Exploring the link between Alport syndrome and multiple intracranial artery stenoses: a case report of COL4A5 mutation (118/120 characters).

BACKGROUND: Alport syndrome is a genetic disorder caused by mutations in the COL4A5 gene, which encodes type IV collagen α5 chain, leading to chronic nephritis, hearing loss, and ocular abnormalities. Recent reports suggest this genetic mutation may also increase the risk of cerebral aneurysms and fibromuscular dysplasia, indicating a potential association with vascular vulnerability. CASE PRESENTATION: A 66-year-old woman was admitted with recurrent transient weakness of the left hand, which had gradually worsened in duration over three months. Her medical history included chronic nephritis since childhood. Her two sons had end-stage renal disease and hearing loss since their 20s, and her mother also had chronic kidney disease and hearing loss. One son had a history of traumatic subarachnoid hemorrhage, and the other had spinal epidural hematoma. On admission, she had reduced renal function with proteinuria, acute cerebral infarction in the subcortical white matter of the right fronto-parietal and parieto-occipital lobes, and multiple intracranial arterial stenoses (ICAS), including the right middle and right posterior cerebral artery. Vessel wall imaging of the right middle cerebral artery showed a concentric stenotic pattern. Genetic tests identified a pathogenic missense mutation in exon 24 of COL4A5 (exon 24:c.G1700 >C: p.(Gly567Arg)) that was heterozygous for the patient and hemizygous for her son. She was diagnosed with Alport syndrome. CONCLUSION: It is important to consider Alport syndrome as a possible cause of ICAS in patients with a family history of renal failure or hearing loss and to conduct a genetic analysis of type IV collagen genes. (249/250 words).

High pillow and spontaneous vertebral artery dissection: A case-control study implicating "Shogun pillow syndrome".

INTRODUCTION: The underlying causes of spontaneous vertebral artery dissection (sVAD) remain insufficiently understood. This study aimed to determine whether high-pillow usage is associated with an increased risk of sVAD and evaluate the frequency of sVAD attributable to high-pillow usage. PATIENTS AND METHODS: This case-control study identified patients with sVAD and age- and sex-matched non-sVAD controls (case-to-control ratio: 1:1) treated at a certified comprehensive stroke center in Japan between 2018 and 2023. The pillow height used at the onset of the index disease was measured and classified into three categories between 12 and 15 cm boundaries. Univariable logistic regression was performed to assess the odds ratio (OR) with a 95% confidence interval (CI) of high-pillow usage for sVAD development. A subgroup of sVAD attributable to high-pillow usage was defined with the following three conditions: high-pillow usage (⩾12 or ⩾15 cm); no minor preceding trauma; and wake-up onset. RESULTS: Fifty-three patients with sVAD and 53 non-sVAD controls (42% women, median age: 49 years) were identified. High-pillow usage (⩾12 and ⩾15 cm) was more common in the sVAD group than in the non-sVAD group (34 vs 15%; OR = 2.89; 95%CI = 1.13-7.43 and 17 vs 1.9%; OR = 10.6; 95%CI = 1.30-87.3, respectively). The subgroup of sVAD attributed to high-pillow usage (⩾12 and ⩾15 cm) was found in 11.3% (95%CI = 2.7%-19.8%) and 9.4% (95%CI = 1.5%-17.3%), respectively. CONCLUSION: High-pillow usage was associated with an increased risk of sVAD and accounted for approximately 10% of all sVAD cases. This tentative subgroup of sVAD may represent a distinct spectrum of disease-Shogun pillow syndrome.

Cost-effectiveness of endovascular therapy for acute stroke with a large ischemic region in Japan: impact of the Alberta Stroke Program Early CT Score on cost-effectiveness.

BACKGROUND: Although randomized clinical trials (RCTs) demonstrated short-term benefits of endovascular therapy (EVT) for acute ischemic stroke (AIS) with a large ischemic region, little is known about the long-term cost-effectiveness or its difference by the extent of the ischemic areas. We aimed to assess the cost-effectiveness of EVT for AIS involving a large ischemic region from the perspective of Japanese health insurance payers, and analyze it using the Alberta Stroke Program Early CT Score (ASPECTS). METHODS: The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT) was a RCT enrolling AIS patients with ASPECTS of 3-5 initially determined by the treating neurologist primarily using MRI. The hypothetical cohort and treatment efficacy were derived from the RESCUE-Japan LIMIT. Costs were calculated using the national health insurance tariff. We stratified the cohort into two subgroups based on ASPECTS of ≤3 and 4-5 as determined by the imaging committee, because heterogeneity was observed in treatment efficacy. EVT was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay of 5 000 000 Japanese yen (JPY)/quality-adjusted life year (QALY). RESULTS: EVT was cost-effective among the RESCUE-Japan LIMIT population (ICER 4 826 911 JPY/QALY). The ICER among those with ASPECTS of ≤3 and 4-5 was 19 396 253 and 561 582 JPY/QALY, respectively. CONCLUSION: EVT was cost-effective for patients with AIS involving a large ischemic region with ASPECTS of 3-5 initially determined by the treating neurologist in Japan. However, the ICER was over 5 000 000 JPY/QALY among those with an ASPECTS of ≤3 as determined by the imaging committee.

