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1.
Conscious Cogn ; 35: 206-24, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25824626

ABSTRACT

Despite extensive research, the spatiotemporal span of neuronal activations associated with the emergence of a conscious percept is still debated. The debate can be formulated in the context of local vs. global models, emphasizing local activity in visual cortex vs. a global fronto-parietal "workspace" as the key mechanisms of conscious visual perception. These alternative models lead to differential predictions with regard to the precise magnitude, timing and anatomical spread of neuronal activity during conscious perception. Here we aimed to test a specific aspect of these predictions in which local and global models appear to differ - namely the extent to which fronto-parietal regions modulate their activity during task performance under similar perceptual states. So far the main experimental results relevant to this debate have been obtained from non-invasive methods and led to conflicting interpretations. Here we examined these alternative predictions through large-scale intracranial measurements (Electrocorticogram - ECoG) in 43 patients and 4445 recording sites. Both ERP and broadband high frequency (50-150 Hz - BHF) responses were examined through the entire cortex during a simple 1-back visual recognition memory task. Our results reveal short latency intense visual responses, localized first in early visual cortex followed (at ∼200 ms) by higher order visual areas, but failed to show significant delayed (300 ms) visual activations. By contrast, oddball image repeat events, linked to overt motor responses, were associated with a significant increase in a delayed (300 ms) peak of BHF power in fronto-parietal cortex. Comparing BHF responses with ERP revealed an additional peak in the ERP response - having a similar latency to the well-studied P3 scalp EEG response. Posterior and temporal regions demonstrated robust visual category selectivity. An unexpected observation was that high-order visual cortex responses were essentially concurrent (at ∼200 ms) with an ultra-fast spread of signals of lower magnitude that invaded selected sites throughout fronto-parietal cortical areas. Our results are compatible with local models in demonstrating a clear task-dependence of the 300 ms fronto-parietal activation. However, they also reveal a more global component of low-magnitude and poor content selectivity that rapidly spreads into fronto-parietal sites. The precise functional role of this global "glow" remains to be elucidated.


Subject(s)
Consciousness , Evoked Potentials, Visual/physiology , Frontal Lobe/physiology , Parietal Lobe/physiology , Visual Cortex/physiology , Visual Perception/physiology , Adult , Brain Mapping , Cerebral Cortex/physiology , Electrocorticography , Female , Humans , Male , Reaction Time , Young Adult
2.
J Clin Neurophysiol ; 27(6): 406-11, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21076338

ABSTRACT

Microseizures are highly focal low-frequency epileptiform-appearing events recorded from the neocortex of epilepsy patients. Because of their tiny, often submillimeter distribution, they may be regarded as a high-resolution window into the epileptic process, providing an excellent opportunity to study the fine temporal structure of their origin and spread. A 16 mm² 96-microelectrode array with 400-µm interelectrode spacing was implanted in seven patients undergoing invasive EEG monitoring for medically refractory epilepsy. Seven microdischarge populations were tested for a substantial contribution by volume conduction to the observed waveform amplitudes. Single-unit activity was examined for specific evidence of neural activity at multiple sites within the microdischarge fields. We found that microdischarges appear to originate at a highly focal source location, likely within a single cortical macrocolumn, and spread to local and more distant sites via neural propagation.


Subject(s)
Action Potentials/physiology , Epilepsy/pathology , Neocortex/physiopathology , Neurons/physiology , Analysis of Variance , Electroencephalography , Epilepsy/physiopathology , Humans , Microelectrodes , Neocortex/pathology , Wavelet Analysis
3.
Brain ; 132(Pt 11): 3047-59, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19745024

ABSTRACT

Interictal high frequency oscillations (HFOs), in particular those with frequency components in excess of 200 Hz, have been proposed as important biomarkers of epileptic cortex as well as the genesis of seizures. We investigated the spatial extent, classification and distribution of HFOs using a dense 4 x 4 mm(2) two dimensional microelectrode array implanted in the neocortex of four patients undergoing epilepsy surgery. The majority (97%) of oscillations detected included fast ripples and were concentrated in relatively few recording sites. While most HFOs were limited to single channels, approximately 10% occurred on a larger spatial scale with simultaneous but morphologically distinct detections in multiple channels. Eighty per cent of these large-scale events were associated with interictal epileptiform discharges. We propose that large-scale HFOs, rather than the more frequent highly focal events, are the substrates of the HFOs detected by clinical depth electrodes. This feature was prominent in three patients but rarely seen in only one patient recorded outside epileptogenic cortex. Additionally, we found that HFOs were commonly associated with widespread interictal epileptiform discharges but not with locally generated 'microdischarges'. Our observations raise the possibility that, rather than being initiators of epileptiform activity, fast ripples may be markers of a secondary local response.


