A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy.

BACKGROUND: Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left-right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy. CASE PRESENTATION: We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left-right body axis. CONCLUSIONS: Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.

Utility of transoral motion-mode ultrasonography to detect tongue fasciculation in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Increasing evidence suggests the utility of the submandibular approach for ultrasonography to detect tongue fasciculation in amyotrophic lateral sclerosis (ALS). We hypothesized that transoral motion-mode ultrasonography (TOMU) would be useful to detect tongue fasciculation in patients with ALS. METHODS: Patients with sporadic ALS showing clinically definite tongue fasciculation were enrolled, and the ultrasonography findings of patients' tongues on TOMU and ultrasonography by the conventional submandibular approach were analyzed. RESULTS: Six patients with clinically definite ALS were enrolled in this study. Although small, irregular muscle movements of 5 to 10 mm in amplitude and 0.1 to 0.2 second in duration were detected in all patients by TOMU, similar muscle movements were detected in only two of the six patients by the submandibular approach. DISCUSSION: TOMU appeared to be useful for detecting tongue fasciculation in ALS patients. Further study is needed to better determine its role as a diagnostic tool for ALS.

The ASCOD Phenotyping of Embolic Strokes of Undetermined Source.

BACKGROUND AND PURPOSE: Various pathogenesis are presumed to be involved in the etiology of embolic stroke of undetermined source (ESUS), which has a high recurrence rate, and much remains unknown about the clinical subtype of recurrent stroke. The purpose of this study was to clarify the pathogenesis of ESUS using the ASCOD classification for ESUS patients and to examine the factors involved in the recurrence of ischemic stroke. METHODS: The subjects of this study were 236 of these patients who fulfilled the criteria for ESUS. The rate of stroke recurrent, subtype of recurrent ischemic stroke, and new-onset atrial fibrillation (AF) in these patients were surveyed retrospectively, and each patient was graded for the A, S, and C categories of the ASCOD classification. RESULTS: Ischemic stroke recurred in 32 patients during the follow-up period (7 days to 12.9 years [median 54.3 months]), and new-onset AF was seen in 44 (18.6%) patients. The most subtype of recurrent ischemic stroke was ESUS again (19 patients). Multivariate analysis with a Cox proportional hazards model, the S score (hazard ratio 5.21; 95% confidence interval (CI) 2.38-11.42; P < .001) and the number of A, S, C categories (hazard ratio 1.90; 95% CI 1.14-3.10; P = .013) were factors significantly related to recurrent ischemic stroke. CONCLUSIONS: Assessment of comorbid conditions in ESUS patients based on the ASCOD classification may be useful in predicting the likelihood of recurrence of ischemic stroke.

The Risk Factors for Death within 6 Months After Ischemic Stroke in Patients with Cancer.

OBJECTIVES: While the intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke patients with cancer is recommended when survival of ≥ 6 months is expected, the risk factors for death and stroke recurrence within 6 months after stroke are not well known. Thus, we aimed to identify markers for death and recurrence risks within six months from stroke onset in patients with cancer. MATERIALS AND METHODS: In a retrospective cohort study, the subjects comprised acute ischemic stroke patients with cancer hospitalized at St. Marianna University hospital from 2008 through 2019. To evaluate the associations between the clinical factors within 24 h of the initial stroke and death or stroke recurrence events within 6 months from stroke onset, Logistic analysis and Cox proportional hazards regression analysis was used respectively. Next, the optimal cutoff point of markers for different mortality groups was determined using the receiver operating characteristic curve analysis and cumulative outcome rate of each group was compared using the Kaplan-Meier method. RESULTS: Among 194 patients with cancer who developed acute stroke, 167 were ultimately selected for analysis. 47 subjects (28.14%) passed away within 6 months following stroke onset, and 20 subjects (11.98%) had stroke recurrence. High D-dimer levels, low fibrinogen levels, high Glasgow prognostic scores (GPS), and multiple vascular territory infarctions was independently associated with death, where higher death rate was significantly confirmed in the group with D-dimer levels of ≥3.95 mg/dl, fibrinogen levels <277.5 mg/dl and GPS scores of 2. Low fibrinogen level, lack of antithrombotic therapy, and the presence of metastasis were associated with stroke recurrence. CONCLUSIONS: When patients with cancer suffer stroke, D-dimer levels, fibrinogen levels, GPS, and multiple vascular territory infarctions would be associated with the risk of death within 6 months. Low fibrinogen levels, lack of antithrombotic therapy, and the presence of metastasis correlated with high risk of stroke recurrence.

