Diffusion tensor MR imaging of the pyramidal tract can predict the need for orthosis in hemiplegic patients with hemorrhagic stroke.

Diffusion tensor magnetic resonance (MR) imaging was used to evaluate motor functions in stroke patients. The aim of this study was to clarify whether imaging can be used to predict orthotic needs in patients with hemiplegia. We studied 25 patients (age range, 16-78 years) with intracerebral hemorrhages (putamen 15, thalamus 7, frontal subcortex 3). Diffusion tensor MR imaging was undertaken on admission at rehabilitation hospital for stroke patients. The fractional anisotropy (FA) value of the pyramidal tract was calculated. We compared the FA value in the ROI of the cerebral peduncle with the necessity for orthosis at discharge from the rehabilitation hospital. As a result, the FA values of the affected side in patients who needed orthosis at discharge were lower than those in patients who did not need orthosis. There was no significant difference in the FA values of the unaffected side. We concluded that the need for orthosis in patients with hemiplegia after stroke rehabilitation could be predicted using the diffusion tensor MR images of corticospinal tractography.

Significance of magnetic resonance angiography-diffusion weighted imaging mismatch in hyperacute cerebral infarction.

Therapeutic results with respect to lesion size were analyzed and compared in patients with hyperacute cerebral infarction with and without major artery lesions on magnetic resonance angiography (MRA) and in those who did and did not receive intravenous (IV) tissue plasminogen activator (t-PA). Of the patients with cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and September 2009, 127 patients with cerebral infarction in the anterior circulation region in whom head magnetic resonance imaging (diffusion-weighted imaging [DWI]) or MRA was performed (81 men and 46 women; mean age, 71 ± 11 years) were enrolled. Major artery lesions (+) were defined as internal carotid artery occlusion and middle cerebral artery (M1/M2 segment) occlusion and ≥50% stenosis. Based on the presence or absence of major artery lesions and the size of DWI lesions, the subjects were divided into 3 groups: MRA-DWI mismatch (+) group [major artery lesion (+) and DWI-ASPECTS ≥6], MRA-DWI mismatch (-) group [major artery lesion (+) and DWI-ASPECTS <6], and major artery lesion (-) group. IV t-PA was given to 21 of the 64 patients in the MRA-DWI mismatch (+) group, to 1 of the 24 patients in the MRA-DWI mismatch (-) group, and to 9 of the 39 patients in the major artery lesion (-) group. In the MRA-DWI mismatch (+) group (n = 64), the median National Institutes of Health Stroke Scale (NIHSS) score on admission was higher in t-PA-treated patients than in t-PA-untreated patients (15 vs 11). The modified Rankin scale (mRS) score at day 90 after onset was more favorable in t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) than in t-PA-untreated patients (0-2 in 12 patients [28%] and 3-6 in 31 patients [72%]). After adjusting for admission NIHSS score, there was a significant difference in outcome (mRS score) between t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) and t-PA-untreated patients (0-2 in 3 patients [9%] and 3-6 in 29 patients [91%]) (P = .002). In the MRA-DWI mismatch (-) group (n = 24), mRS scores at day 90 after onset were poor in both t-PA-treated (3-6 in 1 patient [100%]) and t-PA-untreated patients (0-2 in 1 patient [4%] and 3-6 in 22 patients [96%]). In the major artery lesion (-) group (n = 39), mRS scores at day 90 after onset were favorable in both t-PA-treated (0-2 in 9 patients [100%]) and t-PA-untreated patients (0-2 in 28 patients [93%] and 3-6 in 2 patients [7%]). When comparing major artery lesions in the MRA-DWI mismatch (+) group, outcomes were more favorable in patients with M1/M2 segment lesions who received t-PA than in those who did not receive t-PA. In the MRA-DWI mismatch (+) group, the prognosis was significantly better for t-PA-treated patients than for t-PA-untreated patients, suggesting that IV t-PA is indicated in patients with MRA-DWI mismatch.

Clinical review of 37 patients with medullary infarction.

