Case report: Concurrent low-volume subdural hematoma and ipsilateral ischemic stroke presenting as capsular warning syndrome: a complex case with anticoagulation dilemma and dual pathology.

Background: The simultaneous emergence of low-volume subdural hematoma and ipsilateral ischemic stroke in an atrial fibrillation patient who is under anticoagulation therapy is a rare and intricate clinical case. This report accentuates the diagnostic and treatment complexities associated with these consecutive neurological conditions. Case presentation: An 83 years-old male patient initially presented with acute dyspnea, raising the suspicion of pulmonary embolism. After exclusion of pulmonary embolism through CT angiography, the patient experienced a sudden onset of left-sided hemiparesis without prior history of head trauma but with chronic intake of apixaban due to atrial fibrillation. Subsequent cranial CT tomography revealed a small right parietal subdural hematoma. After reversal of the anticoagulation therapy, surgical evacuation of the subdural hematoma was successfully performed. However, in the postoperative period, the patient developed new neurological symptoms that could not be explained by the reduced size of the subdural hematoma on a follow-up CT scan. Cranial MRI revealed the coexistence of acute ischemic stroke in the right corona radiata. The recent surgical procedure precluded guideline-recommended stroke treatment. Discussion: This case underscores the complexities of diagnosing and treating concomitant small volume subdural hematoma and ischemic stroke, especially if the latter occurs in the corona radiata resulting in fluctuating symptoms known as "capsular warning syndrome." Reversal and secondary discontinuation of anticoagulant therapy for surgical intervention highlight the inherent risk of thrombotic events in anticoagulated patients. The development of tailored treatment strategies requires a multidisciplinary approach, and further research and guidelines are required in similar complex scenarios. Conclusion: The presence of both a small subdural hematoma and an ipsilateral ischemic stroke presenting as capsular warning syndrome in an anticoagulated patient highlights the intricacy of their care. This case calls for a comprehensive and collaborative strategy to address complicated clinical scenarios.

[Cilostazol was effective for capsular warning syndrome during anticoagulant therapy: a case report].

An 88-year-old woman with atrial fibrillation was admitted to our hospital due to the right hemiplegia and aphasia. MRA shows the left middle cerebral artery M2 occlusion. After intravenous rt-PA, her symptoms improved. She was diagnosed with cardioembolic stroke, and was treated with direct oral anticoagulation therapy. However, she had repeated stereotypical transient right hemiparesis a week after index stroke. Her symptoms were considered capsular warning syndrome (CWS). After cilostazol was administered, no further transient neurological deteriorations occurred. CWS can coexist with acute cardioembolic stroke, and cilostazol was effective.

Capsular warning syndrome-a case of atrial fibrillation and corona radiata infarct.

BACKGROUND: Capsular warning syndrome (CWS) is a rare clinical syndrome characterised by recurrent and transient episodes of focal neurological deficits with high risk of infarction. The exact physiological mechanism of CWS remains unclear but is most commonly believed to be a result of haemodynamic insufficiency in diseased, small penetrating vessels. There are no defined treatment guidelines or established effective therapy. CASE PRESENTATION: We describe the case of a 65-year-old man who presented to the emergency department with recurrent episodes of dysarthria coupled with right facial droop and right-sided weakness. Symptoms recurred a total of ten times within a span of 3 h. He had new onset atrial fibrillation. An initial cerebral angiogram showed mild intracranial atherosclerotic disease with no proximal large vessel occlusion or acute infarct. Magnetic resonance imaging 1 h later demonstrated an infarct in the left corona radiata. CONCLUSIONS: This case illustrates an uncommon etiology of CWS. We will also discuss the lack of consensus in treatment options for CWS to mitigate a complete stroke.

Capsular warning syndrome and its clinical awareness and therapeutic approach: two case reports and a systematic review of the literature.

