Stereotactic Thermocoagulation Research Articles

Changes in local and network brain activity after stereotactic thermocoagulation in patients with drug-resistant epilepsy.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) aims to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative lesions. Although RF-TC is hypothesized to functionally modify brain networks, reports of changes in functional connectivity (FC) following the procedure are missing. We evaluated, by means of SEEG recordings, whether variation in brain activity after RF-TC is related to clinical outcome. Interictal SEEG recordings from 33 patients with drug-resistant epilepsy (DRE) were analyzed. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 1 month following RF-TC. Local (power spectral density [PSD]) and FC changes were evaluated in 3-min segments recorded shortly before (baseline), shortly after, and 15 min after RF-TC. The PSD and FC strength values after thermocoagulation were compared with baseline as well as between the responder and nonresponder groups. In responders, we found a significant reduction in PSD after RF-TC in channels that were thermocoagulated for all frequency bands (p = .007 for broad, delta and theta, p <.001 for alpha and beta bands). However, we did not observe such PSD decrease in nonresponders. At the network level, nonresponders displayed a significant FC increase in all frequency bands except theta (broad, delta, beta band: p <.001; alpha band: p <.01), although responders showed a significant FC decrease in delta (p <.001) and alpha bands (p <.05). Nonresponders showed stronger FC changes with respect to responders exclusively in TC channels (broad, alpha, theta, beta: p >.05; delta: p = .001). Thermocoagulation induces both local and network-related (FC) changes in electrical brain activity of patients with DRE lasting for at least 15 min. This study demonstrates that the observed short-term modifications in brain network and local activity significantly differ between responders and nonresponders and opens new perspectives for studying the longer-lasting FC changes after RF-TC.

Author Response: One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia

We thank Dr. Hu and colleagues for their encouraging comments on our article.1 Both of our groups advocate minimal, targeted resections of bottom-of-sulcus dysplasia (BOSD),1,2 and we further promote omitting intracranial EEG monitoring in MRI-positive cases. As noted in references 41–45 in our article, laser interstitial thermal therapy (LITT) and stereotactic thermocoagulation (STC) are reported in BOSD to further minimize surgical intervention and are appropriate for medial, basal frontal, and parietal BOSDs—occurrences which are not as easily accessed with small craniotomy as BOSD on the cerebral convexity. STC is typically undertaken in patients who undergo prior stereo-EEG with an electrode directly sited in an MRI-positive BOSD. The potential disadvantages of LITT and STC are the lack of confirmation of epileptogenicity with electrocorticography, a pathologic diagnosis from histopathology, and identification of genetic variants from deep sequencing of tissue.

Stereotactic Electroencephalography in Patients with Drug-resistant Epilepsy

Stereotactic electroencephalography (SEEG) is an important method for invasive presurgical exploration of candidates for epilepsy surgery by means of stereotactic implantation of intracerebral electrodes without craniotomy. Implantations of intracerebral electrodes through craniotomy in drug-resistant epileptic patients have been performed in Bulgaria in the 1980s, but no further development of epilepsy surgery followed. The aim of our study is to present the first Bulgarian series of patients with drug-resistant epilepsy explored by SEEG. Our study included 53 patients with drug-resistant epilepsy explored by SEEG. Stereotactic Leksell frame, stereotactic software for avascular trajectory planning and depth electrodes with diameter of 0.8 mm and 8–18 contacts were used in all patients. Subsequently, long-term video-SEEG monitoring of various duration was performed and registered interictal and ictal EEG activity in order to evaluate the putative epileptogenic zone. Fifty-three patients were explored by 62 SEEGs because one patient underwent three SEEG procedures and seven patients – two SEEG procedures. We implanted 753 electrodes in these 62 SEEGs (mean: 12 electrodes per exploration; range: 5–20 electrodes). The mean age in our cohort was 23.6 years (4–60 years). The main indication for SEEG was MRI-negative epilepsy (20 patients). Focal cortical dysplasia was found in 17 cases, and hippocampal sclerosis in 8 cases. Surgical intervention was done in 48 patients (91%). Surgical resection of the epileptogenic zone (EZ) as defined by the SEEG was performed in 27 patients; radiofrequency stereotactic thermocoagulation (RFTC) on selected electrode contacts was applied in seven patients, and both procedures (i.e. RFTC followed by resective surgery) were performed on 14 patients. Full seizure control (Engel class I) was achieved in 28 patients (58.3%) and significant improvement – in 17 patients (35.4%). Three patients (6.2%) had no effect from surgery. No complications were observed in our series of 62 SEEGs. SEEG is a major tool for the determination of the EZ in patients with drug-resistant epilepsy who are candidates for epilepsy surgery, including MRI-negative cases or such without congruent data from the clinical, neurophysiological and neuroimaging perspectives. SEEG is a low-risk invasive diagnostic and even a therapeutic method when performed by experienced epilepsy surgery team.

