Masaaki Saiki

Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age

Background:  Taking an advantage of the high sensitivity of 3D T2*‐weighted gradient‐recalled‐echo (GRE) imaging to cerebral microbleeds, we investigated the relationship between cerebral microbleeds and leukoaraiosis.

FDG-PET a Pivotal Imaging Modality for Diagnosis of Stroke-Onset Intravascular Lymphoma

I NTRAVASCULAR LYMPHOMA (IVL) is a rare, fatal disease, often presenting with neurological deficits. Here we describe 2 patients initially diagnosed with recurrent atherosclerotic cerebral infarction followed by accurate diagnosis of IVL by positron emission tomography with fluorodeoxyglucose (FDG-PET). Case 1 is a 65-year-old man with dysarthria and mild right hemiparesis. Two days later, he was diagnosed with left cerebral infarction and severe stenosis of intracranial left internal carotid artery on magnetic resonance imaging.Hisclinicalcourse and radiological findings are summarized in Figure 1. While N-isopropyl-p-[123I]iodoamphetamine single-photon emission computed tomography (IMP-SPECT) studies revealed increased IMP uptake in the left frontal lobe, oxygen 15 gas PET did not reveal any abnormalities. We could not find any appropriate reasons for this discrepancy. Almost 100 days after onset, FDG-PET revealed high FDG uptake in the left frontal lobe. Brain biopsy was performed and revealed large B-cell IVL. The patient received whole-brain irradiationandsteroidtreatment,which transiently improved his symptoms, but he died 7 months after onset. Case2issummarizedinFigure2. A46-year-oldmanpresentedwithtransient dysarthria and left hemiparesis. Diffusion imaging 1.5 hours after onsetshowedahyperintenselesionatthe right insularcortex.Twenty-sixhours afteronset,his consciousnessand left hemiparesisworsened.Magneticresonanceimagingshowedprogressiveinfarctionand irregularmultiple stenosisof the rightmiddlecerebral artery. Ondays6through10,hebecameconfusedandparaplegicandrequired intubation and mechanical ventilation. Use of FDG-PET on day 10 showed high FDG uptake in the right temporal lobe. No other abnormal accumulationofFDGwasseenthroughoutthe body.Therefore,weconsideredtheetiology of his progressive infarction to be IVL and emergently treated him with R-CHOP (cyclophosphamide, doxorubicinhydrochloride,vincristine sulfate, and prednisolone with rituximab)chemotherapyandwhole-brain irradiation.Hisconditiondramatically improved. Five months after onset, 7 cyclesofR-CHOPchemotherapywere accomplished and his clinical condition improved.

Coexistence of multiple cavernous angiomas in the spinal cord and skin: a unique case of Cobb syndrome.

Cobb syndrome is a rare, noninherited, neurocutaneous disease characterized by vascular abnormality of the spinal cord and is associated with vascular lesions in the skin at the same metamere. The majority of spinal vascular lesions are arteriovenous malformations, and skin lesions are mostly port-wine angiomas. The authors report the first case of multiple intramedullary cavernous angiomas (CAs) accompanied by skin CAs within the same metamere. A 42-year-old man presented with an acute onset of gait disturbance, low-back pain, and urinary incontinence. Magnetic resonance imaging of the thoracolumbar spine showed homogeneously enhanced lesions on a contrast-enhanced T1-weighted image and a hypointense area on a T2*-weighted image surrounding this enhanced lesion, between the T-12 and S-1 levels. Purple protruding skin lesions were detected on the left side of his gluteal region. The patient received a laminectomy followed by evacuation of a hematoma and partial removal of the tumor, which completely resolved his neurological symptoms. Pathological examinations showed that the spinal and skin lesions were CAs, suggesting that these vascular lesions developed congenitally. Cavernous angiomas associated with Cobb syndrome present with multiple lesions spanning more than 3 vertebral levels, making it difficult to completely resect these tumors. Although Cobb syndrome is an uncommon disease entity, it should be considered if a patient manifesting with neurological deficits has skin vascular lesions, including CAs.

[Endovascular coil embolization for a ruptured distal anterior choroidal artery aneurysm showing definite short-term enlargement: a case report].

Distal anterior choroidal artery aneurysms are quite rare, and appropriate treatment timing and methods remain unclear. Direct surgery of these aneurysms is difficult due to their deep location, small size, and angioarchitecture;however, pseudoaneurysms might disappear spontaneously with conservative treatment. A 65-year-old man with a history of hypertension was admitted to our hospital with a 5-day history of sudden headache and nausea. Computed tomography revealed an intraventricular hematoma located mainly in the right lateral ventricle. Cerebral angiography 7 days after onset revealed a right distal anterior choroidal artery aneurysm and proximal right middle cerebral artery occlusion caused by atherosclerotic changes. Endovascular coil embolization was performed under general anesthesia 14 days after onset. Preoperative angiography demonstrated definite enlargement of the aneurysm and stasis of the contrast agent in the aneurysm in the venous phase. Detachable platinum coils were delivered into the aneurysm and parent artery. The patient was discharged neurologically intact after the procedure. Follow-up angiography 3 months after coil embolization showed complete occlusion of the aneurysm. In recent years, endovascular surgery has emerged as a less invasive treatment option. Early treatment should be considered for patients with ruptured distal anterior choroidal artery aneurysm because these aneurysms might grow and re-rupture in the short term.