Introduction: Capsular warning syndrome (CWS) is characterized by recurrent stereotyped episodes of unilateral transient motor and/or sensory symptoms affecting the face and upper and lower limbs, without cortical signs in 24 h and with a high risk of developing stroke. Among the possible underlying mechanisms, small perforating artery disease is the most common. The aim was to assess the most common risk factors, the therapeutic alternatives, and the different outcomes in patients with CWS, along with the presentation of two cases treated in our Emergency Department. Methods: Stroke Code, launched at our institution in January 2017, was triggered 400 times, and by December 2022, 312 patients were admitted as having an acute ischemic stroke. Among them, two of them fulfilled the criteria of CWS. A systematic search was carried out in PubMed, Scopus, and Web of Science databases to seek demography and therapeutic approaches in CWS. Results: Of 312 cases, two with acute ischemic stroke exhibited CWS. The first patient had six events of right hemiparesis with recovery in 10-30 min; after MRI and digital subtraction angiography (DSA), he received apixaban and clopidogrel; however, a day after admission, he developed ischemic infarction with partial recovery. The second patient presented five transient events of right hemiparesis. After MRI and DSA with an intra-arterial infusion of nimodipine, oral aspirin, and ticagrelor, he presented another event-developing stroke and was discharged with partial recovery. A systematic review found 190 cases of CWS in 39 articles from 1993 to 2022. Most were male subjects (66.4%), and hypertension (60%), smoking (36%), diabetes (18%), and dyslipidemia (55%) were the most common risk factors. Over 50% of the cases were secondary to small perforating artery disease. The most commonly used treatments were dual antiplatelet therapy (DAT), recombinant tissue plasminogen activator, and anticoagulant therapy (ACT), where the combination of DAT plus ACT was linked to the most positive functional outcomes (82.6%). Conclusion: Our cases fit with the description of patients with partial recovery and risk factors (hypertension, diabetes, and smoking) in male patients. There is a lack of evidence regarding the best treatment option; dual antiplatelet therapy and anticoagulation therapy are strong contenders for a favorable result.

Capsular Warning Syndrome Leading to Acute Ischemic Stroke in a Pediatric Patient Secondary to Varicella Zoster Virus.

We report the case of a 3-year-old boy who presented with recurrent stereotyped transient episodes of left sided weakness consistent with capsular warning syndrome (CWS) which eventually progressed to acute ischemic stroke (AIS). He received thrombolytic therapy with tissue plasminogen activator. Workup was notable for positive CSF varicella (VZV) PCR, and positive CSF and serum VZV IgG and negative IgM. On further history, he was unvaccinated and had a rash consistent with VZV 5 months prior to presentation. This case highlights the importance of recognizing CWS given the increased risk of progression to AIS. In addition, it emphasizes the importance of considering VZV vasculopathy in pediatric AIS and inquiring about infectious history and immunization status despite high rates of vaccination in the United States.

Capsular Warning Syndrome: Features, Risk Profile, and Prognosis in a Large Prospective TIA Cohort.

INTRODUCTION: Features and prognosis of capsular warning syndrome (CWS) have been poorly investigated prospectively. AIMS: The study aimed to characterize CWS clinical features, risk profile, short- and long-term prognosis, among a large TIA cohort. METHODS: Prospective cohort study of consecutive TIAs was conducted from August 1, 2010, to December 31, 2017. Demographic and clinical characteristics, risk profile, primary (stroke and composite outcome) and secondary (TIA recurrence, cerebral hemorrhage, new onset atrial fibrillation) outcomes were compared between CWS, lacunar (L), and nonlacunar (NL) TIAs. RESULTS: 1,035 patients (33 CWS, 189 L-TIAs, 813 NL-TIAs) were enrolled. Newly diagnosed (ND) hypertension, hypercholesterolemia, cigarette smoking, and leukoaraiosis were independent risk factors of CWS (p < 0.05). CWS showed the highest stroke (30.3% vs. 0.5% and 1.5% for L-TIAs and NL-TIAs, respectively) and composite outcome risk at follow-up (p < 0.001), but better 3-month post-stroke prognosis (mRS 0-2 90.0% vs. 36.8%; p = 0.002). CWS-related stroke mostly occurred <48 h (80.0%) and had a small vessel occlusion etiology (100%), affecting more often the internal capsule (60.0%). Dual antiplatelet therapy (DAPT) versus single antiplatelet therapy was associated with lower 3-month cumulative stroke incidence (12.5% vs. 57.1%; p = 0.010). Intravenous thrombolysis (IVT) showed similar 3-month efficacy and safety in strokes after TIAs groups (median mRS 0, IQR 0-1; p = 0.323). CONCLUSIONS: CWS is associated with higher stroke risk and better functional prognosis than L- and NL-TIAs. CWS risk profile is consistent with severe small vessel disease, and ND hypertension could represent a major risk factor. DAPT and IVT seem effective and safe in preventing and treating stroke following CWS.