Reversible Cerebral Vasoconstriction Syndrome after Administering Etanercept during Puerperium.

Our objective is to clarify relationship between reversible cerebral vasoconstriction syndrome and administrating etanercept during puerperium. Several lines of evidence have suggested tumor necrosis factor (TNF) as a mediator of vascular dysfunction associated with estrogen deficiency. A 32-year-old woman resumed etanercept (25 mg/week), a TNF inhibitor, which had been discontinued during pregnancy, because of the deterioration of rheumatoid arthritis. She was admitted to our hospital with upper right quadrant blindness and mild right hemiparesis accompanied by pulsating left occipital pain, which had appeared 4 hours after restarting etanercept (25 mg/week). Magnetic resonance imaging and angiography revealed acute left hippocampal infarction with multiple segmental stenoses of the main intracranial arteries. Reversible cerebral vasoconstriction syndrome was diagnosed based on improvement of the multiple stenoses on magnetic resonance angiography on hospital day 17. A causal relationship was considered to exist between TNF inhibition by etanercept and multiple cerebral vasoconstrictions with brain infarct in this puerperant.

Risk of Hyperglycemia and Hypoglycemia in Patients with Acute Ischemic Stroke Based on Continuous Glucose Monitoring.

BACKGROUND: In patients with acute ischemic stroke, current guidelines recommend maintaining blood glucose levels in a range of 140-180 mg/dL and closely monitoring to prevent hypoglycemia (<60 mg/dL). We aimed to assess glucose variability by continuous glucose monitoring (CGM) and to demonstrate the risk of acute ischemic stroke patients with glucose levels outside of the glucose management recommendations. METHODS: Patients with ischemic stroke admitted within 7 days after onset were prospectively enrolled, and their blood glucose levels were monitored every 15 minutes for 72-hour period using the FreeStyle Libre Pro. Multivariate logistic regression analyses were used to analyze potential predictors for hyperglycemic (>180 mg/dL) and hypoglycemic (<60 mg/dL) events. RESULTS: A total of 39 acute ischemic stroke patients (mean age 75.9 ± 11.5 years) were enrolled, and CGM was started from 58.6 ± 41.9 hours after stroke onset. CGM showed hypoglycemic events in 19 patients and hyperglycemic events in 21 patients, and the frequencies of hypo- and hyperglycemic events during CGM were 10.1 ± 15.7% and 11.9 ± 22.5%, respectively. Hypoglycemic events were mainly observed in the night-time in patients with normoglycemia at admission. Logistic regression analyses demonstrated significant associations between the blood glucose level at admission and hypo- and hyperglycemic events on CGM. CONCLUSIONS: This study of CGM found that many stroke patients have blood glucose levels outside the recommended guideline range in the acute phase. Blood glucose level on admission may be used as a predictor for hypo- and hyperglycemic events after admission.

Rheumatoid meningitis presenting with a stroke-like attack treated with recombinant tissue plasminogen activator: a case presentation.

