Frontotemporal lobar degeneration encompasses a spectrum of clinically, radiologically, and molecularly heterogeneous conditions. Clinical phenotypes are defined based on predominant neuropsychological manifestations and the selective involvement of specific brain regions determines the core symptoms, disability profiles, and care needs. While the unique anatomical patterns of cortical and subcortical degeneration along the FTLD/FTD spectrum are well recognised, the molecular basis of this selective vulnerability remains unclear. A large prospective neuroimaging study has been undertaken to explore topological associations between phenotype-specific atrophy patterns and physiological mitochondrial density along the FTLD/FTD spectrum. Patients with behavioural variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA), C9orf72-positive ALS-FTD, C9orf72-negative ALS-FTD, and a cohort of healthy controls (HC) were included. FTD phenotypes were first contrasted to healthycontrols and the resulting voxelwise maps were correlated to physiological mitochondrial density maps. We have identified voxelwise associations between atrophic change and physiological mitochondrial density. The resulting correlation coefficients over the entire GM mask revealed weak topological associations with r = 0.217 in C9NEG ALS-FTD, r = 0.251 in C9POS ALS-FTD, r = 0.213 in bvFTD, r = 0.182 in nfvPPA, and r = 0.292 in svPPA at p FWE < 0.001. Our region-of-interest analyses revealed moderate-to-strong regional associations between mitochondrial density and focal degenerative change with r values above 0.65 in multiple brain regions in all five FTD subgroups. Brain regions exhibiting the most significant associations between volume loss and mitochondrial density in each FTD subgroup are the very regions that define the core clinical manifestations of the given phenotype. Cortical and subcortical brain regions with high physiological mitochondrial density are particularly vulnerable to neurodegenerative change in FTD. While these anatomical associations do not indicate direct causation, mitochondrial metabolism may represent an important component in the cascade of focal degeneration.

BackgroundInfective endocarditis (IE) is a serious infection of the heart lining and valves, associated with high morbidity and mortality.1 Diagnosis is guided by the Modified Duke’s Criteria, which integrate microbiological, imaging and clinical features, and were most recently updated in 2023.2 Culture-negative IE (CNIE) occurs in up to 20% of cases, often after prior antibiotic exposure or infection with fastidious organisms, making diagnosis particularly difficult.3 Antimicrobial stewardship (AMS), defined as optimizing antimicrobial use to improve outcomes while minimizing toxicity and resistance, is vital to addressing antimicrobial resistance (AMR).4ObjectivesThis abstract presents a complex CNIE case with complete heart block (CHB) and embolic stroke, illustrating the role of Duke’s Criteria, multidisciplinary decision-making and AMS.MethodsA retrospective case review was conducted on a patient admitted in June 2025 with suspected infective endocarditis at an NHS Foundation Trust. Data included clinical presentation, microbiology, imaging, echocardiography, management and multidisciplinary team (MDT) discussions. The case was assessed using the Modified Duke’s Criteria to establish diagnostic certainty and guide clinical decision-making.ResultsAn 85-year-old patient presented with progressive shortness of breath and tiredness. On admission, electrocardiography (ECG) demonstrated CHB with a ventricular rate of 38 bpm. Verapamil was withheld, and the patient was commenced on isoprenaline; a temporary pacing wire was not tolerated. During admission, he developed a right middle cerebral artery (MCA) infarct secondary to an M2 thrombus, resulting in expressive aphasia. No atrial fibrillation or left ventricular thrombus was identified, raising suspicion of septic embolism. Despite persistently negative blood cultures, echocardiography revealed a mobile structure within the aortic root near the non-coronary cusp with trivial regurgitation, and a mobile mass on the posterior mitral leaflet, though difficult to define due to calcification. According to the Modified Duke’s Criteria, the case met one major criterion (positive echocardiographic findings) and three minor criteria (predisposing heart disease, vascular event, clinical features), consistent with likely infective endocarditis. The patient was treated empirically with IV amoxicillin, flucloxacillin and gentamicin. From AMS perspective, broad-spectrum therapy was regularly reviewed by the multidisciplinary team, with toxicity monitoring and consideration of diagnostic refinement to enable targeted treatment.ConclusionsThis case demonstrates the diagnostic complexity of CNIE. Although blood cultures were persistently negative, Duke’s Criteria and multimodal imaging supported the diagnosis. From an AMS perspective, key recommendations include:Optimizing microbiological sampling and using molecular diagnostics before initiating broad-spectrum therapy.Applying guideline-directed empirical regimens with early stewardship review and de-escalation where possible.Close collaboration between microbiology, cardiology, neurology and infectious diseases to tailor therapy to optimize antibiotic use and decrease AMR.Careful monitoring of nephrotoxic combinations (e.g. aminoglycosides) and considering oral or less toxic alternatives in frail patients.

