Consideration of epilepsy surgery in adults should be independent of age.

OBJECTIVES: Epilepsy surgery is performed less frequently in persons over 45 years of age than in younger individuals, probably reflecting biases among patients, referring physicians and neurologists. METHODS: We report on a clinically heterogeneous cohort of patients aged 45 years or older who underwent epilepsy surgery for medically intractable epilepsy. RESULTS: Over a 15-year period, 42 patients with a mean duration of epilepsy of 27.3 years underwent elective surgery. The mean follow-up period was 48 months. Thirty-two patients had an Engel class I outcome, of which 23 were totally seizure-free (Ia). Six patients had a class II outcome (rare disabling seizures), one had a class III outcome (worthwhile improvement), and three had a class IV outcome (no worthwhile improvement). The majority of patients reported an improved quality of life and satisfaction with the epilepsy surgery. A subjective improvement in cognition was reported in 7 patients while a decline was reported in 10 patients. New neuropsychiatric difficulties were reported in three patients while three patients reported improved anxiety after surgery. Only one patient became newly employed after surgery while 23 returned to driving. Permanent complications occurred in four patients (thalamic infarct during a Wada test (n=1) and asymptomatic visual field defect (n=3)). CONCLUSIONS: We report a favorable outcome from epilepsy surgery in a large series of older adults and conclude that age per se is not a contraindication to epilepsy surgery. We emphasize the lack of correlation between outcome from surgery and pre-operative duration of epilepsy.

MR spectroscopic changes in the rat hippocampus following proton radiosurgery.

PURPOSE: To identify MR spectroscopic changes in the rat hippocampus following proton radiosurgery. METHODS AND MATERIALS: A group of 12 rats were treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 30 CGE, 50 CGE, 70 CGE, 90 CGE were delivered to groups of 3 animals using single fraction technique. Animals were imaged using a standard 3 T GE Signa MRI at 4 months following treatment. An untreated animal was also studied. A 3'' surface coil was employed to obtain T1 weighted coronal pre- and post-gadolinium images (TR 600 and TE 30) and dual echo T2 weighted coronal images (TR 3000, TE 30/90). Volumetric analysis with custom software was done to evaluate areas of increased signal on T2 weighted images and the development of hydrocephalus was examined. Animals were sacrificed and specimens of the treated hippocampus were harvested for High Resolution Magic Angle Spinning MR Spectroscopy (HRMAS) followed by histopathology of the tissue samples. Peak values of choline, creatine, N-acetyl aspartate and lipids were evaluated and compared. RESULTS: Peak tissue injury occurred in the surviving 90 CGE animal by both T2 weighted and post-gadolinium imaging. Gadolinium enhancement was seen in decreasing volumes of tissue at dosage levels from 90 to 50 CGE. Hydrocephalus was seen on the untreated side in the 90 CGE animal likely because of mass effect, while it was seen in small degrees in the side of treatment in the 70 and 50 CGE animals. Histopathology showed changes at 90 and 70 CGE, but not at 50 or 30 CGE at this time point using H and E stains. HRMAS showed spectroscopic changes in the surviving 90 and 70 CGE animals but not in the 50 and 30 CGE animals. Statistical significance was not reached because of the small sample size. CONCLUSIONS: Following single dose proton radiosurgery of rat hippocampus, HRMAS is able to identify metabolic changes induced by radiation. Studies built on these principles may help develop non-invasive MR spectroscopic methods to distinguish radiation changes from tumor recurrence.

The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients.

OBJECTIVE: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder.

BACKGROUND: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.

Alfentanil-induced epileptiform activity: a simultaneous surface and depth electroencephalographic study in complex partial epilepsy.

PURPOSE: Alfentanil is a high potency mu opiate receptor agonist commonly used during presurgical induction of anesthesia. This and other opiate receptor agonists have demonstrated proconvulsant effects in animals, but these properties have been less consistently demonstrated in humans. Most human scalp EEG studies have failed to demonstrate induction of epileptiform activity with these agents, which is inconsistent with findings using intracranial EEG. Simultaneous scalp and depth EEG recordings have yet to be performed in this setting. The relationship between opiate dose and proconvulsant activity is unclear. METHODS: Simultaneous scalp and depth electrode recordings were performed on five patients with complex partial epilepsy (CPE) who underwent alfentanil anesthesia induction before depth electrode removal. Consecutive equal bolus doses of alfentanil were administered to each patient according to strict time intervals so as to assess their correlation with any induced epileptiform activity. RESULTS: Epileptiform activity was induced by alfentanil in three of five patients. Two of these patients had electrographic seizures. Epileptiform activity was only detected from the depth electrodes, occurring within 2 min of the first bolus dose in all three cases. Further increase or spread of epileptiform activity did not occur despite cumulative bolus doses of alfentanil. CONCLUSIONS: Alfentanil is proconvulsant in patients with CPE. Induced seizures may be subclinical and lack a scalp EEG correlate. There is a complex dose-response relationship. Alfentanil induction of anesthesia should be approached with caution in patients with CPE.

