosiderin, assumptions are made that resection only of the cavernoma itself may not be sufficient as treatment of symptomatic epilepsy in patients with cavernous malformations. The purpose of this study was to test the hypothesis whether seizure outcome after removal of cavernous malformations may be related to the extent of resection of surrounding hemosiderin-stained brain tissue. METHODS: In this retrospective study, 31 consecutive patients with pharmacotherapy-refractory epilepsy due to a cavernous malformation were included. In all patients, cavernomas were resected, and all patients underwent pre- and postoperative magnetic resonance imaging (MRI). We grouped patients according to MRI findings (hemosiderin completely removed versus not/partially removed) and compared seizure outcome (as assessed by the Engel Outcome Classification score) between the two groups. RESULTS: Three years after resection of cavernomas, patients in whom hemosiderin-stained brain tissue had been removed completely had a better chance for a favorable long-term seizure outcome compared with those with detectable postoperative hemosiderin (p=0.037). CONCLUSIONS: Our study suggests that complete removal of cavernoma-surrounding hemosiderin-stained brain tissue may improve epileptic outcome after resection of cavernous malformations.
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Adele Finardi, Fabrizio Gardoni, Stefania Bassanini, Giovanni Lasio, Massimo Cossu, Laura Tassi, Claudio Caccia, Franco Taroni, Giorgio LoRusso, Monica Di Luca, Giorgio Battaglia (2006)  NMDA receptor composition differs among anatomically diverse malformations of cortical development.   J Neuropathol Exp Neurol 65: 9. 883-893 Sep  
Abstract: Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.
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Lino Nobili, Ivana Sartori, Michele Terzaghi, Francione Stefano, Roberto Mai, Laura Tassi, Liborio Parrino, Massimo Cossu, Giorgio Lo Russo (2006)  Relationship of epileptic discharges to arousal instability and periodic leg movements in a case of nocturnal frontal lobe epilepsy: a stereo-EEG study.   Sleep 29: 5. 701-704 May  
Abstract: We describe the case of a patient with nocturnal frontal lobe epilepsy, presenting with periodic leg movements during sleep and complaining of excessive daytime sleepiness. With the support of intracerebral electroencephalogram recordings and the corroboration of the postoperative outcome, periodic leg movements during sleep and excessive daytime sleepiness appeared to be associated to enhanced arousal instability induced by by recurrent epileptic discharges not detectable on scalp electroencephalogram.
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M Cossu, F Cardinale, L Castana, L Nobili, I Sartori, G Lo Russo (2006)  Stereo-EEG in children.   Childs Nerv Syst 22: 8. 766-778 Aug  
Abstract: BACKGROUND: Stereotactic placement of intracerebral multilead electrodes for chronic EEG recording of seizures or stereoelectroencephalography (SEEG) was introduced 50 years ago at Saint Anne Hospital in Paris, France for the presurgical evaluation of patients with drug-resistant focal epilepsy. SEEG explorations are indicated whenever the noninvasive tests fail to adequately localize the epileptogenic zone (EZ). INDICATIONS: Currently, approximately 35% of our operated-on children require a SEEG evaluation. Arrangement of electrodes is individualized according to the peculiar needs of each child, to verify a predetermined hypothesis of localization of the EZ based on pre-SEEG anatomo-electro-clinical findings. Multilead intracerebral electrodes are designed to sample cortical structures on the lateral, intermediate, and mesial aspect of the hemisphere, as well as deep-seated lesions. Stereotactic stereoscopic teleangiograms and coregistered 3-D MRI are employed to plan avascular trajectories and to accurately target the desired structures. Pre-SEEG stereotactic neuroradiology and electrode implantation are usually performed in separate procedures. Electrodes are removed once video-SEEG monitoring is completed. INTRACEREBRAL ELECTRICAL STIMULATIONS: Intracerebral electrical stimulations are used to better define the EZ and to obtain a detailed functional mapping of critical cortical and subcortical regions. MORBIDITY: Surgical morbidity of SEEG is definitely low in children. SEEG-GUIDED RESECTIVE SURGERY: In 90% of evaluated children, SEEG provides a guide for extratemporal or multilobar resections. SEEG-guided resective surgery may yield excellent results on seizures with 60% of patients in Engel's Class I.
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2005
 
