Rosario R. Trifiletti

Comparison of Transcranial Doppler Ultrasonography and Transesophageal Echocardiography to Monitor Emboli During Coronary Artery Bypass Surgery

BACKGROUND AND PURPOSE Transcranial Doppler ultrasonography (TCD) is the standard technique for monitoring emboli in the cerebral circulation. Embolic signals have been detected with the use of this technique in most patients undergoing coronary artery bypass surgery. We previously reported that the majority of emboli are detected after release of aortic cross-clamps and partial occlusion clamps. In this study we compare the intraoperative use of TCD with transesophageal echocardiography (TEE) to monitor cerebral emboli. METHODS We simultaneously monitored 20 patients undergoing coronary bypass surgery with TCD and TEE. All patients also underwent routine TEE examination of the aorta. RESULTS Embolic signals were detected in all patients by both techniques. Mean total number of emboli was 535 +/- 109 by TEE compared with 133 +/- 28 by TCD. We found correlation between numbers of emboli detected by the two techniques at clamp placement and release (r = .65, P = .002). Clamp placement and release accounted for 84% of all emboli by TEE and 83% by TCD. By TEE, large, highly echogenic particles were detected after clamp release compared with small, barely echodense particles at the onset of bypass. No such distinction was apparent by TCD. We found correlation between severity of aortic atheroma and both TEE- (P = .003) and TCD-detected (P = .009) emboli. CONCLUSIONS TEE and TCD can both be used to continuously monitor emboli during coronary artery bypass surgery. However, TEE is invasive and justified only if it is being performed for intraoperative assessment of aortic atheromatosis or cardiac function.

Impact of Embolization During Coronary Artery Bypass Grafting on Outcome and Length of Stay

BACKGROUND Transcranial Doppler ultrasonography detects emboli in most patients during coronary artery bypass grafting. However, the significance of these emboli has not yet been established. METHODS We monitored 82 patients during coronary artery bypass grafting with this technique and related the numbers of emboli to the outcomes and length of hospital stay. RESULTS We detected cerebral emboli in all patients. Patients with stroke (n = 4; 4.9%) had a mean of 449 emboli, as compared with 169 emboli in patients without stroke (n = 78) (p = 0.005). Patients with major cardiac complications (n = 7) had a mean of 392 emboli, as compared with 163 in patients without such complications (n = 75) (p = 0.003). The mean hospital stay of survivors was 8.6 days in patients with fewer than 100 emboli (n = 40), 13.5 days in patients with 101 to 300 emboli (n = 23), 16.3 days in those with 301 to 500 emboli (n = 16), and 55.8 days in patients with more than 500 emboli (n = 6) (p = 0.0007). This relation was unchanged when patients with complications were excluded. The correlation between embolization and outcome was independent of the extent of aortic atheroma or age. CONCLUSIONS Emboli detected during coronary artery bypass grafting are significantly related to major cardiac and neurologic complications and affect length of stay in all patients, even in the absence of such specific complications.

Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fishers exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.

Determination of size of aortic emboli and embolic load during coronary artery bypass grafting

BACKGROUND Embolic signals have been detected within both the aortic lumen and the intracranial vasculature during coronary artery bypass grafting. Total numbers of these emboli have been reported. The present study examined the size of individual emboli and the total volume of embolization. METHODS Using transesophageal echocardiography, we continuously monitored the aortic lumen of 10 patients undergoing isolated coronary artery bypass grafting. We manually analyzed 720,000 individual echo frames over a 4-minute period after the release of aortic clamps to track and to calculate the volume of 657 individual particles. The embolic load for the entire procedure was calculated from mean volume based on analysis of 1,508 particles. We simultaneously monitored the middle cerebral artery using transcranial Doppler ultrasonography and compared numbers of emboli detected by the two techniques. RESULTS Particle diameter ranged from 0.3 to 2.9 mm (mean, 0.8 mm), and particle volume from 0.01 to 12.5 mm3 (mean, 0.8 mm3). Twenty-eight percent of particles measured 1 mm or more, 44% measured 0.6 to 1.0 mm, and only 27% measured 0.6 mm or less in diameter. Aortic embolic load for the procedure ranged from 0.6 cm3 to 11.2 cm3 (mean, 3.7 cm3). Estimated cerebral embolic load for the procedure ranged from 60 to 510 mm3 (mean, 276 mm3). The fraction of aortic emboli entering the cerebral circulation was very variable (3.9% to 18.1%). Seventy-six percent of the embolic volume after the release of clamps occurred over a 20-second period. Only 1 patient was encephalopathic perioperatively. This patient had the largest estimated cerebral embolic load (510 mm3) and the second largest aortic embolic load (8.4 cm3). CONCLUSIONS We determined the size of individual intraaortic embolic particles and the total volume of embolization during coronary artery bypass grafting, and found the proportion entering the cerebral circulation to be very variable. The constitution of these particles and the neurologic impairment resulting from such embolization remains to be determined.

Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism

Abnormal oxidative processes including a reduction in thiamine-dependent enzymes accompany many neurodegenerative diseases. Thiamine deficiency (TD) models the cellular and molecular mechanisms by which chronic oxidative aberrations associated with thiamine-dependent enzyme deficits cause selective neurodegeneration. The mechanisms underlying selective cell death in TD are unknown. In rodent TD, the earliest region-specific pathological change is breakdown of the blood-brain barrier (BBB). The current studies tested whether nitric oxide and microglia are important in the initial events that couple BBB breakdown to selective neuronal loss. Enhanced expression of endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase reactivity in microvessels, as well as the presence of numerous inducible nitric oxide synthase-immunoreactive microglia, accompanied the increases in BBB permeability. Nitric oxide synthase induction appears critical to TD pathology, because immunoreactivity for nitrotyrosine, a specific nitration product of peroxynitrite, also increased in axons of susceptible regions. In addition, TD elevated iron and the antioxidant protein ferritin in microvessels and in activated microglia, suggesting that these cells are responding to an oxidative challenge. All of these changes occurred in selectively vulnerable regions, preceding neuronal death. These findings are consistent with the hypothesis that the free radical-mediated BBB alterations permit entry of iron and extraneuronal proteins that set in motion a cascade of inflammatory responses culminating in selective neuronal loss. Thus, the TD model should help elucidate the relationship between oxidative deficits, BBB abnormalities, the inflammatory response, ferritin and iron elevation, and selective neurodegeneration.

Aortic Atheroma Is Related to Outcome but Not Numbers of Emboli During Coronary Bypass

BACKGROUND The relation between aortic atheroma severity and stroke after coronary artery bypass grafting is established. The relation between atheroma severity and other outcome measures or numbers of emboli has not been determined. METHODS Using transesophageal echocardiography, we determined the severity of atheroma in the ascending, arch, and descending aortic segments in 84 patients undergoing operations. Seventy patients were monitored using transcranial Doppler ultrasonography. RESULTS The incidence of stroke was 33.3% among 9 patients with mobile plaque of the arch and 2.7% among 74 patients with nonmobile plaque (p = 0.011). Cardiac complications were not significantly related to atheroma severity in any aortic segment. Length of stay was significantly related to atheroma severity in the aortic arch (p = 0.025) and descending segment (p = 0.024). The presence of severe atheroma in both the arch and descending segments was associated with significantly longer hospital stays as compared with patients with severe atheroma in neither segment (p = 0.05). Numbers of emboli were greater in patients with severe atheroma at clamp placement, although the differences did not achieve statistical significance. CONCLUSIONS Aortic atheroma severity is related to stroke and to the duration of hospitalization after coronary artery bypass grafting. The lack of correlation between numbers of emboli and atheroma severity suggests that m any emboli may be nonatheromatous in nature.