Outcomes following staged bilateral pallidotomy in advanced Parkinson's disease.

The authors assessed clinical outcome for up to one year after staged bilateral pallidotomy in 14 patients with advanced PD. One year after surgery, dyskinesias were virtually abolished and there were significant reductions in "off" time (67%) and activities of daily living "off" scores (24%), as well as nonsignificant reduction in "off" motor score (39%); "on" scores were unchanged. One patient developed a visual field deficit; two had transient confusion. Staged bilateral pallidotomy improves motor function in selected patients with advanced PD.

Deficits in visual cognition and attention following bilateral anterior cingulotomy.

A series of eight tests of visual cognitive abilities was used to examine pre- to post-operative performance changes in a patient receiving bilateral anterior cingulotomy. Compared with a set of eight matched control participants, post-operatively, the patient exhibited deficits in (a) the ability to sequence novel cognitive operations required to generate multipart images or rotate perceptual stimuli; (b) the ability to search for, select, and compare images of objects when the instructions did not specify precisely which objects should be visualized; and, (c) the ability to select a controlled and unpracticed response over an automatic one. Other imagery and cognitive tasks were not affected. Results are consistent with the hypothesis that anterior cingulate cortex is a component of an executive control system. One of the anterior cingulate's roles may be to monitor on-line processing and signal the motivational significance of current actions or cognitions.

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology.

A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods.

Improvement in severe self-mutilation following limbic leucotomy: a series of 5 consecutive cases.

BACKGROUND: The efficacy of neurosurgical intervention for self-mutilation behavior associated with severe, intractable psychiatric disorders remains undetermined. We report the effects of limbic leucotomy in 5 consecutive patients with severe self-mutilation behaviors. METHOD: After unsolicited referrals from their psychiatrists and careful consideration by the Massachusetts General Hospital Cingulotomy Assessment Committee (MGH-CAC), 5 patients were treated with limbic leucotomy. Their primary DSM-IV psychiatric diagnoses were either obsessive-compulsive disorder or schizoaffective disorder. Comorbid severe, treatment-refractory self-mutilation was an additional target symptom. Outcome was measured by an independent observer using the Clinical Global Improvement. Current Global Psychiatric-Social Status Rating, and DSM-IV Global Assessment of Functioning scales in addition to telephone interviews with patients, families, their psychiatrists, and treatment teams. The mean postoperative follow-up period was 31.5 months. RESULTS: All measures indicated sustained improvement in 4 of 5 patients. In particular, there was a substantial decrease in self-mutilation behaviors. Postoperative complications were transient in nature. and postoperative compared with preoperative neuropsychological assessments revealed no clinically significant deficits. CONCLUSION: In carefully selected patients as described in this report, limbic leucotomy may be an appropriate therapeutic consideration for self-mutilation associated with severe, intractable psychiatric disorders.

A magnetic resonance imaging study of regional cortical volumes following stereotactic anterior cingulotomy.

The purpose of this study was to test the hypothesis that orbitofrontal cortical volume would be reduced following anterior cingulotomy for obsessive-compulsive disorder (OCD). Whole brain cortical parcellation was performed on magnetic resonance imaging (MRI) data from nine patients, before and 9 (+/-6) months following anterior cingulotomy. No significant volumetric reductions were found in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral temporo-fusiform and posterior cingulate regions were consistent with chance differences, in the face of multiple comparisons. Therefore, though the circumscribed lesions of anterior cingulotomy have recently been associated with corresponding volumetric reductions in the caudate nucleus, no comparable volumetric reductions are evident in cortical territories. Taken together, these results are most consistent with a model of cingulo-striatal perturbation as a putative mechanism for the efficacy of this procedure. While limitations in sensitivity may have also contributed to these negative findings, the methods employed have previously proven sufficient to detect cortical volumetric abnormalities in OCD. The current results may reflect a relatively diffuse pattern of cortico-cortical connections involving the neurons at the site of cingulotomy lesions. Future functional neuroimaging studies are warranted to assess possible cortical or subcortical metabolic changes associated with anterior cingulotomy, as well as predictors of treatment response.

Multimodality neuroimaging: research and clinical applications.

This manuscript reviews the current stance and the pertinent problems of transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) as brain mapping methodologies. The missing structure-function relation limits the use of TMS, whereas the uncertainty about the functional significance of activated cortical regions might render interpretation of fMRI studies difficult. Advances in image processing, however, allowed for 3- dimensional real-time visual guidance of TMS and integration with fMRI data. We describe the method used to coregister TMS and fMRI and present examples where a multimodality neuroimaging approach might add to our understanding of normal and pathological brain function.

Resection of a dominant-hemisphere intraventricular meningioma facilitated by functional magnetic resonance imaging. Case report.