Clinical safety and possible efficacy of tirofiban in combination with intravenous thrombolysis by recombinant tissue plasminogen activator for early treatment of capsular warning syndrome (CWS).

The purpose of this study was to assess the efficacy and safety of the combination of tirofiban with intravenous thrombolysis (IVT) in treating patients with capsular warning syndrome (CWS) who failed to respond to the treatment of intravenous thrombolysis alone. Tirofiban was approved for the treatment of CWS patients with fluctuating symptoms or no substantial improvement after intravenous thrombolysis within 24 h in our hospital from October 2019 to June 2021. Patients were evaluated with the National Institutes of Health Stroke Scale (NIHSS) at admission, at 72 h post-thrombolysis, at 1-week, and at 3-months with the modified Rankin Scales (MRS) score. A total of 12 patients received tirofiban and eight patients received control treatment with a history of CWS in our cohort. Among the patients, 13 patients smoked more than one pack of cigarettes a day, 17 had hypertension, 17 had hypercholesterolemia, 7 had diabetes, 1 had the history of cerebral infarction, 2 had atrial fibrillation, 7 had mild big vascular stenosis, 13 had lesions of the perforating branch by imaging, and 19 had acute capsular infarction. In both the tirofiban and control groups, NIHSS scores were significantly reduced after intravenous thrombolysis or 1-week after onset compared with before intravenous thrombolysis (P < 0.001). Before and after intravenous thrombolysis, there were no differences between the tirofiban group and control group (P = 0.970, P = 0.384, respectively). The tirofiban group, however, showed remarkably lower scores in both 1-week NIHSS and 3-month MRS than the control (P = 0.012, P = 0.003, respectively). Our study revealed that tirofiban did not increase the risk of hemorrhage and had favorable clinical efficacy as a remedial treatment for CWS patients with poor prognosis for intravenous thrombolysis, therefore indicating great potential for broader use.

Stroke warning syndrome.

Stroke Warning Syndrome (SWS) is a form of early recurrent transient ischemic attack (TIA) which carries a high risk of infarction. It is characterized by repeated stereotypical sensorimotor symptoms affecting the face, arm, and leg without associated cortical involvement occurring within a seven-day period after an index TIA. In this systematic review, we identified that 1.5-4.5% of TIAs present as SWS and despite this occurrence, little is known about management strategies and treatment outcomes. Various mechanisms including small vessel disease, artery to artery embolism, hemodynamic instability and periinfarct depolarization may account for its nature. There are no specific guidelines on treatment, but thrombolysis appears safe but does not necessarily provide an advantage over antiplatelet and/or anticoagulation in preventing recurrences. Regardless of treatment, SWS is associated with excellent clinical outcomes.

Attack Interval Is the Key to the Likely Pathogenesis of Multiple Transient Ischemic Attacks.

INTRODUCTION: The aim of this study was to test the hypothesis that the attack interval of multiple transient ischemic attacks (TIAs) is correlated with the underlying pathogenesis of ischemia. METHODS: Patients with multiple TIAs, defined as 2 or more motor deficits within 7 days, were studied. The attack interval between the last 2 episodes was classified into 3 groups: 2 episodes within an hour (Hour group), over hours within a day (Day group), and over days within a week (Week group). Patients with a lacunar syndrome, no cortical lesions, and no embolic sources were recognized as having a small vessel disease (SVD) etiology for their multiple events. RESULTS: Of 312 TIA patients admitted over a 9-year period, 50 (37 males, 13 females, mean 67.6 years) had multiple TIAs. Twelve patients were classified as being within the Hour group, 23 within the Day group, and 15 within the Week group. Lacunar syndromes were observed in 30 (75%, 35%, and 67%), embolic sources were detected in 28 (25%, 65%, and 67%), and a high signal lesion on diffusion-weighted imaging was depicted in 30 (75%, 48%, and 67%) patients (18 cortical, 11 subcortical, and one cerebellar). Patients in the Hour group had a significantly higher prevalence of SVD etiology (75%) than those in the Day and Week groups (30%, p = 0.0165; 27%, p = 0.0213, respectively). Four patients had a subsequent stroke within 7 days. CONCLUSION: Attack intervals of multiple TIAs may be correlated with the underlying pathogenesis of ischemia. Two motor deficits within an hour are more likely to suggest a SVD etiology.

