Tomoyasu Shirakawa

Paramedian Pontine Infarction: Neurological/Topographical Correlation

BACKGROUND AND PURPOSE There have been few reports of pontine syndromes secondary to paramedian pontine infarctions. To clarify the clinicotopographical correlation and prognosis of paramedian pontine infarct syndromes, we analyzed the clinical signs and their association with MRI findings. METHODS We studied 49 patients with acute paramedian pontine infarcts and classified them into three subtypes on the basis of lesion location on MRI. Patient clinical status was assessed by Rankin Disability Scale (RDS) scores on admission and at 60 days after onset of stroke. RESULTS Twenty-seven patients had basal infarcts. Clinical findings included dysarthria (n = 27), hemiparesis with upper extremity predominance (n = 15), brachial monoparesis (n = 4), and pathological laughing (n = 3). Fifteen patients had basal-tegmental infarcts. Clinical findings presented with hemiparesis and horizontal gaze abnormalities, including abducens nerve palsy (n = 1), internuclear ophthalmoplegia (INO) (n = 5), horizontal gaze palsy (n = 1), one-and-a-half syndrome (n = 1), and superficial or proprioceptive sensory dysfunction (n = 8). Seven patients had tegmental infarcts. Clinical findings included INO (n = 1), horizontal gaze palsy (n = 2), one-and-a-half syndrome (n = 3), and sensory changes (n = 2). On both admission and 60 days later, the RDS scores of the patients with upper pontine lesions were significantly better than those with lower pontine lesions (P < .01). The RDS scores of the patients with basal-tegmental infarct in the upper pons were significantly better than those with infarct in the lower pons (P < .02). CONCLUSIONS Paramedian pontine infarcts, which are usually due to thrombosis of perforating arteries, presented with a faciobrachial dominant hemiparesis with dysarthria, somatosensory disturbance, and horizontal gaze abnormalities. The favorable outcome may be related to the level of the pontine lesion, which influences the effect on the corticospinal tract.

Activation of thrombosis and fibrinolysis following brain infarction

To clarify the sequence of alterations in the thrombotic and fibrinolytic systems after acute brain infarction, we prospectively examined sequential changes in coagulatory markers in 38 patients suffering from cardioembolic infarcts (CEI), 41 patients with atherothrombotic infarcts (ATI), 58 patients with lacunar infarcts (LI), and 32 age-matched controls. The plasma level of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FpA), D-dimer, fibrin degradation products-E (FDP-E), fibrinogen, alpha2-plasmin inhibitor-plasmin complex (PIC), and percent activity of antithrombin III (AT-III) were measured within 48 h, at 1 week, and at 3 weeks after the stroke onset. Significantly elevated levels of TAT and FpA, which are both markers of thrombin formation, were observed in CEI patients, and these elevated levels were associated with increasing D-dimer levels for 3 weeks (P<0.0001). D-Dimer in CEI patients was significantly elevated compared to control, LI and ATI levels within 48 h (P<0.001). Percent activity of AT-III was significantly decreased in CEI patients for 3 weeks compared to this activity in controls, LI and ATI (P<0.001). TAT and FpA also increased significantly within 48 h in ATI subjects and declined thereafter. A significant elevation of FDP-E (P<0.001) and D-dimer (P<0.05, P<0.01) was detected in parallel with increasing fibrinogen for 3 weeks. However, there was no significant depletion of percent activity of AT-III in ATI. In LI subjects, no significant elevation of TAT, D-dimer or FDP-E were observed within 1 week. PIC increased significantly in three subtypes of brain infarcts, but did not differ significantly among the three subtypes for 3 weeks. An accurate assessment of sequential alterations in thrombotic and fibrinolytic markers in the acute stage of brain infarct should contribute to the clinical diagnosis of brain infarct subtype. Alterations in these markers in response to activation of the coagulatory system are attributable to the different pathogenesis of ischemic stroke.

Interaction of a Paraneoplastic Cerebellar Degeneration-Associated Neuronal Protein with the Nuclear Helix-Loop-Helix Leucine Zipper Protein MRG X

Paraneoplastic cerebellar degeneration-associated antigen PCD17/cdr2 is a neuronal protein expressed predominantly in the cytoplasm of cerebellar Purkinje cells. The biological activities of this protein are not known; however, the presence of a leucine zipper motif in its amino acid sequence suggests that this protein might interact with other proteins harboring a leucine zipper motif. In this study we found by means of a yeast two-hybrid system, ligand overlay assay, and co-immunoprecipitation assay that PCD17 interacts with a nuclear helix-loop-helix leucine zipper protein, MRG X. Overexpression of MRG X in T98G glioblastoma cells by transfection caused abnormal morphological changes in the nucleus and induced cell death. On the other hand, coexpression of PCD17 with MRG X prevented nuclear morphological changes and cell death in T98G cells. MRG X, which is thought to be functionally related to the cell cycle and cell growth, may be regulated by PCD17/cdr2 in Purkinje cells.

Induction of major histocompatibility complex class I molecules on human neuroblastoma line cells by a flavoid antioxidant

Human major histocompatibility complex (MHC) class I expression is usually suppressed in neuronal cells and neuroblastoma cells. In the present study, we analyzed the effect of a flavonoid antioxidant, silymarin, on the induction of MHC class I molecules in human neuroblastoma line cells. Treatment of neuroblastoma cells with silymarin resulted in the expression of MHC class I molecules. Silymarin treatment enhanced the transcriptional activity of the reporter construct containing MHC class I promoter truncated within -428 bp of transcription initiation, but not the construct containing the promoter truncated within -284 bp. Because an E-box element is located between -428 and -285 bp of the transcription initiation, results suggest that silymarin acts on the enhancer activity of the E-box in the MHC class I promoter. Our findings indicate that silymarin induces the transcriptional factors to enhance the MHC class I promoter through the class I E-box element.

Suppression of the transcriptional activity and DNA binding of nuclear factor-kappa B by a paraneoplastic cerebellar degeneration-associated antigen

Paraneoplastic cerebellar degeneration (PCD) associated with gynecological malignancies is a disorder in which an autoimmune mechanism has been suggested, and both antibody- and cell-mediated immune responses exist against pcd17/cdr2, a neural protein expressed in cerebellar Purkinje neurons and brainstem neurons. In this report, we describe that pcd17 can suppress the basal or activated NF-kappaB-dependent transcriptional activity in a co-transfection study. The DNA binding of constitutive NF-kappaB complexes decreased in the nucleus of TNF-alpha-stimulated neuroblastoma cells, though pcd17 does not bind to classical NF-kappaB consensus site. These data indicate that pcd17 is a potential repressor for NF-kappaB-dependent gene transcription in neurons.

Medullary pyramidal infarction caused by vertebral artery dissecting aneurysm

Dissecting aneurysm of the vertebral artery (VA) can be a cause of lateral medullary infarction [1, 2]. However, medial medullary infarction induced by dissecting aneurysm of the VA is very rare [3– 5]. We present a patient with medullary pyramidal infarction, presenting with pure motor hemiparesis sparing the face, caused by dissecting aneurysm of the VA, as detected by magnetic resonance imaging (MRI).