Thoracic spinal cord injury after surgical removal of a ruptured cerebellar arteriovenous malformation in a patient in the Concorde position: illustrative case.

BACKGROUND: Thoracic spinal cord injury after posterior cranial fossa surgery in younger patients is a rare complication. There have been reports of this complication in tumor and spine fields but not in vascular surgery. OBSERVATIONS: A 22-year-old-man experienced cerebellar arteriovenous malformation rupture, and the malformation was surgically removed with the man in the Concorde position. After surgery, the man had severe paraplegia, and a thoracic spinal cord injury was diagnosed. LESSONS: In younger patients, cervical hyperflexion in the Concorde position can cause thoracic spinal cord injury even in surgery for cerebrovascular disease.

Dysplastic aberrant left subclavian artery originating from a thoracic intersegmental artery associated with a right aortic arch.

PURPOSE: A right aortic arch (RAA) is a rare vascular anomaly that often coexists with an aberrant left subclavian artery (ALSA). Due to the rarity of RAA, the development of an ALSA is not well understood. METHOD: We describe a case in which a 58-year-old man who was scheduled to undergo posterior decompression and fusion surgery for thoracic ossification of the posterior longitudinal ligament from Th1 to Th3 was found to have a RAA and an ALSA. RESULTS: Preoperative computed tomography angiography demonstrated a RAA and an ALSA. The ALSA was extremely tortuous and ran in the paraspinal muscles behind the thoracic laminae, which meant it was in the surgical field. The ALSA arose from the descending aorta and bifurcated into the left segmental arteries of Th1 and Th2, and also bifurcated into the left vertebral artery, which had a normal subsequent course. The dysplastic ALSA was considered to have developed from the thoracic intersegmental artery. Based on preoperative examination findings, we performed spinal surgery without vessel injury. CONCLUSION: We report a rare case of a dysplastic ALSA that developed from the thoracic intersegmental artery with a RAA. The knowledge of this anomaly provides safety in spinal surgery of the cervicothoracic junction.

Replaced posterior cerebral artery.

PURPOSE: Replaced posterior cerebral artery (PCA), defined as a hyperplastic anterior choroidal artery (AChA) supplying all branches of the PCA, is an extremely rare anatomical variation. To the best of our knowledge, there are only a few reports of replaced PCA. METHODS: Herein, we report a case of replaced PCA diagnosed by digital subtraction angiography. RESULTS: A 76-year-old woman visited a neurosurgical clinic because of headache and vertigo. Magnetic resonance imaging and magnetic resonance angiography incidentally revealed a left internal carotid artery aneurysm. She was referred to our hospital for further examination and treatment of the unruptured intracranial aneurysm. Left internal carotid angiography revealed a paraclinoid aneurysm. We also incidentally found an anomalous hyperplastic AChA distal to the aneurysm. This hyperplastic AChA supplied not only the AChA territory but also the entire PCA territory. No vessels that could be a normal AChA or posterior communicating artery were identified along the left internal carotid artery. Vertebral angiography demonstrated that the left PCA was not visualized. With these findings, we diagnosed anomalous hyperplastic AChoA in this case as replaced PCA. CONCLUSION: Careful imaging assessment is important to identify replaced PCA. Both direct findings of a hyperplastic AChA course and perfusion territory and indirect findings of the absence of the original PCA are useful in the diagnosis of replaced PCA.

Endovascular treatment of acute atherothrombotic internal carotid artery occlusion associated with persistent primitive hypoglossal artery.