Subject(s)
Biological Clocks/physiology , Brain Mapping/methods , Epilepsy/physiopathology , Neocortex/physiopathology , Seizures/physiopathology , Adult , Animals , Electrodes, Implanted , Electroencephalography/methods , Epilepsy/surgery , Female , Humans , Male , Microelectrodes , Periodicity , Sleep/physiology , Wakefulness/physiology
4.
Clin Neuropathol ; 26(6): 267-75, 2007.
Article in English | MEDLINE | ID: mdl-18232592

ABSTRACT

OBJECTIVE/BACKGROUND: Patients with medically refractory Parkinson's disease (PD) obtain significant clinical benefit from subthalamic nucleus (STN) stimulation. The degree to which a successful outcome relates to the anatomic location of the stimulating electrode has not yet been clearly established. Many studies have attempted to correlate the clinical result with the electrode location using postoperative magnetic resonance imaging (MRI) and there have been a few that used autopsy-determined locations. In this report, we describe long-term clinical follow-up in a patient with autopsy-determined electrode tip anatomic location. METHODS: A 67-year-old patient with a 27-year history of idiopathic PD complicated by disabling motor fluctuations and dopaminergic dyskinesias underwent bilateral STN deep brain stimulation (DBS). He was prospectively followed in a long-term clinical protocol until his death 40 months after electrode placement. Postoperative magnetic resonance (MR) imaging and postmortem studies of this patient's brain were performed to localize DBS tip locations. RESULTS: STN stimulation produced improvement of the patient's motor fluctuations, dyskinesias and clinical motor performance, especially appendicular tremors, rigidity and bradykinesia. MRI showed the electrode tips to be within 2 mm of the intended target. Postmortem brain analysis identified the right DBS tip location at the dorsomedial edge of the STN, with the left electrode in the vicinity (but not within) the STN. Chronic DBS elicited minor reactive changes were confined to the immediate vicinity of the electrode tracks. The pathological analysis demonstrated numerous cortical Lewy bodies and degenerative encephalopathy, establishing the diagnosis of transitional type diffuse Lewy body disease (DLBD) rather than simple PD. CONCLUSION: This patient obtained clinical benefit from STN stimulation typical of that seen for most PD patients. Both the MR analysis and the autopsy demonstrated electrode placement at or outside the boundaries of the STN, suggesting that that clinical efficacy may not depend on electrode location within the central region of the STN.


Subject(s)
Deep Brain Stimulation/methods , Parkinson Disease/pathology , Parkinson Disease/therapy , Subthalamic Nucleus/pathology , Aged , Autopsy , Deep Brain Stimulation/instrumentation , Diagnosis , Electrodes, Implanted , Follow-Up Studies , Humans , Lewy Body Disease/diagnosis , Magnetic Resonance Imaging , Male , Parkinson Disease/physiopathology , Subthalamic Nucleus/physiopathology , Treatment Outcome
5.
J Neurol Neurosurg Psychiatry ; 77(1): 12-7, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16361585

ABSTRACT

OBJECTIVE: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. METHODS: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation. RESULTS: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. CONCLUSION: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.


Subject(s)
Deep Brain Stimulation/methods , Parkinson Disease/pathology , Parkinson Disease/therapy , Subthalamic Nucleus/pathology , Adult , Aged , Aged, 80 and over , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/epidemiology , Deep Brain Stimulation/adverse effects , Female , Fetal Tissue Transplantation/methods , Globus Pallidus/surgery , Hematoma, Subdural/diagnostic imaging , Hematoma, Subdural/epidemiology , Humans , Male , Microelectrodes , Middle Aged , Parkinson Disease/surgery , Severity of Illness Index , Subthalamic Nucleus/surgery , Thalamus/surgery , Tomography, X-Ray Computed
6.
J Neurol Neurosurg Psychiatry ; 75(9): 1255-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15314110

ABSTRACT

OBJECTIVE: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease. DESIGN: Open label follow up using blinded ratings of videotaped neurological examinations. PATIENTS: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. MAIN OUTCOME MEASURES: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. RESULTS: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. CONCLUSIONS: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.