Felbamate Levels in Patients with Epilepsy

The usefulness of felbamate (FBM) levels in managing epilepsy patients has not been determined. The purpose of the present study was to determine if FBM levels obtained at routine office visits correlated with side effects reported by patients. We determined FBM levels by high‐pressure liquid chromatography (HPLC) of 46 epilepsy patient plasma specimens (41 patients) and assessed medication toxicity and seizure frequency by a questionnaire. Thirty‐six patients were treated with other antiepileptic drugs (AEDs); concomitant AED levels not in ranges believed to cause toxicity. FBM levels ranged from 9 to 134 pg/ml, and were divided into three groups for analysis, resulting in low‐range (9–36 pg/ml), mid‐range (37–54 μg/ml), and high‐level (44–134 pg/ml) groups. Anorexia and complaints of severe side effects were reported significantly more often in the high‐level group as compared with the low‐ and midrange groups. Significantly more patients in the high‐level group (1043) reported decreased seizure frequency, as compared with 12 of 30 of patients in the low‐and midrange groups combined. FBM levels correlated linearly with doses overall, but most closely in FBM monotherapy patients.

White matter changes mimicking a leukodystrophy in a patient with Mucopolysaccharidosis: characterization by MRI

Mucopolysaccharidosis (MPS) type I (alpha-iduronidase deficiency) is characterized by storage and massive urinary excretion of dermatan sulfate and heparan sulfate; it may be distinguished into three different subtypes based on age at onset and severity of the clinical symptoms. We report on progressive white matter involvement documented by serial MR imaging in a patient with the MPS type I, severe skeletal involvement and preserved mental capabilities (intermediate phenotype or Hurler/Scheie syndrome).The natural history of white matter abnormalities in patients with MPS is still unclear; based on the present study, it appears that degenerative changes of the white matter mimicking a leukodystrophy may mark the course of MPS type I. We also suggest that the degree of MR changes in patients with MPS does not always reflect their neurological impairment.

Detection of aortic emboli by transesophageal echocardiography during coronary artery bypass surgery

OBJECTIVE The purpose of this study was to determine whether emboli can be detected within the aortic lumen in patients undergoing coronary artery bypass surgery (CABG) and to relate the appearance of emboli to specific operative events. DESIGN Twenty patients were prospectively studied intra-operatively. SETTING Subjects were inpatients in an academic medical center. PARTICIPANTS All participants were scheduled for elective, isolated CABG. INTERVENTIONS Patients were continuously monitored using transesophageal echocardiography (TEE) from aortic cannulation to bypass discontinuation. After completion of the aortic examination, the probe was focused at the level of the aortic arch, just before the takeoff of the left subclavian artery. Emboli were defined as echogenic intraluminal signals not present in the same position on consecutive cross-sectional frames. RESULTS Intraluminal emboli were detected in all subjects, with a mean number of 535 and range of 8 to 1,885. Embolization was unevenly distributed through the procedure. A mean of 224 (42%) of 535 were detected within 4 minutes of aortic cross-clamp release and another 140 (24%) appeared after partial occlusion clamp release. Together, clamp placement and release represented 84% of all emboli. Emboli detected after clamp release were large, echodense particles easily distinguishable from the small, indistinct, poorly echogenic signals observed at bypass initiation. CONCLUSIONS Emboli can be visualized within the aortic lumen during CABG. Confirming previous reports, the majority of emboli detected are related to manipulation of aortic clamps. The composition and clinical significance of embolic material are unclear. The value of intraoperative TEE monitoring in predicting neurologic outcome remains to be determined.

Horner's syndrome after coronary artery bypass surgery

Article abstract-We established the frequency of Horners syndrome (HS) in 248 elective patients after coronary artery bypass surgery. Patients were evaluated neurologically pre- and post-operatively and 6 months after surgery. Nineteen patients (7.7%) developed unilateral HS postoperatively, 12 involving the left eye. The finding persisted in 10 patients (4%) at 6 months. When assessed 2 to 6 days, or 6 months, postoperatively, HS tended to be isolated and not associated with C8/T1 plexopathy. Among nondiabetic subjects, hypertensive patients had a higher frequency of HS than normotensive patients (10.6% versus 2.9%, p = 0.05). Among normotensive subjects, diabetic patients had a higher frequency than nondiabetic patients (15% versus 2.9%, p = 0.08). There was no association between HS, age, sex, internal mammary artery grafting, or length of cardiopulmonary bypass time. In summary, HS is a common and sometimes persistent complication of coronary artery bypass surgery. Hypertensive, and possibly diabetic, patients appear to be at greatest risk for developing HS. NEUROLOGY 19;: 181-184