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A M Siegel, G D Cascino, C E Elger, O Devinsky, R Laff, S Najjar, M R Sperling, G LoRusso, M Cossu, H Urbach, E Aronica, F B Meyer, B W Scheithauer, F Dubeau, F Andermann (2005)  Adult-onset epilepsy in focal cortical dysplasia of Taylor type.   Neurology 64: 10. 1771-1774 May  
Abstract: Focal cortical dysplasia of Taylor type (FCDT) usually presents with seizures at an early age, whereas adult onset of epilepsy is uncommon. We reviewed the medical records of 213 patients with FCDT. In 21 patients (10%), age at seizure onset ranged from 18 to 55 years (mean 25.3). The outcome of seizures in patients with FCDT and adult-onset epilepsy seems favorable vs childhood-onset seizures.
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L Tassi, N Colombo, M Cossu, R Mai, S Francione, G Lo Russo, C Galli, M Bramerio, G Battaglia, R Garbelli, A Meroni, R Spreafico (2005)  Electroclinical, MRI and neuropathological study of 10 patients with nodular heterotopia, with surgical outcomes.   Brain 128: Pt 2. 321-337 Feb  
Abstract: We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.
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Massimo Cossu, Francesco Cardinale, Laura Castana, Alberto Citterio, Stefano Francione, Laura Tassi, Alim L Benabid, Giorgio Lo Russo (2005)  Stereoelectroencephalography in the presurgical evaluation of focal epilepsy: a retrospective analysis of 215 procedures.   Neurosurgery 57: 4. 706-18; discussion 706-18 Oct  
Abstract: OBJECTIVE: To report on indications, surgical technique, results, and morbidity of stereoelectroencephalography (SEEG) in the presurgical evaluation of patients with drug-resistant focal epilepsy. METHODS: Two-hundred fifteen stereotactic implantations of multilead intracerebral electrodes were performed in 211 patients (4 patients were explored twice), who showed variable patterns of localizing incoherence among electrical (interictal/ictal scalp electroencephalography), clinical (ictal semeiology), and anatomic (magnetic resonance imaging [MRI]) investigations. MRI scanning showed a lesion in 134 patients (63%; associated with mesial temporal sclerosis in 7) and no lesion in 77 patients (37%; with mesial temporal sclerosis in 14 patients). A total of 2666 electrodes (mean, 12.4 per patient) were implanted (unilaterally in 175 procedures and bilaterally in 40). For electrode targeting, stereotactic stereoscopic cerebral angiograms were used in all patients, coupled with a coregistered three-dimensional MRI scan in 108 patients. RESULTS: One hundred eighty-three patients (87%) were scheduled for resective surgery after SEEG recording, and 174 have undergone surgery thus far. Resections sites were temporal in 47 patients (27%), frontal in 55 patients (31.6%), parietal in 14 patients (8%), occipital in one patient (0.6%), rolandic in one patient (0.6%), and multilobar in 56 patients (32.2%). Outcome on seizures (Engel's classification) in 165 patients with a follow-up period of more than 12 months was: Class I, 56.4%; Class II, 15.1%; Class III, 10.9%; and Class IV, 17.6%. Outcome was significantly associated with the results of MRI scanning (P = 0.0001) and with completeness of lesion removal (P = 0.038). Morbidity related to electrode implantation occurred in 12 procedures (5.6%), with severe permanent deficits from intracerebral hemorrhage in 2 (1%) patients. CONCLUSION: SEEG is a useful and relatively safe tool in the evaluation of surgical candidates when noninvasive investigations fail to localize the epileptogenic zone. SEEG-based resective surgery may provide excellent results in particularly complex drug-resistant epilepsies.
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Marco Curtis, Laura Tassi, Giorgio Lo Russo, Roberto Mai, Massimo Cossu, Stefano Francione (2005)  Increased discharge threshold after an interictal spike in human focal epilepsy.   Eur J Neurosci 22: 11. 2971-2976 Dec  
Abstract: It is commonly assumed that interictal spikes (ISs) in focal epilepsies set off a period of inhibition that transiently reduces tissue excitability. Post-spike inhibition was described in experimental models but was never demonstrated in the human epileptic cortex. In the present study post-spike excitability was retrospectively evaluated on intracerebral stereo-electroencephalographic recordings performed in the epileptogenic cortex of five patients suffering from drug-resistant focal epilepsy secondary to Taylor-type neocortical dysplasias. Patients typically presented with highly periodic interictal spiking activity at 2.33 +/- 0.87 Hz (mean +/- SD) in the dysplastic region. During the stereo-electroencephalographic procedure, low-frequency stimulation at 1 Hz was systematically performed for diagnostic purposes to identify the epileptogenic zone. The probability of evoking an IS during the interspike period in response to 1-Hz stimuli delivered close to the ictal-onset zone was examined. Stimuli that occurred early after a spontaneous IS (within 70% of the inter-IS period) had a very low probability of generating a further IS. On the contrary, stimuli delivered during the late inter-IS period had the highest probability of evoking a further IS. The generation of stimulus-evoked ISs is occluded for several hundred milliseconds after the occurrence of a preceding spike discharge. As previously shown in animal models, these findings suggest that, during focal, periodic interictal spiking, human neocortical excitability is phasically controlled by post-spike inhibition.
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Massimo Cossu, Francesco Cardinale, Nadia Colombo, Roberto Mai, Lino Nobili, Ivana Sartori, Giorgio Lo Russo (2005)  Stereoelectroencephalography in the presurgical evaluation of children with drug-resistant focal epilepsy.   J Neurosurg 103: 4 Suppl. 333-343 Oct  
Abstract: OBJECT: The authors report on indications for, techniques of, and results of stereoelectroencephalography (stereo-EEG) monitoring in the presurgical evaluation of childhood drug-resistant focal epilepsy. METHODS: Thirty-five children (24 boys and 11 girls; mean age 8.8 +/- 3.9 years; mean age at seizure onset 2.1 +/- 2.2 years) underwent 37 tailored stereotactic placements of intracerebral, multilead electrodes for intensive monitoring of seizures (stereo-EEG). Two children underwent exploration twice. Investigations prior to stereo-EEG monitoring, including magnetic resonance imaging and video-EEG of the scalp, revealed variable patterns of localizing incoherence among clinical, electrophysiological, and anatomical findings in all cases. A total of 426 electrodes were implanted (mean 11.5 +/- 2.6 per procedure) according to individualized arrangements. The stereo-EEG monitoring enabled recording of 826 seizures (mean 22 +/- 45 per procedure) and mapping of critically functional areas. One untoward event consisted of intracranial breakage of an electrode. Resections of the epileptogenic zone were performed according to results of stereo-EEG recordings. They consisted of cortical removal in seven cases, removal of the lesion and epileptogenic cortex in 26 cases, and lesion removal in two cases. Transient postoperative neurological deficits were observed in 13 patients, and permanent anticipated visual field defects occurred in seven patients. According to the Engel postoperative classification of seizure outcome, 60% of cases were in Class I, 74% had significant improvement (Classes I-III), and 26% were unchanged (mean follow up 31.9 +/- 20.6 months). CONCLUSIONS: Stereoelectroencephalography monitoring is a helpful and well-tolerated technique for the definition of the epileptogenic zone in complex cases of childhood drug-resistant epilepsy. It provides essential information for safe resections that should result in excellent outcomes in a considerable number of patients.
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L Nobili, I Sartori, M Terzaghi, L Tassi, R Mai, S Francione, M Cossu, F Cardinale, L Castana, G Lo Russo (2005)  Intracerebral recordings of minor motor events, paroxysmal arousals and major seizures in nocturnal frontal lobe epilepsy.   Neurol Sci 26 Suppl 3: s215-s219 Dec  
Abstract: The clinical features of nocturnal frontal lobe epilepsy (NFLE) consist of a spectrum of paroxysmal motor manifestations ranging from minor motor events (MMEs) to paroxysmal arousals (PAs) and major seizures. During MMEs and PAs scalp EEG generally does not show definite ictal abnormalities. We describe the clinical and electrophysiological features of three patients affected by drug-resistant NFLE studied with intracerebral electrodes during a presurgical evaluation. The stereo-EEG (SEEG) investigation revealed that MMEs can be fragments of the major seizure and occur during a brief epileptic discharge or on the following arousal. PAs, in the same subject, do not show a definite stereotypy despite the morphological and topographic similarity of the epileptic discharges, thus indicating that other variables may influence the clinical features of PAs.
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R Mai, I Sartori, S Francione, L Tassi, L Castana, F Cardinale, M Cossu, A Citterio, N Colombo, G Lo Russo, L Nobili (2005)  Sleep-related hyperkinetic seizures: always a frontal onset?   Neurol Sci 26 Suppl 3: s220-s224 Dec  
Abstract: Hyperkinetic seizures are considered a typical manifestation of nocturnal frontal lobe epilepsy (NFLE). Patients with temporal lobe epilepsy with mainly sleep-related seizures have been described; however they commonly lack hyperkinetic activity and seizure frequency is low. We retrospectively analysed our population of 442 consecutive patients surgically treated between January 1996 and January 2004. Among these there were 25 patients with sleep-related hyperkinetic epileptic seizures, with a frontal lobe onset in 18 cases and a temporal lobe onset in 7. Patients with sleep-related hyperkinetic seizures with temporal lobe origin had anamnestic and clinical features strikingly similar to those with a frontal onset, with agitated movements, high seizure frequency and no history of febrile convulsions. We confirm our previous findings that this kind of epileptic manifestation is not only peculiar to frontal lobe epilepsy.
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2004
 
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L Nobili, M Cossu, R Mai, L Tassi, F Cardinale, L Castana, A Citterio, I Sartori, G Lo Russo, S Francione (2004)  Sleep-related hyperkinetic seizures of temporal lobe origin.   Neurology 62: 3. 482-485 Feb  
Abstract: Sleep-related hyperkinetic seizures are a common feature of nocturnal frontal lobe epilepsy. Although sleep-related seizures with a temporal lobe origin have been reported, they commonly lack hyperkinetic activity. The authors describe three patients with sleep-related seizures characterized by frenetic, agitated, hyperactive movements (bimanual/bipedal activity, rocking, axial, pelvic, and hemiballistic movements), in whom stereo-EEG investigation and surgical outcome demonstrated a temporal lobe origin of the attacks.
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2003
 