Stroke warning syndromes.

It is important for physicians to be aware of stroke warning syndromes because, although rare, there is a high associated risk of subsequent ischaemic infarction. Stroke warning syndromes present as stereotypical, recurrent transient episodes of focal neurological deficit, in the absence of cortical signs, occurring within a short period of time. They are broadly divided into two main subtypes, based on vascular territory: capsular warning syndrome and pontine warning syndrome. The exact underlying pathophysiology related to stroke warning syndromes is incompletely established, but proposed pathophysiological hypotheses for cerebral hypoperfusion include micro-atherosclerosis (cerebral small vessel disease) and haemodynamic instability (e.g. hypotension). Atherosclerotic disease involving small perforating arteries in the anterior circulation (e.g. lenticulostriatal arteries) gives rise to capsular warning syndrome and subsequent risk of capsular infarcts. Conversely, involvement of the posterior circulation pontine perforator arteries gives rise to pontine warning syndrome, which can result in paramedian pontine infarcts. Although the evidence is limited, recommended treatment modalities include permissive hypertension, intravenous recombinant tissue plasminogen activator, dual antiplatelet therapy and statins.

Capsular warning syndrome: clinical analysis and treatment.

BACKGROUND: Capsular warning syndrome (CWS) is a rare clinical syndrome, which is defined as a recurrent transient lacunar syndrome. The mechanism and clinical management of CWS remain unclear. The aim of the study was to discuss the clinical characteristics of CWS and evaluate the different outcome between rt-PA and no rt-PA therapy. METHODS: The present multicenter retrospective study involved three medical centers, and the clinical data were collected from patients with CWS between January 2013 and December 2018. The clinical characteristics of CWS were analyzed. Patients were divided into two groups: rt-PA and no rt-PA groups. The therapeutic effects and prognosis of these two groups were analyzed. A good prognosis was defined as 3-month modified Rankin Scale (mRS) ≤ 2. RESULTS: Our study included 72 patients, 27 patients were assigned to rt-PA group, 45 in no rt-PA group. Hypertension and dyslipidemia were the most common risk factors. The mean number of episodes before irreversible neurological impairment or the symptoms completely disappeared was five times (range: 3-11 times). A total of 58 (80.55%) patients had acute infarction lesions on the diffusion weighted imaging (DWI). The most common infarct location was the internal capsule (41,70.69%), followed by the thalamus and pons. The difference in therapeutic effects between the rt-PA, single and double antiplatelet groups was not statistically significant (P > 0.05). A good prognosis was observed in 61 (84.72%) patients after 3 months, in which 23 (23/27, 85.19%) patients were from the rt-PA group and 38 (38/45,84.44%) patients were from the no rt-PA group (P > 0.05). After 3 months of follow-up, two patients had recurrent ischemic stroke. CONCLUSION: The most effective treatment of CWS remains unclear. Intravenous thrombolysis is safe for CWS patients. Regardless of the high frequency of infarction in CWS patients, more than 80% patients had a favorable functional prognosis.

Intravenous tirofiban therapy for patients with capsular warning syndrome.