Subject(s)
Electric Stimulation Therapy , Motor Skills Disorders/etiology , Motor Skills Disorders/therapy , Parkinson Disease/therapy , Subthalamic Nucleus/physiology , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Antiparkinson Agents/therapeutic use , Dyskinesias/etiology , Dyskinesias/therapy , Female , Follow-Up Studies , Humans , Male , Mental Status Schedule , Middle Aged , Observer Variation , Severity of Illness Index , Single-Blind Method , Treatment Outcome , Video Recording
7.
Neurology ; 60(9): 1478-83, 2003 May 13.
Article in English | MEDLINE | ID: mdl-12743235

ABSTRACT

BACKGROUND: Language errors induced by cortical stimulation can provide insight into function(s) supported by the area stimulated. The authors observed that some stimulation-induced errors during auditory description naming were characterized by tip-of-the-tongue responses or paraphasic errors, suggesting expressive difficulty, whereas others were qualitatively different, suggesting receptive difficulty. They hypothesized that these two response types reflected disruption at different stages of auditory verbal processing and that these "subprocesses" might be supported by anatomically distinct cortical areas. OBJECTIVE: To explore the topographic distribution of error types in auditory verbal processing. METHODS: Twenty-one patients requiring left temporal lobe surgery underwent preresection language mapping using direct cortical stimulation. Auditory naming was tested at temporal sites extending from 1 cm from the anterior tip to the parietal operculum. Errors were dichotomized as either "expressive" or "receptive." The topographic distribution of error types was explored. RESULTS: Sites associated with the two error types were topographically distinct from one another. Most receptive sites were located in the middle portion of the superior temporal gyrus (STG), whereas most expressive sites fell outside this region, scattered along lateral temporal and temporoparietal cortex. CONCLUSIONS: Results raise clinical questions regarding the inclusion of the STG in temporal lobe epilepsy surgery and suggest that more detailed cortical mapping might enable better prediction of postoperative language decline. From a theoretical perspective, results carry implications regarding the understanding of structure-function relations underlying temporal lobe mediation of auditory language processing.


Subject(s)
Acoustic Stimulation , Brain Mapping , Language , Temporal Lobe/ultrastructure , Verbal Behavior/physiology , Adult , Anterior Temporal Lobectomy/methods , Dominance, Cerebral , Electric Stimulation , Epilepsy, Temporal Lobe/pathology , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/surgery , Female , Humans , Language Disorders/prevention & control , Language Tests , Male , Middle Aged , Names , Postoperative Complications/prevention & control , Preoperative Care , Retrospective Studies , Temporal Lobe/physiopathology
8.
Neuropsychopharmacology ; 25(5): 713-28, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11682255

ABSTRACT

This open pilot study of vagus nerve stimulation (VNS) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD(28) measure, 34.0% for the Montgomery-Asberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-I of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p =.0057). Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression.


Subject(s)
Depressive Disorder/therapy , Electric Stimulation Therapy , Vagus Nerve/physiology , Adolescent , Adult , Aged , Bipolar Disorder/psychology , Bipolar Disorder/therapy , Depressive Disorder/psychology , Drug Resistance , Electric Stimulation Therapy/adverse effects , Electroconvulsive Therapy , Electrodes, Implanted , Female , Humans , Male , Middle Aged , Mood Disorders/psychology , Mood Disorders/therapy , Pilot Projects , Psychiatric Status Rating Scales , Quality of Life , Treatment Outcome
9.
Neurology ; 56(1): 56-61, 2001 Jan 09.
Article in English | MEDLINE | ID: mdl-11148236