Editors' Note: One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia

In “One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia,” Macdonald-Laurs et al. described the performance of corticectomy guided by MRI and electrocorticography (ECoG) in 38 patients with bottom-of-sulcus dysplasia (BOSD). They found that at a median of 6 years postop, 87% of patients were seizure free and noted that their outcomes are similar to those reported in a small series of patients with BOSD who underwent stereotactic thermocoagulation (STC) and laser interstitial thermal therapy (LITT). Hu et al. reported that based on their recent LITT trial, in which they found that 6 of 7 (86%) patients with BOSD were seizure-free 6 months postop, they recommend minimally invasive procedures for BOSD. Harvey et al. agreed with the use of STC or LITT for BOSD in locations that are not easily accessible via a small craniotomy. However, these procedures preclude the use of ECoG to determine epileptogenicity, histopathologic confirmation, and genetic testing of the tissues. In addition, STC and LITT pose risk to surrounding normal cortex and are not widely available. The authors all agree that there is a need for additional long-term outcome data using different treatment strategies in larger cohorts of patients with BOSD. In “One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia,” Macdonald-Laurs et al. described the performance of corticectomy guided by MRI and electrocorticography (ECoG) in 38 patients with bottom-of-sulcus dysplasia (BOSD). They found that at a median of 6 years postop, 87% of patients were seizure free and noted that their outcomes are similar to those reported in a small series of patients with BOSD who underwent stereotactic thermocoagulation (STC) and laser interstitial thermal therapy (LITT). Hu et al. reported that based on their recent LITT trial, in which they found that 6 of 7 (86%) patients with BOSD were seizure-free 6 months postop, they recommend minimally invasive procedures for BOSD. Harvey et al. agreed with the use of STC or LITT for BOSD in locations that are not easily accessible via a small craniotomy. However, these procedures preclude the use of ECoG to determine epileptogenicity, histopathologic confirmation, and genetic testing of the tissues. In addition, STC and LITT pose risk to surrounding normal cortex and are not widely available. The authors all agree that there is a need for additional long-term outcome data using different treatment strategies in larger cohorts of patients with BOSD.

Author Response: One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia.

We thank Dr. Hu et al. for their encouraging comments on our article.1 Both our groups advocate minimal, targeted resections of bottom-of-sulcus dysplasia (BOSD),1,2 and we further promote omitting intracranial EEG monitoring in MRI-positive cases. As noted in references 41–45 in our article, laser interstitial thermal therapy (LITT) and stereotactic thermocoagulation (STC) are reported in BOSD, further minimize surgical intervention, and are appropriate for BOSD on the medial and basal cerebral surfaces—occurrences which are not as easily accessed with a small craniotomy as BOSD on the cerebral convexity. STC is typically undertaken in patients who undergo previous stereo-EEG with an electrode directly sited in an MRI-positive BOSD. The potential disadvantages of LITT and STC are the lack of confirmation of epileptogenicity with electrocorticography, a pathologic diagnosis from histopathology, and identification of genetic variants from deep sequencing of tissue.

Changes in epileptogenicity biomarkers after stereotactic thermocoagulation.

Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery. Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery. After thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross-rate in the epileptogenic zone than patients without clinical improvement (p=.002, p=.02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p<.05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF-TC was found in patients with a favorable outcome of resective surgery (spikes, p=.026; HFOs, p=.03; cross-rate, p=.03). Quantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.

Surgical treatment of hypothalamic hamartomas.

Hypothalamic hamartomas are aberrant masses, composed of abnormally distributed neurons and glia. Along endocrine and cognitive symptoms, they may cause epileptic seizures, including the specific gelastic and dacrystic seizures. Surgery is the treatment of drug-resistant hamartoma epilepsy, with associated positive results on endocrine, psychiatric, and cognitive symptoms. Recently, alternatives to open microsurgical treatment have been proposed. We review these techniques and compare their efficacy and safety. Open resection or disconnection of the hamartoma, either through pterional, transcallosal, or transventricular approach, leads to good epileptological control, but its high complication rate, up to 30%, limits its indications. The purely cisternal peduncular forms remain the only indication of open, pterional approach, while other strategies have been developed to overcome the neurological, endocrine, behavioral, or cognitive complications. Laser and radiofrequency thermocoagulation-based disconnection through robot-guided stereo-endoscopy has been proposed as an alternative to open microsurgical resection and stereotactic destruction. The goal is to allow safe and complete disconnection of a possibly complex attachment zone, through a single intraparenchymal trajectory which allows multiple laser or radiofrequency probe trajectory inside the ventricle. The efficacy was high, with 78% of favorable outcome, and the overall complication rate was 8%. It was especially effective in patients with isolated gelastic seizures and pure intraventricular hamartomas. Stereotactic radiosurgery has proved as efficacious and safer than open microsurgery, with around 60% of seizure control and a very low complication rate. Multiple stereotactic thermocoagulation showed very interesting results with 71% of seizure freedom and 2% of permanent complications. Stereotactic laser interstitial thermotherapy (LiTT) seems as effective as open microsurgery (from 76 to 81% of seizure freedom) but causes up to 20% of permanent complications. This technique has however been highly improved by targeting only the epileptogenic onset zone in the hamartoma, as shown on preoperative functional MRI, leading to an improvement of epilepsy control by 45% (92% of seizure freedom) with no postoperative morbidity. All these results suggest that the impact of the surgical procedure does not depend on purely technical matters (laser vs radiofrequency thermocoagulation or stereotactic vs robot-guided stereo-endoscopy) but relies on the understanding of the epileptic network, including inside the hamartoma, the aim being to plan an effective disconnection or lesion of the epileptogenic part while sparing the adjacent functional structures.

Stereotactic thermocoagulation for insular epilepsy: Lessons from successes and failures.

To assess factors associated with favorable outcome in refractory insular epilepsy treated by volume-based stereotactic radiofrequency thermocoagulation (RFTC). We performed volume-based RFTC in 19 patients (11 males, 7-44years old). The volume for thermocoagulation was identified by multimodal data including electroencephalography (EEG)-video, magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (PET) in all patients, and epileptogenic zone (EZ) was assessed by stereo-electroencephalography (SEEG) in 16. MRI showed insular lesions in four patients (benign tumors, n = 2; focal cortical dysplasia [FCD], n = 1; polymicrogyria, n = 1). MRI was negative in 15 cases; however, PET was positive in 18, and FCD pattern was detected by SEEG in nine cases. The dominant hemisphere was involved in 12 cases. RFTC was performed as a separate procedure after SEEG, or as a single MRI-guided procedure. The insular volume to be coagulated was determined by a tridimensional identification of the epileptogenic cortex using MRI, PET, and SEEG, and was destroyed with coalescent thermal lesions. Seizure-free outcome was achieved in 10 patients (53%), including Engel class IA in three (follow-up = 1-12years, mean = 5.4). The responder rate (including Engel classes I-III) was 89%. Transient postoperative deficits (mild hemiparesia, dysarthria, hypoesthesia, dysgeusia) were observed in eight patients (42%), with rapid and total recovery in all but one with persistent mild dysarthria. Neurological deficits were related to higher number of RFTC procedures (P=.036) and greater volume of RFTC (P=.028). Neuropsychological status was unchanged or improved in all; however, psychiatric status transitorily worsened in three patients. Factors contributing to seizure-free outcome were the detection of FCD pattern (P=.009), localized EZ (P=.038), low RFTC volume (P=.002), low number of RFTC procedures (P=.001), and low RFTC volume/number ratio (P=.012). Optimal volume of RFTC around 2cm3 offered the best compromise between efficacy and safety. RFTC may be curative in insular epilepsy after accurate localization of EZ with SEEG. Best outcome was associated with low volume of thermolesions.