Background: Capsular warning syndrome (CWS) is defined as recurrent episodes of transient ischaemic attacks ≥3 times during a short time frame. There is no effective therapy to stop these attacks. We, herein, report our experience of using intravenous tirofiban to treat CWS. Methods: All patients with CWS in our hospital from January 2013 to September 2017 were reviewed. Patients in tirofiban group (T-group) were treated by intravenous tirofiban at 0.4 µg/kg/min for 30 min followed by 0.1-0.15 µg/kg/min infusion. Other treatments (non-T-group) included thrombolytic, oral antiplatelet agents and anticoagulant. Intracerebral haemorrhage (ICH), systematic bleeding, new attacks after treatment, National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours and modified Rankin Scales (mRSs) at 3 months were recorded. Descriptive statistics were used for analysis. Results: Of 23 patients qualified (15 in T-group, 8 in non-T-group), the duration of symptoms ranged from 2 to 100 min before treatments. After treatment, in T-group, four patients (26.7%) had recurrent attacks, and NIHSS scores were 0 in 11 patients (73.3%) at 24 hours. All patients reached a favourable outcome (mRS ≤2 at 3 months. In non-T-group, five patients (62.5%) had new attacks. NIHSS scores were 0 in two patients (25%) at 24 hours. At 3 months, seven patients (87.5%) reached a favourable outcome. Neither ICH nor systematic bleeding or thrombocytopaenia occurred in both groups of patients. Conclusions: Intravenous tirofiban can be a potentially effective and safe therapy to stop early symptomatic fluctuations and shorten the duration of functional deficits in patients with CWS.

Small vessel occlusion is a high-risk etiology for early recurrent stroke after transient ischemic attack.

BACKGROUND: Recent prospective registration studies of transient ischemic attack in Western countries demonstrated that large artery atherosclerosis is the highest risk etiology for early stroke recurrence under urgent evaluation and treatment. On the other hand, some limited transient ischemic attack studies from East Asian countries showed transient ischemic attack patients due to small vessel occlusion were at a higher early stroke risk. AIMS: We aimed to assess the risk for early stroke in small vessel occlusion-transient ischemic attack patients in a Japanese large transient ischemic attack registry. METHODS: We analyzed the data of a prospective Japanese transient ischemic attack registry including 1320 transient ischemic attack patients within seven days after onset. Small vessel occlusion-transient ischemic attack was defined as the presence of lacunar transient ischemic attack syndrome, without other etiologies. The outcome measure was recurrent stroke within 30 days after transient ischemic attack. The predictors of 30-day recurrent stroke were estimated using the Cox proportional hazards model. RESULTS: The study population had a mean age of 69 ± 12 years and 470 were women. Recurrent stroke was observed in 61 patients (4.6%), and the highest rate was observed with small vessel occlusion-transient ischemic attack (7.8%), followed by large artery atherosclerosis (5.4%). In multivariate analysis, recurrent stroke was independently associated with small vessel occlusion-transient ischemic attack (hazard ratio (HR): 2.01, 95% confidence interval (CI): 1.19-3.35), higher systolic blood pressure (HR: 1.18, 95% CI: 1.08-1.28), and presentation within 3 h after onset (HR: 2.21, 95% CI: 1.27-4.04). Furthermore, small vessel occlusion-transient ischemic attack with acute small deep infarct on diffusion-weighted imaging was a stronger predictor of recurrent stroke (HR: 4.87, 95% CI: 2.09-10.0). CONCLUSION: Small vessel occlusion-transient ischemic attack, especially with acute small deep infarct, had a higher early stroke risk compared with other etiologies in Japanese transient ischemic attack patients who received early management.

The Importance of Combined Antithrombotic Treatment for Capsular Warning Syndrome.

INTRODUCTION: Capsular warning syndrome (CWS) is characterized by recurrent conventional episodes of motor and/or sensory deficits without cortical symptoms. The purpose of this case series study was to evaluate the safety and appropriate treatment for CWS to prevent the development of complete stroke. METHODS: We reviewed our hospital records and previous reports to find patients with neurologically fluctuating profiles, and excluded those with unknown details of initial treatment/final treatment of antiplatelet therapy or radiological findings. RESULTS: We retrieved two cases of CWS from our hospital, which presented motor and/or sensory symptoms followed by complete resolution without complete ischemia. The recurring episodes in both were unable to be stabilized by single antiplatelet therapy but were successfully managed using two or more antiplatelet drugs. In 11 previously reported cases of CWS, the recurring episode was frequency stabilized with plural antiplatelet therapy. CONCLUSION: Multiplicate antiplatelet therapy is important for treatment of CWS, and caution is needed regarding hemorrhagic complications.

Fluctuating locked-in syndrome as a presentation of a bilateral pontine infarction.