ABSTRACT

BACKGROUND AND OBJECTIVE: Visual object naming traditionally has been used to identify cortical areas essential for naming (i.e., word retrieval), and investigators have found critical naming sites in the middle and posterior temporal region in most patients. Based on clinical observation, empirical findings, and the pathophysiology of temporal lobe epilepsy, the authors hypothesized that naming sites identified from auditory cues might also be relevant, and that within the temporal region, these sites would be anatomically distinct and located anterior to naming sites based on visual cues. METHODS: Twenty patients requiring resective surgery involving the left (language dominant) temporal lobe underwent pre-resection language mapping using direct cortical stimulation. Visual and auditory naming were tested at lateral temporal sites extending from 1 cm from the anterior tip to the parietal operculum. RESULTS: Auditory naming was consistently disrupted by stimulation in the anterior temporal lobe, whereas both auditory and visual naming were impaired by stimulation in the posterior temporal region. CONCLUSIONS: This pattern may explain why word finding difficulties sometimes arise or worsen following surgical procedures in which the anterior temporal region is resected without language mapping, or when resection is based on mapping that identifies language cortex exclusively using visual tasks. These results suggest that utilization of auditory based naming tasks might improve pre-resection identification of essential language cortex during direct stimulation cortical mapping, as well as noninvasive localization of dysfunction during presurgical cognitive testing.


Subject(s)
Brain Mapping , Epilepsy, Temporal Lobe/pathology , Epilepsy, Temporal Lobe/physiopathology , Temporal Lobe/anatomy & histology , Temporal Lobe/physiology , Auditory Perception , Dominance, Cerebral , Epilepsy, Temporal Lobe/surgery , Female , Humans , Male , Verbal Behavior , Visual Perception
10.
Mov Disord ; 15(6): 1242-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11104213

ABSTRACT

Fourteen patients with primary or secondary dystonia received intrathecal baclofen (ITB) through an implanted pump following a trial dose. Patients were selected for ITB trial if they had clinically unsatisfactory responses to oral antidystonic medications, including oral baclofen. Patients were rated using the Burke-Fahn-Marsden rating scale by a blinded rater after the dose of ITB was optimized. Five patients experienced improvement in symptoms as determined by a change in rating scale scores, although only two had a clear clinical benefit. Etiology of dystonia did not determine the efficacy of ITB therapy, as benefit or failure was seen in both primary and secondary dystonia.


Subject(s)
Baclofen/administration & dosage , Dystonia/drug therapy , Muscle Relaxants, Central/administration & dosage , Adult , Baclofen/adverse effects , Female , Humans , Infusion Pumps, Implantable , Injections, Spinal , Male , Middle Aged , Muscle Relaxants, Central/adverse effects , Treatment Outcome
11.
Epilepsia ; 41(11): 1463-8, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11077461

ABSTRACT

PURPOSE: New post-resection spikes on electrocorticography (ECoG) after lesionectomy in patients with seizures may represent residual epileptogenic tissue or presumed reactive injury spikes. We investigated the existence of post-resection injury spikes by eliminating the possibility of residual epileptogenic tissue. METHODS: Preresection and post-resection ECoG was performed on seven patients with an intra-axial neocortical tumor (glioblastoma multiforme or metastasis) and no history of seizures. All tumors were gross-totally resected. RESULTS: The mean age of the patients was 59 years. The tumor location was frontal in four patients, parietal in two, and temporal in one. Two patients had preresection spikes with an average rate of 68 spikes/min that disappeared after surgery. Two different patients had new post-resection spikes, with an average firing rate of 4 spikes/min, despite normal preresection ECoG. In one of these patients, the new spikes were superimposed over a burst suppression pattern. Neither patient developed seizures after surgery. CONCLUSIONS: Surgical irritation of the neocortex is sufficient to produce reactive post-resection epileptogenic discharges surrounding an intra-axial neocortical tumor even in the absence of preoperative seizures and spikes. Injury spikes fire at a slow rate and are not predictive of clinical seizures.


Subject(s)
Brain Neoplasms/surgery , Cerebral Cortex/surgery , Electroencephalography/statistics & numerical data , Epilepsy/diagnosis , Glioblastoma/surgery , Postoperative Complications/diagnosis , Adult , Aged , Anticonvulsants/therapeutic use , Cerebral Cortex/physiopathology , Epilepsy/physiopathology , Epilepsy/prevention & control , Female , Humans , Male , Middle Aged , Postoperative Complications/physiopathology , Postoperative Complications/prevention & control , Prospective Studies
12.
J Neurosurg ; 91(1): 20-5, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10389875