Intraventricular meningiomas of the lateral ventricle occur relatively rarely, but they are often large at the time of detection and present more commonly on the left side. Although the ability to resect these tumors safely has greatly improved over time, standard surgical approaches often traverse cortex close to areas of specific cortical function. Precise cortical mapping of language and sensorimotor cortices can be accomplished noninvasively by using functional magnetic resonance (fMR) imaging. The authors used fMR imaging in planning the cortical incision for resection of a large intraventricular trigone meningioma in the dominant hemisphere of a patient who, postoperatively, suffered no aphasia or hemiparesis. The authors discuss the advantages of mapping cortical function preoperatively with fMR imaging when approaching intraventricular lesions.

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.

Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results.

OBJECT: Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate. In this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure. METHODS: Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain. Individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning- and MR imaging-guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery. Seventy-five patients (mean age 61 years, range 38-79 years) underwent unilateral pallidotomy. Significant improvements were observed in the "off' period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total "on" time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 +/- 5.4 mm3. Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect. CONCLUSIONS: Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD.

Surgery for psychiatric disorders.

The modern therapeutic approach to most psychiatric diseases involves a combination of well-supervised psychotherapy, pharmacotherapy, and electroconvulsive therapy. Patients who fail to adequately respond to these modern treatment methods and remain severely disabled may be considered for surgical intervention. Cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy are the most common psychosurgical procedures performed today, with response rates in the 35% to 65% range. Modern stereotactic techniques have reduced complication rates, but controversy remains regarding the optimal surgical procedure. The major psychiatric diagnostic categories that might respond to surgery include treatment-refractory major affective disorders, obsessive-compulsive disorder, and chronic anxiety states. Surgery should be considered as one part of an entire treatment plan and must be followed by an appropriate psychiatric rehabilitation program. It should only be carried out by an expert multidisciplinary team consisting of a neurologist a neurosurgeon, and a psychiatrist with experience in these disorders. Surgical intervention remains a reasonable therapeutic option for select patients with a disabling psychiatric disease and may be underutilized.

Occult vascular malformations and seizures.

Occult vascular malformations are frequently associated with intractable seizures and are a common cause of lesional epilepsy. MR imaging can identify and characterize these lesions with accuracy. The presurgical evaluation must be tailored to the individual patient's presentation and circumstances. Surgical results following lesionectomy plus corticectomy may be slightly superior to lesionectomy alone, but the overall prognosis is excellent.

Accuracy of EEG dipole source localization using implanted sources in the human brain.

OBJECTIVES: The location of electrical sources in the brain can be estimated by calculating inverse solutions in which the location, amplitude and orientation of the electrical sources are fitted to the scalp EEG. To assess localization accuracy of the moving dipole inverse solution algorithm (ISA), we studied two patients who had depth electrodes implanted for presurgical planning of epilepsy surgery. METHODS: Artificial dipoles were created by connecting a single sine wave pulse generator to different pairs of electrodes in multiple orientations and depths. Surface EEG recordings of the resulting pulses were evaluated with the ISA using a 4-shell spherical head model and plotted on the subjects' MRI. Dipole localization errors were evaluated with respect to the number of averaged pulses, different electrode montages and different dipole locations and orientations. RESULTS: Dipoles located at 40-57 mm from the scalp surface had localization errors that were greater than those located at 62-85 mm. Localization accuracy improved with increasing numbers of pulses and recording electrodes. Results with a standard 10-20 array of 21 electrodes showed an average localization error of 17 mm, whereas 41 electrodes improved this to 13 mm. Mean angular errors were 31 and 30 degrees, respectively. CONCLUSIONS: The ISA was able to differentiate between tangential and radial dipoles. We conclude that our implementation of the ISA is a useful and sound method for localizing electrical activity in the brain.

Visual discrimination after anterior temporal lobectomy in humans.

OBJECTIVE: To determine whether right anterior temporal lobectomy (RTL) results in perceptual deficits, and whether the perception of particular stimulus features (i.e., shape, motion, color) is affected differentially. BACKGROUND: RTL results in abnormal visual discrimination, recognition, and recall of pictorial material that cannot be easily specified verbally, such as designs and faces. It is unclear whether stimuli must be conceptually meaningful to elicit perceptual deficits. METHODS: Tests were constructed to assess a wide spectrum of basic visual discrimination abilities with simple, meaningless stimuli. The performance of nine patients who underwent left temporal lobectomy (LTL) and nine patients who underwent RTL were compared with that of normal control individuals. The mean excision size along lateral cortex was 3.7 cm for the LTL group and 5.6 cm for the RTL group; mean mesial excision size was 5.2 cm for LTL and 4.6 cm for RTL. RESULTS: Basic visual discrimination capacities were demonstrated to be essentially intact after LTL and RTL, except for a mild loss of blue color discrimination after RTL. CONCLUSIONS: There is little evidence that RTL produces perceptual impairments limited to the domain of pattern perception, or generalizable to nonmeaningful stimuli. The perceptual loss after RTL may be largely restricted to extraction of meaning, and related to the disruption of the circuits that connect the outcome of visual analysis to previously stored semantic information.