The Charcôt-Bouchard aneurysm controversy: impact of a new histologic technique.

For over a century a controversy has existed about the prevalence and significance of Charcôt-Bouchard (C-B) aneurysms, especially regarding their relationship to intracerebral hemorrhage (ICH) in man. We reassessed C-B aneurysms by staining thick brain sections from 35 hypertensives and 20 normotensives with the alkaline phosphatase (AP) endothelial stain followed by light microscopy and high-resolution microradiography. Charcôt-Bouchard aneurysms were conspicuously absent in both groups which included four cases of hypertensive ICH. The three-dimensional perspective and enhanced ability to trace vessels with these techniques helped to identify arteriolar coils and twists that can be mistaken for aneurysms when demonstrated by injection methods. Routine brain pathologic sections from 2,800 autopsies over a decade showed rare examples of parenchymal aneurysms. We conclude that elimination in our study of a) injection artifacts and b) misinterpretations shows that C-B aneurysms are uncommon and have little relationship to ICH. Despite this, and in view of the original contribution of Charcôt and Bouchard, the occasional examples of brain parenchymal aneurysms should continue to bear their names.

Arteriolar tortuosity of the white matter in aging and hypertension. A microradiographic study.

Previous studies have shown tortuous arteries and arterioles in the brains of older people, but the effects of age and other factors have not been studied. To examine the effects of hypertension, age, race and sex on white matter (WM) arteriolar tortuosity (AT), we performed high-resolution microradiography and morphometry of human brains taken at autopsy from 44 subjects of various ages (range 30-96 years; 31 hypertensives/13 normotensives). About 70% of tortuosities in the WM were found at the gray-white interfaces of the insular region and adjacent subcortical-WM of the inferior frontal and superior temporal gyri. Six morphologic types of tortuous profiles were identified. The number of tortuous profiles increased with age, but not significantly. Hypertension, sex and race had no effect on tortuosity. Our findings also suggest that 1) WM AT is found mostly at the interfaces between gray matter and WM and, therefore, 2) the physical properties of the WM somehow predispose to the development of AT; 3) AT is not associated with tortuosity in the veins; and 4) the location of complex arteriolar coils supports a recent claim that they can be mistaken for the Charcôt-Bouchard microaneurysms if injection of contrast media and low-magnification radiography of the brain slices are employed for that purpose.

Laser microprobe mass spectrometric study of aluminum and silicon in brain emboli related to cardiac surgery.

Recent investigations have shown numerous fatty microemboli, which we previously termed small capillary and arteriolar dilatations (SCADs), in brain microvessels of patients who died after cardiac surgery assisted by cardiopulmonary bypass (CPB). The hypothesis of this study was that extraneous trace elements such as aluminum (Al) and silicon (Si) might be contaminating the blood and causing the formation of SCADs or coating the SCADs already formed in the extracorporeal circulation during CPB. Small capillary and arteriolar dilatations were identified in thick celloidin sections of the brains of 8 patients who died after cardiac surgery supported with a membrane oxygenator, and of 2 dogs that underwent CPB with a bubble oxygenator. The sections were infiltrated with Spurr's embedding medium for electron microscopy. Resin sections 0.5 microm thick were placed on 100-mesh copper grids and analyzed with laser microprobe mass spectrometry. Brain sections without SCADs from 3 patients (controls) whose deaths were not related to cardiac surgery were processed similarly. In SCADs and nearby neuropil sites of the 8 patients who had cardiac surgery, both Al and Si values were higher than in the neuropil, including vessels of the 3 controls. Si values were also high in the 2 dogs, in which a bubble oxygenator was used. Our results indicate that contamination with Al and Si continues to occur during cardiac surgery assisted by CPB. Our data also suggest that switching to membrane oxygenators from bubble oxygenators for CPB may have reduced Si contamination of blood. Further refinements of CPB aimed at eliminating microemboli formation and Al and Si entry into the circulation are warranted.

Cephalic fibromuscular dysplasia in 32 patients: clinical findings and radiologic features.