Background Intravenous thrombolysis (IVT) is most effective in acute ischemic stroke (AIS) when administered promptly; however, efforts to reduce treatment times may increase the risk of treating stroke mimics (SM). This retrospective single-center study aimed to determine the prevalence of SM among patients treated with IVT, compare them with AIS cases, evaluate the clinical implications of IVT administration, and identify possible predictors of SM. Methods Patients who received IVT for suspected AIS between January 2022 and December 2024 were retrospectively analyzed. Only patients without early ischemic changes on non-contrast CT and without intracranial occlusion on CT angiography were included. Based on clinical presentation, imaging, and discharge diagnosis, patients were classified as AIS or SM. Data collected included demographics, clinical features, risk factors, treatment times, NIHSS scores, mRS scores, and post-IVT complications. Results Of 724 patients treated with IVT, 330 met the inclusion criteria. Among them, 293 (88.8%) had confirmed AIS and 37 (11.2%) were SM. SM patients were significantly younger (mean age 57.4 vs. 70.2 years, p &amp;lt; 0.001), had fewer vascular risk factors, and higher rates of migraine, epilepsy, and vestibular disorders. Sensory symptoms and headache were more common in SM, whereas motor symptoms and aphasia were more frequent in AIS. Although initial NIHSS scores were comparable, SM demonstrated greater improvement at 1 and 24 h post-IVT. Functional outcomes were better in SM, with 92% achieving a discharge mRS of 0 compared to 19% in AIS ( p &amp;lt; 0.001). No intracranial hemorrhage or seizures were observed in the SM group. LASSO selection and Firth’s bias-reduced logistic regression analysis identified younger age, presence of sensory symptoms, history of migraine or epilepsy, and absence of atrial fibrillation as independent predictors of SM. Conclusion Stroke mimics accounted for 11.2% of cases treated with intravenous thrombolysis and differed significantly from AIS in clinical and demographic characteristics. IVT was safe in SM, with no major complications observed. Several clinical predictors may aid in early differentiation. However, these findings should be interpreted cautiously due to the limited number of mimic cases.

Broca's aphasia is a type of aphasia characterized by non-fluent, effortful and agrammatic speech production with relatively good comprehension. Since traditional aphasia treatment methods are often time-consuming, labour-intensive, and do not reflect real-world conversations, applying natural language processing based approaches such as Large Language Models (LLMs) could potentially contribute to improving existing treatment approaches. To address this issue, we explore the use of sequence-to-sequence LLMs for completing Broca's aphasic sentences. We first generate synthetic Broca's aphasic data using a rule-based system designed to mirror the linguistic characteristics of Broca's aphasic speech. Using this synthetic data (without authentic aphasic samples), we then fine-tune four pre-trained LLMs on the task of completing agrammatic sentences. We evaluate our fine-tuned models on both synthetic and authentic Broca's aphasic data. We demonstrate LLMs' capability for reconstructing agrammatic sentences, with the models showing improved performance with longer input utterances. Our result highlights the LLMs' potential in advancing communication aids for individuals with Broca's aphasia and possibly other clinical populations.