Long-term survival from progressive multifocal leukoencephalopathy in living-donor liver transplant recipient with preformed donor-specific antibody.

Intensive immunosuppression has enabled liver transplantation even in recipients with preformed donor-specific antibodies (DSA), an independent risk factor for graft rejection. However, these recipients may also be at high risk of progressive multifocal encephalopathy (PML) due to the comorbid immunosuppressed status. A 58-year-old woman presented with self-limited focal-to-bilateral tonic-clonic seizures 9 months after liver transplantation. She was desensitized using rituximab and plasma exchange before transplantation and was subsequently treated with steroids, tacrolimus, and everolimus after transplantation for her preformed DSA. Neurological examination revealed mild acalculia and agraphia. Cranial MRI showed asymmetric, cortex-sparing white matter lesions that increased over a week in the left frontal, left parietal, and right parieto-occipital lobes. Polymerase chain reaction (PCR) of the cerebrospinal fluid for the JC supported the diagnosis of PML. Immune reconstitution by reducing the immunosuppressant dose stopped lesion expansion, and PCR of the cerebrospinal fluid for the JC virus became negative. Graft rejection occurred 2 months after immune reconstitution, requiring readjustment of immunosuppressants. Forty-eight months after PML onset, the patient lived at home without disabling deficits. Intensive immunosuppression may predispose recipients to PML after liver transplantation with preformed DSA. Early immune reconstitution and careful monitoring of graft rejection may help improve outcomes.

P-wave terminal force in lead V1 and atrial fibrillation burden in cryptogenic stroke with implantable loop recorders.

Implantable loop recorders (ILRs) are useful for the detection of atrial fibrillation (AF) in patients with cryptogenic stroke (CS). P-wave terminal force in lead V1 (PTFV1) is associated with AF detection; however, data on the association between PTFV1 and AF detection using ILRs in patients with CS are limited. Consecutive patients with CS with implanted ILRs from September 2016 to September 2020 at eight hospitals in Japan were studied. PTFV1 was calculated by 12-lead ECG before ILRs implantation. An abnormal PTFV1 was defined as ≥ 4.0 mV × ms. The AF burden was calculated as a proportion based on the duration of AF to the total monitoring period. The outcomes included AF detection and large AF burden, which was defined as ≥ 0.5% of the overall AF burden. Of 321 patients (median age, 71 years; male, 62%), AF was detected in 106 patients (33%) during the median follow-up period of 636 days (interquartile range [IQR], 436-860 days). The median time from ILRs implantation to AF detection was 73 days (IQR, 14-299 days). An abnormal PTFV1 was independently associated with AF detection (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.00-2.90). An abnormal PTFV1 was also independently associated with a large AF burden (adjusted odds ratio, 4.70; 95% CI, 2.50-8.80). In patients with CS with implanted ILRs, an abnormal PTFV1 is associated with both AF detection and a large AF burden.Clinical Trial Registration Information: UMIN Clinical Trials Registry 000044366.

[Development of the Japanese version of the 16-Item Informant Questionnaire on Cognitive Decline for the Elderly (J-IQCODE 16) for the Diagnosis of Prestroke Dementia].

The 16-Item Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE 16) has been frequently used to diagnose prestroke dementia, an important determinant of stroke prognosis. We developed the Japanese version of the IQCODE 16 (J-IQCODE 16) using standardized translation methods. We applied the J-IQCODE 16 to 102 patients with stroke (19 with prestroke dementia diagnosed with DSM-5) admitted to the stroke care unit in our hospital. The cohort was randomly divided into a derivation cohort and a validation cohort containing 51 patients each. In the derivation cohort, the median J-IQCODE 16 score was 3.06, and the area under the receiver operating characteristic curve for prestroke dementia was 0.96, with an optimal cutoff value of 3.25 determined using the Youden index. When applied this cut-point to the validation cohort, the sensitivity and specificity of the J-IQCODE 16 for prestroke dementia were 90% and 85%, respectively. The J-IQCODE 16 is considered useful for the diagnosis of prestroke dementia.