The clinical and angiographic features of 32 patients with cephalic fibromuscular dysplasia (FMD) are reported. All of our patients were women, 78% of whom were between 41 and 70 years of age. At examination, 18 (56%) patients had the sudden onset of focal ischemic neurologic deficits. Seven (22%) patients had intracranial berry aneurysms, which ruptured in five patients but were asymptomatic in two. The most common angiographic pattern was the "string of beads" deformity, which involved both extracranial internal carotid arteries at or distal to the third cervical vertebral level. The vertebral artery was affected in six cases, while three cases had intracranial involvement. Less common angiographic findings in this series consisted of segmental fusiform dilation of the artery, and lesions in the form of a septum that extended across the lumen. Twelve patients were followed up for an average of four years. Progression of FMD lesions was shown in two of the six patients who had repeated angiograms. The literature contains reports of only nine cases of cephalic FMD with repeated angiograms, three of which demonstrated progression. Our experience suggests a beneficial role for surgery in patients with specific symptoms in the distribution of the affected vessel, when coexistent disease is negligible or absent.

Clinical and computerized tomographic study of hypertensive intracerebral hemorrhage.

Historical, neurological, and computerized tomographic findings were correlated in 32 patients with hypertensive intracerebral hemorrhage. The mortality figures given in standard texts appear to be too high; the more acceptable figure would seem to be approximately 40%. Special attention was given to intraventricular rupture, which complicated 62% of the cases. Sudden onset of coma appears to correlate with the presence of intraventricular rupture. The "ring sign," if looked for, will be seen in most cases of resolving intracerebral hematoma.

A comparison of brain imaging with gamma camera, single-photon emission computed tomography, and transmission computed tomography: concise communication.

We have evaluated the utility of a single-photon axial tomographic scanner (ECT) in brain imaging, using routine tracers in 238 patients. When compared with routine delayed gamma-camera images (DGCI), there was agreement in 191 negative studies and 39 positive studies. Four patients had positive DGCI and negative ECT studies, and four had positive ECT and negative DGCI. In the 102 patients in this series who also had transmission CT (TCT) studies, there were five who had positive emission studies and negative TCT, and 38 with an abnormal TCT and normal ECT. The ECT was occasionally helpful in distinguishing brain and skull metastases, in better portrayal of deep lesions, and in resolving equivocal DGCI findings. For the ECT to become clinically rewarding, however, we feel that it will need development of new tracers that will provide functional information in addition to that already attainable by routine gamma-camera images.

Cerebral microvascular alterations in aging, leukoaraiosis, and Alzheimer's disease.

We have been using alkaline phosphatase (AP) histochemical staining, formerly a research tool for the study of cerebral cortical vascular morphology, to examine pathological changes in the cortex and deep cerebral structures. Deep structures stain similarly to the cortex. The AP stain is found in the afferent vessels (small arteries, arterioles, and capillaries), but not in venules and veins. The stain is also present in leaky vessels, such as those in the area postrema. The vascular supply to the cerebrum is not homogeneous. Supply to the deep white matter, for instance, derives from the leptomeningeal border zone, and then medullary arterioles must wind their way for up to 4 cm before arriving at their ultimate destination. Adding to the difficulties, tortuosities develop in some of these vessels with aging. According to some calculations, hypertensive levels of blood pressure would be required to maintain irrigation through some of these vessels. We have identified a venous alteration that attends aging: periventricular venous collagenosis (PVC) is a previously unrecognized, noninflammatory, mural disease of the periventricular veins. In severe cases, examples can be found of veins that are completely occluded by this process. PVC is found in 65% of subjects over 60 years old, and it strongly correlates with leukoaraiosis. In addition to previously mentioned aging-related changes, we have found extreme tortuosity, multiplications, and aneurysms of the smallest arterioles and lumpy-bumpy capillaries in the deep structures of patients with Alzheimer's disease.

Cerebrovascular pathology in Alzheimer's disease and leukoaraiosis.

A high percentage of patients with Alzheimer's disease (AD) show evidence of white matter degeneration known as leukoaraiosis (LA), which is due to chronic ischemia. We found that the periventricular veins tend to become occluded by multiple layers of collagen in the vessel walls in the elderly. This collagen deposition is particularly excessive in LA lesions. Therefore, it is present in the brains of many AD patients, along with other ischemia-causing cerebrovascular pathology. We found evidence that there is severe loss of oligodendrocytes in LA, due to extensive apoptosis. No evidence of inflammation was found in the LA lesions. In thick celloidin sections of AD brain, we have obtained detailed 3D views of small (early) deposits of amyloid (stained with beta-amyloid antibody) around capillaries (stained with collagen IV antibody).