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R Mai, L Tassi, M Cossu, S Francione, G Lo Russo, R Garbelli, A Ferrario, C Galli, F Taroni, A Citterio, R Spreafico (2003)  A neuropathological, stereo-EEG, and MRI study of subcortical band heterotopia.   Neurology 60: 11. 1834-1838 Jun  
Abstract: The authors performed an MRI, stereo-EEG, and pathology study on a woman with subcortical band heterotopia and partial epilepsy. Clinical manifestations of seizures always started when ictal discharges were present in outer and heterotopic cortices. Simultaneous activation of both cortices and presence of differentiated neurons in the white matter and the heterotopia strongly suggest that the cortices were anatomically and functionally interconnected.
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Giorgio Lo Russo, Laura Tassi, Massimo Cossu, Francesca Cardinale, Roberto Mai, Laura Castana, Nadia Colombo, Manuela Bramerio (2003)  Focal cortical resection in malformations of cortical development.   Epileptic Disord 5 Suppl 2: S115-S123 Sep  
Abstract: Malformations of cortical development may be associated with drug-resistant partial epilepsy suitable for surgical therapy. From the anatomopathological point of view, this categorisation has been used in reference to a wide range of alterations of the cortical mantle. Focal cortical dysplasias represent the main group of malformations of cortical development, but there are also other types of alterations, such as heterotopias, double cortex or polymicrogyria. Defining candidacy for surgical therapy and tailored resection requires thorough pre-surgical evaluation so that the approach will be individualised for each patient. We present our series of 126 patients with malformation of cortical development selected from 321 consecutively operated patients. Within this group encompassing different types of malformation of cortical development, including periventricular heterotopia (nine patients), polymicrogyria (three patients), hemimegalencephaly (one patient) and subcortical band heterotopia (one patient), the largest group was 81 individuals with focal cortical dysplasia. For this last group, we propose a simplified classification defining 42 architectural dysplasias, 12 cytoarchitectural dysplasias and 27 Taylor's focal cortical dysplasias. In addition, at routine neuropathological investigation, the only morphological alteration shown by 31 patients was diffuse neuronal heterotopia. All patients underwent scalp EEG and video-EEG, and 75 patients (59.5%) also underwent stereo-EEG. Magnetic resonance imaging and stereotactic stereoscopic angiography represented the indispensable premises for further studies, in particular stereo-EEG, and for planning surgery and tailoring resection. Magnetic resonance imaging was unhelpful in 17 out of 81 patients with focal cortical dysplasia and in seven out of 31 with neuronal heterotopia, while signal alterations were present in all other cases. Common characteristics corresponding to clinical-histopathological homogeneous subgroups were found within the focal cortical dysplasia group. In patients with architectural dysplasia, the epileptogenic zone was mainly in the temporal lobe and there was a lower seizure frequency than in patients with Taylor's focal cortical dysplasia. Patients with Taylor's type had an epileptogenic zone that was mainly extra-temporal, and a distinctive interictal stereo-EEG. The best outcome was observed in patients with Taylor's type dysplasia: 69% seizure-free (Engel class Ia) after at least 1 year of follow-up, compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients.
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PMID 
C Deblieck, G Pesenti, P Scifo, F Fazio, E Bricolo, G Lo Russo, G Scialfa, M Cossu, G Bottini, E Paulesu (2003)  Preserved functional competence of perilesional areas in drug-resistant epilepsy with lesion in supplementary motor cortex: fMRI and neuropsychological observations.   Neuroimage 20: 4. 2225-2234 Dec  
Abstract: We report a presurgical fMRI study and a longitudinal behavioral and structural MRI study in a 26-year-old right-handed woman with drug-resistant epilepsy of the supplementary motor region with cytoarchitectural dysplasia and minimal cortico-subcortical gliotic damage. fMRI scans were acquired during a silent phonemic verbal fluency task (VF), an automatic counting task (CT), and a finger-tapping motor task (MT). These were all compared with rest. Presurgical neuropsychological assessment was substantially normal with only a minor deficit in the domain of visuo-constructive and complex motor-planning skills. Noticeably, performance on phonemic verbal fluency was normal. Presurgical fMRI results revealed a normal specialization of left SMA and pre-SMA, including a fine-grained somatotopy for mouth and hand representations despite epilepsy. Immediately after surgical removal of the epileptogenic zone (the posterior third of the superior and middle frontal gyri including pre-SMA and part of SMA, and part of the anterior cingulate region--all of which were active presurgically at the fMRI tests), the patient suffered from transcortical motor aphasia temporarily. One year after surgery, she still showed impaired performance in the verbal fluency tasks while naming and comprehension were recovered. The patient was now free from seizures. This fMRI study supports the case that repeated seizures per se may not be sufficient to alter the distribution of neural representations of cognitive function. Selective behavioral impairment after surgical removal of brain areas that were activated during presurgical fMRI permits us to establish a causal link between these activations and task performance. This link could not have been made on the basis of activation patterns or lesion data taken on their own. These findings support the case that some epileptic patients may represent a unique opportunity for cognitive neuroscience studies.
Notes:
 
PMID 
Lino Nobili, Stefano Francione, Roberto Mai, Laura Tassi, Francesco Cardinale, Laura Castana, Ivana Sartori, Giorgio Lo Russo, Massimo Cossu (2003)  Nocturnal frontal lobe epilepsy: intracerebral recordings of paroxysmal motor attacks with increasing complexity.   Sleep 26: 7. 883-886 Nov  
Abstract: PURPOSES: To show the results of the investigation conducted with intracerebral electrodes in a patient with drug-resistant nocturnal frontal lobe epilepsy, characterized by sleep-related paroxysmal motor attacks of increasing complexity ranging from simple and brief stereotyped motor events to paroxysmal arousals and major attacks. METHODS: The patient was studied with long-term video-stereo-electroencephalographic monitoring by means of stereotactically implanted intracerebral electrodes. RESULTS: Video-stereo-electroencephalography demonstrated that minor events and paroxysmal arousals, as well as major attacks, were correlated with a discharge in the right supplementary motor area and central cingulate gyms. The increasing complexity of these sleep-related ictal motor behaviors reflected a different pattern of discharge, with a progressive spread to other frontal and extrafrontal areas in the fully developed attacks. Surgical resection of the right supplementary motor area and central cingulate gyrus was performed. In the 5 years since the operation, the patient has remained completely seizure free. CONCLUSION: This study clearly demonstrates the ictal origin of minor events in nocturnal frontal lobe epilepsy. The increasing complexity of the motor behaviors from minor to major attacks reflects different duration, amplitude, and spread of the epileptic discharge.
Notes:
2002
 
