Cerebral hyperperfusion syndrome after endovascular reperfusion therapy for medium vessel occlusion: A case report.

Cerebral hyperperfusion syndrome is a rare but serious complication after revascularization procedures for cerebrovascular diseases. Cerebral hyperperfusion syndrome can develop after treatment of acute ischemic stroke, including intravenous thrombolysis and endovascular treatment of large vessel occlusion. However, to the best of our knowledge, there are no previous reports describing cerebral hyperperfusion syndrome after endovascular treatment of medium vessel occlusion (eg, anterior cerebral artery A2/3 segment). We report a case of cerebral hyperperfusion syndrome after endovascular reperfusion therapy for medium vessel occlusion. A 70-year-old woman with a history of hypertension and dyslipidemia was transferred by ambulance to our hospital because of immobility and slurred speech. She had mild right lower extremity paralysis, and her symptoms appeared improved compared with onset. She was diagnosed with cerebral infarction in the left frontal lobe. After hospitalization, her neurological symptoms worsened and she was referred to our department. We performed endovascular reperfusion therapy for left anterior cerebral artery A2 occlusion. Recanalization was achieved with residual stenosis. Despite the lack of complications associated with the procedure, the patient had prolonged disorientation, severe hemiplegia, and aphasia. Arterial spin labeling demonstrated hyperperfusion in the left anterior cerebral artery area. The symptoms gradually improved under strict blood pressure control. This report provides evidence that cerebral hyperperfusion syndrome can occur even after endovascular treatment for medium vessel occlusion. Arterial spin labeling was useful in detecting hyperperfusion.

Mechanical thrombectomy for middle cerebral artery occlusion caused by intracranial internal carotid artery stenosis: A case report.

Tandem internal carotid artery (ICA)/middle cerebral artery (MCA) occlusions are occasionally observed in patients with acute ischemic stroke. Most of them are caused by lesions at the origin of the ICA. In cases of intracranial ICA stenosis, the formation of a large thrombus causing MCA occlusion is extremely rare. Herein We report a case of acute MCA occlusion caused by intracranial ICA stenosis. A 62-year-old female presented with aphasia, right-side weakness, and a National Institute of Health Stroke Scale (NIHSS) score of 5. Magnetic resonance imaging (MRI) showed early ischemic infarction at the precentral gyrus. Left ICA and M1 occlusion were suspected on magnetic resonance angiography. However, the patient had complained of right-side numbness 6 days before the onset. Hence the stroke was assumed to have progressed slowly, and acute occlusion of the left ICA was eliminated as a suspected diagnosis. After admission, the symptoms worsened. MRI showed enlargement of the cerebral infarction. Computed tomography angiography showed complete occlusion of the left M1 and recanalization of the left ICA with severe stenosis of the petrous portion. The etiology of the MCA occlusion was determined to be atherothromboembolism. Percutaneous transluminal angioplasty (PTA) was performed for ICA stenosis, followed by mechanical thrombectomy (MT) for the MCA occlusion. Recanalization of the MCA was achieved. After Seven days, the NIHSS score reduced from a pre-MT assessment of 17-2. PTA followed by MT was safe and effective for treating MCA occlusion caused by intracranial ICA stenosis.

Bilateral vertebral artery dissection extending to the left posterior cerebral artery: A case report.

Intracranial artery dissection accounts for a small percentage (1%-2%) of all ischemic strokes. Vertebral artery dissection sometimes extends to the basilar artery but very rarely to the posterior cerebral artery. We report a case of bilateral vertebral artery dissection extending to the left posterior cerebral artery with the characteristic distribution of intramural hematoma. A 51-year-old woman presented with right hemiparesis and dysarthria 3 days after sudden neck pain. Magnetic resonance imaging on admission revealed infarcts in the left thalamus and temporo-occipital lobe and findings suggestive of bilateral vertebral artery dissection. No infarct was detected in the brainstem. The patient was treated conservatively. Initially, we suspected that infarction in the left posterior cerebral artery territory had been caused by artery-to-artery embolism from the dissected vertebral arteries. However, T1-weighted imaging on day 15 of admission revealed intramural hematoma extending from the left vertebral artery to the left posterior cerebral artery. Therefore, we diagnosed bilateral vertebral artery dissection extending to the basilar artery and the left posterior cerebral artery. The patient's symptoms subsequently improved with conservative treatment, and she was discharged with a modified Rankin Scale score of 1 on day 62 of admission. In this case, intramural hematoma of the basilar artery was found in the anterior vessel wall. Brainstem infarction is less likely when intramural hematoma is located in the anterior vessel wall of the basilar artery in vertebrobasilar artery dissection. T1-weighted imaging is useful for the diagnosis of this rare condition and can predict potentially impaired branches and possible symptoms.

