Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.

OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Transient splenial lesions of the corpus callosum and infectious diseases.

Transient splenial lesion of the corpus callosum can be observed in various diseases such as cancer, drug use, metabolic disorders, and cerebrovascular disorders, as well as in patients with infectious diseases. During the coronavirus disease 2019 (COVID-19) pandemic, there were increasing reports of these lesions being detected on brain imaging tests performed in patients with neurological symptoms. On brain magnetic resonance imaging, findings suggestive of cytotoxic edema are observed in the splenium; these are known to disappear with improvement of clinical symptoms. Cytokinopathy caused by infection increases the permeability of the blood-brain barrier and activates the glial cells of the brain to induce cytotoxic edema. Most patients have a good prognosis. The causes, mechanism, diagnosis, treatment and prognosis of transient splenial lesions of the corpus callosum will be summarized in this review.

Stroke of Other Determined Etiology: Results From the Nationwide Multicenter Stroke Registry.

BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Isolated intracranial fibromuscular dysplasia of the posterior cerebral artery.

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arterial disease that most commonly affects the renal and internal carotid arteries, but intracranial FMD is very rare. We report a patient with FMD involving the posterior cerebral arteries (PCAs). A 24year old female was presented with a 4day history of right homonymous hemianopsia with throbbing headache in the left temporo-occipital area. The brain magnetic resonance imaging (MRI) revealed an acute ischemic stroke in the left PCA territory, while the Time of Flight (TOF) magnetic resonance angiogram (MRA) showed segmental luminal irregularities in the left proximal PCA. The conventional angiogram revealed the "string of beads" appearance, a characteristic that is pathognomonic for FMD. The patient's inhospital clinical course was stable, while there was no recurrence of stroke. This is the second report of FMD of the PCA. Notwithstanding incredibly rare incidences of isolated intracranial FMD and nonspecific findings of MRA, such a pathophysiology should be considered as the cause for a stroke in young patients, especially those with no cardiovascular risk factor.

Recurrent optic neuritis and neuromyelitis optica-IgG following first and second human papillomavirus vaccinations.

Human papillomavirus (HPV) vaccine is widely used to prevent cervical cancer caused by certain types of HPV in girls and young women. Demyelinating disorders within months following HPV innoculation have been reported, but the causal link between HPV vaccination and the onset of demyelinating disorders have not been certain. We report a case of neuromyelitis optica spectrum disorder (NMOSD) that was noteworthy because optic neuritis (ON) occurred in a very close temporal association with both the first and second HPV vaccinations, which might suggest an association between HPV vaccination and the development of NMO-IgG and recurrent ON. This emphasizes the necessity for continuing surveillance for adverse events after HPV vaccination.

A case of rheumatoid meningitis: pathologic and magnetic resonance imaging findings.

Central nervous system (CNS) involvement is extremely rare in patients with rheumatoid arthritis (RA). Additionally, most patients with CNS involvement have chronic and severe RA. We present a report of a 66-year-old man who was diagnosed with rheumatoid meningitis and CNS vasculitis without a history of RA. His initial symptom was seizure. Brain magnetic resonance imaging showed leptomeningeal enhancement.CSF analysis revealed slight increase in the number of white blood cells. An examination of viral markers and culture studies for infectious etiology were unremarkable. However, the rheumatoid factor was positive and the levels of anti-cyclic citrullinated peptide antibody were very high. The patient was diagnosed with rheumatoid meningitis and received steroid therapy. However, he developed CNS vasculitis. We suggested that the possibility of rheumatoid meningitis should be considered during the differential diagnosis stage in patients with uncontrolled meningitis, even though RA does not typically show CNS involvement.

Magnetic resonance imaging of pachymeningeal enhancement in Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease is a systemic disease consisting of bilateral granulomatous panuveitis combined with cutaneous and neurologic manifestations. However, there have been few reports of brain magnetic resonance imaging (MRI) in VKH disease. A 54-year-old Korean woman presented with severe periorbital pain, blurred vision and meningismus. Ophthalmologic examination disclosed bilateral optic disc edema with peripapillary nerve fiber hemorrhages. Lumbar puncture revealed monocytic pleocytosis. After a diagnosis of VKH disease was made, the patient was treated with high-dose corticosteroid. Brain MRI showed diffusely thickened posterior ocular walls with retinal detachment and perineural infiltrative changes along the optic nerves and adjacent pachymeningeal enhancement of the anterior temporal lobes bilaterally. We report a case of VKH disease with panuveitis and meningeal involvement of the anterior temporal lobe detected by brain MRI.

A case of cerebral venous thrombosis as the presenting sign of occult prostate cancer.

BACKGROUND: Cerebral venous thrombosis (CVT) is a distinct disorder with highly variable symptoms and courses. Malignancy is known to be one of the predisposing factors of CVT. CASE REPORT: We present the case of a 69-year-old man with sudden behavioral changes. Brain MRI, magnetic resonance venography, and positive D-dimer assay confirmed the presence of CVT. The work-up for detecting the cause of the CVT revealed occult prostate cancer. CONCLUSIONS: Occult malignancy including prostate cancer should be strongly suspected in older patients with idiopathic CVT.

Successful Hemostasis with Recombinant Activated Factor VII in a Patient with Massive Hepatic Subcapsular Hematoma.

Recombinant activated coagulation factor VII (rFVIIa) is known to be effective in the management of acquired deficiencies of factor VII and platelet function defects. But recently, rFVIIa has been successfully used to treat ongoing bleeding in disseminated intravascular coagulopathy (DIC) condition. The patient reported here was suspected to be suffering from toxic hepatitis on admission. After percutaneous liver biopsy, bleeding occurred and did not stop even after right hepatic artery embolization. The patient developed a severe hemorrhage that resulted in hypovolemic shock, hemoperitoneum, and a massive subcapsular hematoma. The patient then developed DIC due to massive transfusion, as well as acute liver necrosis. The patient was given 400 mug/kg of rFVIIa. Recombinant factor VIIa was administered in an attempt to control the bleeding. This stabilized the hemoglobin levels of the patient. The patient gradually recovered in 4 months. In conclusion, this case suggests that rFVIIa can be successfully used for the hemostasis of uncontrolled bleeding in DIC.