Quantifying structural brain changes is critical for diagnosing and monitoring neurodegenerative diseases. Although magnetic resonance imaging (MRI) is the silver standard, limited accessibility and cost hamper routine use. We developed a deep learning–based framework using the nnU-Net for brain segmentation using computed tomography (CT) to assess cerebrospinal fluid (CSF) volume changes, as an indirect marker of tissue loss, and evaluated its utility across Alzheimer’s disease (AD) stages and frontotemporal dementia (FTD) subtypes. We included 2357 participants: cognitively unimpaired (CU, n = 595), mild cognitive impairment (MCI, n = 954), dementia of Alzheimer’s type (DAT, n = 663), and FTD subtypes (FTD, n = 145, behavioral variant FTD (bvFTD, n = 66), nonfluent variant primary progressive aphasia (nfvPPA, n = 29), and semantic variant PPA (svPPA, n = 50). CT-based segmentation was trained and validated using 3D T1-weighted MRI as reference. We assessed (1) segmentation accuracy via Dice similarity coefficients (DSCs), (2) reliability and precision using correlation and Bland–Altman analyses, and (3) clinical utility by identifying stage- and region-specific changes in CSF volumes. Key regions, including anterior and posterior lateral ventricles, showed DSCs above 0.93 and correlations ranging from 0.822 to 0.996. CT-based measurements revealed increasing CSF volumes from CU to DAT and distinct patterns of CSF volume enlargement across FTD subtypes. This framework enables accurate, reliable assessment of CSF volume changes as an indirect marker of atrophy, and supports early detection and differential diagnosis.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26604-x.

Anomaly changes in the functional connectome of post-operative neurosurgical patients: A case series.

Context. The speech therapy assessment of aphasia should be conducted, as much as possible, in all the languages of a bilingual or multilingual patient. However, tests are not necessarily available for all languages worldwide, particularly for regional or minority languages. Adapting language tests to the latter category of languages is complex because they are generally less standardized than official languages and also have many linguistic variants. Objectives. The objective of this article is to provide an example of the adaptation of the Screening BAT (Guilhem et al., 2013) established for one of the dialectal varieties of Basque spoken in France (Low Navarrese), but also to discuss the difficulties generated by this type of work and, finally, to provide the first clinical data collected with this tool. Methods. We describe in detail the process of adapting the test, which was done in several stages, including, among other things, the selection of relevant items taking into account the dialectal specificities of Basque. The Screening BAT was then administered to two bilingual patients (L1 dialectal Basque and L2 French) suffering from non-fluent aphasia following a left stroke, as well as to two bilingual control subjects, matched in age and socio-professional level. The four participants were also evaluated with the French Screening BAT. Results. The results obtained with the Screening BAT for both languages show performances consistent with the clinical picture of bilingual aphasic patients established by their speech therapists. The comparison with the control subjects also confirms that the adaptation of the Screening BAT to the Basque language is discriminative and suitable for the dialectal variant examined here. Conclusions. The study highlights the importance of the test adaptation approach to account for the full range of competencies of bilingual patients. The Basque Screening BAT (in its Low Navarrese version) is now ready to undergo the normalization process that will determine its psychometric characteristics.

Introduction Ischemic stroke has well-established risk factors such as hypertension, diabetes, hyperlipidemia and atrial fibrillation. However, strokes can also occur in the context of less common etiologies such as malignancies, particularly as certain malignancies are associated with hypercoagulable states. Adrenocortical carcinoma (ACC) is unique malignacy in relation to stroke as it can also present with a hypercortisolemic state, which can further exacerbate cancer coagulopathy and the traditional metabolic risk factors of stroke. Case Presentation A 60 year old woman presented with expressive aphasia and was found to have multifocal acute infarcts on magnetic resonance imaging. She underwent a thorough cardiac, coagulopathy and paraneoplastic work up and was found to have a right adrenal mass and was biochemically hypercortisolemic. The patient underwent surgical resection of the adrenal mass and pathology confirmed the diagnosis of adrenocortical carcinoma. Conclusion The discovery of this rare malignancy underscores the complex interplay between malignancy, hormonal imbalances, hypercoagulability in stroke and the importance of a comprehensive clinical diagnostic evaluation.

Cognitive and behavioral deficits in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) arise alongside gray matter atrophy and altered functional connectivity, yet the structure-function relationship across the dementia spectrum remains unclear. Here we combine structural and functional MRI from 221 patients—AD (n = 82), behavioral variant FTD (n = 41), corticobasal syndrome (n = 27), and nonfluent (n = 34) or semantic (n = 37) variant primary progressive aphasia—and 100 cognitively normal individuals. Partial least-squares regression reveals three structure–function components. Component 1 links cumulative atrophy to sensorimotor hypo-connectivity and hyper-connectivity in association cortical and subcortical brain regions. Components 2 and 3 tie focal, syndrome-specific atrophy to peri-lesional hypo-connectivity and distal hyper-connectivity. Structural and functional component scores explain 34% of the variance in global and domain-specific cognitive deficits on average. The functional connectivity changes reflect alterations of intrinsic activity gradients. Eigenmode analysis shows that atrophy relates to reduced gradient amplitudes and narrowed phase angles between gradients, offering a mechanistic account of network collapse in neurodegeneration.

