Recanalization of Chronic Occlusion of the Middle Cerebral Artery With Tissue Plasminogen Activator Treatment: A Case Report.

OBJECTIVES: Patients with chronic proximal middle cerebral artery (MCA) occlusion do not present with severe symptoms, but early recanalization of acute occlusion is associated with high morbidity and mortality. Tissue plasminogen activator (tPA) is a recombinant thrombolytic agent approved for treating ischemic stroke, although only a few cases of tPA administration in chronic MCA occlusion have yielded positive results. METHODS: A 71-year-old patient had a history of right MCA territorial infarction with the occlusion occurring 12 years ago (November 2005). Although the patient was treated with antiplatelet agents, MCA recanalization was not achieved. The patient was referred to our hospital again (January 2017) for newly discovered symptoms. We immediately administered tPA because the patient presented 2 hours after onset of symptoms. RESULTS: Neurological symptoms resolved within 24 hours of treatment, and magnetic resonance angiography confirmed recanalization of the right MCA territorial lesion. No neurological abnormalities were observed during the 12-week follow-up. CONCLUSIONS: At present, tPA is the only approved treatment for acute ischemic stroke, although it presents a limited time frame to avoid severe medication-related adverse effects. Our report suggests nonatherosclerotic chronic MCA occlusion as an alternative application of tPA therapy.

Thrombocytopenia induced by dabigatran: two case reports.

BACKGROUND: Vitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These agents have been mainstays of anticoagulation for people older than 60 years. However, their administration is associated with a risk of bleeding and requires careful monitoring of patients. Novel oral anticoagulants (NOACs), such as dabigatran, are significantly safer in preventing thromboembolism than warfarin and heparin (sporadically causes thrombocytopenia) and are more specific for their target protein, thrombin. The major advantage of dabigatran, a direct thrombin inhibitor, is that it reversibly inhibits both free and clot-bound thrombin by tight binding affinity and the predictable pharmacodynamic effect. A few studies, however, reported that dabigatran can cause thrombocytopenia, although the underlying mechanism remains unclear. Thus, an antidote for dabigatran was developed to prevent thrombocytopenia. CASE PRESENTATION: In this report, we discuss two cases of thrombocytopenia and purpura after dabigatran treatment. A 73-year-old man showed hemorrhagic necrotic skin lesions on his neck and right hand. He was administered dabigatran (220 mg/day) for cerebral infarction for three days and his platelet count decreased abruptly (6000/µL). This suggested that dabigatran had caused thrombocytopenia and purpura; therefore, dabigatran administration was discontinued. The results of a blood test, performed 14 days after stopping dabigatran treatment, showed that the platelet count had recovered to the normal range of more than 150,000/µL. A 75-year-old woman had taken warfarin continuously for 8 years. However, she had a new cerebral infarction. Therefore, warfarin treatment was replaced with dabigatran (300 mg/day). Her platelet count decreased (41,000/µL) significantly and dabigatran treatment was discontinued. The blood test results show that platelet counts gradually recovered to the normal range. CONCLUSIONS: Dabigatran application may cause bleeding; therefore, careful monitoring during dabigatran treatment is required to prevent thrombocytopenia. An explanation is that the interaction of dabigatran with thrombin, because of its strong binding affinity, may cause the observed thrombocytopenia.

Structural Analyses of Zinc Finger Domains for Specific Interactions with DNA.

Zinc finger proteins are among the most extensively applied metalloproteins in the field of biotechnology owing to their unique structural and functional aspects as transcriptional and translational regulators. The classical zinc fingers are the largest family of zinc proteins and they provide critical roles in physiological systems from prokaryotes to eukaryotes. Two cysteine and two histidine residues (Cys2His2) coordinate to the zinc ion for the structural functions to generate a ßßα fold, and this secondary structure supports specific interactions with their binding partners, including DNA, RNA, lipids, proteins, and small molecules. In this account, the structural similarity and differences of well-known Cys2His2-type zinc fingers such as zinc interaction factor 268 (ZIF268), transcription factor IIIA (TFIIIA), GAGA, and Ros will be explained. These proteins perform their specific roles in species from archaea to eukaryotes and they show significant structural similarity; however, their aligned amino acids present low sequence homology. These zinc finger proteins have different numbers of domains for their structural roles to maintain biological progress through transcriptional regulations from exogenous stresses. The superimposed structures of these finger domains provide interesting details when these fingers are applied to specific gene binding and editing. The structural information in this study will aid in the selection of unique types of zinc finger applications in vivo and in vitro approaches, because biophysical backgrounds including complex structures and binding affinities aid in the protein design area.

Sensory pathways in the human embryonic spinal accessory nerve with special reference to the associated lower cranial nerve ganglia.