PMID 
L Tassi, N Colombo, R Garbelli, S Francione, G Lo Russo, R Mai, F Cardinale, M Cossu, A Ferrario, C Galli, M Bramerio, A Citterio, R Spreafico (2002)  Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome.   Brain 125: Pt 8. 1719-1732 Aug  
Abstract: Since the original description by Taylor, the term focal cortical dysplasia has been used to refer to a wide range of alterations of the cortical mantle. More recently, these conditions have been described from neuroimaging, neuropathological and genetic standpoints, generating several classifications. It is widely recognized that these classifications are unsatisfactory. We propose a simplified classification of focal cortical dysplasias based on easily recognized neuropathological characteristics. We retrospectively re-examined histological sections of cortex from 52 of 224 (23%) patients operated on for drug-resistant partial epilepsy in which cortical dysplasia was present but not associated with other brain pathologies except hippocampal sclerosis. Three subgroups were identified: (i) architectural dysplasia (31 patients) characterized by abnormal cortical lamination and ectopic neurones in white matter; (ii) cytoarchitectural dysplasia (six patients) characterized by giant neurofilament-enriched neurones in addition to altered cortical lamination; and (iii) Taylor-type cortical dysplasia (15 patients) with giant dysmorphic neurones and balloon cells (all but two patients) associated with cortical laminar disruption. The patients with architectural dysplasia had lower seizure frequency than those with cytoarchitectural and Taylor-type dysplasia, and the epileptogenic zone was mainly in the temporal lobe. In patients with Taylor-type dysplasia, the epileptogenic zone was mainly extratemporal, and interictal stereo-EEG was distinctive. MRI was unrevealing in 34% of patients, but distinctive signal alterations characterized most patients with Taylor-type dysplasia, while focal hypoplasia with MRI abnormalities was found in architectural dysplasia. Patients with Taylor-type dysplasia had the best outcome, with 75% seizure-free (Engel class Ia) after at least a year of follow-up compared with 50% of cytoarchitectural dysplasia and 43% of architectural dysplasia patients seizure-free. This three-category classification is based on easily recognized histopathological characteristics and avoids complicated terminology, while the distinctive ensemble of other characteristics defines clinically homogeneous groups.
Notes:
2000
 
PMID 
F Ferrillo, M Beelke, F De Carli, M Cossu, C Munari, G Rosadini, L Nobili (2000)  Sleep-EEG modulation of interictal epileptiform discharges in adult partial epilepsy: a spectral analysis study.   Clin Neurophysiol 111: 5. 916-923 May  
Abstract: INTRODUCTION: In order to define accurately the relationship between EEG components (spindles, delta and theta frequencies) and the occurrence of interictal epileptiform discharges (IED) during sleep in partial epilepsy, a correlation study between spike overnight distribution and EEG spectral power time series was performed. METHODS: Eighteen patients (mean age: 24.7+/-5.5 years) affected by partial epilepsy underwent continuous EEG-polysomnography. The temporal series of Slow Wave Activity (SWA), Sigma Activity (SA) and Theta Band (TB), derived from spectral analysis, were obtained from a spike-free and pathologic alteration-free derivation, contralateral to the most active lead, where the IED count was performed. Relationships between SA, SWA and TB and time series of IED were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IED and SWA in 12 subjects; a significantly higher correlation between IED and SA in three subjects and a significant correlation with TB in three cases. CONCLUSIONS: Data suggest that in most adult patients with partial epilepsy IED production during sleep is facilitated by the action of synchronizing mechanisms which are active during NREM sleep and lead to the appearance of EEG delta waves. Nevertheless evidence is given of two smaller groups of patients. In one of them IED are more sensitive to the promoting action of the spindle generating mechanism, active during stage 2 of NREM sleep. In the other one the promoting action of TB, characterizing EEG during stage 1 and REM sleep, is evident.
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DOI   
PMID 
G Bonanno, R Sala, L Cancedda, P Cavazzani, M Cossu, M Raiteri (2000)  Release of dopamine from human neocortex nerve terminals evoked by different stimuli involving extra- and intraterminal calcium.   Br J Pharmacol 129: 8. 1780-1786 Apr  
Abstract: The release of [(3)H]-dopamine ([(3)H]-DA) from human neocortex nerve terminals was studied in synaptosomes prepared from brain specimens removed in neurosurgery and exposed during superfusion to different releasing stimuli. Treatment with 15 mM KCl, 100 microM 4-aminopyridine, 1 microM ionomycin or 30 mM caffeine elicited almost identical overflows of tritium. Removal of external Ca(2+) ions abolished the overflow evoked by K(+) or ionomycin and largely prevented that caused by 4-aminopyridine; the overflow evoked by caffeine was completely independent of external Ca(2+). Exposure of synaptosomes to 25 microM of the broad spectrum calcium channel blocker CdCl(2) strongly inhibited the 4-aminopyridine-induced tritium overflow while that evoked by ionomycin remained unaffected. The Ca(2+) chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N' tetraacetic acid (BAPTA), reduced significantly the K(+)- and the caffeine-induced tritium overflow. The effect of caffeine was attenuated by exposure to the ryanodine receptor blocker dantrolene or when the membrane-impermeant inositol trisphosphate receptor antagonist, heparin, was entrapped into synaptosomes; the combined treatment with dantrolene and heparin abolished the release elicited by caffeine. Tetanus toxin, entrapped into human neocortex synaptosomes to avoid prolonged incubation, inhibited in a concentration-dependent manner the K(+)- or the 4-aminopyridine-evoked tritium overflow; in contrast, the release stimulated by ionomycin and by caffeine were both totally insensitive to the same concentrations of tetanus toxin. Western blot analysis showed about 50% reduction of the content of the vesicular protein, synaptobrevin, in synaptosomes poisoned with tetanus toxin. In conclusion, the release of dopamine from human neocortex nerve terminals can be triggered by Ca(2+) ions originating from various sources. It seems that stimuli not leading to activation of voltage-sensitive Ca(2+) channels elicit Ca(2+)-dependent, probably exocytotic, release that is insensitive to tetanus toxin.
Notes:
1999
 
PMID 
E Fedele, G Fontana, C Munari, M Cossu, M Raiteri (1999)  Native human neocortex release-regulating dopamine D2 type autoreceptors are dopamine D2 subtype.   Eur J Neurosci 11: 7. 2351-2358 Jul  
Abstract: Dopamine (DA) autoreceptors expressed at DA nerve terminals regulate DA release. Considerable evidence has indicated that, in rodents, these autoreceptors belong to the D2 type of the DA receptor family, which, in turn, comprises the D2, D3 and D4 subtypes. We investigated here, for the first time, the subclassification of native human DA autoreceptors by studying the release of [3H]DA evoked by electrical stimulation in fresh human neocortical slices. The results have been compared with those obtained in three animal systems: rat neocortical and striatal slices and rat mesencephalic neuronal cultures. In human neocortical slices, the D2/D3 receptor agonist quinpirole (1 nM-10 microM) inhibited tritium release with a calculated EC50 of 17 nM and a maximal inhibition of approximately 75% reached at 1 microM. In the presence of the D2/D3 receptor antagonist (-)-sulpiride (0.1 and 1 microM), the concentration-response curve of quinpirole was shifted to the right, and the apparent pA2 mean value was 8.5 (8.14-8.77); on the other hand, the inhibitory effects of quinpirole were not affected by the D3 receptor-selective antagonist [7-N,N-dipropylamino-5,6,7, 8-tetrahydro-naphtho(2,3b) dihydro,2,3-furane] (S 14297) and the D4 receptor-selective antagonist 3-(4-[4-chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2,3-b]pyridine (L-745,870) (0.01-1 microM in each case). Superimposable results have been obtained when the release was elicited from rat striatal slices or dopamine mesencephalic neurons in culture, whereas quantitative differences emerged in the case of rat cortical slices. It is concluded that in human brain, as well as in rat brain, the release of DA in the terminal region of midbrain dopaminergic neurons is regulated through autoreceptors of the D2 subtype.
Notes:
 