Persistent primitive hypoglossal artery is a relatively rare anatomical variation and a type of persistent carotid-basilar anastomosis. Acute internal carotid artery occlusion associated with persistent primitive hypoglossal artery is rare, and atherothrombotic occlusion is extremely rare. We present a case of acute atherothrombotic internal carotid artery occlusion associated with persistent primitive hypoglossal artery that was successfully treated by endovascular treatment. A 70-year-old male with a history of left internal carotid artery stenosis was transferred to our hospital by ambulance because of abnormal behaviors and aphasia. He was diagnosed with cerebral infarction and left internal carotid artery occlusion. Left carotid angiography revealed the persistent primitive hypoglossal artery arising from the cervical internal carotid artery and complete internal carotid artery occlusion distal to the origin of the persistent primitive hypoglossal artery. Therefore, we performed endovascular treatment. Mechanical thrombectomy was performed under minimal flow arrest with consideration of brain ischemia causing coma. After additional balloon angioplasty, recanalization was achieved, and the patient's symptoms improved. During the 1.5-year follow-up period, no recurrence or restenosis was observed. This report provides evidence that atherosclerotic internal carotid artery stenosis associated with persistent primitive hypoglossal artery can occur even distal to the origin of the persistent primitive hypoglossal artery and that the lesion may become acutely occluded, leading to acute stroke. Endovascular treatment considering brain ischemia was effective in this case.

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.

Long-term efficacy and safety of adjunctive perampanel in patients from the Asia-Pacific region with refractory focal-onset seizures in Study 335 open-label extension.

OBJECTIVE: To evaluate the long-term efficacy, safety, and tolerability of adjunctive perampanel for the treatment of patients with refractory focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), from the Asia-Pacific region. METHODS: Study 335 (NCT01618695) was a randomized, double-blind, placebo-controlled, Phase III study. Patients aged ≥12 years with refractory FOS who completed the Core Study could enter an open-label extension (OLEx) Phase (6-week Conversion and ≥46-week Maintenance Period). Endpoints included median percent reduction in seizure frequency per 28 days, 50% responder and seizure-freedom rates, and treatment-emergent adverse events (TEAEs). RESULTS: The Intent-to-Treat Analysis Set included 704 patients (529 received perampanel and 175 received placebo during the Core Study; all patients received perampanel during OLEx). The median percent reduction in seizure frequency and 50% responder rates in patients who received perampanel during the Core Study were maintained throughout the OLEx Phase (Week 64-75: 55.9% and 54.3%, respectively). Seizure freedom for ≥12 consecutive months at any time during perampanel treatment was achieved by 4.1% of patients with FOS and 14.2% of patients with FBTCS. Among patients treated with perampanel 4 mg/day (n = 83), median reduction in seizure frequency was lower in those who received concomitant enzyme-inducing anti-seizure medications (EIASMs) than those who received non-EIASMs. The most common TEAE was dizziness (n = 318; 46.8%); 141 (20.8%) patients had TEAEs that led to study/drug withdrawal. SIGNIFICANCE: Overall, long-term seizure control was achieved with adjunctive perampanel in patients with refractory FOS, with or without FBTCS, in an Asia-Pacific population.

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.

Use of preoperative contrast-enhanced computed tomography in damage control strategy for blunt liver injury: A case report.

For patients with unstable abdominal trauma unresponsive to initial transfusion, the damage control strategy includes prompt hemostasis by open surgery and packing. Recently, a hybrid treatment that combines packing and transcatheter arterial embolization as a damage control strategy was reported to be effective; however, the indications and techniques are yet to be established. A 25-year-old male patient who was in shock due to severe liver injury after a traffic accident was brought to our emergency room by emergency services. After initial resuscitation, including resuscitative endovascular balloon occlusion of the aorta and blood transfusion, preoperative contrast-enhanced computed tomography indicated grade IV liver injury with active bleeding from the right hepatic artery. Damage control strategy with packing and subsequent transcatheter arterial embolization was determined to be useful. During treatment, bile leakage was observed. An endoscopic nasobiliary drainage tube was inserted, and the patient was treated conservatively. He was discharged on day 83 of hospitalization. Although using preoperative contrast-enhanced computed tomography before damage control surgery remains controversial, it can provide useful information to determine damage control strategy, including morphological evaluation of the injured area and the presence of active bleeding.

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.

FOXM1-Mediated Regulation of Reactive Oxygen Species and Radioresistance in Oral Squamous Cell Carcinoma Cells.

