Tailored resections for intractable rolandic cortex epilepsy in children: a single-center experience with 48 consecutive cases

A single-center experience with pediatric patients who underwent surgery for intractable rolandic epilepsy was reviewed with the aim of identifying putative factors that could influence postoperative seizure outcome in this population. Clinical data of 48 patients under 18 years of age with diagnosis of intractable rolandic epilepsy who underwent surgery from January 1996 to September 2009 were reviewed. Patients` mean age at surgery was 9.9 +/- 5.3 years; mean age at epilepsy onset was 3.9 years; mean seizure duration prior to surgery was 6 years; and mean follow-up was 5.1 years. The most frequent etiologies were cortical dysplasia, astrogliosis, tumors, tuberous sclerosis complex, and Sturge-Weber syndrome, which were observed in 20/48 (41.6%), 10/48 (20.8%), 10/48 (20.8%), 5/48 (10.4%), and 3/48 (6.2%) of the patients, respectively. After surgery, 20 patients (41.6%) showed neurological deficits, which in turn recovered within no longer than 6 months after surgery. Seizure outcome was classified as Engel class I in 29 (60.4%), Engel class II in 10 (20.8%), and Engel class III in 9 (18.8%) of the patients. The factors significantly related with seizure outcome were histological features (tumor versus non-tumor cases, p = 0.04) and lesion site (focal lesions versus non-focal lesions, p = 0.04). Tailored resection of rolandic cortex for intractable epilepsy can be safely performed in children. Accurate mapping of both functional cortex and epileptogenic areas may lead to improved seizure outcome. Tumor as well as focal lesions in hand and face motor areas are associated with good seizure outcome.

Low-threshold monopolar motor mapping for resection of primary motor cortex tumors

Microsurgery within eloquent cortex is a controversial approach because of the high risk of permanent neurological deficit. Few data exist showing the relationship between the mapping stimulation intensity required for eliciting a muscle motor evoked potential and the distance to the motor neurons; furthermore, the motor threshold at which no deficit occurs remains to be defined.

Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy

Purpose: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. Methods: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. Results: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=.1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R. = 2.9; 95% C.I. = 1.1-7.7; p=0.033); normal MRI (H.R. = 4.8; 95% C.I. = 1.4-16.6; p = 0.012), and MRI with lesion involving eloquent cortex (H.R. = 3.8; 95% C.I. = 1.2-12.0; p = 0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long-term surgical outcome in up to 80% of patients. Conclusion: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series. (C) 2011 Elsevier B.V. All rights reserved.

Can you tell your clunis from your cubitus? A benchmark for functional imaging

Advances in functional brain imaging have allowed the development of new investigative techniques with clinical application—ranging from presurgical mapping of eloquent cortex to identifying cortical regions involved in religious experiences. Similarly a variety of methods are available to referring physicians, ranging from metabolic measures such as functional magnetic resonance imaging and positron emission tomography to measurements based on electrical activity such as electroencephalography and magnetoencephalography. However, there are no universal benchmarks by which to judge between these methods. In this study we attempt to develop a standard for functional localisation, based on the known functional organisation of somatosensory cortex. Studies have shown spatially distinct sites of brain activity in response to stimulation of various body parts. Generally these studies have focused on areas with large cortical representations, such as the index finger and face. We tested the limits of magnetoencephalography source localisation by stimulation of body parts, namely the clunis and the cubitus, that map to proximal and relatively poorly represented regions of somatosensory cortex.

Low-threshold monopolar motor mapping for resection of lesions in motor eloquent areas in children and adolescents

Object Resection of lesions close to the primary motor cortex (M1) and the corticospinal tract (CST) is generally regarded as high-risk surgery due to reported rates of postoperative severe deficits of up to 50%. The authors' objective was to determine the feasibility and safety of low-threshold motor mapping and its efficacy for increasing the extent of lesion resection in the proximity of M1 and the CST in children and adolescents. Methods The authors analyzed 8 consecutive pediatric patients in whom they performed 9 resections for lesions within or close (≤ 10 mm) to M1 and/or the CST. Monopolar high-frequency motor mapping with train-of-five stimuli (pulse duration 500 μsec, interstimulus interval 4.0 msec, frequency 250 Hz) was used. The motor threshold was defined as the minimal stimulation intensity that elicited motor evoked potentials (MEPs) from target muscles (amplitude > 30 μV). Resection was performed toward M1 and the CST at sites negative to 1- to 3-mA high-frequency train-of-five stimulation. Results The M1 was identified through high-frequency train-of-five via application of varying low intensities. The lowest motor thresholds after final resection ranged from 1 to 9 mA in 8 cases and up to 18 mA in 1 case, indicating proximity to motor neurons. Intraoperative electroencephalography documented an absence of seizures during all surgeries. Two transient neurological deficits were observed, but there were no permanent deficits. Postoperative imaging revealed complete resection in 8 patients and a very small remnant (< 0.175 cm(3)) in 1 patient. Conclusions High-frequency train-of-five with a minimal threshold of 1-3 mA is a feasible and safe procedure for resections in the proximity of the CST. Thus, low-threshold motor mapping might help to expand the area for safe resection in pediatric patients with lesions located within the precentral gyrus and close to the CST, and may be regarded as a functional navigational tool. The additional use of continuous MEP monitoring serves as a safety feedback for the functional integrity of the CST, especially because the true excitability threshold in children is unknown.

Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome.

OBJECT Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. METHODS The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. CONCLUSIONS A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.

Cerebral Cortex Involvement In Machado-joseph Disease.

Machado-Joseph disease (MJD/SCA3) is the most frequent spinocerebellar ataxia, characterized by brainstem, basal ganglia and cerebellar damage. Few magnetic resonance imaging based studies have investigated damage in the cerebral cortex. The objective was to determine whether patients with MJD/SCA3 have cerebral cortex atrophy, to identify regions more susceptible to damage and to look for the clinical and neuropsychological correlates of such lesions. Forty-nine patients with MJD/SCA3 (mean age 47.7 ± 13.0 years, 27 men) and 49 matched healthy controls were enrolled. All subjects underwent magnetic resonance imaging scans in a 3 T device, and three-dimensional T1 images were used for volumetric analyses. Measurement of cortical thickness and volume was performed using the FreeSurfer software. Groups were compared using ancova with age, gender and estimated intracranial volume as covariates, and a general linear model was used to assess correlations between atrophy and clinical variables. Mean CAG expansion, Scale for Assessment and Rating of Ataxia (SARA) score and age at onset were 72.1 ± 4.2, 14.7 ± 7.3 and 37.5 ± 12.5 years, respectively. The main findings were (i) bilateral paracentral cortex atrophy, as well as the caudal middle frontal gyrus, superior and transverse temporal gyri, and lateral occipital cortex in the left hemisphere and supramarginal gyrus in the right hemisphere; (ii) volumetric reduction of basal ganglia and hippocampi; (iii) a significant correlation between SARA and brainstem and precentral gyrus atrophy. Furthermore, some of the affected cortical regions showed significant correlations with neuropsychological data. Patients with MJD/SCA3 have widespread cortical and subcortical atrophy. These structural findings correlate with clinical manifestations of the disease, which support the concept that cognitive/motor impairment and cerebral damage are related in disease.

Orbitofrontal Cortex Volumes in Medication Naive Children with Major Depressive Disorder: A Magnetic Resonance Imaging Study

Objectives: Adults with major depressive disorder (MDD) are reported to have reduced orbitofrontal cortex (OFC) volumes, which could be related to decreased neuronal density. We conducted a study on medication naive children with MDD to determine whether abnormalities of OFC are present early in the illness course. Methods: Twenty seven medication naive pediatric Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) MDD patients (mean age +/- SD = 14.4 +/- 2.2 years; 10 males) and 26 healthy controls (mean age +/- SD = 14.4 +/- 2.4 years; 12 males) underwent a 1.5T magnetic resonance imaging (MRI) with 3D spoiled gradient recalled acquisition. The OFC volumes were compared using analysis of covariance with age, gender, and total brain volume as covariates. Results: There was no significant difference in either total OFC volume or total gray matter OFC volume between MDD patients and healthy controls. Exploratory analysis revealed that patients had unexpectedly larger total right lateral (F = 4.2, df = 1, 48, p = 0.05) and right lateral gray matter (F = 4.6, df = 1, 48, p = 0.04) OFC volumes compared to healthy controls, but this finding was not significant following statistical correction for multiple comparisons. No other OFC subregions showed a significant difference. Conclusions: The lack of OFC volume abnormalities in pediatric MDD patients suggests the abnormalities previously reported for adults may develop later in life as a result of neural cell loss.

Harmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus

A growing body of evidence has suggested that reactive oxygen species (ROS) may play an important role in the physiopathology of depression. Evidence has pointed to the beta-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) or saline in lipid and protein oxidation levels and superoxide dismutase (SOD) and catalase (CAT) activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and beta-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation.

Antinociceptive effect of stimulating the occipital or retrosplenial cortex in rats

A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon. Perspective: This study presents evidence that stimulation of the retrosplenial or occipital cortex produces antinociception in rat models of acute pain. These findings enhance our understanding of the role of the cerebral cortex in control of pain. (C) 2010 by the American Pain Society

Prefrontal cortex involvement in selective letter generation: A functional magnetic resonance imaging study

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pairfed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs, that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity. (C) 1999 Elsevier Science B.V. All rights reserved.

Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Background: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). Methods: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or nore-pineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. Results: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. Conclusions: Our study suggests that vmPFC DES in rats maybe useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.