PMID 
M Cossu, S Gennaro, A Rossi, M A Balestrero, F Cella, G L Viale (1999)  Autoregulation of cortical blood flow during surgery for ruptured intracranial aneurysms.   J Neurosurg Sci 43: 2. 99-105; discussion 105 Jun  
Abstract: BACKGROUND: Little information is available about the extent and the time course of possible impairment of cerebral circulation occurring after aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to correlate cerebral autoregulation, neurological impairment at surgery and timing of surgery in patients with ruptured intracerebral aneurysms. METHODS: Cortical blood flow (CoBF) was measured intraoperatively by a thermal diffusion probe in 77 patients during surgery for ruptured supratentorial aneurysms, who were operated on at different time intervals after bleeding. An autoregulation index (AI), expressed as the ratio between the change in CoBF and the change of mean arterial blood pressure at the time of rising the systemic blood pressure after occlusion of the aneurysm(s), was determined in each case. RESULTS: Among good-grade patients (WFNS grade I-II), those operated on days 0-2 after SAH had a significantly better autoregulatory response, compared either with patients who underwent surgery on days 3-7 after bleeding (p<0.01), or with those whose aneurysm was occluded more than 7 days after rupture (p<0.03). The mean AI of poor-grade patients (WFNS grade IV-V), who received surgery on days 0-2 after SAH, was significantly higher (p<0.01) compared with the corresponding value of good-grade patients. No significant difference was found between the mean AIs of patients who subsequently did, or did not, develop symptomatic vasospasm. CONCLUSIONS: It is concluded that good-grade patients operated on within 48 hours after bleeding take advantage of a preserved autoregulatory function during controlled hypotension.
Notes:
1998
 
PMID 
F Carta, D Siccardi, M Cossu, C Viola, M Maiello (1998)  Removal of tumours of the orbital apex via a postero-lateral orbitotomy.   J Neurosurg Sci 42: 4. 185-188 Dec  
Abstract: BACKGROUND: The surgical management of pure apical tumours of the orbit may be problematic with traditional approaches. A postero-lateral approach, specifically designed for apical growths, provides a more favourable angle of vision through a relatively small bone opening. METHODS: A series of 103 consecutive cases of intraorbital tumours, operated on in a community-based institution, was retrospectively reviewed. Out of this series, 8 patients, harbouring lesions located in the posterior intraconal space, underwent a postero-lateral orbitotomy. This approach, through a small opening on the orbital and temporal portions of the greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate of the frontal bone, the lateral rim of the orbit being maintained intact, allowed adequate exposure of the orbital apex and successful extirpation of the tumours. In four patients the histological examination disclosed a cavernoma; the other patients had, respectively, a dermoid cyst, a lymphoma, a hemangiopericytoma and a metastatic melanoma. RESULTS: No recurrences were observed in a follow-up period ranging from 1 to 7 years postoperatively (the patient with melanoma died 16 months after operation for systemic complications of her illness). One patient showed transient weakness of lateral rectus muscle due to surgical manipulation, which subsided in few months. CONCLUSIONS: The postero-lateral orbitotomy represents a reliable alternative to other traditional surgical approaches when dealing with tumours of the orbital apex, providing excellent exposure of this region with a low rate of operative morbidity.
Notes:
1997
 
DOI   
PMID 
G Fontana, E Fedele, M Cossu, C Munari, M Raiteri (1997)  Activation of brain nitric oxide synthase in depolarized human temporal cortex slices: differential role of voltage-sensitive calcium channels.   Br J Pharmacol 122: 5. 930-934 Nov  
Abstract: 1. Nitric oxide (NO) synthase activity was studied in slices of human temporal cortex samples obtained in neurosurgery by measuring the conversion of L-[3H]-arginine to L-[3H]-citrulline. 2. Elevation of extracellular K+ to 20, 35 or 60 mM concentration-dependently augmented L-[3H]-citrulline production. The response to 35 mM KCl was abolished by N(G)-nitro-L-arginine (100 microM) demonstrating NO synthase specific conversion of L-arginine to L-citrulline. Increasing extracellular MgCl2 concentration up to 10 mM also prevented the K+ (35 mM)-induced NO synthase activation, suggesting the absolute requirement of external calcium ions for enzyme activity. 3. However, the effect of high K+ (35 mM) on citrulline synthesis was insensitive to the antagonists of ionotropic and metabotropic glutamate receptors dizocilpine (MK-801), 6-nitro-7-sulphamoylbenzo(f)-quinoxaline-2-3-dione (NBQX) or L-2-amino-3-phosphonopropionic acid (L-AP3) as well as to the nicotinic receptor antagonist, mecamylamine. 4. The 35 mM K+ response was insensitive to omega-conotoxin GVIA (1 microM) and nifedipine (100 microM), but could be prevented in part by omega-agatoxin IVA (0.1 and 1 microM). The inhibition caused by 0.1 microM omega-agatoxin IVA (approximately 30%) was enhanced by adding omega-conotoxin GVIA (1 microM) or nifedipine (100 microM). Further inhibition (up to above 70%) could be observed when the three Ca2+ channel blockers were added together. Similarly, synthetic FTX 3.3 arginine polyamine (sFTX) prevented (50% at 100 microM) the K+-evoked NO synthase activation. This effect of sFTX was further enhanced (up to 70%) by adding 1 microM omega-conotoxin GVIA plus 100 microM nifedipine. No further inhibition could be observed upon addition of MK-801 or/and NBQX. 5. It was concluded that elevation of extracellular [K+] causes NO synthase activation by external Ca2+ entering cells mainly through channels of the P/Q-type. Other Ca2+ channels (L- and N-type) appear to contribute when P/Q-channels are blocked.
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PMID 
R Guido, S Valenti, L Foppiani, D De Martini, M Cossu, M Giusti (1997)  Prolactin decrease and shift to a normal-like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma.   J Endocrinol Invest 20: 5. 289-293 May  
Abstract: Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated phosphorylated, deamidated and sulphated forms. The profiles of the forms, as determined by isoelectrofocusing (IEF), differ in physiological and pathological conditions. The case of a 72-year-old woman affected by an invasive prolactinoma is described. The patient had undergone surgical treatment followed by radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10 mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l as determined by IRMA, after dilution). We therefore treated the patient with quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600 micrograms/die on day 220. This treatment progressively lowered PRL to 23.2 micrograms/l. In addition to a decrease in PRL levels, a progressive change in the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very acidic and during treatment they progressively shifted toward a more basic range. For purpose of comparison PRL profiles were also determined in 8 women with pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1-170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels: 3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17-52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A had a single major peak at isoelectric point (pI) 6.5, while the group B and C profiles were more heterogeneous displaying multiple minor peaks, the majority of the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for group C). During treatment, the profiles of our subject at first resembled those of group A; subsequently, when the PRL levels had normalised, the profile resembled those noted in group B. Altered (immature?, more glycosilated?, less bioactive?) PRL molecules could be secreted by the tumour. These data show that quinagolide successfully reduced PRL levels, while inducing secretion of forms more similar to those found in women affected by pathological hyperprolactinaemia or in normal women.
Notes:
1995
 
