Robert C. Frysinger

Incidence of symptomatic hemorrhage after stereotactic electrode placement

OBJECT Intracranial hemorrhage (ICH) is the most significant complication associated with the placement of stereotactic intracerebral electrodes. Previous reports have suggested that hypertension and the use of microelectrode recording (MER) are risk factors for cerebral hemorrhage. The authors evaluated the incidence of symptomatic ICH in a large cohort of patients with various diseases treated with stereotactic electrode placement. They examined the effect of comorbidities on the risk of ICH and independently assessed the risks associated with age, sex, use of MER, diagnosis, target location, hypertension, and previous use of anticoagulant medications. The authors also evaluated the effect of hemorrhage on length of hospital stay and discharge disposition. METHODS Between 1991 and 2005, 567 electrodes were placed by two neurosurgeons during 337 procedures in 259 patients. Deep brain stimulation (DBS) was performed in 167 procedures, radiofrequency lesioning (RFL) of subcortical structures in 74, and depth electrodes were used in 96 procedures in patients with epilepsy. Electrodes were grouped according to target, patient diagnosis, use of MER, patient history of hypertension, and patient prior use of anticoagulant medication (stopped 10 days before surgery). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities. The CCI score, patient age, length of hospital stay, and discharge status were continuous variables. Symptomatic hemorrhages were grouped as transient or leading to permanent neurological deficits. RESULTS The risk of hemorrhage leading to permanent neurological deficits in this study was 0.7%, and the risk of symptomatic hemorrhage was 1.2%. A patient history of hypertension was the most significant factor associated with hemorrhage (p = 0.007). Older age, male sex, and a diagnosis of Parkinson disease (PD) were also significantly associated with hemorrhage (p = 0.01, 0.04, 0.007, respectively). High CCI scores, specific target locations, and prior use of anticoagulant therapy were not associated with an increased risk of hemorrhage. The use of MER was not found to be correlated with an increased hemorrhage rate (p = 0.34); however, the number of hemorrhages in the patients who underwent DBS was insufficient to draw definitive conclusions. The mean length of stay for the DBS, RFL, and depth electrode patient groups was 2.9, 2.6, and 11.0 days, respectively. For patients who received DBS and RFL, the mean duration of hospitalization in cases of symptomatic hemorrhage was 8.2 days compared with 2.7 days in those without hemorrhaging (p < 0.0001). Three of the seven patients with symptomatic hemorrhages were discharged home. CONCLUSIONS The placement of stereotactic electrodes is generally safe, with a symptomatic hemorrhage rate of 1.2%, and a 0.7% rate of permanent neurological deficit. Consistent with prior reports, this study confirms that hypertension is a significant risk factor for hemorrhage. Age, male sex, and diagnosis of PD were also significant risk factors. Patients with symptomatic hemorrhage had longer hospital stays and were less likely to be discharged home.

Functional magnetic resonance imaging responses to expiratory loading in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by diminished upper airway muscle phasic and tonic activation during sleep, but enhanced activity during waking. We evaluated neural mechanisms underlying these patterns with functional magnetic resonance imaging procedures during baseline and expiratory loading conditions in nine medication-free OSA and 16 control subjects. Both groups developed similar expiratory loading pressures, but appropriate autonomic responses did not emerge in OSA cases. Reduced neural signals emerged in OSA cases within the frontal cortex, anterior cingulate, cerebellar dentate nucleus, dorsal pons, anterior insula and lentiform nuclei. Signal increases in OSA over control subjects developed in the dorsal midbrain, hippocampus, quadrangular cerebellar lobule, ventral midbrain and ventral pons. Fastigial nuclei and the amygdala showed substantially increased variability in OSA subjects. No group differences were found in the thalamus. OSA patients show aberrant responses in multiple brain areas and inappropriate cardiovascular responses to expiratory loading, perhaps as a consequence of previously-demonstrated limbic, cerebellar and motor area gray matter loss.