Achieving a cure for hypothalamic hamartomas: aSisyphean quest?

Achieving a cure for hypothalamic hamartomas: aSisyphean quest?

Cognition in epilepsy: current clinical issues of interest.

This review provides an update and summary of recent neuropsychological findings in epilepsy focusing on three major clinical topics among the many developments in the field. We will critically outline the current state with regard to cognition in new-onset epilepsies, social cognition in epilepsy, and the long-term outcome of epilepsy surgery and the cognitive outcomes of superselective surgical procedures. Current studies indicate that neuropsychological impairments are prevalent already at the onset of epilepsy and even before, social cognition (i.e., emotion recognition and theory of mind) is impaired in different epilepsy populations, the long-term outcome of epilepsy surgery is mostly characterized by a stable or even improved cognitive status, and superselective epilepsy surgeries are associated with a promising neuropsychological outcome. The high prevalence of cognitive deficits around epilepsy onset challenges the assumption that epilepsy is the major cause of cognitive problems and calls for early neuropsychological diagnostics. Social cognition seems to be a relevant domain that is not yet routinely considered in epilepsy. The cognitive long-term outcome of epilepsy surgery is mostly positive. Stereotactic thermocoagulation and gamma knife surgery appear to be cognitively safe procedures.

Stereotactic laser thermocoagulation in epilepsy surgery

In common with other stereotactic procedures, stereotactic laser thermocoagulation (SLT) promises gentle destruction of pathological tissue, which might become especially relevant for epilepsy surgery in the future. Compared to standard resection, no large craniotomy is necessary, cortical damage during access to deep-seated lesions can be avoided and interventions close to eloquent brain areas become possible. We describe the history and rationale of laser neurosurgery as well as the two available SLT systems (Visualase® and NeuroBlate®; CE marks pending). Both systems are coupled with magnetic resonance imaging (MRI) and MR thermometry, thereby increasing patient safety. We report the published clinical experiences with SLT in epilepsy surgery (altogether approximately 200 cases) with respect to complications, brain structural alterations, seizure outcome, neuropsychological findings and treatment costs. The rate of seizure-free patients seems to be slightly lower than for resection surgery. Due to the inadequate quality of studies, the neuropsychological superiority of SLT has not yet been unambiguously demonstrated.

Adult-onset refractory epilepsy with hypothalamic hamartoma and no gelastic seizures successfully treated by stereotactic thermocoagulation: A case report

Adult-onset refractory epilepsy with hypothalamic hamartoma and no gelastic seizures successfully treated by stereotactic thermocoagulation: A case report

Lesion focused stereotactic thermo-coagulation of focal cortical dysplasia IIB: A new approach to epilepsy surgery?