Gamma oscillation regularity-guided intraoperative language-area visualization and functional monitoring of language-related cortical recruitment under general anesthesia in glioma surgery.

ABSTRACT Background Cognitive control skills, including working memory updating and resisting interference are often impaired in people with aphasia (PWA), however, the results from nonverbal tasks are inconsistent. This is in part because the groups of PWA in most studies are heterogeneous, including different subtypes of aphasia, and cognitive control is often measured with tasks that target multiple functions simultaneously. Aims Our objective was to systematically examine working memory updating and resisting interference in PWA, with stroke without aphasia and neurotypical controls using both verbal- and nonverbal tasks to determine whether the weaknesses in cognitive control are influenced more by the language disorder or the stroke itself. Methods This research employed a mixed quasi-experimental design (4 x 2 x 2) to examine group differences in speed of processing. Participants (N = 47; 40–70 years) included individuals with Broca’s aphasia (n = 9), with transcortical motor aphasia (TMA; n = 13), with stroke without aphasia (n = 12), and neurotypical controls (n = 13). Computerized verbal and nonverbal cue-based retrieval tasks were used to examine working memory updating and interference control. Mixed-effects modelling was used to analyse the data with fixed and random effects. We ran increasingly complex models, removing predictors that did not improve model fit at each step. Baseline conditions were used as references to experimental (cue) conditions. Results Participants with Broca’s aphasia showed significantly slower processing in both verbal and nonverbal tasks than the other groups (Verbal CRP: Group: (F(3, 49.1) = 6.35, p < .001; Nonverbal CRP: Group: (F(3, 47.6) = 6.36, p < .01). In contrast, individuals with TMA performed similar to the group with stroke without aphasia. Both groups showed an overall slowness compared to the neurotypical controls, but were faster and exhibited more efficient resistance to interference than the group with Broca’s aphasia. Conclusions Cognitive control and language show a strong relationship; the more severe the language disorder, the slower the speed of processing in working memory updating and interference control. In addition to the language problems, the stroke itself also contributed to slower performance on cognitive control tasks. Individuals with Broca’s aphasia showed both aphasia- and stroke-specific effects in cognitive control, whereas individuals with TMA showed a stroke-related slowness with relatively good interference control.

Time reference is often impaired in people with aphasia (PWA), but most research has focused on verb tense production in sentence-level tasks. Few studies have examined how PWA manage time reference in discourse, particularly in fluent aphasia. This study thus investigated how people with fluent and nonfluent aphasia produce verb tenses in discourse and how task type influences performance. Additionally, we explored linguistic patterns associated with time reference in PWA, namely, reduced verb diversity and increased use of temporal adverbs. We conducted a cross-sectional observational study with 21 PWA (11 nonfluent, 10 fluent) and 21 healthy controls. Participants completed two discourse tasks: a sequential picture description (past, present, and future frameworks) and a semistandardized interview (past and future frameworks). Verb tense production, verb diversity, and temporal adverbs were analyzed using generalized linear mixed models. Both aphasia groups produced a comparable number of inflected verbs to control when controlling for word count, aligning with the expected temporal framework. Task effects were observed across all participants, with more present tense verbs in the interview and more future tense verbs in the picture description task, irrespective of the temporal framework. Regarding the linguistic patterns associated with time reference, individuals with nonfluent aphasia exhibited a trade-off effect in the past framework of the picture description task: higher verb diversity was associated with lower past-tense verb production. Conversely, individuals with fluent aphasia relied more on temporal adverbs. The study demonstrates that both fluent and nonfluent aphasia impact discourse-level time reference, each with distinct associated linguistic patterns. It also highlights the need for task-specific assessments in clinical practice. https://doi.org/10.23641/asha.30329683.