Superficial siderosis of the central nervous system after ventriculoperitoneal shunt

The authors report a case of superficial siderosis of the CNS that developed after ventriculoperitoneal (VP) shunt placement for normal-pressure hydrocephalus. A 65-year-old woman had undergone VP shunt insertion for normal-pressure hydrocephalus. Her gait disturbance, memory disturbance, and urinary incontinence all improved after the procedure. Two years later, however, her gait became ataxic and her appetite became poor. Brain MR imaging revealed a rim of hypointensity on T2-weighted sequences, enveloping the surface of the cortical fissure, cerebellum, and brainstem. Superficial siderosis of the CNS was diagnosed. Steroid administration improved her symptoms. The authors know of only one case of superficial siderosis developing after VP shunt surgery in the English-language literature. Superficial siderosis should be acknowledged as a possible complication of VP shunt.

Arsenic trioxide sensitizes glioblastoma to a myc inhibitor.

Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC) of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs) than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM.

Thrombus Removal by Acute-phase Endovascular Reperfusion Therapy to Treat Cerebral Embolism Caused by Thrombus in the Pulmonary Vein Stump after Left Upper Pulmonary Lobectomy: Case Report

Thrombus formation in a pulmonary vein stump after pulmonary lobectomy is extremely rare, but can trigger cerebral embolism of unknown cause. We encountered a case of cerebral embolism in a 58-year-old man 2 days after left upper lobectomy. Since intravenous administration of recombinant tissue plasminogen activator was contraindicated, thrombus removal by endovascular reperfusion therapy was performed. Cerebral angiography showed left internal carotid artery occlusion. Thrombus removal using a retrieval device was performed and complete recanalization of the left internal carotid artery was obtained. Although blood abnormalities or arrhythmia such as atrial fibrillation were not observed, thrombus in the left upper pulmonary vein stump was detected with contrast-enhanced computed tomography of the body trunk, which was therefore considered as the source of cerebral embolism. The patient is continuing on anticoagulant therapy to prevent embolism recurrence caused by thrombus formation in the pulmonary vein resection stump. To the best of our knowledge, this is the first report of thrombus removal by acute-phase endovascular reperfusion therapy to treat cerebral embolism likely caused by thrombus formation in the pulmonary vein stump after left upper lobectomy. When cerebral embolism of unknown cause develops after left upper lobectomy, thrombus formation in the pulmonary vein stump should be considered among the differential diagnoses. For acute-phase onset of cerebral embolism after pulmonary lobectomy, thrombus removal by endovascular reperfusion therapy may be considered as one of the therapies.

Metastatic brain tumor from urothelial carcinoma of the prostatic urethra

Background: Urothelial carcinoma occurs in the bladder, upper urinary tract, and lower urinary tract, including prostatic urethra. A majority of the reported cases of intracranial metastasis from urothelial carcinoma originates from the bladder and upper urinary tract. Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. Case Description: A 72-year-old male presented with a metastatic brain tumor and a 3-year history of urothelial carcinoma of the prostatic urethra treated with cystourethrectomy and chemotherapy with gemcitabine-cisplatin. Pathological diagnosis for tumor removal was compatible with metastatic brain tumor from urothelial carcinoma. Conclusion: Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. It is an extremely rare case, however, we should be careful of brain metastasis during follow-up for urothelial carcinoma in the lower urinary tract.

Complications Associated with Surgical Treatment of Hydrocephalus

Excessive accumulation of cerebrospinal fluid (CSF) in the brain is a condition known as hydrocephalus. It may cause a life-threatening increase in intracranial pressure (ICP). Nonsurgical treatment of hydrocephalus includes continuous CSF drainage, repetitive lumbar punctures (Lim et al., 2009), or osmotic diuretics such as mannitol or glycerol, but their effects are transient and limited. Surgical treatment is needed to resolve the critical condition caused by increased ICP. Hydrocephalus can be classified as communicating or obstructive (non-communicating). In selecting surgical treatment, it is important to judge which is involved. Communicating hydrocephalus occurs when CSF flow is not blocked at any part of the passages connecting the ventricles. In obstructive hydrocephalus, CSF flow is blocked along one or more narrow passages between the ventricles. Hydrocephalus is treated by surgical insertion of a shunt system, such as a ventriculoperitoneal shunt (VP shunt), lumboperitoneal shunt (LP shunt) or ventriculoatrial shunt (VA shunt). The LP shunt should not be used in patients with obstructive hydrocephalus, because it can induce tentorial herniation leading to death. A limited number of patients with obstructive hydrocephalus are candidates for third ventriculostomy by neuroendoscope. Below, we review articles focusing on complications associated with various types of CSF diversion procedure.

Severe Hypoglycemia-induced Right Hemiparesis with Reversible Diffusion Restriction in the Left Internal Capsule Due to Combination Therapy Using Disopyramide and Clarithromycin

Severe hypoglycemia is known to cause acute focal neurological symptoms. In cases with a medical history of diabetes mellitus (DM), the diagnosis and treatment of hypoglycemia-induced neurological symptoms are simple. However, severe hypoglycemia can occur in patients who are not taking hypoglycemic agents such as insulin or long-acting sulfonylurea drugs. We describe a 95-year-old man with sudden onset of right hemiparesis who showed high signal intensity on diffusion-weighted imaging involving the left internal capsule with corresponding reduced apparent diffusion coefficient hypointensity. Laboratory findings revealed severe hypoglycemia (27 mg/dl). However, he was not taking insulin or long-acting sulfonylurea drugs but disopyramide and clarithromycin had been administered. In addition, he had kidney dysfunction with an estimated glomerular filtration rate (GFR) of 42.9 ml/min/1.73 m2. After the blood glucose level was normalized, the left hemiparesis completely recovered and abnormal findings of magnetic resonance imaging (MRI) study also became normal. A combination of disopyramide and clarithromycin may cause severe hypoglycemia-induced neurological symptoms particularly in patients with kidney dysfunction. Even in a patient with sudden-onset hemiparesis and no history of DM, the possibility of hypoglycemia-induced neurological deficit should be considered.