Intraoperative functional mapping of calculation in parietal surgery. New insights and clinical implications.

BACKGROUND: Parietal areas play a crucial role in calculation processing. The purpose of this study is to report our experience in the assessment of calculation processing during awake surgery in parietal areas, focusing on clinical implications and new insights provided by this approach. METHODS: We retrospectively reviewed clinical and surgical data of 13 patients who underwent parietal surgery with calculation mapping. Cortical and sub-cortical areas (in 13 and five patients, respectively) involved in single-digit multiplications and additions were identified using bipolar electro-stimulation. RESULTS: Cortical stimulation data showed that the inferior parietal lobule and the intraparietal sulcus were specifically related to calculation in all cases, regardless of the side (100% of cases, in both sides). Conversely, the superior parietal lobule was inconstantly involved in calculation processing (40% of cases in the left and 75% in the right side), whereas the somatosensory area was never involved. Sub-cortical stimulation was able to detect functional areas for calculation in all patients: in 90% of cases the sub-cortical sites positive for calculation were in close anatomical connection with the cortical sites mapping for the same function. The intraoperative preservation (-or damaging-) of functional sites correlated with the absence (- or occurrence-) of post-operative calculation processing impairment. CONCLUSIONS: Our findings support the specificity of the reported technique in the intraoperative identification of sites functional for calculation. Our data show the bilateral involvement of parietal cortex, especially of the inferior lobule, in calculation processing. Furthermore, our study suggests the existence of a sub-cortical pathway specific for calculation, whose better understanding might be crucial for the clinical outcome of patients.

5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature.

BACKGROUND: Only few data are available on the specific topic of 5-aminolevulinic acid (5-ALA) guided surgery of high-grade gliomas (HGG) located in eloquent areas. Studies focusing specifically on the post-operative clinical outcome of such patients are yet not available, and it has not been so far explored whether such approach could be more suitable for some particular subgroups of patients. METHODS: Patients affected by HGG in eloquent areas who underwent surgery assisted by 5-ALA fluorescence and intra-operative monitoring were prospectively recruited in our Department between June 2011 and August 2012. Resection rate was reported as complete resection of enhancing tumor (CRET), gross total resection (GTR) >98 % and GTR > 90 %. Clinical outcome was evaluated at 7, 30, and 90 days after surgery. RESULTS: Thirty-one patients were enrolled. Resection was complete (CRET) in 74 % of patients. Tumor removal was stopped to avoid neurological impairment in 26 % of cases. GTR > 98 % and GTR > 90 % was achieved in 93 % and 100 % of cases, respectively. First surgery and awake surgery had a CRET rate of 80 % and 83 %, respectively. Even though at the first-week assessment 64 % of patients presented neurological impairment, there was a 3 % rate of severe morbidity at the 90th day assessment. Newly diagnosed patients had a significantly lower morbidity (0 %) and post-operative higher median KPS. Both pre-operative neurological condition and improvement after corticosteroids resulted significantly predictive of post-operative functional outcome. CONCLUSIONS: 5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.

Gender-based outcomes after eversion carotid endarterectomy from 1998 to 2009.

BACKGROUND AND PURPOSE: Although the benefit of carotid endarterectomy (CEA) in reducing the risk of stroke in selected symptomatic and asymptomatic patients has been well documented, the higher incidence of adverse events after CEA for women than for men remains controversial. The purpose of this study was to analyze the effect of female gender on perioperative (30-day) and long-term outcomes after eversion CEA (eCEA). METHODS: Patients entered into a prospectively compiled computerized database of all primary consecutive eCEAs performed at our institution from September 1998 to December 2009 were analyzed. Endpoints were perioperative death and stroke, late carotid restenosis or occlusion, and long-term freedom from stroke and survival rates. Long-term follow-up was obtained in 96.8% of patients (97.5% of the women). RESULTS: Among 1294 patients who underwent 1458 eCEAs under general anesthesia with continuous electroencephalographic monitoring and selective shunting, 409 (31.6%) were women (466 eCEAs). More women than men were over 80 years old (P = .001), and female patients were more likely to have arterial hypertension (P = .02) or hyperlipidemia (P = .006) than male patients. Preoperative statin medication (P = .01), contralateral carotid occlusion (P = .02), and shunting use (P = .03) were more frequent among female patients. No perioperative deaths occurred in the series as a whole, while the perioperative stroke risk (0.6% vs 0.5%), and the combined late carotid restenosis and occlusion rate (1.1% vs 0.4%) were comparable between female and male patients. The 7-year stroke-free survival and overall survival rates did not differ significantly between female and male patients (98.3% vs 98.8% and 87.2% vs 93.8%, respectively). CONCLUSIONS: This single-center university hospital study shows that although women have a different cardiovascular risk profile from men when they undergo eCEA, there is no evidence of a different gender effect on perioperative and long-term outcomes.