Abstract INTRODUCTION Paraneoplastic neurological syndromes (PNS) are rare, immune-mediated complications of systemic cancer that can affect the central, peripheral, and autonomic nervous systems. PNS secondary to prostate cancer is exceptionally rare. Our case catalogs an uncommon presentation of occult prostate cancer, offering insight that may aid in resolving diagnostic dilemmas in the complex landscape of cancer-associated neurological syndromes. CASE DESCRIPTION A 73-year-old man with no medical history presented with generalized tonic-clonic seizures witnessed by bystanders, followed by left-sided Todd’s paralysis. Before arrival, he reported intermittent expressive aphasia and memory impairment over the preceding few days. Upon arrival to the ED, contrasted brain MRI showed focal leptomeningeal enhancement in the right parietal region. LP showed increased nucleated cells of 16, with 50% neutrophils and protein of 59. The CSF VZV and herpes PCR were negative. He had no improvement with broad-spectrum meningitis coverage or antifungals, so they were stopped after CSF results. Due to concern for autoimmune disease, he underwent contrasted chest, abdomen, and pelvis CT, which showed abdominopelvic lymphadenopathy. His CSF and serum autoimmune panels were negative. LN biopsy was positive for metastatic prostate adenocarcinoma. Other differential considerations included lymphoproliferative disorder versus Leptomeningeal carcinomatosis (LC). LC was ruled out by neuroimaging and three consecutive LPs, which were negative for atypical or malignant cells. PSA at that time was found to be 41 ng/mL. Hormonal therapy for prostate cancer was started, which showed significant improvement of his neurological symptoms and clearance of the leptomeningeal enhancement in subsequent MRI after 6 months. He has remained seizure-free for over 2 years. DISCUSSION While paraneoplastic epilepsy is a rare neurological manifestation of prostate adenocarcinoma, its recognition is crucial for early oncologic diagnosis and intervention. Our case highlights a unique intersection of multidisciplinary collaboration while expanding the recognized spectrum of paraneoplastic presentations in prostate cancer.

Rationale:Multiple myeloma (MM), ranking as the second most prevalent hematologic malignancy. Despite prolonged survival in MM due to novel therapies, infections remain a leading cause of mortality. While bacterial pneumonias and viral reactivations are well-documented, Listeria monocytogenes (L monocytogenes) (a rare but aggressive pathogen) is underrecognized in MM.Patient concerns:In this report, we report a 60-year-old male patient with newly diagnosed IgA-λ MM (Durie–Salmon stage IIIA, ISS stage III with 1q21 amplification) who developed high-grade fever (39.8 °C) and expressive aphasia during the second cycle of bortezomib–lenalidomide–dexamethasone induction therapy. Initial workup revealed neutrophilia (absolute neutrophil count 1.94 × 10⁹/L) with elevated inflammatory markers (C-reactive protein 118.14 mg/L). Cerebrospinal fluid analysis showed albuminocytologic dissociation (protein 1116.3 mg/L, glucose 1.77 mmol/L, chloride 114.75 mmol/L) without positive cultures. Contrast-enhanced brain MRI demonstrated neither abscess formation nor acute ischemia.Diagnoses:Repeated blood cultures drawn at fever onset, L monocytogenes bacteremia was confirmed 48 hours after-afebrile through blood culture. The patient has been diagnosed MM with bacteremia and meningitis caused by L monocytogenes infection.Interventions:Empiric meropenem was initiated promptly, achieving defervescence within 72 hours. Upon availability of antimicrobial susceptibility testing (intravenous penicillin G 8 million units every 8 hours), with documented blood culture clearance at 72 hours.Outcomes:On the second day of medication, the patient’s aphasia symptoms were resolved, the fever subsided on the 3rd day, and the blood culture turned negative on the 10th day. The patient completed a 21-day targeted antibiotic course without neurologic sequelae and was discharged with planned resumption of anti-myeloma therapy.Lessons:This case underscores the need for early empiric coverage for Listeria in MM patients with unexplained fever or neurological symptoms, particularly given its high mortality in immunocompromised hosts.