[Autoimmune polyglandular syndrome type 3 diagnosed with cerebral venous sinus thrombosis: a case report].

A 67-year-old woman with a history of diabetes mellitus was admitted to our hospital with convulsions due to bilateral frontal subcortical hemorrhages. MR venography showed a defect in the superior sagittal sinus, and thrombi were demonstrated in the same lesion with head MRI three-dimensional turbo spin echo T1-weighted imaging. She was diagnosed with cerebral venous sinus thrombosis. As precipitating factors, we found high levels of free T3 and T4, low levels of thyroid stimulating hormone, anti-thyroid stimulating hormone receptor antibody, and anti-glutamic acid decarboxylase antibody with her. We diagnosed her with autoimmune polyglandular syndrome type 3 with Graves' disease and slowly progressive type 1 diabetes mellitus. Since she also had nonvalvular atrial fibrillation, she was treated with apixaban subsequently to intravenous unfractionated heparin in the acute phase, resulting in partial regression of the thrombi. Autoimmune polyglandular syndrome should be considered when multiple endocrine disorders are identified as precipitating factors for cerebral venous sinus thrombosis.

Anti-Lactosylceramide antibody positive combined central peripheral demyelination emerging from long-standing juvenile-onset chronic inflammatory polyradiculoneuropathy; a report of two cases.

Anti-Lactosylceramide (LacCer) antibodies are associated with neurological inflammation involving both the peripheral and central nervous system (PNS, CNS respectively), however, the documented number of cases is small. Uncertainty remains whether its positivity can identify a unique clinical entity. Here, we describe two anti-LacCer antibody positive cases, both with long histories (> 30 years) of teenage-diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). CNS lesions including the medulla oblongata were observed for the first time in adulthood. We suggest that this secondary progression of CNS lesions in juvenile-onset CIDP can be one of the characteristic features of anti-LacCer antibody associated neurological disorder.

Removal of Insertable Cardiac Monitor for Cryptogenic Stroke: A Technical Note.

OBJECTIVES: Insertable cardiac monitors (ICM) allow continuous long-term electrocardiogram monitoring and the detection of paroxysmal atrial fibrillation (PAF) in patients with cryptogenic stroke (CS). Several years have passed since ICM was indicated for CS, and many stroke neurologists will experience cases in which ICM removal is required. As a standard protocol, reincision of the wound at the time of implantation has been proposed by ICM brands. However, it may be difficult due to adhesions of subcutaneous tissue, migration of the device from its original position, and the capsule formed around the device. Our objective is to describe simple alternative techniques for successful ICM removal. MATERIALS AND METHODS: From December 2016 to September 2021, 37 patients with CS underwent ICM removal at our institution. The device was removed through an incision directly above the proximal end of the device, perpendicular to the wound at the time of ICM implantation. The subcutaneous tissue was removed bluntly using forceps along the edges of the proximal end of the device. When a capsule was attached to the device, we cut the capsule with the blade to release the device. Once the device was visible, the proximal end of the device was grasped with forceps, and the device was pulled from the pocket with gentle traction. All patients undergoing ICM removal received a systematic check for wound dehiscence, wound infection, bleeding, and tissue ischemia at an outpatient examination of 1 week. The 37 patients who underwent removal of ICM were retrospectively reviewed in the medical record and analyzed for procedural success, intraoperative complications, and wound course at one week. RESULTS: All patients achieved procedural success. There were no intraoperative complications, wound dehiscence, bleeding, or skin ischemia at one week postoperatively. The reasons for removal were battery depletion in 65%, early removal before battery life after PAF detection in 32%, and exposure to the body surface in 3%. The devices removed were 62% Reveal LINQ (Medtronic, Minneapolis), 30% Confirm Rx (Abbott, Illinois), and 8% BioMonitor 2 (BIOTRONIK, Berlin), indicating that our method is effective regardless of model. CONCLUSION: We describe a simple technique for ICM removal for CS that is safe, reliable, and potentially effective in wound healing.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with End-Stage Renal Disease on Hemodialysis: A Narrative Review.