PMID 
M Cossu, A Pau, G L Viale (1995)  Postero-lateral microsurgical approach to orbital tumors.   Minim Invasive Neurosurg 38: 3. 129-131 Sep  
Abstract: A modification of the lateral orbitotomy is reported for the microsurgical approach to tumors located in the posterior intraconal space. The orbital apex is entered through a small bone opening on the orbital and temporal portions of the greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate of the frontal bone, and the lateral orbital rim being left intact. This surgical technique was employed in 8 cases of pure apical tumors, out of a consecutive series of 103 orbital growths. It proved to be reliable with regard to either adequate exposure and radical excision of the lesions or low rate of operative morbility.
Notes:
1994
 
PMID 
M Cossu, A Pau, D Siccardi, G L Viale (1994)  Infratentorial ischaemia following experimental cerebellar haemorrhage in the rat.   Acta Neurochir (Wien) 131: 1-2. 146-150  
Abstract: Early changes of cerebellar and cerebral blood flow, as well as subsequent infratentorial ischaemia, were evaluated in an experimental model of cerebellar haemorrhage. Eight anaesthetized male adult Sprague-Dawley rats received an injection of autologous arterial blood (50 microliters) into the right cerebellar hemisphere. Eight animals were sham-operated and served as controls. Cerebellar blood flow, measured at regular time intervals in the hemispheric cortex ipsilateral to the lesion by the hydrogen clearance method, was significantly depressed in the experimental group as compared with the control animals. This drop in cerebellar blood flow was evident 5, 30, 60, 90, and 120 min postoperatively, with a return to pre-injection values recorded 180 min after surgery. No significant difference in supratentorial blood flow was detected over the entire period examined between the two groups of animals. Enzyme histochemistry demonstrated areas of ischaemia around the clot and within the brain stem in animals with an intracerebellar haemorrhage at the end of the experiment. These results provided evidence of ischaemic damage within the infratentorial compartment after the induction of experimental cerebellar haemorrhage.
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PMID 
G L Viale, M Cossu, F Cella, M Balestrero, A Rossi, D Masoni (1994)  Cortical blood flow recorded during early or delayed surgery for ruptured intracranial aneurysms.   Acta Neurochir (Wien) 131: 1-2. 1-5  
Abstract: Forty-three patients were operated on for ruptured intracranial aneurysms during a 12-month-period. Intraoperative evaluation of cortical blood flow by means of a thermal diffusion probe was performed in 23 out of the 41 patients who were operated on for aneurysms of the anterior circulation. The autoregulation index was determined at the time of raising the systemic blood pressure after clipping of the aneurysm(s). No statistically significant difference was found between the averages of the autoregulation indexes calculated in the subgroups of patients submitted respectively to early or delayed surgery. There was no correlation of both cortical blood flow and autoregulation with either age of the patients, or preoperative neurological grade. On the contrary, the autoregulation index showed a statistically significant correlation with outcome.
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PMID 
G L Viale, E V Sehrbundt, M Cossu, C Viola, G Rodriguez, A Pau, C Bernucci (1994)  Longitudinal study of cerebral blood flow following early or delayed surgery for ruptured intracranial aneurysms.   Acta Neurochir (Wien) 131: 1-2. 6-11  
Abstract: Out of a series of 43 cases operated on for ruptured intracranial aneurysms over a 12-month-period, 32 patients were followed up to 12 months postoperatively with repeated evaluations of cerebral blood flow, using the Xenon133 inhalation technique. No statistically significant differences in cerebral perfusion were detected between the subgroups of good-grade patients, who were submitted respectively to early, or delayed surgery. Depression of flow in the affected hemisphere of poor-grade patients was principally related to the preoperative occurrence of an intracerebral haematoma. The overall results were not consistent with the hypothesis that early surgical intervention results in long-lasting effects on the cerebral circulation.
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PMID 
A Pau, M Cossu, S Turtas (1994)  Association of aneurysm and arteriovenous malformation on the posterior inferior cerebellar artery. Report of three further cases and review of the literature.   Acta Neurol (Napoli) 16: 1-2. 52-57 Feb/Apr  
Abstract: As far as we know, only 20 patients with association of aneurysm and arteriovenous malformation (AVM) on the posterior inferior cerebellar artery (PICA) have been reported so far. Further three personal cases are presented here and the pertinent literature is reviewed, the coexistence of aneurysm(s) and AVM on the PICA district increases the risk of intracranial bleeding compared with patients harbouring this association in the cerebral hemispheres. The direct approach of both lesions (excision of the AVM and clipping of the aneurysm) in one-stage operation is the treatment of choice.
Notes:
1993
 
PMID 
M Cossu, A Pau, S Turtas, C Viola, G L Viale (1993)  Subsequent bleeding from ruptured intracranial aneurysms treated by wrapping or coating: a review of the long-term results in 47 cases.   Neurosurgery 32: 3. 344-6; discussion 347 Mar  
Abstract: Forty-seven patients, who underwent surgery over a 34-year period by the wrapping or coating of ruptured intracranial aneurysms, have been retrospectively evaluated. The following materials were used in the surgical procedures: muscle with gelatin sponge (7 cases), gauze (2 cases), oxidized cellulose with Biobond (28 cases), Histoacryl with gauze or fascia (10 cases). The patients were monitored for up to 37 years (mean, 13.7 +/- 8.2 yr). One or more subsequent bleedings occurred in eight patients (17%). Three patients had additional bleeding and died in the early postoperative phase (within 1 mo after surgery). In five patients, the subsequent bleeding occurred between 1 and 15 years postoperatively, with two fatalities. One patient experienced two recurrences. Therefore, the mortality rate for postoperative bleedings was 10.6% (five patients) in the whole series, and the incidence of early (within 1 mo after surgery) fatal bleedings was 6.4%. After the first month from the initial hemorrhage, the global risk of subsequent bleeding was 0.93%/yr. Among the nine patients whose aneurysms were wrapped with muscle, gelatin sponge, or gauze, four additional bleedings occurred, whereas four relapses were observed among the 38 cases treated by employing bioadhesive agents (P < 0.04; Fisher's exact test). The rate of further bleeding was higher (25%) in patients undergoing surgery in the premicrosurgical era compared with that (8.7%) recorded in patients treated by microsurgery (difference statistically not significant).
Notes:
 
PMID 
A Rossi, M A Balestrero, F Cella, M Cossu, D Masoni, G Rodriguez, E Sehrbundt Viale, G Viale (1993)  Intra- and postoperative cerebral blood flow in patients with subarachnoid hemorrhage from a ruptured aneurysm   Minerva Anestesiol 59: 11. 567-570 Nov  
Abstract: The CBF of eight patients, who underwent surgery for ruptured aneurysm, was monitored using the termodiffusion technique (TDF). The device employed in this investigation allowed a continuous monitoring in "real time" of the cortical flow. The purpose of the study was to detect disorders of autoregulation, which were evaluated with the autoregulation index (AI). Autoregulation was correlated with the neurological preoperative grading, the postoperative changes of CBF (Xe133 clearance) and the outcome. The results of this preliminary study showed a correlation between these parameters and stressed the value of CBF monitoring during surgery.
Notes:
 