Acute reperfusion therapy via occluded vertebral artery using a guiding sheath for posterior circulation tandem occlusion: illustrative case.

BACKGROUND: Vertebral artery (VA) size, anatomy, and occlusion status should be considered when selecting endovascular access for basilar artery mechanical thrombectomy. In a patient with concomitant basilar artery and VA occlusion and a patent but hypoplastic contralateral VA, the occluded VA should be selected. The authors report a technique that utilizes advancing a guiding sheath with attached dilator via an occluded VA. OBSERVATIONS: A 65-year-old male presented with disturbed consciousness because of an acute infarction of the brainstem and cerebellum caused by a basilar artery occlusion. Cerebral angiography showed a hypoplastic right VA and occlusion of the left VA at the origin. A regular wire was easily advanced through the occlusion and a 4-Fr diagnostic catheter was advanced into the distal left VA. A 6-Fr guiding sheath with attached dilator was placed in the left VA beyond the occlusion by exchanging it over a long wire. After removing the basilar artery thrombus, balloon angioplasty was performed at the left VA origin. Complete revascularization of the posterior circulation was achieved. LESSONS: A guiding sheath with dilator can advance across and dilate a VA occlusion at the origin to provide rapid access to the basilar artery.

Proximal migration of a tapered open-cell stent after carotid artery stenting for restenosis following endarterectomy.

OBJECTIVES: Stent migration is an uncommon but serious complication of carotid artery stenting. Shortening and migration of closed-cell stents after carotid artery stenting has been reported, but migration of open-cell stents is extremely rare. MATERIALS AND METHODS: Herein, we report a case of proximal migration of a tapered-design open-cell stent after carotid artery stenting for restenosis following endarterectomy for radiation-induced stenosis. RESULTS: A 70-year-old man with a history of radiation therapy for tongue cancer approximately 10 years earlier was diagnosed with transient ischemic attack owing to severe stenosis of the right cervical internal carotid artery and was referred to our hospital. We performed carotid endarterectomy with a patch graft; 6 months later, restenosis was observed. Therefore, we performed carotid artery stenting with a self-expandable tapered-design open-cell stent. On the second day after the procedure, asymptomatic downward migration of the stent was detected. During the 3-year follow-up period after stent placement, no restenosis or further stent migration was observed. CONCLUSIONS: This report provides evidence that migration of implanted carotid stents can occur even with an open-cell stents. In particular, to our knowledge, there are no reports describing migration of tapered-design open-cell stents in the early postoperative period.

Mechanical thrombectomy for acute fetal posterior cerebral artery occlusion with a hidden unruptured cerebral aneurysm: illustrative case.

BACKGROUND: Fetal posterior cerebral artery occlusion is rare and often presents with severe neurological symptoms. Although acute recanalization therapy is commonly used for cerebral vessel occlusion, unruptured cerebral aneurysms can be hidden distal to the occluded vessels. OBSERVATIONS: An 87-year-old man presented with consciousness disturbance and right hemiparesis. The authors diagnosed left fetal posterior cerebral artery occlusion and performed mechanical thrombectomy. A stent retriever was deployed from the middle cerebral artery M1 segment across the mural thrombus of the internal carotid artery. After the first pass, the fetal posterior cerebral artery remained occluded, with confirmation of a contrast effect around the thrombus. Because the anatomical course of the fetal posterior cerebral artery was unidentified, the procedure was stopped. At 1-week recovery, magnetic resonance imaging revealed complete recanalization and a fetal posterior cerebral artery aneurysm hidden within the occluded site. Blood flow was directed to the aneurysm, and the thrombus within the aneurysm simultaneously occluded the fetal posterior cerebral artery. LESSONS: To avoid critical complications following mechanical thrombectomy for fetal posterior cerebral artery occlusion, hidden aneurysms should be suspected when a "fried egg-like" contrast effect is observed around the thrombus.

Large vessel occlusions requiring repeated mechanical thrombectomy caused by silent myocardial infarction in a young adult.