ABSTRACT

OBJECT: Ventricular size often shows no obvious change following third ventriculostomy, particularly in the early postoperative period, making postoperative evaluation difficult without expensive and often invasive testing in patients with equivocal clinical responses. The authors hypothesized that performing careful volumetric measurements would show decreases in size within the first 3 weeks after surgery. METHODS: Volumetric measurements were calculated from standard 3 x 3-mm axial computerized tomography (CT) scans obtained immediately before and 3 and 21 days after surgery. Two independent investigators measured third ventricular volume in a series of 16 patients and lateral ventricular volume in 10 of the patients undergoing stereotactically guided endoscopic third ventriculostomy for noncommunicating hydrocephalus. Fifteen patients were symptomatically improved at the time the follow-up scan was obtained. Third ventricular volume decreased in all patients by a mean of 35% (range 7.8-95.1%) and lateral ventricular volume decreased in all patients by a mean of 33% (range 4.5-80.3%). The degree of change correlated with the length of preoperative symptoms (p < 0.005). The one patient who experienced no improvement showed no decrease in third ventricular volume. In seven of 10 patients, the decrease in third ventricular volume exceeded the decrease in lateral ventricular volume. Repeated measurements indicated that the 95% confidence interval for the authors' calculations varied around the mean by 2.5% for third ventricular volume and 1.2% for lateral ventricular volume. Long-term outcome was excellent, with only one case of delayed failure. The mean follow-up duration was 12 months. CONCLUSIONS: Volumetric measurements calculated from standard CT scans will show a demonstrable decrease in ventricular volume soon after successful third ventriculostomy and can be helpful in assessing patients postoperatively. Although the third ventricle may exhibit a greater decrease, the lateral ventricular measurements are more accurate. Patients with more indolent symptoms show the smallest change.


Subject(s)
Cerebral Ventricles/pathology , Hydrocephalus/pathology , Ventriculostomy , Adolescent , Adult , Aged , Cerebral Ventricles/surgery , Child , Child, Preschool , Endoscopy , Female , Humans , Hydrocephalus/surgery , Infant , Male , Middle Aged , Prospective Studies , Stereotaxic Techniques , Treatment Outcome , Ventriculostomy/methods
13.
Mov Disord ; 14(2): 256-61, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10091619

ABSTRACT

Twenty consecutive patients with idiopathic Parkinson's disease underwent stereotactic posteroventral pallidotomy. Schwab and England ADL scores in the "off" state were improved by 18% and in the "on" state the scores declined by 2%. Three patients also reported marked improvement in "off" state dystonia. One-year data are available on 12 patients who underwent evaluations according to the Core Assessment Program for Intracerebral Transplantation protocol preoperatively and at 3, 6, and 12 months after surgery. Significant improvements in Unified Parkinson's Disease Rating Scale sections II and III scores in the "off" state, composite "off" state scores of bradykinesia and rigidity, contralateral tremor in the "off" state, and contralateral dyskinesias were observed. Although there was reduction in the daily levodopa dose, this did not reach statistical significance. Major complications (15%) included hemiparesis (one of 20) and visual field cuts (two of 20); minor complications (45%) included mild cognitive dysfunction (four of 20), reading difficulty not related to visual disturbance (one of 20), and 5-10 lb weight gain (four of 20).


Subject(s)
Globus Pallidus/surgery , Movement Disorders/surgery , Parkinson Disease/surgery , Stereotaxic Techniques/standards , Activities of Daily Living , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Monitoring, Intraoperative , Recovery of Function , Stereotaxic Techniques/adverse effects , Time Factors , Treatment Outcome
14.
Ann Neurol ; 44(5): 749-57, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9818930

ABSTRACT

The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Ten MR studies were read prospectively as showing FCD; these case histories, electroencephalographic studies, and neuroimaging data were reviewed. Eight of these patients subsequently underwent focal cortical resection guided by intraoperative electrocorticography. The MR findings were correlated with pathological findings in these 8 patients. For purposes of radiological-pathological correlation, the FCD lesions were divided into two classes. Radiological classification was based on the absence (type A) or presence (type B) of T2 prolongation of the subcortical white matter. Pathological grading as type I or type II was based on a previously described pathological grading system. Specific MR findings associated with FCD included focal blurring of the gray-white matter interface (n = 9), thickening of the cortical ribbon (n = 7), and T2 prolongation of the subcortical white matter (n = 4). In 3 patients, the only MR finding that suggested FCD was localized blurring of the gray-white matter junction. In 2 of these 3 patients, the MR diagnosis of FCD could be made only by FMPIR. FCD was confirmed histologically in 7 of 8 patients, with insufficient tissue for complete histopathological evaluation in 1 case. Radiological classification of FCD agreed with pathological classification in 5 of 7 cases. Correlation of MR findings with intraoperative electrocorticography results indicated that the MR study localized the epileptogenic lesion correctly in 8 of 8 cases. Scalp ictal electroencephalographic studies localized the epileptogenic lesion in 5 of 8 cases; positron emission tomographic scans were focally abnormal in 3 of 3 cases. FMPIR MR imaging permitted accurate diagnosis and localization of FCD in all patients with pathologically proved FCD. MR identification of FCD aided presurgical planning and intraoperative management of these patients.