BACKGROUND: Clinical features of medullary infarction were compared between patients with lateral medullary infarction and medial medullary infarction METHODS: Thirty-seven patients with medullary infarction (29 with lateral medullary infarction and 8 with medial medullary infarction) who were admitted to our center between April 1, 2007 and March 31, 2010 were examined. Background factors, neurologic signs and symptoms, imaging findings, cause of disease, and outcomes were assessed for patients with lateral and those with medial medullary infarction. RESULTS: Examination of the clinical symptoms and neurologic findings suggested that among patients with medial medullary infarction, few demonstrated all of the symptoms of Dejerine syndrome at onset, and many had lesions that were difficult to locate based only on neurologic findings. Both lateral and medial medullary infarction were frequently caused by atherothrombosis. However, cerebral artery dissection was observed in 31% of patients with lateral medullary infarction and 12.5% of those with medial medullary infarction. In 13% of patients with lateral and 37% of patients with medial medullary infarction, magnetic resonance imaging diffusion-weighted images on the day of onset did not show abnormalities, and the second set of diffusion-weighted images confirmed infarction lesions. For lateral medullary infarction, a more rostral lesion location was correlated with a poorer 90-day outcome. For medial medullary infarction, a more dorsal lesion location was correlated with a poorer 90-day outcome. CONCLUSIONS: The diagnosis rate of medullary infarction using imaging examinations at onset--particularly medial medullary infarction--is not necessarily high. The imaging examinations need to be repeated for patients who are suspected to have medullary infarction based on neurologic signs and symptoms.

Prominent persisting Eustachian valve initiates spontaneous right-to-left shunt and paradoxical embolism in a patient with patent foramen ovale.

The Eustachian valve (EV) is an embryological remnant of the inferior vena cava valve that prenatally directs the oxygenated blood from inferior vena cava across the patent foramen ovale (PFO) into systemic circulation. We present a 30-year-old man with PFO whose prominent EV initiated spontaneous right-to-left shunt without Valsalva maneuver and promoted paradoxical embolism. Even when the persistence of EV is prominent in adult, it has been considered to be benign finding in the absence of the associated cardiac anomalies. EV should be considered as an adjunctive risk factor for paradoxical embolism in patients with PFO.

Significance of clinical-diffusion mismatch in hyperacute cerebral infarction.

In recent years, patient selection for intravenous tissue plasminogen activator (t-PA) therapy based on clinical-diffusion mismatch (CDM) has been closely examined. We investigated the relationship between prognosis and CDM in patients with hyperacute cerebral infarction within 3 hours of onset and compared CDM with diffusion-perfusion mismatch (DPM). Of 122 patients with hyperacute cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and November 2008, 85 patients with cerebral infarction in the anterior circulation who underwent head magnetic resonance imaging diffusion-weighted imaging (DWI)/magnetic resonance angiography (MRA) (51 men and 34 women; average age, 74 ± 10 years) were enrolled. Seventeen of these patients underwent CT perfusion imaging. CDM-positive cases were those with a National Institute of Health Stroke Scale (NIHSS) score ≥ 8 and a DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≥ 8; CDM-negative cases were those with an NIHSS score ≥ 8 and an ASPECTS-DWI < 8. The other patients were classified as belonging to the NIHSS score < 8 group. Of the 32 CDM-positive cases, 10 received t-PA infusion. These patients had markedly higher modified Rankin Scale scores 90 days after onset compared with the 22 patients who did not receive t-PA infusion. The 8 CDM-positive cases included 4 DPM-positive cases and 4 DPM-negative cases, and a discrepancy was confirmed between CDM and DPM. In all DPM-positive cases, MRA confirmed lesions in major intracranial arteries. CDM may enable more accurate prediction of outcomes in patients with hyperacute cerebral infarction. In addition, the combination of CDM findings and MRA findings (stenosis or occlusion in major intracranial arteries) may be an alternative to DPM for determining the indications for IV t-PA therapy in patients with hyperacute cerebral infarction.

[Takotsubo cardiomyopathy and cerebral infarction].

Takotsubo cardiomyopathy is reversible left ventricular dysfunction and apical ballooning resembling acute myocardial infarction. Although Takotsubo cardiomyopathy is a well-known complication of subarachnoid hemorrhage, it is rare in patients with acute cerebral infarction. We reviewed the findings of thirty previously published cases with both Takotsubo cardiomyopathy and cerebral infarction. These cases were divided into three groups (A-C) according to etiology. A; Dysfunction of central autonomic network associated with cerebral infarction caused Takotsubo cardiomyopathy, B; Left ventricular thrombus associated with Takotsubo cardiomyopathy caused cardioembolic stroke. C; The unknown relation of cause and effect. Most patient were elderly women in all groups. Group A mostly included the territory of middle cerebral artery or basilar artery as the infarcts area. The cardiomyopathy in group A often occurred within 24 hours after stroke onset and was commonly asymptomatic. On the other hand, the cardiomyopathy in group B often was commonly symptomatic. But some cases with mild cardiac symptom in group B was diagnosed by embolic event. Takotsubo cardiomyopathy can notably be both the cause and effect of stroke. The 'chicken or egg' issue regarding stroke etiology in group C is sometimes not simple to resolve.