OBJECTIVES: Silent myocardial ischemia, defined as objective evidence of myocardial ischemia without symptoms, is associated with ischemic stroke. Nevertheless, silent myocardial infarction is a rare cause of ischemic stroke, especially in young adults with no medical history. MATERIALS AND METHODS: Herein, we report a young adult patient with acute ischemic stroke treated with repeated mechanical thrombectomy for recurrent large vessel occlusions caused by left ventricular thrombus following a silent myocardial infarction. RESULTS: A 40-year-old man was transferred by ambulance to our hospital because of a generalized seizure. He was diagnosed with cerebral infarction and left middle cerebral artery occlusion. We performed intravenous thrombolysis and mechanical thrombectomy. Recanalization was achieved and his symptoms gradually improved. However, the day after treatment he developed bilateral cerebellar infarction and basilar artery occlusion. We performed a second mechanical thrombectomy and recanalization was achieved. Transthoracic echocardiography revealed a mobile left ventricular thrombus. Although he had no previous chest symptomatic episodes, cardiac examination confirmed myocardial infarction of unknown onset. He was diagnosed with acute ischemic stroke with large vessel occlusions caused by left ventricular thrombus following a silent myocardial infarction. Anticoagulation therapy reduced the amount of thrombus. At 1-year follow-up, he had not experienced any recurrences or symptoms. CONCLUSIONS: Silent myocardial infarction should be considered a cause of ischemic stroke in young adults, even without any vascular risk factors. Recurrent large vessel occlusion may occur in patients with left ventricular thrombus, and repeated mechanical thrombectomy should be considered for treatment.

The endothelialization on carotid web treated with dual layer stent placement: a case report.

Carotid webs are known to cause acute ischemic stroke in younger adults and have a high recurrence rate. Herein, we report a case of a symptomatic carotid web in a 51-year-old man who was transferred to our hospital after developing consciousness disturbance and left hemiparesis. He was diagnosed with right middle cerebral artery occlusion and underwent mechanical thrombectomy. Because his carotid web was the likely embolic source, we performed carotid artery stenting using a dual-layer stent to crimp the vessel wall and secure closure of the web pocket. Follow-up angiography was performed at 3 weeks after stenting, and endothelialization on the web pocket was confirmed. The high scaffolding effect of the dual layer stent may promote the endothelialization on the carotid web.

Efficacy and Safety of the Long-Acting Diquafosol Ophthalmic Solution DE-089C in Patients with Dry Eye: A Randomized, Double-Masked, Placebo-Controlled Phase 3 Study.

INTRODUCTION: DE-089C is a newly developed long-acting formulation of diquafosol ophthalmic solution with less frequent administration (three times daily) than the currently approved and clinically used diquafosol ophthalmic solution (six times daily), hereinafter referred to as DQS. DE-089C is desirable for achieving better patient adherence in clinical practice for dry eye therapy. The objective of this study was to confirm the efficacy and safety of DE-089C in patients with dry eye compared to placebo. METHODS: This randomized, multicenter, double-masked, placebo-controlled, parallel-group phase 3 study was conducted in Japan. Patients with aqueous-deficient dry eye satisfying Schirmer's test I results ≤ 5 mm/5 min were included. A total of 337 patients with dry eye were randomized in an equal ratio to treatment with DE-089C or placebo ophthalmic solution, three times daily for 4 weeks. The primary endpoint for efficacy was change in fluorescein corneal staining score from baseline to week 4. The incidence of adverse drug reactions was investigated for safety evaluation. RESULTS: The background characteristics of patients in the two groups were similar. Primary endpoint of change in fluorescein corneal staining score at week 4 in the DE-089C group was significantly improved compared with the placebo group (least squares mean difference - 0.51, 95% CI - 0.754 to - 0.269, P < 0.0001). The secondary endpoint of the Lissamine green conjunctival staining score was also significantly improved in the DE-089C group compared to that in the placebo group, while other secondary endpoints were not achieved in this study. Commonly (incidence ≥ 1%) reported adverse drug reactions in the DE-089C group were eye irritation (3.6%) and eye discharge (1.8%) with mild severity, and the incidences of these two events were not higher than those in previous clinical studies on DQS. CONCLUSION: The efficacy and safety of DE-089C administered three times daily at half the dosage of DQS in patients with dry eye were confirmed in this study. TRIAL REGISTRATION: Japan Pharmaceutical Information Center ID, JapicCTI-205177.

Aberrant right subclavian artery with right type 1 proatlantal artery and segmental dysplasia of the right internal carotid artery: a case report.