Cortical and subcortical brain shift during stereotactic procedures

OBJECT The success of stereotactic surgery depends upon accuracy. Tissue deformation, or brain shift, can result in clinically significant errors. The authors measured cortical and subcortical brain shift during stereotactic surgery and assessed several variables that may affect it. METHODS Preoperative and postoperative magnetic resonance imaging volumes were fused and 3D vectors of deviation were calculated for the anterior commissure (AC), posterior commissure (PC), and frontal cortex. Potential preoperative (age, diagnosis, and ventricular volume), intraoperative (stereotactic target, penetration of ventricles, and duration of surgery), and postoperative (volume of pneumocephalus) variables were analyzed and correlated with cortical (frontal cortex) and subcortical (AC, PC) deviations. RESULTS Of 66 cases, nine showed a shift of the AC by more than 1.5 mm, and five by more than 2.0 mm. The largest AC shift was 5.67 mm. Deviation in the x, y, and z dimensions for each case was determined, and most of the cortical and subcortical shift occurred in the posterior direction. The mean 3D vector deviations for frontal cortex, AC, and PC were 3.5 +/- 2.0, 1.0 +/- 0.8, and 0.7 +/- 0.5 mm, respectively. The mean change in AC-PC length was -0.2 +/- -0.9 mm (range -4.28 to 1.66 mm). The volume of postoperative pneumocephalus, assumed to represent cerebrospinal fluid (CSF) loss, was significantly correlated with shift of the frontal cortex (r = 0.640, 64 degrees of freedom, p < 0.001) and even more strongly with shift of the AC (r = 0.754, p < 0.001). No other factors were significantly correlated with AC shift. Interestingly, penetration of the ventricles during electrode insertion, whether unilateral or bilateral, did not affect volume of pneumocephalus. CONCLUSIONS Cortical and subcortical brain shift occurs during stereotactic surgery as a direct function of the volume of pneumocephalus, which probably reflects the volume of CSF that is lost. Clinically significant shifts appear to be uncommon, but stereotactic surgeons should be vigilant in preventing CSF loss.

Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea.

We hypothesized that neural processes mediating deficient sensory and autonomic regulatory mechanisms in obstructive sleep apnea (OSA) would be revealed by responses to inspiratory loading in brain regions regulating sensory and motor control. Functional magnetic resonance imaging (fMRI) signals and physiologic changes were assessed during baseline and inspiratory loading in 7 OSA patients and 11 controls, all male and medication-free. Heart rate increases to inspiratory loading began earlier and load pressures were achieved later in OSA patients. Comparable fMRI changes emerged in multiple brain regions in both groups, including limbic, cerebellar, midbrain, and primary motor cortex. However, in OSA subjects, altered signals appeared in primary sensory thalamus and sensory cortex, supplementary motor cortex, cerebellar cortex and deep nuclei, cingulate, medial temporal, and insular cortices, right hippocampus, and midbrain. Signal delays occurred in basal ganglia. We conclude that areas mediating sensory and autonomic processes, and motor timing, are affected in OSA; many of these areas overlap regions of previously demonstrated gray matter loss.

Interictal heart rate patterns in partial seizure disorders

Epileptogenic mesial temporal damage may alter interictal autonomic patterning. Analysis of heart rate variability in 19 patients with complex partial seizures revealed cases of persistent, high-amplitude, 4 to 9 per minute fluctuations in heart rate during alert waking. This pattern was most pronounced in poor candidates for anterior temporal lobe resection (2/19). The 4 to 9 per minute heart-rate variability pattern may emerge following diffuse, extratemporal, or bilateral mesial temporal damage, which interferes with descending forebrain influences on cardiovascular regulation.

Cardiac and respiratory correlations with unit discharge in human amygdala and hippocampus

Animal studies have shown that epileptiform seizures can cause cardiac arrhythmias and death. The amygdala and hippocampus are implicated in epileptogenesis and autonomic and respiratory control. We examined cardiac and respiratory correlations with single cell discharge in hippocampus and amygdala of patients with epilepsy. We recorded respiration, ECG, and neuronal discharge of amygdala and hippocampus from patients undergoing chronic depth electrode monitoring. Cross-correlation histograms were used to test for neuronal discharge timing relationships with inspiration or the ECG. Inspiratory time, respiratory period and heart rate were calculated for each breath, and linear regression was used to test for correlations with tonic unit rate. Of 183 cells from 24 patients, 20% had cardiac timing relationships and 23% showed tonic correlations with changes in heart rate. Only 2% had timing relationships with the respiratory cycle, while 15% showed tonic rate relationships with respiratory period. Recording sites did not differ in mean discharge rate or proportion of cells showing these correlations. These results indicate that a significant number of human forebrain cells show discharge modulation by the cardiac cycle and discharge rate correlation with changes in respiration and heart rate. This is supportive of animal models designed to explore the role of mesial temporal lobe structures in regulation of cardiovascular and respiratory systems, although a lower proportion of cells in human temporal lobe showed timing relationships with respiration and there was no clear evidence of anatomic specificity between amygdala and hippocampus.

Cardiac and Respiratory Correlations with Unit Discharge in Epileptic Human Temporal Lobe

Summary We recorded respiratory activity and electrocardiogram (ECG) together with single cell activity from the amygdala and hippocampus of epileptic patients who later received anterotemporal lobectomy. Cross‐correlation histograms were used to test for neuronal discharge timing relationships with inspiration or ECG. Linear regression was used to test for correlations of inspiratory time, respiratory period, and heart rate (HR) with tonic unit rate for each breath. Of 129 cells from 16 patients who later had resection, 89 were contralateral and 40 were ipsilateral to the resected lobe. Of the contralateral cells, 19% had a timing relationship with the cardiac cycle and only 1% had such a relationship with the respiratory cycle. Tonic correlations with HR were noted in 22% and with respiratory period and inspiratory time in 11 and 6%. Neither these percentages nor mean discharge rate differed between structures, although variance in rate was much higher on the resected side. Amygdala cells on the resected side showed more correlations with the cardiac cycle (55 vs. 20%), respiratory period (46 vs. 3%), and inspiratory time (27 vs. 7%) and were more likely to show several types of correlation. The results suggest a selective loss of ipsilateral amygdala cells and/or afferents, favoring relationships with cardiac‐ and respiratory‐related systems and a possible synaptic reorganization of remaining cardiorespiratory afferents.