Subject(s)
Cerebral Cortex/pathology , Epilepsies, Partial/pathology , Magnetic Resonance Imaging/methods , Adolescent , Adult , Cerebral Cortex/diagnostic imaging , Child , Child, Preschool , Epilepsies, Partial/classification , Epilepsies, Partial/diagnostic imaging , Female , Fluorodeoxyglucose F18 , Humans , Infant , Male , Neocortex/pathology , Radiopharmaceuticals , Tomography, Emission-Computed
16.
Neurosurgery ; 43(3): 639-44; discussion 644-5, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9733324

ABSTRACT

INTRODUCTION: Although technically challenging to obtain, ictal functional magnetic resonance imaging has been used to localize ictal onset zones in a small number of patients. We used this technique to demonstrate the inherent epileptogenicity of dysplastic cortex. METHODS: We present a 16-year-old female patient with intractable left-sided sensorimotor seizures and a congenital dysplastic cleft lying along the right rolandic fissure. Preoperative functional magnetic resonance imaging (blood oxygen level-dependent sequence, 1.5 T) localized the motor and sensory cortices to the anterior border of the cleft. During a speech activation run, the patient experienced a 20-second seizure. Initial activation was seen within the dysplastic cortex along the deep posterior margin of the cleft. Intraoperative median nerve stimulation produced a distinct N20/P20 wave inversion over the dysplastic cleft. Stimulation mapping performed with the patient awake confirmed the location of the sensorimotor cortex on the anterior border of the cleft, and preresection electrocorticography identified abundant interictal spikes along the posterior border after opening the cleft. RESULTS: After surgical resection of the dysplastic cortex, the patient exhibited transient minimal weakness and mild neglect, which resolved within 1 week. Two years after surgery, she was neurologically intact and seizure-free. CONCLUSION: This study used functional magnetic resonance imaging to demonstrate the inherent epileptogenicity of dysplastic cortex and to simultaneously map ictal and functional cortex. The N20 wave inversion can be a useful intraoperative tool for identifying the central sulcus (or its equivalent), even in the presence of abnormal cortical architecture.


Subject(s)
Magnetic Resonance Imaging , Seizures/diagnosis , Adolescent , Brain/pathology , Brain Mapping , Electrophysiology , Female , Follow-Up Studies , Humans , Intraoperative Period , Motor Activity/physiology , Seizures/physiopathology , Seizures/surgery , Sensation/physiology
17.
Ann Neurol ; 43(5): 576-85, 1998 May.
Article in English | MEDLINE | ID: mdl-9585351

ABSTRACT

The adult mammalian forebrain harbors neuronal precursor cells in the subependymal zone (SZ). Neuronal progenitors also persist in the adult human SZ and have been cultured from epileptic temporal lobe. In the present study, we sought to identify these neural progenitors in situ, and to direct their expansion and neuronal differentiation in vitro. We prepared explants of adult human SZ, obtained from temporal lobe resections of refractory epileptics. The resultant cultures were treated with fibroblast growth factor-2 (FGF-2) for a week, with concurrent exposure to [3H]thymidine, then switched to media containing brain-derived neurotrophic factor (BDNF) for up to 2 months. Sporadic neuronal outgrowth, verified antigenically and physiologically, was observed from SZ cultures regardless of FGF-2/BDNF treatment; however, only FGF-2/BDNF-treated cultures exhibited profuse outgrowth, and these displayed neuronal survival as long as 9 weeks in vitro. In addition, cortical cultures derived from two brains generated microtubule-associated protein-2+ neurons, which incorporated [3H]thymidine and exhibited significant calcium increments to depolarization. In histological sections of the subependyma, both uncommitted and restricted progenitors, defined respectively by musashi and Hu protein expression, were identified. Thus, the adult human subependyma harbors neural progenitors, which are able to give rise to neurons whose numbers can be supported for prolonged periods in vitro.