γ-Hydroxybutyric acid-induced psychosis and seizures.

Disulfiram and γ-hydroxybutyric acid (GHB) are used to treat alcohol dependence and may both increase dopamine brain levels and modulate GABAergic transmission. We describe a patient affected by bipolar disorder (on valproate as mood-stabilizing treatment) and alcohol dependence who developed a disulfiram-induced hypomanic episode and in whom the switch from disulfiram to GHB induced recurrent convulsive seizures, not responsive to treatment with diazepam, and psychosis. Seizures and psychiatric symptoms ceased after GHB discontinuation. We outline the deregulation of the neurotransmitter systems (GABAergic and dopaminergic networks) that are involved in these drug-drug interactions and that might be responsible for both psychosis and generalized tonic-clonic seizures resistant to standard treatments.

Predictors of electroencephalographic changes needing shunting during carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is associated with a risk of cerebral ischemia during carotid clamping, hence various cerebral protection strategies, including pharmacological management and routine or selective shunting, are commonly available. This study aimed to analyze the results of CEA with intraoperative electroencephalographic (EEG) monitoring to identify factors associated with EEG changes consistent with cerebral ischemia which needed shunting. METHODS: A prospectively compiled, computerized database of all primary CEAs performed at our institution with EEG monitoring for symptomatic or asymptomatic severe carotid lesions between January 1990 and June 2009 was analyzed. RESULTS: In all, 1,914 CEA procedures were performed on 1,696 patients, of which 218 had staged bilateral CEAs. EEG changes were recorded in 392 patients (20.5%), but a shunt was inserted during 312 CEA procedures (16.3%). Multivariate analysis showed that a symptomatic presentation (odds ratio [OR], 1.37; 95% confidence intervals [CI], 1.07-1.76; p = 0.012), prior stroke (OR, 2.28; 95% CI, 1.66-3.13; p < 0.001), contralateral carotid occlusion (OR, 2.14; 95% CI, 1.18-3.91; p = 0.019), and moderate (<80%) ipsilateral carotid disease (OR, 1.95; 95% CI, 1.08-3.52; p = 0.033) predicted the need for shunting. CONCLUSIONS: EEG was an excellent detector of cerebral ischemia and a valuable tool in guiding the need for shunting. Patients who were symptomatic or had a history of stroke, a contralateral carotid occlusion, or an ipsilateral moderate carotid stenosis were more prone to EEG changes consistent with cerebral ischemia. Surgeons should consider EEG changes during clamping as an effective criterion for selective shunting.

Early and long-term outcomes of carotid endarterectomy in the very elderly: an 18-year single-center study.

OBJECTIVE: To evaluate the perioperative (30-day) and long-term outcomes of carotid endarterectomy (CEA) in elderly patients with severe symptomatic and asymptomatic carotid disease. Although the efficacy of CEA in preventing stroke in selected patients has been clearly demonstrated, concern has been expressed about the role of CEA in people over 80 years old. METHODS: An analysis was conducted on a prospectively compiled computerized database of all primary CEAs performed at our institution from 1990 to 2007. Descriptive demographic data, risk factors, surgical details, perioperative strokes and deaths, and other complications were recorded. All patients underwent postoperative duplex ultrasound scanning and clinical follow-up at one, six, and 12 months, and yearly thereafter. Survival analyses were performed using Kaplan-Meier life-tables. Long-term relative survival after CEA was assessed against age- and gender-matched controls. RESULTS: In all, 1769 CEAs were performed in 1562 patients, 193 of them (207 CEAs; group I) were > or = 80 years old and 1371 were younger (1562 CEAs; group II). All CEA procedures were performed with patients under deep general anesthesia with continuous perioperative EEG monitoring for selective shunting. No strokes or deaths occurred in group I, whereas there were 11 perioperative strokes and three deaths in group II (1%). A complete follow-up (median, 5.2 years) was obtained in 185 elderly patients: no late occlusions or restenoses were detected, while the seven-year freedom from stroke and death were 96.6% and 52.4%, respectively. The relative seven-year survival rate was 99.8%. CONCLUSIONS: CEA in elderly patients proved safe and effective, with an excellent long-term durability. The long-term relative survival after CEA in elderly patients was better than in an age-and gender-matched population, so the likelihood of living long enough to benefit from CEA is not jeopardized by being very elderly.

Carotid endarterectomy within 2 weeks of minor ischemic stroke: a prospective study.