PURPOSE: We present a case of an aberrant right subclavian artery (ARSA) with extremely rare vascular anomalies. CASE REPORT: A 69-year-old woman was suspected to have right internal carotid artery (ICA) stenosis. Computed tomography angiography demonstrated an ARSA and hypoplasia of the right ICA. The proximal segment of the right vertebral artery (VA) was aplasia, and a right type 1 proatlantal artery (PA) arose from the right common carotid artery. Cerebral angiography demonstrated segmental dysplasia of the right ICA. The ascending intrapetrous segment and the ascending foramen lacerum-horizontal intracavernous segment of the right ICA demonstrated hypoplasia. The collateral pathways promoted reconstitution of each of the distal segments. Left internal carotid angiography demonstrated anterior communicating artery aneurysm and sufficient cross flow to the contralateral middle cerebral artery via the AcomA. DISCUSSION: A type 1 PA with an ARSA may result in the regression of the right dorsal aorta with persistence of the first cervical intersegmental artery. Although there are few findings of a relationship between an ARSA and intracranial artery anomalies, a developmental error of the right dorsal aorta may cause such complex vascular anomalies. CONCLUSION: Knowledge of anatomical variations in patients with ARSA is useful when performing angiography or endovascular therapy, as well as during clinical follow-up.

Extremely tortuous superior cerebellar artery mimicking an aneurysm.

BACKGROUND: An extremely tortuous superior cerebellar artery is a rare anomaly. We report a case of an extremely tortuous superior cerebellar artery mimicking an aneurysm. CASE DESCRIPTION: A 77-year-old woman was initially diagnosed with unruptured cerebral aneurysm at the right basilar artery-superior cerebellar artery junction by magnetic resonance angiography. Catheter angiogram revealed that there was no apparent aneurysm at the basilar artery-superior cerebellar artery junction and the lesion was actually an extremely tortuous superior cerebellar artery. CONCLUSION: Although an extremely tortuous superior cerebellar artery is rare, it should be considered when examining other vascular lesions.

Acute Megakaryoblastic Leukemia Harboring a Subclone Expressing BCR-ABL1 Fusion Gene Product.

Acute myeloid leukemia (AML) with BCR-ABL1, also termed Philadelphia chromosome-positive AML (Ph+ AML), is a rare leukemia subtype classified by the World Health Organization in 2016. The characteristics of Ph+ AML have not been fully identified yet. We herein report a patient with Ph+ AML who phenotypically exhibited megakaryoblastic characteristics, FAB:M7 and harbored a subclone expressing BCR-ABL1 gene fusion products. This case suggests that BCR-ABL1 was acquired as a subclone due to a secondary event that might have occurred late during leukemia evolution. Our findings may aid in deciphering the mechanism underlying Ph+ AML development in future studies.

Evaluation of Medication Adherence and Pharmacokinetics of Dasatinib for Earlier Molecular Response in Japanese Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Pilot Study.

BACKGROUND: Tyrosine kinase inhibitors markedly improve the survival for patients with chronic myeloid leukemia (CML). However, a decrease in adherence leads to undesired therapeutic outcomes. In this study, the relationships among adherence, pharmacokinetics, response, and adverse effects for dasatinib treatment were prospectively investigated. METHODS: This study was a prospective cohort study of patients with newly diagnosed CML at 4 general hospitals and 1 university hospital. Patients started to receive dasatinib 100 mg once daily. A Medication Event Monitoring System was used to assess medication adherence and the medication possession ratio during the 12 months. Plasma concentrations of dasatinib were measured using liquid chromatograph-tandem mass spectrometry (LC-MS/MS), and therapy responses were assessed at 3, 6, and 12 months after treatment. RESULTS: Ten patients were included. An extremely high medication adherence for dasatinib was observed; the median medication possession ratio was 99.4%. All 9 CML patients with breakpoints in the major BCR-ABL achieved major molecular response (MMR; major BCR-ABL transcript level below 0.1% on the International Scale) within 12 months, and 5 achieved MMR within 6 months. The receiver operating characteristic curve analysis revealed that the cutoff value for the dasatinib area under the concentration-time curve was 336.1 ng × h/mL (accuracy 88.9%, sensitivity 80.0%, specificity 100%, and receiver operating characteristic curve-area under the concentration-time curve 0.800) for achieving MMR within 6 months. Two patients had interrupted dasatinib treatment because of pleural effusion and diarrhea with intestinal edema, respectively. These edematous adverse events developed after plasma dasatinib Cmin surpassed 3.0 ng/mL. CONCLUSIONS: A Medication Event Monitoring System was applied for the direct evaluation of oral dasatinib adherence for the first time, and the clinical effect of dasatinib was investigated under the strict monitoring of patient adherence. Although this study had a small sample size, the plasma concentration monitoring of dasatinib is considered to be useful to predict an earlier molecular response with fewer edematous adverse events.