Subject(s)
Brain-Derived Neurotrophic Factor/pharmacology , Drosophila Proteins , Ependyma/cytology , Fibroblast Growth Factor 2/pharmacology , Neurons/drug effects , Stem Cells/drug effects , Adult , Age Factors , Biomarkers , Calcium/metabolism , Cell Differentiation/drug effects , Cell Division/drug effects , Cell Size , Cells, Cultured , Child , ELAV Proteins , Electric Stimulation , Ependyma/chemistry , Female , Humans , Infant , Male , Middle Aged , Nerve Tissue Proteins/analysis , Neurons/cytology , Neurons/metabolism , RNA-Binding Proteins/analysis , Stem Cells/cytology , Stem Cells/metabolism
18.
Neurosurgery ; 42(4): 858-67; discussion 867-8, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9574651

ABSTRACT

The damaged adult mammalian brain is incapable of significant structural self-repair. Although varying degrees of recovery from injury are possible, this is largely because of synaptic and functional plasticity rather than the frank regeneration of neural tissues. The lack of structural plasticity of the adult brain is partly because of its inability to generate new neurons, a limitation that has severely hindered the development of therapies for neurological injury or degeneration. However, a variety of experimental studies, as well as moderately successful clinical engraftment of fetal tissue into the adult parkinsonian brain, suggests that cell replacement is evolving as a valuable treatment modality. Neural stem cells, which are the self-renewing precursors of neurons and glia, have been isolated from both the embryonic and adult mammalian central nervous system. In the adult human brain, both neuronal and oligodendroglial precursors have been identified, and methods for their harvest and enrichment have been established. Neural precursors have several characteristics that make them ideal vectors for brain repair. They may be clonally expanded in tissue culture, providing a renewable supply of material for transplantation. Moreover, progenitors are ideal for genetic manipulation and may be engineered to express exogenous genes for neurotransmitters, neurotrophic factors, and metabolic enzymes. Thus, the persistence of neuronal precursors in the adult mammalian brain may permit us to design novel and effective strategies for central nervous system repair, by which we may yet challenge the irreparability of the structurally damaged adult nervous system.


Subject(s)
Brain Diseases/therapy , Genetic Therapy/methods , Neuroglia/physiology , Neurons/physiology , Stem Cell Transplantation , Stem Cells/physiology , Animals , Cell Line, Transformed , Embryo, Mammalian/physiology , Humans , Nervous System/embryology
20.
Neurosurgery ; 41(1): 20-4, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9218291

ABSTRACT

OBJECTIVE: Because hypothermia enhances human tolerance for cerebral ischemia, profound hypothermia is induced in many centers so that the circulation can be arrested while clips are applied to high-risk giant cerebral aneurysms. Brain temperature is measured directly with an intracerebral probe that avoids the uncertainty of surrogate monitoring. However, when there is a large thermal gradient between brain temperature and that of the operating room, even direct measurements can sometimes be misleading. This study was undertaken to determine how deeply a thermal sensor must be embedded in the cerebral parenchyma to ensure that the ambient environment does not distort the measurement of brain temperature. METHODS: Each of 39 normothermic patients had a thermocouple sensor inserted into a temporal lobe seizure focus just before its resection. Brain temperature was measured as the sensor was withdrawn in stages. RESULTS: At both 3 and 2 cm beneath the cortical surface, the temperature of the brain was essentially the same. However, when the sensor was withdrawn to 1 cm, recorded temperature decreased from 35.7 +/- 0.9 to 34.3 +/- 1.4 degrees C (P < 0.001) and irrigation in the vicinity caused major thermal change. At shallower depths, even lower brain temperatures were recorded. No morbidity was attributable to the temperature measurements. CONCLUSION: Direct intraoperative measurement of human brain temperature is feasible and safe, but accuracy requires that the temperature sensor be inserted at least 2 cm into the cerebral cortex.


Subject(s)
Hypothermia, Induced/instrumentation , Intracranial Aneurysm/surgery , Monitoring, Intraoperative/instrumentation , Thermometers , Body Temperature Regulation/physiology , Brain Mapping/instrumentation , Electrodes , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/surgery , Feasibility Studies , Humans , Intracranial Aneurysm/physiopathology , Psychosurgery/instrumentation , Temporal Lobe/physiopathology , Temporal Lobe/surgery
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