The "pontine warning syndrome" is characterized by recurrent episodes of motor hemiparesis, dysarthria and horizontal gaze palsy associated with basilar artery branch infarction. We report a case of a patient who presented with recurrent, self-limited episodes of locked-in syndrome, related to a bilateral pontine infarction. As far as we know, this clinical presentation as a subtype of pontine warning syndrome has never been described. We discuss the case, the differential diagnosis of the neuroimaging and the possible underlying mechanism.

Value of higher-resolution MRI in assessing middle cerebral atherosclerosis and predicting capsular warning syndrome.

PURPOSE: To investigate the correlation between middle cerebral atherosclerosis and capsular warning syndrome (CWS) and assess the value of higher-resolution magnetic resonance imaging (MRI) in prognostication. MATERIALS AND METHODS: In all, 97 transient ischemic attack (TIA) patients who underwent an MRI from February 2010 to December 2013 were included in the retrospective study and divided into either a CWS or middle cerebral artery (MCA) TIA group according to their eventual clinical diagnosis. 3T MRI included fast-spin echo T2 -weighted imaging, double-inverse recovery T1 -weighted imaging, and T1 contrast-enhanced scan sequences. Baseline characteristics, MRI results in terms of MCA plaque formation, plaque characteristics such as enhancement, and development of infarction were compared between the two groups to study the distribution and characteristics of cerebral atherosclerotic plaques. Multivariate analysis identified factors associated with infarction 1 week after plaque identification. RESULTS: Based on the MR images, 76% of both groups of patients had middle cerebral atherosclerosis. Compared to TIA patients, the median age of CWS patients was younger (58 [range 42-73] vs. 67 [36-84] years, P = 0.003), and CWS patients had a lower rate of stroke history (10.9% vs. 41.2%, P = 0.001). Infarction was more common in CWS patients than in TIA patients (52.2% vs. 20.5%, P = 0.003) and a superior plaque was correlated with infarction occurrence (odds ratio 5.674, 95% confidence interval 1.112-28.958). CONCLUSION: Patients with CWS have large arterial plaques, including MCA plaques. There was a correlation between CWS and the MCA plaque location. J. Magn. Reson. Imaging 2016;44:1277-1283.

Síndrome de alertamiento capsular asociado con el síndrome antifosfolípidos: reporte de un caso / Capsular Warning Syndrome Associated with Antiphospholipid Syndrome: Case Report / Síndrome de advertência capsular associado à síndrome antifosfolípide: reporte de um caso

El síndrome de alertamiento es definido como ataques isquémicos transitorios esterotipados y recurrentes, los cuales se manifiestan con síntomas motores y/o sensitivos de un hemicuerpo. Las lesiones, generalmente, son de pequeño vaso de la cápsula interna. Entre un 40% y 60% de los casos terminan con infarto del territorio sintomático. El proceso fisiopatológico exacto aún se desconoce y, a pesar de algunos casos exitosos, no existe consenso sobre el manejo óptimo de este síndrome. Se presenta un caso de síndrome de alertamiento capsular de un en paciente con historia de síndrome antifosfolípidos, a la fecha no hay casos publicados que describan la correlación de estas dos condiciones clínicas.

The capsular warning syndrome is defined as recurrent and stereotyped transient ischemic attacks that manifest themselves with motor and/or sensory symptoms. Generally, injuries take place in the small vessel of the internal capsule. Between 40 and 60% of cases will have a stroke.The pathophysiological process is still unknown, and despite some success cases, there is no consensus for the optimal management of the condition.This case of the capsular warning syndrome is presented in a patient with a history of antiphospholipid syndrome. To date, there are no published cases describing the correlation between these two conditions.

A síndrome de advertência é definida como ataques isquêmicos transitórios estereotipados e recorrentes, os quais manifestam-se com sintomas motores e/ou sensitivos de um hemicorpo. As lesões são geralmente de pequeno vaso da capsula interna.Entre um 40% e 60% dos casos terminam com infarto do território sintomático. O processo fisiopatológico exato ainda desconhece-se e apesar de alguns casos de sucesso não existe consenso sobre o manejo óptimo desta síndrome.Apresenta-se um caso de síndrome de advertência capsular de um paciente com história de síndrome antifosfolípide; até esta data não há casos publicados que descrevam a correlação destas duas condições clínicas.