Co-registration of cortical magnetic stimulation and functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are noninvasive techniques recently used to investigate cortical motor physiology. However, these modalities measure different phenomena, and in studies of human motor control they have given inconsistent results. We have developed a reproducible technique which co-registers TMS and fMRI, using a frameless method. In four normal subjects, the TMS map and fMRI activation were present on the primary motor cortex contralateral to the target hand, with some extension into primary sensory cortex. fMRI activation alone was also present in the medial motor cortex bilaterally and in the sensorimotor cortex ipsilateral to the target hand. This technique allows a more comprehensive evaluation of the physiologic events involved in motor control.

Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study.

Emboli in brain tissue after cardiopulmonary bypass were reported in the literature 30 years ago, but there is little objective evidence confirming the presence of emboli in the brain after cardiopulmonary bypass with more modern equipment and techniques. Recently, with alkaline phosphatase vascular staining, we found an acellular fatty material in brain microvasculature from autopsy material of patients who died shortly after cardiopulmonary bypass. These fatty intravascular collections range in diameter from 10 to 70 microns, a size that lodges in the smallest vessels of the microvasculature. They have been found in numbers sufficient to cause detectable neurologic dysfunction and are believed, but not proved, to be emboli. By sequentially injecting colored microspheres, we can determine when emboli occur during experimental cardiopulmonary bypass. In ongoing related studies, magnetic resonance imaging was performed before cardiac valve replacement in 39 patients for whom preoperative and postoperative neurologic and neuropsychologic testing was available. Preliminary results suggest that magnetic resonance imaging evidence of prior stroke is not a significant risk factor for cognitive or motor decrement after cardiopulmonary bypass.

Cardiotomy suction: a major source of brain lipid emboli during cardiopulmonary bypass.

BACKGROUND: Brain injury remains a significant problem in patients undergoing cardiac surgery assisted by cardiopulmonary bypass (CPB). Autopsy brain specimens of patients after cardiac operations with CPB reveal numerous acellular lipid deposits (10 to 70 microm) in the microvasculature. We hypothesize that these small capillary and arterial dilatations result from a diffuse inflammatory response to CPB or from emboli delivered by the bypass circuit. This study was undertaken to determine which aspect of CPB is most clearly associated with these dilatations. METHODS: Thirteen dogs were studied in four groups: group I (n = 3), right-heart CPB; group II (n = 2), lower-extremity CPB; group III (n = 3), hypothermic CPB; and group IV (n = 5), hypothermic CPB with cardiotomy suction. All dogs in all groups were maintained on CPB for 60 minutes and then euthanized. Brain specimens were harvested, fixed in ethanol, embedded in celloidin, and stained with the alkaline phosphate histochemical technique so that dilatations could be counted. RESULTS: All dogs completed the protocol. The mean density of dilatations per square centimeter for each group was as follows: group I, 1.77 +/- 0.77; group II, 4.17 +/- 1.65; group III, 4.54 +/- 1.69; and group IV, 46.5 +/- 14.5. In group IV (cardiotomy suction), dilatation density was significantly higher than in group III (hypothermic cardiopulmonary bypass) (p = 0.04) and all other groups (p = 0.04). CONCLUSIONS: Blood aspirated from the surgical field and subsequently reinfused into dogs undergoing CPB produces a greater density of small capillary and arterial dilatations than CPB without cardiotomy suction, presumably because of lipid microembolization.

Processing scavenged blood with a cell saver reduces cerebral lipid microembolization.