BACKGROUND: Rheumatoid meningitis presenting with a stroke-like attack (RMSA) is a rare manifestation of rheumatoid arthritis (RA). When the patients arrive within the time-window for recombinant tissue plasminogen activator (rt-PA) infusion therapy, no diagnostic protocol has been established. CASE PRESENTATION: A 55-year-old woman was brought by ambulance to our hospital with complaints of sudden-onset dysarthria and left arm numbness. The National Institutes of Health Stroke Scale (NIHSS) score was 5, and the Alberta Stroke Program Early CT Score was 8. She was diagnosed with acute embolic stroke. At 4 h, 6 min after onset, intravenous administration of rt-PA (alteplase, 0.6 mg/kg) was started. Her neurological deficits improved rapidly, and her NIHSS score was 1. Brain MRI was then performed. There was no hemorrhagic transformation, but the MRI findings were not compatible with ischemic stroke. She had a past history of RA diagnosed 6 months earlier, and she had been treated with methotrexate (10 mg daily). She was diagnosed with RMSA, and continuous infusion of methylprednisolone 1000 mg daily was started for 3 days. The high signal intensity on the FLAIR image disappeared. CONCLUSION: CT-based decision-making for rt-PA injection is reasonable, but MRI is needed for the early diagnosis of RMSA. In this case, it is particularly important that neither adverse events nor bleeding complications were observed, suggesting the safety of CT-based thrombolytic therapy in RMSA.

Magnetic Resonance Imaging White Matter Hyperintensity as a Predictor of Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: This study aimed to investigate factors associated with stroke recurrence and new-onset atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). METHODS: Between January 2005 and March 2012, a total of 1514 consecutive patients were admitted to our hospital with a diagnosis of acute ischemic stroke within 7 days after onset. Of these, 236 patients met the diagnostic criteria for ESUS. A retrospective analysis was performed of the following characteristics of these ESUS patients: medical history, comorbidities, and magnetic resonance imaging (MRI) findings including the deep and subcortical white matter hyperintensity (DSWMH) grade, drugs used for preventing recurrence, and clinical information such as NIH Stroke Scale scores on admission and outcomes evaluated by modified Rankin scale. The rate of recurrence after discharge and the frequency of new-onset AF were also determined. RESULTS: There were 236 ESUS patients (141 men, mean age 70.2 ± 12.1 years). During the follow-up period, ranging from 7 days to 12.9 years (median 54.3 months), 32 (13.6%) and 44 (18.6%) of these patients had a recurrent ischemic stroke and new-onset AF, respectively. The most prevalent subtype of recurrent ischemic stroke was ESUS itself; this type of stroke occurred in 19 (59.3%) patients. AF was observed at stroke recurrence, but only 2 patients were diagnosed with cardioembolism. Multivariate analysis with a Cox proportional hazard model demonstrated that DSWMH grade greater than or equal to 3 was significantly associated with both recurrent ischemic stroke (hazard ratio 3.66, 95% confidence interval 1.69-7.92, P = .001) and new-onset AF (2.00, 1.03-3.90, .04). CONCLUSIONS: MRI classification of white matter hyperintensity could be effectively used as a predictor for recurrent ischemic stroke and new-onset AF in patients with ESUS.

Effectiveness of spinal cord stimulation for painful camptocormia with Pisa syndrome in Parkinson's disease: a case report.