Background: Patent foramen ovale (PFO) is a recognized contributor to embolic stroke, especially in hypercoagulable states (HCSs). However, patients with HCSs, including malignancy, were excluded from major PFO closure trials, creating a significant evidence gap. Objectives: This narrative review examines the role of PFO closure in secondary stroke prevention among patients with HCSs, including malignancy. We highlight key studies and current evidence in this understudied population. Methods: A systematic search of PubMed was conducted using pertinent MeSH terms. Due to limited data, a narrative synthesis of the literature was performed. Case Presentation and Narrative Review of Literature: A 43-year-old lady with a history of metastatic breast cancer and recent bilateral pulmonary emboli on anticoagulation (AC), presented with expressive aphasia. MRI brain confirmed a Broca-area infarct. Biopsy of an expansile pelvic mass yielded a diagnosis of ovarian mucinous cystadenocarcinoma. TEE demonstrated a PFO; an embolic stroke driven by hypercoagulability of malignancy was diagnosed. PFO closure was offered for secondary stroke prevention after risk-benefit discussion, as opposed to AC alone. While early trials (CLOSURE I, PC) showed no benefit of closure, subsequent studies (RESPECT, REDUCE, DEFENSE-PFO) favored it in selected patients, but notably, these trials excluded patients with HCSs and malignancy. The benefit of PFO closure in this population thus comes largely from observational data. Abrahamyan et al. found that PFO closure could be safely offered in patients with thrombophilia to prevent recurrent stroke. Liu et al., in their prospective study, noted that among patients with cryptogenic stroke and thrombophilia, PFO closure lowered the risk of recurrence. Similarly, a retrospective study from Greece found benefit from PFO closure in this population. Buber et al. found that among patients with HCSs and stroke, PFO closure offered a five-fold risk reduction from future CVA/TIA. The Society for Cardiovascular Angiography and Interventions (SCAI) guidelines recommend PFO closure in patients with thrombophilia for secondary stroke prevention (conditional recommendation- low certainty of evidence). Conclusions: Data on PFO closure for secondary stroke prevention in HCSs and malignancy are scant, necessitating individualized decision making. Current evidence supports PFO closure, but future studies are needed specifically in this vulnerable population.

Introduction: Cardiac tamponade typically results from pericardial fluid accumulation that impairs diastolic filling. Rarely, extracardiac structures can cause similar physiologic compromise. We report a case of extracardiac tamponade caused by a large paraesophageal hernia, emphasizing the need to maintain a broad differential diagnosis of causes in patients with hemodynamic instability. Case: An 87-year-old male with stage IV chronic kidney disease, prior stroke with expressive aphasia, paroxysmal atrial fibrillation, and poor functional status became hypoxic during an outpatient echocardiogram. On arrival to the ED, he was alert, oriented, and denied chest pain, palpitations, or dyspnea. Vitals showed BP 125/61 mmHg and oxygen saturation of 88% on room air, improved with 2L nasal cannula. ECG revealed a normal sinus rhythm with first-degree AV block. Chest CT showed a large paraesophageal hernia, fluid-filled esophagus, and bilateral pleural effusions (Figure 1). Transthoracic echocardiogram (TTE) showed preserved LV ejection fraction but significant diastolic compression of the inferior and inferolateral walls, with increased mitral and tricuspid inflow variability—findings consistent with tamponade physiology (Figure 2). Notably, no pericardial effusion was seen. He was deemed too high risk for any surgical or endoscopic intervention. A nasogastric (NG) tube was placed, and 500 cc of gastric contents were aspirated. Repeat TTE still showed tamponade physiology, prompting continued NG decompression for 48 hours. Follow-up imaging demonstrated resolution of LV compression and improvement in inflow variability (Figure 3). Discussion: While cardiac tamponade is most often due to pericardial effusion, external cardiac compression from adjacent thoracic structures can produce a similar pathophysiology. Large hernias can compress cardiac structures, particularly the posterior LV, leading to hemodynamic compromise. This case emphasizes the importance of considering extracardiac causes when tamponade features are present without pericardial effusion. Extracardiac tamponade should be suspected in patients with tamponade physiology and no effusion. Cross-sectional imaging and interdisciplinary management are essential. Conservative decompression may be effective in high-risk patients.

