4-Hydroxyl-2-Nonenal Localized Expression Pattern in Retrieved Clots is Associated with Large Artery Atherosclerosis in Stroke Patients.

OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).

Catastrophic Multiple Microbleeds Caused by Infective Endocarditis Following Intravenous Thrombolysis and Endovascular Thrombectomy.

Ischemic stroke is one of the most common complications of infective endocarditis (IE). IE must be considered as one of the causes of acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO), but early diagnosis of IE is difficult. AIS with ELVO must be treated using endovascular thrombectomy (EVT), with or without intravenous thrombolysis (IVT). IVT for AIS due to IE is not well established and remains controversial because of the risk of intracranial hemorrhage. A 42-year-old man suffered from right hemiparesis and disorientation, and AIS with ELVO was diagnosed. EVT with IVT was successfully performed and recanalization was achieved, but catastrophic multiple cerebral microbleeds appeared after treatment. EVT without IVT could be chosen for AIS caused by IE to avoid hemorrhagic complications. Hypointense signal spots on T2*-weighted magnetic resonance imaging (MRI) and susceptibility-weighted MRI could facilitate early diagnosis of IE.

Endovascular Treatment of Idiopathic Intracranial Hypertension with Stenting of the Transverse Sinus Stenosis.

For many years, the pathophysiology of idiopathic intracranial hypertension (IIH) was interpreted as "secondary intracranial hypertension," and IIH was considered to be caused by brain edema due to obstructive sleep apnea. Another theory proposed cerebrospinal fluid (CSF) absorption impairment due to excessive medication with vitamin A derivatives. Other reports pointed out the importance of obesity, which may cause an impairment of intracranial venous drainage due to elevated right atrial pressure. Patients with medically refractory IIH have traditionally undergone a CSF diversion. Venous outlet impairment on IIH has recently been reported as a causative or contributory cause, and thus focused venoplasty of the stenotic sinus with a stent has emerged as a new treatment strategy. We report the cases of two patients who presented with headache and papilledema with IIH. They successfully underwent stent placement at the stenosis of the transverse sinus and experienced complete resolution of symptoms.

Infiltrated Embolization of Meningioma with Dilute Cyanoacrylate Glue.

We describe the efficacy and technical aspects of infiltrated preoperative embolization of meningioma by penetration of very dilute glue. In this method, a 13% n-butyl-cyanoacrylate (NBCA)-lipiodol mixture is injected extremely slowly from the middle meningeal artery (MMA) in a similar manner to plug and push injection of ethylene vinyl alcohol copolymer mixed with tantalum and dimethyl sulfoxide (Onyx®) after the tortuous side feeders are proximally embolized. The glue is infiltrated into small tumor arteries and extends to inaccessible feeders from deep meningeal arteries. Since 2011, we have used this technique in the embolization of 32 cases preoperatively diagnosed with meningioma. Intratumoral embolization was possible in 30 cases (94%), and a greater than 50% reduction in contrast area of contrast-enhanced T1-weighted MR imaging (T1-WI) was achieved in 18 cases (56%). Two cases achieved complete devascularization, showing a remarkable shrinkage in tumor size after embolization. If excessive reflux of embolization and the resulting migration of glue into normal arteries is achieved, this method provides extremely effective devascularization on surgical extirpation. It might also be applicable to surgically untreatable meningiomas as a semi-radical treatment option.

Diagnosing intra-cranial and cervical artery dissection using MRI as the initial modality.

Dissection of cranial and cervical arteries is a relatively frequent clinical condition. However, it is difficult to diagnose a dissection when patients present with relatively mild symptoms. Various radiological techniques are used as diagnostic tools. This study analyzed retrospectively the characteristics of cranial and cervical artery dissections using "MR first concept", with MRI as the first-choice diagnostic modality for all new patients with neurological symptoms. The patients who were admitted in Ohnishi neurological center between January 2001 and December 2014 were included. MRI was used as the initial investigation for all new patients, including those with mild symptoms such as headache or vertigo only. The patients were divided into carotid group and vertebral group. The statistical comparison was performed between these two groups. A total of 164 patient cases were analyzed. In 44 (26.8%) and 120 (73.2%) patients, dissection occurred in the carotid group and vertebral group, respectively. Concerning the type of onset, 52 patients presented with only subjective symptoms accompanied with ischemic or hemorrhagic lesions, 97 patients with ischemic symptoms and 15 patients with subarachnoid hemorrhage. There were statistically significant differences between the carotid and vertebral groups in terms of hemiparesis, aphasia, history of trauma, headache and vertigo. Patients with only a headache and those with no ischemic features had no worsening symptoms. The symptom of headache or neck pain only is more frequent than previously reported. The "MR first concept" would prove useful for early diagnosis of dissections and early treatment.

Enhanced expression of coproporphyrinogen oxidase in malignant brain tumors: CPOX expression and 5-ALA-induced fluorescence.

In photodynamic diagnosis, 5-aminolevulinic acid (5-ALA) is widely used for the fluorescence-guided resection of malignant brain tumors, where 5-ALA is converted to protoporphyrin IX, which exhibits strong fluorescence. Little is known, however, about the detailed molecular mechanisms underlying 5-ALA-induced fluorescence. To resolve this issue, we analyzed transcriptome profiles for the genes encoding enzymes, transporters, and a transcription factor involved in the porphyrin-biosynthesis pathway. By quantitative real-time (qRT)-PCR, we measured the mRNA levels of those genes in a total of 20 tumor samples that had been surgically resected from brain tumor patients at the Department of Neurosurgery of Osaka Medical College from 2008 to 2009. We selected 10 tumor samples with no 5-ALA-induced fluorescence, among which 2 were glioblastomas and 8 were metastatic brain tumors. Another 10 tumor samples were selected with strong fluorescence, among which 7 were glioblastomas and 3 were metastatic brain tumors. The qRT-PCR analysis study of these latter 10 samples revealed predominantly high levels of the mRNA of the coproporphyrinogen oxidase (CPOX) gene. The high mRNA level of CPOX expression was significantly well correlated with the phenotype of strong 5-ALA-induced fluorescence (P = .0003). These findings were further confirmed by immunohistochemical studies with a CPOX-specific antibody. It is concluded that induction of CPOX gene expression is one of the key molecular mechanisms underlying the 5-ALA-induced fluorescence of malignant brain tumors. The induction mechanism for the CPOX gene in brain tumors remains to be elucidated.

Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors.

Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX) exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA) or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR) analysis to design potent ABCG2-inhibitors.

Ischaemia-induced vascular vulnerability resulting in intracerebral haemorrhage with ipsilateral internal carotid artery occlusion.

Intracerebral haemorrhage accompanied with cervical internal carotid artery (ICA) occlusion on the same side without moyamoya-like vessels is rare. A 73-year-old man with left ICA occlusion and no presence of moyamoya disease criteria underwent xenon-enhanced computed tomography with acetazolamide challenge test. The findings showed hypoperfusion and no vasoreactivity in the territory of the left middle cerebral artery. During follow-up he suffered bleeding in the left frontoparietal lobe. Cerebral angiography showed left ICA occlusion and cross flow via the anterior communicating artery without moyamoya vessels. Long-term ischaemia would make perforating or anastomotic arteries vulnerable. These arteries were easily ruptured by hypertension, resulting in intracerebral haemorrhage.