BACKGROUND: Spinal cord stimulation (SCS) has recently been reported to be effective for truncal postural abnormalities such as camptocormia and Pisa syndrome in Parkinson's disease. In this case report, we describe a case of a woman with Parkinson's disease in whom SCS was effective for painful camptocormia with Pisa syndrome. CASE PRESENTATION: A 65-year-old woman was admitted to our hospital because of painful camptocormia. She had noticed resting tremor in the left upper limb and aprosody at 48 years of age. She was diagnosed as having Parkinson's disease (Hoehn & Yahr stage 1) at 53 years of age. Cabergoline was started during that same year, with subsequent addition of selegiline hydrochloride; the symptoms of parkinsonism disappeared. Wearing-off occurred when she was 57 years old, 3 years after starting carbidopa/levodopa, and truncal postural abnormalities-painful camptocormia with Pisa syndrome to the right-appeared at 58 years of age. These symptoms worsened despite adjustment of her oral medications, and deep brain stimulation (DBS) was performed when she was 60 years old. The truncal postural abnormalities improved after DBS, and she could travel abroad at 61 years of age. However, from 62 years of age, painful camptocormia with Pisa syndrome to the right reappeared. The pain was unsuccessfully treated with oral analgesics, radiofrequency coagulation of the dorsal and medial branches of the lumbar spinal nerve, and lumbar epidural block. Finally, SCS was performed for the pain relief. The pain disappeared immediately after SCS and her posture then gradually improved. Unified Parkinson's Disease Rating Scale score improved from 48 to 34 points and Timed Up and Go Test improved from 15 s to 7 s after SCS. CONCLUSIONS: This case suggests that SCS may be effective for improving painful truncal postural abnormalities and motor complications of Parkinson's disease. Pain relief or a direct effect on the central nervous system by SCS was considered to explain the alleviation of these symptoms.

Impact of life and family background on delayed presentation to hospital in acute stroke.

The over-65 population stands at 29 million, more than 20% of the total population in Japan. This is the highest rate in the world. One-person households and older couple households will be increasing. The aim of the present study was to identify whether life and family background are significant factors for delayed presentation to hospital after stroke onset. A total of 253 patients (mean age, 70.7 ± 13.2 years) with stroke was examined. Patients who presented to hospital within 3 hours of onset were categorized as the early presentation group, and the other patients were categorized as the late presentation group. Life and family background were classified into 3 categories, namely 1-person households, 2-person households, and patients living with 3 or more persons. Two-person households were further subdivided by the age of family members. Multivariate logistic regression analysis demonstrated that 1-person households (odds ratio [OR]: 2.980, 95% confidence interval [CI]: 1.108-8.011) and 2-person households with individuals 65 years and older (OR: 3.059, 95% CI: 1.297-7.217) were significant independent factors for delayed presentation, in addition to stroke subtype, time of stroke onset, and route of admission. Onset-to-door time in patients with night-time onset was significantly different among different types of households. Significant delay was demonstrated in 2-person households with 2 individuals 65 years and older compared with that in patients living with 3 or more persons (P = .038). Our findings show that delayed presentation to hospital is more likely in stroke patients living in an elderly couple household, especially those with evening onset in an aging society.

[Neurological Complications Associated with Kidney Disease].

The kidneys filter the blood to excrete waste products and excess salt from the body as urine, while reabsorbing what the body needs and keeping it in the body. For this reason, when the function of the kidneys deteriorates, urine cannot be produced, and homeostasis of electrolytes and acid-bases cannot be maintained. As a result, waste products accumulate in the body, resulting in uremia and the need for dialysis induction or kidney transplant. This paper provides an overview of the neurological complications that appear in kidney disease and their treatment.

Knowledge of transient ischemic attack among the Japanese.

Stroke is often preceded by a transient ischemic attack (TIA). To properly recognize TIA and take prompt initial action, all citizens should be fully educated about TIA. Our objective is to evaluate how much knowledge of TIA has spread among Japanese citizens. As a preliminary study with this goal, we conducted an Internet-based questionnaire survey of 30,000 Japanese citizens aged 20 years or more, excluding health care professionals, from across Japan to investigate their awareness and knowledge of stroke and TIA. Valid responses were obtained from 11,121 Japanese citizens, aged 44.8 ± 13.1 (mean ± SD) years. The most frequent response pertaining to initial action at TIA onset was "visit the family doctor" (41.8%), followed by "immediately call an ambulance" (22.4%). Tokushima, Kagawa, and Kumamoto were the top 3 prefectures with the highest ambulance request rates. Factors contributing to immediately calling an ambulance were respondents' confidence about the involvement of stroke (odds ratio [OR] 2.290, 95% confidence interval [CI] 1.250-4.318, P = .009) and knowledge of the importance of initiating treatment within 3 hours of symptom onset (OR 2.273, 95% CI 1.923-2.825, P = .000). Although television was the primary source of information about stroke for all groups of age, older respondents obtained more information from newspapers than younger respondents. The results showed that many Japanese citizens would fail to call an ambulance in response to TIA, and diagnosis by a primary care physician appears to be the main triage system for the treatment of TIA. Rather than instituting a nationally uniform strategy of education for the promotion of TIA awareness among Japanese citizens, education programs should account for age-specific and regional differences among citizens.