Radioresistance is a major obstacle to the successful treatment of oral squamous cell carcinoma (OSCC). To help overcome this issue, we have developed clinically relevant radioresistant (CRR) cell lines generated by irradiating parental cells over time, which are useful for OSCC research. In the present study, we conducted gene expression analysis using CRR cells and their parental lines to investigate the regulation of radioresistance in OSCC cells. Based on gene expression changes over time in CRR cells and parental lines subjected to irradiation, forkhead box M1 (FOXM1) was selected for further analysis in terms of its expression in OSCC cell lines, including CRR cell lines and clinical specimens. We suppressed or upregulated the expression of FOXM1 in OSCC cell lines, including CRR cell lines, and examined radiosensitivity, DNA damage, and cell viability under various conditions. The molecular network regulating radiotolerance was also investigated, especially the redox pathway, and the radiosensitizing effect of FOXM1 inhibitors was examined as a potential therapeutic application. We found that FOXM1 was not expressed in normal human keratinocytes but was expressed in several OSCC cell lines. The expression of FOXM1 was upregulated in CRR cells compared with that detected in the parental cell lines. In a xenograft model and clinical specimens, FOXM1 expression was upregulated in cells that survived irradiation. FOXM1-specific small interfering RNA (siRNA) treatment increased radiosensitivity, whereas FOXM1 overexpression decreased radiosensitivity, and DNA damage was altered significantly under both conditions, as well as the levels of redox-related molecules and reactive oxygen species production. Treatment with the FOXM1 inhibitor thiostrepton had a radiosensitizing effect and overcame radiotolerance in CRR cells. According to these results, the FOXM1-mediated regulation of reactive oxygen species could be a novel therapeutic target for the treatment of radioresistant OSCC; thus, treatment strategies targeting this axis might overcome radioresistance in this disease.

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.

Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings.

STUDY OBJECTIVES: Patients with chronic insomnia may respond differently to therapeutic modalities. This study examined differences in response of individuals with 2 insomnia phenotypes-short sleep duration (I-SSD; < 6 hours) and normal sleep duration (I-NSD; ≥ 6 hours) determined by polysomnography-to treatment with lemborexant and zolpidem tartrate extended-release 6.25 mg (zolpidem ER), compared with placebo. METHODS: Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729) was a global, randomized, double-blind, placebo, and active comparator-controlled, parallel-group study comparing lemborexant 5 and 10 mg in individuals aged ≥ 55 years with insomnia disorder. In this analysis, changes in subjective (self-reported) variables based on sleep diaries and objective variables based on polysomnographs were assessed after 1-month administration of study drugs. Data from participants with I-SSD and I-NSD were compared. RESULTS: In the I-SSD subgroup, both lemborexant doses provided significant benefit for sleep-onset latency (SOL), total sleep time (TST), and wake after sleep onset (WASO) vs placebo; zolpidem ER also provided significant benefit for TST and WASO, but not SOL, on both measures vs placebo. In the I-NSD subgroup, lemborexant and zolpidem ER provided significant benefit for TST and WASO vs placebo objectively but not subjectively; both doses of lemborexant provided significant benefit for SOL vs placebo subjectively, but not objectively. CONCLUSIONS: Both drugs, but lemborexant more consistently, showed subjective and objective benefits compared with placebo in participants with insomnia with objective short sleep duration. However, neither lemborexant nor zolpidem provided consistent benefits for participants with normal sleep duration on sleep-onset and sleep maintenance variables. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1); URL: https://clinicaltrials.gov/ct2/show/record/NCT02783729; Identifier: NCT02783729. CITATION: Inoue Y, Nishida M, Kubota N, et al. Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings. J Clin Sleep Med. 2023;19(3):519-528.

Regulation of neural stem cell proliferation and survival by protein arginine methyltransferase 1.