Astroglial swelling for removed rat brain enlargement incubated in deoxygenated mock cerebrospinal fluid.

The source and target of edema fluid for ischemic brain swelling clinically often observed in "malignant infarction" was examined in ex vivo. Wister rat brain hemispheres were removed and incubated air-tightly in a deoxygenated artificial cerebrospinal fluid at 37 degrees for 30 min. Ionic movement into the brain tissue was calculated from their concentration changes in the incubation fluid. We found a weight increase by 11.3+/-2.5% (p<0.01) and a decrease in Na+ from 148.0 to 139.0 +/- 8.2 mEq/l (p<0.01) and an increase in K+ from 4.3 to 11.2 +/- 1.2 mEq/l. Video tape recording revealed that the brain swelling started immediately upon the incubation, and the electronmicroscopical investigation of the swollen cortical tissue revealed that the fluid moved mainly into astroglial cells. The astroglial swelling was quite similar to that of specimen taken from clinical cases at autopsy. The driving force of the water shift can be explained by discharge of thermodynamic potential, i.e., a coupled transport of water with Na+ across the cell membrane (anomalous osmosis). The swelling was not affected by addition of aquaporin blocker, mercuric chloride. It is concluded that cerebrospinal fluid bathing the brain in situ can be the source of edema fluid for ischemic brain swelling.

Capillo-venous flow in the brain: significance of intravascular RBC aggregation for venous flow regulation.

Despite numerous reports on the regulation of cerebral arterial blood flow, little work has been done on that of the capillary and venous system. We have examined capillo-venous blood flow in the rat intraparenchymal cerebral cortex, employing a high-speed video confocal fluorescence microscope and our own software (KEIOIS-2) to track individual RBCs and to document velocity changes in single capillaries and veins. We found temporal and spatial heterogeneous changes in capillary RBC density (hematocrit), RBC recruitment, oscillation of capillary flow or vasomotion, and capillary density unrelated to arteriolar diametric changes. In veins, blood flow was also quite variable in time and space, and at a high frame rate venous blood per se was observed as a moving column of amorphous RBC aggregates with irregular edges; we believe this is the first report of such an observation under physiological conditions. The formation of such intravascular RBC aggregates would enforce slowing of blood flow and vice versa: RBC aggregation was in turn entirely flow-dependent. In rapid venous flow, RBCs appeared as a straight gathering of individually separated and dispersed cells. At capillo-venous junctions, an "RBC pouring" process appeared to occur, with RBCs either being sucked up from the capillary, merging, or being held back in the capillary. Changes in venous blood viscosity due to RBC aggregation are likely to be involved in this process. These findings suggest that the capillo-venous junction somehow participates in the regulation of appropriate tissue capillary flow in toto.

Initial oligemia with capillary flow stop followed by hyperemia during K+-induced cortical spreading depression in rats.

Local cerebral blood volume (CBV) and capillary flow changes in regions of depolarizing neurons during K(+)-induced cortical spreading depression (CSD) in the cerebral cortex of alpha-chloralose-urethane-anesthetized rats were examined employing a transillumination (550 nm) video system. Capillary flow was calculated as the reciprocal of mean transit times of blood in pixels of 40 microm x 40 microm, each of which contains a few capillaries. Potassium microinjection into the cortex evoked repetitive wave-ring spreads of oligemia at a speed of ca. 2.33 +/- 0.48 mm/min. During the spread of CSD, tracer (either saline or carbon black) was injected into the internal carotid artery. Colocated with the oligemic wave, we detected capillary flow stop as evidenced by disappearance of the hemodilution curves. At any location in the region of interest within the cerebral cortex, we observed cyclic changes of capillary flow stop/hyperperfusion in synchrony with oligemia/hyperemia fluctuations. The initial flow stop and oligemia were ascribed to capillary compression by astroglial cell swelling, presumably at the pericapillary endfeet, since the oligemia occurred before larger vessel changes. We conclude that local depolarizing neurons can decrease adjacent capillary flow directly and immediately, most likely via astroglial cell swelling, and that the flow stop triggers upstream arteriolar dilatation for capillary hyperperfusion.

Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke-prone rats.