Migraine treated using a prophylactic combination of candesartan and hydrochlorothiazide (ECARD Combination Tablets LD).

We describe the use of the antihypertensive, candesartan, with hydrochlorothiazide (ECARD Combination Tablets LD) as a preventive therapy that decreased the frequency of migraine accompanied by premonitory leg edema. Two women (aged 26 and 50 years) presented to hospital with an increasing frequency of migraine without aura accompanied by leg edema. We prescribed ECARD half tablet (candesartan, 2 mg and hydrochlorothiazide, 3.125 mg), and the migraines and leg edema disappeared. The use of ECARD to treat a series of migraines by controlling premonitory leg edema has not been reported. ECARD, combined with a low-dose diuretic, may have been helpful in these patients with the premonitory migraine symptom of leg edema.

[Varicella-Zoster Myelitis with Medullary Infarction: A Case Report].

We present the case of a 62-year-old woman who was receiving treatment for herpes zoster and experienced paraplegia, and bladder and bowel disturbance. The brain MRI diffusion-weighted image showed an abnormal hyperintense signal and apparent diffusion coefficient decreased in left medulla oblongata. The spinal cord MRI T2-weighted image showed abnormal hyperintense lesions in the left side of cervical spinal cord and thoracic spinal cord. We diagnosed varicella-zoster myelitis with medullary infarction, because varicella-zoster virus DNA was detected in the cerebrospinal fluid by polymerase chain reaction. The patient recovered with early treatment. This case shows the importance of evaluating not only skin lesions, but also distant lesions. (Received 15 November, 2022; Accepted 12 Jaunuary, 2023; Published 1 March, 2023).

Usefulness of carotid duplex ultrasonography in predicting residual large-vessel occlusions after intravenous recombinant tissue plasminogen activator therapy in patients with acute ischemic stroke.

PURPOSE: Endovascular therapy (EVT) preceded by intravenous thrombolysis with recombinant tissue plasminogen activator (iv-rtPA) has been established as a standard treatment in patients with stroke caused by large-vessel occlusion (LVO). Primary stroke centers without EVT competence need to identify patients with residual LVO after iv-rtPA therapy and transport them to an EVT-capable facility. Carotid ultrasonography (CUS) is easily applicable at bed side and useful for detecting extra- and intracranial LVO. This study aimed to determine whether CUS findings at admission are useful to predict patients with residual LVO after iv-rtPA. METHODS: Patients scheduled to undergo iv-rtPA for acute cerebral infarction were registered. Before iv-rtPA, they underwent CUS, followed by CTA or MRA evaluation within 6 h after iv-rtPA. A model that can achieve 100% sensitivity for detecting residual LVO after iv-rtPA was studied. RESULTS: This study included 68 of 116 patients treated with iv-rtPA during the study period. National Institutes of Health Stroke Scale (NIHSS) score (cutoff value = 10) on arrival, hyperdense MCA sign on non-contrast CT, end-diastolic (ED) ratio on CUS, and eye deviation were significantly different between patients with residual LVO after iv-rtPA and those without. If any of these clinical features are positive in the screening test, residual LVO could be predicted with 100% sensitivity, 50% specificity, 64% positive predictive value, and 100% negative predictive value. CONCLUSION: Prediction of residual LVO with 100% sensitivity may be feasible by adding CUS to NIHSS score > 10, the presence of eye deviation, and hyperdense MCA sign.

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy.