BACKGROUND AND PURPOSE: Muscles supplied by the spinal accessory nerve are particularly prone to the development of trigger points characteristic of myofascial pain. This study aimed to confirm sensory pathways in the spinal accessory nerve and to describe sensory ganglion cell distributions along the lower cranial nerve roots. METHODS: Using sagittal sections of ten human embryos at 6-7 weeks and horizontal sections of three 15- to 16-week-old embryos, we analyzed ganglion cell distributions along the lower cranial nerve roots, including the spinal accessory (XI) nerve. RESULTS: In all ten 6- to 7-week-old embryos, the XI nerve root contained abundant ganglion cells, which were evenly distributed along the XI nerve root at levels between the jugular foramen and the dorsal root of the second cervical nerve. However, the hypoglossal (XII) nerve roots did not contain ganglion cells and did not communicate with nearby roots in the dural space. Thus, the so-called Froriep's occipital ganglion is unlikely to be associated with the XII nerve but rather with the XI nerve roots. According to observations of three larger fetuses (15-16 weeks), most of Froriep's ganglion cells seemed to have degenerated during early fetal life. CONCLUSION: Nociceptive sensory pathways in the adult human XI nerve may be much more limited in number than would be expected based on previous animal studies. However, it is possible that sensory ganglion cells in the embryonic XI nerve root send axons toward the developing spinal accessory nerve fibers outside of the jugular foramen.

Ectopic choroid plexus found in fetal sections: a case report with literature consideration.

We incidentally found an ectopic choroid plexus (CP) attached to the posterior side of the cervicothoracic spinal cord (C4-T6) in a 16-week aborted fetus. The cytoarchitecture of the cord and segmental nerves showed normal development. The fourth ventricle did not contain the usual CP but a red blood cell cluster due to hemorrhage, although the cause, whether spontaneous or traumatic, was unknown. The ectopic CP was associated with thick neuroepithelium that was strongly positive for glial fibrillary acidic protein, vimentin, nestin, and proliferating cell nuclear antigen, but did not contain any CD34-positive vessels. Thus, the ectopic neuroepithelium seemed not to carry growth factor for vascular development. On the inferior side of the ectopic CP, the lower thoracic cord was wavy, folded, and packed in a limited space as a folding fan. Despite the strange gross appearance, however, we found no abnormality in the dorsal root ganglion, the spinal nerve root, or the cytoarchitecture of the lower thoracic cord. Therefore, the abnormality in the lower thoracic cord seemed to be secondarily induced by trophic factor(s) from the ectopic CP and/or the associated neuroepithelium. This may be the first report on an ectopic CP associated with ectopic neuroepithelium.

Association of aortic knob calcification with intracranial stenosis in ischemic stroke patients.

BACKGROUND AND PURPOSE: Aortic knob calcification (AC) is associated with increased risks of cardiovascular and cerebrovascular events. We evaluated the clinical importance of AC in ischemic stroke patients with intracranial (IC) stenosis using simple, non-invasive and routine chest radiography. METHODS: The presence of AC was assessed in a chest posteroanterior view in 307 acute ischemic stroke patients admitted from May 2009 to April 2010, and who underwent magnetic resonance angiography or distal subtraction angiography. The association of AC with IC stenosis was analyzed. RESULTS: Patient age (68.3±8.7 vs. 65.9±8.27 years, P=0.04), and the prevalence of IC stenosis (70.7 vs. 41.3%, P<0.01) were higher in patients with AC than in patients without calcification. After adjusting for age, gender and vascular risk factors, logistic regression analysis showed that AC (Odds ratio, 3.54; 95% confidence interval, 1.90 to 6.61, P<0.01) and age (Odds ratio, 1.79; 95% confidence interval, 1.01 to 3.19; P=0.04) were independent factors affecting IC stenosis. CONCLUSIONS: AC appears to be a reliable predictor for IC stenosis, an important mechanism of ischemic stroke.

Tooth loss may predict poor cognitive function in community-dwelling adults without dementia or stroke: the PRESENT project.

Periodontal disease is a potential predictor of stroke and cognitive impairment. However, this association is unclear in adults aged 50 yr and above without a history of stroke or dementia. We evaluated the association between the number of teeth lost, indicating periodontal disease, and cognitive impairment in community-dwelling adults without any history of dementia or stroke. Dental examinations were performed on 438 adults older than 50 yr (315 females, mean age 63±7.8 yr; 123 males, mean age 61.5±8.5 yr) between January 2009 and December 2010. In the unadjusted analysis, odds ratios (OR) of cognitive impairment based on MMSE score were 2.46 (95% CI, 1.38-4.39) and 2.7 (95% CI, 1.57-4.64) for subjects who had lost 6-10 teeth and those who had lost more than 10 teeth, respectively, when compared with subjects who had lost 0-5 teeth. After adjusting for age, education level, hypertension, diabetes, hyperlipidemia, and smoking, the relationship remained significant (OR, 2.0; 95% CI, 1.08-3.69, P=0.027 for those with 6-10 teeth lost; OR, 2.26; 95% CI, 1.27-4.02, P=0.006 for those with more than 10 teeth lost). The number of teeth lost is correlated with cognitive impairment among community-dwelling adults aged 50 and above without any medical history of stroke or dementia.