PurposeOver the last few decades, preferred epilepsy surgical approaches have developed from standard lobectomies to individually tailored resections. Yet, it remains uncertain how small surgical interventions can be without compromising the success of the surgery. Particularly in patients with epileptogenic lesions identified by magnetic resonance imaging (MRI), it is unresolved whether resection or destruction of the lesion suffices to eliminate the epileptogenic zone. We present a minimally invasive surgical approach that may provide insight into this issue. MethodsTwo patients with pharmacoresistant epilepsy due to focal cortical dysplasia type IIB demonstrated by 3Tesla MRI were treated with lesion-focused stereotactic radio-frequency thermo-coagulation. In both patients, pathognomonic epileptic discharges were recorded from the lesion via a stimulation device prior to coagulation. In one patient, the suspected proximity of the lesion to the pyramidal tract was verified by eliciting motor evoked potentials from the depths of the lesion. ResultsFollowing complete and near complete lesion destruction, seizures (several per day or per week, respectively) ceased in patients A and B, with no seizures for 12 months and 5 months, respectively, at the time of this publication. Neither patient acquired persistent postoperative neurological deficits. ConclusionThe fact that seizure activity stopped after destruction of small bottom-of-sulcus dysplasias implies that in these cases, the epileptogenic zone and the epileptogenic lesion may overlap. If future studies can replicate this finding, focused lesion destruction could be a further development of individually tailored epilepsy surgery. The technique described here is especially suited for high-precision surgery close to eloquent brain structures.

Stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma with intractable gelastic seizures

Management of hypothalamic hamartoma with intractable gelastic epilepsy remains controversial. We have used stereotactic thermocoagulation for treatment of hypothalamic hamartoma with intractable gelastic epilepsy since 1997. Herein, we review our experience in five cases to clarify the usefulness of this treatment. A total of five patients with hypothalamic hamartoma were treated by stereotactic thermocoagulation at our hospital during the period October 1997 through February 2004. In all patients, the hamartoma was less than 10mm in diameter and was located on the floor of the third ventricle with sessile attachment to the wall. To identify ictal onset, chronic intracranial electroencephalography was performed in three patients with the use of a depth electrode implanted in the hamartoma. Attempts were made to induce gelastic seizure by electrical stimulation of the hamartoma in three patients. After magnetic resonance imaging-guided targeting, radiofrequency thermocoagulation of the boundary between the hamartoma and normal hypothalamus was performed to achieve disconnection effects. Marked reductions in seizure frequency were obtained in all cases, with three patients becoming seizure-free after the procedure. No intraoperative complications occurred except in one patient who experienced acute and transient panidrosis with hot flushes during coagulation. Our results suggest that stereotactic thermocoagulation of hypothalamic hamartoma is an acceptable treatment option for patients with intractable gelastic seizures.

Alteration in cardiovascular function and body surface temperature during percutaneous stereotactic upper thoracic ganglionectomy and sympathectomy in palmar hyperhidrotic patients.

We assessed changes in cardiovascular function, specifically arterial blood pressure and heart rate in 6 palmar hyperhidrotic patients before, during, and after T2 and T3 ganglionectomy and sympathectomy. We also assessed changes in skin temperature, specifically at the forehead, axilla, thumb, loin, and sole of the foot (all bilaterally) in 10 palmar hyperhidrotic patients before, during, and after T2 ganglionectomy and sympathectomy. In both methods, ganglionectomy and sympathectomy were done by percutaneous stereotactic thermocoagulation, under local anesthesia, at room temperature 21.4 +/- 0.6 degrees C. During the procedure we found a significant acute decrease in systolic and pulse pressures, from 153 +/- 10 to 127 +/- 9 and from 80 +/- 7 to 56 +/- 4mmHg respectively, and a lesser decrease in diastolic pressure; heart rate showed no statistically significant changes. We also noted a marked increase in thumb temperature, from 21.2 +/- 0.6 to 36.0 +/- 0.1 degrees C, with a mean increase of 14.8 degrees C, at a room temperature 21.4 +/- 0.6 degrees C, after complete bilateral T2 ganglionectomy and sympathectomy. Skin temperature at the forehead, axilla, loin, and sole of the foot, all measured bilaterally, showed no significant increase, although there was a decrease in sweating in both forehead and axillary regions. The decrease in systolic and pulse pressures observed during the thermocoagulation procedure were temporary effects. The increase in thumb temperature, however, appears to be a permanent effect for palmar hyperhidrotic patients. Finally, the data indicate that the sympathetic innervation of the blood vessel in the periphery presents a segmental organization.