A 27-year-old woman on 4th postpartum day presented to ED with fatigue, dysphagia, and chest tightness. Appeared anxious and had sinus tachycardia. Labs revealed leukocytosis, elevated hsTrop, and pro-BNP. TTE demonstrated LV systolic dysfunction (EF 35%), with basal hypokinesis and preserved apical function, raising suspicion for reverse Takotsubo cardiomyopathy. Workup for dysphagia included brain MRI, which revealed a CLIPPERS-like brainstem lesion. She was treated with high-dose IV steroids, DAPT for 21 days, and GDMT. Readmitted within days with new-onset expressive aphasia and right lower extremity weakness. MRI showed an acute infarct in the left anterior cerebral artery (ACA) territory. Cerebral angiography confirmed moderate to severe vasculitis and vasospasm of the bilateral ACA and left MCA. Steroids were escalated, and rituximab was initiated for presumed steroid-refractory postpartum vasculitis. Immunosuppressive therapy included prednisone and mycophenolate mofetil. Further testing confirmed VZV CNS vasculitis (positive VZV IgM, oligoclonal bands, and angiographic vasculitis); valacyclovir was later added. Repeat echocardiogram two weeks later showed EF normalization to 55–60% with no regional wall motion abnormalities, confirming transient rTTC. This case illustrates an unusual neurocardial interaction: VZV-induced CNS vasculitis triggered reverse Takotsubo cardiomyopathy in a postpartum woman. The catecholaminergic surge and neuroinflammatory milieu a/w CNS involvement likely contributed to myocardial stunning. The postpartum period may further predispose to immune dysregulation, explaining the fulminant course of vasculitis. rTTC is classically associated with neurological insults like subarachnoid hemorrhage or seizures, but to our knowledge, this is the first reported case linking VZV vasculitis to rTTC . This emphasizes the need to consider stress cardiomyopathy variants in postpartum patients presenting with cardiac and neurological symptoms and supports early echocardiography and CNS imaging in such scenarios. We report a rare and complex case of reverse Takotsubo cardiomyopathy secondary to VZV-induced CNS vasculitis in the postpartum period. This case highlights the critical interplay between the central nervous system and cardiac function, the importance of early multidisciplinary involvement, and the potential reversibility of both cardiac and neurological complications with timely immunosuppressive and antiviral therapy.

Description of Case: A 47-year-old female with history of thrombophilia (PAI-1 4G/4G genotype), Barlow syndrome with native leaflet repair then mechanical mitral valve (MV) replacement on warfarin, and previous stroke due to MV thromboembolism, presented with more than 24-hour onset of expressive aphasia. CT head showed showed acute ischemic stroke (AIS) in left parietal lobe with left middle cerebral artery (MCA) distal occlusion on CTA-head despite warfarin use and therapeutic INR-2.5. Within hours of admission, she had neurological deterioration and brain MRI demonstrated new left frontal-temporal intracranial hemorrhage (ICH) with cerebral herniation. She emergently received 4F-PCC/vitamin K, underwent decompression craniectomy. TTE showed MV severe stenosis. TEE (Figure 1) confirmed MV thrombus, similar embolic mechanism to prior AIS. To balance the concomitant high risks of strokes given mechanical MV thrombus requiring uninterrupted anticoagulation (AC) and ICH recurrence with AC, she was started on low-dose heparin infusion without bolus day 8. Transcranial Doppler (TCD) (Figure 2) was utilized to determine risk of cerebral embolization from MV thrombus via detection of microemboli or high-intensity transient signals (HITS) within bilateral MCA. Although patient anticoagulated with heparin, we detected 16 HITS in 15 mins of embolic monitoring suggesting high risk of recurrent ischemic stroke. AC was switched to enoxaparin at 1mg/kg twice daily and repeated TCD-emboli on day 15 showed continued AIS risk with 11 HITS even with a therapeutic anti-Xa level of 0.7 (goal 0.6-1.0). Enoxaparin dosage increased guided by emboli monitoring until HITS resolved. She was discharged to stroke rehab with plan to bridge to warfarin (INR goal 3.5-4.0) after 4 week. At one-month follow-up, she remained on warfarin 10mg daily with therapeutic INR and free of recurrent AIS or ICH. Discussion: Microembolic signals detected on TCD can be used as biomarkers to predict stroke risk and guide therapeutic interventions. Our patient was at risk of further ICH after decompressive hemicraniectomy but without anticoagulation she had high risk of embolic stroke from mechanical MV thrombus. TCD emboli monitoring played a pivotal role in guiding the timing of AC initiation and determining the therapeutic dose to reduce risk of both recurrent emboli and hemorrhagic complications.

Recursive self-feedback enables target language production in aphasia with pathological language mixing.

Autoimmune encephalitis following bevacizumab therapy in ovarian carcinoma: A case report and review.