PMID 
M Cossu, A Lucano, F Sardanelli, A Pau (1993)  Pituitary adenoma associated with dural arteriovenous fistula. Case report.   Acta Neurol (Napoli) 15: 6. 442-448 Dec  
Abstract: The association of a pituitary adenoma with a dural arteriovenous fistula supplied by the posterior branches of the middle meningeal artery and draining into the transverse sinus is reported. Among the possible etiopathogenic explanations of such an unusual association, a progressive mechanical obstacle to the dural venous blood drainage to the left wing of the compressed cavernous sinus and subsequent opening of embryonic dural arterio-venous shunts with reversal of flow has been considered.
Notes:
1992
 
PMID 
B Cagetti, M Cossu, A Pau, C Rivano, G Viale (1992)  The outcome from acute subdural and epidural intracranial haematomas in very elderly patients.   Br J Neurosurg 6: 3. 227-231  
Abstract: Out of a consecutive series of 1082 operations performed on head-injured patients over a 9-year period, 28 cases of acute subdural haematomas (SDHs) or epidural haematomas (EDHs) occurring in patients aged between 80 and 100 years were selected. Mortality rates in these patients (100% in 2 EDHs, 88% in 26 SDHs) were significantly higher (p less than 0.01) compared with patients under 80 years (12% in 308 EDHs, 57% in 215 SDHs). Pre-existing diseases, primary events precipitating falls, and multiple system failure complicating the postoperative course accounted for most of the deaths. None of the patients operated upon with a Glasgow Coma Scale score of 11 or less survived. A typical 'talk and die' course occurred in two cases. Three patients, all operated on for SDH, survived and returned to their pre-injury conditions. It was concluded that, whilst the question as to whether to submit very old comatose patients to life-prolonging measures remains unsettled, there is a case for the prompt evacuation of extra-axial clots in patients with minimal impairment of consciousness.
Notes:
1991
 
PMID 
M Cossu, A Dorcaratto, A Pau, G Rodriguez, E Sehrbundt Viale, D Siccardi, G L Viale (1991)  Changes in infratentorial blood flow following experimental cerebellar haemorrhage. A preliminary report.   Ital J Neurol Sci 12: 3 Suppl 11. 69-73 Jun  
Abstract: The temporal progression of changes in blood flow within the hemispheric cerebellar cortex, following an experimental cerebellar ipsilateral haemorrhage, was investigated in rats by using the hydrogen clearance technique. Stereotactical injection of 50 microliters of fresh autologous blood into the paramedian white matter was found to produce an early drop of cerebellar blood flow, with subsequent rise toward higher values. An increase of the intracranial pressure only occurred at the time of injection of blood. Arterial blood gases, mean arterial blood pressure and blood glucose levels did not exhibit significant changes. Histochemical evaluations of glycogen phosphorylase showed a posthaemorrhagic pattern of enzyme depletion, consistent with the occurrence of an ischaemic damage in both the cerebellum and the brain stem.
Notes:
 
PMID 
A Pau, M Brambilla, M Cossu, N Francaviglia, D Siccardi, C Silvestro (1991)  Spinal subarachnoid hematoma of unknown etiology. A case report.   Neurochirurgia (Stuttg) 34: 5. 151-153 Sep  
Abstract: A case of spinal subarachnoid hematoma at T3-T7 level is reported in a 60-year-old hunter, who developed progressive spinal cord impairment after receiving the recoil of his shotgun. Both clinical and neuroradiological investigations, including the selective spinal angiography, failed to demonstrate the origin of the bleeding. The combination of an apparently trivial spinal trauma with temporary increase of the intrathoracic pressure might be considered as possible etiologic factor.
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1990
 
PMID 
A Pau, M Brambilla Bas, D Siccardi, M Cossu (1990)  Transient upper monoballism in the presence of contralateral chronic subdural hematoma.   Acta Neurol (Napoli) 12: 3. 237-241 Jun  
Abstract: A case of chronic subdural hematoma associated with contralateral upper monoballism is reported. Intracranial midline shift and transtentorial herniation of the ipsilateral temporal lobe were the only demonstrated CT abnormalities. Complete neurological recovery followed the evacuation of the hematoma. Direct mechanical injury caused by the marked brain compression and distortion, and transient ischemic changes within cerebral areas whose damages may result in ballism, may be considered important causative factors of such an unusual neurological complication.
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PMID 
H S Goldsmith, P Bacciu, M Cossu, A Pau, G Rodriguez, G Rosadini, P Ruju, E Sehrbundt Viale, S Turtas, G L Viale (1990)  Regional cerebral blood flow after omental transposition to the ischaemic brain in man. A five year follow-up study.   Acta Neurochir (Wien) 106: 3-4. 145-152  
Abstract: Regional cerebral blood flow, recorded by the 133Xenon inhalation method, was measured preoperatively and over a five years postoperative period in six patients with completed stroke and stabilized neurological deficits, who had undergone omental transposition for revascularization of the ischaemic brain. Comparisons of the preoperative blood flow values with those recorded following surgery demonstrate a postoperative increase of blood flow in five patients, with a high statistical degree of significance in four of them at the final examination. The flow increase was noted over the infarcted areas of the brain, upon which the omentum had been placed, as well as areas of the ischaemic hemisphere without omental placement and the contralateral hemisphere. Out of the five patients who demonstrated preoperative flow values below the expected norm for age, four showed final postoperative cerebral blood flow within the normal limits for their age. The results are consistent with the assumption that the transposed omentum played a role in postoperative blood flow increase, by adding collateral circulation to the ischaemic brain.
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PMID 
M Cossu, T Arcuri, B Cagetti, M Brambilla Bas, D Siccardi, A Pau (1990)  Gas bubbles within acute intracranial epidural haematomas.   Acta Neurochir (Wien) 102: 1-2. 22-24  
Abstract: In order to assess the actual incidence of gas bubbles trapped within acute intracranial epidural haematomas, as revealed by computed tomography (CT) of the skull, a series of 204 patients with surgically verified epidural haematomas was retrospectively reviewed. Gas bubbles were observed on CT scan in 22.5% of the cases, with the incidence rising to 37% when CT scanners of the last generation were employed. The available data failed to demonstrate the actual source of intracranial gas. No correlation was found between the presence of gas bubbles and outcome. No patient in the whole series showed any sign of intracranial infection.
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1989
 