BACKGROUND: Microembolization during cardiopulmonary bypass (CPB) can be detected in the brain as lipid deposits that create small capillary and arteriolar dilations (SCADs) with ischemic injury and neuronal dysfunction. SCAD density is increased with the use of cardiotomy suction to scavenge shed blood. Our purpose was to determine whether various methods of processing shed blood during CPB decrease cerebral lipid microembolic burden. METHODS: After hypothermic CPB (70 minutes), brain tissue from two groups of mongrel dogs (28 to 35 kg) was examined for the presence of SCADs. In the arterial filter (AF) group (n = 12), shed blood was collected in a cardiotomy suction reservoir and reinfused through the arterial circuit. Three different arterial line filters (Pall LeukoGuard, Pall StatPrime, Bentley Duraflo) were used alone and in various combinations. In the cell saver (CS) group (n = 12), shed blood was collected in a cell saver with intermittent preocessing (Medtronic autoLog model) or a continuous-action cell saver (Fresenius Continuous Auto Transfusion System) and reinfused with and without leukocyte filtration through the CPB circuit. RESULTS: Mean SCAD density (SCAD/cm2) in the CS group was less than the AF group (11 +/- 3 vs 24 +/- 5, p = 0.02). There were no significant differences in SCAD density with leukocyte filtration or with the various arterial line filters. Mean SCAD density for the continuous-action cell saver was 8 +/- 2 versus 13 +/- 5 for the intermittent-action device. CONCLUSIONS: Use of a cell saver to scavenge shed blood during CPB decreases cerebral lipid microembolization.

The corpus callosum, a unique white-matter tract: anatomic features that may explain sparing in Binswanger disease and resistance to flow of fluid masses.

The corpus callosum exhibits several unusual features: arteriole-venule pairs, perivascular fibrous alae, and recurrent companion arterioles. These and other anatomic aspects are compared and contrasted with those of the centrum semiovale. Vascular changes occurring with aging or hypertension, commonly seen in the centrum semiovale, rarely develop in the corpus callosum. The vascular supply to the central zone of the genu and body of the corpus callosum, via short penetrating arterioles, is similar to that of the cerebral cortex, whereas the vascular supply to the extreme lateral corpus callosum, centrum semiovale, and basal ganglia is substantially carried by long end-arteries. When observed critically, the anatomic features of the corpus callosum may explain such clinically observed phenomena as its relative resistance to flow of fluid masses, radiation injury, Binswanger disease, lacunar infarction, hypoxia, and hypoperfusion.

Brain slice holder for MR.

We made an MR-compatible brain slice holder that ensures that the images have the same location and orientation as the subsequent histologic sections. This device encloses the unfixed tissues, thus reducing the danger of exposure to pathogens. MR imaging time is saved by scanning selected slices rather than the whole brain; this technique is especially useful when brain sections at varying angles, rather than parallel slices, are taken.

Features of the cerebral vascular pattern that predict vulnerability to perfusion or oxygenation deficiency: an anatomic study.

In an ongoing study of brain microvasculature in humans at autopsy, we had the opportunity to analyze the overall scheme of this vascular supply. The native endothelial membrane enzyme, alkaline phosphatase, is used to precipitate black lead sulfide salt in the vessel wall, rendering the brain microvasculature visible by both light microscopy and microradiography. There are six distinct patterns of intraparenchymal afferent blood supply to the supratentorial brain: short arterioles from a single source (e.g., those in the cortex); short- to intermediate-length arterioles, single source (anterior two-thirds of the corpus callosum); short- to intermediate length arterioles and arteries, dual source (subcortical U fibers); intermediate-length arterioles and arteries, triple source (extreme/external capsule and claustrum); long arteries and arterioles, single source (centrum semiovale); and large, long muscular arteries, single source (thalamus and basal ganglia). The nature of this arrangement offers some protection to certain regions of the cerebrum from circulatory challenges such as hypotension, while leaving other areas vulnerable. The distal arterioles supplying two of these protected regions, the U-fiber area and the extreme/external capsule and claustrum area, also exhibit the feature of interdigitation, which can offer additional collateral potential from one arteriolar territory to the next. Aging, hypertension, diabetes mellitus, and atherosclerosis can have a significant impact on brain microcirculation. The way in which vascular patterns dictate the distribution of these effects is discussed. The ability to stain the cerebral microvessels and demonstrate the finer points of their patterns in sections and microradiographs has enabled us to resolve some long-standing questions about vascular connections and directions.(ABSTRACT TRUNCATED AT 250 WORDS)

Madelung disease: MR findings.