Long-term Assessment of Percutaneous Stereotactic Thermocoagulation of Upper Thoracic Ganglionectomy and Sympathectomy for Palmar and Craniofacial Hyperhidrosis in 1742 Cases

Long-term Assessment of Percutaneous Stereotactic Thermocoagulation of Upper Thoracic Ganglionectomy and Sympathectomy for Palmar and Craniofacial Hyperhidrosis in 1742 Cases

Long-term assessment of percutaneous stereotactic thermocoagulation of upper thoracic ganglionectomy and sympathectomy for palmar and craniofacial hyperhidrosisin 1742 cases.

We sought to determine the long-term outcome of percutaneous stereotactic thermocoagulation for upper thoracic ganglionectomy and sympathectomy in patients with palmar and craniofacial hyperhidrosis with the use of a three-dimensional system of coordinates for the location of the T2 and T3 ganglia on the basis of the findings in a cadaveric study. From November 1986 to May 1998, upper thoracic ganglionectomy and sympathectomy with the use of percutaneous stereotactic thermocoagulation were performed in 1688 patients with palmar hyperhidrosis and 54 patients with craniofacial hyperhidrosis as outpatient surgical procedures based on a three-dimensional coordinate system for determining the location of the thermocoagulation point, which was developed by the authors in a cadaveric study. The technique requires only local anesthesia. After initial thermocoagulation, sweating stopped in 3465 (99.5%) of 3484 sides. Hyperhidrosis recurred within 2 to 59 months of treatment in 268 procedures. All patients in whom hyperhidrosis recurred were retreated successfully, resulting in a final success rate of 99.9%. Complications of treatment included pneumothorax in seven procedures (0.2%) and partial Horner's syndrome in five procedures (0.15%). Decreased plantar sweating was noted during follow-up in 92% of patients. The results of this study indicate that upper thoracic ganglionectomy and sympathectomy performed with the use of percutaneous thermocoagulation are a very effective treatment for palmar and craniofacial hyperhidrosis that provides excellent immediate and long-term results as well as a low complication rate. The method is also effective as a retreatment for recurrences. Our data also suggest that performing ganglionectomy and sympathectomy in both T2 and T3 is unnecessary, because the procedure had equal long-term effectiveness when performed in T2 alone.

Effect in cat locus coeruleus lesions on the response of cerebral blood flow and cardiac output to altered p aCO 2

In pentobarbital-anesthetized cats, over arterial p aCO 2 values of 20–60 mm Hg, cerebral blood flow (CBF, Xenon) and cardiac output (CO, thermal dilution) show positively inflected curves with slopes significantly greater than zero. To examine the role of the locus coeruleus (LC) in these responses, bilateral stereotactic thermo-coagulation lesions of the LC were made. The effect of lesions confirmed to involve the LC bilaterally (n= 10), were compared with the effects of misdirected lesions placed in the cerebellum abd lateral to the LC (n= 10) and sham lesions (n= 10). Ted days after the lesioning procedure, the animals were re-anesthetized with pentobarbital and p aCO 2 response curves were determined for CBF and CO prior to and following intravenous administration of propranolol (1 mg/kg, i.v.). The results obtained with the sham-operated animals and the animals with lesions outside of the LC were indistinguishable. Bilateral LC lesions had no significant effect on normocapnic CBF as compared to control animals. They did, however, significantly reduce the slope of the CBF p aCO 2 response curve. Propranolol produced a significant reduction in CBF in lesioned and non-lesioned animals measured at all levels of pCO 2 and did not alter the slope of the pCO 2 response curve for any group as compared to predrug values. Bilateral lesions of the LC did not significantly alter either normacapnic CO or the slope of the CO-p aCO 2 relationship, but did reduce the elevation in mean arterial blood pressure otherwise observed during hypercarbia. Measurement of norepinephrine levels in cortex indicate a close indicate a correlation between the ability of the lesion to reduce norepinephrine content and produce the observed physiological effects. The results of these experiments suggest that the hypercapnic response of CBF, but not CO to arterial p aCO 2 is modulated by systems which traverse the dorsal brainstem. The role of the locus coeruleus-catecholamine cell bodies in this effect, however, must be considered speculative until further transmitter-selective interventions are carried out.