PURPOSE: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0-5) in population #2. RESULTS: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. CONCLUSIONS: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy.

Soleal vein dilatation in the early phase of hospitalization is associated with subsequent development of deep vein thrombosis in patients with acute stroke.

PURPOSE: To evaluate the usefulness of soleal vein (SOV) diameter as a predictor of new onset of deep vein thrombosis (DVT) in acute stroke patients. METHODS: A total of 121 acute stroke patients who were admitted within 48 h of onset underwent a calf vein ultrasonography (CVUS) examination within 7 days after hospitalization. They were evaluated for the presence of DVT and risk factors including maximum SOV diameter. Next, the patients in whom DVT was not detected at the first CVUS examination underwent a second CVUS examination on the 21st hospital day, and were evaluated for the presence of new DVT. RESULTS: DVT was detected in 27 of 121 patients at the first CVUS examination. A significant association was noted between the presence of DVT and higher levels of soluble fibrin monomer, D-dimer, and C-reactive protein, and a higher rate of having cancer concomitantly. Furthermore, 50 of 94 patients without DVT at the first CVUS examination underwent a second CVUS examination. Of the 94 patients, 44 were excluded, because they were discharged by the 21st day. Note that DVT was newly developed in 12 of the 50 patients who underwent the second CVUS. A significant association was found between the presence of new DVT and the rate of history of stroke, hematocrit level, and maximum SOV diameter at the first examination. CONCLUSION: In our acute stroke patients, SOV dilation, history of stroke, and elevated hematocrit level were found to be associated with risk of developing a new DVT.

Leber's hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri: illustrative case.

BACKGROUIND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. OBSERVATIONS: The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2'-deoxyguanosine positivity, suggesting the presence of oxidative stress. LESSONS: LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.

Prediction of recurrent stroke among ischemic stroke patients with atrial fibrillation: Development and validation of a risk score model.

BACKGROUND: There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF. METHODS: AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine-Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset. RESULTS: The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA). CONCLUSIONS: Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF.

Effectiveness of the traditional Japanese Kampo medicine Yokukansan for chronic migraine: A case report.

RATIONALE: The traditional Japanese Kampo medicine Yokukansan (TSUMURA Yokukansan extract granules) was originally used to treat neurosis, insomnia, night crying, and irritability and/or agitation in infants and recently it has also been used for neuropsychiatric symptoms in Alzheimer's disease or other dementia in Japan. Furthermore, several recent studies have reported the efficacy of Kampo medicines for various types of headache. Here, we report a case of severe chronic migraine refractory to prophylactic therapy using various western medicines and Japanese Kampo medicines that had resulted in a leave of absence from work, but for which the frequency and severity were markedly decreased by Yokukansan (2.5 g 3 times/d), enabling the patient to return to work fully. PATIENT CONCERNS: The patient was a 39-year-old woman with a diagnosis of migraine without aura, which started around the age of 17 years and had been well managed with oral triptan preparations. However, due to lifestyle changes after childbirth, the frequency and severity of migraine increased at 38 years of age, prompting her to visit our hospital. DIAGNOSES: Our initial examination found no neurological abnormality, and our diagnosis was also migraine without aura based on the International Classification of Headache Disorders version 3. INTERVENTIONS: Her migraine had become refractory to several western medicines (lomerizine hydrochloride, propranolol, sodium valproate, amitriptyline, and duloxetine) and 2 Japanese Kampo medicines (Goshuyuto and Chotosan). The migraine episodes worsened, and consequently she took a leave of absence from work. OUTCOMES: Yokukansan was then tried, and this markedly improved the chronic migraine, enabling her full return to work. LESSONS: Yokukansan might have exerted a prophylactic effect on chronic migraine via its action on the glutamatergic and serotonergic systems, inhibitory action on orexin A secretion, and anti-inflammatory action. Yokukansan might be useful as a prophylactic for migraine worldwide, and a future large-scale clinical study is warranted.