Two cases of Madelung disease (benign symmetrical lipomatosis) are presented. The MR findings in this striking condition are demonstrated. Short-repetition-time/short-echo time sequences nicely show the relationship of the cervical lipomatous accumulations to the airway and major neurovascular structures in the carotid spaces. Fat-suppression techniques add no additional information in the radiologic evaluation of these patients.

Apoptosis in leukoaraiosis.

We report a case of leukoaraiosis that was studied for apoptosis. In the neuropil, the number of cells that showed DNA fragmentation was 2.5 times as great in the area of leukoaraiosis as in the adjacent white matter (P = .004) and 25 times as great as in the nearby cortex (P < .001). Our findings suggest that apoptosis, predominantly of oligodendrocytes, is involved in the pathogenesis of leukoaraiosis. Within the area of leukoaraiosis, we also found numerous small veins that were partially occluded by severe collagenous thickening of the vessel walls. This collagenosis may have contributed to or resulted from chronic ischemia in that area.

Human germinal matrix: venous origin of hemorrhage and vascular characteristics.

PURPOSE: To examine the vascular supply and architecture of the germinal matrix in the preterm neonatal brain and to determine whether veins or arterioles are the source of germinal matrix hemorrhage. METHODS: Brains from eight preterm neonates (24 to 35 weeks' gestation) and two full-term infants were fixed in alcohol, embedded in celloidin, sectioned at 100- and 500-micron thicknesses, stained for alkaline phosphatase, and examined with light microscopy. High-resolution contact radiographs of 500-micron-thick sections were also mounted on glass slides for microscopic examination. RESULTS: The upper and middle regions of the germinal matrix are supplied by branches of the lateral striate arteries, whereas the inferior part is supplied by branches of the recurrent artery of Heubner. In brain sections from four of the preterm infants, we found 15 circumscribed hemorrhagic foci within the germinal matrix. The largest was 5 mm in diameter; the smallest, 1 mm. All hemorrhages but one were closely associated with veins, with significant involvement of the perivenous space. The other hemorrhage appeared to be associated with an arteriole. In term and preterm infants, we found no arteriolar-to-arteriolar shunts, precapillary arteriolar-to-venules shunts, or vascular rete. At all gestational ages, the terminal vascular bed had only conventional branchings and connections. CONCLUSION: In preterm neonates, staining for endogenous alkaline phosphatase allows visual differentiation between afferent and efferent vessels. Germinal matrix hemorrhage in preterm neonates is primarily venous in origin. A hemorrhage can tunnel along the venous perivascular space, collapsing the vein and rupturing the tethered connecting tributaries. Extravasation of blood from the arterial circulation appears to be much less common.

MRI of corpus callosal syndromes.

Six patients, 6 to 13 years old, with corpus callosal abnormalities diagnosed by electroencephalography or CT were studied with a 0.15 T MR imager to determine the effectiveness of MRI in evaluating midline anomalies. Spin-echo images in the coronal, axial, and sagittal planes were obtained in two patients with Aicardi's syndrome and partial agenesis of the corpus callosum, in one patient with Dandy-Walker syndrome, and in two patients with septooptic dysplasia. Inversion recovery and spin-echo images were obtained in one patient with lipoma of the corpus callosum. Partial agenesis of the corpus callosum was seen in septooptic dysplasia, an association that has not been reported previously in the radiologic literature. Direct sagittal and coronal MRI provided better anatomic visualization of the brain and ventricles than did reformatted CT. T1-weighted images are sufficient to diagnose and delineate the extent of midline cerebral abnormalities. The unique capability of direct sagittal imaging makes MRI the best procedure for evaluating corpus callosal and other midline abnormalities.

Chronic seizure disorders: contribution of MR imaging when CT is normal.

One hundred consecutive patients with complex partial seizures were studied by magnetic resonance (MR) imaging and computed tomography (CT). Thirty-four patients had seizures of more than 5 years' duration, yet neurologic examinations and previous pre- and postinfusion CT scans had been normal. MR imaging demonstrated surgical lesions of potentially therapeutic significance in four of these 34 patients. Two patients underwent surgery with removal of a thrombosed arteriovenous malformation and a glioma. Although CT has been found to detect structural abnormalities, its yield of therapeutically significant abnormalities has been low.