OBJECTIVES: Acute ischemic stroke (AIS) is a significant and devastating complication in patients with end-stage renal disease on hemodialysis (ESRD/HD). Since one-third of AIS in ESRD/HD patients occurs during or soon after dialysis, patients are more likely to present within the time window when intravenous thrombolysis (IVT) can be performed. IVT may improve prognosis in ESRD/HD patients with AIS. However, ESRD/HD patients have been excluded from large trials and may have been withheld from IVT due to concerns about bleeding complications. To date, there is no clear evidence and firm guidance on the safety and efficacy of IVT in ESRD/HD patients with AIS. This narrative review aimed to evaluate critical scientific data on the benefits and risks of IVT use in patients with ESRD/HD and AIS. MATERIALS AND METHODS: We searched the electronic database of PubMed for studies evaluating the relationship between AIS, ESRD/HD, and IVT. Reference sections and additional publications were also searched manually. Studies on AIS in patients with ESRD/HD requiring maintenance dialysis that referred to IVT were included. RESULTS: In total, 560 studies were found in the PubMed electronic database during the period covered, of which 10 met the selection criteria. IVT for AIS in ESRD/HD patients could improve neurological outcomes and be safely performed even with the possibility of hemorrhagic complications associated with hypertension. Despite the high complication and mortality rates in ESRD/HD patients with AIS after IVT, the association with IVT was unclear. CONCLUSIONS: IVT for AIS in ESRD/HD patients may improve outcomes and should not be withheld based solely on ESRD/HD status.

Fatal Cerebral Venous Thrombosis in a Pregnant Woman with Inherited Antithrombin Deficiency after BNT162b2 mRNA COVID-19 Vaccination.

Antithrombin deficiency is a high-risk factor for venous thromboembolism during pregnancy, whereas cerebral venous thrombosis is rare. Cerebral venous thrombosis related to coronavirus disease 2019 (COVID-19) vaccines has been reported; however, there are a few reports of cerebral venous thrombosis after a messenger RNA (mRNA) vaccination. A 25-year-old female in her sixth week of pregnancy presented with headache 24 days after BNT162b2 mRNA COVID-19 vaccination. The following day, she presented with altered sensorium and was diagnosed with severe cerebral venous thrombosis. She demonstrated heparin resistance and was found to have an inherited antithrombin deficiency. A heterozygous missense variant in SERPINC1 (c.379T>C, p.Cys127Arg, 'AT Morioka') was detected by DNA analysis. Despite intensive care with unfractionated heparin, antithrombin concentrate, and repeated endovascular treatments, she died on the sixth day of hospitalization. Cerebral venous thrombosis in pregnant women with an antithrombin deficiency can follow a rapid and fatal course. Treatment with unfractionated heparin and antithrombin concentrate may be ineffective in severe cerebral venous thrombosis cases with antithrombin deficiency. Early recognition of antithrombin deficiency and an immediate switch to other anticoagulants may be required. Although the association between cerebral venous thrombosis and the vaccine is uncertain, COVID-19 vaccinations may require careful evaluation for patients with prothrombic factors.

[Cerebral venous sinus thrombosis presenting transient ischemic attack after recovery from COVID-19 with Graves' disease and IgG4-related ophthalmic disease: a case report].

A 57-year-old man presented with headache, transient right upper extremity weakness and numbness one month after recovery from coronavirus disease 2019 (COVID-19). His medical history included Graves' disease and IgG4-related ophthalmic disease. He had been administered prednisolone. His weakness and numbness were transient and not present on admission. Contrast-enhanced CT and MRI of the head showed thrombi in the superior sagittal sinus, right transverse sinus, sigmoid sinus, and the right internal jugular vein. Digital subtraction angiography showed occlusion at the same sites and mild perfusion delay in the left frontoparietal lobe. We diagnosed the patient with cerebral venous sinus thrombosis and treated him with anticoagulation. The thrombi partially regressed three months later, and perfusion delay became less noticeable. Cerebral venous sinus thrombosis is an important complication of COVID-19. Patients with predisposing factors, including Graves' disease and IgG4-related ophthalmic disease, may be at increased risk of developing cerebral venous sinus thrombosis even after recovery from COVID-19.

[Detection of secondary atrial fibrillation following percutaneous foramen ovale closure for cryptogenic stroke using an insertable cardiac monitor: a case report].

A 61-year-old man presented with transient dysarthria and left upper extremity numbness. Head MRI showed an acute infarct in the left temporal lobe and multiple old infarcts in the bilateral cortices. A transesophageal echocardiogram revealed a patent foramen ovale with a large shunt. No deep vein thrombosis was found. He suffered a recurrent cerebral infarction while taking antiplatelet therapy. An insertable cardiac monitor was implanted on the 41st day, and the antiplatelet treatment was changed to warfarin. The insertable cardiac monitor did not detect atrial fibrillation, even when the patient had a recurrent transient ischemic attack on the 57th day under warfarin therapy. The patient underwent percutaneous foramen ovale closure on the 63rd day. On postoperative days 18-25, an insertable cardiac monitor detected brief atrial fibrillation, and he took rivaroxaban for three months. Atrial fibrillation may occur secondary to percutaneous patent foramen ovale closure for cryptogenic stroke. The insertable cardiac monitor may help diagnose the pathogenesis of secondary atrial fibrillation and determine the optimal antithrombotic therapy.