Protein arginine methyltransferase 1 (PRMT1), a major type I arginine methyltransferase in mammals, methylates histone and non-histone proteins to regulate various cellular functions, such as transcription, DNA damage response, and signal transduction. PRMT1 is highly expressed in neural stem cells (NSCs) and embryonic brains, suggesting that PRMT1 is essential for early brain development. Although our previous reports have shown that PRMT1 positively regulates oligodendrocyte development, it has not been studied whether PRMT1 regulates NSC proliferation and its survival during development. To examine the role of PRMT1 in NSC activity, we cultured NSCs prepared from embryonic mouse forebrains deficient in PRMT1 specific for NSCs and performed neurosphere assays. We found that the primary neurospheres of PRMT1-deficient NSCs were small and the number of spheres was decreased, compared to those of control NSCs. Primary neurospheres deficient in PRMT1 expressed an increased level of cleaved caspase-3, suggesting that PRMT1 deficiency-induced apoptosis. Furthermore, p53 protein was significantly accumulated in PRMT1-deficient NSCs. In parallel, p53-responsive pro-apoptotic genes including Pmaip1 and Perp were upregulated in PRMT1-deficient NSCs. p53-target p21 mRNA and its protein levels were shown to be upregulated in PRMT1-deficient NSCs. Moreover, the 5-bromo-2'-deoxyuridine (BrdU) incorporation assay showed that the loss of PRMT1 led to cell cycle defects in the embryonic NSCs. In contrast to the above in vitro observations, NSCs normally proliferated and survived in the fetal brains of NSC-specific PRMT1-deficient mice. We also found that Lama1, which encodes the laminin subunit α1, was significantly upregulated in the embryonic brains of PRMT1-deficient mice. These data implicate that extracellular factors provided by neighboring cells in the microenvironment gave a trophic support to NSCs in the PRMT1-deficient brain and recovered NSC activity to maintain brain homeostasis. Our study implies that PRMT1 plays a cell-autonomous role in the survival and proliferation of embryonic NSCs.

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.

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.

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial.

OBJECTIVE/BACKGROUND: Lemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2). PATIENTS/METHODS: Study 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: For all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache. CONCLUSIONS: LEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Efficacy and safety of lemborexant in adults with insomnia: comparing Japanese and non-Japanese subgroups from the global, phase 3, randomized, double-blind, placebo-controlled SUNRISE 2 study.

STUDY OBJECTIVE: Whether there are racial differences in the efficacy/safety of hypnotics has not been sufficiently investigated. We aimed to evaluate the efficacy/safety of lemborexant 5 mg and lemborexant 10 mg vs placebo once daily in a subset of Japanese patients with insomnia and to compare the results with those of non-Japanese patients. METHODS: This subanalysis reports the results of the first 6 months (period 1, placebo-controlled) of SUNRISE 2, a 12-month, global, randomized, double-blind, phase 3 study. Changes in patient-reported sleep onset latency, patient-reported sleep efficiency, and patient-reported wake after sleep onset with lemborexant 5 mg or lemborexant 10 mg vs placebo were evaluated. Treatment-emergent adverse events were evaluated for safety. RESULTS: In total, 949 patients were randomized (Japanese, n = 161; non-Japanese, n = 788). Groups were balanced at baseline except for the male/female ratio (P = .0002) and body mass index (P < .0001) in the Japanese vs non-Japanese subgroups. Overall, the efficacy and safety of lemborexant were similar between subgroups. In the Japanese subgroup, the subjective sleep onset latency change from baseline was significant after 7 nights and 6 months with lemborexant 10 mg vs placebo, the subjective sleep efficiency change from baseline was significant after 7 nights with lemborexant 10 mg vs placebo, and the subjective wake after sleep onset change from baseline was significant at 6 months with lemborexant 5 mg vs placebo. The incidence and severity of treatment-emergent adverse events were consistent between both subgroups. CONCLUSIONS: Lemborexant 5 mg and 10 mg improved sleep onset and sleep maintenance over 6 months and was well-tolerated in both the Japanese and non-Japanese patients. The safety profiles of lemborexant 5 mg and 10 mg were consistent between the subgroups. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2); URL: https://clinicaltrials.gov/ct2/show/NCT02952820; Identifier: NCT02952820; and Registry: ClinicalTrialsRegister.eu; Identifier: 2015-001463-39.