Cochlear implantation in complete remission in a patient with leukemia.

Patients with leukemia have an increased risk of developing sensorineural hearing loss. This is a retrospective review of a profoundly deafened patient with acute myelogenous leukemia who underwent cochlear implantation. The 26-year-old patient was successfully implanted with a Nucleus cochlear implant in the complete remission after peripheral blood stem cell transplantation. To date, with a follow-up of 1 year, the patient has not experienced any complication and has regained useful open-set speech perception. To our knowledge, this is the first reported case of successful cochlear implantation in a patient deafened by acute myelogenous leukemia.

Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.

We report a patient with primary histiocytic sarcoma of the spleen associated with prominent hemophagocytosis. Although thrombocytopenia, probably due to hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of platelets, and splenic irradiation, partial splenic embolization was effective and facilitated splenectomy for a diagnosis. The majority of the spleen showed necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible. The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were negative for lymphoid, myeloid, and epithelial cell markers. CD163, a monocyte/macrophage-specific molecule, was positive in only some of them. Despite multiagent chemotherapy, the patient died of the disease, showing a rapidly progressive clinical course. Although the preoperative diagnosis of primary splenic histiocytic sarcoma is difficult, it has been confirmed in patients with splenomegaly of unknown etiology that clinicolaboratory features suggestive of hemophagocytosis may be important clues suggestive to the disease. CD163 expression by neoplastic cells could be confirmed only after careful observation, because the molecule may only be seen in some of the neoplastic cells.

Molecular analysis of PDGFRalpha/beta genes in core binding factor leukemia with eosinophilia.

Eosinophilia sometimes occurs in acute myeloid leukemia (AML), especially in core binding factor (CBF) leukemia. However, the pathogenesis of the differentiation from leukemic progenitors to eosinophils is not well understood in this type of leukemia. Recent reports showed that a novel fusion tyrosine kinase, Fip1-like1 (FIP1L1) platelet-derived growth factor receptor alpha (PDGFRalpha), is found in idiopathic hypereosinophilic syndrome. The involvement of another chimeric gene, PDGFRbeta, was also reported in myeloproliferative disorder with eosinophilia. These chimeric genes cause constitutive activation of PDGFR tyrosine kinases. On the other hand, a two-hit model for the pathogenesis of AML, which seems to be caused by inactivating mutations in transcription factors and genetic lesions in tyrosine kinase resulting in constitutive activation, has been proposed. On the basis of these findings, we screened for the expression of the FIP1L1-PDGFRalpha fusion gene and for mutations in the juxtamembrane and tyrosine kinase domains of PDGFRalpha/beta genes in 22 cases of CBF leukemia with eosinophilia. Among these cases, no FIP1L1-PDGFRalpha fusion gene was found. Although cDNA sequencing also detected three types of single-nucleotide alterations at kinase domains in PDGFRalpha/beta genes, all of them were silent changes and polymorphisms. Therefore, PDGFRalpha/beta genes do not appear to play a significant pathogenetic role in eosinophilia or leukemogenesis of CBF leukemia.

Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism.

Based on the hypothesis that long-term fetomaternal microchimerism is associated with acquired immunologic hyporesponsiveness to noninherited maternal antigens (NIMAs) or inherited paternal antigens (IPAs), several groups have recently reported successful cases of non-T-cell-depleted hematopoietic stem cell transplantation (SCT) from HLA-haploidentical family members mismatched for NIMAs. In this study, we examined the outcomes of 35 patients with advanced hematologic malignancies who underwent HLA-2-antigen- or HLA-3-antigen-incompatible SCT from a microchimeric NIMA-mismatched donor. After standard-intensity or reduced-intensity preparative regimens, all patients had sustained hematopoietic recovery with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. Grade II/IV acute GVHD occurred in 19 (56%) of 34 evaluable patients, while extensive chronic GVHD developed in 13 (57%) of 23 patients who could be evaluated. Multivariate analysis demonstrated that NIMA mismatch in the GVH direction was associated with a lower risk of severe grade III-IV acute GVHD when compared with IPA mismatch (P = .03). Fifteen patients were alive and 14 of them were disease-free with a median follow-up of 20 (range, 8 to 37) months. These results indicate that T cell-replete SCT from an HLA-haploidentical NIMA-mismatched donor can offer durable remission with an acceptable risk of GVHD in selected patients with advanced hematologic malignancies who lack immediate access to a conventional stem cell source.