OBJECTIVE: Data from multicenter symptomatic trials have shown that benefit from carotid endarterectomy (CEA) was greatest in patients with carotid disease operated within 2 weeks of their last ischemic event. We prospectively analyzed the safety and benefit of CEA performed within 2 weeks of a stroke. METHODS: The study involved patients with acute minor stroke admitted to two stroke units who underwent CEA within 2 weeks of their last ischemic event, once they were considered neurologically stable. Preoperative workup included scoring ischemia-related symptoms according to a modified ranking scale (mRS), carotid duplex scan, transcranial Doppler ultrasound, and head computed tomography or magnetic resonance imaging. All patients underwent neurological assessment on admission, 1 day before and 2 days after CEA, and at discharge. A complete neurological and ultrasound follow-up was performed at 1, 6, and 12 months after CEA, then yearly. All procedures were eversion CEA under deep general anesthesia, with selective shunting. Endpoints were perioperative (30-day) stroke/mortality rate or cerebral bleeding and long-term stroke recurrence or cerebral hemorrhage. RESULTS: Between 2000 and 2005, 102 patients with a mRS

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center.

Epilepsy is the most common comorbidity in patients with brain tumors. STUDY AIMS: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study.

UNLABELLED: Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Trial name: Repetitive transcranial magnetic stimulation (rTMS) in cocaine abusers, URL:〈http://www.isrctn.com/ISRCTN15823943?q=&filters=&sort=&offset=8&totalResults=13530&page=1&pageSize=10&searchType=basic-search〉, REGISTRATION NUMBER: ISRCTN15823943.

Functional mapping of left parietal areas involved in simple addition and multiplication. A single-case study of qualitative analysis of errors.

All electrostimulation studies on arithmetic have so far solely reported general errors. Nonetheless, a classification of the errors during stimulation can inform us about underlying arithmetic processes. The present electrostimulation study was performed in a case of left parietal glioma. The patient's erroneous responses suggested that calculation was mainly applied for addition and a combination of retrieval and calculation was mainly applied for multiplication. The findings of the present single-case study encourage follow up with further data collection with the same paradigm.

Early versus delayed carotid endarterectomy after a nondisabling ischemic stroke: a prospective randomized study.

BACKGROUND: Although many retrospective and a few prospective studies have analyzed the outcome of early and delayed carotid endarterectomy (CEA) after a recent minor or nondisabling stroke (ie, a minimal and stabilized focal neurologic deficit of acute onset persisting for more than 24 hours and not leading to a handicap or to a significant impairment of daily living activities), the optimal timing of surgery remains uncertain. The purpose of this study was to prospectively compare the perioperative death and stroke rates of CEA performed within 30 days (early group) or more than 30 days (delayed group) after a nondisabling ischemic stroke in patients with carotid bifurcation disease. METHODS: During a 4-year period, of 86 patients experiencing a minor stroke, 45 were randomized to undergo early CEA and 41 to undergo delayed CEA. All patients underwent preoperative cerebral computed tomography, duplex ultrasonographic scanning and angiography of the supra-aortic trunks. All CEAs were carotid eversion endarterectomies and were performed by the same surgeon, using deep general anesthesia, with continuous electroencephalographic monitoring for the selective shunting. The perioperative death and stroke rates were compared between the 2 groups. RESULTS: No perioperative deaths occurred in either group. No recurrent strokes occurred during the waiting period in the delayed group. The incidence of perioperative stroke was comparable in the 2 groups (1 of 45, 2% vs 1 of 41, 2%). The mean follow-up was 23 months (range, 6 to 50 months). Survival rates after 1, 2, and 3 years were similar in the 2 groups. CONCLUSIONS: Early CEA after a nondisabling ischemic stroke can be performed safely with perioperative mortality and stroke rates comparable with those of delayed CEA. The timing of surgery does not seem to influence the benefit of the CEA.

Top-down regulation of left temporal cortex by hypnotic amusia for rhythm: a pilot study on mismatch negativity.

To evaluate the effect of hypnotically induced amusia for rhythm (a condition in which individuals are unable to recognize melodies or rhythms) on mismatch negativity (MMN), 5 highly (HH) and 5 poorly (LH) hypnotizable nonmusician volunteers underwent MMN recording before and during a hypnotic suggestion for amusia. MMN amplitude was recorded using a 19-channel montage and then processed using the low-resolution electromagnetic tomography (LORETA) to localize its sources. MMN amplitude was significantly decreased during hypnotic amusia (p < .04) only in HH, where the LORETA maps of MMN showed a decreased source amplitude in the left temporal lobe, suggesting a hypnotic top-down regulation of activity of these areas and that these changes can be assessed by neurophysiological investigations.

Ictal visual hallucinations due to frontal lobe epilepsy in a patient with bipolar disorder.

In ictal psychosis with complex visual hallucinations (VHs), widespread functional changes of cortical networks have been suggested. We describe the clinical and EEG findings of a patient with bipolar disorder who manifested complex VHs associated with intense emotional symptoms caused by frontal epileptic seizures. This description highlights the challenges of diagnosing the epileptic nature of new psychotic phenomena in patients with previous psychiatric disorders and shines light into the role of the frontal cortex in the genesis of complex VHs.

Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

OBJECT: The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. METHODS: Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. RESULTS: In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. CONCLUSIONS: These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.