Respiratory modulation of neuronal discharge in the central nucleus of the amygdala during sleep and waking states

The relationship between neuronal discharge in the central nucleus of the amygdala (ACE) and timing of the respiratory cycle was assessed during quiet and active sleep and during the waking state. Of 169 neurons recorded from the ACE in intact, drug-free cats, 22% discharged phasically with the respiratory cycle during at least one sleep or waking state. The dependency between neuronal discharge and the respiratory cycle was typically strong in only one state. Forty-three percent of the respiratory-related neurons were most strongly correlated with the respiratory cycle during the waking state (AW). An additional 30% were most strongly related to the respiratory cycle during quiet sleep (QS), whereas only 11% showed the strongest dependency during rapid eye movement (REM) sleep. Half of the ACE neurons (49%) discharged at frequencies less than 10 spikes per second, and the most common trend in firing rate across states was one in which neurons fired more rapidly during AW and REM than during QS. No relationship between discharge rate of ACE neurons in the three states and propensity for phasic discharge with the respiratory cycle could be demonstrated.

Sulcal and ventricular trajectories in stereotactic surgery.

OBJECT The authors analyzed deep brain stimulation electrode trajectories on MR images to identify risks of cerebrovascular complications associated with the number of electrode insertions, traversal of a sulcus, and penetration of the ventricle. METHODS Pre- and postoperative MR volumes were fused to determine the proximity of electrodes to a sulcus or ventricle and whether there were cortical, subcortical, or intraventricular complications. Complications were further classified as hemorrhagic or nonhemorrhagic and symptomatic or asymptomatic. The authors examined 258 electrode implantation for deep brain stimulation. There were 4 symptomatic events (1.6% incidence): 3 hemorrhagic and 1 nonhemorrhagic, all within the cortex. Asymptomatic events included cortical hemorrhage in 1 patient, nonhemorrhagic cortical changes in 6, pallidal hemorrhage in 1, thalamic infarction in 1, and intraventricular hemorrhage (IVH) in 5 patients. RESULTS Proximity to a sulcus was a significant risk factor for hemorrhagic and nonhemorrhagic cortical complications (p = 0.001). There was a complication rate of 10.1% within the trajectories penetrating or adjacent to a sulcus, and a 0.7% rate with trajectories clearly positioned within the gyrus. Asymptomatic IVH was observed in 5% of ventricular penetrations. A history of hypertension was a risk factor for cortical hemorrhage (p = 0.019), but not for cortical ischemic/edematous events (p = 0.605). The number of electrode penetrations did not differ between patients with and without complications (p = 0.868), and the sequence of electrode insertions was not a risk factor in bilateral surgeries. CONCLUSIONS Symptomatic cortical complications occur when electrodes traverse close to a sulcus. Asymptomatic IVH occurs infrequently with ventricular penetration. Despite intraoperative efforts to avoid cortical sulci, a higher than expected incidence of electrode proximity to the sulci was identified on careful postoperative trajectory analysis. This finding emphasizes the importance of assiduously planning trajectories and reviewing cases with thorough MR analysis.

Correlation between MRI-Based Stereotactic Thalamic Deep Brain Stimulation Electrode Placement, Macroelectrode Stimulation and Clinical Response to Tremor Control

In this study we compared the position of the electronically active contact of the thalamic (Vim) deep brain stimulation (DBS) electrode to the stereotactic location of its tip. Fifteen patients with either Parkinson’s disease (PD) or essential tremor (ET) underwent stereotactic, MRI-based placement of the Medtronic quadripolar DBS electrode. An overall improvement of 69% was achieved in the tremor scores during a period of 1–13 months after implantation of the DBS electrode. Eleven patients with ET showed 70% clinical improvement of tremor, compared to a 58% response observed in the 4 patients with PD. The electrode tip center was 11.2 ± 1.54 mm lateral to the third ventricular wall, 5.38 ± 1.02 mm anterior to the posterior commissure and 2.9 ± 3.57 mm inferior to the level of AC–PC line. The most significant deviation from the planned stereotactic target was observed in the Z-coordinate. In our group of patients, stimulation settings favored the contacts closer to the AC–PC line, correcting the electrode tip position to 0.80 ± 2.84 mm (p < 0.001) inferior to the level of the AC–PC line. In our experience, thalamic DBS offers a reversible and adjustable ‘lesion’ to compensate for the anatomic variabilities encountered in the positioning of the DBS electrode tip.