BACKGROUND AND PURPOSE: Inflammatory and immune mechanisms can precipitate cerebrovascular thrombosis and hemorrhage. Immunologic tolerance can be induced to a specific antigen by intranasal instillation of that antigen. Lymphocytes tolerized in this way provide local immunosuppression on restimulation with the same antigen. This study tests whether tolerization of lymphocytes to E-selectin can suppress local vessel activation and prevent stroke. METHODS: Spontaneously hypertensive genetically stroke-prone rats (n=113) were distributed among the following studies: comparison of ischemic infarcts/intraparenchymal hemorrhages after single or repetitive tolerization schedules with ovalbumin, E-selectin, or PBS; comparison of E-selectin tolerization- and PBS tolerization-induced suppression of delayed-type hypersensitivity in animals subsequently sensitized to E-selectin; and comparison of PBS-, ovalbumin-, and E-selectin-tolerized groups (after intravenous lipopolysaccharide to activate vessels) regarding transforming growth factor-beta1-positive splenocyte counts, plasma interferon-gamma levels, anti-human E-selectin antibodies, endothelial intercellular adhesion molecule-1, and anti-endothelial cell antibodies. RESULTS: Nasal instillation of E-selectin, which is specifically expressed on activated endothelium, potently inhibited the development of ischemic and hemorrhagic strokes in spontaneously hypertensive stroke-prone rats with untreated hypertension. Repeated schedules of tolerization were required to maintain the resistance to stroke. Suppression of delayed-type hypersensitivity to E-selectin and increased numbers of transforming growth factor-beta1-positive splenocytes showed that intranasal exposure to E-selectin induced immunologic tolerance. E-selectin tolerization also reduced endothelial activation and immune responses after intravenous lipopolysaccharide, as shown by marked suppression of intercellular adhesion molecule-1 expression, anti-endothelial cell antibodies on luminal endothelium, and plasma interferon-gamma levels compared with the control condition. CONCLUSIONS: The novel findings in this study support further investigation of immunologic tolerance as applied to the prevention of stroke.

Dynamic observation of oxygenation-induced contraction of and transient fiber-network formation-disassembly in cultured human brain microvascular endothelial cells.

Oxygenation-induced contraction of nonconfluent cultured human brain microvascular endothelial cells (HBECs, n = 30) was examined by video-enhanced contrast-differential interferential contrast microscopy. After administering a continuous gentle blow of pure oxygen gas to the surface of the medium just above the flattened HBEC, the plasma membrane exhibited tensioning and wrinkling, resulting in a strong contraction of the cell body by 14 +/- 7% (P < 0.001). When the cell stopped contracting, transient formation of a fiber network starting from certain spots (possibly adhesion plaques, though these were not visible in the majority of cases) and expanding to the whole cell was observed. The occurrence of fiber network formation was statistically significant (26 of 30 separate cells, P < 0.05). After cessation of oxygen delivery, the observed network of fibers broke up rapidly (in a period of 3.3 +/- 1.2 seconds) into small particles of <0.5 microm in diameter, which subsequently fused into the cellular structure. The HBEC completely recovered the control appearance. The sequential process was completed within 30 seconds and was reproduced in individual cells each time that oxygen gas was supplied. The authors conclude that the HBEC strongly contracts in response to a transient oxygenation stimulus, followed by rapid formation/disassembly of a network structure.

Moment analysis of microflow histogram in focal ischemic lesion to evaluate microvascular derangement after small pial arterial occlusion in rats.

The authors' high-spatial-resolution optical method was used to examine microvascular derangement in a focal cerebral cortex lesion in 12 Sprague-Dawley rats anesthetized with alpha-chloralose-urethane. A pial artery (approximately 40- to 50 microm diameter) was occluded by laser-beam cauterization (n = 6). Diluted carbon black suspension was injected into the internal carotid artery, and images in a 2-mm x 2-mm region of interest during tissue dye-dilution were recorded. Sequential frames were analyzed with Matlab software to evaluate blood distribution and mean transit time, affording a two-dimensional microflow map and histogram with first, second, third, and fourth moments. In the early phase of ischemia, blood distribution and average flow decreased (both P < 0.01), and the second moment (microflow heterogeneity) and third moment (skew to the left owing to increase in low-flow components) increased (P < 0.05 and P < 0.01, respectively). At approximately 2 hours, blood distribution decreased further in 3 cases, apparently because capillary stasis prevented carbon black filling. However, average microflow unexpectedly increased in 4 of 5 rats, presumably due to exclusion of unperfused (low flow at the earlier stage) channels from the calculation. The authors conclude that flow in ischemic tissue is quite heterogeneous and that an averaged flow value tends to smear important information about ischemic microvascular derangement.

Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K(+)-induced spreading depression in rats and cats.