Tooth loss is associated with brain white matter change and silent infarction among adults without dementia and stroke.

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 ± 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.

Site-specific distribution of CD68-positive microglial cells in the brains of human midterm fetuses: a topographical relationship with growing axons.

Using 5 fetuses of gestational age (GA) of 15-16 weeks and 4 of GA of 22-25 weeks, we examined site- and stage-dependent differences in CD68-positive microglial cell distribution in human fetal brains. CD68 positive cells were evident in the floor of the fourth ventricle and the pons and olive at 15-16 weeks, accumulating in and around the hippocampus at 22-25 weeks. At both stages, the accumulation of these cells was evident around the optic tract and the anterior limb of the internal capsule. When we compared CD68-positive cell distribution with the topographical anatomy of GAP43-positive developing axons, we found that positive axons were usually unaccompanied by CD68-positive cells, except in the transpontine corticofugal tract and the anterior limb of the internal capsule. Likewise, microglial cell distribution did not correspond with habenulointerpeduncular tract. Therefore, the distribution of CD68-positive cells during normal brain development may not reflect a supportive role of these microglia in axonogenesis of midterm human fetuses.

Serum YKL-40 levels correlate with infarct volume, stroke severity, and functional outcome in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: YKL-40 is associated with various neurological disorders. However, circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS. METHODS: Serum YKL-40 and C-reactive protein (CRP) levels were monitored over time in AIS patients (n = 105) and compared with those of stroke-free controls (n = 34). Infarct volume and stroke severity (National Institutes of Health Stroke Scale; NIHSS) were measured within 48 hours of symptom onset, and functional outcome (modified Rankin Scale; mRS) was measured 3 months after AIS. RESULTS: Within 12 hours of symptom onset, levels of YKL-40 (251 vs. 41 ng/mL) and CRP (1.50 vs. 0.96 µg/mL) were elevated in AIS patients compared to controls. The power of YKL-40 for discriminating AIS patients from controls was superior to that of CRP (area under the curve 0.84 vs. 0.64) and YKL-40 (r = 0.26, P<0.001) but not CRP levels were correlated with mRS. On day 2 of admission (D2), YKL-40 levels correlated with infarct volume and NIHSS. High YKL-40 levels predicted poor functional outcome (odds ratio 5.73, P = 0.03). YKL-40 levels peaked on D2 and declined on D3, whereas CRP levels were highest on D3. CONCLUSIONS: Our results demonstrate serial changes in serum YKL-40 levels immediately following AIS and provide the first evidence that it is a valid indicator of AIS extent and an early predictor of functional outcome.

The anatomy of fetal peripheral lymphatic vessels in the head-and-neck region: an immunohistochemical study.

Using D2-40 immunohistochemistry, we assessed the distribution of peripheral lymphatic vessels (LVs) in the head-and-neck region of four midterm fetuses without nuchal edema, two of 10 weeks and two of 15 weeks' gestation. We observed abundant LVs in the subcutaneous layer, especially in and along the facial muscles. In the occipital region, only a few LVs were identified perforating the back muscles. The parotid and thyroid glands were surrounded by LVs, but the sublingual and submandibular glands were not. The numbers of submucosal LVs increased from 10 to 15 weeks' gestation in all of the nasal, oral, pharyngeal, and laryngeal cavities, but not in the palate. The laryngeal submucosa had an extremely high density of LVs. In contrast, we found few LVs along bone and cartilage except for those of the mandible as well as along the pharyngotympanic tube, middle ear, tooth germ, and the cranial nerves and ganglia. Some of these results suggested that cerebrospinal fluid outflow to the head LVs commences after 15 weeks' gestation. The subcutaneous LVs of the head appear to grow from the neck side, whereas initial submucosal LVs likely develop in situ because no communication was evident with other sites during early developmental stages. In addition, CD68-positive macrophages did not accompany the developing LVs.

Tuberculous Abscess of the Psoas Muscle in a Patient with Acute Lumbar Burst Fracture: A Missed Diagnosis.

The authors present a rare case of tuberculous spondylitis and a large abscess in the left psoas muscle that occurred after spinal surgery for an acute traumatic burst fracture of the L2 vertebral body. We retrospectively reviewed the patient's first magnetic resonance imaging (MRI) we found that some unusual findings, indicative of psoas abscess had been overlooked. As a result, diagnosis and treatment of tuberculous psoas abscess and spondylitis were considerably delayed. Despite the critical condition of patients in a similar emergency, surgeons should always pay close attention to the radiological findings and clinical symptoms of the patient before considering a surgical intervention or biopsy.