PMID 
A Pau, M Brambilla, M Cossu, R Schoenhuber, D Siccardi, S Turtas (1989)  Parkinsonism in the presence of intracranial extracerebral haematomas.   Acta Neurochir (Wien) 96: 3-4. 159-160  
Abstract: Bilateral Parkinsonism has been observed in a 60-year-old female with a chronic subdural intracranial haematoma. Scattered, poorly marginated, hypodense areas within the ipsilateral pallidus and putamen were evident on the preoperative CT scans. The rapid neurological improvement following the surgical drainage of the subdural clot and the evolution of the densitometric features of the nuclear lesions, which became clear-cut, though smaller, in the following months, suggest a cause-and-effect relation between the haematoma and the clinical symptomatology. To the best of our knowledge this is the first case in which anatomical lesions within the basal ganglia could be detected neuroradiologically.
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PMID 
A Pau, M Cossu, S Turtas, G Zirattu (1989)  Spinal cord dysfunction from lumbar disk herniation.   Acta Neurol (Napoli) 11: 6. 439-443 Dec  
Abstract: Two patients with a herniated disk respectively at the level of the L4-L5 and of the L5-S1 intervertebral spaces presented with pyramidal signs, bladder paralysis and radicular impairment. The symptoms subsided immediately following surgical removal of the prolapsed disk. The role of transient ischemia in the lower segments of the spinal cord as possible cause of this uncommon clinical picture is discussed, and the pertinent literature is reviewed.
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PMID 
G Rosadini, M Cossu, F De Carli, S Marenco, F Nobili, G Rodriguez (1989)  Evaluation of cerebral blood flow data in stroke patients using a mapping system.   Stroke 20: 9. 1182-1189 Sep  
Abstract: We retrospectively examined regional cerebral blood flow values in 78 patients in the stabilized phase of stroke to evaluate the consistency of lateralization compared with computed tomographic imaging. Examinations were performed using the xenon-133 inhalation technique, and the data were processed and displayed by a computer-assisted system of our own design that allows statistical analysis in real time and is suitable for clinical use. The consistency of lateralization correlated with computed tomographic findings was tested for absolute values, percent distribution, and asymmetries. The latter yielded the highest degree of sensitivity (in 83.3% of the patients the affected hemisphere was correctly identified). Absolute values showed at least one hypoperfused area in the affected hemisphere in 48.7% of the patients, and percent distribution did so in 57.7%. Furthermore, the combination of the three methods of data analysis yielded a sensitivity of 91%; the remaining 9% of the patients, however, exhibited some abnormalities of regional cerebral blood flow (bilateral or contralateral hypoperfusion). Although good agreement was found for lateralization by computed tomography and by the combined use of the three methods of analysis, a complete overlap between functional and structural examinations should not be expected. Problems concerning the sensitivity of the xenon-133 inhalation technique under conditions of low blood flow and the statistical analysis of regional cerebral blood flow data are discussed.
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1987
 
PMID 
M Cossu, A Martelli, A Pau, E S Viale, D Siccardi, G L Viale (1987)  Axonal elongation into peripheral nerve grafts between thalamus and somatosensory cortex of the rat. An experimental model.   Brain Res 415: 2. 399-403 Jul  
Abstract: After destruction of the thalamocortical projections of one side in 12 adult rats, the ipsilateral thalamic ventrobasal nucleus was connected with the contralateral somatosensory cortex through an autologous peripheral nerve graft. Three months after the implanting procedure, horseradish peroxidase was applied to the transected nerve. Retrograde labeling of cells occurred in all examined animals. Evidence of newly formed thalamocortical connections provides the experimental basis to a model suitable for functional evaluations.
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PMID 
A Pau, M Brambilla, M Cossu, E Sehrbundt Viale, S Turtas (1987)  Long term follow-up of the surgical treatment of the intracranial hydatid disease.   Acta Neurochir (Wien) 88: 3-4. 116-118  
Abstract: Long term results of the surgical treatment of intracranial hydatid disease ist reported in 11 personal cases. Nine patients are alive 9 to 15 years following the operation, only one of them being disabled. The remaining two patients died respectively 6 months and 2 years after the first operation.
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1986
 
PMID 
G L Viale, T Capuzzo, M Cossu, A Pau, E Sehrbundt Viale (1986)  Anatomo-surgical classification and surgical treatment of arteriovenous malformations in the posterior cranial fossa   Minerva Med 77: 25. 1187-1194 Jun  
Abstract: An increasing number of arteriovenous malformations of the posterior cranial fossa can be radically extirpated with good functional results, by using microsurgical techniques. Extensive involvement of the brain stem represents the limit for effective surgery. An anatomo-surgical classification of these lesions is presented, and the surgical indications are discussed.
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PMID 
A Pau, M Cossu, E S Viale, D Siccardi, S Turtas, G L Viale (1986)  Echinococcosis of the spine   Zentralbl Neurochir 47: 4. 316-321  
Abstract: 21 patients with hydatid disease of the spine were operated on upon a 30-year period. The follow-up ranged up to 24 years. 12 cases underwent one or more reoperations, due to recurrences. 8 patients died between 1 and 21 years after the first operation. The surgical treatment usually allows only a transient remission and does not avoid recurrence or progression of the illness. Although the parasite cannot be wholly eradicated surgically, a prolonged and acceptable life with the disease can result from repeat surgical interference.
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1985
 
PMID 
F Arvigo, M Cossu, B Fazio, A Gris, A Pau, G Rodriguez, G Rosadini, E Sehrbundt Viale, D Siccardi, S Turtas (1985)  Cerebral blood flow in minor cerebral contusion.   Surg Neurol 24: 2. 211-217 Aug  
Abstract: Seventeen patients with minor cerebral contusion were selected from a series of patients with head injuries of various severity, who had undergone repeat evaluations of the regional cerebral blood flow. The mean global flow (expressed as mean global initial slope index) on early examination was found to be significantly lower, compared with that recorded in healthy volunteers. A tendency towards the recovery of higher flow values was apparent in repeat evaluations that were performed several weeks after the injury. Interhemispheric asymmetries of flow were a common occurrence, with lower perfusion and reduced attenuation values on computed tomography scans being, however, in good agreement only in approximately half of the cases.
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1984
 
PMID 
M Cossu, F Lubinu, G Orunesu, A Pau, E Sehrbundt Viale, M G Sini, S Turtas (1984)  Subchoroidal approach to the third ventricle. Microsurgical anatomy.   Surg Neurol 21: 4. 325-331 Apr  
Abstract: The third ventricle can be approached by performing a few surgical maneuvers: (a) dividing the ependyma on the inferolateral aspect of the choroid plexus of the lateral ventricle; (b) separating leptomeningeal bundles within the tela chorioidea, and (c) dividing the roof of the third ventricle along the stria medullaris. Main landmarks are the thalamostriate vein and the direct lateral vein. Small subependymal veins or neural branches of the posterior medical choroidal artery, or both, occasionally cross the access route. The third ventricle is seen through both the opening in the roof and the foramen of Monro. A wider exposure can be obtained by cutting the terminal segment of the thalamostriate vein.
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1982
 
PMID 
M Cossu, M Cabri, F De Carli, V Montano, G Rodriguez, A Siccardi, R Traverso, G Rosadini (1982)  Regional cerebral blood flow: normal values in healthy volunteers obtained by a 32 probes xenon 133 inhalation system.   Boll Soc Ital Biol Sper 58: 12. 766-772 Jun  
Abstract: Regional cerebral blood flow (CBF) was measured in 15 healthy young volunteers in psycho-sensorial rest by the 32 probes Xe133 inhalation system. The mean hemispheric values are in good agreement with those reported in literature and obtained with a limited number of probes. The regional values of the flow in the gray matter are higher in the basal-temporal and frontal regions. This regional pattern is not evident for the other considered parameters (flow in the white matter, mean flow, "weight" of the gray matter).
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