Vascular changes accompanying spreading depression (SD) remain controversial. We examined dynamic alterations of local cerebral blood volume (CBV) during SD by observing light transmission at an isosbestic point of hemoglobin (550 nm) in seven rats and five cats under alpha-chloralose/urethane anesthesia. The two species were used for comparison between the lissencephalic and gyrencephalic brains. We found that a concentrated K(+) solution microinjected into the sensorimotor cortex provoked CBV changes that appeared as a repetitive propagation of concentric wave-rings of ischemia followed by hyperemia expanding peripherally from the injection site at speeds of 1.9-3.2 mm/min. The dynamic CBV changes continued repeatedly every 1-5 min for more than 30 min in three rats, ceased within 30 min in three rats and remained at the site of K(+) injection in one rat. Similar repeated CBV changes occurred in two out of five cats.

Recurrent transient hemiparesis in a patient with a giant persisting Eustachian valve and patent foramen ovale: atypical hemiplegic migraine or paradoxical cerebral embolism?

We encountered a patient with the overlapping disorders of migraine with aura, migraine-triggered seizures and recurrent transient hemiparesis caused by atypical hemiplegic migraines with motor weakness during headache attacks, but not during the aura period, or paradoxical cerebral embolism. The patient displayed a giant Eustachian valve and patent foramen ovale, through which a spontaneous right-to-left shunt was revealed on transesophageal echocardiography. We considered that the overlapping disorders in the present case were closely related to the spontaneous right-to-left shunt caused by the giant Eustachian valve.

Delayed recurrent ischemic stroke after initial good recovery from pneumococcal meningitis.

We describe unusual delayed recurrent episodes of ischemic stroke in a patient with initial good recovery from pneumococcal meningitis due to progressive arterial stenosis for over 3 months. We postulate that any of the following may have been responsible for his condition: widespread cerebral vasculopathy due to the effects of purulent material bathing the base of the brain, an immune-mediated para-infectious condition, or a rebound effect of the primary inflammatory reaction that was initially suppressed by dexamethasone. This case demonstrates that progressive arterial stenosis can evolve months after bacterial meningitis and should be recognized as a potential vascular complication.

Progressive multiple cranial nerve palsies as the presenting symptom of meningeal carcinomatosis from occult colon adenocarcinoma.

We herein describe a rare case of meningeal carcinomatosis in a 77-year-old woman who had bilateral deafness as the initial symptom of a previously undetected colon cancer malignancy. Meningeal carcinomatosis should be considered in the differential diagnosis in cases of abrupt-onset sensorineural deafness. Both MRI scans and cerebrospinal fluid evaluation are necessary diagnostic tools, and should be used in conjunction as each of these procedures could have false-negative results. This should apply even when there is no known primary malignancy.

Patent foramen ovale as a risk factor for cryptogenic brain abscess: case report and review of the literature.

We encountered a patient with brain abscess presumably caused by dental infection. The patient displayed patent foramen ovale (PFO) and a giant Eustachian valve, through which spontaneous right-to-left shunt was revealed by transesophageal echocardiography. Reviewing the literature, we find additional cases where brain abscess originated from an increased amount of flora commonly found in the oral cavity that bypassed the pulmonary vascular bed and the lymphatic system through PFO. Additionally, a Eustachian valve should be considered an adjunctive risk factor for initiating a spontaneous right-to-left shunt and predisposing cryptogenic brain abscess in patients with PFO.

Factors related to recurrence of paradoxical cerebral embolism due to patent foramen ovale.

Patent foramen ovale (PFO) is an important etiology of ischemic stroke in young adults. We investigated factors contributing to recurrent ischemic stroke in patients with PFO. Subjects comprised 47 patients (mean age, 56.8 ± 14.2 years; range 23-74 years) with ischemic stroke due to PFO who were admitted to our hospital between April 2007 and February 2011. Mean duration of follow-up was 34.5 ± 13 months. Recurrence occurred in 11 cases. Annual recurrence rate was 23.4%. We investigated relationships between recurrence of ischemic stroke and size of PFO (large, >4 mm; medium, 2-3.9 mm; small, <1.9 mm; absent group), maximal number of microbubbles (determined as the number of microembolic signals: small, 0-5; moderate, 6-25; and multiple, ≥ 26), massive bubble on contrast transesophageal echocardiography or atrial septal aneurysm, D-dimer level and antithrombotic therapy. Univariate analysis showed size of the PFO (P = 0.013), number of microbubbles (P = 0.021), and presence of a massive bubble on echocardiography (P = 0.04) were related to recurrence of ischemic stroke. Logistic analysis identified size of the PFO (P < 0.05) and massive bubble on echocardiography (P < 0.05) as factors related to recurrence of ischemic stroke. In conclusion, size of the PFO and presence of a massive bubble were considered to be factors associated with recurrence of ischemic stroke due to PFO.