Intravenous Thrombolysis With Alteplase at 0.6 mg/kg in Patients With Ischemic Stroke Taking Direct Oral Anticoagulants.

Background We elucidated the safety of treatment with alteplase at 0.6 mg/kg within 24 hours for patients on direct oral anticoagulants (DOACs) before ischemic stroke onset. Methods and Results Consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis using alteplase at 0.6 mg/kg from 2011 to 2021 were enrolled from our single-center prospective stroke registry. We compared outcomes between patients taking DOACs and those not taking oral anticoagulants within 48 hours of stroke onset. The primary safety outcome was the rate of symptomatic intracranial hemorrhage with a ≥4-point increase on the National Institutes of Health Stroke Scale score from baseline. The efficacy outcome was defined as 3-month modified Rankin Scale score of 0 to 2 after stroke onset. Of 915 patients with acute ischemic stroke who received intravenous thrombolysis (358 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 10), 40 patients took DOACs (6 took dabigatran, 8 took rivaroxaban, 16 took apixaban, and 10 took edoxaban) within 24 hours of onset and 753 patients did not take any oral anticoagulants. The rate of symptomatic intracranial hemorrhage was comparable between patients on DOACs and those not on oral anticoagulants (2.5% versus 2.4%, P=0.95). The rate of favorable outcomes was comparable between the 2 groups (59.4% versus 58.2%, P=0.46), although the admission National Institutes of Health Stroke Scale score was higher in patients on DOACs. No significant differences showed in any intracranial hemorrhage within 36 hours or mortality at 3 months. Conclusions Intravenous thrombolysis would be safely performed for patients on DOACs following the recommendations of the Japanese guidelines. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02251665.

Late-onset cerebral embolism after transcatheter aortic valve implantation under direct oral anticoagulant therapy.

Ischemic stroke is a devastating complication of transcatheter aortic valve implantation (TAVI), mainly occurring in the early postoperative period. The risk of a transplanted heart valve (THV) thrombosis causing stroke may be underestimated in the late postoperative phase. We describe the case of a 92-year-old woman with delayed valve thrombosis causing stroke after TAVI, who developed recurrent strokes eight months after TAVI for severe aortic valve stenosis. Transesophageal echocardiography and cardiac computed tomography revealed a string-like thrombus attached to the implanted valve. With the administration of warfarin, the clot regressed, and the patient was discharged home without recurrence of stroke. Our case demonstrates the importance of THV thrombosis as an embolic source of stroke even in the late postoperative phase and provides a discussion on optimal antithrombotic therapy after TAVI.

Left Ventricular Abnormality and Covert Atrial Fibrillation in Embolic Stroke of Undetermined Source.

AIMS: The relationship between left ventricular (LV) function and AF detection in embolic stroke of undetermined source (ESUS) patients with insertable cardiac monitors (ICMs) remains unclear. We investigated the association between LV function and AF detection in patients with ESUS after ICMs implantation. METHODS: We enrolled patients with ESUS who underwent ICMs implantation from September 2016 to September 2020 using a single-center, prospective registry. LV systolic and diastolic functions were assessed on precordial echocardiography by LV fractional shortening (LVFS) and average E/e', respectively. Associations between characteristics of LV function and detection of AF by ICMs were analyzed. RESULTS: Participants comprised 101 patients (median age, 74 years; male, 62%). During a median follow-up period of 442 days (interquartile range (IQR), 202-770 days), AF was detected in 24 patients (24%). Median duration from ICMs implantation to AF detection was 71 days (IQR, 13-150 days). When LVFS and E/e' were dichotomized by cutoff value, each of low LVFS (＜35.5%; adjusted hazard ratio (HR), 4.77; 95% confidence interval (CI), 1.77-12.9) and high E/e' (≥ 8.65; adjusted HR, 4.56; 95%CI, 1.17-17.7) were independently associated with AF detection after adjusting for age and sex. When patients were divided into four groups according to dichotomized LVFS and E/e', the combination of low LVFS and high E/e' was independently associated with AF. CONCLUSIONS: In patients with ESUS after ICMs implantation, the LV characteristics of low LVFS and high E/e' were associated with AF detection.

[MRI and intravenous thrombolysis for unclear-onset stroke during the COVID-19 pandemic: a case report].

During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.